Use of Antipsychotics to Treat Cocaine Toxicity?

Abstract

We read with interest the recent article1 suggesting that diazepam and ziprasidone have equal efficacy for preventing lethality from cocaine poisoning in a mouse model. Despite these interesting preliminary animal results, we feel that the data are insufficient to support the routine use of antipsychotics for the treatment of acute cocaine toxicity in humans. A major flaw in the study design relates to the fact that all study drugs were given intraperitoneally in close temporal relationship. Because the protocol did not involve measuring cocaine concentrations, it is quite possible that pretreatment with either ziprasidone or diazepam altered the rate and or amount of cocaine absorbed. The limitations of this model are further underscored by the failure to observe sedation in the animals given diazepam. Clearly one would not expect a benefit from diazepam at a dose that produced no sedation in the absence of cocaine. In addition, and possibly most importantly, there are several reasons a priori why we think antipsychotics may be inappropriate to administer to patients with cocaine toxicity. Many have associated anticholinergic effects that may impair heat dissipation in a population at risk for life-threatening hyperthermia.2,3 They may also lower the seizure threshold.4 Furthermore, both cocaine5,6 and ziprasidone7,8 prolong the QT interval, which may cause lethal dysrhythmias if combined. We therefore disagree with the authors’ assertion that safety is implied in the setting of cocaine toxicity because the use of antipsychotics demonstrates a lack of “significant adverse events with widespread use.”1 Previous well-controlled animal experiments fail to show a benefit of antipsychotics in acute cocaine toxicity.9,10 We look forward to continued work on this important topic, but we must emphasize that this model is too limited to have any applicability to humans.