title: Clozapine: a clinical review of adverse effects and management.
abstract: Clozapine (Clozaril) is a novel and unique prototype atypical, tricyclic, dibenzodiazepine-derivative, antipsychotic agent. It has been proven effective and significantly superior to placebo, as well as to conventional neuroleptics, in several placebo-controlled, double-blind studies in treatment-resistant schizophrenia. It has also been found to produce an incidence of extrapyramidal symptoms (EPS) as low as that found with placebo. Approximately 30-60% of all schizophrenic patients who fail to respond to typical antipsychotics may respond to clozapine. It was the first major advance that marked a turning point in the treatment of schizophrenia and other psychotic disorders since the introduction of the typical antipsychotic agents, i.e., chlorpromazine and haloperidol in the 1950s and 1960s, respectively. After its introduction in clinical studies in the United States in the early 1970s, it was withdrawn in 1974, and was not approved for clinical use in the United States until February 1990, because of the risk of agranulocytosis. Its novel pharmacological profile, lack of propensity to cause EPS in both short- and long-term uses, lack of effects on serum prolactin, and ameliorative effects on tardive dyskinesia have resulted in the expansion of its use from refractory schizophrenia to schizoaffective disorders, affective disorders, some neurological disorders, aggression, as well as psychosis in patients with dementia and parkinsonism. This review covers the history, pharmacology, management of side effects, and fetal and neonatal effects of clozapine.
authors.affiliation: Department of Psychiatry, State University of New York, Upstate Medical University, Syracuse, New York 13210, USA. iqbalmo@upstate.edu
authors.forename: Mohammad Masud
authors.initials: MM
authors.lastname: Iqbal
authors.forename: Atiq
authors.initials: A
authors.lastname: Rahman
authors.forename: Zahid
authors.initials: Z
authors.lastname: Husain
authors.forename: Syed Zaber
authors.initials: SZ
authors.lastname: Mahmud
authors.forename: Wlliam G
authors.initials: WG
authors.lastname: Ryan
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Feldman
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D003024:Clozapine / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007774:Lactation / Q000187:drug effects; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine