Association between bipolar spectrum features and treatment outcomes in outpatients with major depressive disorder

JAMA Psychiatry, 04/06/2011

Perlis RH et al. – Self-reported psychoticlike symptoms were common in a community sample of outpatients with MDD and strongly associated with poorer outcomes. Overall, the data do not support the hypothesis that unrecognized bipolar spectrum illness contributes substantially to antidepressant treatment resistance.


  • Open treatment followed by sequential randomized controlled trials
  • Male and female outpatients aged 18 to 75 years with DSM-IV diagnosis of nonpsychotic MDD who participated in Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study


  • Of 4041 subjects who entered study, 1198 (30.0%) endorsed at least 1 item on psychosis scale and 1524 (38.1%) described at least 1 recent maniclike/hypomaniclike symptom
  • Irritability and psychoticlike symptoms at entry significantly associated with poorer outcomes across up to 4 treatment levels, as were shorter episodes and some neurovegetative symptoms of depression
  • Other indicators of bipolar diathesis including recent maniclike symptoms and family history of bipolar disorder as well as summary measures of bipolar spectrum features were not associated with treatment resistance

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