What is clozapine?

Second generation antipsychotics (sometimes referred to as ‘atypical’ antipsychotics) such as clozapine are a newer class of antipsychotic medication than first generation ‘typical’ antipsychotics. Second generation antipsychotics are effective for the positive symptoms of schizophrenia. It is sometimes claimed that they are more effective than first generation antipsychotics in treating the negative symptoms of schizophrenia, although the evidence for this is weak. Negative symptoms include a lack of ordinary mental activities such as emotional expression, social engagement, thinking and motivation, whereas positive symptoms include the experiences of perceptual abnormalities (hallucinations) and fixed, false, irrational beliefs (delusions). Second generation antipsychotics may also cause less extra-pyramidal side effects. These include dyskinesias such as repetitive, involuntary, and purposeless body or facial movements, Parkinsonism (cogwheel muscle rigidity, pill-rolling tremor and reduced or slowed movements), akathisia (motor restlessness, especially in the legs, and resembling agitation) and dystonias such as muscle contractions causing unusual twisting of parts of the body, most often in the neck. These effects are caused by the dopamine receptor antagonist action of these drugs.

What is the evidence for clozapine?

Moderate to high quality evidence suggests clozapine may provide benefit for symptoms, global state, reducing relapse, and increasing study retention compared to first generation antipsychotics. Clozapine may provide no advantage over first generation antipsychotics for outcomes of mortality, ability to work, or suitability for early hospital discharge. Moderate quality evidence suggests clozapine may be associated with less movement disorders, increased blood problems, increased drowsiness, hypersalivation and temperature compared to first generation antipsychotics.

Moderate quality evidence suggests clozapine may produce better clinically significant response and reduced symptom severity when compared to second generation zotepine, as well as fewer hospital admissions than other second generation antipsychotics. Clozapine is associated with fewer extrapyramidal effects than risperidone and zotepine. More hypersalivation, white blood cell reduction, triglycerides, sedation, seizures, and weight gain are reported with clozapine than risperidone, olanzapine, or quetiapine.

Moderate quality evidence suggests no differences in global state or relapse rates between clozapine and clozapine plus sulpiride. There is less hypersalivation, appetite loss, weight gain and abdominal distension with clozapine plus sulpiride compared to clozapine alone.

October 2020

Last updated at: 4:36 am, 14th October 2020
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