Hormonal contraceptive use and depressive symptoms: systematic review and network meta-analysis of randomised trials

Background Observational studies suggest that hormonal contraceptive use may increase depressive symptoms in women, but it is unclear whether the effect is causal. Aims To quantitatively examine the evidence from randomised clinical trials for the link between hormonal contraceptive use and depressive symptoms. Method We performed a systematic review and network meta-analysis of randomised clinical trials comparing women randomised to any form of a hormonal contraceptive with women randomised to any other form of a (non-)hormonal contraceptive or placebo. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Web of Science, PsycINFO, EMCare and EMBASE, from inception to 1 May 2020. Certainty of the evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. A random-effect Bayesian network meta-analysis was conducted, with change in depressive symptoms between baseline and three cycles as outcome. Results This review identified 3492 records, of which 14 trials were eligible and 12 could be included in the network meta-analysis. These trials included 5833 participants (mean age per study range: 16.8-32.4 years) and compared 10 different interventions. Compared with placebo, hormonal contraceptive use did not cause worsening of depressive symptoms (standardised mean difference: median, -0.04; range, -0.17 [95% credible interval -0.46 to 0.13] to 0.13 [95% credible interval -0.28 to 0.56]). Conclusions This study suggests that hormonal contraceptive use does not lead to an increase in depressive symptoms in adult women. Future studies should include first-time users, to confirm the results in young women.