Guidelines for the recognition and management of mixed depression

CNS Spectr. 2017 Apr;22(2):203-219. doi: 10.1017/S1092852917000165. Epub 2017 Feb 28.


A significant minority of people presenting with a major depressive episode (MDE) experience co-occurring subsyndromal hypo/manic symptoms. As this presentation may have important prognostic and treatment implications, the DSM-5 codified a new nosological entity, the "mixed features specifier," referring to individuals meeting threshold criteria for an MDE and subthreshold symptoms of (hypo)mania or to individuals with syndromal mania and subthreshold depressive symptoms. The mixed features specifier adds to a growing list of monikers that have been put forward to describe phenotypes characterized by the admixture of depressive and hypomanic symptoms (e.g., mixed depression, depression with mixed features, or depressive mixed states [DMX]). Current treatment guidelines, regulatory approvals, as well the current evidentiary base provide insufficient decision support to practitioners who provide care to individuals presenting with an MDE with mixed features. In addition, all existing psychotropic agents evaluated in mixed patients have largely been confined to patient populations meeting the DSM-IV definition of "mixed states" wherein the co-occurrence of threshold-level mania and threshold-level MDE was required. Toward the aim of assisting clinicians providing care to adults with MDE and mixed features, we have assembled a panel of experts on mood disorders to develop these guidelines on the recognition and treatment of mixed depression, based on the few studies that have focused specifically on DMX as well as decades of cumulated clinical experience.

Keywords: Mixed; bipolar; depression; guidelines; unipolar.

Publication types

  • Review

MeSH terms

  • Algorithms
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Antimanic Agents / adverse effects
  • Antimanic Agents / therapeutic use
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use
  • Bipolar Disorder / classification
  • Bipolar Disorder / diagnosis*
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / psychology
  • Depressive Disorder, Major / classification
  • Depressive Disorder, Major / diagnosis*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / psychology
  • Depressive Disorder, Treatment-Resistant / classification
  • Depressive Disorder, Treatment-Resistant / diagnosis
  • Depressive Disorder, Treatment-Resistant / drug therapy
  • Depressive Disorder, Treatment-Resistant / psychology
  • Diagnosis, Differential
  • Diagnostic and Statistical Manual of Mental Disorders
  • Drug Substitution
  • Drug Therapy, Combination
  • Electroconvulsive Therapy
  • Guideline Adherence*
  • Humans
  • Psychiatric Status Rating Scales
  • Self Report
  • Treatment Outcome


  • Antidepressive Agents
  • Antimanic Agents
  • Antipsychotic Agents