Hormonal and Pharmacologic Interventions for Depressive Symptoms in Peri- And/Or Post-Menopausal Women: A Network Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Although various pharmacological interventions and hormone replacement therapies for depressive symptoms in menopausal women have been investigated, their relative efficacies and safety remain unclear. Methods: Based upon literature search on PubMed, Cochrane Library, and ScienceDirect, randomized controlled trials (RCTs) examining all the pharmacological interventions or hormone replacement therapy for depressive symptoms in menopausal women had been included. Data that met inclusion criteria were extracted from RCTs. The current network meta-analysis was conducted under the frequentist model. Findings: Seventy RCTs in total were included with a total of 18,530 women (mean age = 62.5). The network meta-analysis (NMA) demonstrated that fluoxetine plus oral combined therapy [standardized mean difference (SMD) = -1.59, 95% confidence interval (CI) = -2.69 to -0.50], transdermal estradiol (SMD = -0.67, 95% CIs= -1.15 to -0.19), tibolone only (SMD = -0.64, 95% CIs= -1.18 to -0.09), and oral estrogen therapy (SMD = -0.55, 95% CIs= -0.92 to -0.18) were associated with significantly better overall improvement in depressive symptoms than that for placebos in menopausal women. Fluoxetine plus oral combined therapy was ranked the best among all the interventions. Similar findings were also noted in the subgroup of participants with definite diagnosis of depression; while for patients without diagnosis of depression, no pharmacological or hormone replacement therapy was better than placebo. Finally, most medications showed good tolerability with drop-out rate and rate of discontinuation due to adverse events comparable to those in placebo groups. Interpretation: This NMA demonstrated that fluoxetine plus oral combined therapy was associated with the best improvement in menopausal depressive symptoms among the investigated interventions. Future large-scale RCTs on pharmacologic relief of depressive symptoms in menopausal women, especially in aspect of antidepressant regimens, are warranted to support or refute the results of the current study. Funding Statement: The authors of this work were supported by the following grants: Brendon Stubbs is 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 is 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. Declaration of Interests: The authors report no financial interests or potential conflicts of interest.