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. K E Y W O R D S bipolar disorder, guidelines, mixed features, pharmacotherapy TA B L E 1 Characteristics of bipolar disorder with mixed presentations Earlier age of onset Increased risk for hospitalization Higher rates of medical and psychiatric comorbidities Poorer treatment response More frequent and severe episodes (less time euthymic) Poorer response to maintenance treatments Higher risk for suicidal behavior

Findings suggest that in patients with bipolar disorder, intact task-specific cognitive self-appraisals may fail to generalize to or to modify inaccurate global cognitive self-appraisals. Further research using more comprehensive metacognitive tasks is warranted in bipolar disorder.

Lower cognitive functioning in specific domains predicts increasing BMI in patients with BD and healthy young adults. Targeting cognition may be important for minimizing weight gain in BD.

Although deficits in all domains of cognitive function are seen in patients early in the course of bipolar disorder, depressive episodes do not confer additional burden on cognitive function. However, poorer verbal memory may serve as a marker for increased susceptibility to depression recurrence early in the course of illness.