The number of past manic episodes is the best predictor of antidepressant-emergent manic switch in a cohort of bipolar depressed patients.

The present study sought to identify factors associated with the onset of a manic or hypomanic episode during the month following a new antidepressant therapy in depressed bipolar patients. Patients receiving mood stabilizers for ≥3 months were screened from 400 French centers and were assessed for a 4-week period following prescription of a first or a new antidepressant. Of the 1242 included participants, 4.8% (n=60) experienced antidepressant-emergent manic switch (AEMS). AEMS was more frequently associated with lifetime manic, depressive, and total mood episodes, and with past AEMS. A higher score at two items of the Montgomery-Åsberg Depression Rating Scale (pessimistic and suicidal thoughts) were significantly associated with AEMS. Logistic regression analysis showed that the number of lifetime manic episodes and past AEMS were the two most factors associated with an AEMS. Having more than four past manic episodes was associated with a 2.84 fold increased risk of AEMS. Cumulative number of past mood episodes seems to be the most important factor for switching to a manic episode following antidepressants in patients with bipolar disorder. Longer-term studies are required to further delineate antidepressant causality from natural disease course.