Schizophrenia: Clinical Guidelines

List of Abbreviations

SGA – second-generation antipsychotic

AD – antidepressants

FGA – first-generation antipsychotic

BT – rapid tranquilization

HPR – hyperprolactinemia

NMS – neuroleptic malignant syndrome

LAI – long-acting injectable antipsychotics

CBT – cognitive behavioral therapy

CR – cognitive remediation

ABG – acid-base balance

CK – creatine kinase

ICD-10 – International Statistical Classification of Diseases and Related Health Problems 10th Revision

MCT – metacognitive training

MRI – magnetic resonance imaging

BV – blood volume.

PE – psychoeducation

FPE – first psychotic episode

RCTs – Randomized Controlled Trials

RUSP – Russian Society of Psychiatrists

SSRIs – Selective Serotonin Reuptake Inhibitors

SNRI – serotonin-norepinephrine reuptake inhibitor

ESR – erythrocyte sedimentation rate

LCE – level of confidence of evidence

GRS – grade of recommendation strength

rTMS – Transcranial magnetic stimulation

SST – social skills training

TCA – tricyclic antidepressants

CPZ – chlorpromazine equivalent

SZ – schizophrenia

FC – febrile catatonia

ECG – electrocardiography

EPS – extrapyramidal symptoms

ECT – electroconvulsive therapy

Echo-EG – echoencephalography

EEG – electroencephalography

** drug is included in the list of Vital and Essential Drugs

# – this disease or disorder is not specified in the instructions for use

Terms and Definitions

Schizophrenia is a mental disorder characterized by a combination of positive (hallucinatory-delusional, catatonic-hebephrenic, affective, etc.) and negative (apathy, abulia, alogia, emotional and social withdrawal, etc.) symptoms, behavioral and cognitive impairments (memory, attention, thinking, etc.), leading to adverse social and economic consequences.

Antipsychotic drugs (neuroleptics) are a group of psychopharmacological agents with psycholeptic action that suppress dopamine neurotransmission by blocking type II dopamine receptors and are capable of reducing psychotic symptoms and psychomotor agitation.

Typical (conventional) neuroleptics or first-generation antipsychotics (FGAs) unify antipsychotic drugs that first appeared in clinical practice.

Atypical antipsychotics or second-generation antipsychotics (SGAs) have better neurological tolerability due to the characteristics of their neurochemical profile of action (e.g., antagonism at type 2 serotonin receptors, partial agonism at dopamine receptors, etc.).

Long-acting injectable antipsychotics (LAIAs) constitute a separate group among first- and second-generation drugs and, due to the pharmacokinetic characteristics of the gradual release of the active drug from intramuscular depots or the degradation of biomolecules, have the ability to maintain a therapeutic plasma concentration for a long time after a single injection (usually from 2 weeks to 3 months).

Non-pharmacological biological intervention methods are therapeutic interventions that are not pharmacological and use other physical treatment methods (e.g., electroconvulsive therapy, plasmapheresis, transcranial magnetic stimulation, laser therapy, etc.).

Psychosocial therapy and rehabilitation is the development or restoration of deficient or lost skills, knowledge, abilities to interact, solve problems, and use coping strategies (in conditions impaired as a result of the disease's cognitive, motivational, and emotional personal resources) in psychiatric patients with impaired social adaptation, ensuring their integration into society.

Consciousness disorders are acute transient disorders of mental activity accompanied by impaired perception of the environment, disorientation in time and place, impaired thinking with difficulty in making judgments, and subsequent more or less pronounced amnesia. Consciousness disorders are the most frequent psychopathological syndromes that occur in psychiatric patients during critical states.

Oneiroid state is a state of altered consciousness with a rush of dreamlike, scenelike, visual pseudohallucinations, fantastic derealization and depersonalization, acute sensory delusions with catatonic symptoms, phenomena of double orientation with complete amnesia of objective reality and partial preservation of memories of painful experiences.

Catatonic syndrome is a syndrome of motor dysregulation. Diagnosis of catatonic syndrome requires the presence of at least two of 12 symptoms: 1) stupor, 2) catalepsy, 3) waxy flexibility, 4) mutism, 5) negativism, 6) posturing, 7) mannerisms, 8) stereotypies, 9) agitation, 10) grimacing, 11) echolalia, 12) echopraxia.

Febrile catatonia syndrome is a combination of catatonic disorders with hyperthermia, a complex of somatovegetative disorders, and impaired consciousness.

Malignant neuroleptic syndrome (MNS) is a rare but extremely dangerous complication of neuroleptic therapy, proceeding with the development of central hyperthermia, muscle hypertonus, catatonic symptoms, impaired consciousness, and a complex of somatovegetative disorders.

Febrile schizophrenia is acute attacks of schizophrenia or schizoaffective psychosis occurring with catatonic symptoms, phenomena of endogenous toxicosis, and hyperthermia with impaired consciousness.

Efferent therapy methods are active detoxification methods based on the removal of harmful substances along with a portion of the patient's blood plasma (plasmapheresis) or by sorption fixation of toxic products circulating in the blood and their subsequent removal (extracorporeal hemisorption).

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Schizophrenia is a mental disorder characterized by a combination of positive (hallucinatory, delusional, catatonic, affective, etc.) and negative (apathy, abulia, alogia, emotional and social withdrawal, etc.) symptoms, behavioral and cognitive impairments (memory, attention, thinking, etc.).

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Currently, the stress-diathesis model of the origin of schizophrenia is generally accepted, reflecting the concept of the importance of not only hereditary but also environmental, including social, factors in the development of the disease.

Schizophrenia is a heterogeneous, polygenic-multifactorial disease with multiple common genetic polymorphisms, each of which makes a small contribution to disease susceptibility. The risk of developing schizophrenia in children if one parent suffers from the disease is 7-13% (if both are sick, 27-46%), in grandchildren – 5%. The probability of falling ill for a parent in the event of a child's illness is 6%. In heterozygous twins, the risk is considered to be 17%, in monozygotic twins – 41-65%, in siblings – 9%, in half-siblings – 3-8%, in cousins (uncles/aunts) – 2%, in nephews/nieces – 4% [1-3].

Along with genetic and epigenetic factors, environmental factors play a significant role in the development of the disease [4]. Thus, the risk of schizophrenia increases in individuals living in an urban environment compared to those living in rural areas (odds ratio ~2), in migrants (odds ratio 2-5), and in cannabis users (odds ratio 1.5-2.0) [5]. Risk factors also include obstetric and gynecological complications (premature birth, fetal hypoxia), infectious diseases and maternal malnutrition in the first and early second trimesters of pregnancy, infectious diseases during pregnancy – influenza, rubella, toxoplasmosis, herpes (odds ratio 3.06), as well as early childhood psychological trauma (odds ratio 5.94) [6, 7]. In recent years, special attention regarding the development of schizophrenia has been paid to the microbiota [8].

The complex of these unfavorable factors leads to abnormalities in brain development and diathesis phenomena with personal vulnerability, which, in the presence of supra-threshold external stimuli, contribute to a progressive cerebral process manifested by psychopathological (positive and negative) symptoms.

Manifest psychosis in schizophrenia is preceded by a long pathological process occurring in the central nervous system for many years [9]. In particular, this is manifested by a mildly pronounced but statistically significant decrease in intracranial volume in recently onset schizophrenia patients (effect size = 0.2) [10], which indicates a disruption in brain development even before the onset of the disease. In the postpubertal period, there is a further decrease in brain tissue, including both gray and white matter (effect size = 0.4). The reduction in brain volume (more markedly in the frontal and temporal areas) continues after the manifestation of schizophrenia, especially in the first years of the disease.

The pathophysiological mechanisms of the development of schizophrenia are driven by at least three interrelated processes: dopaminergic dysregulation, impaired glutamatergic neurotransmission, and pro-inflammatory processes in the brain.

According to the dopamine hypothesis of the development of schizophrenia, the onset of psychotic symptoms is closely associated with increased dopamine neurotransmission and hypersensitivity of dopamine receptors in the mesolimbic system of the brain, while negative symptoms are caused by decreased dopamine activity in the mesocortical system. At the same time, the dopamine theory is currently not viewed in isolation, but is a significant component of a broader neurotransmitter theory [11] that takes into account coupled abnormalities in various systems, in particular, the serotonergic and GABAergic systems.

The brain's glutamatergic system plays a significant role in the development of psychosis by modulating the increased activity of dopamine neurons in the mesolimbic pathway [9]. In addition, dysregulation of glutamatergic neurotransmission underlies cognitive impairment. Aberration of synaptic plasticity resulting from impaired modulation of N-methyl-D-aspartate (NMDA) receptors leads to a failure in the formation of efferent copies (neurophysiological "predictions" of sensory signals that should occur as a result of an action), which causes a mismatch between the expectation and the result of the action, manifesting at the phenomenological level as cognitive impairment and various psychopathological symptoms, in particular, the syndrome of psychic automatism.

Another potential mechanism for the development of schizophrenia is associated with inflammation, as indicated by elevated plasma concentrations of certain pro-inflammatory cytokines, reflecting microglial response to various pathological (in particular, autoimmune) processes in the brain [9, 213]. An excess of free radicals resulting from microglial activation has a damaging effect and leads to impaired neurogenesis and white matter pathology in patients with schizophrenia.

Special forms of schizophrenia include so-called febrile schizophrenia [343-347], known in international literature as lethal catatonia [343]. Febrile schizophrenia comprises conditions presenting with catatonic symptoms combined with hyperthermia, a complex of somatovegetative disorders, and impaired consciousness. Thus, the main characteristic of these conditions is the combination of catatonic disorders with hyperthermia, i.e., the development of febrile catatonia (FC) syndrome. In some cases, FC attacks develop spontaneously as a result of an extremely acute course of psychosis [343-347]. In others, the psychopathological symptoms typical of the course of uncomplicated forms of schizophrenia transform into FC as a result of a severe complication of antipsychotic therapy known as "neuroleptic malignant syndrome" (NMS) [343-347]. Most researchers view FC as a special form of schizophrenia occurring with the highest degree of endotoxicosis. This is reflected in the synonym for FC, "hypertoxic schizophrenia." Postmortem studies of deceased patients have shown non-specific toxic-dystrophic changes in internal organs, such as those observed in various intoxications [346, 347]. At the same time, an important role in the development of endotoxicosis is attributed to immunological disorders with altered blood-brain barrier permeability, leading to neurosensitization of the organism followed by autoimmune damage to the central nervous system (CNS) and internal organs [346, 347, 350]. Evidence for this is the detection of autoantibodies to various brain antigens [347, 350].

1.3 Epidemiology of the Disease or Condition

The median incidence of schizophrenia is 15.2 per 100,000 population per year, with an 80% confidence interval ranging from 8 to 43 per 100,000 population [12]; the lifetime prevalence ranges from 0.3% to 2.0%, with a mean of 0.7% [13]. The point prevalence median is at the level of 3.3-4.6 per 1,000 population, with an 80% confidence interval ranging from 1.3 to 12.1 [14, 15]. In the Russian Federation, the number of individuals newly diagnosed with schizophrenia in 2021 was 9.4 per 100,000 population; the overall prevalence (2021) was 309.0 per 100,000 population [330].

Manifestation of the disease occurs before the age of 30 in almost half of the cases (peak incidence: 18-25 years); another 30% of cases debut between the ages of 31 and 45 [18].

The disability rate for schizophrenia in 2021 was 226.7 per 100,000 population. In 2021, 4.6 per 100,000 population were newly recognized as disabled due to schizophrenia [330].

The risk of developing diabetes in patients with schizophrenia is 11%-23%, compared to an 8.5% risk of developing the disease in the general population [19]. Comorbid somatic diseases (cardiovascular diseases, type II diabetes, etc.) and suicides (lifetime suicide rate is 4%-13%) are the leading causes of premature mortality and reduce the life expectancy of patients with schizophrenia by an average of 10-20 years compared to the general population [20-22].

FC is a relatively rare condition. No special epidemiological studies have been conducted to determine its incidence. The incidence of NMS presenting with FC syndrome ranges from 0.01% to 0.02% of all hospital admissions receiving antipsychotic therapy, regardless of the underlying nosology [346, 347, 351].

1.4 Features of Coding the Disease or Condition

F20.0 – Paranoid schizophrenia.

F20.1 – Hebephrenic schizophrenia.

F20.2 – Catatonic schizophrenia.

F20.3 – Undifferentiated schizophrenia.

F20.4 – Post-schizophrenic depression.

F20.5 – Residual schizophrenia.

F20.6 – Simple schizophrenia.

F20.8 – Other schizophrenia.

F20.9 – Schizophrenia, unspecified.

1.5 Classification of the disease or condition

According to ICD-10, the disease is classified both by clinical forms (paranoid schizophrenia, hebephrenic schizophrenia, catatonic schizophrenia, undifferentiated schizophrenia, simple schizophrenia, residual schizophrenia, etc.) and by the type of course (first episode, episodic with progressive deficit, episodic with stable deficit, continuous, low-progressive, etc.). It is also important to identify individual symptom complexes (dimensions) of psychopathological symptoms (positive symptoms, negative symptoms, speech and thought disorganization, affective symptoms, cognitive impairment, catatonic symptoms, etc.), which can vary widely in severity individually and determine the diversity of the clinical picture of the disease.

1.6 Clinical presentation of the disease or condition

Prodromal phenomena may precede an acute psychotic episode for weeks, months, or even years. Prodromal symptoms include loss of interest in work, social activities, personal appearance, and hygiene habits, as well as cognitive impairment and motor changes, which may be combined with isolated perceptual disturbances, anxiety, depression not reaching syndromal severity, or other non-specific psychopathological symptoms [23, 24].

The most active period of the disease is the first 5 years after the manifestation of psychotic symptoms ("first-episode psychosis" – FEP), when the most pronounced biological disorders and significant social losses occur for patients [25, 26]. This group of patients requires special approaches both in the organizational form of psychiatric care (FEP units) and in drug therapy and rehabilitation methods [27].

According to ICD-10, several forms of schizophrenia are distinguished: paranoid, hebephrenic, catatonic, undifferentiated, residual, and simple.

For the paranoid form, the clinical picture must prominently feature hallucinations and/or delusions: hallucinatory voices that are threatening or commanding, or auditory hallucinations without verbal form, olfactory or gustatory hallucinations, sexual or other somatic sensations; delusions of persecution, influence, reference, significance, high birth, special mission, bodily change, or jealousy. Emotional flattening or incongruity, catatonic symptoms, or incoherent speech must not dominate the clinical picture, although they may be present to a mild degree.

The hebephrenic form usually debuts in adolescence or young adulthood. There should be clear and persistent emotional flattening or incongruity; behavior that is characterized by silliness rather than goal-directedness; distinct thought disorders in the form of incoherent speech. Hallucinations or delusions must not dominate the clinical picture, although they may be present to a mild degree.

In catatonic schizophrenia, one or more of the following catatonic symptoms must be clearly identifiable for a minimum of two weeks: stupor or mutism; excitement; posturing; negativism; rigidity; waxy flexibility; obedience (automatic execution of instructions).

Phasic schizophrenia attacks typically develop at a young age, more frequently in women, in the context of episodic forms of schizophrenia [346, 347]. From the first days of the attack's manifestation, an extreme severity of psychopathological disorders is characteristic, with the rapid development of oneiric clouding of consciousness and pronounced catatonic disorders—stupor with phenomena of waxy flexibility and negativism, or agitation with impulsivity, motor and speech stereotypies [343-347]. The temperature rises from the first days of the attack's manifestation, has an irregular pattern (atypical for any somatic and infectious disease), and does not decrease upon the administration of analgesics. Simultaneously with hyperthermia, tachycardia and blood pressure fluctuations occur. Water-electrolyte disturbances join rapidly. A complete blood count reveals an accelerated erythrocyte sedimentation rate (ESR), moderate leukocytosis, and lymphopenia. A blood chemistry panel reveals increased activity of transaminases and creatine phosphokinase (CPK) [346, 347].

In undifferentiated schizophrenia, the symptoms are either insufficient to identify another form of schizophrenia, or there are so many symptoms that the criteria for more than one form of schizophrenia are met.

In the simple form, a slow development over at least one year of all three signs is noted: 1) a distinct change in the premorbid personality, manifested by a loss of drives and interests, inactivity and aimless behavior, self-absorption and social autization; 2) the gradual appearance and deepening of negative symptoms, such as pronounced apathy, speech impoverishment, hypoactivity, emotional flattening, passivity and lack of initiative, poverty of nonverbal communication; 3) a distinct decrease in social, academic, or occupational productivity. The absence of hallucinations or sufficiently fully formed delusional ideas of any kind, meaning the clinical case must not meet the criteria for any other form of schizophrenia or any other mental disorder. No evidence of dementia or another organic mental disorder.

In the residual form of schizophrenia, there is a transition from an active course of the process—i.e., psychotic episodes with a predominance of positive symptoms—to a chronic stage with persistent negative symptoms, such as psychomotor retardation, reduced activity, emotional flattening, passivity, and lack of initiative; poverty of speech, both in content and in quantity; poverty of nonverbal communications; and insufficiency of self-care skills and social productivity.

The following types of disease course are distinguished: continuous, episodic with a progressive deficit, episodic with a stable deficit, and episodic remitting.

Clinical manifestations of an exacerbation (attack) of schizophrenia: manifestation or intensification of positive psychopathological symptoms in the form of delusions, hallucinations, thought disorders, often accompanied by fear, anxiety, escalating behavioral changes, various types of psychomotor agitation, catatonic and hebephrenic symptoms, and frequently suicidal thoughts and actions.

Remission is a lessening of the psychopathological symptoms of the acute period of the illness. Remissions are subdivided into complete and incomplete, spontaneous (persisting regardless of psychopharmacotherapy) and drug-dependent (continuing as long as maintenance and relapse-prevention therapy is carried out). Complete remission implies the absence of positive disorders, usually with the restoration of critical insight into the endured psychosis and a shallow level of personality changes. In incomplete remission, psychopathological disorders are largely de-actualized, devoid of affective saturation, and become the patient's "private matter," not affecting their actions or affecting them only to a minimal degree, while maintaining relatively orderly, socially acceptable behavior, including without aggressive and auto-aggressive tendencies.

According to the recommendations of the working group on the development of remission criteria in schizophrenia [28, 29], the severity of symptoms should not exceed a mild degree for each of the following disease manifestations: delusions, unusual thought content, hallucinations, conceptual (formal) disorganization, mannerisms and posturing, blunted affect, passive-apathetic social withdrawal, and impairment of spontaneity and fluency of speech. A six-month period is the minimum required to diagnose a remissional state with the aforementioned severity of disorders. More differentiated criteria for remission have also been developed for individual forms and types of the course of schizophrenia, taking into account the achieved level of functional recovery [179, 218].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria

F20.0-F20.3 General criteria for paranoid, hebephrenic, catatonic, and undifferentiated schizophrenia:

G1. For the greater part of a psychotic episode lasting at least one month (or for some time on most days), at least one of the signs listed in list (1) or at least two signs from list (2) must be present.

1) At least one of the following signs:

1. thought "echo," thought insertion or withdrawal, or thought broadcasting;

2. delusions of control, influence, or passivity, clearly referred to body movements or limbs, or to thoughts, actions, or sensations; delusional perception;

3. hallucinatory "voices" running a running commentary on the patient's behavior, or discussing them among themselves, or other types of hallucinatory "voices" coming from some part of the body;

4. persistent delusions of other kinds that are culturally inappropriate and completely impossible in content, such as identity with religious or political figures, claims of superhuman abilities (e.g., the ability to control the weather or communicate with extraterrestrials).

2) Or at least two signs from the following:

1. chronic hallucinations of any kind, if they occur daily for at least one month and are accompanied by delusions (which may be unsteadfast and semi-formed) without clear affective content;

2. neologisms, thought blocks leading to incoherence or irrelevance in speech;

3. catatonic behavior, such as agitation, posturing or waxy flexibility, negativism, mutism, and stupor;

4. "negative" symptoms, such as marked apathy, speech impoverishment, and blunting or incongruity of emotional responses (it must be clear that these are not due to depression or neuroleptic therapy).

G2. Most commonly used exclusion criteria:

1) If the case also meets the criteria for a manic episode (F30-) or a depressive episode (F32-), the above criteria G1.1 and G1.2 must have developed BEFORE the mood disorder.

2) The disorder cannot be attributed to organic brain disease (as outlined in F00-F09) or alcohol or drug intoxication (F1x.0), dependence (F1x.2), or withdrawal state (F1x.3 and F1x.4).

Given the significant variability in the course of schizophrenic disorders, it may be advisable (especially for research purposes) to specify the type of course using the fifth character. The course should be coded with an observation period of at least one year (for remission, see note 5 in the introduction).

F20.x0 continuous (throughout the entire observation period, there are no remissions in psychotic symptoms)

F20.x1 episodic with progressive development of a deficit (progressive development of "negative" symptoms between psychotic episodes)

F20.x2 episodic with a stable deficit (persistent but non-progressive "negative" symptoms between psychotic episodes)

F20.x3 episodic remitting with complete or virtually complete remissions between psychotic episodes

F20.x4 incomplete remission

F20.x5 complete remission

F20.x8 other type of course

F20.x9 course not specified, observation period too short

F20.0 Paranoid schizophrenia

A. The general criteria for schizophrenia must be met (F20.0-F20.3)

B. Delusions and hallucinations must be prominent (such as delusions of persecution, reference, high lineage, special mission, bodily change, or jealousy; "voices" of a threatening or imperative nature, olfactory or gustatory hallucinations, sexual or other bodily sensations).

C. Emotional flattening or incongruity, catatonic symptoms, or disorganized speech must not dominate the clinical picture, although they may be present to a mild degree.

F20.1 Hebephrenic schizophrenia

A. The general criteria for schizophrenia must be met (F20.0-F20.3).

B. Either (1) or (2) must be present:

1) prominent and persistent emotional flattening;

2) prominent and persistent emotional incongruity.

C. Either (1) or (2) must be present:

1) behavior that is characterized more by aimlessness and inconsequentiality than by goal-directedness;

2) a distinct thought disorder manifested by incoherent speech

G. Hallucinations or delusions must not dominate the clinical picture, although they may be present to a mild degree.

F20.2 Catatonic schizophrenia

A. General criteria for schizophrenia (F20.0-F20.3) must be met, although this may not be possible initially due to the patient's inability to communicate.

B. For a minimum of two weeks, one or more of the following catatonic symptoms are clearly manifested:

1) stupor (significant decrease in reactivity to external stimuli and reduction of spontaneous movements and activity) or mutism;

2) excitement (purposeless motor activity not influenced by external stimuli);

3) posturing (voluntary assumption and maintenance of inappropriate or bizarre postures);

4) negativism (motiveless resistance to all instructions and attempts to be moved, or even movement in the opposite direction);

5) rigidity (maintenance of a rigid posture despite attempts to change it);

6) waxy flexibility (maintenance of body limbs in positions molded by others);

7) automatic obedience (automatic compliance with instructions).

Febrile catatonia

A. General diagnostic criteria for schizophrenia and schizoaffective disorder (F20-F20.3) must be met.

B. The following main manifestations must be present:

1) Catatonic symptoms in the form of stupor with phenomena of negativism, mutism, catalepsy, motor and speech stereotypies;

2) Central hyperthermia not associated with an infectious or inflammatory disease;

3) Somatovegetative disorders (tachycardia, blood pressure instability, pallor or hyperemia of the skin, increased sweating);

4) Laboratory changes in the form of accelerated ESR, moderate leukocytosis without a shift to the left, lymphopenia, and increased plasma CK activity.

