Pharmacological interventions and hormonal therapies for depressive symptoms in peri- and post-menopausal women: a network meta-analysis of randomized controlled trials.

Although significant portion of women experience depressive symptoms during or after menopausal transition, there has been considerable controversy over the benefits of hormone replacement therapy (HRT) and antidepressants due to insufficient evidence supporting the superiority of either treatment. This frequentist model based network meta-analysis (NMA) included randomized controlled trials (RCTs) of menopausal depression symptoms management in menopausal women. Seventy RCTs involving a total of 18,530 women (mean age 62.5) were analyzed. The results demonstrated that fluoxetine plus oral HRT [standardized mean difference (SMD)=-1.59, 95% confidence interval (95%CIs)=-2.69 to -0.50] were associated with the largest improvement in depressive symptoms than placebos in overall menopausal women. Similar findings were also noted in the subgroup of participants with a definite diagnosis of depression, while no pharmacological or hormone replacement therapy was better than placebo in the subgroup of post-menopausal women (amenorrhea > 1 year) or in patients without diagnosis of depression. This NMA presented evidence that fluoxetine plus HRT may be beneficial to menopausal women with a definite diagnosis of depression but not to those without depression or post-menopausal women. Trial registration: PROSPERO (CRD42020167459).
Competing Interests: Declaration of Competing Interest The authors report no financial interests or potential conflicts of interest. The authors of this work were supported by the following grants: Brendon Stubbs was supported by a Clinical Lectureship (ICA-CL-2017-03-001) jointly funded by Health Education England (HEE) and the National Institute for Health Research (NIHR). Brendon Stubbs was partly funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust. Brendon Stubbs was also supported by the Maudsley Charity, King's College London and the NIHR South London Collaboration for Leadership in Applied Health Research and Care (CLAHRC) funding.
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