List of Abbreviations
BP – blood pressure
WHO – World Health Organization
HPLC-MS – high-performance liquid chromatography-mass spectrometry
GC-MS – gas chromatography-mass spectrometry
DA – Dopamine
ICT – immunochromatographic rapid diagnostic test
CA – catecholamines
VS – volatile solvents
Russian Ministry of Health – Russian Ministry of Health
ICD-10 – International Classification of Diseases, 10th Revision
NA – noradrenaline
psychoactive substance – psychoactive substance
PD – psychotic disorder
AI – acute intoxication
HR – heart rate
RR – respiratory rate
ECG – electrocardiogram
GPP – good practice point
X-ray – radiography
US – ultrasound examination
CT – computed tomography
MRI – magnetic resonance imaging
GABA – gamma-aminobutyric acid
NMDA receptors – glutamate (N-methyl-D-aspartate) receptors
Terms and Definitions
Psychoactive substance (PAS)-induced psychotic disorder (PD) is a disorder occurring during or immediately after the use of PAS, characterized by vivid hallucinations (usually auditory, but often involving more than one sensory modality), false recognitions, delusions, and/or ideas of reference (often of a paranoid nature), psychomotor disorders, and abnormal affect ranging from intense fear to ecstasy [1].
Psychoactive substance – a substance of natural or synthetic origin capable of producing effects desired by the user upon single administration, and mental and physical dependence upon systematic use.
Hallucinations – a perception disorder in the form of images and representations arising without a real object.
Delusions — a set of morbid ideas, reasoning, and conclusions that dominate the patient's consciousness, distort reality, and are not amenable to external correction.
Psychomotor disorders — disturbances of voluntary actions, facial expressions, and pantomime, presenting as stupor or excitation. In stupor, the patient freezes in one posture, becomes inactive, stops answering questions, stares fixedly into space, and refuses food. In psychomotor agitation, the patient is constantly in motion, talks incessantly, sometimes grimaces, and may be foolish, aggressive, and impulsive (performing unexpected, unmotivated acts).
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
PAS-induced PD is a condition occurring during, immediately after, or within 2 weeks of PAS use. It is characterized by vivid hallucinations (usually auditory, but often involving more than 1 sensory modality), false recognitions, delusions, and/or ideas of reference (often of a paranoid or persecutory nature), psychomotor disorders (excitation or stupor), and abnormal affect ranging from intense fear to ecstasy. Consciousness is usually clear, though some degree of clouding may occur without progressing to severe confusion. Psychotic symptoms persist for more than 48 hours. The disorder typically resolves at least partially within 1 month and completely within 6 months. PAS-induced PDs may vary in symptoms depending on the type of substance used and the personality of the user. At the same time, the clinical picture of PDs induced by different PAS may share certain similarities. PD can occur at any stage of dependence, but predominantly in the middle and late stages [1].
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
The cause of the psychotic disorder is an imbalance in neurotransmitter system activity resulting from prolonged, systematic use of a PAS (or multiple PASs). The onset of a PAS-induced psychosis is likely associated with dysfunctions in one or more neurotransmitter systems: the dopaminergic system, primarily concerning stimulants and psychedelic substances; the cannabinoid system, with cannabis and synthetic cannabinoids; and the serotonergic system, with hallucinogenic plants, newer phenethylamines, and tryptamine derivatives. Glutamate receptors (NMDA receptors) are also implicated in psychotic disorders, with a proven link to ketamine and phencyclidine [2].
The triggering moment in the development of a psychotic disorder is typically the prolonged duration of a recent PAS binge and/or unusually high doses of the consumed PAS. The main cause of psychoses is considered to be not so much the direct effect of the PAS on the brain as metabolic disturbances and a certain predisposition to psychotic reactions. This tendency is most pronounced in alcohol-induced PDs [3, 4]. More than 50% of individuals abusing PAS exhibit some comorbid psychiatric disorder: 26% with an affective disorder (depression or mania, occurring 4.7 times more frequently than in non-PAS-dependent individuals), 28% with an anxiety disorder (2.5 times more frequently), 17.8% with antisocial personality disorder (13.4 times more frequently), and 6.8% with schizophrenia (6.2 times more frequently) [4, 5]. It is believed that psychotic disorders caused by the use of certain PASs are risk factors for schizophrenia-spectrum disorders. Schizophrenia is diagnosed within eight years in 46% of individuals who experienced cannabis-induced psychosis and 30% of those who experienced amphetamine psychosis [6]. High activity of natural and synthetic cannabinoids as triggering factors for the development of psychoses with a schizophrenia-like picture has been demonstrated [7, 8].
The pathogenesis of PAS-induced PD remains insufficiently studied to date. Most researchers view psychosis as the result of the simultaneous influence of multiple factors (hypoxia, hypercapnia, ischemia, cerebral metabolic disorders, dyscirculatory vascular changes, etc.). According to A.V. Snezhnevsky (1974), the action of exogenous factors actualizes the body's existing predisposition to the formation of certain psychopathological states. With prolonged PAS exposure, the roles of age, sex, additional somatogenic and constitutional factors, and the selective action of toxic substances on various body systems become apparent. The clinical picture is also significantly influenced by endocrine status and various socio-psychological factors [9].
1.3 Epidemiology of the Disease or Condition
Worldwide, the most prevalent psychoses are those developing during the alcohol withdrawal period. According to the World Health Organization (WHO), alcoholic psychoses occur in 10% of patients with alcoholism, while domestic authors report up to 15% [10]. According to epidemiological studies, the prevalence of dependence on alcohol and other PASs in Russia has slightly decreased over recent years. Thus, in 2021, the number of patients with alcohol dependence seeking addiction treatment was 818.2 per 100,000 population, of whom 25.2 per 100,000 population had alcoholic psychoses. Meanwhile, in the same year, the number of patients with psychoactive substance dependence syndrome was 155.5 per 100,000 population, and with non-psychoactive substance dependence syndrome, 3.5 per 100,000 population [11].