C. Symptoms of group B must not be the consequence of a developing or ongoing inflammatory somatic or neurological disease (viral or autoimmune encephalitis, meningoencephalitis, vascular or space-occupying CNS lesion, etc.) [343, 344, 345, 346, 347-349, 353]

Comment: Assessment of catatonic symptoms can be performed using the Bush-Francis Catatonia Rating Scale [358].

F20.3 Undifferentiated schizophrenia.

A. The general criteria for schizophrenia must be met (F20.0-F20.3).

B. One of the following two:

1. the symptoms are insufficient to meet the criteria for any of the subtypes F20.0, F20.1, F20.2, F20.4, or F20.5;

2. the symptoms are so numerous that the criteria for more than one of the subtypes listed above in B (1) are met.

F20.4 Post-schizophrenic depression.

A. General criteria for schizophrenia (F20.0-F20.3) must have been met within the past 12 months, but are currently absent.

B. One of the states noted in criterion G1 (2) a), b), c), or d) in categories F20.0-F20.3 must persist.

C. Depressive symptoms must be sufficiently prolonged, pronounced, and diverse to meet the criteria for at least a mild depressive episode (F32.0).

F20.5 Residual schizophrenia.

A. General criteria for schizophrenia (F20.0-F20.3) must have been met at some time in the past, but are currently absent.

B. At least 4 of the following "negative" symptoms must have been present during the preceding 12 months:

1) psychomotor retardation or hypoactivity;

2) distinct emotional flattening;

3) passivity and lack of initiative;

4) impoverishment of speech in volume or content;

5) poverty of nonverbal communication, as determined by facial expression, eye contact, voice modulation, or posture;

6) poor social productivity or poor self-care.

F20.6 Simple schizophrenia.

A. Slow progressive development over at least one year of all three features:

1) a distinct change in premorbid personality, manifested by loss of drives and interests, inactivity and aimless behavior, self-absorption, and social autism;

2) gradual emergence and deepening of "negative" symptoms, such as pronounced apathy, speech impoverishment, hypoactivity, emotional flattening, passivity and lack of initiative, poverty of nonverbal communication (determined by facial expression, eye contact, voice modulation, or posture);

3) a distinct decline in social, academic, or occupational productivity.

B. Absence at any time of abnormal subjective experiences indicated in G1 in F20.0-F20.3, as well as hallucinations or fully formed delusional ideas of any kind, i.e., the clinical case must never meet the criteria for any other type of schizophrenia or any other psychotic disorder.

Absence of evidence for dementia or other organic mental disorder as presented in section F00-F09.

F20.8 Other schizophrenia.

F20.9 Schizophrenia, unspecified.

2.1 Complaints and Anamnesis

• For all patients during the initial examination (during the conversation with patients and their relatives) in order to establish a diagnosis, it is recommended [30, 31]:

- collection of complaints and anamnesis (objective and subjective) – it is necessary to ascertain the patient's complaints, family history of mental illness; premorbid personality features, including those related either to accentuations or to psychopathic-level features; age of onset of the first signs of the disease; prodromal phenomena when the disease was first diagnosed (neurosis- and psychopathy-like disorders, affective fluctuations, overvalued ideas, social functioning impairments, transient subpsychotic episodes) (service code A01.29.001);

- to assess the features of the patient's social status and social functioning, noting not only problems and difficulties, but also favorable and positive features. Data are grouped into the following categories: marital status and family characteristics; immediate (personally significant) environment; characteristics of the study period (past or present) and level of education obtained; occupational engagement; financial situation; self-care; housing conditions; leisure; medical care problems; legal problems and problems related to interaction with state (including law enforcement) authorities; other psychosocial problems;

- to collect anamnestic data on the presence of trauma, infectious diseases of the brain, somatic diseases directly preceding the development of symptom disorders.

- to conduct a targeted survey of the patient and family members to rule out the use by the patient, immediately before the onset of an exacerbation, of psychoactive substances or medications that can cause psychotic or affective symptoms.

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comments:

- mental status (patient's behavior, orientation in place, time, own personality, accessibility regarding painful experiences, description of identified psychopathological (positive and negative) disorders, presence or absence of insight into them, their situation, and the illness as a whole);

- social status (education, marital status, employment status, features of social functioning, circle and style of communication – isolation, indiscriminate contacts, tendency to aggression or passive obedience, etc.);

- features of the prior dynamics of the disease (the nature of the course of the disease and its progression).

A step-by-step algorithm for the diagnosis of schizophrenia in general terms is presented in algorithm B1. Conditions corresponding to the above criteria but lasting less than a month (regardless of whether the patient was treated or not) should be classified as acute schizophreniform psychotic disorder or recoded if symptoms persist for a longer period (algorithm B1). The diagnosis of schizophrenia should not be made in the presence of pronounced depressive or manic symptoms unless the aforementioned schizophrenic symptoms preceded the affective disorders. Schizophrenia should not be diagnosed in the presence of clear signs of brain disease or in the presence of drug intoxication or withdrawal states (algorithm B1).

Diagnosis of depression in schizophrenia

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: Depressive symptoms can occur at all stages of schizophrenia, specifically in the prodromal phase, within the structure of psychosis, and following the onset of remission as residual symptoms of schizophrenia [40, 92–98]. For a more accurate diagnosis, the Calgary Depression Scale for Schizophrenia (Appendix G3) may be used [91]. Depressive symptoms must be differentiated from side effects of antipsychotic therapy (primarily neuroleptic dysphoria, akinesia, and akathisia) and primary negative symptoms of schizophrenia (Appendix B6) [99–106]. However, the initial diagnostic step in this case is to identify potential manifestations of psychosis that may be causing the depression (Appendix B6) [41, 107, 108]. In this scenario, the sole therapeutic choice should be the intensification of antipsychotic therapy. Depressive symptoms during acute psychoses often resolve in parallel with hallucinatory-delusional symptoms and do not require the prescription of an antidepressant [106–108]. It is also necessary to identify any potential link between depression and reactive mechanisms or maladaptation. In such cases, psychotherapy and rehabilitation measures are indicated (Appendix B6) [108]. The primary indication for adjusting therapy is the duration and severity of depressive symptoms (Appendix B6) [108].

2.2 Physical Examination

There are no physical examination methods required for the diagnosis of schizophrenia.

• All patients with schizophrenia are recommended to undergo a standard physical and neurological examination to rule out organic causes of psychotic symptoms [31].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• All patients with schizophrenia are recommended to have their weight and body mass index determined (A02.01.001) [31].

Level of evidence reliability – 5, Level of recommendation consensus – C.

2.3 Laboratory Diagnostics

There are no laboratory diagnostic methods specific for schizophrenia.

• All patients with schizophrenia are recommended to undergo laboratory diagnostics in the following scope: general (clinical) urine analysis (B03.016.006), complete blood count (differential white blood cell count) (B03.016.003) (investigation of total hemoglobin level in blood (A09.05.003), hematocrit evaluation (A12.05.117), investigation of erythrocyte count in blood (A12.05.118), investigation of leukocyte count in blood (A12.05.119), investigation of platelet count in blood (A12.05.120), erythrocyte sedimentation rate determination (A12.05.001)) as part of the initial assessment, upon admission to the inpatient facility, and during follow-up monitoring to clarify the degree of disease activity and diagnose involvement of organs and systems [30].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• All patients with schizophrenia are recommended to undergo a routine general clinical biochemical blood test: determination of potassium level (A09.05.031), sodium (A09.05.030), chloride (A09.05.034), glucose (A09.05.023), creatinine (A09.05.020), total protein (A09.05.010), urea (A09.05.017), uric acid (A09.05.018), total bilirubin (A09.05.021), free and conjugated bilirubin (A09.05.022), determination of aspartate aminotransferase activity (A09.05.041) and alanine aminotransferase activity (A09.05.042), C-reactive protein (A09.05.009)), determination of thyroid-stimulating hormone (TSH) level in blood (A09.05.065) as part of the initial assessment, upon admission to the inpatient facility, and during follow-up monitoring to assess renal and hepatic function, as well as thyroid function and to rule out inflammation [30, 31].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Level of evidence reliability – 5, Level of recommendation consensus – C.

• All patients with schizophrenia are recommended to undergo testing for antibodies to hepatitis B virus surface antigen (HbsAg) in blood (A26.06.040), antibodies to hepatitis C virus in blood (A26.06.041), antibodies to Treponema pallidum in blood (A26.06.082), antibodies of classes M and G (IgM, IgG) to human immunodeficiency virus HIV-1 in blood (A26.06.048), antibodies of classes M and G (IgM, IgG) to human immunodeficiency virus HIV-2 in blood (A26.06.049) as part of the initial assessment, upon admission to the inpatient facility, and subsequently every 12 months to rule out association with HIV infection, hepatitis, and syphilis [30, 31].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• All patients suspected of having febrile catatonia are recommended to undergo determination of creatine kinase activity in blood (A09.05.043) for diagnostic purposes [321, 348, 351, 353, 355, 356, 357].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• All patients diagnosed with febrile catatonia are recommended to undergo an investigation of total protein in blood (A09.05.010), albumin level in blood (A09.05.011), sodium (A09.05.030) and potassium (A09.05.031) levels in blood as part of a routine biochemical blood test (B03.016.004), investigation of blood hydrogen ion concentration (pH) as part of an acid-base balance and blood gas analysis (B03.016.011), and hematocrit evaluation (A12.05.117) as part of a complete blood count (B03.016.002) to determine the nature and scope of infusion therapy [346, 347, 356, 357, 360, 361].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• All patients diagnosed with febrile catatonia are recommended to undergo determination of antibodies to glutamate NMDA receptors in blood serum (A12.06.064) to rule out autoimmune NMDA encephalitis [348, 359, 360, 361].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: In a number of cases, cerebrospinal fluid analysis may be required to rule out encephalitis and meningoencephalitis of various etiologies. Since 2007, more than 500 cases of so-called autoimmune anti-NMDA receptor encephalitis have been described, presenting with psychotic symptoms, including catatonic disorders and autonomic disturbances with hyperthermia [362, 363]. The diagnosis of autoimmune encephalitis is based on detecting antibodies to glutamate NMDA receptors in the blood and cerebrospinal fluid (CSF). There are several features that, even prior to serological analysis of the CSF, allow for differential diagnosis of autoimmune anti-NMDA receptor encephalitis from febrile schizophrenia and neuroleptic malignant syndrome with a high degree of probability. These include young age and female predominance, high comorbidity with tumors (teratoma or carcinoma), presence of seizures and dyskinesias, cognitive impairment with memory deficits, mild pleocytosis with lymphocytic predominance in the cerebrospinal fluid, and a high frequency (up to 45%) of MRI abnormalities revealing hyperintense signals in various brain structures, as well as diffuse EEG changes [348, 359, 360, 362–364].

2.4 Instrumental Diagnostics

There are no instrumental diagnostic methods specific for schizophrenia.

• In patients with schizophrenia in whom cardiovascular pathology cannot be ruled out with a high degree of reliability based on anamnesis, physical and neurological examination, and laboratory test results, it is recommended to perform exercise electrocardiography (ECG) (A12.10.001) to rule out this pathology [31].

Level of evidence – 5, Grade of recommendation – C.

• In patients with schizophrenia in whom anamnesis, physical and neurological examination, and laboratory test results reveal signs of potential cardiac arrhythmias, it is recommended to perform Holter ECG monitoring (A05.10.008) to rule out this pathology [31, 267].

Level of evidence – 3, Grade of recommendation – B.

• In patients with schizophrenia in whom anamnesis, physical and neurological examination, and laboratory test results reveal signs of potential neurological pathology or organic brain damage, it is recommended to perform electroencephalography with provocative tests (A05.23.001.002), echoencephalography (A04.23.002), and brain magnetic resonance imaging (A05.23.009) to rule out this pathology [31].

Level of evidence reliability – 5, Level of recommendation consensus – C.

2.5 Other Procedures

• To clarify the clinical status and specific features of a patient with schizophrenia, it is recommended to:

determine the presence and severity of affective symptoms [32];

Level of evidence reliability – 5, Level of recommendation consensus – C.

determine the presence and severity of thought and speech disorganization [33–35];

Level of evidence – 3, Grade of recommendation – B.

determine the presence and severity of self-directed aggressive and/or suicidal thoughts and tendencies [36];

Level of evidence – 3, Grade of recommendation – B.

determine the presence and severity of aggressive behavior [37];

Level of evidence reliability – 5, Level of recommendation consensus – C.

perform psychological testing – during initial diagnosis (to clarify the diagnosis) and subsequently, when determining disease dynamics (if necessary) [30, 31];

Level of evidence reliability – 5, Level of recommendation consensus – C.

performing a neuropsychological assessment (including the clarification of impairments in memory, attention, information processing speed, and problem-solving behavior) in order to detect cognitive impairment (if necessary) (B03.035.004) [38].

Level of evidence reliability – 5, Level of recommendation consensus – C.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1. Psychotic episode (first-line therapy)

• All patients with an established diagnosis of schizophrenia are recommended psychopharmacological treatment to relieve the symptoms of schizophrenia. The baseline pharmacological class for treating both acute symptoms of schizophrenia and for long-term relapse-prevention therapy consists of antipsychotic drugs (neuroleptics) [30, 39-41, 175].

Level of evidence – 1, Strength of recommendation – B.

Comment: The goals and strategies of pharmacotherapy are determined by the characteristics of psychopathological symptoms, including the severity of its individual dimensions, as well as the severity and stage of the disease course. Despite the fact that all modern guidelines recommend adhering to monotherapy, the diversity of clinical manifestations of schizophrenia and numerous comorbid conditions in reality often require the use of combinations of various drugs, which significantly increases the risk of drug interactions, side effects, and overall premature mortality in patients. In these cases, side effects and clinical efficacy should be evaluated more frequently [42-45, 308, 309].

3.1.1 First psychotic episode of schizophrenia (manifest attack)

• As first-choice drugs for patients with a first episode of schizophrenia to relieve symptoms, both first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) are recommended [30, 40, 42-45, 268, 269].

Level of evidence – 1, Strength of recommendation – B.

• Due to the lower risk of extrapyramidal symptoms in patients with a first episode of schizophrenia, the prescription of SGAs is recommended to relieve symptoms [46-50].

Level of evidence – 2, Strength of recommendation – C.

Comment: In patients with a first episode of schizophrenia, the effective dose of an antipsychotic drug may be lower compared to chronic patients [40, 48-50]. Antipsychotic therapy should be carried out with great caution due to the high risk of developing extrapyramidal symptoms (EPS). In this regard, gradual dose titration of the antipsychotic with the aim of using the minimum effective dose possible is optimal. Particular attention at this stage of the disease should be paid to creating an optimal drug regimen for conducting psychotherapeutic and social rehabilitation measures, as well as for building adherence to therapy [257, 310].

3.1.2 Schizophrenia with recurrent psychotic episodes (relapse)

• All SGAs and FGAs are recommended as antipsychotic therapy in patients with schizophrenia to relieve acute psychotic symptoms (Appendices B2 and B3) [41, 49-51].

Level of evidence – 2, Strength of recommendation – C.

Comment: The choice of antipsychotic therapy should be based on previous treatment experience, taking into efficacy and tolerability of previous therapy methods, the dosage form of the drug, the presence of comorbid mental and somatic disorders, and potential drug interactions with concomitant therapy. Unfortunately, evidence-based studies examining the differentiated effects of various antipsychotics on individual clinical syndromes and forms of schizophrenia have not been conducted [41,42,216,217]. Most of them were conducted in patients with the paranoid form of schizophrenia. However, there is some evidence regarding the treatment of patients with catatonia (catatonic form of schizophrenia), a high proportion of individual domains (factors or dimensions) of schizophrenia symptoms, including depressive, negative (residual and simple forms of schizophrenia) and cognitive (thought disorder) symptoms, as well as in treatment-resistant cases [44-51,214-218,402] (see corresponding sections of the guidelines). Evidence-based studies on the therapy of hebephrenic and other early-onset (nuclear) forms of schizophrenia have not been conducted. Nevertheless, there is expert opinion regarding the advantage in these cases of FGAs and SGAs possessing a more potent global antipsychotic effect (haloperidol**, zuclopenthixol**, clozapine, olanzapine**, risperidone**).

• SGAs are characterized by a lower risk of neurological (extrapyramidal) side effects, particularly tardive dyskinesia and neuroleptic malignant syndrome (NMS), and are recommended in patients with schizophrenia with high sensitivity to the development of EPS for psychopharmacotherapy [41, 43, 45].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• SGAs are recommended for prescription in patients with schizophrenia, including for the purpose of improving compliance and adherence to therapy [41, 51-54].

Level of evidence – 1, Strength of recommendation – B.

Comment: SGAs have certain advantages regarding better compliance and premature discontinuation of therapy [41, 51-54].

• Certain SGAs may have an advantage over other SGAs and FGAs regarding overall efficacy in schizophrenia patients and in specific clinical situations in which they should be recommended for more successful treatment and a lower risk of adverse effects (Appendix B4) [41, 42, 48].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• In case of insufficient therapeutic efficacy, switching the drug in patients with schizophrenia to reduce persistent psychopathological symptoms is recommended only after therapy with the current antipsychotic (ATX: N05A), provided it is well tolerated, has been administered for at least 4-6 weeks at an optimal therapeutic dosage [30, 40-42].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: As an intermediate step in the absence of a therapeutic effect, it is advisable to increase the antipsychotic dose to the maximum allowed in the drug instructions approved for use in the Russian Federation (Appendix B3).

Antipsychotic therapy is quite frequently accompanied by the development of extrapyramidal symptoms (EPS). In this case, therapeutic measures must be applied to relieve them (see section "Management of Side Effects" and Table 3). If EPS persists subsequently despite its correction, switching to another antipsychotic with a more favorable neurological tolerability profile is advisable (Appendices B3, B4).

• If a therapeutic effect is achieved in patients with schizophrenia receiving FGAs without the development of severe side effects, switching from FGAs to SGAs for further therapy is not recommended [43-47].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• In case of FGA ineffectiveness in schizophrenia, switching to SGA therapy is recommended to reduce psychopathological symptoms (Appendix B3) [41, 42, 50].

Level of evidence – 2, Strength of recommendation – B.

Comment: In case of ineffectiveness of the second course of an antipsychotic drug, psychotic symptoms are regarded as treatment-resistant, requiring special therapeutic measures (see section "Treatment-Resistant Schizophrenia" and Appendix B3).

The most important parameter determining the choice of an antipsychotic is the expected ratio of efficacy and tolerability of the drug in a particular patient. In certain clinical situations, there is evidence of the superiority of certain antipsychotic drugs. These data for SGAs are summarized in Appendix B4.

• Clozapine as a first-choice drug is recommended in patients with schizophrenia to relieve treatment-resistant psychopathological symptoms [40, 41, 43-45, 55-57, 279, 399].

Level of evidence – 1, Strength of recommendation – A.

• Clozapine as a first-choice drug is recommended in patients with schizophrenia to reduce suicide risk [55-58, 398].

Level of evidence – 2, Strength of recommendation – A.

• In neuroendocrine disorders associated with hyperprolactinemia, to prevent their worsening in patients with schizophrenia, it is not recommended to prescribe FGAs, amisulpride, and risperidone** [40, 41, 43-45, 273].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• In cardiac arrhythmias, to prevent an increase in the QTc interval in patients with schizophrenia, it is not recommended to prescribe sertindole**, ziprasidone, and thioridazine** [40, 41, 43-45, 267, 275, 276].

Level of evidence – 3, Grade of recommendation – B.

• In seizure disorders or lowered seizure threshold in patients with schizophrenia, it is not recommended to prescribe clozapine and chlorpromazine** [40, 41, 43-45].

Level of evidence – 2, Strength of recommendation – B.

Comment: When initially choosing an antipsychotic drug, the patient's individual somatic and neurological status should be considered. Complete symptom reduction cannot be expected in all psychotic episodes. This applies only to the treatment of acute psychoses, which are predominated by sensory delusions and circular affect. When paranoid symptoms account for a large proportion and there are signs of a continuous course, only partial reduction of psychosis can be expected [40]. In cases of unstable remission achieved during maintenance or stabilizing antipsychotic therapy, the doses of the effective antipsychotic remain unchanged or are slightly reduced [30, 40, 41].

3.1.3 Drug dosages

• In the treatment of an acute episode of schizophrenia, in order to minimize the risk of side effects, it is recommended to consider using lower therapeutic dosages of drugs [30, 41, 42, 173, 175, 277].

Level of evidence – 1, Strength of recommendation – B.

Comment: When initially prescribing antipsychotic pharmacotherapy, a thorough allergy history must be taken and, if possible, a small test dose should be used to prevent severe allergic reactions and neuroleptic malignant syndrome (NMS). When treating with either first-generation or second-generation antipsychotics, the therapeutic dosage of the drug can be reached quite quickly if necessary. In many cases, dose escalation should not be rapid to prevent potentially dangerous side effects.

• Rapid dose escalation strategies, the use of high loading doses, and high dosages to increase treatment response in patients with schizophrenia are not recommended, as they have not demonstrated greater therapeutic efficacy but are associated with an increased number of side effects [30, 41, 43, 173, 175, 277].

Level of evidence – 1, Strength of recommendation – B.

Comment: In some cases, there are recommendations for rapid dose escalation (e.g., quetiapine** up to 800 mg/day over 4 days with steps of 200 mg/day), which allows for a significant reduction of acute psychotic symptoms by day 4-5 of therapy [333].

• In patients with schizophrenia, in order to achieve an optimal therapeutic effect, it is recommended to use antipsychotics at dosages in the range of 400-800 mg chlorpromazine equivalents (CPE) (A3.2, Tables 1 and 2) [57-61, 277, 278].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: Daily dosages below 300 mg CPE are in most cases insufficient to provide an optimal therapeutic effect, while dosages above 900 mg CPE do not provide an increase in effect compared to the recommended ones [57].

3.2. Treatment resistance

• In patients with treatment-resistant schizophrenia—i.e., in the absence of effect from two adequate courses of antipsychotic pharmacotherapy lasting 4-6 weeks—clozapine is recommended as a first-line choice for the relief of psychotic symptoms (Appendix B3) [42, 54, 62].

Level of Evidence – 1, Grade of Recommendation – A.

• In patients with treatment-resistant schizophrenia, to increase treatment efficacy, a target clozapine dosage in the range of 100-600 mg/day is recommended [42, 54, 62, 234, 279].

Level of evidence – 2, Strength of recommendation – B.

Comment: Treatment-resistant schizophrenia is diagnosed in the absence of a reduction in the severity of psychopathological symptoms and/or other key symptoms during therapy with two antipsychotics of different chemical classes (at least one of the antipsychotics must be a second-generation antipsychotic) at recommended therapeutic dosages for at least 6-8 weeks for each drug [42].

The first step when treatment resistance is indicated should be adherence monitoring, including, if possible, by determining drug concentrations in blood plasma [46-50]. Patients receiving clozapine therapy require monitoring for hematological and cardiological side effects, as well as monitoring for possible EEG changes (decreased seizure threshold). In international clinical studies of clozapine, a daily dosage in the range of 100-900 mg was used; a similar daily dose range was also recommended in the product monograph for the original clozapine drug previously registered in the Russian Federation [45, 133, 135, 234]. In certain cases, in the absence of a therapeutic effect, other treatment alternatives may be used, such as other second-generation antipsychotics, augmentation strategies (antidepressants, mood stabilizers, adrenergic agents) taking into account the presence of key target symptoms [45, 63-73, 311]. In addition, combination therapy of antipsychotics with ECT, as well as a course of TMS or insulin coma therapy, is possible [63-73, 311, 312, 313].

