Mphil student The University of Hong Kong, Hong Kong
Background: Despite the increasing use of antidepressants, patients with depression do not always experience symptom alleviation due to varying responsiveness to antidepressant monotherapy. Metformin, a commonly used antidiabetic drug, has gained traction for its potential anti-depressive effect due to anti-inflammatory, anti-oxidizing and neuroprotective features, but evidence on improvement of the risk and outcome of depression is mixed.
Objectives: We aimed to evaluate the potential of metformin in alleviating depression by systemically aggregating evidence from observational studies in real-world settings.
Methods: We systematically searched four databases including PubMed, Cochrane Library, Web of Science, and Embase, using designated search terms updated to 19 October 2022 to identify literature reporting the risk of depression following metformin use. Inclusion criteria were quantitative observational studies with metformin use as the exposure and depression as the outcome. All eligible studies underwent quality assessment before review. We used random effects models to synthesize the reported effects of metformin based on study designs. Subgroup analysis was conducted by stratifying continents and complications to assess the effects of metformin among different populations. We also performed meta-regression to explore the sources of heterogeneity.
Results: 11 studies published from 10 countries or regions, involving 1,104,399 participants, were included. Of these, 9 were included in the quantitative analysis. In the pooled analysis of case-control studies (N=3), metformin was associated with a significant depression risk reduction (OR=0.92, 95%CI=0.89-0.96, p< 0.01); pooled cohort studies (N=4) showed similar but non-significant depression risk reduction (RR=0.69, 95%CI=0.42-1.02, p=0.06). Subgroup analysis by region showed that metformin significantly reduced the risk of depression in Asians (pooled effect size=0.67, 95%CI=0.50-0.91, p=0.01), but was not significant in Europeans. Univariate meta-regression indicated that the effect of metformin on depression was significantly associated with regions (p=0.02).
Conclusions: Current evidence showed metformin was associated with a lower risk of depression in the case-control studies but not in other observational study settings. The effect on risk reduction of depression was significant in Asian populations. Metformin has the potential as a repurposed drug to improve depression management, and the underlying biological mechanism of primary founded Asian-specific effect warrants further investigation.
.jpeg.jpg "Yin Zhang, MPH (she/her/hers) photo")
