Antidepressant-induced hypomania in treatment-resistant depression

The authors propose that isolated treatment-associated hypomanic episodes in patients with chronic treatment-resistant major depressive disorder are not indicative of true bipolar depression. This proposal is in contrast to most studies that support the notion that antidepressant-induced hypomania reflects an underlying bipolar condition in such depressed patients. However, the patients described in the literature have not had treatment-resistant depression.

Records of 146 patients with treatment-resistant major depression seen at a university-based tertiary referral center were reviewed for evidence of treatment-associated mania or hypomania. Treatment histories, clinical characteristics, and family histories of these patients were assessed.

Of the 146 patients, 16 patients had evidenced treatment-induced hypomania or hypomanic-like episodes. The number of antidepressant trials these patients had received ranged from 2 to 13. The hypomanic episodes did not occur with the first antidepressant treatment trial except in one patient. All of the 16 patients had antidepressant treatment trials subsequent to the trial during which they experienced hypomania, but only one of them experienced further episodes of hypomania. In addition, only 1 of the 16 patients had a family history of bipolar disorder, a rate of bipolar family history that is considerably less than we have found among bipolar patients.

These findings support the concept of antidepressant-induced hypomania presented in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, revised (DSM-IV-TR). However, we argue that this term should be restricted to patients with chronic treatment-resistant major depression who infrequently evidence mania or hypomania.