3.3. Negative symptoms

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: To more accurately identify negative symptoms in patients with schizophrenia, the Brief Negative Symptom Scale (BNSS) can be used (Appendix G2) [75]. The first diagnostic step in this case is to identify potential manifestations of psychosis that may "mask" negative symptoms (Appendix B5). In this case, the only therapeutic choice should be to intensify antipsychotic therapy. Negative symptoms must also be differentiated from extrapyramidal side effects of antipsychotic therapy (primarily akinesia) and from manifestations of depression. Clinical assessment can be supplemented by using the PANSS scale (Appendix G1), the Calgary Depression Scale for Schizophrenia (Appendix G3), and the SAS scale for extrapyramidal side effects (Appendix G7) [41, 74].

Negative symptoms are considered persistent if they are of moderate to high severity for 6 months or more in the absence and/or minimal severity of positive and depressive symptoms, as well as pseudoparkinsonism [74, 314, 402].

Therapeutic tactics in patients with primary persistent negative symptoms and a long duration of illness with multiple psychotic episodes require clinical evaluation regarding the possibility of switching from first-generation to second-generation antipsychotics (Appendix B5) [76, 319, 402]. The clinical evaluation of the feasibility of switching from first-generation to second-generation antipsychotics is based on a careful weighing of risks and potential benefits. First and foremost, this relates to assessing the risk of exacerbation of psychotic symptoms. When a decision is made to change treatment, the switch between drugs should be cross-tapered [41]. In cases of ineffectiveness of the prescribed second-generation antipsychotic regarding dominant negative symptoms in patients with a long duration of illness, further therapeutic interventions should be carried out in accordance with the algorithm (see Appendix B5).

• In patients with a first episode of schizophrenia with persistent negative symptoms, the administration of cariprazine** is recommended for their correction [77, 78].

Level of Evidence – 1, Grade of Recommendation – A.

• In patients with schizophrenia and primary negative symptoms, the use of amisulpride at a dose of 50-300 mg/day is recommended for their correction [79, 80].

Level of evidence – 2, Strength of recommendation – B.

• In patients with schizophrenia and predominantly negative symptoms, the use of olanzapine** and quetiapine** is recommended for their correction, with some limitations on efficacy data [81-82].

Level of Evidence – 2, Grade of Recommendation – A.

• In patients with schizophrenia and predominantly negative symptoms, the combined use of #mirtazapine (30 mg/day) and #mianserin (15 mg/day) with antipsychotic drugs is recommended for their correction [83, 84, 292, 293].

Level of Evidence – 1, Grade of Recommendation – A.

Comment: To augment the anti-negative effect of antipsychotic drugs in resistant negative symptoms in patients with schizophrenia, antidepressants and other agents with pronounced adrenolytic action (alpha-2 adrenergic receptor blockers) are more effective [311, 402]. When carrying out such therapy, careful blood pressure monitoring is required.

• For the treatment of persistent negative symptoms when other treatment methods are insufficiently effective, it is recommended to consider the use of TMS [72, 128, 397].

Level of evidence – 2, Strength of recommendation – B.

Comments: Non-invasive neuromodulatory stimulation techniques aimed at reducing the severity of negative symptoms in schizophrenia target the frontal regions, specifically the dorsolateral prefrontal cortex. The positive effect of TMS is associated with a higher frequency (10-20 Hz) and intensity (100-110% of the motor threshold) of stimulation, as well as a longer course of therapy (>3 weeks) [128, 397, 403]. The effect of TMS on negative symptoms in schizophrenia is rated as moderate (effect size 0.27-0.63). These figures exceed those for antipsychotic drugs (0.17-0.21), which highlights the promise of this therapeutic method for patients with schizophrenia [128, 397, 403].

In the event of the inefficiency of individual therapeutic steps, subsequent clinical decisions in first-episode and chronic patients with predominant negative symptoms are made in accordance with the treatment algorithm (Appendix B5).

3.4. Cognitive symptoms

• In patients with schizophrenia presenting with cognitive impairment, the prescription of SGA is recommended for their correction [85-87].

Level of Evidence – 1, Grade of Recommendation – A.

Comments: The presence of cognitive impairment is one of the main barriers to the social and occupational rehabilitation of patients with schizophrenia [38-40]. Antipsychotic drugs have small to moderate efficacy regarding cognitive impairment [41, 85-87].

The results of comparing FGA and SGA are contradictory. Some studies report data on the superiority of SGA, while others report no differences. However, none of the studies report data on the superiority of FGA [41, 86, 87]. There is limited evidence regarding the efficacy of certain anticholinesterase agents (#donepezil and #galantamine[1] [2]) and antidepressants (#fluvoxamine) when added to an antipsychotic [88, 260, 261, 292, 293, 303]. Studies of left-sided or bilateral prefrontal high-frequency TMS for the correction of cognitive dysfunction in schizophrenia have shown contradictory results; a moderate degree of short-term improvement was demonstrated only for working memory [403].

3.5. Depressive symptoms, suicide risk assessment

• When switching antipsychotic medication in patients with schizophrenia presenting with depressive symptoms, it is recommended to prioritize agents with a prominent thymoleptic component of action, such as quetiapine**, lurasidone**, or other SGAs with the exception of risperidone** (Appendix B6) for symptom correction [109-113, 315].

Level of evidence – 2, Strength of recommendation – B.

Comment: Data on the antidepressant effect of antipsychotic drugs in remission are limited. In most antipsychotic trials in schizophrenia, the assessment of depressive symptoms was not a primary objective, their severity was not specified in inclusion criteria, and depression reduction was not considered a criterion for treatment efficacy [41, 106, 113].

• The prescription of antidepressants for the treatment of depressive symptoms in patients with schizophrenia is recommended to be restricted primarily to so-called post-psychotic depressions when other therapeutic measures are ineffective [40, 41, 108, 114-116].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• If it is necessary to prescribe antidepressants to treat depressive symptoms in schizophrenia, the choice of SSRIs (ATX code: N06AB) is recommended, and if they are ineffective – SNRIs (ATX code: N06AX) and TCAs (ATX code: N06AA) (Appendix B6) [108, 109-117, 170, 315].

Level of evidence – 2, Strength of recommendation – B.

Comment: The prescription of antidepressants for the treatment of depressive symptoms in patients with schizophrenia should be limited primarily to so-called post-psychotic depressions when other therapeutic measures are ineffective [41, 108, 114-117, 121]. First-line drugs are SSRIs. If no effect is observed within 4-6 weeks, the antidepressant should be replaced with a drug having a different mechanism of action (SNRIs /ATC code N06AX – other antidepressants/, tricyclic antidepressants/ATC code N06AA – non-selective monoamine reuptake inhibitors/, #mirtazapine [115-125]. In combination therapy, to prevent drug interactions, it is advisable to avoid using drugs that share a common metabolic pathway via cytochrome P450 isoenzymes [404]. An alternative option at this stage is replacing the antipsychotic with quetiapine**, aripiprazole, or lurasidone** while continuing the previous antidepressant therapy [40, 109-113, 121].

• In cases of treatment-resistant depressive symptoms, the implementation of anti-resistance measures is recommended for their correction in patients with schizophrenia [40, 108, 121] (Appendix B6).

Level of evidence reliability – 5, Level of recommendation consensus – C.

• For the treatment of persistent depressive symptoms, the use of TMS is recommended [70-72, 397, 403].

Level of Evidence – 3, Strength of Recommendation – C.

• For the treatment of resistant depressive symptoms, it is recommended to consider the use of ECT [64, 70-72].

Level of Evidence – 3, Strength of Recommendation – C.

Comment: If depressive symptoms persist for 6-8 weeks, it is recommended to proceed with sequential anti-resistance measures, including TMS and ECT [64, 70-72, 108, 121, 128, 397]. High-frequency TMS (10-15 Hz) of the left DLPFC is not inferior in its thymoleptic properties to traditional methods of psychopharmacotherapy for depression within schizophrenia, and also possesses anti-resistance effects [70-72, 397, 403]. If the latter are not feasible, one should continue adjusting psychopharmacotherapy using other antipsychotics (amisulpride, ziprasidone, flupentixol**, clozapine, sulpiride**, paliperidone**, sertindole**, olanzapine**, cariprazine**) and antidepressants, or adjuvant therapy with antiepileptic drugs (valproic acid** in flexible doses of 500-3000 mg/day or carbamazepine** in doses of 200-1600 mg/day) [108, 262, 263, 296, 297, 305, 306, 315, 391, 412, 413]).

• When suicide risk factors are identified in patients with schizophrenia, especially when associated with existing psychotic symptoms, it is recommended to consider the use of clozapine to reduce suicide risk [129-135, 398].

Level of evidence – 2, Strength of recommendation – B.

• In the presence of suicidal risk, to reduce it in patients with schizophrenia, especially in the presence of affective fluctuations in the course of the disease, it is recommended to use adjuvant therapy with #lithium carbonate in a flexible dose from 600 to 1500 mg/day under the control of blood plasma lithium concentration in the range from 0.4 to 1.0 mmol/l [136, 264, 295].

Level of Evidence – 1, Grade of Recommendation – A.

Comments: Determining suicide risk in patients with schizophrenia is a primary diagnostic step [41, 108, 132, 316]. It includes a targeted clinical and anamnestic examination followed by the identification and dynamic assessment of suicide risk factors. For this purpose, the SAD PERSONS scale and the Columbia-Suicide Severity Rating Scale can be used (Appendices G5 and G6) [132].

Level of Evidence – 4, Strength of Recommendation – C.

3.6. Agitation and aggression

• To monitor the patient's condition and establish compliance at the initial pre-psychopharmacological stage of managing a patient with schizophrenia presenting with agitation, it is recommended to consider the use of the de-escalation technique (Appendix B7) [137-139].

Level of Evidence – 3, Strength of Recommendation – C.

Comment: De-escalation techniques include several components simultaneously. First of all, it involves continuous risk assessment and situation control while modeling a safe environment around the patient. An essential condition is maintaining a safe distance for the patient and staff, avoiding provocations and coercion, treating the patient with respect, showing empathy, and identifying the patient's needs. It is necessary to establish verbal contact, try to distract the patient, and persuade them to rethink the situation (Appendix B7) [135-137].

• Oral, buccal (orodispersible tablets) psychopharmacotherapy in schizophrenia is recommended as a first step to establish a therapeutic alliance and improve treatment adherence, provided it is applicable (compliance is present) (Appendix B7) [140-143, 317].

Level of evidence – 2, Strength of recommendation – B.

• Lorazepam** is recommended in patients with schizophrenia for the treatment of agitation; the drug is preferred among other benzodiazepine derivatives due to its short half-life and absence of a depressing effect on the respiratory system [41, 137, 151, 153, 243].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• To minimize side effects, the treatment of agitation in patients with schizophrenia using low-potency antipsychotics (chlorpromazine**, levomepromazine**) is recommended to be carried out with caution due to their poorer tolerability [41, 137, 144].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comments: In cases of mild agitation and patient compliance, oral medications with a sedative component may be preferred. In this case, benzodiazepine derivatives (primarily lorazepam**), #promethazine, and antipsychotics demonstrate comparable efficacy in treating agitation and aggression (Appendix B7) [137, 144-147, 219]. At this stage of therapy, the patient requires hourly monitoring [137].

• Parenteral therapy for the management of psychotic agitation in patients with schizophrenia is recommended when oral therapy is ineffective, impractical, or due to initial severity of symptoms [41, 137, 145, 147-151].

Level of evidence – 2, Strength of recommendation – B.

• Parenteral forms of SGA are recommended for patients with schizophrenia to treat psychotic agitation, as they are not inferior in efficacy to intramuscular haloperidol**, but cause fewer neurological side effects [152-155].

Level of evidence – 1, Strength of recommendation – B.

Comment: Therapeutic approaches for agitation and aggression must be differentiated. Manifestations of aggression, as well as conditions with a high risk of its development, require urgent therapeutic interventions. These include rapid tranquilization (RT), and, if necessary, physical restraint or seclusion [41, 137, 156, 157]. Concurrently, behavioral therapy techniques should be applied. In cases of mild aggression (verbal aggression, etc.), RT may be inappropriate. Performing RT requires skills in assessing risks associated with potential deep sedation (development of arterial hypotension and respiratory depression) [137, 157]. It is also desirable to have technical equipment necessary for emergency management of side effects, including the availability of flumazenil (a benzodiazepine receptor antagonist) [157].

At the beginning of therapy, drugs should be prescribed at the lowest effective doses, which can be gradually increased if necessary. More severe forms of agitation require parenteral therapy (Appendix B7) [41, 137, 158]. When arresting agitation, it is desirable to achieve the therapeutic effect at the level of calming or mild sedation. If necessary, in cases of severe refractory agitation with aggressive manifestations, achieving deep sedation or even anesthesia is permitted [41, 137, 159, 160]. The use of RT to control agitation is considered a last resort [137, 157]. However, in extremely severe agitation associated with risks of aggression, it should be used immediately.

• To control agitation in patients with schizophrenia when intramuscular monotherapy is ineffective, combined intramuscular psychopharmacotherapy is recommended [41, 42, 137, 157].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: When using this combination, the increased risk of side effects must be taken into account, requiring continuous patient monitoring. Commonly used combinations include haloperidol** with benzodiazepine derivatives (primarily recommended is lorazepam**) or #promethazine at a dosage of up to 50 mg [146, 150, 157, 219, 282].

• Due to the risk of respiratory failure and to ensure the safety of therapy in patients with schizophrenia, the combined use of intramuscular benzodiazepine derivatives with clozapine is not recommended [41, 137].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• When combined parenteral intramuscular therapy is ineffective for controlling agitation in patients with schizophrenia, the intravenous administration of benzodiazepine derivatives or antipsychotics (haloperidol**, chlorpromazine**, droperidol**) is recommended [137, 159, 162, 225, 232, 239-240, 243, 290, 291].

Level of Evidence – 2, Grade of Recommendation – A.

Comment: When using the intravenous route, an infusion pump (drip method) is preferred. Intravenous administration of drugs requires continuous bedside staff monitoring, ECG, blood pressure, and oxygen saturation monitoring [137, 159, 160]. Due to the risk of QT interval prolongation, ECG monitoring is strictly mandatory when using droperidol** intravenously [160, 162]. These requirements are feasible in an intensive care unit setting. In cases of resistant psychotic agitation, subsequent therapeutic steps are decided collegially, including involving specialists from other fields (intensivists and neurologists) [160-163].

In this case, further management of the patient is carried out in a psychointensive care unit. Additional examination of the patient is advisable to potentially clarify the diagnosis. One of the main therapeutic options is the use of ECT, especially in the presence of affective symptoms, catatonic symptoms, and a history of a good response to it in the past [41]. As alternative therapeutic options, the use of #dexmedetomidine and #ketamine** should be considered [137, 163, 164, 220, 255].

3.7. Catatonic symptoms

• As a first step in managing patients with schizophrenia presenting with catatonic symptoms, excluding other causes of their development is recommended to prescribe rational therapy [41].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: Catatonia is considered an independent multi-etiology syndrome developing in certain psychiatric and neurological disorders, as well as due to a number of metabolic and toxic disorders. When performing a differential diagnostic assessment of a patient with catatonia, encephalitides of various origins (including anti-NMDA receptor encephalitis) should be excluded first. As an additional tool, along with immunological studies, a benzodiazepine test can be used with a single parenteral dose of benzodiazepines, against which the severity of catatonia is assessed. If symptoms decrease in severity, it is presumed that their nature is endogenous [165, 166]. The Bush-Francis Catatonia Rating Scale is used to assess the severity of catatonic symptoms (Appendix G8).

• In catatonia, to reduce muscle tone, benzodiazepine derivatives (diazepam**, lorazepam**) are recommended as drugs of choice [165-167, 239, 243].

Level of evidence – 1, Strength of recommendation – B.

Comment: There is no conclusive evidence on the efficacy of bromdihydrochlorphenylbenzodiazepine** in treating catatonic symptoms, but there are case reports demonstrating its positive effect [168, 238].

With a good response to therapy with benzodiazepine derivatives, the effect usually develops within a few days [166, 167, 168].

• If there is no/insufficient effect within a few days of therapy and with the aim of rapid resolution of persistent symptoms (e.g., malignant catatonia), considering earlier application of ECT is recommended [169, 389].

Level of evidence – 3, Grade of recommendation – B.

Comment: Most national clinical guidelines on ECT recommend its use in catatonia using a bilateral technique, with the possibility of administering the first 3–7 procedures daily [169]. It is known that the efficacy of ECT in catatonia is quite high, and in most cases, when applied to catatonia developing within the framework of acute psychosis, it is possible to completely abort the symptoms.

• To treat catatonic symptoms and in case of insufficient efficacy of other therapy methods, considering the use of TMS is recommended [393, 394, 395, 396].

Level of Evidence – 3, Strength of Recommendation – C.

Comment: Electromagnetic pulse modulation of neuronal activity in brain regions such as the orbitofrontal cortex allows indirect modulation of subcortical structures involved in the pathogenesis of catatonia. Data on the use of TMS of the supplementary motor area and left dorsolateral prefrontal cortex in catatonia in patients with schizophrenia are limited to two studies, including one small crossover RCT [393, 395], and individual case reports [393, 394]. In most cases, high-frequency stimulation at 10–20 Hz was used, the number of pulses per session ranged from 800 to 3000, and the number of sessions – from 7 to 108 [395, 396].

• To treat catatonic symptoms in schizophrenia, considering the use of SGAs with a favorable neurological tolerability profile, as well as chlorpromazine**, is recommended [41, 165, 233].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: In general, prescribing antipsychotics for catatonic symptoms in the acute period of schizophrenia is considered inappropriate due to the high risks of symptom exacerbation and the development of neuroleptic malignant syndrome (NMS). An exception can be made for antipsychotics with a good neurological tolerability profile (clozapine, to a lesser extent chlorpromazine**), which are used at very low therapeutic doses and at later stages of therapy [41].

3.7.1 Lethal catatonia

• All patients with LF are recommended to receive infusion therapy with plasma-substituting crystalloid and colloid solutions (ATX group: Blood substitutes and perfusion solutions) in order to restore circulating blood volume and correct water-electrolyte, acid-base balance (ABB), and hemodynamic disorders [318, 343-347].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: Treatment is carried out according to the principles of intensive care aimed at restoring basic parameters of homeostasis, hemodynamics, and vital organ function under the control of laboratory parameters (ABB, protein and water-electrolyte balance, circulating blood volume), as well as relieving psychomotor agitation and preventing the development of cerebral edema.

• All patients with LF are recommended to be prescribed high doses of benzodiazepine derivatives in order to relieve agitation and catatonic symptoms:

lorazepam** [346-348, 365-368]

Level of Evidence – 4, Strength of Recommendation – C.

diazepam** [346,347, 352,353].

Level of evidence reliability – 5, Level of recommendation consensus – C.

bromdihydrochlorophenylbenzodiazepine** [347, 348].

Level of Evidence – 4, Strength of Recommendation – C.

• All patients with LF are not recommended to be prescribed antipsychotic medications for the purpose of relieving agitation and catatonic disorders [346, 347, 353, 370].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: The prescription of antipsychotic drugs in LF to relieve psychomotor agitation and catatonic disorders may lead to a deterioration in the mental and somatic condition of patients [346, 347, 353]. Data on the efficacy of chlorpromazine** are contradictory and based on non-randomized and uncontrolled studies [343, 348].

• Patients with LF, in the absence of an effect from benzodiazepine derivatives, are recommended to undergo electroconvulsive therapy (ECT) to relieve catatonic symptoms [343, 344, 346, 347, 353, 371, 372].

Level of Evidence – 3, Strength of Recommendation – C.

Comment: ECT is an effective treatment method for LF, exerting a global antipsychotic effect [405]. ECT is performed after preliminary correction of water-electrolyte disturbances and restoration of hemodynamics. Timely application of ECT allows for a rapid reduction of catatonic symptoms with normalization of body temperature and somatovegetative parameters. ECT is ineffective in severe cases where the patient's condition is determined by amentia, obtundation, stupor, or coma arising against the background of increasing cerebral edema phenomena [346, 347].

• Patients with LF, in the absence of an effect from infusion therapy, are recommended to undergo standard extracorporeal detoxification and immunomodulation therapies:

  plasmapheresis (A18.05.001) [347, 348, 373, 374].

  hemosorption (A18.05.006) [344, 346, 375, 376].

Level of evidence reliability – 5, Level of recommendation consensus – C.

3.8. Long-term (maintenance/relapse-prevention) therapy

• Antipsychotic medications in patients with SZ are recommended for use as long-term relapse-prevention therapy to prevent psychosis relapses [30, 39-45].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: Antipsychotic drugs are effective agents for relapse prevention, reducing the probability of their occurrence by several times compared to placebo [30, 39-45].

• For long-term therapy in SZ, FGAs and SGAs are recommended [170,171].

Level of Evidence – 1, Grade of Recommendation – A.

Comment: FGAs and SGAs do not differ from each other in the degree of symptom reduction during long-term therapy [170, 171]. There is a body of data favoring certain SGAs in terms of discontinuation rates and relapse prevention (Appendix B3) [170-172].

• To reduce the risk of neurological side effects (particularly tardive dyskinesia) during long-term therapy in patients with SZ, the use of SGAs is recommended (Appendix B3) [170-172].

Level of Evidence – 1, Grade of Recommendation – A.

• During long-term therapy, when secondary negative symptoms become less pronounced, it is recommended to consider the use of certain SGAs that have a number of advantages in these clinical situations in order to correct primary negative symptoms (Appendix B5, algorithm 5) [41, 170].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• During long-term therapy in patients with SZ, to increase its safety, it is recommended to provide continuous monitoring, early detection, and treatment of tardive dyskinesia and metabolic side effects, which have the greatest impact on the patient's health status, for timely identification and correction [41, 170].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• When conducting long-term relapse-prevention therapy in patients with SZ, to maintain therapeutic continuity, it is recommended to use the antipsychotic medication that demonstrated the best efficacy and tolerability in the specific patient during the acute episode and state stabilization phases, i.e., in the early stages of therapy [41, 42, 170].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: The selection of an antipsychotic drug for each patient must be carried out individually, taking into account the history of previous use of certain drug groups and the side-effect profile [41, 170].

• In patients with a first episode, continuous antipsychotic therapy for at least one year is recommended to prevent a potential relapse [30, 41-45, 170].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• In patients with multiple episodes, maintenance therapy for 2-5 years is recommended to prevent relapse (lifelong therapy in cases of persistent symptoms and frequent relapses) [30, 41-45, 170, 283, 284].

Level of Evidence – 4, Strength of Recommendation – C.

Comment: If therapy is discontinued within 1-2 years after an acute psychosis, there is a high risk of relapse. First of all, long-term multi-year therapy is indicated for continuous schizophrenia, as well as malignant and early-onset forms. In episodic courses, the duration of relapse-prevention therapy is determined by the principle of reasonable sufficiency. Nevertheless, the duration of treatment must be determined individually, taking into account the patient's motivation, psychosocial situation, and several other factors. In patients with suicide attempts, gross aggressive behavior, and frequent relapses, continuing antipsychotic therapy for an indefinitely long period is also recommended [30, 41-45, 170].

• In all cases of a relapsing chronic course of schizophrenia, continuous antipsychotic pharmacotherapy is recommended to prevent relapses [30, 41-45, 170, 285].

Level of evidence – 2, Strength of recommendation – B.

Comment: Intermittent therapy strategies may only be suitable for patients who refuse a continuous maintenance regimen or have contraindications to continuous maintenance therapy.

