Exploring real-world evidence to uncover unknown drug benefits and support the discovery of new treatment targets for depressive and bipolar disorders

•An unmet need for effective treatments in major depressive and bipolar disorders exists.•Associations between 1933 drugs and the disorders were studied using real world data.•Eight medications were associated with >=50% reduction in risk of these disorders.•Several potential mechanisms of action were identified.•These findings could help to inform future drug research and development. Major depressive and bipolar disorders are associated with impaired quality of life and high economic burden. Although progress has been made in our understanding of the underlying pathophysiology and the development of novel pharmacological treatments, a large unmet need remains for finding effective treatment options. The purpose of this study was to identify potential new mechanisms of actions or treatment targets that could inform future research and development opportunities for major depressive and bipolar disorders. A self-controlled cohort study was conducted to examine associations between 1933 medications and incidence of major depressive and bipolar disorders across four US insurance claims databases. Presence of incident depressive or bipolar disorders were captured for each patient prior to or after drug exposure and incident rate ratios were calculated. Medications that demonstrated ≥50% reduction in risk for both depressive and bipolar disorders within two or more databases were evaluated as potential treatment targets. Eight medications met our inclusion criteria, which fell into three treatment groups: drugs used in substance use disorders; drugs that affect the cholinergic system; and drugs used for the management of cardiovascular-related conditions. This study was not designed to confirm a causal association nor inform current clinical practice. Instead, this research and the methods employed intended to be hypothesis generating and help uncover potential treatment pathways that could warrant further investigation. Several potential drug targets that could aid further research and discovery into novel treatments for depressive and bipolar disorders were identified.