Despite the numerous adverse effects seen with antipsychotic agents, their therapeutic index is high, and lethal ingestion is rare. The most recent Toxic Exposure Surveillance System summary of fatal exposures from the American Association of Poison Control Centers lists only 21 deaths associated with antipsychotic agents and, in all but three of those cases, other agents were involved.12
In general, overdose with these drugs features an exaggerated version of the response that is expected, based on knowledge of the aforementioned adverse effects. Central nervous system depression, ranging from mild sedation to deep coma, frequently occurs and is attributable to anticholinergic and antihistaminic effects. Some degree of sedation is generally seen with overdose of any antipsychotic drug, but has been found to occur more frequently with chlorpromazine. 13 Seizures may be seen, as well as dysfunction in temperature regulation. 2,1 l4 Anticholinergic and extrapyramidal effects may occur as with nontoxic ingestion and tend to vary with the potency of the drug: low-potency compounds tend to cause anticholinergic effects, and high-potency agents tend to cause extrapyramidal disorders. 23
Cardiovascular effects may be seen as alterations in heart rate, blood pressure, and cardiac conduction. Tachycardia can be attributed both to anticholinergic effects and to a reflex response to vasodilatation; it is seen more often with the low-potency agents.13 Hypotension is due to both aradrenergic blockade and a direct depressant effect on the myocardium.15!6 A variety of cardiac conduction disturbances may occur, from asymptomatic prolongation of the QT interval to fatal ventricular dysrhythmia. The piperidine phenothiazines (e.g., thioridazine) are the antipsychotic drugs with the highest potential for serious dysrhythmia: they may behave like type Ia antidysrhythmics in overdose, resulting in wide-complex tachycardia and possibly torsade de pointes. 13,14,15 and 16 Atrioventricular and intraventricular conduction disturbances may also occur. 13,14,15 and 16 Interestingly, intravenous haloperidol has been rarely associated with torsade de pointes during treatment of agitated patients; although the preponderance of experience suggests it may be safely administered via this route, some feel it may be more prudent to administer it intramuscularly.317
Clinical experience with overdose of the newer atypical agents is limited. Clozapine, with its profound anticholinergic effects, has been found to cause central nervous system depression and seizures, but appears to be unlikely to cause cardiac conduction disturbances or agranulocytosis. 11 Reports thus far with risperidone, olanzapine, and quetiapine suggest that patients should be monitored for obtundation, respiratory depression, and cardiac conduction abnormalities. 18,19 nad 20
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