• For long-term therapy of SZ to prevent schizophrenia relapses, the use of long-acting injectable antipsychotics is recommended [41, 170, 286, 287].

Level of Evidence – 4, Strength of Recommendation – C.

Comment: It is not possible to identify reliable differences in efficacy between oral drugs and depot formulations [41, 170]. At the same time, there is currently sufficient evidence supporting the use of depot antipsychotics for long-term SZ therapy. Long-acting injectable antipsychotics have a number of advantages:

– Maximum continuity of therapeutic effect and reliable control over antipsychotic intake, which reduces the need for the physician to monitor treatment adherence;

– More stable and lower blood concentration of the neuroleptic (reduction of the risk of "peak" side effects);

– Safer achievement of the minimum effective dose principle (stepwise reduction);

– A more convenient drug regimen for patients, which has important psychotherapeutic significance as it mitigates the feeling of dependence on medications;

– Avoidance of gastrointestinal absorption issues and first-pass hepatic metabolism effects (more predictable metabolism and rarer drug interactions);

– Reduction of the risk of accidental or intentional overdose.

Disadvantages of long-acting antipsychotics include reduced treatment flexibility, a long period for titrating the optimal dose, a long elimination half-life in case of adverse reactions, and local injection-site reactions.

Treatment with long-acting injectable antipsychotics (LAIAs) is usually initiated in an inpatient setting immediately after the resolution of acute psychotic symptoms. While continuing oral medication, an intramuscular injection of the drug is administered at the minimum dose. If the patient has previously received corrective agents, they are not discontinued. In case of good tolerability (no side effects during the 1st week of treatment), the dose of the long-acting drug is gradually increased, and the oral tablets are discontinued. The goal of treatment is to maintain the patient's optimal functional level using the minimum effective dose. After stabilization of the mental state, the neuroleptic dose can be gradually reduced in two ways: either by decreasing the single dose or by increasing the interval between injections (the latter rule does not apply to long-acting risperidone** and paliperidone**) (Appendix A3.2 Table 3).

Dose selection is carried out individually. Approximate doses and duration of action of the drugs are given in Appendix A3.2 Table 1 and Table 2. When switching a patient from one drug to another, the following approximate equivalents can be used:

– Flupentixol**, solution for i.m. injection 40 mg every 2 weeks;

– Fluphenazine**, solution for i.m. injection 25 mg every 2 weeks;

– haloperidol**, solution for i.m. injection 100 mg every 4 weeks;

– zuclopenthixol**, solution for i.m. injection 200 mg every 2 weeks;

– risperidone**, powder for suspension for i.m. injection

extended-release 37.5 mg every 2 weeks;

– paliperidone**, extended-release (monthly) suspension for i.m. injection 75 mg every 4 weeks;

– paliperidone**, extended-release (three-monthly) suspension for i.m. injection 263 mg every 3 months.

– aripiprazole, extended-release (monthly) suspension for i.m. injection 400 mg every 4 weeks;

These equivalents cannot be extrapolated to maximum doses.

3.9. Side effects of antipsychotic pharmacotherapy

3.9.1 Extrapyramidal side symptoms (EPS)

• The prescription of anticholinergic agents for the prevention of EPS in schizophrenia patients during antipsychotic therapy is unjustified and is not recommended, since they do not develop in every patient [30, 40-46, 170, 177].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: EPS include acute dystonia, akathisia, pseudoparkinsonism, tardive dyskinesia (TD), and neuroleptic malignant syndrome (NMS). The addition of an anticholinergic drug (trihexyphenidyl**, biperiden**), a dose reduction of a typical antipsychotic, or switching to second-generation antipsychotic (SGA) treatment (currently, such a substitution is preferred) constitute the options of choice when EPS occur [216, 236, 237]. EPS develop most frequently with the use of first-generation antipsychotics (FGAs); some SGAs may also cause dose-dependent EPS (Appendix A3.2, Table 4) [30, 41-45, 177]. The risk of EPS is higher during treatment with neuroleptics from the piperazine phenothiazine and butyrophenone groups [39-46, 170, 407]. EPS are easily recognized; however, their occurrence is very difficult to predict, as it is related partly to the dosage, partly to the characteristics of the drug itself, and partly to the patient's individual sensitivity.

Parkinsonian symptoms disappear after drug discontinuation or can be reduced by the addition of central anticholinergic agents, the so-called neuroleptic therapy correctors (Appendix A3.2, Table 4) [30, 40-45, 236, 237, 406].

• When symptoms of TD are detected, to reduce their severity, it is recommended to consider the possibility of antipsychotic discontinuation or dosage reduction (Appendix B8) (Table 3) [30, 170, 177, 318].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• In patients with manifestations of TD, to reduce their severity and when antipsychotic therapy cannot be discontinued, it is recommended to switch the drug to clozapine or quetiapine** (Appendix A3.2, Table 4 and Appendix B8) [30, 170, 170, 319].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• In the presence of persistent and severe manifestations of TD, to reduce their severity, therapy with tetrabenazine** is recommended (Appendix A3.2, Table 4 and Appendix B8) [319, 339-342].

Level of Evidence – 4, Strength of Recommendation – C.

Comments: Tardive dyskinesia (TD) is a group of movement disorders of hyperkinetic and hypokinetic types, including choreiform movement disorders, akathisia, dystonia, tics, and tremor. A combination of different types of abnormal movements is frequently observed. TD is detected, according to various estimates, in 10 to 50% of patients receiving antipsychotic therapy [319]. During SGA therapy, the prevalence of TD is lower (5-20%), but these figures also do not allow the risks of its development during SGA therapy to be considered insignificant. Factors increasing the risk of TD include older age, female sex, high doses of drugs, long-term antipsychotic treatment, and simultaneous prescription of multiple antipsychotic drugs. Antiparkinsonian drugs can contribute to the development of tardive dyskinesia and worsen its course, as well as cause drug dependence and cognitive impairment [30, 40-46, 170, 177, 319]. One of the main recommended therapeutic measures after the detection of TD symptoms is the discontinuation or dosage reduction of the antipsychotic (Appendix B8) [319]. If discontinuation/dosage reduction is not possible, switching to clozapine or quetiapine**, which surpass other APs in neurological tolerability, is recommended. As separate therapeutic options, the use of the vesicular monoamine transporter type 2 (VMAT2) inhibitor tetrabenazine** should be considered, and in cases of severe and persistent TD – deep brain stimulation (a functional neurosurgery method) [319, 341-342]. There are isolated descriptions of the alleviation of hyperkinetic disorders in TD with the addition of #fluvoxamine at a dose of 100 mg/day [408].

• In NMS, infusion therapy with plasma-substituting solutions (ATC: B05C) with the discontinuation of antipsychotic drugs is recommended to replenish circulating blood volume, correct water-electrolyte disorders, acid-base balance, and hemodynamics (Appendix B9) [317, 318, 320, 321].

Level of Recommendations CLevel of Evidence 5Level of Recommendation – C, Level of Evidence – 5.

• In NMS, for the relief of agitation and manifestations of catatonia, parenteral administration of benzodiazepine derivatives: lorazepam**, diazepam**, and bromdihydrochlorphenylbenzodiazepine is recommended (Appendix B9) [318, 321].

Level of Recommendations CLevel of Evidence 5Level of Recommendation – C, Level of Evidence – 5.

• When catatonic symptoms have a high specific weight and severity in NMS, for the rapid resolution of clinical manifestations, electroconvulsive therapy (ECT) is recommended (Appendix B8) [318, 321].

Level of Recommendations CLevel of Evidence 5Level of Recommendation – C, Level of Evidence – 5.

Comment: The incidence of NMS ranges from 0.01 to 0.02% of all hospitalized patients receiving antipsychotic therapy, regardless of nosology [318, 343, 346, 348, 351]. NMS usually develops within four weeks of starting AP therapy, and in 2/3 of cases already in the first week. Risk factors for NMS include male sex, therapy with a high-potency AP, high doses and their rapid escalation, parenteral administration of APs, and the use of depot formulations. An increased risk of NMS is present in patients with episodes of NMS and catatonia in the past, concomitant somatic diseases, in women in the postpartum period, with signs of dehydration and malnutrition [318]. Treatment of NMS is carried out in intensive care units and is aimed at restoring basic homeostasis parameters, hemodynamics, and vital organ functions under the control of laboratory parameters (acid-base balance, protein and water-electrolyte balance, circulating blood volume), as well as relieving psychomotor agitation, catatonic symptoms, and preventing the development of cerebral edema [318, 321, 347]. A number of authors recommend the use of dopaminergic agents (dopamine agonists) #amantadine** [318, 388] and #bromocriptine** [318, 351, 356, 357, 378, 379] in NMS, however, convincing data on their efficacy are currently lacking, with only isolated case reports showing a positive outcome [318, 346, 377, 381, 382].

3.9.2 Neuroendocrine, Metabolic, and Other Side Effects

• In the presence of clinical manifestations of hyperprolactinemia (galactorrhea, menstrual irregularities, sexual dysfunctions, gynecomastia) in schizophrenia patients, for its diagnosis and monitoring, it is recommended to test the blood prolactin level [30, 41-45, 170].

Level of Recommendations CLevel of Evidence 5Level of Recommendation – C, Level of Evidence – 5.

Comment: To minimize the development of hyperprolactinemia, the following risk factors must be considered: women of reproductive age, children, adolescents, and the presence of hyperprolactinemia during previous therapy [320]. Additional risk factors include fertility and gestation problems in women and the presence of gynecomastia, erectile dysfunction, decreased libido, and reduced hair growth in men. Hyperprolactinemia is most frequently caused by FGAs, but also by amisulpride, risperidone**, and paliperidone** [30, 40-45, 170].

• To prevent the deterioration of the somatic condition in patients with schizophrenia and metabolic disorders, it is not recommended to prescribe clozapine, olanzapine, as well as quetiapine** and risperidone** for a prolonged period, as they somewhat less frequently cause weight gain; in patients with schizophrenia and type 2 diabetes, the use of clozapine and olanzapine is not recommended [43-45, 331, 332].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comments: Metabolic side effects are more frequently observed with second-generation antipsychotics (Appendix A3.2, Table 5) [18, 30, 41-45, 331, 332]. First and foremost, they frequently develop with the use of clozapine and olanzapine**[3] [4], somewhat less frequently with quetiapine** and risperidone**, and rarely with other second-generation antipsychotics [43-44, 47-49, 178].

• In cardiac rhythm disturbances, to prevent QT interval prolongation, it is not recommended to prescribe sertindole**, ziprasidone, and thioridazine** [40, 41, 43-45].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: QT interval prolongation is a risk factor for sudden cardiac death. A QT interval of more than 450 ms in men and more than 470 ms in women is considered prolonged [43-45, 390, 401].

• In convulsive syndrome or lowered seizure threshold, to prevent the development of seizures, it is not recommended to prescribe clozapine and certain first-generation antipsychotics [40, 41, 43-45].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• For patients with schizophrenia who are intolerant to sedation, in order to prevent its development among second-generation antipsychotics, it is not recommended to use clozapine and quetiapine**, and to a lesser extent, olanzapine** and lurasidone** [40, 41, 43-45].

Level of evidence reliability – 5, Level of recommendation consensus – C.

• To prevent somatic adverse events during long-term antipsychotic pharmacotherapy, it is recommended to regularly perform the following laboratory and clinical examinations (Appendix A3.2, Table 6) [30, 41-45, 18].

GCR CLoE 5Grade of Recommendation – C, Level of Evidence – 5.

3.10. Psychotherapy

Cognitive behavioral therapy (CBT) is an evidence-based form of psychotherapy that is time-limited, structured, and focused on cognitive and behavioral changes. CBT aims to modify cognitive schemas, correct thinking errors, and develop adaptive behavioral skills [211]. Cognitive behavioral therapy is recommended to be used at the following stages of the disease: subacute, remission formation stage / remission.

Cognitive behavioral therapy is conducted in a hospital, day hospital, or outpatient setting. Greater severity of mental illness and pronounced neurocognitive deficit are not absolute contraindications for CBT [205].

• Cognitive behavioral therapy (CBT) is recommended for patients with schizophrenia with social-cognitive impairments in order to improve the quality and effectiveness of treatment [208-210].

Level of evidence – 2, Strength of recommendation – B.

• Family therapy is recommended for patients with schizophrenia with impaired family relationships in order to improve the quality and effectiveness of treatment [334].

Level of evidence – 2, Strength of recommendation – B.

Comments: The family is the most significant source of support in achieving successful social adaptation and effective functioning in patients with schizophrenia. However, an inadequate family communication style (high expressed emotion) can be a source of disease exacerbations. Work with the families of patients with schizophrenia aims to harmonize the family communication style, develop coping strategies for emerging social problems, and develop problem-solving competence. As a result of family therapy, the ability of the patient with schizophrenia to withstand stress increases, compensating for psychobiological vulnerability to stress and reducing the likelihood of disease exacerbation [34].

3.11. Criteria for evaluating treatment efficacy

• All patients receiving therapy for schizophrenia are recommended to undergo an assessment of treatment efficacy for evidence-based therapeutic decision-making [30, 41-45].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: In practice, it is useful to distinguish three levels of therapeutic response efficacy:

1. Treatment is effective, the effect is substantial and profound – the overall severity of symptoms has decreased by more than 50%.

2. Treatment is effective, the effect is partial – the overall severity of symptoms has decreased by at least 20%.

3. Treatment is ineffective – the overall severity of symptoms has decreased by less than 20%.

The levels given above are orientational and should be considered together with the physician's overall clinical impression and the degree of impairment in the patient's social functioning. The PANSS scale can be used as an auxiliary tool (Appendix G1).

The timeframe for assessing treatment efficacy depends on the specific treatment goal. To qualify the antipsychotic effect, the assessment is possible no earlier than 4 weeks of treatment, and in cases of suspected treatment resistance, the assessment period is extended to 6–8 weeks. When managing psychotic agitation, the assessment of treatment efficacy is conducted after 2 hours. Therapy is considered effective upon complete reduction of aggressive manifestations and a significant decrease in the level of agitation assessed clinically. Verification of the anti-negative effect is evaluated after 10–15 weeks of therapy (the BNSS scale can be used for this purpose, Appendix G2) [75].

The ultimate goal of patient treatment is to achieve remission, i.e., a stable alleviation or disappearance of schizophrenia symptoms (absence of sufficient criteria required to confirm the initial diagnosis of schizophrenia) with improvement or restoration of the patient's social functioning and quality of life. The PSP scale can be used as an auxiliary tool for assessing social functioning (Appendix G4) [176]. The quality of therapeutic remission varies significantly across different clinical forms and types of the course of schizophrenia and requires a differentiated clinical and functional assessment [179].

• To assess recovery in the process of therapy regarding social functioning indicators and the achievement of remission in all patients with schizophrenia, it is recommended to consider using the PSP scale (Appendix G4) [176].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comment: Antipsychotic drugs improve social functioning and quality of life in patients with schizophrenia, although there is no evidence to support any specific drug or group [30, 41-45, 191]. There is some evidence that subjective well-being indicators improve during treatment with certain second-generation antipsychotics [30, 41-45, 175]. The presence of side effects is a significant factor, and their reduction and control are important for improving the social functioning and quality of life of patients [30, 41-45, 175].

3.12. Medical nutrition therapy

The organization of therapeutic dietary nutrition for patients with schizophrenia during inpatient treatment in medical organizations is carried out in accordance with the Orders of the Russian Ministry of Health No. 330 dated August 5, 2003, “On Measures to Improve Therapeutic Nutrition in Treatment and Prophylactic Institutions of the Russian Federation,” No. 395n dated June 21, 2013, “On Approval of Therapeutic Nutrition Norms,” and No. 1008n dated September 23, 2020, “On Approval of the Procedure for Providing Patients with Therapeutic Nutrition” (Appendix A3).

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Psychosocial interventions and rehabilitation in patients with schizophrenia are aimed at the formation or restoration of personality resources, skills, knowledge, abilities to interact, solve problems, and use coping strategies that are deficient or lost as a result of the disease in psychiatric patients with impaired social adaptation, ensuring their integration into society [31].

Psychosocial therapy and psychosocial rehabilitation, along with pharmacotherapy, represent necessary and complementary therapeutic strategies [180, 181].

Psychosocial work with patients can be carried out at any stage of psychiatric care provision. Before starting the intervention, it is necessary to determine the nature and degree of social maladaptation, the need for a specific form of psychosocial intervention, and to formulate the goal of each intervention with a defined time period during which the specified goal is expected to be achieved [30, 31, 181].

Group work formats are usually conducted; however, if it is impossible to include the patient in a group (for example, in case of patient refusal, etc.), the work is conducted in an individual format. Following the completion of active psychosocial interventions, supportive psychosocial activities are carried out [30, 31, 181].

• For patients with schizophrenia who have impairments in social functioning, it is recommended to conduct psychosocial treatment and rehabilitation measures aimed at the formation or restoration of personality resources that are deficient or lost as a result of the disease [31, 181-184].

Level of evidence reliability – 5, Level of recommendation consensus – C.

Comments: Special attention should be paid to psychosocial therapy for patients with a first psychotic episode (FPE), since the development of schizophrenia is usually accompanied, on the one hand, by severe impairments in social and communication skills, and on the other hand, by stigmatization and discrimination existing in public consciousness towards people suffering from this disease; the realization of the fact of illness affects the emotional state of the patient, alters their self-perception, self-esteem, behavior, and relationships with others, and makes adjustments to future plans [212].

When conducting psychosocial work with patients with schizophrenia belonging to a particular "problem" group (patients with frequent hospitalizations, living alone, with prolonged hospital stays, with unstable occupational adaptation), it is recommended to identify specific dominant tasks in order to determine the forms of intervention [31].

Psychosocial treatment and rehabilitation measures include: group psychoeducational work with patients with mental disorders and behavioral disorders (B04.035.006), social skills training, family therapy, supported employment programs, cognitive behavioral therapy, cognitive remediation, metacognitive training [30, 181].

• Cognitive remediation (CR) is recommended for patients with schizophrenia and cognitive impairments to overcome cognitive deficits and achieve sustained and general improvement in cognitive processes (attention, memory, executive functions, social cognitions, or metacognitions) [30, 31, 194, 195].

Level of evidence – 1, Strength of recommendation – B.

Comments: The use of CR [185-188, 195] is due to the fact that cognitive dysfunction is recognized as one of the key features of schizophrenia [189], the high prevalence of deficits in basic neurocognition and social cognition [190-193], and the fact that it is the main cause of social maladjustment during remission [188] and recurrent exacerbations [194].

CR is used both in patients with schizophrenia with a "first episode" [212] and in the chronic course of the disease. The main task of CR is to minimize the impact of cognitive impairments on daily functioning. For patients with a chronic course of the schizophrenic process, the use of compensatory strategies relying on preserved cognitive functions with the help of reinforcement is recommended. For patients with a "first episode", the use of programs to restore impaired functions is recommended [30, 31, 194, 195].

CR is carried out in a hospital, day hospital, or outpatient setting during the subacute or remission stages of the disease.

Contraindications: acute psychotic state with disorganized behavior.

• Metacognitive training (MCT) is recommended for patients with schizophrenia and cognitive impairments to eliminate the impact of social-cognitive deficits on daily functioning [323-329, 334, 336-338].

Level of evidence – 1, Strength of recommendation – B.

Comment: The use of MCT is due to the fact that one of the key signs of schizophrenia is the development of social-cognitive deficits that impair the daily functioning of patients with schizophrenia. MCT allows for the development of a number of rehabilitation interventions aimed at eliminating social-cognitive deficits [323, 327-329, 336-338]. MCT is carried out on the basis of cognitive remediation principles (creating a sustained and general improvement in cognitive processes: memory, attention, executive functions, social cognitions, or metacognitions in combination with skills training in everyday reality). The main task of MCT is to reduce the impact of social-cognitive deficits on the daily functioning of a patient with schizophrenia by developing rehabilitation interventions at the initial stages of the disease and in its chronic course. MCT is carried out in a hospital, day hospital, or outpatient setting during the subacute or remission stages of the disease.

Contraindications: acute psychotic state with disorganized behavior.

• Social skills training (SST) is recommended in the treatment of chronic patients with schizophrenia to form instrumental and interpersonal interaction skills [196-202].

Level of evidence – 1, Strength of recommendation – B.

Comment: During SST, training of various functions is carried out sequentially, incorporating them into socially significant situations.

SST uses approaches including training in the following areas: goal setting and role changes using behavioral training and rehearsals with positive reinforcement and corrective feedback. Problem-solving training and homework assignments are also used to reinforce acquired skills and facilitate their implementation into the patient's daily life [30, 31, 196-202].

Stages of the disease: subacute, stage of remission formation/remission.

SST is carried out in a hospital, day hospital, or outpatient setting.

Contraindications: acute psychosis stage with behavioral disorganization; severe cognitive deficit.

The use of SST is due to the high prevalence of social cognition impairments in patients with schizophrenia [196] and their negative impact on the outcome of the disease [196-200].

• Psychoeducation (PE) is recommended for patients suffering from schizophrenia, including at the stage of the first psychotic episode, patients with impaired insight into their illness, and medication adherence issues, as well as for problem groups of patients with schizophrenia in order to increase treatment efficacy and therapeutic adherence [203-207, 323].

Level of evidence – 1, Strength of recommendation – A.

Comment: Psychoeducation is a step-by-step system of interactive psychosocial interventions aimed at informing the patient and their relatives about mental disorders, early recognition of signs of an incipient exacerbation, increasing compliance, and teaching methods for coping with specific problems caused by the manifestations of the disease. The psychoeducational process is carried out in a strict sequence of stages from problem formulation and understanding to skills training and further to the application of developed skills in daily life. Various psychoeducation models have been developed taking into account problem groups of patients with schizophrenia:

- for patients with schizophrenia with frequent hospitalizations, inclusion of compliance problems and pharmacotherapy regimen adherence, recognition of early relapse manifestations, elimination of factors contributing to exacerbation, and modification of family interaction styles for the families of these patients is recommended;

- for patients living alone, inclusion of communication and other social skills, compliance, and independent living problems in the program is recommended, along with patient-centered interventions and work to activate the social network;

- for patients with schizophrenia with prolonged hospital stays under conditions of social deprivation, inclusion of an independent living module and social skills in the program is recommended;

- for patients with unstable occupational adaptation, inclusion of compliance therapy and occupational rehabilitation in the program is recommended

When working with patients with schizophrenia having a "first episode", it is recommended to include the following components:

1) assistance in overcoming stress due to the experienced psychotic episode and mitigating social risk factors for its occurrence and recurrence;

2) provision of adequate information about mental disorders, appropriate forms and services of care for the patient, family members, and other significant members of the immediate environment;

3) explanation of the connection between clinical improvement and the prescribed treatment;

4) achievement of compliance and prevention of recurrent exacerbations;

5) early recognition of recurrent exacerbation and prompt intervention upon its onset;

6) reduction of suicide risk;

Psychoeducation is recommended for use at the following stages of the disease: subacute, stage of remission formation/remission.

Psychoeducation is carried out in a hospital, day hospital, or outpatient setting. Contraindications to psychoeducation are: acute stage of the disease with behavioral disorganization; severe cognitive disorders.

The earliest possible inclusion of psychoeducation in the rehabilitation system for patients with schizophrenia is preferred. Interventions involving family members are more effective [204]. Psychoeducation helps reduce relapse rates, promotes adherence to medication therapy regimens, and also shortens the duration of hospital stays for patients [203, 206, 207].

• Supported employment programs are recommended for patients with schizophrenia and unstable employment adaptation or disability [322, 323, 326].

