Mixed Depression in Bipolar Disorder: Prevalence Rate and Clinical Correlates During Naturalistic Follow-Up in the Stanley Bipolar Network

Shefali Miller, Trisha Suppes, Jim Mintz, Gerhard Hellemann, Mark A Frye, Susan L McElroy, Willem A Nolen, Ralph Kupka, Gabriele S Leverich, Heinz Grunze, Lori L Altshuler, Paul E Keck, Robert M Post

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OBJECTIVE: DSM-5 introduced the "with mixed features" specifier for major depressive episodes. The authors assessed the prevalence and phenomenology of mixed depression among bipolar disorder patients and qualitatively compared a range of diagnostic thresholds for mixed depression.

METHOD: In a naturalistic study, 907 adult outpatients with bipolar disorder participating in the Stanley Foundation Bipolar Network were followed longitudinally across 14,310 visits from 1995 to 2002. The Inventory of Depressive Symptomatology-Clinician-Rated Version (IDS-C) and the Young Mania Rating Scale (YMRS) were administered at each visit.

RESULTS: Mixed depression, defined as an IDS-C score ≥15 and a YMRS score >2 and <12 at the same visit, was observed in 2,139 visits (14.9% of total visits, and 43.5% of visits with depression) by 584 patients (64.4% of all patients). Women were significantly more likely than men to experience subthreshold hypomania during visits with depression (40.7% compared with 34.4%). Patients with one or more mixed depression visits had more symptomatic visits and fewer euthymic visits compared with those with no mixed depression visits. DSM-5-based definitions of mixed depression (ranging from narrower definitions requiring ≥3 nonoverlapping YMRS items concurrent with an IDS-C score ≥15, to broader definitions requiring ≥2 nonoverlapping YMRS items) yielded lower mixed depression prevalence rates (6.3% and 10.8% of visits, respectively) but were found to have similar relationships to gender and longitudinal symptom severity.

CONCLUSIONS: Among outpatients with bipolar disorder, concurrent hypomanic symptoms observed during visits with depression were common, particularly in women. The DSM-5 diagnostic criteria for depression with mixed features may yield inadequate sensitivity to detect patients with mixed depression.

Original languageEnglish
Pages (from-to)1015-1023
Number of pages9
JournalAmerican Journal of Psychiatry
Issue number10
Publication statusPublished - 2016


  • Journal Article

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