Ketamine for bipolar depression: an updated systematic review

Background: The therapeutic potential of subanesthetic doses ketamine appears promising in unipolar depression; however, its effectiveness treating bipolar depression (BD) remains uncertain. Objective: This systematic review aimed to summarize findings on the use for treatment BD by assessing efficacy, safety, and tolerability. Design: Systematic review. Methods: We conducted a studies that investigated adults with BD. searched PubMed Embase relevant randomized-controlled trials, open-label retrospective chart analyses published from inception 13 March 2023. Results: Eight were identified [pooled n = 235; mean (SD) age: 45.55 (5.54)]. All participants who received intravenous (IV) administered dose 0.5–0.75 mg/kg as an adjunctive mood-stabilizing agent, whereas esketamine dosage ranging 28 84 mg. Flexible dosing was used real-world analyses. A total 48% receiving achieved response (defined ⩾50% reduction baseline severity), only 5% placebo. Real-world demonstrated lower rates (30%) compared average across clinical trials (63%). Reductions suicidal ideation noted some studies, although not all statistically significant. Ketamine well tolerated most participants; six (2% overall sample pool, 5 ketamine) developed hypomanic/manic symptoms after infusions. Significant dissociative observed at 40-min mark trials. Conclusion: Preliminary evidence suggests IV being safe effective Future should focus investigating effects repeated acute maintenance infusions using randomized study design.