Psychoses developing against the background of the use or withdrawal of PASs other than alcohol are much less studied. Epidemiological studies conducted in Scandinavian countries investigated psychoses resulting from cannabis and stimulant use, estimating their prevalence at 2.7 cases per 100,000 population per year [12]. In recent years, there has been a significant increase in the incidence of psychoses induced by synthetic cannabinoids and stimulants among youth and adolescents [7]. Psychotic disorders resulting from caffeine use are not encountered in clinical practice.
Reliable data on the prevalence of psychoses associated with the use of other PASs are lacking.
1.4 Features of Coding the Disease or Condition
The diagnosis is coded using the International Classification of Diseases, 10th Revision (ICD-10). The ICD-10 variant adapted for Russia uses 7 characters, which allow for the formalization of the diagnosis of the disorder detected in the patient.
In ICD-10, PD induced by various PASs (alcohol, opioids, cannabinoids, sedatives and hypnotics, cocaine, other stimulants including caffeine, hallucinogens, volatile solvents) and induced by concurrent PAS use are discussed in the respective sections according to the type of substance. The presence of PD is designated by the fourth character 5 (F1x.5x). (Table 1) [1].
In categories F13, F15, F16, and F19, where a specific substance may be classified as either a narcotic or a substance subject to abuse (toxicomania), additional letter codes are introduced. If the psychotic disorder (PD) is caused by a narcotic substance, the Russian letter "H" is appended to the end of the code. A narcotic substance is a psychoactive substance (PAS) included in lists 1 and 2 of the official "List of Narcotic Drugs, Psychotropic Substances, and Their Precursors Subject to Control in the Russian Federation". If the PAS is not narcotic, the substance is classified as a substance subject to abuse, and the Russian letter "T" is appended to the end of the code [1].
Table 1. ICD-10 diagnosis formalization.
ICD-10 Diagnosis Code | ICD-10 Diagnosis |
|---|---|
F10.5 | Alcohol-induced psychotic disorder |
F12.5 | Cannabinoid-induced psychotic disorder |
F13.5 | Sedative- or hypnotic-induced psychotic disorder (F13.-T; F13.-H) |
F14.5 | Cocaine-induced psychotic disorder |
F15.5 | Other stimulant-induced psychotic disorder, including caffeine (F15.-T; F15.-H) |
F16.5 | Hallucinogen-induced psychotic disorder (F16.-T; F16.-H) |
F19.5 | Multiple drug use and use of other psychoactive substances-induced psychotic disorder (F19.-T; F19.-H) |
The diagnosis of a psychotic disorder is specified by the 5th character depending on the predominant type of psychotic disturbance (Table 2):
Table 2. Specification of psychotic disorder diagnosis.
ICD-10 Diagnosis Code | ICD-10 Diagnosis |
|---|---|
F1x.50 | Schizophrenia-like disorder |
F1x.51 | Predominantly delusional disorder |
F1x.52 | Predominantly hallucinatory disorder |
F1x.53 | Predominantly polymorphic psychotic disorder |
F1x.54 | Disorder with predominantly depressive psychotic symptoms |
F1x.55 | Disorder with predominantly manic psychotic symptoms |
1.5 Classification of the disease or condition
PDs caused by PAS use are classified as exogenous or symptomatic psychoses. The key factor in their classification is the type of psychotic disturbance predominating in the clinical picture—hallucinations, delusions, persistent affective disturbance. PAS-induced PDs are also classified according to the substance that caused the psychosis. Any PD is a severe mental disorder and requires immediate specialized medical care [1].
1.6 Clinical presentation of the disease or condition
The clinical picture of PD due to PAS use is characterized by productive psychopathological symptoms of psychotic level in the form of perceptual disturbances (illusions, hallucinations, and pseudohallucinations) and delusions, as well as affective disorders, behavioral disturbances, psychomotor agitation or retardation, and the inability to comprehend one's actions and direct them.
2. Diagnostics, medical indications and contraindications for diagnostic methods
The diagnosis of PD due to PAS use is based on the presence of persistent psychotic disturbances (lasting 2 days or more) in a patient who has used PAS: perceptual disturbances and/or thought disorders. Disturbances of consciousness (delirium, oneiroid state) may occur with hallucinogen use.
2.1 Complaints and Anamnesis
It is recommended that all patients in a psychotic state with suspected PAS-induced PD, for the purpose of establishing this diagnosis, when eliciting complaints and taking the medical history, pay attention to the following diagnostic criteria according to the International Classification of Diseases, 10th Revision [1]:
- presence of hallucinations (usually auditory, but often involving more than 1 sensory modality) and/or delusions, combined with psychomotor disturbances (agitation or stupor), affective disorders;
- presence of clear consciousness (some degree of clouding is possible, but not progressing to severe confusion);
- onset of PD during PAS use or within 2 weeks of intake;
- persistence of psychotic symptoms for more than 48 hours;
- development of PD at any stage of dependence syndrome, but most frequently in the middle and terminal stages;
- development of PD against the background of high-dose PAS use and/or prolonged intake;
- reduction of psychotic symptoms after cessation of PAS use in the majority of cases.
