Oral Contraceptives and the Risk of Psychiatric Side Effects: A Review

Abstract

Importance: Oral contraceptives (OCs) are an essential medicine used by millions of people every day. Given the widespread usage of these medicines, even a small increase in psychiatric risk could be of clinical significance. Although mood-related side effects are a common reason for OC hesitancy and discontinuation, studies investigating psychiatric responses to OC treatment have had inconsistent results. Observations: While OCs are beneficial for most users, there is evidence that a subgroup of users are susceptible to mood side effects. Randomized controlled trials have generally failed to find differences in mood symptoms between OC and placebo users, but observational studies comparing OC users to non-users have reported increases in symptoms of depression, anxiety, and eating disorders. Additionally, observational evidence suggests that OC users may be more likely to use prescription psychotropic medications and to attempt or die by suicide. However, responses to OC treatment are highly heterogeneous, and some users report mood improvement. A variety of factors may increase the likelihood of negative psychiatric side effects, including younger age, previous experience of side effects from OCs, and pre-existing psychiatric disorders. Progestin-only pills may confer a higher psychiatric risk than combination pills. Conclusions and Relevance: Further research investigating factors that contribute to susceptibility to the mood-related side effects of OCs is clearly warranted. Genomic approaches may provide insight as to why some users experience side effects while others do not. Research elucidating who is most at risk and why will be essential to addressing prevalent concerns about the psychiatric risk of OCs.