Level of Evidence – 1, Grade of Recommendation – B

Comments: The highest results of social and occupational rehabilitation in patients with schizophrenia have been demonstrated with a combination of supported employment and other options of psychosocial rehabilitation, especially cognitive remediation [325] and metacognitive training [327].

5. Prevention and Dispensary Observation

Prevention of schizophrenia is based on modern knowledge of the etiology and pathogenesis involving environmental and biological factors of this mental disorder. An important role in the prevention of schizophrenia is assigned to the early detection and treatment of initial psychopathological symptoms of the disease, cognitive impairments, elimination of stress-vulnerability factors, and the ongoing maintenance pharmacotherapy to reduce the risk of recurrent relapses, increased disease progression, negative symptoms, cognitive deficits, and, consequently, social maladjustment.

Dispanserizatsiya observation plays a key role in preventing adverse outcomes of schizophrenia and minimizing its manifestations and consequences, including those related to the social functioning of patients. It is carried out through regular examinations by a psychiatrist and the provision of necessary medical and psychosocial care by a professional multidisciplinary team, including a medical psychologist, a social work specialist, a social worker, and other specialists. Dispanserizatsiya observation may be established regardless of the consent of the person suffering from a mental disorder or their legal representative in cases provided for by the legislation of the Russian Federation.

The tasks of dispanserizatsiya observation for a patient with schizophrenia include: clinical monitoring of the dynamics of psychopathological disorders (including remission quality) and prescribing additional examinations (if necessary), determining the features of the social status, social functioning, and quality of life of patients, implementing maintenance and anti-relapse treatment and adjusting it if necessary, relieving outpatient-level exacerbations, ensuring continuity of care after discharge from a psychiatric hospital or day patient facility, identifying and managing side effects and complications of pharmacotherapy, assessing the level of treatment adherence, conducting psychosocial rehabilitation, and preventing socially dangerous acts and suicidal behavior of patients. The frequency of dispanserizatsiya visits (examinations, consultations), the scope of preventive, diagnostic, and therapeutic measures, and the need for and scope of psychosocial rehabilitation are determined by the psychiatrist based on the patient's clinical and social status in accordance with the features of the course of schizophrenia and the current clinical status of patients in accordance with Order No. 453n of the Russian Ministry of Health dated June 30, 2022, "On Approval of the Procedure for Dispanserizatsiya Observation of a Person Suffering from a Chronic and Prolonged Mental Disorder with Severe Persistent or Frequently Exacerbating Disease Manifestations" based on clinical guideline data. Dispanserizatsiya observation is terminated upon recovery or significant and sustained improvement in the mental state of the person suffering from schizophrenia.

6. Organization of Medical Care

Psychiatric care for patients with schizophrenia is provided by medical and other organizations of the state, municipal, and private healthcare systems holding a corresponding license to carry out medical activities in the field of mental disorders and behavioral disorders.

Psychiatric care for a patient suffering from schizophrenia is provided on a voluntary basis (subject to informed voluntary consent) except for cases provided for by the legislation of the Russian Federation. Establishing a diagnosis of schizophrenia, making a decision on the provision of psychiatric care on an involuntary basis, or issuing an opinion for the consideration of this issue are the exclusive right of a psychiatrist or a commission of psychiatrists.

Psychiatric care for patients with schizophrenia may be provided outside a medical organization (at the location of a dispatch of emergency, including specialized emergency, medical care); on an outpatient basis (in conditions that do not provide for around-the-clock medical observation and treatment), including at home upon a medical worker's call; in a day hospital (in conditions providing for medical observation and treatment during the day, but not requiring round-the-clock observation and treatment); as an inpatient (in conditions ensuring round-the-clock medical observation and treatment). It is preferable to provide psychiatric care to patients with schizophrenia in the least restrictive conditions—on an outpatient basis or in a day hospital.

When organizing and providing psychiatric care, telemedicine technologies may be used for remote interaction between medical workers, as well as between medical workers and patients and/or their legal representatives.

7. Additional Information

Factors (predictors) contributing to an unfavorable course:

• alcohol and psychoactive substance abuse,

• low treatment adherence,

• lack of family/social support,

• lack of social rehabilitation measures,

• prolonged duration of untreated psychosis (DUP),

• presence of prolonged distress,

• nicotine dependence,

• comorbid somatic disorders, including metabolic disorders.

Criteria for Evaluating the Quality of Medical Care

Quality Assessment Criteria for Primary Health Care Provided to Adults with Schizophrenia

Quality Assessment Criteria for Specialized Medical Care Provided to Adults with Schizophrenia

References

Appendix A1. Working Group Composition

1. Malin Dmitry Ivanovich – MD, Professor, Chief Researcher, Department of Psychopharmacotherapy, Department of Mental Illness Therapy, Moscow Research Institute of Psychiatry – Branch of the V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, member of the Russian Society of Psychiatrists (RSP).

2. Maslenikov Nikita Valerievich – Researcher, Department of Intensive Care and Non-Drug Treatment Methods, Moscow Research Institute of Psychiatry – Branch of the V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, member of the RSP.

3. Mosolov Sergey Nikolaevich – MD, Professor, Honored Scientist of the Russian Federation, Head of the Department of Mental Illness Therapy, Moscow Research Institute of Psychiatry – Branch of the V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, Head of the Department of Psychiatry, Russian Medical Academy of Continuous Professional Education of the Russian Ministry of Health, member of the RSP Executive Board.

4. Kiryanova Elena Mikhailovna – PhD in Medicine, Head of the Psychotic Spectrum Disorders Department, Moscow Research Institute of Psychiatry – Branch of the V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, member of the RSP.

5. Tsukarzi Eduard Eduardovich – PhD in Medicine, Head of the Department of Intensive Care and Non-Drug Treatment Methods, Moscow Research Institute of Psychiatry – Branch of the V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, member of the RSP.

6. Shmukler Alexander Borisovich – MD, Professor, Deputy General Director for Scientific Work at the V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology of the Russian Ministry of Health, Acting Director of the Moscow Research Institute of Psychiatry – Branch, member of the RSP.

Conflict of interest: none.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Psychiatrists

2. Psychotherapists

3. Narcological Psychiatrists

4. Medical psychologists

5. Social Work Specialists

1. Scale for evaluating levels of evidentiary validity (LEV) for diagnostic methods (diagnostic interventions)

2. Levels of Evidence (LoE) rating scale for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

3. Grades of Recommendation (GoR) rating scale for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Clinical practice guidelines update procedure – revision once every 3 years and no more frequently than once every 6 months

Appendix A3. Reference Materials

A3.1 Legal documents (orders and instructions)

1. Federal Law No. 323-FZ dated November 21, 2011, "On the Fundamentals of Protecting Citizens' Health in the Russian Federation";

2. Law of the Russian Federation No. 3185-1 dated July 2, 1992, "On Psychiatric Care and Guarantees of Citizens' Rights in Its Provision";

3. Order of the Russian Ministry of Health No. 668n dated October 14, 2022, "On Approval of the Procedure for Providing Medical Care for Mental Disorders and Behavioral Disorders" (Registered with the Ministry of Justice of Russia on November 14, 2022, No. 70940)

4. Order of the Russian Ministry of Health No. 453n dated June 30, 2022, "On Approval of the Procedure for Dispensary Observation of Persons Suffering from Chronic and Prolonged Mental Disorders with Severe, Persistent, or Frequently Relapsing Disease Manifestations" (Registered with the Ministry of Justice of Russia on July 28, 2022, No. 69429)

5. Order of the Russian Ministry of Health No. 451n dated June 30, 2022, "On Approval of the Procedure for Conducting Medical Psychiatric Examinations" (Registered with the Ministry of Justice of Russia on July 28, 2022, No. 69435)

6. Order of the Russian Ministry of Health No. 342n dated May 20, 2022, "On Approval of the Procedure for Mandatory Psychiatric Examination of Employees Performing Certain Types of Activities, Its Frequency, and the Types of Activities Requiring Psychiatric Examination" (Registered with the Ministry of Justice of Russia on May 30, 2022, No. 68626)

7. Order of the Ministry of Health of the Russian Federation No. 1104n dated November 26, 2021, "On Approval of the Procedure for Conducting Medical Examinations for the Presence of Medical Contraindications to Weapon Ownership, Including Unscheduled Examinations, and the Procedure for Issuing Medical Certificates Based on the Results Thereof, Forms 85 of the Medical Certificate on the Absence of Medical Contraindications to Weapon Ownership and the Medical Certificate on the Absence of Narcotic Drugs, Psychotropic Substances and Their Metabolites in the Body"

8. Order of the Ministry of Health of the Russian Federation No. 330 dated August 5, 2003, "On Measures to Improve Therapeutic Nutrition in Healthcare Institutions of the Russian Federation."

9. Order of the Ministry of Health of the Russian Federation No. 395n dated June 21, 2013, "On approval of therapeutic nutrition standards".

10. Order of the Ministry of Health of the Russian Federation No. 1008n dated September 23, 2020, "On Approval of the Procedure for Supplying Patients with Clinical Nutrition."

A3.2 Reference materials and dosage tables for the medications mentioned in the text

Table 1. Recommended drug doses used in the treatment of schizophrenia [223-255]

Note: chlorpromazine equivalents do not always accurately reflect equivalent doses of antipsychotic drugs (APDs), therefore, one should additionally refer to the conversion of antipsychotic doses into olanzapine equivalents (see Table 2) [57].

Table 2. Equivalent dosages of antipsychotics

Table 3. Approximate doses and duration of action of long-acting injectable antipsychotics [223, 224, 230, 248, 249, 253]

Table 4. Management of extrapyramidal adverse effects of antipsychotic therapy

Table 5. Frequency of adverse effects associated with SGAs and haloperidol**

Note: 0 – none, (+) – isolated cases (no difference from placebo), + – very rare adverse effects (less than 1%), ++ – rare adverse effects (less than 10%), +++ – frequent adverse effects (more than 10%), ? – data not available.

* – weight gain over 6-10 weeks: + – slight (0-1.5 kg), ++ – moderate (1.5-3 kg), +++ – severe (more than 3 kg).

Table 6. Schedule for monitoring certain somatic parameters during antipsychotic pharmacotherapy (monitoring frequency for a number of parameters is regulated by Order of the Russian Ministry of Health No. 453n dated June 30, 2022)

Note: * – when using clozapine, weekly for the first 18 weeks, then once a month.

Appendix B. Physician Action Algorithms

Appendix B1. Algorithm for the diagnosis of schizophrenia

Appendix B2. Algorithm for patient care in schizophrenia

Appendix B3. Algorithm for biological therapy of acute schizophrenia exacerbation

Appendix B4. Algorithm for antipsychotic selection in specific clinical scenarios of schizophrenia

Appendix B5. Pharmacotherapy algorithm for primary (dominant and persistent) negative symptoms (DPNS) in schizophrenia

Appendix B6. Algorithm for the treatment of depression in schizophrenia

Appendix B7. Algorithm for emergency therapy of an acute psychiatric disorder with agitation and aggression

Algorithm for emergency therapy of an acute psychotic disorder with agitation and aggression

Appendix B8. Algorithm for the treatment of tardive dyskinesia

Appendix B9. Algorithm for the diagnosis and treatment of neuroleptic malignant syndrome (NMS)

Appendix C. Patient Information

General questions

Schizophrenia is a mental disorder characterized by a combination of positive (psychotic) and negative (apathy, emotional and social withdrawal, etc.) symptoms, behavioral and cognitive impairments (memory, attention, thinking, etc.).

The cause of schizophrenia remains unknown to date. Research results show that the symptoms of the disease are caused by a disruption of biochemical processes in the dopaminergic and glutamate systems of the brain, which mediate various forms of its activity: control of perception, thinking, emotions, and memory. Approximately 1% of the population suffers from schizophrenia. At the same time, no cultural, ethnic, or geographical differences in the prevalence of this disease have been established. In most cases, it begins between the ages of 15 and 35.

Diagnosis of schizophrenia

The diagnosis is made on the basis of a clinical psychiatric evaluation, which relies on a combination of data on the history of the disease, the sequence of symptom formation, and family history. Information provided by people close to the patient is often very important and useful for such an evaluation. Diagnosis is based on identifying characteristic signs of the disease. To confirm the diagnosis, it is necessary to exclude the presence of other conditions that can cause similar symptoms.

Diagnosis and treatment of schizophrenia are performed by psychiatrists.

Treatment of schizophrenia

The main method of treatment for schizophrenia is drug therapy.

The earlier the disease is detected and treatment is started, the greater the chances of arresting the disease, and the less damage it will have time to inflict on the patient and their loved ones.

The key goal of schizophrenia therapy is to achieve remission, which is understood as the complete or substantial resolution of disease symptoms with the achievement, whenever possible, of the pre-morbid level of social functioning. To date, this goal is achievable only with long-term continuous drug therapy, as is the case with many other chronic conditions (hypertension, diabetes mellitus, etc.). To select therapy at the initial stage, a fairly long-term regular contact with a doctor is required, which should be carried out in an outpatient setting. The minimum period required to assess drug efficacy is 4–6 weeks. Subsequently, drug therapy is continued indefinitely depending on the clinical effect. The question of discontinuing such therapy can be raised no earlier than 1 year after the first episode of the disease and 5 years after recurrent episodes, provided that no signs of the disease have been observed during this period. At the same time, it should be remembered that discontinuing therapy even after a multi-year "stable" period is associated with the risk of disease recurrence. Medications for such long-term therapy must be selected so that they do not cause discomfort related to their side effects. Drug tolerability varies among individuals and is determined by individual sensitivity. If the initially prescribed drug causes side effects, it should be replaced with another, but treatment must continue. The arsenal of modern medications allows for significant success in achieving the stated goal. In the vast majority of cases, side effects are reversible and disappear after drug discontinuation. Issues related to drug tolerability should be discussed with your doctor.

In addition to pharmacotherapy, an essential element of care is psychosocial therapy and psychosocial rehabilitation, aimed at the fullest possible social and personal recovery of a person who has suffered an episode of this disease, and improving their quality of life. Furthermore, psychosocial treatment and rehabilitation measures allow for the prevention of recurrent episodes and relapses of the disease. Regular specialist examinations and adjustment of therapeutic tactics serve the same purpose, helping to avoid adverse consequences of the disease.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

G1. Positive and Negative Syndrome Scale (PANSS)

Original title: Positive and negative symptoms scale (PANSS)

Source: Kay S.R., Opler L.A., Fiszbein A., 1986

Mosolov S.N. Scales for psychometric assessment of schizophrenia symptoms and the concept of positive and negative disorders. - M.: Noviy tsvet, 2001. - 238 p.

Type (underline):

- scale

- index

- questionnaire

- other (specify):

Purpose:

Assessment of the presence and severity of schizophrenia symptoms

Content (template): consists of 3 subscales: positive, negative, and general psychopathological symptoms

Key (interpretation): In clinical practice, it is used to assess the effectiveness of antipsychotic therapy. A substantial and profound effect is considered a reduction in the total score by 50% or more. A partial effect is a reduction in the overall symptom severity from 20 to 50%. With a reduction in the total score by less than 20%, the therapy is considered ineffective.

Criteria for diagnosis and assessment of symptom severity

Positive and Negative Syndrome Scale (PANSS)

Positive Syndrome Scale (P)

P1. DELUSIONS

False beliefs, conviction in groundless, unrealistic, and idiosyncratic (unusual) ideas. Evaluated based on the content of thoughts expressed in conversation and their impact on the patient's social relations and behavior (according to medical staff and relatives).

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: presence of one or two vague, poorly formed, and unstable delusional ideas that do not impair the patient's thinking, behavior, or relationships with others.

4. Moderate: kaleidoscopic alternation of many poorly formed and unstable delusional ideas or the presence of several clearly formed ideas that occasionally interfere with the patient's normal thinking and affect their relationships with others and behavior.

5. Severe: presence of numerous, clearly formed, and stable delusional ideas that periodically affect the patient's thinking, social relations, and behavior.

6. Very severe: presence of a complex of formed, often systematized, stable delusional ideas that noticeably disrupt the thinking process, the patient's relationships with others, and their behavior.

7. Extreme: presence of a stable complex of numerous or detailed systematized delusional ideas that have a significant impact on the main aspects of the patient's life, leading to inappropriate and irresponsible actions that in some cases pose a danger to the patient and others.

P2. CONCEPTUAL DISORGANIZATION

Disorganization of the thinking process characterized by the fragmentation of goal-directed train of thought, i.e., excessive detail (circumstantiality), superficiality, overinclusion, tangentiality, looseness of associations, inconsistency, paralogogical thinking, or "thought blocking" (sperrung), evaluated based on the state of the thought and speech process during conversation.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild severity: circumstantial, superficial, paralogical thinking, or with derailments ("tangential responses"). The patient experiences some difficulty in goal-directed thinking (when trying to focus on a single thought); when the physician persists, random associations may appear.

4. Moderate severity: during concrete and brief communication, the ability to focus on specific thoughts is preserved; however, under the slightest pressure or in more complex situations, thinking becomes amorphous (vague) and devoid of goal-directedness.

5. Marked severity: the patient almost always experiences difficulty in organizing a goal-directed flow of thoughts, which manifests as derailments, incoherence, vagueness, and some loss of connectedness of thinking even in the absence of external pressure.

6. Severe severity: mental activity is severely disturbed and unsystematic; clear incoherence and loosening of associations are observed almost constantly.

7. Extreme severity: loosening of associations reaches the degree of incoherence. There is pronounced loosening of associative connections, leading to a complete loss of the ability to communicate, up to "word salad" or mutism.

P3. HALLUCINATIONS

Perceptual abnormalities or behavior indicating perception without a corresponding external stimulus. Pathological perception may occur in the auditory, visual, olfactory, or somatic spheres. Assessed based on verbal reports or external manifestations during the interview, as well as information obtained from medical staff or relatives of the patient.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild severity: one or two rare but distinct hallucinations, or several vague pathological perceptions that do not affect the patient's thinking and behavior.

4. Moderate severity: frequent but not constant hallucinations; the patient's thinking and behavior are mildly disturbed.

5. Marked severity: frequent hallucinations affecting sometimes more than one sensory modality and noticeably disturbing thinking and/or behavior. Delusional interpretation of hallucinatory experiences with corresponding emotional and sometimes verbal accompaniment is possible.

6. Severe severity: almost continuous hallucinations that significantly disturb the patient's thinking and behavior. Perceptual disturbances are experienced as real events with frequent emotional and verbal reactions to them, severely impairing the patient's adaptive capabilities.

7. Extreme severity: the patient's personality is almost completely engulfed by hallucinations, which essentially determine the direction of their thinking and behavior. Hallucinations are accompanied by persistent delusional interpretation, verbal and behavioral reactions, including complete compliance with imperative hallucinations.

P5. GRANDiosity

Elevated self-esteem and unfounded conviction in one's superiority, including delusions of possessing special abilities, wealth, knowledge, fame, power, and moral righteousness. Assessed by the content of thoughts revealed during the interview and their reflection in the patient's behavior (according to medical staff and relatives).

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild severity: some expansiveness and boastfulness are noted. Clearly formulated delusions of grandeur are not detected.

4. Moderate severity: a clear and unrealistic sense of superiority over others; poorly formulated delusions of special status or abilities may be present, which, however, do not determine the patient's behavior.

5. Marked severity: clearly formulated delusions of outstanding abilities, power, or exceptional status that influence the formation of attitudes, but do not manifest in behavior.

6. Severe severity: clearly formulated delusions of superiority in multiple parameters simultaneously (wealth, knowledge, fame, etc.) manifest not only in statements, but also in relationships with other people, as well as in certain actions.

7. Extreme severity: thinking, interpersonal relationships, and behavior are almost completely determined by multiple delusions of extraordinary abilities, wealth, knowledge, fame, and/or moral virtues, which may acquire an absurd character.

P6. SUSPICIOUSNESS / PERSECUTION

Unfounded or exaggerated ideas of persecution, manifested in a feeling of wariness, distrust, suspicious vigilance, and more overt delusional conviction in the hostility of others. Assessed by the content of thoughts expressed during the interview and their impact on the patient's behavior, including information from medical staff and relatives.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild severity: the patient shows wariness or even overt distrust, but thinking, behavior, and interpersonal relationships are virtually undisturbed.

4. Moderate severity: distrust is prominent enough to hinder the interview with the physician and affect the patient's behavior; nevertheless, persecutory delusions are absent. On the other hand, some patients may exhibit poorly formulated persecutory delusions that seemingly do not affect behavior and interpersonal relationships.

5. Marked severity: distrust is so strong that it leads to the breakdown of relationships with other people. Formulated persecutory delusions may be observed, somewhat altering the nature of interpersonal relationships and the patient's behavior.

6. Severe severity: formulated persecutory delusions tending to expand, systematize, and significantly impair the patient's relationships with others.

7. Extreme severity: a ramified complex of systematized persecutory delusions that almost completely determines the patient's train of thought, social relations, and behavior.

P7. HOSTILITY

Verbal or other manifestations of anger and antagonism, including sarcasm, passive-aggressive behavior, threats, and overt assault. Assessed by behavior during the interview and information obtained from medical staff and relatives.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild severity: indirect or covert manifestations of anger, such as sarcasm, disrespect, hostile remarks, episodes of irritability.

4. Moderate severity: overt hostility, quick irritability, and direct manifestations of anger or indignation.

5. Marked severity: the patient is extremely irritable, sometimes resorting to verbal insults and threats.

6. Severe severity: contact with the patient is hindered due to verbal insults and threats, which also significantly impairs relationships with others. The patient may be belligerent and prone to destructive behavior, but does not commit physical assaults on people.

7. Extreme severity: intense anger with almost complete lack of contact with the physician and other people, or episodes of physical assault.

Scale for the Assessment of Negative Symptoms (SANS)

N1. BLUNTED AFFECT

Diminished emotionality, manifested by reduced expressiveness of facial expressions, inability to display feelings, and communicative gesturing. Assessed by observing the physical manifestations of the patient's affective expressiveness and emotionality during the interview.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild severity: facial expressions and communicative gesturing appear strained, forced, artificial, or impoverished.

4. Moderate severity: a reduction in the range of facial expressiveness and gesturing determines a characteristic "bored" (expressionless) appearance.

5. Marked severity: affect is typically blunted (flattened), facial expressions are meager, and gesturing is impoverished.

6. Severe severity: significant affective blunting and deficiency of emotional reactions are observed most of the time. Occasionally, extremely intense, uncontrollable affective outbursts in the form of agitation, fits of rage, or motiveless laughter are possible.

7. Extreme severity: facial modulations and communicative gesturing are virtually absent; facial expression is persistently indifferent or frozen ("wooden").

N2. EMOTIONAL WITHDRAWAL

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild severity: the patient shows insufficient initiative in communication.

4. Moderate severity: when encouraged, engages in communication and activities.

5. Marked severity: the patient cannot be engaged in communication or occupational activities.

6. Severe severity: overt indifference to others, neglect of own needs (requires care).

7. Extreme severity: withdrawn, inaccessible.

N3. POOR RAPPORT

Lack of empathy, openness, and frankness in conversations, along with a lack of interest or involvement with the interlocutor, manifested by difficulty in establishing interpersonal contacts and a reduction in the volume of verbal and non-verbal communication. Assessed by the patient's behavior and attitude toward the physician during the interview.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: in communication with the patient, a certain artificiality, stiffness, and high-flown manner are felt. The patient's speech lacks emotional depth and is often impersonal in character.

4. Moderate: the patient generally appears alienated, keeps a distance from the interlocutor, answers questions mechanically, and their behavior expresses boredom or a lack of interest in the conversation.

