Carcinogenicity of psychotropic drugs: A systematic review of US Food and Drug Administration-required preclinical in vivo studies.
To the Editor: We read with interest the recently published study by Sivertsen et al.  about the sleep medications use and cancer risk. We were interested to seewhether European population results would be generalizable to Asian population. We investigated the long-term use of benzodiazepines and cancer risk . We designed a longitudinal population-based case– control study by using 12 years (1998–2011) Taiwan National Health Insurance Database. We identified cases diagnosed with cancer with age over 20 years using International Classification of Diseases, Ninth Revision, and Clinical Modification (ICD-9-CM) codes and medication from prescriptions using Anatomical Therapeutic Chemical (ATC) drug classification codes (N05CD02, N05CD03, and N05CD06) for hypnotics and sedatives benzodiazepines. For each case, six eligible controls were matched for age, sex, and the index date by using propensity score. We observed the outcomes with length of exposure and defined daily dose. We also adjusted for potential confounding factors (ie, medications and comorbid diseases) during the study period to mimic bias . We found that among hypnotics and sedatives, nitrazepam (adjusted odds ratio [AOR] 0.98; 95% confidence interval [CI], 0.80– 1.21) was safer for cancer risk as compared to flunitrazepam (AOR, 1.16; 95% CI, 1.04–1.30) and lorametazepam (AOR, 1.19; 95% CI, 1.02– 1.38). Although there are some studies that reported no association with an overall increase in cancer risk , others reported that hypnotics are associated with three-fold mortality risk . It has also been reported by the US Food and Drug Administration preclinical studies that the marketed benzodiazepines and sedativehypnotics have carcinogenic risk . We believe that our finding of nitrazepam being safer than any other hypnotics will stimulate further discussion regarding hypnotic use and carcinogenicity. It is important, however, to emphasize the importance of hypnotics and sedatives evaluation via randomized clinical trials to demonstrate any association in terms of morbidity andmortality of developing cancer while using hypnotics.