Koukopoulos' diagnostic criteria for mixed depression: A validation study

Gabriele Sani, Paul A. Vöhringer, Flavia Napoletano, Niki S. Holtzman, Shannon Dalley, Paolo Girardi, S. Nassir Ghaemi, Athanasios Koukopoulos

Research output: Contribution to journalArticlepeer-review


Background Mixed depression (MxD) is one subtype of depressive experiences within the depressive spectrum. MxD definition is debated among experts. Koukopoulos' proposed diagnostic criteria focused primarily on psychic agitation, marked irritability, and intense mood lability as markers of a mixed depressive episode. The present study validates Koukopoulos' criteria as diagnostic for MxD. Methods A sample of 435 patients from the International Mood Network (IMN), multi-center, international network of sites, and the Centro LucioBini of Rome was analyzed. Koukopoulos' criteria were assessed in all patients. Results The most prevalent MxD criteria were "absence of psychomotor retardation" (84%), "mood lability or marked reactivity" (78%), and "psychic agitation or inner tension" (75%). Multivariable predictors of a MxD (+) diagnosis were: higher current CGI (OR=1.23, 95% CI 1.23, 2.84), lower rates of previous bipolar type I diagnosis (OR=0.54, 95% CI-3.28,-0.13), mixed symptoms on the index episode (OR=10.02, 95% CI 2.32, 24.12), rapid cycling course (OR=2.6 95% CI 1.45, 3.56), past substance abuse (OR=3.02, 95% CI 2.01, 5.67) and lower education status (OR=0.44, 95% CI-3.23,-0.98). This model showed a sensitivity of 76.4%, specificity of 86.3%, negative predictive value of 75%, and positive predictive value of 86%. Limitations An external validation of these criteria in an independent sample is warranted. Conclusion A broad definition of mixed depression was internally validated with multiple diagnostic validators and was sensitively and specifically predicted. Contrary to DSM-5, Koukopoulos' broad criteria include agitation, irritability and mood lability as core features.

Original languageEnglish
Pages (from-to)14-18
Number of pages5
JournalJournal of Affective Disorders
Publication statusPublished - Aug 1 2014


  • Diagnostic criteria
  • DSM-5
  • Excitatory symptoms
  • Mixed depression
  • Mood disorders

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology


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