Carcinogenicity of psychotropic drugs: A systematic review of US Food and Drug Administration-required preclinical in vivo studies.

ABSTRACT

OBJECTIVE: The US Food and Drug Administration approval process for psychotropic drugs requires safety studies of carcinogenicity in animals. These studies are consistently conducted and provide a database for assessment of potential biological risk of carcinogenicity in humans. This report is a systematic review of that database for psychotropic drugs. METHOD: US Food and Drug Administration-approved registration data ('package inserts') were examined, where available, for all psychotropic drugs in the following classes antidepressants, antipsychotics, benzodiazepines/sedative-hypnotics, amphetamines and anticonvulsants. RESULTS: Overall, new generation (atypical) antipsychotics (90%, 9/10 agents) and anticonvulsants (85.7%, 6/7 agents) showed the highest evidence of carcinogenicity among psychotropic drugs classes assessed. Antidepressants (63.6%, 7/11) and benzodiazepines/sedative-hypnotics (70%, 7/10) were next, and stimulants (with the exception of methylphenidate) were last (25%, 1/4 agents). Overall, 71.4% of all drugs examined (30/42) showed evidence of carcinogenicity in 43.2% (38/88) of specific experimental studies. CONCLUSIONS: US Food and Drug Administration-based analyses demonstrate that almost all atypical antipsychotics and anticonvulsants are carcinogenic in animals, as are the majority of antidepressants and benzodiazepines and methylphenidate. These animal-based results are not sufficient to draw definitive conclusions in humans, but they provide data that could be acknowledged in the informed consent process of clinical treatment.