Hypnotics and Risk of Cancer: A Meta-Analysis of Observational Studies

Background and objectives: The association between hypnotic drugs and risk of cancer remains controversial. Therefore, we performed a meta-analysis to investigate this association. Materials and Methods: Pubmed and Embase were searched systematically to identify publications up to April 2020. The Newcastle-Ottawa scale for observational studies was used to assess the quality of studies. All included studies were evaluated by two reviewers independently; any discrepancies were resolved through discussion. Results: Twenty-eight studies including 22 case-control studies and 6 cohort studies with 340,614 hypnotics users and 1,828,057 non-users were included in the final analyses. Hypnotics (benzodiazepines and Z-drugs) use was significantly associated with an increased risk of cancer (odds ratio [OR] or relative risk [RR] 1.17; 95% confidence interval 1.09-1.26) in a random-effects meta-analysis of all studies. Subgroup meta-analysis by anxiolytics/sedatives effect (anxiolytics benzodiazepines vs. sedatives group (include sedatives benzodiazepines and Z-drugs)) revealed that a significant association in sedatives group (pooled OR/RR 1.26, 95% CI, 1.10-1.45), whereas no significant relationship was observed in anxiolytics benzodiazepines (pooled OR/RR 1.09, 95% CI, 0.95-1.26). Moreover, a significant dose-response relationship was observed between the use of hypnotics and the risk of cancer. Conclusions: This meta-analysis revealed association between use of hypnotics drugs and risk of cancer. However, the use of lower dose hypnotics and shorter duration exposed to hypnotics seemed to be not associated with an increased risk of cancer. Moreover, the use of anxiolytics effect benzodiazepines seemed to be lower risk than sedatives benzodiazepines. A high heterogeneity was observed among identified studies, and results were inconsistent in some subgroups. Randomized control trials are needed to confirm the findings in the future.