Antidepressant treatment in bipolar versus unipolar depression

Am J Psychiatry. 2004 Jan;161(1):163-5. doi: 10.1176/appi.ajp.161.1.163.


Objective: Antidepressant responses were compared in DSM-IV bipolar and unipolar depression.

Method: The authors analyzed clinical records for outcomes of antidepressant trials for 41 patients with bipolar depression and 37 with unipolar depression, similar in age and sex distribution.

Results: Short-term nonresponse was more frequent in bipolar (51.3%) than unipolar (31.6%) depression. Manic switching occurred only in bipolar depression but happened less in patients taking mood stabilizers (31.6% versus 84.2%). Cycle acceleration occurred only in bipolar depression (25.6%), with new rapid cycling in 32.1%. Late response loss (tolerance) was 3.4 times as frequent, and withdrawal relapse into depression was 4.7 times less frequent, in bipolar as in unipolar depression. Mood stabilizers did not prevent cycle acceleration, rapid cycling, or response loss. Modern antidepressants, in general, did not have lower rates of negative outcomes than tricyclic antidepressants.

Conclusions: The findings suggest an unfavorable cost/benefit ratio for antidepressant treatment of bipolar depression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antidepressive Agents, Tricyclic / adverse effects*
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / epidemiology
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / epidemiology
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Humans
  • Male
  • Middle Aged
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Sex Distribution


  • Antidepressive Agents, Tricyclic
  • Serotonin Uptake Inhibitors