In reply

Abstract

We thank Manini and colleagues for their comments on our article. They imply that we are suggesting antipsychotic medications (APMs) as a first-line treatment for cocaine toxicity. We made no such assertion in our article and agree that benzodiazepines should remain the standard treatment. The authors reiterate several of the limitations we noted in our article. We used a standard model, similar to one used by the author’s group (who also did not measure cocaine levels),1 but we agree that without measuring cocaine levels we cannot exclude altered cocaine pharmacokinetics as a cause of our findings. Manini and colleagues state “Clearly one would not expect a benefit from diazepam at a dose that produced no sedation in the absence of cocaine.” Because we demonstrated that diazepam improved survival compared to placebo, this statement is inaccurate. Furthermore, this dose of diazepam attenuates cocaine toxicity in other rodent models.2 Finally, the authors state “Previous well-controlled animal experiments fail to show a benefit of antipsychotic medications in acute cocaine toxicity.” This is inaccurate; the Catravas article cited in their letter reported that all animals pretreated with chlorpromazine (an APM) survived the LD-100 dose of 39.5 mg/kg.3 Our previous ziprasidone study also demonstrated increased survival.4 Our purposes for performing studies of atypical APMs in the setting of acute cocaine toxicity are threefold. First, APMs are often administered to patients with undifferentiated agitation that might be due to cocaine toxicity. If we identified an adverse effect, suggesting that APMs worsen cocaine toxicity, this practice would have to be reconsidered. Second, studying the effects of medications with novel pharmacologic activity provides insight into the mechanisms that produce cocaine toxicity. Finally, there are some patients who do not respond to benzodiazepine therapy; APMs may offer a useful adjunct in these cases. Our animal work is meant to be a foundation for future human studies that will ultimately determine the role of APMs for acute cocaine toxicity.