Why do clinicians maintain antidepressants in some patients with acute mania? Hints from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM), a large naturalistic study.

Objective: Antidepressants are supposed to be withdrawn during a manic episode. The aim of this study was to analyze the characteristics of manic patients who received antidepressants during a manic phase in a large, naturalistic study.

Method: The European Mania in Bipolar Longitudinal Evaluation of Medication was a 2-year prospective observational study of inpatients and outpatients with acute mania/mixed mania (DSM-IV or ICD-10 criteria) conducted in 14 European countries. Of 2,416 manic patients who continued into the maintenance phase of the study, 345 (14%) were taking an antidepressant and 2,071 (86%) were not taking an antidepressant at baseline, week 1, and/or week 2 postbaseline. Demographic and clinical variables were collected at baseline and each study visit up to 24 months. Outcome measures included the Clinical Global Impressions-Bipolar Disorder scale (CGI-BP overall, mania, and depression scores) at 12 weeks and 24 months, the 5-item Hamilton Depression Rating Scale (HDRS-5), and the Young Mania Rating Scale (YMRS) at 12 weeks only. The present study was conducted from December 2002 to June 2004.

Results: More antidepressant maintenance use was seen in patients with mixed episodes (P < .001), rapid cyclers (P < .02), patients with more previous depressive episodes (P < .001), and patients with higher mean HDRS-5 score at baseline (P < .001)-specifically patients with anxiety (P = .013). Patients in the antidepressant group had significantly higher CGI-BP depression scores (P < .001) and a significantly higher rate of depression relapse (P < .001) at both 12 weeks and 24 months.

Conclusions: Patients with mania receiving antidepressants are more likely to be outpatients with mixed episodes, anxiety, or rapid cycling and have a higher risk of depression relapse during follow-up.