Do antidepressants induce mania in patients with bipolar depression?

Use of antidepressants does not contribute to the risk of mania, as shown in a study. There is also no association observed between antidepressants and recurrence of bipolar depression.

A total of 979 individuals with bipolar depression recently discharged from a psychiatric ward were enrolled in this study, which emulated a target trial using observational data from nationwide Danish health registers. Of these, 358 were treated with antidepressants and 621 were not.

The authors established the occurrence of mania and bipolar depression in the following year. They also analysed the intention-to-treat effect of antidepressants using Cox proportional hazards regression, adjusting for baseline covariates, to emulate randomized open-label treatment allocation.

Treatment with an antidepressant was not significantly associated with the risk of mania in the full sample (hazard ratio [HR], 1.08, 95 percent confidence interval [CI], 0.72‒1.61), in the subsample concomitantly treated with a mood-stabilizing agent (HR, 1.16, 95 percent CI, 0.63‒2.13), and in the subsample not treated with a mood-stabilizing agent (HR, 1.16, 95 percent CI, 0.65‒2.07).

In secondary analyses, treatment with an antidepressant also showed no statistically significant association with bipolar depression recurrence.

“These findings suggest that the risk of antidepressant-induced mania is negligible and call for further studies to optimize treatment strategies for individuals with bipolar depression,” the authors said.