Pharmacological treatment of mixed states

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)
319 Downloads (Pure)


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
Issue number2
Early online date18 Apr 2017
Publication statusE-pub ahead of print - 18 Apr 2017


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


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