Minimal dose for severe poisoning and influencing factors in acute human clozapine intoxication: a 13-year retrospective study.

OBJECTIVES

Clozapine is an atypical antipsychotic drug used in the treatment of resistant schizophrenia. Intoxications with this drug are frequently observed. The aim of the present study was to identify a minimal dose and the dose bearing a 50% risk of developing moderate or severe intoxication symptoms. We also investigated the influence of age, sex, effect of decontamination measures, and pretreatment with clozapine on the severity of poisoning.

METHODS

A retrospective case study of 73 acute clozapine monointoxications reported by physicians to the Swiss Toxicological Information Centre between 1995 and 2007.

RESULTS

The most common symptoms were central nervous system depression (63.1%), tachycardia (39.7%), restlessness/agitation (16.4%), confusion/disorientation (15.1%), dysarthria (15.1%), arterial hypertension (10.9%), bradykinesia (9.6%), respiratory depression (9.6%), and QTc prolongation (8.2%). We found a significant correlation between ingested clozapine dose and severity of poisoning. The minimal dose for both moderate and severe intoxications was 0.1 g. The dose for a 50% risk of developing moderate or severe intoxications was 0.9 g in patients older than 50 years and 14.5 g in patients younger than 50 years. Patients older than 50 years had a significantly increased risk for a severe clinical course (odds ratio, 6.41; 95% confidence interval, 1.88-21.90). We found no significant correlation between pretreatment, sex or decontamination, and the severity of the intoxication.

CONCLUSIONS

Moderate and severe clozapine intoxications can already occur after ingestion of doses in the low therapeutic range, especially in patients older than 50 years. Poisoned patients have to be monitored for central nervous system depression, tachycardia, blood pressure abnormalities, respiratory depression, and QTc prolongation.