Pharmacological treatment of mixed states

Alessandro Cuomo, Viktoriya L. Nikolova, Nefize Yalin, Danilo Arnone, Andrea Fagiolini, Allan H. Young

Research output: Contribution to journalReview articlepeer-review

11 Citations (Scopus)


Mixed states in bipolar disorder have been neglected, and the data concerning treatment of these conditions have been relatively obscure. To address this, we systematically reviewed published pharmacological treatment data for mixed states/episodes in mood disorders, including with mixed features in DSM-5. We searched PubMed, MEDLINE, The Cochrane Library,, and (with different combinations of the following keywords: Mixed states/features, bipolar, depressive symptoms/bipolar depression, manic symptoms, treatment, DSM-5) through to October 2016. We applied a quality-of-evidence approach: First-degree evidence=randomized placebo-controlled studies of pharmacological interventions used as monotherapy; second-degree evidence=a similar design in the absence of a placebo or of a combination therapy as a comparative group; third-degree evidence=case reports, case series, and reviews of published studies. We found very few primary double-blind, placebo-controlled studies on the treatment of mixed states: The preponderance of available data derives from subgroup analysis performed on studies that originally involved manic patients. Future research should study the effects of treatments in mixed states defined using current criteria.

Original languageEnglish
Pages (from-to)186-195
Number of pages10
JournalCNS Spectrums
Issue number2
Publication statusPublished - Apr 1 2017
Externally publishedYes


  • DSM-5
  • Mixed states/episodes
  • depressive symptoms
  • manic symptoms
  • mood disorders
  • pharmacological interventions
  • pharmacotherapies
  • treatment

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health


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