Mixed features in major depressive disorder: diagnoses and treatments

CNS Spectr. 2017 Apr;22(2):155-160. doi: 10.1017/S1092852917000256.


For the first time in 20 years, the American Psychiatric Association (APA) updated the psychiatric diagnostic system for mood disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Perhaps one of the most notable changes in the DSM-5 was the recognition of the possibility of mixed symptoms in major depression and related disorders (MDD). While MDD and bipolar and related disorders are now represented by 2 distinct chapters, the addition of a mixed features specifier to MDD represents a structural bridge between bipolar and major depression disorders, and formally recognizes the possibility of a mix of hypomania and depressive symptoms in someone who has never experienced discrete episodes of hypomania or mania. This article reviews historical perspectives on "mixed states" and the recent literature, which proposes a range of approaches to understanding "mixity." We discuss which symptoms were considered for inclusion in the mixed features specifier and which symptoms were excluded. The assumption that mixed symptoms in MDD necessarily predict a future bipolar course in patients with MDD is reviewed. Treatment for patients in a MDD episode with mixed features is critically considered, as are suggestions for future study. Finally, the premise that mood disorders are necessarily a spectrum or a gradient of severity progressing in a linear manner is argued.

Keywords: Atypical antipsychotics; diagnosis; major depression; mixed features; mixed symptoms; mood disorders; treatment.

Publication types

  • Review

MeSH terms

  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Bipolar Disorder / classification
  • Bipolar Disorder / diagnosis*
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / psychology
  • Comorbidity
  • Depressive Disorder, Major / classification
  • Depressive Disorder, Major / diagnosis*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / psychology
  • Diagnosis, Differential
  • Diagnostic and Statistical Manual of Mental Disorders
  • Drug Therapy, Combination
  • Humans
  • Prognosis
  • Treatment Outcome


  • Anticonvulsants
  • Antidepressive Agents
  • Antipsychotic Agents