Contents · 12 sections
In a nutshell. Schizophrenia is a chronic mental disorder characterized by positive (delusions, hallucinations, disorganization), negative (avolition, alogia, anhedonia, affective flattening), and cognitive symptoms. Onset at 15–35 years, prevalence ~1%. Diagnosis is clinical (ICD-11, DSM-5): symptoms $\ge$ 1 month, with DSM-5 requiring a total duration of $\ge$ 6 months. The mainstay of treatment is antipsychotics (D2 blockade): typical (haloperidol) and atypical (olanzapine, risperidone, aripiprazole); for treatment-resistant cases — clozapine. Negative and cognitive symptoms respond poorly to pharmacotherapy; psychosocial rehabilitation and CBT are essential.
1. Epidemiology and etiology
- Prevalence ~1% in the general population, with no significant gender differences.
- Onset: males 15–25 years, females 25–35 years.
- Genetics: concordance rate in monozygotic twins 40–50%, 10% risk for a child of an affected parent.
- Neurobiology: dopamine hypothesis ($\uparrow$ D2 in the mesolimbic system — positive symptoms; $\downarrow$ D1 in the prefrontal cortex — negative/cognitive symptoms), glutamate hypothesis (NMDA hypofunction), serotonin hypothesis (5-HT2A).
- Environmental factors: prenatal infections, birth hypoxia, cannabis use in adolescence, urbanization, migration.
2. Symptomatology
Positive symptoms
- Delusions: persecutory, of reference, of control, grandiose.
- Hallucinations: most commonly auditory ("voices"), less commonly visual or tactile.
- Speech disorganization: derailment, neologisms, tangentiality.
- Disorganized/catatonic behavior.
- Schneider's first-rank symptoms: thought echo, voices in dialogue, third-person commentary voices, somatic passivity, thought withdrawal, thought insertion, thought broadcasting, delusional perception.
Negative symptoms (the "5 A's")
- Avolition — decrease in motivation.
- Alogia — poverty of speech.
- Anhedonia — inability to experience pleasure.
- Affective flattening.
- Asociality.
Cognitive symptoms
- Impairment in attention, working memory, and executive functions.
- Determine social and occupational prognosis more than positive symptoms do.
3. Diagnostic criteria
ICD-11 (6A20)
- At least 2 symptoms from: delusions, hallucinations, thought disorganization, experiences of control, negative symptoms, grossly disorganized behavior, psychomotor disturbances.
- At least one of the first four.
- Duration $\ge$ 1 month.
DSM-5
- $\ge$ 2 symptoms (delusions, hallucinations, speech disorganization, disorganized/catatonic behavior, negative symptoms) for $\ge$ 1 month of the active phase.
- Total duration $\ge$ 6 months (including prodromal or residual phases).
- Significant social and occupational decline.
- Exclusion criteria: schizoaffective disorder, bipolar disorder, organic disorders, substance-induced disorders.
4. Differential diagnosis
| Condition | Key differentiator |
|---|---|
| Schizoaffective disorder | Affective episodes concurrent with psychosis; psychotic symptoms also occur outside of mood episodes for $\ge$ 2 weeks |
| Bipolar disorder with psychotic features | Psychotic symptoms occur exclusively during affective episodes |
| Major depressive disorder with psychotic features | Mood-congruent delusions/hallucinations |
| Delusional disorder | Non-bizarre/systematized delusions without hallucinations or disorganization |
| Acute and transient psychotic disorder | Rapid onset, duration < 1 month, full recovery |
| Substance-induced psychosis | Cannabis, amphetamines, PCP, ketamine — remission after cessation |
| Organic psychosis | Brain tumor, epilepsy, stroke, SLE, anti-NMDA receptor encephalitis, HIV |
5. First-episode evaluation
- Complete history (incl. family history), substance use.
- Laboratory tests: CBC, biochemistry (glycemia, lipids, liver and kidney function, TSH), HIV, RPR.
- Brain MRI — to rule out organic pathology (tumor, demyelination, encephalitis).
- EEG if epilepsy is suspected.
- Urine toxicology screening.
- Autoimmune markers in young onset and atypical clinical presentation: anti-NMDAR, thyroid peroxidase.
6. Pharmacotherapy
Typical (first-generation)
- Haloperidol, chlorpromazine, trifluoperazine, zuclopenthixol.
- Strong D2 blockade → effective against positive symptoms, but high extrapyramidal toxicity.