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
2.2 Physical Examination
It is recommended that all patients in a psychotic state with suspected PAS-induced PD undergo an examination to assess the dynamics of the patient's condition and the safety of ongoing therapy, including examination of the skin, muscle tone, liver, kidneys, heart, lungs, blood pressure, heart rate, and respiratory rate [13].
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
It is recommended that all patients with suspected PAS-induced PD undergo a neurological examination to assess the dynamics of the patient's condition and the safety of ongoing therapy: presence or absence of nystagmus, tremor, state of the peripheral nervous system — tactile and pain sensitivity, static and dynamic coordination [13].
LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).
2.3 Laboratory Diagnostics
It is recommended that patients in a psychotic state, to confirm a provisional diagnosis of "PAS-induced PD" based on clinical and anamnestic data, undergo forensic chemical and chemical-toxicological testing (analysis) of blood, urine, and internal organs for alcohol, narcotic drugs and psychotropic substances, toxic agents, and medicinal products using thin-layer chromatography (TLC), high-performance liquid chromatography with mass spectrometric detection (HPLC-MS), or gas chromatography with mass spectrometric detection (GC-MS) [14].
LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).
Comments: Thin-layer chromatography is relatively inexpensive in terms of capital equipment and other initial costs, but less sensitive. Gas chromatography and high-performance liquid chromatography provide high sensitivity and specificity. [14].
It is recommended that all patients in a psychotic state with suspected PAS-induced PD be prescribed a complete blood count (CBC) with differential to rule out comorbid conditions and assess potential therapy complications [13].
LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).
It is recommended that all patients in a psychotic state with suspected PAS-induced PD be prescribed a general clinical blood chemistry panel (testing blood total bilirubin, blood gamma-glutamyl transferase activity, blood alanine aminotransferase activity, blood aspartate aminotransferase activity, blood total protein, blood urea, blood creatinine, blood glucose) to rule out comorbid conditions and assess potential therapy complications [13].
LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).
It is recommended that all patients in a psychotic state with suspected PAS-induced PD be prescribed a urinalysis to rule out comorbid conditions and assess potential therapy complications [13].
LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).
2.4 Instrumental Diagnostics
Performing these diagnostic procedures does not refine the diagnosis of PAS-induced PD. However, they are necessary for the early diagnosis of existing complications of chronic PAS use, which can significantly affect the outcome of PD.
It is recommended that all patients in a psychotic state with suspected PAS-induced PD undergo an electrocardiogram (ECG) recording with decoding, description, and interpretation of electrocardiographic data to rule out comorbid conditions and assess potential therapy complications [13].
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
2.5 Other Procedures
2.5.1 Psychopathological examination
Diagnosis of clinical variants of PD is based on identifying psychotic symptoms characteristic of the given variant using the psychopathological method. For each clinical variant, there are core features that predominate in its clinical picture [1].
2.5.1.1 Schizophrenia-like disorder F1x.50
Clinical manifestations of schizophrenia-like disorder due to PAS use practically do not differ from the symptoms of schizophrenic psychosis. The core features for establishing the F1x.50 diagnosis in a patient with schizophrenia-like symptoms are anamnestic and laboratory data indicating that the development of these symptoms was preceded by the patient's use of certain PAS. Approximately 1/3 of patients are subsequently diagnosed with true schizophrenia-spectrum disorders, but such a diagnosis is valid only if PD persists for more than 6 months, provided the patient has not used PAS during this period [1].
It is recommended that all patients in a psychotic state with suspected schizophrenia-like PD due to PAS use rely on the presence of the following features characteristic of schizophrenia to confirm this diagnosis [1, 13, 15]:
- thought disorders in the form of incoordination, sperrung, difficulty concentrating and making correct decisions with preserved consciousness and memory (in some cases, anterograde and congrade amnesia are possible);
- hallucinations;
- delusions;
- phenomena of psychic automatism;
- psychomotor agitation;
- catatonic disorders, such as: agitation, freezing or waxy flexibility, negativism, mutism, and stupor;
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
Comments:
After cessation of psychoactive substance use, the clinical picture shows a gradual reduction of psychotic disorders without the formation of a schizophrenic defect. This variant of psychotic disorder is typical for patients dependent on cannabinoids, stimulants, and hallucinogens, and is rarely observed in alcohol-dependent individuals [1, 7, 13, 15-19].
2.5.1.2 Predominantly delusional disorder F1x.51
It is recommended for all patients in a psychotic state with suspected predominantly delusional psychotic disorder due to psychoactive substance use, in order to confirm this diagnosis, to rely on the following key feature:
predominance in the clinical picture of psychosis of persistent delusions (primary or secondary, developing after a relatively short period of hallucinatory experiences) [1, 10, 13].
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
Comments:
Most commonly, delusional disorder manifests as acute paranoid syndrome, developing suddenly with affective disorders in the form of anxiety and fear. Perceptual disturbances in the form of auditory illusions and/or verbal hallucinations are characteristic. Then the patient develops the conviction that they are being watched, discussed, and that there is a conspiracy to harm them. Perceptual disturbances are usually of short duration, whereas delusions are typically persistent, prone to chronicity and relapse. The patient's behavior is determined by their personality traits (they may attack others to eliminate an imaginary threat, hide, etc.). Acute paranoid states develop in patients dependent on alcohol, cocaine and other stimulants, sedatives, hypnotics, and cannabinoids [10, 13].
