Introduction Depression and antidepressants are among risk factors for osteoporosis. However, there are still inconsistencies in literature regarding bone consequences of antidepressant drugs and the role of age and the natural decline of bone health in patients with depression. Objective To investigate the relationship between antidepressant and bone mineral density (BMD). Methods We conducted a systematic review and metanalysis according to PRISMA guidelines searching on PubMed/Medline, Cochrane Database, and Scopus libraries and registered with PROSPERO (registration number CRD42021254006) using generic terms for antidepressants and BMD. Search was restricted to English language only and without time restriction from inception up to June 2021. Methodological quality was assessed with the Newcastle-Ottawa scale. Results Eighteen papers were included in the qualitative analysis and five in the quantitative analysis. A total of 42,656 participants affected by different subtypes of depression were identified. Among the included studies, 10 used serotonin reuptake inhibitors (SSRIs) only, 6 involved the use of SSRIs and tricyclic antidepressants, and 2 the combined use of more than two antidepressants. No significant studies meeting the inclusion criteria for other most recent categories of antidepressants, such as vortioxetine and esketamine. Overall, we observed a significant effect of SSRI on decrease of BMD with a mean effect of 0.28 (95% CI = 0.08, 0.39). Conclusion Our data suggest that SSRIs are associated with a decrease of BMD. We aim to raise clinicians’ awareness of the potential association between the use of antidepressants and bone fragility to increase monitoring of bone health.

Although antidepressant drugs appear to play an active role in increasing fracture risk, their weight is still unclear. We conducted a PRISMA compliant systematic review and meta-analysis through PubMed/Scopus/Cochrane libraries and registered with PROSPERO (registration number CRD42021254006) to investigate the relationship between antidepressant drugs categories, including SSRIs, SNRIs, and TCAs, and the risk of hip and vertebral fractures. After screening 3122 items, we finally found 26 papers for qualitative analysis and 11 for quantitative synthesis. A total of 15,209,542 adult and elderly patients were identified, with a mean follow-up of 51 months and a major prevalence of women. We identified results largely for SSRIs, with only a small amount of data for SNRIs, TCAs, and NaSSA. No data were found among the most recent categories of antidepressants, such as vortioxetine and esketamine. All included studies reported hip fractures, while three of them also included vertebral fractures. Overall, we observed a significant effect of SSRIs on fracture risk with a mean effect of 0.98 (95% CI = 0.75–1.20). This meta-analysis reveals that the use of SSRIs increases the risk of fractures. Clinicians’ awareness in antidepressant prescription should optimize their potential while reducing this risk.