Large international real-world data study confirms no significant increase in mania risk with antidepressants in bipolar depression

An international research team led by Beijing Anding Hospital recently published a landmark real-world study in the journal Health Data Science, analyzing data from five major medical databases across China, the US, France, and Germany. The study evaluated the risk of switching to mania or hypomania among 122,843 outpatients diagnosed with bipolar depression between 2013 and 2017, employing propensity score matching to control for confounding factors.

Results showed no significant difference in the two-year risk of mania or hypomania between patients treated with antidepressants and those not treated (HR=1.04, 95% CI: 0.96–1.13). Furthermore, the risk was similar whether antidepressants were used alone or in combination with mood stabilizers or antipsychotics.

Despite longstanding cautionary guidelines regarding antidepressant use in bipolar depression, their clinical usage remains widespread. The data indicated that antidepressants were prescribed at the initial diagnosis in 60.6% of patients, varying greatly by country and healthcare system, from as low as 17.7% to as high as 69.5%.

Senior author Prof. Gang Wang from Beijing Anding Hospital stated: “Our research provides reliable real-world evidence that antidepressants do not significantly increase the risk of manic episodes in bipolar depression, potentially offering clinicians more flexible treatment options.” Lead author Dr. Lei Feng emphasized that future studies will further investigate different antidepressant classes, dosage specifics, and long-term follow-up data to inform personalized treatment strategies.

The study employed the internationally recognized OMOP Common Data Model for multi-source data integration, providing a valuable methodological reference for assessing psychiatric medication safety. It also offers robust real-world evidence supporting future refinements in clinical treatment guidelines for bipolar depression.