In alcohol-dependent individuals, a typical delusional disorder is alcohol-induced jealousy delusions (alcoholic paranoia). It is usually observed in elderly patients; the development of psychosis is preceded by ideas of marital infidelity appearing during alcohol intoxication or alcohol withdrawal. With the development of alcoholic paranoia, an irresistible conviction of the wife's infidelity arises, while any facts, sometimes directly contradicting the idea of marital infidelity, are interpreted in its favor. The patient constructs a whole system of evidence that the wife has been cheating on him for many years, that the children were born from a lover, etc. Quite often, ideas of jealousy are accompanied by ideas of material loss (the patient is sure that the wife married him to take over his property), poisoning, litigiousness, etc. Alcoholic paranoia is often accompanied by altered behavior with rudeness and aggression towards the wife, less often towards the imaginary rival. During treatment, paranoid delusions usually give way to persistent residual ones [10, 13].
Other variants of delusions may also be observed:
- delusions of control (most frequently observed in cannabinoid-dependent patients);
- hypochondriacal delusions (most characteristic of patients dependent on cocaine and other stimulants, and alcohol) [10, 13].
2.5.1.3 Predominantly hallucinatory disorder F1x.52
It is recommended for all patients in a psychotic state with suspected predominantly hallucinatory psychotic disorder due to psychoactive substance use, in order to confirm this diagnosis, to rely on the following key feature:
- predominance of hallucinatory disorders in the clinical picture of psychosis [1, 10, 13].
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
Comments:
Acute hallucinosis typically manifests with the appearance of elementary and simple perceptual disorders (knocking, noises, music). Perceptual disturbances are accompanied by affective disorders in the form of anxiety, fear, perplexity, and sleep disturbance. Then hallucinations acquire a verbal character, most often in the form of a conversation between two or more people discussing the patient's personality, accusing them, condemning them, and threatening them with various punishments. Perceptual disturbances are usually true in nature, meaning that in the patient's perception they possess the same signs of reality as surrounding objects and phenomena (i.e., for example, a hallucinatory voice sounds the same as the voice of a real interlocutor), and they naturally fit into the environment (i.e., hallucinatory images are projected into the surrounding space). Patients are convinced that they perceive these images in the exact same way as the rest of the world, i.e., through their sense organs. Often it seems to them that those around them experience the exact same feelings but conceal it for incomprehensible reasons. Against this background, secondary delusions (of reference, accusation, etc.) frequently develop. Unlike delusional and schizophrenia-like psychoses, delusional ideas in hallucinatory disorders are usually closely tied to the hallucinatory plot, are interpretative and unstable in nature, and critical insight may be preserved even at the height of experienced hallucinations. The patient's behavior is determined by the content of hallucinatory experiences and their personality traits. In addition to verbal hallucinosis, other types may be observed – visual, tactile, and visceral. The most common is hallucinatory disorder caused by alcohol use. Hallucinatory psychotic disorders can also arise due to the use of stimulants, sedatives, hypnotics, and cannabinoids. Hallucinatory disorder caused by cocaine use is characterized by tactile hallucinations in the form of sensations of insects crawling on the skin or penetrating under it [10, 13].
2.5.1.4 Predominantly polymorphic psychotic disorder F1x.53
It is recommended for all patients in a psychotic state with suspected predominantly polymorphic psychotic disorder due to psychoactive substance use, in order to confirm this diagnosis, to rely on the following key features [1, 10, 13]:
- a combination in the clinical picture of various persistent psychotic disorders – perceptual disturbances and delusions, which are markedly variable and change from day to day, or even from hour to hour.
- lability and a wide range of affective reactions (intense transient feelings of happiness and ecstasy, anxiety, and irritability).
- polymorphism and instability, with a changing clinical picture of psychosis.
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
Comments:
A predominantly polymorphic psychotic disorder is characterized by a combination of illusory and/or hallucinatory disorders with delusions (most commonly of persecution). Increased excitability, motor activity, and affective disturbances are characteristic. It develops in patients dependent on alcohol, cocaine and other stimulants, sedatives, hypnotics, and cannabinoids [1, 10, 13].
2.5.1.5 Psychotic disorder with predominantly depressive psychotic symptoms F1x.54
It is recommended for all patients in a psychotic state with suspected psychotic disorder due to psychoactive substance use with predominantly depressive symptoms, in order to confirm this diagnosis, to rely on the presence of the following features [1, 10, 13]:
- predominance of depressive disorders in the clinical picture (persistent decrease in mood, self-esteem, mental activity, anhedonia);
- presence of psychotic symptoms (hallucinations and/or delusions).
RUD CLOE 5Level of Recommendations Confidence C (Level of Evidence 5) Comments:
This psychotic disorder is characterized by a combination of depressive disorders (decreased mood, self-esteem, activity, pessimistic assessment of current events) with psychotic symptoms. Psychotic disorder with predominantly depressive psychotic symptoms manifests with verbal hallucinations accusing the patient, instilling thoughts of worthlessness, and suicidal thoughts. Delusional ideas of guilt, reference, and self-depreciation are possible, along with suicidal actions. Diurnal mood fluctuations are characteristic: signs of depression are most pronounced in the morning hours, and the condition may improve towards evening. Sleep disturbances (insomnia or hypersomnia) and eating disorders are frequently observed. According to ICD-10 criteria, depressive states are diagnosed if the listed symptoms are present and persist for more than two weeks. At the same time, this diagnosis can also be established in cases characterized by a shorter timeframe, but with unusually severe and rapidly onset symptoms. Psychotic disorder with predominantly depressive symptoms is observed in patients with dependence on cocaine and other stimulants, alcohol, sedatives and hypnotics, and hallucinogens (ketamine, phencyclidine) [1, 10, 13].
