Clozapine

Clozapine, sold under the brand name Clozaril among others, is a psychiatric medication and was the first atypical antipsychotic to be discovered.^[6] It is used primarily to treat people with schizophrenia and schizoaffective disorder who have had an inadequate response to two other antipsychotics, or who have been unable to tolerate other drugs due to extrapyramidal side effects. In the US, clozapine is also approved for use in people with recurrent suicidal behavior in people with schizophrenia or schizoaffective disorder.^[7] It is also used for the treatment of psychosis in Parkinson's disease.^[8][9]

Clozapine is recommended by multiple international treatment guidelines, after resistance to two other antipsychotic medications, and is the only treatment likely to result in improvement if two (or one^[10]) other antipsychotic has not had a satisfactory effect.^{[11][12][13][14][15][16][17]} Long term follow-up studies from Finland show significant improvements in terms of overall mortality including from suicide and all causes.^[18] Clozapine is on the World Health Organization's List of Essential Medicines.^[19] It is available as a generic medication.^[20] Common adverse effects include drowsiness, constipation, hypersalivation (increased saliva production), tachycardia, low blood pressure, blurred vision, significant weight gain, and dizziness.^[20] Clozapine is not normally associated with tardive dyskinesia (TD) and is recommended as the drug of choice when this is present, although some case reports describe clozapine-induced TD.^[21] Serious adverse effects include agranulocytosis, seizures, myocarditis (inflammation of the heart), and hyperglycemia (high blood glucose levels). The use of clozapine may result rarely in clozapine-induced, gastric hypomotility syndrome, which may lead to bowel obstruction and death.^[22][23] The mechanism of action is not clear.^[20]