Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) recommendations for the management of patients with bipolar disorder with mixed presentations

Bipolar Disord. 2021 Dec;23(8):767-788. doi: 10.1111/bdi.13135. Epub 2021 Nov 1.


Objectives: The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic treatment recommendations for bipolar disorder (BD). While these guidelines included commentary on how mixed features may direct treatment selection, specific recommendations were not provided-a critical gap which the current update aims to address.

Method: Overview of research regarding mixed presentations in BD, with treatment recommendations developed using a modified CANMAT/ISBD rating methodology. Limitations are discussed, including the dearth of high-quality data and reliance on expert opinion.

Results: No agents met threshold for first-line treatment of DSM-5 manic or depressive episodes with mixed features. For mania + mixed features second-line treatment options include asenapine, cariprazine, divalproex, and aripiprazole. In depression + mixed features, cariprazine and lurasidone are recommended as second-line options. For DSM-IV defined mixed episodes, with a longer history of research, asenapine and aripiprazole are first-line, and olanzapine (monotherapy or combination), carbamazepine, and divalproex are second-line. Research on maintenance treatments following a DSM-5 mixed presentation is extremely limited, with third-line recommendations based on expert opinion. For maintenance treatment following a DSM-IV mixed episode, quetiapine (monotherapy or combination) is first-line, and lithium and olanzapine identified as second-line options.

Conclusion: The CANMAT and ISBD groups hope these guidelines provide valuable support for clinicians providing care to patients experiencing mixed presentations, as well as further influence investment in research to improve diagnosis and treatment of this common and complex clinical state.

Keywords: bipolar disorder; guidelines; mixed features; pharmacotherapy.

Publication types

  • Practice Guideline
  • Review

MeSH terms

  • Antipsychotic Agents* / therapeutic use
  • Anxiety
  • Aripiprazole / therapeutic use
  • Bipolar Disorder* / diagnosis
  • Bipolar Disorder* / drug therapy
  • Canada
  • Humans
  • Olanzapine / therapeutic use
  • Valproic Acid / therapeutic use


  • Antipsychotic Agents
  • Valproic Acid
  • Aripiprazole
  • Olanzapine