Overdose profiles of new antipsychotic agents

Abstract

Although the more recently introduced antipsychotic drugs are increasing in popularity, the pattern of symptomatology when taken in overdose is not well defined. We monitored all enquiries to the National Poisons Information Service, London (NPIS, London) concerning antipsychotic drugs over a 9-month period in 1997 and report our findings concerning four drugs (olanzapine, clozapine, risperidone and sulpiride). All overdoses involving a single agent were followed up by a letter to the enquirer requesting details and outcome of the case. Although a total of 574 enquiries involving the selected antipsychotic drugs were received, only 45 of these cases involved overdose with a single agent. There were no fatalities or cases of convulsions in the series. Cardiac arrhythmias were only noted with sulpiride. Symptoms were most marked with clozapine, with a majority of patients experiencing agitation, dystonia, central nervous system (CNS) depression and tachycardia. Olanzapine and sulpiride produced a range of different symptoms, while most patients who had taken risperidone were asymptomatic. Monitoring poisons centre enquiries is a useful way of comparing overdose toxicities. We conclude that at least two of the novel antipsychotic agents, olanzapine and risperidone, appear to have a favourable overdose profile, which suggests that they are safer in overdose than the phenothiazines and butyrophenones.

Fatal toxicity of drugs used in psychiatry

“…Similarly, there were very few reports of deaths involving risperidone (4 deaths, England andWales, 1993-2002) despite the widespread prescription of this drug. Although in part this could be due to the prescription of injected risperidone, this indication of relatively low potential for fatal poisoning is corroborated by the paucity of literature reports on this topic (Capel et al, 2000).…”

“…For many antipsychotics the proportion of mentions either alone or with alcohol was 25-45% (Table 3), but for clozapine, olanzapine and quetiapine such mentions totalled 65-71% (25, 24 and 10 deaths, respectively). The reports of poisoning deaths associated with olanzapine do not fit well with clinical data-there are relatively few clinical reports of serious olanzapine-related poisoning despite the widespread prescription of this drug (Capel et al, 2000;Davis et al, 2005). 1 9 9 4 1 9 9 5 1 9 9 6 1 9 9 7 1 9 9 8 1 9 9 9 2 0 0 0 In contrast, although quetiapine may not always prolong the QT interval after overdosage, coma, respiratory depression and seizures have been reported, and there have been a number of literature reports of fatalities involving this drug (Griffiths and Flanagan, 2005).…”

Atypical antipsychotic medication poisoning: An evidence-based consensus guideline for out-of-hospital management

“…Reported doses were between 1100 and 5500 mg, and most of the patients developed at least some clinical effects. These included confusion, aggression, agitation, CNS depression, respiratory depression, tachycardia, hypertension, vomiting, mydriasis, dysarthria, dystonia, and increased muscle tone/hyperreflexia (26). There were also five cases reported in three level 4 or 6 articles (27-29).…”

“…These articles reported the doses as ranges, making it impossible to determine which patients had effects. Two of the articles (25,26) included patients less than 12 years of age, making it difficult to ascertain which doses referred to patients of what age. One was a description of 150 clozapine ingestions (143 adult and seven children) reported to the manufacturer or in the literature.…”

“…However, there were three level 4 or 6 retrospective reviews that included patients 12 years of age or older with acute olanzapine ingestions from which some dose-toxicity information could be extracted (26,61,62). Most of these reviews reported the doses as ranges making it impossible to associate doses and effects.…”