5. Marked: overt alienation and disinterest of the patient in the conversation impede productive contact with them. The patient tries to avoid eye contact with the interlocutor.

6. Severe: the patient is highly indifferent to the surroundings, keeps a distance from the interlocutor, avoids eye contact, and cannot sustain a reciprocal gaze. Answers are monosyllabic and superficial. Attempts at non-verbal contact with the patient are practically left unanswered.

7. Extreme: the patient cannot be engaged in conversation, appears completely indifferent, and persistently avoids verbal and non-verbal contact with the interlocutor.

N4. PASSIVE/APATHETIC SOCIAL WITHDRAWAL

Reduced interest and initiative in social relationships due to passivity, apathy, loss of energy, and motivational drives, leading to decreased sociability and neglect of daily activities. Assessed based on information regarding the patient's social behavior obtained from medical staff and relatives.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: occasionally shows interest in social communication, but has low initiative. Enters into contact with other people only upon the latter's initiative.

4. Moderate: passively, mechanically, and without interest participates in most types of social activity, trying to stay in the background.

5. Marked: takes passive participation in a very narrow range of activities, showing practically no interest in them or initiative. Spends little time communicating with other people.

6. Severe: the patient is apathetic most of the time, tends toward self-isolation, very rarely shows any social activity, and at times neglects their own needs. Only occasionally initiates social contact themselves.

7. Extreme: the patient is profoundly apathetic, socially isolated, and neglects their own needs.

N5. DIFFICULTY IN ABSTRACT THINKING

Impairment of abstract-symbolic thinking, manifested by difficulty in classification and generalization, as well as an inability to move away from concrete or egocentric modes of problem-solving. Assessed by responses to questions about the semantic commonality of objects and concepts, the interpretation of proverbs, and the predominance of concrete thinking over abstract thinking during the interview.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: there is a tendency to give literal or personally colored interpretations of complex proverbs; difficulties may arise when interpreting abstract or remote concepts.

4. Moderate: the patient frequently resorts to concrete thinking, experiences difficulties in interpreting most proverbs and some abstract concepts, and tends to be distracted by functional aspects and the most obvious features.

5. Marked: thinking is predominantly concrete; the patient experiences difficulties in interpreting most proverbs and concepts.

6. Severe: the patient is incapable of understanding the abstract meaning of any of the suggested proverbs or figurative expressions, classifying only the most elementary objects by functional similarity. Thinking is completely depleted or limited to functional aspects, the most obvious features, or idiosyncratic (absurd) interpretations.

7. Extreme: the patient retains only concrete thinking, completely lacks understanding of proverbs, common metaphors or comparisons, and simple concepts, and loses the ability to classify objects and phenomena even on the basis of the most obvious features and functional properties. This score can also be used to evaluate patients with whom conversation is practically impossible due to severely pronounced cognitive impairments.

N6. SPONTANEITY AND FLOW OF CONVERSATION

Impairment of normal communication due to apathy, diminished motivational drives, a defensive stance, or cognitive deficit, manifested as a disruption in the fluency and productivity of the verbal-communicative process. Assessed by disturbances in cognitive-verbal functions during the interview.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: the patient shows little initiative during the conversation, their answers are brief and devoid of details, and obtaining information requires asking direct and leading questions.

4. Moderate: communication with the patient lacks fluency and is uneven or halting. To obtain adequate answers and continue the conversation, leading questions must frequently be asked.

5. Marked: the conversation clearly suffers from a lack of spontaneity and frankness on the part of the patient; answers to questions are limited to one or two short sentences.

6. Severe: the patient's answers are reduced to a few words or short phrases aimed at terminating the conversation or sharply reducing the volume of communication with the physician (e.g., "I don't know," "I can't talk about this"). As a result, the conversation is severely hindered and unproductive.

7. Extreme: verbal communication is extremely limited and mainly boils down to occasional utterances; conversation with the patient is impossible.

N7. STEREOTYPED THINKING

Impairment of the fluency, spontaneity, and flexibility of thinking, manifested in rigidity, repetitiveness, or depletion (contentlessness) of thoughts. Assessed by the nature of the cognitive-verbal process during the interview.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: some rigidity of attitudes and ideas is detected. The patient may refuse to consider alternative viewpoints or experience difficulty in switching from one thought to another.

4. Moderate: the conversation continually returns to the same topic; the patient has difficulty switching to another topic.

5. Marked: the rigidity and stereotypy of thinking are so pronounced that the conversation, despite the physician's counteraction, is limited to two or three prevailing topics.

6. Severe: uncontrollable repetition of demands, statements, individual thoughts, or questions, which significantly impedes the conversation.

7. Extreme: thinking, behavior, and speech are dominated by constantly repeated ideas or individual phrases, leading to pronounced rigidity, inadequacy, and a sharp limitation of the patient's communication.

General Psychopathology Scale (G)

G1. SOMATIC CONCERN

Complaints about physical health or conviction of having a somatic disease or disorder, which can range from vague bodily sensations to distinct delusions of catastrophic (fatal) somatic illness. Assessed based on the patient's statements during the interview.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: noticeable preoccupation with one's health or physical condition, manifested in occasional questions asked and a desire to receive reassurance from the physician.

4. Moderate: complaints of poor health or disorder of individual bodily functions, but there is no delusional conviction; the state can be overcome by encouraging and reassuring the patient.

5. Marked: the patient frequently or constantly complains of a physical illness or dysfunction of bodily functions. One or two delusional ideas on this topic may be present, which do not completely determine the patient's thoughts and behavior.

6. Severe: the patient is sufficiently absorbed by one or more distinct delusional ideas of physical illness or organic lesion of various bodily functions. However, complete engulfment of the personality, including its affective sphere, by delusional ideas is not observed. The physician has difficulty distracting the patient from these thoughts.

7. Extreme: numerous and frequently expressed delusional ideas of somatic illness or several delusional ideas of a catastrophic outcome of the disease, completely absorbing the patient's thoughts and feelings.

G2. ANXIETY

Subjective experience of nervousness, anxiety, apprehension, and foreboding of trouble, ranging from excessive concern about the present or future to panic reactions. Assessed based on information obtained during the interview and corresponding physical manifestations.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: The patient reports some agitation, apprehension, or subjective anxiety, not accompanied, however, by any somatic or behavioral reactions.

4. Moderate: The patient reports increased nervousness and anxiety, accompanied by mild physical signs such as fine hand tremor or sweating.

5. Severe: The patient reports anxiety accompanied by somatic and behavioral reactions such as marked tension, impaired concentration, palpitations, or sleep disturbances.

6. Very severe: Almost constant subjective experience of fear, accompanied by phobias, marked anxiety, and various somatic manifestations.

7. Extreme: The patient's life is significantly disrupted by a nearly constant feeling of anxiety, which may occasionally escalate into panic attacks.

G3. GUILT FEELINGS

Feelings of remorse or self-blame regarding past real or imagined misdeeds. Assessed based on the patient's statements during the interview about feelings of guilt and the degree of their impact on life attitudes and thinking.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: Questioning reveals a vague sense of guilt and self-blame ideas regarding a minor misdeed, which, however, does not heavily preoccupy the patient.

4. Moderate: The patient expresses clear concern about a real misdeed in their life, which, however, does not affect the patient's behavior or fully occupy their attention.

5. Severe: The patient experiences intense guilt with ideas of self-deprecation or punishment. The guilt may be delusional in nature, arise spontaneously, serve as a source of preoccupation and/or depressed mood, and does not subside after a conversation with the physician.

6. Very severe: Persistent ideas of guilt reach delusional proportions and are accompanied by feelings of hopelessness and worthlessness. The patient is convinced that they will soon be punished for their misdeeds and may interpret ongoing events as such a measure of punishment.

7. Extreme: The patient's entire life is subjugated by an unshakeable idea of their guilt. They believe they deserve severe punishment up to and including life imprisonment, torture, or death. Suicidal thoughts or a tendency to attribute problems facing others to their own past misdeeds may concurrently arise.

G5. MANNERISMS AND POSTURING

Unnatural movements and/or postures that impart an awkward, pretentious, dysplastic (disorganized), or eccentric (bizarre) character to the patient's behavior. Assessed based on observation of the physical manifestations of the disorder during the interview, as well as information obtained from relatives and medical staff.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: Some awkwardness (clumsiness) of movements or slight tension (rigidity) of posture.

4. Moderate: Noticeable clumsiness or dysplasticity (discoordination) of movements; the patient may assume unnatural postures for short periods.

5. Severe: The patient occasionally performs strange, ritual-like movements or freezes in unnatural, distorted postures for longer periods.

6. Very severe: Frequent repetition of bizarre, "ritualistic" movements, mannerisms, or stereotyped movements; freezing in unnatural (bizarre) postures may be observed for prolonged periods.

7. Extreme: Normal functioning is severely impaired due to the patient's nearly constant execution of ritualistic and stereotyped movements, pronounced mannerisms, or prolonged freezing in unnatural postures.

G6. DEPRESSION

Experience of sadness, despondency, helplessness, and pessimism. Assessed based on the patient's statements regarding their mood during the interview and corresponding changes in interpersonal relationships and behavior.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: Subjective feelings of sadness and depressed mood can be elicited only through targeted questioning; appearance and behavior remain unchanged.

4. Moderate: Distinct experiences of sadness or hopelessness, which the patient may mention spontaneously, but which do not substantially affect their behavior and social activity. The patient is generally amenable to cheering up.

5. Severe: Markedly depressed mood with sadness, pessimism, loss of life interests, psychomotor retardation, and some sleep and appetite disturbances. Cheering the patient up is difficult.

6. Very severe: Severely depressed mood with persistent experiences of hopelessness, worthlessness, and self-abasement; the patient weeps at times. Concurrently, there is a significant deterioration in sleep and appetite, decreased motor activity, impairment of social functions, and possible lapses in self-care.

7. Extreme: Depressive experiences significantly impair the patient's functioning. Marked somatic disorders, psychomotor retardation, loss of all social interests, lapses in self-care, and impaired concentration are observed. The patient weeps frequently; depressive or nihilistic delusions, as well as suicidal thoughts and actions, may develop.

G7. MOTOR RETARDATION

Reduction in motor activity manifested as slowed movements and speech, sluggish reactions to stimuli, and decreased physical tone. Assessed both through behavior during the interview and from reports by medical staff and relatives.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: Slight but noticeable slowing of movements and speech. Some reduction in productivity during conversation and gesturing may occur.

4. Moderate: The patient's movements are clearly slowed, speech may be unproductive, the patient ponders at length before answering questions, and prolonged pauses and a slowed tempo appear in conversation.

5. Severe: Motor activity is sharply reduced, rendering communication with the patient unproductive and hindering the performance of social and occupational duties. The patient lies or sits for long periods.

6. Very severe: Movements are extremely slowed; motor and speech activity are minimal. The patient spends entire days sitting aimlessly or lying in bed.

7. Extreme: The patient is virtually completely motionless and responds poorly to external stimuli.

G8. UNCOOPERATIVENESS

Active refusal to cooperate and comply with instructions from the physician, medical staff, or relatives, which may be related to distrust, defensive reactions, stubbornness, negativism, rejection of authority, hostility, or combativeness. Assessed by behavior during the interview and information obtained from medical staff and relatives.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: The patient complies with requirements while exhibiting displeasure, impatience, or a sarcastic attitude, and tries to avoid conversations on undesirable topics.

4. Moderate: At times, the patient openly refuses to perform elementary communal living requirements, such as making the bed, following the daily routine, etc.; may display hostile and negativistic defensive reactions, which, however, in most cases does not preclude the possibility of reaching an agreement with them.

5. Severe: The patient frequently fails to observe communal rules; those around them characterize them as an "outcast" or as someone with a severely impaired ability to communicate; during the interview, they are irritable or withdrawn and try to evade answering many questions.

6. Very severe: The patient actively resists cooperation and rapport, exhibits active negativism, and is sometimes hostile; they refuse to follow most communal rules and often do not wish to start or end the conversation.

7. Extreme: Active resistance severely impedes the performance of almost all important social functions. Refusal to participate in any social activities, including personal hygiene rules and conversations with relatives or medical staff, is possible. Even brief dialogue with the patient is difficult.

G9. UNUSUAL THOUGHT CONTENT

Thinking is characterized by the emergence of bizarre, fantastic, or eccentric ideas, varying in content from atypical or detached from reality to distorted, unnatural, or clearly absurd. It is evaluated based on the content of thoughts expressed by the patient during the interview.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: somewhat bizarre or idiosyncratic (non-conventional) thought content, or the use of known ideas in an unusual context.

4. Moderate: frequent distortion of thoughts, sometimes reaching the level of eccentricity.

5. Severe: the patient expresses many bizarre and fantastic thoughts (e.g., believing they are the adopted son of a king or that they just escaped death), and occasionally clearly absurd ones (e.g., having hundreds of children, receiving signals from cosmos through a dental filling).

6. Very severe: the patient expresses numerous illogical, absurd, or extremely eccentric ideas (e.g., having three heads, being an alien from another planet).

7. Extreme: thinking is overloaded with absurd, eccentric, and fantastic ideas.

O10. DISORIENTATION

loss of awareness of one's relationships with reality, including place, time, and surrounding people, due to confusion or detachment from reality. Evaluated based on targeted questioning of the patient.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: general orientation is largely preserved; the patient experiences difficulty with certain specific questions. For example, they may know where they live but confuse the exact address; recognize medical staff by face but not know their duties; know the month but confuse days of the week or err in dates by at least two days. Sometimes a narrowing of the patient's scope of awareness may be noted: they may be oriented within their immediate environment but not beyond it (e.g., the patient knows the staff they have to deal with, but does not know the names of political figures such as the mayor, governor, or president).

4. Moderate: the patient does not always recognize people or correctly name the place or time of stay. For example, they may know they are in a hospital but not its name; know the name of the city but not the region, district, or street; know the attending physician's name but not the names of many other staff members attending to them; can name the year and season, but are confused about the month.

5. Severe: the patient recognizes people with great difficulty, has a very vague idea of their whereabouts, and most people around them seem unfamiliar. They can more or less correctly name the year, but do not know the current month, day of the week, or even the season.

6. Very severe: the patient almost completely fails to recognize people and does not know the time and place of their stay. For example, they have no idea where they are, are off by more than a year in determining the date, and can barely name one or two people who have been around them recently.

7. Extreme: the patient has completely lost orientation regarding people, place, and time; is completely unaware of or incorrectly perceives their whereabouts and the current year; does not recognize the closest people, such as parents, husband (wife), friends, or the attending physician.

O11. ATTENTION IMPAIRMENTS

Impairment of goal-directed attention, manifested by a lack of concentration, increased distractibility by internal and external stimuli, and difficulties in focusing, maintaining, or shifting attention to new objects. Evaluated through observation of the patient throughout the interview.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: limited ability to concentrate attention, manifested by some distractibility or weakening of attention at the end of the interview.

4. Moderate: the interview with the patient is difficult due to increased distractibility, the inability to maintain attention on a given topic for long, or conversely, to quickly switch to new topics.

5. Severe: communication with the patient is seriously impaired due to poor concentration, frequent distractibility, and/or difficulty switching to other topics.

6. Very severe: the patient's attention can be engaged only for a short time or with great difficulty, due to frequent distraction by internal experiences or extraneous external stimuli.

7. Extreme: attention is so severely impaired that even a short conversation becomes impossible.

O12. REDUCED INSIGHT AND AWARENESS OF ILLNESS

Inadequate awareness or understanding of one's mental state and current life situation, manifested by the inability to acknowledge the presence of a disease or its symptoms in the past and present, denial of the need for psychiatric hospitalization or treatment, making decisions without adequate consideration of their consequences, and building unrealistic short- and long-term plans for the future. Evaluated by the content of thoughts expressed by the patient during the interview.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: the patient acknowledges the presence of a mental illness, but underestimates its severity and the need for treatment or prevention. The ability to adequately plan future actions may be impaired.

4. Moderate: the patient has only a vague or formal (superficial) understanding of their illness. At times, they may deny its presence or fail to understand what the main symptoms of the illness are, such as delusions, thought disorders, suspiciousness, or social withdrawal.

   The patient may acknowledge the need for treatment only for manifestations such as anxiety, tension, and sleep disturbances.

5. Severe: the patient acknowledges the presence of mental illness in the past, but not in the present. When questioned, they may point to the presence of some minor or unrelated symptoms, showing a tendency to misinterpret or even delusionally elaborate them. The need for psychiatric treatment is also denied.

6. Very severe: does not consider themselves mentally ill; denies the presence of any psychopathological symptoms both in the past and in the present; while formally agreeing to hospitalization and treatment, they do not understand their meaning and necessity.

7. Extreme: the patient resolutely denies the presence of mental illness both in the past and in the present; interprets hospitalization and treatment through delusional mechanisms (e.g., as punishment for misbehavior, as actions of persecutors, etc.). Consequently, the patient usually refuses to cooperate with medical staff, tries to avoid taking medications, and fails to follow the treatment regimen.

O13. VOLITIONAL IMPAIRMENTS

Impairments of volitional initiative, the ability to achieve goals, and control one's thoughts, behavior, movements, and speech. Evaluated based on the patient's statements and behavior during the interview.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: some indecisiveness is manifested in the patient's speech and thoughts, which has only a minor effect on verbal and cognitive processes.

4. Moderate: the patient is frequently ambivalent and experiences difficulty in making decisions. The interview with the patient is somewhat hindered by the scattered nature of their thoughts, leading to impaired verbal and cognitive functions.

5. Severe: volitional impairments affect both the patient's thinking and behavior; pronounced indecisiveness is detected, which impedes spontaneous motor and social activity and may also manifest as speech disturbances (hesitations).

6. Very severe: volitional impairments hinder the execution of even the simplest, automatic actions, such as dressing and self-care; distinct speech disorders are noted.

7. Extreme: virtually complete absence of volitional acts, manifested by suppression of speech and motor functions up to complete immobility and/or mutism.

O14. IMPAIRED IMPULSE CONTROL (AGGRESSIVENESS)

Impairment in the regulation and control of internal drives, leading to unexpected, unmodulated, voluntary, and non-goal-directed discharge of tension and emotions without regard for potential consequences. Evaluated based on behavior during the interview, as well as reports from medical staff and relatives.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: under stress or when a desire is unfulfilled (delayed gratification), the patient is easily irritated or upset, but rarely acts impulsively in accordance with their experiences.

4. Moderate: the patient becomes angry and prone to verbal attacks at the slightest provocation, occasionally resorting to threats. One or two episodes of physical resistance, quarrels with others, or a tendency toward minor destructive actions may be noted.

5. Severe: Impulsive outbursts are periodically observed, accompanied by insults, property damage, or threats of physical violence. One or two episodes of attacking people (participation in fights) are possible, necessitating patient isolation, physical restraints, or parenteral administration of sedatives.

6. Very severe: Frequent impulsive (uncontrolled) outbursts of aggression are observed; the patient constantly threatens, makes demands, or destroys property without clearly realizing the consequences of these actions. The patient exhibits a clear tendency to participate in fights and other violent acts, including sexually motivated attacks. Behavior may be driven by compliance with imperative hallucinations.

7. Extreme: The patient makes repeated attacks on people with the intent to kill or rape, or commits acts of self-harm, displaying extreme cruelty. Due to the inability to control dangerous impulses, the patient requires constant supervision, isolation, or physical restraint.

O15. PREOCCUPATION WITH INTERNAL EXPERIENCES (DETACHMENT FROM REALITY)

Preoccupation with internal experiences (thoughts, feelings, or autistic fantasies) leading to impaired adaptation and orientation in the surrounding situation. Severity is assessed based on the patient's responses and behavior during the interview.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: Excessive preoccupation with one's needs and problems, manifested in constant attempts to steer the conversation toward topics of concern to the patient, with a lack of interest in the needs of others.

4. Moderate: At times the patient appears withdrawn, absorbed in daydreams or internal experiences, which somewhat hinders conversation.

5. Severe: The patient is absorbed in autistic fantasies or internal experiences, which affects behavior and significantly impairs social and communicative activity. Occasionally, the patient sits with a vacant stare, whispers and/or talks to themselves, and makes stereotyped movements.

6. Very severe: The patient is almost completely absorbed in internal experiences, which significantly impairs the ability to concentrate, participate in conversation, and orient to the surroundings. The patient frequently smiles or laughs at something, whispers, or talks to themselves.

7. Extreme: Complete preoccupation with internal experiences, accompanied by a sharp decline in the level of adaptation. The patient's behavior is entirely governed by hallucinations; they pay little attention to surrounding people and the environment.

O16. ACTIVE SOCIAL WITHDRAWAL

Reduction in social activity driven by groundless fear, hostility, or suspiciousness. Assessed based on information regarding the patient's social activity obtained from medical staff and relatives.

1. Absent: the patient's condition does not meet the definition of the disorder.

2. Minimal: questionable pathology; evaluated signs may represent the upper limit of normal.

3. Mild: The patient feels uncomfortable in the presence of other people and prefers to spend time alone, although they exhibit social activity when necessary.

4. Moderate: The patient is reluctant to participate in all (or most) social activities, requires constant encouragement and coaxing, and may suddenly withdraw from participation if anxiety, suspicion, or hostility arises.

5. Severe: The patient refuses most social contacts with fear or anger, despite attempts by others to engage them. Spends most of the time alone without purpose.

6. Very severe: Due to intense fear, hostility, or suspiciousness, the patient exhibits only the bare minimum of social activity. When approached by others, the patient shows a clear desire to avoid contact and generally tries to stay away from people.

7. Extreme: The patient cannot be engaged in social relationships due to intense fear, hostility, or persecutory delusions. They strive by all means to avoid contact.

G2. Brief Negative Symptom Scale (BNSS)

Original title: Brief Negative Symptoms Scale (BNSS)

Source: Kirkpatrick B, Strauss G, Nguyen L, Fischer B, Daniel D, Cienfuegos A, Marder S. The Brief Negative Symptom Scale: Psychometric Properties. Schizophr Bull 2011 Mar; 37(2): 300-305.

©2014, GREGORY STRAUSS, Ph.D. AND BRIAN KIRKPATRICK, M.D. BNSS_Workbook_ru_V2.1_19SEPT2018_source

Russian version reviewed by Oleg Papsuev, MD, PhD (Armida Mucci, Annarita Vignapiano, Istvan Bitter, Stephen F. Austin, Camille Delouche, Sonia Dollfus, Andreas Erfurth, W. Wolfgang Fleischhacker, Giulia M. Giordano, Igor Gladyshev, Birte Glenthoj. Karoline Gutter, Alex Hofer, Jan Hubenak, Stefan Kaiser, Jan Libiger, Ingrid Melle, Mette 0. Nielsen, Oleg Papsuev, Janusz K. Rybakowski, Gabriele Sachs, Alp Ucok. Pawel Wojciak, Silvana Galderisi. A large European, multicenter, multinational validation study of the Brief Negative Symptom Scale, European Neuropsychopharmacology, Volume 29, Issue 8,2019, 947-959)

Papsuev OO, Movina LG, Gladyshev IO, Shmukler AB. PSYCHOMETRIC PROPERTIES OF THE RUSSIAN-LANGUAGE VERSION OF THE BRIEF NEGATIVE SYMPTOM SCALE (BNSS) IN PATIENTS WITH SCHIZOPHRENIA AND SCHIZOPHRENIA-SPECTRUM DISORDERS // Social and Clinical Psychiatry. 2020; 30(2): 22-30.