2.5.1.6 Psychotic disorder with predominantly manic psychotic symptoms F1x.55
It is recommended for all patients in a psychotic state with suspected psychotic disorder due to psychoactive substance use with predominantly manic symptoms, in order to confirm this diagnosis, to rely on the presence of the following features [1, 10, 13]:
- persistent elevated mood;
- acceleration of the thought tempo with facilitation of the associative process (reduction of the latency between thoughts, loosening of criteria for the emergence of associations);
- increased drive and motor activity;
- presence of psychotic symptoms (hallucinations and/or delusions).
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
Comments:
The development of this mental and behavioral disorder (MBD) is characterized by agitation, increased motor and ideational activity, combined with hallucinatory disorders and delusions (of grandeur, reference, and persecution). It is observed in patients with dependence on cocaine and other stimulants, hallucinogens, alcohol, sedatives, and hypnotics [1, 10, 13].
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
3.1 General aspects of the treatment of psychotic disorders
MBDs resulting from the use of various psychoactive substances (PAS) can manifest with identical psychopathological symptoms, and conversely, the use of the same PAS can lead to the development of different MBDs. Treatment strategy and tactics should be based primarily on the current symptoms that directly determine the patient's mental status.
3.2 Specific aspects of the treatment of psychotic disorders
3.2.1 Physical restraint of the patient
It is recommended to ensure physical restraint of a patient with an MBD due to PAS use in the event of psychomotor agitation, in order to prevent inappropriate, aggressive, or auto-aggressive actions on their part and to safely administer psychopharmacotherapy [13].
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
Comments:
Restraint should be performed as delicately as possible, using soft, non-traumatic means (towels, sheets, cloth straps, etc.). Each limb and the shoulder girdle must be securely restrained; compression of nerve trunks and blood vessels must be avoided. The restrained patient must be constantly within the field of vision of the staff. Restraint does not imply the removal of supervision, but rather requires constant monitoring of the patient's condition. The use of patient restraint requires a mandatory entry in the medical documentation.
3.2.2 Pharmacotherapy
It is recommended to prescribe a drug from the "anxiolytics" group, diazepam** or bromdihydrochlorophenylbenzodiazepine** intravenously or intramuscularly, to patients with MBDs due to PAS use for the treatment of psychomotor agitation [13, 20].
LeR CLoE 5Level of Evidence Recommendations C (Level of Data Validity 5).
Comments:
Diazepam** is prescribed as a 0.5% solution, administered slowly, not exceeding 60 mg per day. In children older than 5 years, Diazepam** is prescribed intravenously and slowly at 1 mg every 2–5 minutes until a maximum dose of 10 mg is reached. If necessary, treatment is repeated after 2–4 hours. An alternative to diazepam** is bromdihydrochlorophenylbenzodiazepine** (up to 6 mg per day intravenously or intramuscularly) [13]. Bromdihydrochlorophenylbenzodiazepine** is contraindicated under the age of 18.
It is recommended to prescribe drugs from the "antipsychotic drugs" group to patients with MBDs due to PAS use for comprehensive MBD therapy, provided there are no contraindications to specific drugs in accordance with the instructions [7, 13, 21, 20, 22, 23].
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
Comments: Antipsychotic drugs are symptomatically prescribed to patients with MBDs for the treatment of psychotic disorders—hallucinations and/or delusions [7, 13, 20–27]. Atypical antipsychotics are the most effective and safe. #Olanzapine** is prescribed orally at a dose of 5 mg to 20 mg per day, or #quetiapine** orally at a dose of 100 to 300 mg per day. These drugs are contraindicated under the age of 18. As an alternative, #risperidone** may be prescribed orally at a dose of 2 to 6 mg/day. For patients aged five years and older with a body weight of 50 kg or more, the recommended starting dose is 0.5 mg once daily. If necessary, this dose may be increased by 0.5 mg daily, no more frequently than every other day. For most patients, the optimal dose is 1 mg daily. However, some patients prefer 0.5 mg daily, while others require an increase to 1.5 mg daily.
For patients with a body weight of less than 50 kg, the recommended starting dose is 0.25 mg once daily. If necessary, this dose may be increased by 0.25 mg daily, no more frequently than every other day. For most patients, the optimal dose is 0.5 mg daily. However, some patients prefer 0.25 mg daily, while others require an increase to 0.75 mg daily. In cases of psychomotor agitation or aggressive behavior, periciazine** is prescribed orally at a dose of 5 to 30 mg per day (in short courses, combined with anxiolytics) [13]. In children aged 3 years and older, periciazine is prescribed for severe behavioral disorders with agitation and excitability. Periciazine is contraindicated in patients under 3 years of age. In cases of psychomotor agitation or refusal of enteral medications by a patient with an MBD, haloperidol** is administered intramuscularly or intravenously at a single dose of 5 mg, with a maximum daily dose of 60 mg. In children aged over 3 years, haloperidol** is prescribed at 0.025–0.05 mg per day, with a maximum daily dose of 0.15 mg/kg. Haloperidol is not prescribed to patients under 3 years of age. Despite the high efficacy of haloperidol** regarding psychotic disorders, the drug is used in short courses for emergency indications due to the potential development of severe complications (neuroleptic malignant syndrome, cardiac rhythm disturbances, dyskinesia, etc.) [13].
It is recommended to prescribe sleeping pills belonging to the group of "benzodiazepine-like agents" to adult patients with MBDs due to PAS use for the treatment of insomnia [28, 29].
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
Comments:
It is advisable to prescribe zopiclone** 7.5–15 mg or zolpidem 5–10 mg [28, 29]. These drugs are contraindicated in patients under 18 years of age.
3.2.3 Rehydration therapy
It is recommended to prescribe drugs from the group "Oral rehydration salt formulations" or infusion therapy with drugs from the group "solutions affecting water-electrolyte balance" to patients with MBDs due to PAS use in the presence of water-electrolyte balance disorders [13, 30].
