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Objectives: Clinicians are often hesitant to prescribe psychostimulants in bipolar disorder (BD) due to concerns of inducing (hypo)mania, despite limited published evidence on associations between prescribed psychostimulant use and recurrence of mood episodes in BD. The current systematic review and meta‐analysis evaluated the emergence of (hypo)manic symptoms in patients with BD receiving prescribed psychostimulants or other pro‐cognitive medications in euthymic or depressive states. Methods: A systematic search was performed of MEDLINE, Embase, and PsychINFO from inception to April 5, 2023 and search of Clinicaltrials.gov and Clinicaltrialsregister.eu for unpublished data. References of included studies were hand‐searched. Randomized trials and prospective longitudinal studies that evaluated psychostimulants and non‐stimulant medications recommended for the treatment of ADHD by the Canadian ADHD practice guidelines were included. The review was reported in line with PRISMA guidelines and was preregistered on PROSPERO (CRD42022358588). Results: After screening 414 unique records, we included 27 studies, of which five reported data that was quantitatively synthesized (n = 1653). The use of psychostimulants in BD was not associated with increased scores on the Young Mania Rating Scale in patients who were in a euthymic or depressed state (SMD IV −0.17; 95% CI, −0.40 to 0.06) compared to placebo. There was a high degree of study‐level heterogeneity (I2 = 80%). A qualitative synthesis of studies revealed a limited risk of medication‐induced manic symptoms. Conclusions: Our review provides preliminary evidence to suggest psychostimulants and non‐stimulant ADHD medications have a limited risk of precipitating (hypo)mania symptoms. More extensive studies evaluating the safety and efficacy of these medications are warranted. [ABSTRACT FROM AUTHOR]

Background: Clinical trials have demonstrated rapid antidepressant effects with intravenous (IV) ketamine for major depressive disorder, with relatively less research specifically for bipolar depression. Herein, we describe the real‐world effectiveness of repeated ketamine infusions for treatment‐resistant bipolar depression. Methods: This study was conducted in a community clinic in Mississauga, Ontario (Canadian Rapid Treatment Centre of Excellence; Braxia Health). In this observational study (NCT04209296), patients with treatment‐resistant bipolar I/II depression (n = 66) received four sub‐anesthetic doses of IV ketamine (0.5–0.75 mg/kg) over a two‐week period. Symptoms of depression, suicidality, anxiety, and functioning were assessed with validated self‐report measures. Results: Statistically and clinically significant antidepressant effects were observed in the overall sample, as measured by the Quick Inventory for Depression Symptomatology‐Self Report‐16 (QIDS‐SR16) with further reductions in depressive symptoms observed after each subsequent infusion (n = 66; mean QIDS‐SR16 reduction of 6.08+/−1.39; p < 0.0001). Significant reductions of suicidal thoughts (QIDS‐SR16‐Suicide Item) and anxiety (Generalized Anxiety Disorder‐7) were also observed with functional improvements on the Sheehan Disability Scale (p < 0.0001 on all measures). Moreover, the response rate (QIDS‐SR16 total score decrease ≥50% from baseline) was 35% and remission rate (QIDS‐SR16 total score ≤5) was 20% after four infusions. Infusions were generally well tolerated with treatment‐emergent hypomania observed in only three patients (4.5%) with zero cases of mania or psychosis. Conclusions: Real‐world effectiveness of IV ketamine for bipolar depression was observed. Repeated doses were associated with greater symptom reduction and adequate tolerability. [ABSTRACT FROM AUTHOR]

Background: The association between impaired social cognition and bipolar disorder (BD) is well established. However, to our knowledge, there has not been a recent systematic review that characterizes disparate dimensions of social cognition in BD. Herein, this systematic review and meta‐analysis aimed to synthesize the literature on core aspects of social cognition (i.e., Theory of Mind, emotion recognition, and social judgment) to identify potential areas of impairment. Methods: Online databases (i.e., PubMed, Cochrane Libraries, PsycINFO) and Google Scholar were searched from inception to May 2021. Studies with populations ages ≥16 with DSM‐IV or DSM‐5 defined BD (I or II) either in a euthymic or symptomatic state were included. The risk of bias was measured using the ROBINS‐1 tool, and the quality of the sources was evaluated using GRADE criteria. The results of the studies were quantitatively measured by synthesizing Hedge's g effect sizes through a random effects meta‐analytic approach. Results: A total of 29 studies were included in the final review (i.e., 12 studies on the Theory of Mind, 11 on emotion recognition, and 6 on social judgment). Overall, results demonstrated social cognition to be moderately impaired in individuals with BD (d = 0.59). The individual domains ranged in effect size (0.38 < d < 0.70), providing evidence for variation in impairment within social cognition. Discussion: Individuals with BD exhibit clinically significant deficits in social cognition during euthymic and symptomatic states. Social cognition impairments in individuals with BD are an important therapeutic target for treatment discovery and development. [ABSTRACT FROM AUTHOR]