Clozapine

Clozapine, sold under the brand name Clozaril among others, is an atypical antipsychotic medication. It is mainly used for schizophrenia that does not improve following the use of other antipsychotic medications. In those with schizophrenia and schizoaffective disorder it may decrease the rate of suicidal behavior. It is more effective than typical antipsychotics, particularly in those who are treatment-resistant. It is used by mouth, or by injection into a muscle. Clozapine, sold under the brand name Clozaril among others, is an atypical antipsychotic medication. It is mainly used for schizophrenia that does not improve following the use of other antipsychotic medications. In those with schizophrenia and schizoaffective disorder it may decrease the rate of suicidal behavior. It is more effective than typical antipsychotics, particularly in those who are treatment-resistant. It is used by mouth, or by injection into a muscle. Clozapine is associated with a relatively high risk of low white blood cells (agranulocytosis), a condition of suppressed immunity which may result in death. To decrease this risk, it is recommended that the white blood cell count be regularly monitored. Other serious risks include seizures, inflammation of the heart, high blood sugar levels, and, in older people with psychosis as a result of dementia, an increased risk of death. Common side effects include drowsiness, decreased or increased saliva production, low blood pressure, blurred vision, and dizziness. The potentially permanent movement disorder tardive dyskinesia occurs in about 5% of people. Its mechanism of action is not entirely clear. Clozapine was first made in 1958 and sold commercially in 1972. It was the first atypical antipsychotic. It is on the WHO Model List of Essential Medicines, which lists the most effective and safe medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world is between US$0.05 and US$2.10 per day as of 2014. Clozapine is an atypical antipsychotic drug primarily used in people who are unresponsive to or intolerant to other antipsychotics. This means that they have failed to respond satisfactorily to at least two different antipsychotics. It has been shown to be more effective in reducing symptoms of schizophrenia than typical antipsychotics, with more pronounced effects in those who have responded poorly to other medication. Clozapine is usually given by mouth in tablet or liquid form, however a short-acting intramuscular injectable formulation is available. It is not a depot injection, and instead has a similar duration of action as clozapine by mouth. The injectable formulation may be used in highly agitated people with schizophrenia who consistently refuse clozapine by mouth, but are predicted to respond well to clozapine therapy, with the injection being administered with the intention of transitioning the person to oral clozapine. The injectable form is reportedly difficult to use due to painful administration, higher doses requiring injection into multiple sites simultaneously, and even more stringent monitoring than oral clozapine (with the additional difficulty of withdrawing blood samples for testing from agitated individuals). In a 2013 study in a comparison of 15 antipsychotic drugs in effectiveness in treating schizophrenic symptoms, clozapine was ranked first and demonstrated very high effectiveness. 25% more effective than amisulpride (2nd), 33% more effective than olanzapine (3rd), and twice as effective as haloperidol, quetiapine, and aripiprazole. The effect of clozapine, however, is not (at least in the short term) reflected in measures of global functioning such as ability to leave the hospital and maintain an occupation. The relapse rate is lower and patient acceptability is better. There is some evidence clozapine may reduce propensity for substance abuse in schizophrenic patients. It may be better than other antipsychotics in people with both schizophrenia and Parkinson's disease.