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
Comments: Patients with MBDs are characterized by increased physical and mental activity; body temperature, respiratory rate, and sweating may increase. Consequently, fluid loss increases. In most cases, oral rehydration is sufficient. In cases where the patient cannot drink independently or refuses fluid intake, infusion therapy is prescribed. The volume and duration of infusion therapy are determined by the severity of volume disorders [13, 30].
3.3 Psychotherapy for psychotic disorders resulting from psychoactive substance use
The possibilities of using various psychotherapy methods in MBDs are limited. Family counseling must be conducted in such a way as to involve family members and significant others in the therapeutic program to prevent the continuation of PAS use. Psychotherapy is indicated for the patient after the abatement of psychotic phenomena.
It is recommended to conduct family psychotherapy for all patients with MBDs due to PAS use and their relatives or significant others to increase the efficacy of complex treatment [31–34].
Level of Recommendation ALevel of Evidence 1Level of Evidence Reliability A (Level of Evidence 1)
4. Medical Rehabilitation and Sanatorium-Resort Treatment
Specific rehabilitation of patients who have suffered MBDs caused by PAS use is not carried out. After the abatement of MBDs and the treatment of dependence syndrome, rehabilitation measures are carried out in the same way as for other patients with PAS dependence syndrome [13].
5. Prevention and Dispensary Observation
In MBDs caused by PAS use, tertiary (modification) prevention is of the utmost importance; it is predominantly medical, individual, and oriented towards individuals with established PAS dependence. Such prevention is aimed at preventing the recurrence of the psychotic disorder and reducing harmful consequences for the mental and somatic sphere of the patient who has suffered psychosis.
It is recommended that all patients with MBDs due to PAS use, after the reduction of psychotic disorders, undergo dispensary observation in accordance with the Procedure for Dispensary Observation of Individuals with Mental Disorders and/or Behavioral Disorders Associated with PAS Use [13].
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
6. Organization of Medical Care
Recommendations regarding the organization of medical care for patients with MBDs caused by PAS use are given in accordance with Order of the Ministry of Health of the Russian Federation No. 1034 dated December 30, 2015 (registered with the Ministry of Justice of Russia on March 22, 2016, No. 41495) "On approval of the procedure for providing medical care in the profile 'psychiatry-narcology' and the procedure for dispensary observation of individuals with mental disorders and/or behavioral disorders associated with the use of psychoactive substances."
It is recommended to perform an examination of a patient with an MBD due to PAS use by a psychiatrist-narcologist [13].
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
It is recommended in cases of MBDs due to PAS use with persisting hallucinatory and delusional disorders lasting more than 30 days to transfer patients to a psychiatric hospital [13].
GCR CLEL 5Grade of Recommendations C (Level of Evidence 5)
Comments: In accordance with Order of the Russian Ministry of Health No. 372n dated June 1, 2012, "On Approval of the Standard of Specialized Medical Care for Adults with Mental and Behavioral Disorders Caused by Psychoactive Substance Use (Psychotic Disorder) (Diagnostics and Treatment)", the recommended average duration of a treatment course is 20 days. In most cases, reduction of psychotic symptoms of substance-induced psychotic disorders occurs within 2-14 days. In rare cases, when the duration of the psychotic disorder exceeds 30 days, it is advisable to transfer the patient to a psychiatric hospital, since the treatment of such patients in a substance abuse (narcological) inpatient facility currently lacks legal grounds. At the same time, Federal Law No. 3185-I of July 2, 1992, "On Psychiatric Care and Guarantees of Citizens' Rights in Its Provision", allows for the continuation of treatment for such patients in a psychiatric hospital.
7. Additional Information
The development of a psychoactive substance-induced psychotic disorder requires immediate medical care in a substance abuse (narcological) or psychiatric inpatient facility. Due to the danger the psychotic disorder poses to the health and life of the patient and others, involuntary hospitalization of such patients is possible (Federal Law No. 3185-I of July 2, 1992, "On Psychiatric Care and Guarantees of Citizens' Rights in Its Provision").
Criteria for Evaluating the Quality of Medical Care
Quality criteria for specialized medical care for adults with psychotic disorders caused by the use of psychoactive substances (ICD-10 codes: F10.5; F12.5; F13.5; F14.5; F15.5; F16.5; F19.5)
№ | Quality criteria | Level of evidence | Grade of Recommendation |
|---|---|---|---|
1. | Examination by a psychiatrist-narcologist performed | 5 | C |
2. | Forensic chemical and chemical-toxicological examination (assay) performed for the content of alcohol, narcotic drugs and psychotropic substances, toxic agents, and medications in blood, urine, and internal organs using thin-layer chromatography (TLC), high-performance liquid chromatography with mass spectrometric detection (HPLC-MS), or gas chromatography with mass spectrometric detection (GC-MS). | 5 | C |
3. | Electrocardiogram recording performed | 5 | C |
4. | General therapeutic biochemical blood analysis performed (assay of total bilirubin level in blood, determination of gamma-glutamyl transferase, alanine aminotransferase, and aspartate aminotransferase activity, assay of total protein level in blood, assay of urea level, assay of creatinine level in blood, assay of glucose level in blood) | 5 | C |
5. | A complete blood count (differential) was performed | 5 | C |
6. | A general (clinical) urinalysis was performed | 5 | C |
7. | Therapy with medications from the "antipsychotics" group administered (in the absence of medical contraindications) | 5 | C |
8. | Therapy for psychomotor agitation with medications from the "anxiolytics" group administered (in the absence of medical contraindications) | 5 | C |
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Appendix A1. Working Group Composition
Co-Chairs:
Klimenko, Tatyana Valentinovna, MD, Prof.
