Tricyclic Antidepressant Use and Risk of Fractures: A Meta-Analysis of Cohort Studies through the Use of both Frequentist and Bayesian Approaches

Background: Research findings regarding the association between tricyclic antidepressant (TCA) treatment and the risk of fracture are not consistent; we aimed to assess whether people who take TCAs are at an increased fracture risk. Methods: Relevant studies published through June 2020 were identified through database searches of MEDLINE, EMBASE, Scopus, PsycINFO, ISI Web of Science, WorldCat Dissertations and Theses from each database’s inception, as well as through manual searches of relevant reference lists. Two researchers independently performed literature searches, study selection, data abstraction and study appraisal by using a standardized protocol. Frequentist and Bayesian hierarchical random-effects models were used for the analysis. The heterogeneity and publication bias were evaluated in this study. Results: Eight studies met the inclusion criteria. Overall, TCA use was associated with a significantly increased risk of fracture in both the frequentist approach (Risk Ratio (RR), 1.23; 95% CI, 1.06–1.42; p = 0.007) and the Bayesian method (RR, 1.24, 95% Credible Interval (CrI), 1.01–1.56). These results were consistent in multiple sensitivity and subgroup analyses. Significant heterogeneity was observed in the meta-analysis; however, no significant publication bias was detected. Conclusion: TCA medication may indicate an increased risk of fracture. TCA should be prescribed with caution in the clinic.