Type (underline):

- scale

- index

- questionnaire

- other (specify):

Purpose:

Assessment of the presence and severity of negative symptoms of schizophrenia

Content (template):

Key (interpretation): The BNSS consists of 13 items grouped into six subscales: anhedonia (intensity/frequency/expected pleasure), distress experience, social withdrawal (manifestations/internal experiences), avolition (manifestations/internal experiences), blunted affect (facial expression/speech/gestures), and alogia (speech quantity/spontaneity).

The scale includes a manual, rating sheet, and methodological guide. The manual defines terms used in the scale, provides examples for each item, and gives instructions for the semi-structured interview, including recommended questions. The methodological guide clarifies recommended questions and examples, and provides reference data for the clinician during the examination.

Across all items of the six subscales, higher scores correspond to greater impairment/manifestations of symptoms. The total score on the scale is calculated by summing the 13 individual items; subscale scores are calculated by summing the individual items within each subscale. The distress experience subscale has only a single item that determines the degree of absence of distress experience, but otherwise this subscale is processed similarly. The total BNSS score ranges from 0 to 78 points.

The scale allows for the assessment of two domains of the negative symptom complex in patients with schizophrenia-spectrum disorders. The apathetic-abulic domain is assessed by summing scores on the subscales of anhedonia, avolition, and social withdrawal. Expressive deficit is assessed using the blunted affect and alogia subscales.

1. ANHEDONIA SUBSCALE

Questions for the patient. Items 1 and 2

SOCIAL ACTIVITY: Who did you spend time with last week? What did you do? How did you feel when you interacted with this person? How often did you spend time with him/her?

PHYSICAL SENSATIONS: Was there anything else that gave you pleasant physical sensations last week—some smell, taste, or feeling? If yes: How did you feel about it? And how often did you do this?

RECREATION AND LEISURE: What did you do last week to relax or have fun? How did you feel when doing it? How often did you enjoy it?

WORK AND STUDY: Do you like working (or studying)? If yes: How much do you like it? How often do you enjoy the process of work or study?

Item 1. Intensity of pleasure derived from activities

1. Normal: The patient is able to experience pleasure to the fullest extent when engaging in various activities; fully within the normal range.

2. Questionable: Experiences pleasure during activities, but to a lesser degree compared to many other people, yet within the normal range.

3. Mild: A slight loss in the intensity of pleasure derived from activities.

4. Moderate: A slight loss of pleasure intensity across most activities or a moderate loss of pleasure intensity in some activities.

5. Marked: At least a moderate loss of pleasure intensity across most activities; a profound loss of intensity in one activity is possible.

6. Severe: A profound loss of pleasure intensity across most activities; some ability to experience pleasure remains; only moderate pleasure may be experienced even when the degree of experienced pleasure should be high.

7. Extreme: Complete absence of pleasure under any circumstances.

Item 2. Frequency of activities that bring pleasure to the patient

0. Normal: The patient frequently engages in pleasurable activities; no impairment in frequency of experienced pleasure.

1. Questionable severity: The patient engages in pleasure-seeking activities less often than many people, but the rate may still fall within the normal range.

2. Mild severity: A slight decrease in the frequency of pleasure-seeking activities, falling outside the normal range.

3. Moderate severity: A minor loss in the frequency of experienced pleasure during most activities, or a moderate loss in the frequency of experienced pleasure during some activities.

4. Marked severity: At least a moderate loss in the frequency of experienced pleasure during most activities; a profound loss of intensity in a single activity is possible.

5. Severe severity: A profound loss in the frequency of experienced pleasure during most activities; some capacity to experience pleasure remains, but it occurs rarely, even in situations where the degree of experienced pleasure should be high.

6. Extreme severity: Total absence of experienced pleasure throughout the entire past week.

Item 3. Intensity of expected pleasure during future activities. Questions for the patient.

If the patient experienced pleasure from certain activities last week: You mentioned that you enjoyed (list activities above). Do you plan to do this again soon?

If yes: How do you think you will feel when you are doing this? Are you looking forward to it?

If no: Do you want to do this again? Is there anything else you would do with pleasure? (If yes: How do you think you will feel when you are doing this?)

If the patient did not experience pleasure from any activities last week: Are there any activities you are looking forward to? Is there anything else you are looking forward to?

0. Normal: The patient is able to experience pleasure when thinking about carrying out various activities in the future; entirely within the normal range.

1. Questionable severity: Experiences pleasure when thinking about carrying out various activities in the future, but to a lesser extent compared to many other people, though still within the normal range.

2. Mild severity: Experiences pleasure when thinking about carrying out various activities in the future, but to a slightly lesser extent than expected by norm.

3. Moderate severity: Experiences pleasure when thinking about carrying out various activities in the future, but to a much lesser extent than expected by norm, while still experiencing some degree of pleasure.

4. Marked severity: May experience significant pleasure when thinking about carrying out certain future activities, but as a rule, this does not happen.

5. Severe severity: Rarely experiences pleasure when thinking about carrying out various future activities, even when it involves an activity that usually brings great pleasure.

6. Extremely severe: Does not experience pleasure when thinking about carrying out various future activities, regardless of the activity in question.

II. DEFICIT IN NORMAL DISTRESS EXPERIENCE

Item 4. Deficit in normal distress experience

Questions for the patient

Did anything cause you to experience unpleasant emotions last week? Did anything happen that you did not like? Did anything happen that made you sad, or left you feeling down/depressed? Did anything worry or alarm you? Did anything anger you or cause irritation?

If nothing unpleasant happened: Which of the events that occurred in the past caused you unpleasant feelings? And how do you perceive them now?

1. Normal: The normal capacity to experience distress or unpleasant emotions.

2. Questionable severity: The patient experiences distress due to unpleasant events, but to a lesser extent than many other people, though within the normal range.

3. Mild severity: Experiences distress due to unpleasant events, but to a slightly lesser extent than normal.

4. Moderate severity: Clearly much less upset by unpleasant events than normal, yet experiences some degree of distress.

5. Marked severity: May experience significant distress, but as a rule, this requires a serious problem.

6. Severe severity: Experiences only moderate distress, even when a serious problem exists.

7. Extremely severe: Experiences no distress regardless of the problem encountered.

III. SOCIAL WITHDRAWAL SUBSCALE

Item 5. Social withdrawal: behavioral forms/patterns/stereotypes

Questions for the patient

(To be asked about the people mentioned in items 1–3.) When you spent time together, did you contact them or did they contact you / who initiated contact — you or they? How often did you talk to them about personal, intimate matters? Did you try to contact anyone else?

1. No impairment: The patient frequently interacts with other people, openly discusses personal matters with one or several people; well within the normal range.

2. Minimal deficit: Forms close relationships with one person in which most personal matters can be discussed; actively interacts with other people; discusses some personal matters with others.

3. Mild deficit: Social contacts are frequent, but the patient is not as active as most people; only a few personal matters are discussed; relationships formed are neither close nor deep.

4. Moderate deficit: Lacks close, deep relationships with other people; relationships and communication at events are superficial and shallow, but generally does not avoid other people.

5. Marked deficit: Contacts and communication with other people are mostly infrequent and superficial; tends to avoid others. As a rule, does not discuss personal matters with other people.

6. Significantly marked deficit: Interaction with other people is almost always superficial; spends little time with others by choice.

7. Severe deficit: Rarely contacts other people, may actively avoid others most of the time.

Item 6. Social withdrawal: inner experiences

Questions for the patient

If the patient is socially active: Some people like being alone, while others prefer being around people. What do you prefer? Do you feel that the people mentioned above are close to you? Do you think a lot about the people mentioned above? Would you like to have closer relationships? Do you sometimes feel lonely?

If the patient is not socially active: Would you like to communicate more with people? Do you think about this a lot? How do you feel about being alone most of the time? Are these relationships important to you?

1. No impairment: The patient is very interested in relationships, views relationships with others as one of the most important parts of life; when isolated, frequently feels lonely and thinks it would be better if he/she were not alone.

2. Minimal deficit: The patient considers relationships important; takes an interest in other people; when isolated, sometimes feels lonely and thinks it would be better if he/she were not alone.

3. Moderate impairment: The patient considers close relationships with family member(s) somewhat important, shows moderate interest in other people; lacks close and deep relationships with others; occasionally thinks about relationships.

4. Moderate deficit: The patient considers close relationships unimportant; rarely has a desire to be closer to other people.

5. Marked deficit: When it comes to establishing close relationships with other people, he/she may be indifferent to whether or not they enter into a relationship. As a rule, has no desire to discuss personal matters with others, rarely feels a lack of close relationships or a wish to be in closer relationships.

6. Significantly marked deficit: The patient believes relationships hardly matter at all; shows extremely low interest in close relationships with others, does not feel lonely.

7. Severe deficit: the patient is uninterested in relationships with other people, does not need any close relationships, and categorically prefers to remain alone.

IV. VOLITIONAL IMPAIRMENT RATING SUBSCALE

Item 7. Volitional impairment: forms/models/patterns of behavior

Questions for the patient

General questions: Tell me how you spend your time. Do you spend a lot of time just sitting and doing nothing?

Work and studies:

If currently working or studying:

How much time did you spend at work (or at an educational institution, or devoted to studying) this week? Do you get there on your own? Do you wait for others to tell you what to do, or do you start work (or studies) on your own?

(If undergoing treatment and such a question is appropriate). Have you participated in group activities during the course of your treatment?

If yes: Did someone suggest that you do this, or did you do it on your own?

If currently not working or studying:

Have you tried to find a job or choose a place of study over the past week? Did anyone suggest this to you, or did you do it on your own? What are your goals?

If yes: What exactly did you do?

If no: Why not? (Ask the patient to clarify in their answer whether it is a matter of opportunity or motivation).

Recreation and leisure/hobbies/pastimes: (Information on active recreation and pastimes in items 1–3 must be taken into account). Do you spend a lot of time watching television? (If the answer to the last question is "yes"). Are you interested in what you are watching, or are you just passing time?

Self-care: How often did you take a shower/bath last week? How often did you clean your apartment/room/house? Did anyone have to remind you to do this? Did anyone else remind you to do this? (If appropriate in this case). Did you have a need to look for housing? What did you do for this?

1. No deficit: the patient initiates and continues work or studies, recreation and leisure/hobbies/pastimes, and self-care; well within the normal range.

2. Minimal deficit: the patient is somewhat less consistent in initiating and continuing activities compared to many other people, but the clinical significance is questionable.

3. Mild deficit: moderate impairment in initiating and continuing activities; for example, the patient was able to properly begin an activity last week, but continues with moderate persistence; or initiative came from other people as often as from the patient.

4. Moderate deficit: noticeable impairment in the process of initiating or continuing activities; may fail to begin various activities frequently enough or fail to continue initiated actions for a very long time; other people can often provide the prompt for any activities.

5. Marked deficit: significant impairment regarding initiation; may begin a few activities but not continue them for very long. As a rule, other people provide the prompt for any activities.

6. Severe deficit: evident severe reduction in initiation

and continuation of activities; in some cases may begin activities but barely continue them. Almost always, other people provide the prompt for the patient's various activities.

7. Profound deficit: virtually complete absence of initiation of activities.

Item 8. Volitional impairment: inner experiences Questions for the patient

Work and studies:

If currently working or studying: Is your work (or studies) important to you? Do you think about it a lot? Do you feel interested in/motivated for your work (studies)?

If not working or studying: Do you think about finding a job or enrolling in studies? Do you miss work (or studies)?

If yes: What did you do?

If no: Why not? (Ask the patient to clarify in their answer whether it is a matter of opportunity or motivation).

Recreation and leisure/hobbies/pastimes: What do you do in your free time? What hobbies do you have? Have you thought about them this week?

Self-care: Did you feel motivated to take care of yourself this week? (Clarify if necessary: motivated to wash yourself, clean your home, take care of your health, etc.)

If yes: Why did you want to do this?

1. No impairment: the patient is highly motivated, interested in studies and work, recreation and leisure, and self-care; frequently thinks about them and states that these things matter to him/her. Fully within the norm in this area.

2. Minimal deficit: somewhat less motivated and interested in such things compared to many other people, but the clinical significance is questionable.

3. Mild impairment: as a rule, the patient is motivated in these activities, but in some cases does not show sufficient interest or lacks sufficient motivation; thinks about this and states that these things matter to him/her, but to a somewhat lesser extent than normal.

4. Moderate deficit: the patient is motivated to some extent in these activities, but at the same time some impairment in motivation and interest is evident; may have a job but be uninterested in achieving higher results, or thinks little about relationships or pastimes.

5. Marked deficit: the patient has only weak motivation in these activities; only occasionally thinks about them.

6. Severe deficit: evident lack of interest or motivation in these activities; very rarely thinks about these things and is almost indifferent to them.

7. Profound deficit: essentially a lack of interest in these activities; does not think about them and is completely indifferent to them.

V. BLUNTED AFFECT RATING SUBSCALE

Facial expression

When assessing facial expression, it is necessary to consider mimic movements of all parts of the face, including the eye region (e.g., raised eyebrows), mouth (smiles and grimaces), and midface (e.g., wrinkled nose when the patient experiences disgust).

Item 9. Facial expression

0. No impairment: well within the normal range; the patient talks animatedly about their emotional experiences, while their facial expression changes appropriately many times.

1. Minimal deficit: very slight reduction in the frequency of changes in facial expression and expressive mimicry when talking about emotional experiences, clinical significance is questionable.

2. Mild impairment: moderate reduction in the frequency of changes in facial expression and expressive mimicry; facial expression changes at least twice during the discussion of each emotional experience.

3. Moderate deficit: noticeable reduction in the frequency of changes in facial expression and expressive mimicry, e.g., facial expression changes only once in response to each question.

4. Marked deficit: significant reduction in the frequency of facial expressions and expressive mimicry when talking about emotional experiences, where the facial expression changes in response to only one or two questions; throughout the entire interview, the facial expression may change only three or four times.

5. Severe deficit: evident profound reduction in mimicry reflecting both positive and negative emotions in response to all questions; throughout the entire interview, the facial expression may change slightly only once or twice.

6. Profound deficit: complete or almost complete absence of changes in facial expression throughout the entire interview.

Item 10. Emotional expressiveness of speech (acoustic expressiveness)

0. No impairment: normal variation in all three parameters: speech rate, volume, and pitch during speech.

1. Minimal deficit: mild reduction in one of the three parameters.

2. Mild impairment: moderate reduction in two parameters or a medium-degree reduction in one parameter.

3. Moderate deficit: medium-degree reduction in one parameter.

4. Marked deficit: medium-degree reduction in two or more parameters, or a profound reduction in one parameter.

5. Severe deficit: profound reduction in at least one parameter and a medium-degree reduction in at least one other parameter.

6. Severe deficit: a profound reduction in two or more parameters (speech rate, volume, and pitch during speech).

Item 11. Expressive gestures

0. No deficit: gestures are well within the normal range; the patient uses a wide variety of hand, arm, shoulder, head, and/or body gestures when discussing emotional experiences.

1. Minimal deficit: a very slight reduction in the frequency of expressive gestures; questionable clinical significance; a slight reduction in the use of hands, arms, head, or body is observed.

2. Mild deficit: a moderate reduction in the frequency of expressive gestures; uses at least two expressive gestures when discussing each emotional experience.

3. Moderate deficit: a noticeable reduction in the frequency of expressive gestures; may use a single barely perceptible gesture in response to each question.

4. Marked deficit: significant impairment in the use of expressive gestures, with only a single gesture used in response to only one or two questions; may use only three or four gestures throughout the entire interview.

5. Severe deficit: marked impairment in the use of expressive gestures. A reduction in the number of gestures used is observed across all questions; may use only one or two barely perceptible gestures throughout the entire interview.

6. Extreme deficit: an almost complete absence of expressive gestures; virtually no hand, arm, head, or body movements are used when discussing all emotional experiences.

VI. ALOGIA RATING SCALE

Item 12. Quantity of speech

1. No deficit: the amount of speech is within normal limits or the patient talks very much.

2. Minimal deficit: questionable reduction in speech quantity; responses are mostly laconic.

3. Mild deficit: responses are generally brief.

4. Moderate deficit: many responses consist of one or two words.

5. Marked deficit: at least half of the responses consist of one or two words.

6. Severe deficit: the majority of responses consist of one or two words.

7. Extreme deficit: all or almost all responses consist of one or two words.

Item 13. Spontaneous elaboration

0. No deficit: the patient generally provides more information than is necessary to answer the question; this information may or may not be relevant; the patient may even be overly talkative or exhibit pressured speech.

1. Minimal deficit: the patient frequently provides more information than is necessary to answer the question, although occasionally more information would have been appropriate.

2. Mild deficit: the patient provides additional information several times, but responses are generally limited to the requested information.

3. Moderate deficit: the patient occasionally provides additional information; the interviewer may occasionally need to prompt for details/elaboration.

4. Marked deficit: the patient rarely provides more information than is necessary to answer the question. The interviewer may need to prompt for elaboration several times.

5. Severe deficit: virtually all responses contain only the necessary information or less than necessary; the interviewer may need to repeatedly prompt for more information.

6. Extreme deficit: absence of spontaneous speech at any stage of the interview.

G3. Calgary Depression Scale for Schizophrenia (CDSS)

Original title: Depression rating scale for schizophrenia.

Source: Addington D, Addington J, Schissel B. A depression rating scale for schizophrenics. Schizophr Res. 1990 Jul-Aug; 3(4):247-51.

Type (underline):

- scale

- index

- questionnaire

- other (specify):

Purpose:

Assessment of the presence and severity of depressive symptoms in schizophrenia

Content (template): consists of 9 items, each scored from 0 to 3. Evaluates 3 factors: "depression-hopelessness", "guilt ideas", and "early awakenings"

Scoring (interpretation): a total score of 6 or higher indicates the presence of depression; a total score of 11 and above indicates severe depression

The first question in each section should be asked exactly as written. Follow-up probing questions and clarifications can be used at your discretion.

The time frame referred to is the past two weeks, unless otherwise specified.

The final item, #9, is based on observations made throughout the entire interview.

(1) Depression

How would you describe your mood over the past 2 weeks? Have you been reasonably cheerful or have you been in a severe depression or low spirits lately? Over the past 2 weeks, how often have you been (patient's words) every day? All day?

0. Absent

1. Mild – Expresses some sadness and low spirits.

2. Moderate – Clearly depressed mood for up to half of the time over the past 2 weeks; present daily.

3. Severe – Marked depressed mood, present daily for more than half of the time, interferes with normal physical and social activity.

(2) Hopelessness

How do you see your future? Can you imagine any future, or does life seem quite hopeless to you?

Have you given up, or do you still feel there is some reason to keep trying?

0. Absent

1. Mild – Hopelessness has been felt from time to time over the past week, but there is still some hope for the future.

2. Moderate – Persistent feeling of moderate hopelessness over the past week. The patient can be reassured that things might get better.

3. Severe – Persistent and distressing feeling of hopelessness.

(3) Self-deprecation

How do you rate yourself compared to other people? Do you consider yourself better, worse, or about the same as most others? Do you feel inferior or even worthless?

0. Absent

1. Mild – The patient feels somewhat inferior, but not to the point of feeling worthless.

2. Moderate – The patient feels worthless, but less than 50% of the time.

3. Severe – The patient feels worthless more than 50% of the time. He/she can be reassured.

(4) Ideas of persecution

Do you have a feeling that people are criticizing you for something or even that you are the victim of a false accusation? For what? (This does not include justified criticism or accusations, nor does it include delusions of guilt)

0. Absent

1. Mild – The patient feels that he/she is being criticized, but not accused, less than 50% of the time.

2. Moderate – Constantly feels that he/she is being criticized and/or occasionally feels that he/she is being accused.

3. Severe – Constantly feels that he/she is being accused. If reassured by the interviewer, he/she admits that this is not the case.

(5) Pathological sense of guilt

Do you have a tendency to blame yourself for minor misdeeds, perhaps committed in the past?

Do you think this is a valid cause for concern?

0. Absent

1. Mild – The patient experiences excessive guilt regarding a minor misdeed, but less than 50% of the time.

2. Moderate – The patient usually (more than 50% of the time) experiences feelings of guilt regarding past actions, the significance of which he/she exaggerates.

3. Severe – The patient usually reproaches themselves for everything that went wrong, even if it is not his/her fault.

(6) Diurnal variation

When you felt depressed over the past 2 weeks, did you notice whether the depression was worse at a specific time of day?

0. Absent – No depression

1. Mild – Depression is present, but does not vary throughout the day.

2. Moderate – Without prompting from the interviewer, the patient notes that depression is worse in the morning.

3. Severe – Depression is substantially worse in the morning, accompanied by impaired functioning, with improvement in the second half of the day.

(7) Early awakening

Do you wake up in the morning earlier than is normal for you? How many times a week does this happen?

0. Absent – No early awakening.

1. Mild – Occasionally (up to twice a week) wakes up 1 hour or more before the normal waking time or alarm clock.

2. Moderate – Frequently (up to five times a week) wakes up 1 hour or more before the normal waking time or alarm clock.

3. Severe – Wakes up daily 1 hour or more before the normal waking time.

(8) Suicide

Have you ever had the feeling that life is not worth living?

Have you ever wanted to end your life? How did you intend to do it? Have you ever attempted to do so?

0. Absent

1. Mild – Frequently thought that it would be better to die, or occasionally contemplated suicide.

2. Moderate – Seriously considered suicide and had a plan, but made no attempts.

3. Severe – A suicide attempt was organized in such a way that it should have led to death, but was accidentally discovered, or ineffective means were used.

(9) Observed depression

Based on the interviewer's observations throughout the interview. The question "Do you feel like crying?", asked at appropriate points in the interview, may provide useful information for this observation.

0. Absent

1. Mild – The patient appears sad and gloomy even during emotionally neutral discussions with the interviewer.

2. Moderate – The patient appears sad and gloomy throughout the interview, speaks in a dreary, monotonous voice, and at times weeps or is ready to cry.

3. Severe – The patient falls silent when discussing distressing topics, frequently sighs deeply, and openly weeps or is in a state of grief-stricken stupor.

G4. Personal and Social Performance Scale (PSP)

Original title: Personal and Social Performance scale (PSP)

Source: Morosini PL, Magliano L, Brambilla L, Ugolini S, Pioli R. Development, reliability and acceptability of a new version of the DSM-IV Social and Occupational Functioning Assessment Scale (SOFAS) to assess routine social functioning. Acta Psychiatrica Scandinavica 2000: 101: 323-329.

Type (underline):

- scale

- index

- questionnaire

- other (specify):

Purpose:

Assessment of social functioning in patients with schizophrenia

Content (template): evaluates the degree of difficulty experienced by the patient over the past 7 days in 4 main areas of social functioning: socially useful activities, relationships with close friends and relatives and other social relationships, self-care, and disturbing and aggressive behavior. Scores are given on a scale from 1 to 100, divided into 10 equal intervals, where each interval corresponds to a specific degree of difficulty in social functioning.

Key (interpretation): Total score of 71 to 100: mild impairment of social functioning; total score of 31 to 70: significant impairment of social functioning; more severe difficulties of varying degrees; total score of 1 to 30 points: difficulties in social and socially oriented functioning are so significant that such patients require constant care and supervision.

Instructions for using the PSP scale

The PSP scale is used to assess the degree of difficulty experienced by the patient over the past 7 days in 4 main areas of social functioning: socially useful activities, relationships with close friends and relatives and other social relationships, self-care, and disturbing (i.e., disturbing the peace of others) and aggressive behavior. Scores are given on a scale from 1 to 100, divided into 10 equal intervals, where each interval corresponds to a specific degree of difficulty in social functioning.