Krupitsky, Evgeny Mikhailovich, MD, Prof.
Secretary:
Gubanov, Georgy Alexandrovich
Working Group Members:
Agibalova, Tatyana Vasilyevna, MD
Arkus, Maxim Leonidovich, PhD
Buzik Oleg Zhanovich, Doctor of Medical Sciences
Vinnikova, Maria Alekseevna, MD
Vyshinsky Konstantin Vitalievich, Candidate of Medical Sciences
Korchagina, Galina Alexandrovna, MD, Prof.
Ilyuk Ruslan Dmitrievich, D.Sc. in Medicine
Lobacheva Anna Stanislavovna, Ph.D. in Medicine
Mikhailov Mikhail Albertovich, D.Sc. in Medicine
Nadezhdin Alexey Valentinovich, Ph.D. in Medicine
Nenastyeva Anna Yuryevna, Candidate of Medical Sciences
Poplevchenkov Konstantin Nikolaevich, Ph.D. in Medicine
Rybakova Ksenia Valeryevna, D.Sc. in Medicine
Fadeeva Evgenia Vladimirovna, Candidate of Psychological Sciences
Authors:
Mikhailov Mikhail Albertovich, Doctor of Medical Sciences. Russian Association of Narcologists (Professional Community of Addiction Physicians). Russian Society of Psychiatrists.
Utkin Sergey Ionovich, Candidate of Medical Sciences. Russian Association of Narcologists (Professional Community of Addiction Physicians). Russian Society of Psychiatrists. Federation of Anesthesiologists and Reanimatologists.
Conflict of interest: none
All working group members confirmed the absence of financial support/conflict of interest that needs to be disclosed.
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience of these clinical guidelines:
Psychiatrist-narcologist
District psychiatrist-narcologist
Adolescent psychiatrist
Psychiatrist
District psychiatrist
Psychotherapist
Medical psychologist
General Practitioner
Neurologist
The following information resources were used in the development of these clinical guidelines:
· "Requirements for the preparation of clinical guidelines for placement in the Rubricator." Letter of the First Deputy Minister of Health I.N. Kagramanyan dated September 01, 2016, No. 17-4/10/1-4939.
· Analysis of scientific literature sources and other data, as well as internet resources over the past 10 years:
- domestic: medical guidelines, scientific publications in periodicals, e-library scientific electronic library, State Register of Medicines, Register of Medicines, Federal State Statistics Service of the Russian Federation;
- foreign: Cochrane Library, Medline, MedScape, PubMed, National Institute on Alcohol Abuse and Alcoholism (NIAAA), Substance Abuse and Mental Health Services Administration (SAMSHA), European Monitoring Centre for Drugs and Drug Addiction (EMCDDA);
- Regulatory documents of the Government of the Russian Federation and the Ministry of Health of the Russian Federation.
Rating schemes for assessing the levels of evidence reliability (1, 2, 3, 4, 5) (Appendix 1, 2) and the levels of recommendation validity (A, B, C) (Appendix 3) were used in the development of these clinical guidelines.
Appendix 1. Scale for assessing levels of evidence reliability (LER) for diagnostic methods (diagnostic interventions)
LoE | Definition |
|---|---|
1. | Systematic reviews of studies with reference standard control or systematic reviews of randomized controlled trials with meta-analysis |
2. | Individual studies with reference standard control or individual randomized controlled trials and systematic reviews of studies of any design, except randomized controlled trials, with meta-analysis |
3. | Studies without consecutive reference standard control or studies with a reference standard not independent of the test method, or non-randomized comparative studies, including cohort studies |
4. | Non-comparative studies, case report |
5. | Only justification of mechanism of action or expert opinion is available |
Appendix 2. Scale for assessing levels of evidence reliability (LER) for methods of prevention, treatment, and rehabilitation (preventive, therapeutic, rehabilitation interventions)
LoE | Definition |
|---|---|
1. | Systematic review of randomized controlled trials with meta-analysis |
2. | Individual randomized controlled trials and systematic reviews of studies of any design, except randomized controlled trials, with meta-analysis |
3. | Non-randomized comparative studies, including cohort studies |
4. | Non-comparative studies, case report or case series, case-control study |
5. | Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available |
Appendix 3. Scale for assessing levels of recommendation validity (LRV) for methods of prevention, diagnosis, treatment, and rehabilitation (preventive, diagnostic, therapeutic, rehabilitation interventions)
GoR | Definition |
|---|---|
A | Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent) |
B | Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent) |
C | Weak recommendation (lack of adequate quality evidence (all considered efficacy criteria (outcomes) are unimportant, all studies are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
Appendix A3. Reference Materials
Instructions for the medicinal products recommended in these clinical guidelines are available on the State Register of Medicines website: https://grls.minzdrav.gov.ru/
Various psychotic-spectrum disorders (illusions, hallucinations, delusions) characteristic of substance-induced psychotic disorders can also be observed during acute substance intoxication. In acute intoxication, such disturbances are short-lived and transient. An exception is acute intoxication with hallucinogens (F16.0xx), following which psychotic disorders may persist for a considerable time. In this case, a diagnosis of a psychotic disorder can only be made if the psychotic symptoms cannot be explained by the intoxicant effect of the hallucinogen. It is necessary to consider the possibility of a psychotic disorder developing as a result of another pathological process not related to substance use or aggravated (accelerated) by such use: for example, schizophrenia (F20.-), affective disorders (F30-F39), paranoid or schizoid personality disorder (F60.0x; F60.1x). In such cases, the diagnosis of a substance-induced psychotic disorder would be incorrect.