- Depot formulations (haloperidol decanoate, zuclopenthixol decanoate) work well in poor compliance.
Atypical (second-generation)
- Olanzapine, risperidone, quetiapine, aripiprazole, paliperidone, lurasidone, ziprasidone.
- D2 + 5-HT2A blockade → fewer EPS, better for negative symptoms.
- Side effects: metabolic syndrome (olanzapine, quetiapine), hyperprolactinemia (risperidone, paliperidone), akathisia (aripiprazole).
- Long-acting injectable (depot) formulations: risperidone, paliperidone, aripiprazole 1 × 1 mo.
Clozapine
- Indicated for resistance to ≥ 2 antipsychotics at adequate doses and duration ≥ 6 wk.
- The only drug with a reduction in suicide risk.
- Risk of agranulocytosis (0.8%): weekly CBC for the first 18 wk, then monthly.
- Other side effects: myocarditis, thromboembolism, hypersalivation, seizures, intestinal obstruction, metabolic syndrome.
7. Treatment strategy
- First episode: atypical antipsychotic monotherapy, titration to the minimum effective dose.
- Duration: after the first episode — at least 1–2 years, after recurrent episodes — ≥ 5 years or lifelong.
- In case of inefficacy — switch medication after 4–6 wk.
- Antipsychotic combinations are not recommended (except clozapine + another in severe cases).
- Depot formulations — for poor compliance, already after the 1st episode, and not as a last resort.
- Anticholinergics (trihexyphenidyl) — only for EPS, not for prophylaxis.
8. Side effects of antipsychotics
| Effect | Typical | Atypical |
|---|---|---|
| EPS (parkinsonism, dystonia, akathisia) | ++++ | + (except risperidone) |
| Tardive dyskinesia | 5%/year | 1%/year |
| NMS | + | + (rarer) |
| Weight gain, diabetes | + | +++ (olanzapine, quetiapine) |
| Hyperprolactinemia | +++ | +++ (risperidone, paliperidone) |
| QT prolongation | + (haloperidol IV) | + (ziprasidone) |
| Agranulocytosis | rarely (chlorpromazine) | clozapine 0.8% |
9. Neuroleptic malignant syndrome (NMS)
- Triad: hyperthermia, muscle rigidity, autonomic instability.
- Lab: ↑↑ CK, leukocytosis, ↑ transaminases, myoglobinuria, ARF.
- Mortality 10–20%.
- Therapy: discontinuation of antipsychotic, intensive supportive care, dantrolene, bromocriptine, amantadine, ECT for resistance.
10. Non-pharmacological treatment
- CBT for psychosis: addressing delusions, coping with hallucinations.
- Psychoeducation of the patient and family — reduction of relapses.
- Assertive Community Treatment (ACT).
- Vocational/social rehabilitation, supported employment.
- Cognitive remediation — cognitive function training.
- ECT — for catatonia, treatment resistance, suicidality, pregnancy with severe psychosis.
11. Prognosis and course
- Rule of thirds: one-third good recovery, one-third partial recovery with relapses, one-third chronic severe course.
- Good predictors: female sex, late onset, acute onset, predominance of positive symptoms, preserved affect, family support.
- Suicide risk — 5–10% of patients; higher in the first years and in depression.
- Reduction in life expectancy by 15–20 years (CVD, suicides, metabolic syndrome).
12. FAQ
What is ARMS / clinical high risk for psychosis?
"At-risk mental state" — attenuated or transient psychotic symptoms in young people. 20–30% convert to psychosis within 3 years. Management: CBT, omega-3, for severe symptoms — low-dose atypical antipsychotics.
When to prescribe clozapine?
After failure of ≥ 2 antipsychotics (one being atypical) at adequate doses for ≥ 6 weeks. Clozapine is often delayed for years — this is a mistake; early switch improves outcomes.
Is it safe to pregnancy while on antipsychotics?
Olanzapine and quetiapine have the most safety data; gestational diabetes monitoring is required. Discontinuation increases the risk of relapse (30–50%). The decision is individual.
Why is cannabis dangerous?
Regular use in adolescence ↑ the risk of psychosis by 2–4 times, especially with genetic predisposition (COMT Val/Val, AKT1).
How does schizoaffective disorder differ?
There are periods of psychosis without affective symptoms for ≥ 2 weeks, but the overall picture includes significant affective episodes. Treatment — antipsychotic + mood stabilizer / antidepressant.
See also: Bipolar disorder · Depression · Antidepressants · Epilepsy · Psychiatry catalog