• antidepressant response;
  • bipolar disorder;
  • depression;
  • major depressive disorder;
  • switching


Whether responses to antidepressants differ in bipolar and unipolar depression remains unresolved.


We analyzed patient characteristics and outcomes of antidepressant treatment of 1036 depressed patients with bipolar-I or bipolar-II disorder, or unipolar major depression, using bivariate and multivariate methods and survival analysis, testing the hypothesis that responses would be superior in unipolar depression.


Antidepressants were given to 84.8% (878/1036) of depressed patients: 58.9% of 93 bipolar-I, 80.1% of 117 bipolar-II, and 91.3% of 668 unipolar disorder cases. The 158 not given antidepressants had more manias/year, spent more months in mania and depression, and were far more likely to receive mood stabilizers or antipsychotics long term. Improvement of HDRS21 depression ratings ranked: bipolar-II (69.6%) > bipolar-I (62.9%) > unipolar (57.9%; < 0.0001), independent of initial illness severity. Responder rates (≥50% improved without switching) ranked: bipolar-II (77.0%) > bipolar-I (71.6%) > unipolar (61.7%; < 0.0001). Remission rates (final HDRS < 7) ranked: 54.0%, 50.6%, and 40.8% respectively (= 0.02); 67.5% remitted within 12 weeks of treatment. Survival-computed median time to remission (15.0 weeks, overall) was shortest for bipolar-II patients (10.7 weeks). The 3-month risk of switching into mania–hypomania ranked: bipolar-II (15.8%) > bipolar-I (8.60%) > unipolar (0.56%). Multivariate modeling found bipolar diagnosis, shorter latency to remission, more recent trial year, and fewer weeks depressed before treatment to be associated with greater percent improvement of HDRS ratings.


Selective use of antidepressants with or without mood stabilizers in non-agitated, depressed bipolar disorder patients for short periods was effective with moderate risk of potentially dangerous, manic mood elevation.