Fatalities associated with therapeutic use and overdose of atypical antipsychotics

Since 1989, several novel antipsychotic drugs have become available for use including clozapine, risperidone, olanzapine, quetiapine and ziprasidone. These agents represent a substantial improvement in the treatment of schizophrenia and related disorders and are considered to have a favourable adver...

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Bibliographic Details
Published in:CNS drugs 2003, Vol.17 (5), p.307-324
Main Authors: TRENTON, Adam J, CURRIER, Glenn W, ZWEMER, Frank L
Format: Article
Language:English
Subjects:
Antipsychotic Agents - adverse effects
Antipsychotic Agents - poisoning
Biological and medical sciences
Dose-Response Relationship, Drug
Drug Interactions
Drug intoxications. Doping
Drug Overdose
Humans
Medical sciences
Pharmacology. Drug treatments
Psychotic Disorders - drug therapy
Psychotic Disorders - mortality
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Summary:Since 1989, several novel antipsychotic drugs have become available for use including clozapine, risperidone, olanzapine, quetiapine and ziprasidone. These agents represent a substantial improvement in the treatment of schizophrenia and related disorders and are considered to have a favourable adverse effect profile relative to traditional antipsychotics. Nonetheless, in rare cases, people have died as a result of taking atypical antipsychotic drugs at therapeutic and supratherapeutic doses. Toxic doses of atypical antipsychotics are highly variable: some patients have died while taking therapeutic doses and others have survived massive overdoses. Toxicity may be increased by coingestion of other agents, particularly drugs with similar metabolic pathways. Atypical antipsychotics are metabolised predominantly by cytochrome p450 (CYP) isoenzymes, particularly CYP1A2 (clozapine and olanzapine), CYP3A4 (clozapine, quetiapine and ziprasidone) and CYP2D6 (olanzapine and risperidone). Concurrent prescription of other drugs that inhibit these isoenzymes may increase the probability of adverse events in patients taking atypical antipsychotics. Deaths due to atypical antipsychotic toxicity are often related to cardiovascular complications, but pulmonary, neurological, endocrine and gastrointestinal complications have also caused fatalities. Prevention and management of atypical antipsychotic overdose are of increased clinical relevance as prescription of these drugs increases.
ISSN:1172-7047
1179-1934
DOI:10.2165/00023210-200317050-00002