Validating antidepressant-associated hypomania (bipolar III): a systematic comparison with spontaneous hypomania (bipolar II)

J Affect Disord. 2003 Jan;73(1-2):65-74. doi: 10.1016/s0165-0327(02)00325-7.


Background: According to DSM-IV and ICD-10, hypomania which occurs solely during antidepressant treatment does not belong to the category of bipolar II (BP-II).

Methods: As part of the EPIDEP National Multisite French Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 144 (29.2%) fulfilled the criteria for bipolar II with spontaneous hypomania (BP-II Sp), and 52 (10.5%) had hypomania associated solely with antidepressants (BP-H AA).

Results: BP-II Sp group had earlier age at onset, more hypomanic episodes, and higher ratings on cyclothymic and hyperthymic temperaments, and abused alcohol more often. The two groups were indistinguishable on the hypomania checklist score (12.2+/-4.0 vs. 11.4+/-4.4, respectively, P=0.25) and on rates of familial bipolarity (14.1% vs. 11.8%, respectively, P=0.68). But BP-H AA had significantly more family history of suicide, had higher ratings on depressive temperament, with greater chronicity of depression, were more likely to be admitted to the hospital for suicidal depressions, and were more likely to have psychotic features; finally, clinicians were more likely to treat them with ECT, lithium and mood stabilizing anticonvulsants.

Limitation: Naturalistic study, where treatment was uncontrolled.

Conclusion: BP-H AA emerges as a disorder with depressive temperamental instability, manifesting hypomania later in life (and, by definition, during pharmacotherapy only). By the standards of clinicians who have taken care of these patients for long periods of time, BP-H AA appears as no less bipolar than those with prototypical BP-II. We submit that familial bipolarity ('genotypic' bipolarity) strongly favors their inclusion within the realm of bipolar II spectrum, as a prognostically less favorable depression-prone phenotype of this disorder, and which is susceptible to destabilization under antidepressant treatment. These considerations argue for revisions of DSM-IV and ICD-10 conventions. BP-HAA may represent a genetically less penetrant expression of BP-II; phenotypically; it might provisionally be categorized as bipolar III.

MeSH terms

  • Adult
  • Age of Onset
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use*
  • Bipolar Disorder / chemically induced*
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / psychology*
  • Diagnosis, Differential
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Prognosis
  • Temperament


  • Antidepressive Agents