Antidepressant medications in women aged 40 and older and the risk of fragility fractures: a systematic literature review and meta-analysis

Antidepressants and menopause are risk factors which are independently associated with an increased risk of fractures. This review aims to investigate the risk of fragility fractures in women aged 40 and older and prescribed antidepressants. A literature search was conducted using PubMed, Ovid Embase, Ovid PsychINFO, Web of Science, and Scopus from inception to 1 June 2024. Relevant citations were identified and screened against our inclusion/exclusion criteria. The study population comprised women over 40 years. The risk of fragility fractures was compared between users and non-users of antidepressants. Risk of bias assessment was carried out using the ROBINS-I tool. A meta-analysis of cohort studies was performed to assess fracture risk associated with prescribing of any antidepressant agents, and SSRIs specifically. Of the 3,676 articles retrieved, five observational studies were found eligible for inclusion (<i>n</i> = 1,240,354). In a meta-analysis of 4 studies, an increased risk of fractures in women was associated with the prescribing of antidepressants (HR = 1.62, 95% CI: 1.15–2.28; I² = 96.50%) and SSRIs in particular (HR = 1.36, 95% CI: 1.20–1.55; I² = 40.32%). Findings from this review suggest that prescribing of antidepressants is associated with an increased risk of fractures in women aged 40 and older. Substantial heterogeneity between studies may have affected the results of the meta-analysis.

抗抑郁药物（antidepressants）与更年期（menopause）均为独立与骨折风险升高相关的危险因素。本综述旨在探究40岁及以上服用抗抑郁药物女性的脆性骨折（fragility fractures）发生风险。本研究以PubMed、Ovid Embase、Ovid PsychINFO、Web of Science及Scopus数据库为检索源，检索时限自建库至2024年6月1日。依据本研究的纳入/排除标准，对检索获得的相关文献题录进行筛选。本研究的研究对象为40岁以上女性，对比抗抑郁药物使用者与非使用者的脆性骨折发生风险。本研究采用ROBINS-I（Risk Of Bias In Non-randomised Studies - of Interventions）工具开展偏倚风险评估。通过队列研究的meta分析，评估任意抗抑郁药物及选择性5-羟色胺再摄取抑制剂（Selective Serotonin Reuptake Inhibitors, SSRIs）相关的骨折风险。在检索获得的3676篇文献中，最终有5项观察性研究符合纳入标准（样本量n=1240354）。对4项研究的meta分析结果显示，女性使用抗抑郁药物与骨折风险升高相关（风险比（Hazard Ratio, HR）=1.62，95%置信区间（95% Confidence Interval, 95%CI）：1.15~2.28；异质性指数I²=96.50%），其中尤以选择性5-羟色胺再摄取抑制剂（SSRIs）更为显著（HR=1.36，95%CI：1.20~1.55；I²=40.32%）。本综述结果表明，40岁及以上女性使用抗抑郁药物与骨折风险升高存在相关性。研究间存在显著异质性，可能对本次meta分析的结果造成了影响。