Klotsapiini

Klotsapiini, known in English as clozapine, is an atypical antipsychotic used primarily for treatment-resistant schizophrenia and, in many countries, to reduce suicidality in schizophrenia. It is typically considered after failure of at least two other antipsychotics.

Pharmacology: Clozapine has a distinctive receptor profile, with relatively weak D2 antagonism but high affinity for 5-HT2A receptors. It also blocks muscarinic, histaminergic, and adrenergic receptors. This profile contributes to efficacy in resistant cases and a lower risk of extrapyramidal symptoms, but increases the likelihood of metabolic effects and other adverse reactions.

Medical uses: Indicated for treatment-resistant schizophrenia; some guidelines also support use for schizoaffective disorder and for reducing suicidality in schizophrenia. It is generally prescribed when other antipsychotics have failed to provide adequate symptom control.

Dosing and administration: Administered orally as tablets or suspension. Initiation must be gradual to minimize adverse effects. Typical starting dose is 12.5–25 mg daily, titrated over days to weeks to a target daily dose commonly in the 300–600 mg range; some patients may require up to 900 mg/day depending on response and tolerability.

Monitoring and safety: Clozapine carries a risk of agranulocytosis and requires ongoing hematologic monitoring through a formal program. Absolute neutrophil count is usually checked weekly for the first 6 months, then biweekly for 6 months, then monthly thereafter. Other safety concerns include myocarditis, weight gain, dyslipidemia, diabetes risk, seizures at higher doses, constipation, and sedation. Drug interactions include increased clozapine levels with CYP1A2 inhibitors and decreased levels with smoking.

History: Clozapine was developed by Janssen in the mid-20th century and became widely used after regulatory approvals in the late 20th century, particularly for treatment‑resistant forms of schizophrenia.