Order of the Ministry of Health and Social Development of the Russian Federation No. 40 dated January 27, 2006, "On the Organization of Chemical and Toxicological Research in the Analytical Diagnosis of the Presence of Alcohol, Narcotics, Psychotropic, and Other Toxic Substances in the Human Body." Registered by the Ministry of Justice of Russia on February 26, 2006.
Order of the Ministry of Health of the Russian Federation No. 108 dated April 8, 1998, "On Emergency Psychiatric Care."
Letter of the Ministry of Health of the Russian Federation No. 2510/12967-02-32 dated December 26, 2002, "On Measures of Physical Restraint in the Provision of Psychiatric Care."
Order of the Ministry of Health of the Russian Federation No. 1034 dated December 30, 2015 (registered with the Ministry of Justice of Russia on March 22, 2016, No. 41495), "On Approval of the Procedure for Providing Medical Care in the Profile 'Psychiatry-Narcology' and the Procedure for Dispensary Observation of Persons with Mental Disorders and/or Behavioral Disorders Associated with Psychoactive Substance Use."
Appendix B. Physician Action Algorithms
![Appendix B. Physician Action Algorithms — Mental and behavioral disorders due to psychoactive substance use [alcohol, cannabinoids, sedatives and hypnotics, cocaine, other stimulants (except caffeine), hallucinogens, and multiple psychoactive substances] Psychotic disorder](/cr/img/817/a1.webp)
Appendix C. Patient Information
In addictology, psychoses (psychotic disorders) are understood as the most prominent manifestations of mental illnesses in which the patient's mental activity is disrupted, manifested in behavioral disorders, impaired reasoning, inability to make correct decisions, and disorientation in space and time. The main manifestations of psychoses are:
Perceptual disturbances (hallucinations). These can be simple (ringing, noise, calling) or complex (speech, scenes). The most common are auditory hallucinations, so-called "voices," which a person may hear coming from the outside or sounding inside the head, and sometimes the body. In most cases, the voices are perceived so vividly that the person has not the slightest doubt about their reality. Voices can be threatening, accusing, neutral, or imperative (commanding). Imperative voices are considered the most dangerous, as people often obey the voices' commands and commit acts dangerous to themselves or others.
Delusions — judgments and conclusions that do not correspond to reality, completely take over the patient's consciousness, and are not amenable to correction through persuasion and explanation. Most commonly encountered: delusions of persecution (being watched, desire to kill, intrigues woven, conspiracies organized), delusions of influence (by psychics, aliens, intelligence agencies using radiation, "black" energy, witchcraft, spoilage), delusions of damage (poison being added, things stolen or ruined, attempts to evict from an apartment), hypochondriacal delusions (the person is convinced they suffer from some disease, often terrible and incurable, stubbornly arguing that their internal organs are affected, demanding surgical intervention). Delusions of jealousy, invention, grandeur, reformism, special origin, love, litigiousness, etc., are also encountered.
Motor disorders, manifested in the form of retardation (stupor) or excitation. In stupor, the person freezes in one posture, becomes immobile, stops answering questions, stares fixedly at a single point, and refuses food. Conversely, people in a state of psychomotor agitation are constantly in motion, talk incessantly, sometimes grimace, mimic, act foolishly, and are aggressive and impulsive (committing unexpected, unmotivated acts).
Mood disorders, manifested by depressive or manic states. Depression is characterized by lowered mood, anguish, despondency, motor and intellectual retardation, disappearance of desires and drives, reduced energy, pessimistic evaluation of the past, present, and future, ideas of self-blame, and thoughts of suicide. A manic state is manifested by groundlessly elevated mood, acceleration of thinking and motor activity, overestimation of one's own capabilities with the construction of unrealistic, sometimes fantastic plans and projects, disappearance of the need for sleep, and disinhibition of drives (abuse of alcohol, drugs, indiscriminate sexual relations).
Psychotic disorders caused by the use of specific psychoactive substances can only be diagnosed given reliable life history data regarding the recent use of a specific psychoactive substance. Such a diagnosis is established only if no more than 2 weeks have passed from the time of the last psychoactive substance intake to the onset of psychosis. In addition, there must be reliable evidence of systematic abuse of the given psychoactive substance. Psychotic disorders require mandatory inpatient treatment. After the psychotic disorder is resolved, the patient requires treatment for psychoactive substance dependence.
Recommended algorithm of actions for relatives of individuals who have developed a psychotic disorder:
Stay calm. When communicating with the patient, maintain a calm tone and demonstrate your support and understanding. Avoid judging them or denying their experiences, as this may worsen their condition.
Establish an emotional connection with the patient, showing them that you are ready to listen and understand them. Be patient and give them the opportunity to express their thoughts and feelings.
Contact the emergency psychiatric service (by calling 103 or 112), as a patient in a psychotic state requires treatment in a specialized psychiatric or narcological hospital setting. Sometimes it is necessary to make decisions about care without regard for the patient's own opinion; however, one should always strive for the patient's consent to treatment, as this is a primary principle in providing care.
Support the treatment regimen. Your support and participation in the treatment process play an important role. Participate in their inpatient treatment by supporting them during hospital visits, and help the patient follow the doctor's recommendations after discharge from the hospital.
Obtain necessary information. Seek help from professional psychiatrists-narcologists to get additional information about psychosis and the best ways to respond and support the patient. This will help you better prepare for situations that may arise and more effectively help your loved one.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Scales and questionnaires are not used for the diagnosis of substance-induced psychotic disorders.