Patients scoring 71 to 100 points experience mild difficulties, 31 to 70 experience more serious difficulties of varying severity; patients scoring 1 to 30 points have difficulties in social and socially oriented functioning that are so significant that such patients require constant supervision.

How to complete the PSP scale

• Enter the patient's Case Report Form (CRF) number and patient initials in the PSP WORK SHEET in the appropriate section of the PSP SCORING INSTRUCTIONS.

• Complete the PSP WORK SHEET

(1) Assess the degree of difficulty experienced by the patient over the past 7 days:

(a) in socially useful activities, including work and study

(b) in relationships with close friends and relatives and other social relationships,

(c) in self-care, and

(d) the degree of disturbing and aggressive behavior

(2) To assess the degree of difficulty, follow the prescribed operational criteria. Note that there are two different sets of criteria: one for areas a–c, and a separate one for area d.

(3) Assess the frequency of the patient's disturbing and aggressive behavior (area d) over the past 7 days

If aggressive behavior occurred only once, but the circumstances of the behavior and/or the patient's medical history give the rater reason to believe that it will not recur in the near future, the severity score may be reduced by 1 point (e.g., from "severe" to "marked").

Follow the PSP SCORING INSTRUCTIONS

(4) On the work sheet, select the 10-point interval based on the responses for areas a–d

(5) Select the final score within the chosen 10-point interval, taking into account the level of functioning in other areas specified in the PSP SCORING INSTRUCTIONS (item 5).

(6) Enter the final score in the CRF, and enter the rater's initials and the date of completion.

PSP WORK SHEET

Patient initials:___________ Medical record number:__________

(1) Please evaluate the patient according to the level of functional impairment observed in him/her over the past 7 days. This scale assesses impairments in 4 main areas of functioning:

Absent Mild Apparent Marked Severe Very severe

a) socially useful activities, including work and study

b) relationships with close friends and relatives and other social relationships

c) self-care

d) disturbing and aggressive behavior

(2) The scale provides 2 sets of operational criteria for assessing the degree of difficulty: one for areas a–c, and a separate one for area d.

Severity degrees for areas a–c

(i) Absent

(ii) Mild: known only to very close people

(iii) Moderate: difficulties are obvious to anyone in the patient's environment, but do not significantly impair the patient's ability to function in this area, taking into account the patient's socio-cultural status, age, gender, and education level

(iv) Marked: difficulties strongly interfere with functioning in this area; nevertheless, the patient is still able to function without professional or social assistance, even if not always adequately and/or episodically; with external assistance, he/she is able to reach the previous level of functioning

(v) Severe: the existing difficulties make functioning in this area impossible without professional assistance, or lead to destructive behavior, but nevertheless, there is no threat to life

(vi) Very severe: impairments and difficulties are so pronounced that the patient's life is in danger

Severity levels for domain d

(i) Absent

(ii) Weakly expressed: comes across as somewhat rude, withdrawn, or constantly complaining

(iii) Moderate: for example, speaks too loudly, talks to others too familiarly, or eats in a socially unacceptable manner

(iv) Marked: publicly insults others, breaks or damages things, behavior is often socially unacceptable but not dangerous (e.g., public nudity or urination)

(v) Severe: frequent verbal threats or frequent physical violence, without the intent or ability to cause serious physical harm.

(vi) Very severe: defined as frequent aggressive acts aimed at causing serious physical harm, or acts that are highly likely to lead to serious physical harm.

(3) Assess the frequency of the patient's disruptive and aggressive behavior (domain d) over the past 7 days. If the aggressive behavior occurred only once, but the circumstances of its occurrence and/or the patient's medical history give the assessor reason to believe it will not recur in the near future, the severity score may be reduced by 1 point (e.g., from "severe" to "moderate").

PSP SCORING INSTRUCTIONS

Select a 10-point interval

The 10-point interval is selected based on four main domains: (a) socially useful activities, including work and study; (b) personal and social relationships, (c) self-care, (d) disturbing and aggressive behavior

Full functioning in all four main domains. The patient's positive qualities are highly regarded by others, they cope successfully with everyday problems, and their interests and activities are diverse

Good level of functioning in all four main domains, with only such problems or difficulties as are experienced by all people

Mild difficulties in one or more domains a-c

Marked, but not reaching a severe level, difficulties in one or more domains a-c or mild problems in domain d

Marked difficulties in one of the domains a-c or marked problems in domain d

Marked difficulties in two or more domains a-c, or severe difficulties in one of the domains a-c, with or without marked problems in domain d

Severe difficulties in one and marked difficulties in at least one of the domains a-c, or marked problems in domain d

Severe difficulties in two domains a-c or severe problems in domain d, with or without impairments in domains a-c

Severe impairments in all domains a-d or very severe problems in domain d, with or without impairments in the main domains a-c. If the patient responds to external stimuli, they fall into the 20-16 point interval; if not, into the 15-11 point interval.

Aspontaneity combined with gross behavioral disturbances without danger to the patient's life (scores 6-10) or with danger to the patient's life, e.g., threat of death due to starvation, dehydration, infections, inability to assess a dangerous situation (scores 5-1).

Select a score within the 10-point interval.

When choosing the final score within the 10-point interval (e.g., in the range from 31 to 40), the level of impairment in other domains should be taken into account, such as:

- care for physical and psychological well-being

- ability to maintain the living environment (house, apartment, room) in good condition

- participation in household chores, family life, or inpatient unit life

- intimate and sexual relationships

- childcare

- social connections, relationships with friends and caregivers

- compliance with social rules

- range of interests

- financial management

- use of transport and telephone

- ability to cope with crisis situations

Suicidal behavior and suicide risk are not assessed in this scale

(6) Record the final score, date of completion, and evaluator's initials

Score Date of completion Evaluator's initials

PSP WORKING SHEET

Please evaluate the patient according to the level of functional impairment observed in him/her over the past 7 days.

This scale assesses impairments in 4 main domains of functioning:

The scale provides 2 sets of operational criteria for assessing the severity of difficulties:

one for domains a-c, and a separate one for domain d.

Severity levels for domains a-c Severity levels for domain d

Very severe: impairments and difficulties are so pronounced that the patient's life is in danger

Instructions for scoring the final PSP score

71-100: Scores in this range correspond only to mild difficulties

31-70: Scores in this range correspond to varying degrees of limited functioning

1-30: Scores in this range correspond to extremely severe deterioration in functioning, requiring active support or supervision.

PSP SCORING INSTRUCTIONS

More detailed scoring instructions are provided in the brief description of the PSP scale.

100–91 Good functioning in all four main areas. The patient's positive qualities are highly appreciated by others, they cope successfully with everyday problems, and their interests and activities are diverse.

90–81 Good level of functioning in all four main areas, with only such problems or difficulties as are experienced by all people.

80–71 Slight difficulties in one or more areas a-c

70–61 Noticeable, but not major difficulties in one or more areas a-c or slight problems in area d

60–51 Moderate difficulties in one of the areas a-c or noticeable problems in area d

G5. Urgent Suicide Risk Assessment Scale

Original title: SAD-Persons scale for suicide risk assessment

Source: Patterson W et al, Psychosomatics, 1983, 24, 343-349

Type (underline):

- scale

- index

- questionnaire

- other (specify):

Purpose: screening scale for urgent assessment of suicide risk

Content: a short 10-item scale, each scored 2 points (0 – absence of the sign; 1 – presence of the sign) corresponding to a suicide risk factor.

Key (interpretation): presented directly on the scale form itself. Depending on the identified severity of suicide risk, the authors propose an algorithm of therapeutic measures ranging from outpatient care to involuntary hospitalization.

Data interpretation

G6. Columbia-Suicide Severity Rating Scale (C-SSRS)

Original title: Columbia-suicide severity rating scale (C-SSRS)

Source: Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification Algorithm of Suicide Assessment (C-CASA): Classification of Suicidal Events in the FDA’s Pediatric Suicidal Risk Analysis of Antidepressants. Am J Psychiatry, 2005; 164:1035- 1043.

Russian version: Tsukarsi E.E. Suicide: risk assessment and first aid. Modern Therapy of Mental Disorders, 2011: 2, 30-40

Type (underline):

- scale

- index

- questionnaire

- other (specify):

Purpose: comprehensive assessment of suicide risk

Content (template): consists of 3 blocks: suicidal ideation, intensity of suicidal ideation, and suicidal behavior. It is a semi-structured interview.

Key (interpretation): The scale is essentially a "roadmap" for a comprehensive assessment of a patient at risk for suicide. It has no quantitative score. Clinical application is based on the ability to identify and evaluate various aspects that determine suicide risk. It is recommended to compare the current assessment with retrospective data (at the time of suicide attempts). Can be used for dynamic assessment of suicide risk.

SUICIDAL IDEATION

Ask questions 1 and 2. If the answer to both is negative, proceed to the "Suicidal Behavior" section. If the answer to question 2 is "yes", then ask questions 3, 4, and 5. If the answer to question 1 and/or 2 is "yes".

fill out the "Intensity of Suicidal Ideation" section below.

I. Desire to die

The patient confirms experiencing thoughts about the desire to die or Yes No

to stop living, or the desire to fall asleep and not wake up. □ □

Have you had a desire to die or fall asleep and not wake up?

If yes, describe:

If yes, describe:

5. Current suicidal ideation with specific plan and intent Suicidal thoughts, including a plan with fully or partially elaborated details and some intent by the patient to carry out this plan.

Have you started developing or have you already developed a detailed suicide plan?

Do you intend to carry out this plan?

If yes, describe:

I. Duration

When you have such thoughts, how long do they last?

1. They are fleeting - a few seconds or minutes

2. Less than an hour / short duration

3. 1-4 hours / long duration

4. 4-8 hours / most of the day

5. More than 8 hours / they are persistent or constant

Controllability

Could / can you stop thinking about suicide or the desire to die if you wanted to?

1. Can easily control such thoughts

2. Can control such thoughts with minor difficulty

3. Can control such thoughts with some difficulty

4. Can control such thoughts with great difficulty

5. Unable to control such thoughts

SUICIDAL IDEATION

Ask questions 1 and 2. If the answer is negative in both cases, proceed to the "Suicidal Behavior" section. If the answer to question 2 is "yes", then ask questions 3, 4, and 5. If the answer to question 1 and/or 2 is "yes".

fill out the "Suicidal Ideation Intensity" section below.

1. Wish to die

Patient confirms experiencing thoughts of a desire to die or stop living, or a desire to fall asleep and not wake up.

Have you had a desire to die or fall asleep and not wake up?

If yes, describe:

2. Active non-specific suicidal thoughts

General non-specific thoughts of wanting to end one's life / commit suicide

"I thought about killing myself" in the absence of thoughts about methods/means of suicide, intent, or a plan during the observation period.

Have you actually thought about killing yourself?

If yes, describe:

3. Active suicidal ideation, including thoughts about a method of suicide (not a plan), with no intent to act. The patient confirms having thoughts of suicide and that during the observation period he/she thought of at least one method of suicide. This situation differs from when the patient has developed a specific plan: time, place, or details of the suicide method (e.g., the patient thought of a suicide method, but not a specific plan). This includes people who say: "I thought about a pill overdose, but never made a specific plan about when, where, and how to do it... And I would never go through with it"

Have you thought about how you might do it?

If yes, describe:

4. Active suicidal ideation, including some intent to act in the absence of a specific plan.

Active suicidal thoughts with the patient stating some intent to act on these thoughts, as opposed to a statement such as: "I have these thoughts, but I definitely won't do anything about them."

Have you had such thoughts, and did you have any intent to act on them?

If yes, describe:

5. Current suicidal ideation with specific plan and intent Suicidal thoughts, including a plan with fully or partially elaborated details and some intent by the patient to carry out this plan.

0. Does not attempt to control such thoughts

Deterrents

Is there anything or anyone (e.g., family, religion, fear of pain/death) that keeps you from wishing to die or from trying to act on suicidal thoughts?

1. Deterring factors would definitely keep you from attempting suicide

2. It is likely that deterrent factors held you back

3. You are not sure whether deterrent factors held you back

4. Most likely, deterrent factors did not hold you back

5. Deterrent factors definitely did not hold you back

0. Not applicable

Basis for Suicidal Ideation

What reasons did you have for thinking about the desire to die or suicide? Did you want to die to end the pain or stop experiencing what you were experiencing (in other words, you could not continue living while experiencing this pain or what you were experiencing), or was your goal to attract attention, seek revenge, or get a response from others? Or both?

1. Solely to attract attention, take revenge, or elicit a response from others

2. Mostly to attract attention, take revenge, or elicit a response from others

3. Equally to attract attention, take revenge, or elicit a response from others and to end/stop the pain

4. Mostly to end/stop the pain (you could not continue living while experiencing this pain or what you were experiencing)

5. Solely to end or stop the pain (you could not continue living while experiencing this pain or what you were feeling)

0. Not applicable

SUICIDAL BEHAVIOR

(Check all that apply, provided they refer to different instances; you must ask about all types of suicide attempts)

Actual suicide attempt:

An act potentially directed against oneself, performed with at least some desire to die as a result of the act. The actions taken were partly intended as a way to kill oneself. The intent to kill oneself does not necessarily have to be 100%. An act can be considered a true suicide attempt if even the slightest intention or desire to die is associated with it. Actual self-injury or maiming is not strictly necessary; the potential for self-injury or maiming is sufficient.

If a person pulls the trigger while holding a gun in their mouth, but the gun jams and therefore the person sustains no injury, this is considered a suicide attempt.

Establishing intentionality: Even if a person denies the intention or desire to die, the intentionality of their actions can be clinically established based on their behavior or circumstances. For example, cases involving a lethal action that is definitely not an accident, and therefore suicide is the only possible explanation for such an action (e.g., shooting oneself in the head, jumping from a high-floor window). Intentionality of a suicide attempt can also be inferred if the person denies the intent to die, but believes that their actions could lead to death.

Have you made a suicide attempt?

Have you taken any actions with the purpose of harming yourself? Have you taken any dangerous actions that could have led to your death?

What did you do?

Did you commit [the act] as a way to end your life?

Did you want to die (even a little bit) when you

Did you try to end your life when you, or did you believe you could die from

Or did you do this for entirely different reasons / without any intention to kill yourself (e.g., to relieve tension, feel better, elicit compassion, or because you wanted something to happen)? (Non-suicidal self-injurious behavior, without suicidal intent)

If yes, describe:

Was non-suicidal self-injurious behavior noted in the patient?

Aborted suicide attempt:

When a person is interrupted and fails (due to circumstances) to initiate an act potentially directed against oneself (otherwise a true suicide attempt would have occurred).

Overdose: The person is holding pills in their hand, but is prevented from swallowing them. As soon as the person swallows the pills, the attempt is considered true rather than aborted. Shooting: A person points a gun at themselves, but someone takes the weapon away or someone/something prevents them from pulling the trigger. As soon as the person pulls the trigger, even if it misfires, the attempt is considered true. Jumping: A person is ready to jump, but is grabbed and pulled back from the edge. Hanging: A person ties a noose around their neck, but has not yet hanged themselves—they are stopped.

Has it ever happened that when you started performing actions to end your life, someone or something stopped you before you actually did anything?

If yes, describe:

General

number

attempts

Yes No □ □

General

number

interrupted

attempts

Aborted suicide attempt:

When a person begins taking steps toward making a suicide attempt, but stops themselves before actually engaging in self-destructive behavior. Examples of aborted suicide attempts are similar to those of interrupted suicide attempts, except that the individual stops themselves rather than something else stopping him / her.

Have there been times when you started to do something to end your life, but stopped yourself before you actually did anything?

If yes, describe:

medical attention (e.g., patient is conscious but drowsy, partially responsive to external stimuli, second-degree burns, bleeding from a major vessel).

3. Moderately severe physical injury: requires hospitalization and likely intensive care (e.g., comatose state with preserved reflexes, third-degree burns covering less than 20% of the body, severe but non-fatal blood loss, major fractures).

4. Severe physical injury: requires hospitalization and intensive care (e.g., comatose state without reflexes, third-degree burns covering more than 20% of the body, severe blood loss with unstable vital signs, major damage to vital organs).

5. Death.

0 = Behavior unlikely to result in injury

1 = Behavior likely to result in injury, but unlikely

to result in death

2 = Behavior likely to result in death despite available medical care

Simpson-Angus Scale for Extrapyramidal Symptoms (SAS)

1. Source (official developer website, validation publication): Simpson GM, Angus JWS. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand. 1970;212 (suppl 44):11-19.

2. Type (underline):

- scale

- index

- questionnaire

- other (specify):

Purpose:

Content (template): The examination should be conducted in a room that allows the patient to walk a distance naturally, at their usual pace, for example, 15 steps. Each body part is assessed; if the disorder is more pronounced in one body part than another, the more severe one is scored. The cogwheel phenomenon may be palpated during the examination of items 3, 4, 5, and 6. This is the only supplementary method for determining rigidity, but it is not scored separately. The presence of this symptom only indicates that a score of at least 2 must be given.

Scoring (interpretation) key:

Evaluated across 10 parameters on a scale from 0 to 4. The total score ranges from 0 to 40 (furthermore, a scale score can be obtained by dividing the total sum by 10 to yield a score between 0 and 4)

Scoring:

>3 – within normal limits;

>6 – mild symptom severity;

>12 – pronounced EPS manifestations;

>18 – severe EPS

1. Gait

Assessed by observing the patient entering the examination room; their gait, arm movements, and overall posture together form the basis for the general score on this item.

0. Normal

1. Slightly noticeable reduction in arm swing during walking

2. Definite reduction in arm swing indicating shoulder girdle rigidity

3. Stiff gait with barely noticeable or absent arm swing

4. Rigid gait with slightly pronated arms; or patient is heavily stooped, shuffling, forward movement is difficult

2. Arm dropping

Patient and examiner both raise the patient's arms to shoulder level and let them drop freely. In a normal response, a loud slap against the body is clearly heard. In marked parkinsonism, the arms descend very slowly.

3. Shoulder shaking

The patient's arms are bent at the elbows at a right angle; the examiner holds one hand by the wrist while simultaneously grasping the other at the elbow. The upper arm is pushed back and forth while the humerus is rotated outward. Resistance is assessed according to the specified grades. The procedure is repeated with palpation of the shoulder during rotation.

4. Elbow rigidity

Arms bent at right angles at the elbows are passively flexed and extended one by one, while the patient's biceps are inspected and palpated. Resistance to the procedure is assessed.

0. Normal, free arm drop, clear slap heard, rebound present

1. Slightly slowed drop, weakened slap sound, minimal rebound

2. Slowed drop, no rebound

3. Marked slowing of the drop, absence of slap

4. Arms descend as if overcoming resistance; "as if through glue"

3. Shoulder shaking

The patient's arms are bent at the elbows at a right angle; the examiner holds one hand by the wrist while simultaneously grasping the other at the elbow. The upper arm is pushed back and forth while the humerus is rotated outward. Resistance is assessed according to the specified grades. The procedure is repeated with palpation of the shoulder during rotation.

0. Normal

1. Slight stiffness and resistance

2. Moderate stiffness and resistance

3. Marked rigidity, difficulty with passive movements

4. Pronounced stiffness and rigidity, joint almost "frozen"

4. Elbow rigidity

Arms bent at right angles at the elbows are passively flexed and extended one by one, while the patient's biceps are inspected and palpated. Resistance to the procedure is assessed.

0. Normal

1. Slight stiffness and resistance

2. Moderate stiffness and resistance

3. Marked rigidity, difficulty with passive movements

4. Pronounced stiffness and rigidity, joint almost "frozen"

The examiner holds the patient's wrist with one hand and their fingers with the other, flexing and extending the patient's hand at the wrist joint in ulnar and radial directions, or the extended hand is released to drop under its own weight, or the grasp can be made above the wrist to shake the patient's hand. A score of "1" corresponds to a hand that easily extends, drops freely, or dangles up and down with ease.

0. Normal

1. Slight stiffness and resistance

2. Moderate stiffness and resistance

3. Marked rigidity, difficulty with passive movements

4. Pronounced stiffness and rigidity, joint almost "frozen"

6. Head rotation

The patient, sitting or standing, is informed that their head will be turned from side to side, that it will not hurt, and that they should relax. (Inquiries regarding potential neck pain and movement limitations must be made in advance to avoid causing pain). Cup the patient's head between your palms with your fingers resting on the occiput. Gently rotate the head three times and assess resistance to this movement.

0. Rotates easily, without resistance

1. Slight resistance to movement, although rotation time does not change

2. Noticeable resistance, rotation time increased

3. Clear resistance, rotation slowed

4. The head appears rigid, rotation is difficult

7. Glabellar tap

The patient is asked to open their eyes wide and not blink. The glabella region is tapped at a constant, rapid rate. The number of times the patient manages to blink is noted. You should stand behind the patient so they do not see the finger strikes. It is not necessary to see the entire blink; it may be a muscle contraction if the periocular muscles twitch each time in response to the finger stimulus. Vary the tapping speed to ensure the muscles react correspondingly to the strikes.

0. 0-5 blinks

1. 6-10 blinks

2. 11-15 blinks

3. 16-20 blinks

4. 21 blinks or more

8. Tremor

Observe the patient as they enter the examination room and continue to observe while they flex their arms at the elbows at a right angle and spread their fingers as wide as possible.

0. Within normal limits

1. Mild finger tremor, visible to the eye and palpable

2. Irregular tremor of the hands or arms

3. Persistent tremor of one or more limbs

4. Whole-body tremor

9. Salivation

The patient is observed during conversation, then asked to open their mouth and raise their tongue.

0. Within normal limits

1. Salivation is increased such that with the mouth open and tongue raised, an accumulation of saliva is visible in the mouth

2. Salivation is increased to the extent that it occasionally causes speech difficulties

3. Speech is impaired due to excessive salivation

4. Profuse drooling

10. Akathisia

The patient is examined for motor restlessness. If present, the question is asked: "Do you feel inner motor restlessness or inner trembling; is it difficult for you to stay still?" The patient's subjective opinion is not strictly necessary, but it can help with accurate assessment.

0. Motor restlessness is neither reported by the patient nor observed

1. Mild motor restlessness observed

2. Moderate motor restlessness observed

3. Motor restlessness observed frequently

4. Motor restlessness was observed constantly

G8. Bush-Francis Catatonia Rating Scale (BFCRS)

Russian name: Bush-Francis Catatonia Rating Scale

Original name: The Bush-Francis Catatonia Rating Scale (BFCRS)

Source (official developer website, validation publication): Bush G, Fink M, Petrides G, Dowling F, Francis A. Catatonia. I. Rating scale and standardized examination // Acta Psychiatr Scand. - 1996.- Vol.93. № 3. P.129-136.

Type (underline):

- rating scale

- index

- questionnaire

- other (specify):

Purpose: Assessment of catatonia symptom severity during therapy.

Comment: The scale consists of 23 catatonia symptoms. The first 17 items of the scale are scored depending on the severity of the symptom ranging from 0 to 3 points. For the remaining 6 items, 0 points are given if the symptom is absent, and 3 points if the symptom is present. The reliability of the scale was tested in 44 simultaneous assessments of 28 cases defined by the presence of > or = 2 signs in the first 14 items selected for screening. The inter-rater reliability of the total score on the rating scale was 0.93, and the average item agreement was 88.2% (SD 9.9). The inter-rater validity of the total score for the screening tool was 0.95, and the average item agreement was 92.7% (SD 4.9). Diagnostic consistency was high based on catatonia criteria proposed by other authors [48]. The patient is assessed based on observations of their behavior. To establish catatonia, two or more of the first 14 screening symptoms must be present for more than 24 hours[451]