Ketamine for bipolar depression: an updated systematic review
Farhan Fancy, Sipan Haikazian, Danica E. Johnson, D. Chen-Li, Anastasia Levinta, M. I. Husain, R. Mansur, J. Rosenblat
Therapeutic Advances in Psychopharmacology January 1, 2023 DOI: 10.1177/20451253231202723 via Semantic Scholar
Summary
Ketamine given intravenously at subanesthetic doses (0.5–0.75 mg/kg) or as esketamine (28–84 mg) appears safe and effective as an add-on treatment for bipolar depression when combined with a mood stabilizer. Across eight studies (235 participants), 48% of those receiving ketamine achieved at least a 50% reduction in depression severity, compared with 5% on placebo. Real-world response rates were lower (30%) than in clinical trials (63%). Some studies noted reductions in suicidal ideation, though not all findings were statistically significant. Ketamine was generally well tolerated, but 2% of participants (five receiving ketamine) developed hypomanic or manic symptoms, and significant dissociative effects occurred at 40 minutes in some trials.
Study at a glance
| Characteristics | Systematic review Randomized Open-label Peer reviewed |
|---|---|
| Sample size | 235 |
| Population | Adults with bipolar depression |
| Keywords | Medicine |
| Citations | 23 |
| Key finding | Intravenous ketamine as an adjunct to a mood stabilizer produced a 48% response rate in bipolar depression, significantly higher than the 5% response with placebo, though real-world effectiveness was lower. |
Abstract
Background: The therapeutic potential of subanesthetic doses of ketamine appears promising in unipolar depression; however, its effectiveness in treating bipolar depression (BD) remains uncertain. Objective: This systematic review aimed to summarize findings on the use of ketamine for the treatment of BD by assessing its efficacy, safety, and tolerability. Design: Systematic review. Methods: We conducted a systematic review of studies that investigated the use of ketamine for adults with BD. We searched PubMed and Embase for relevant randomized-controlled trials, open-label trials, and retrospective chart analyses published from inception to 13 March 2023. Results: Eight studies were identified [pooled n = 235; mean (SD) age: 45.55 (5.54)]. All participants who received intravenous (IV) ketamine were administered a dose of 0.5–0.75 mg/kg as an adjunctive treatment to a mood-stabilizing agent, whereas participants who received esketamine were administered a dosage ranging from 28 to 84 mg. Flexible dosing was used in real-world analyses. A total of 48% of participants receiving ketamine achieved a response (defined as ⩾50% reduction in baseline depression severity), whereas only 5% achieved a response with a placebo. Real-world studies demonstrated lower rates of response (30%) compared to the average across clinical trials (63%). Reductions in suicidal ideation were noted in some studies, although not all findings were statistically significant. Ketamine and esketamine were well tolerated in most participants; however, six participants (2% of the overall sample pool, 5 receiving ketamine) developed hypomanic/manic symptoms after infusions. Significant dissociative symptoms were observed at the 40-min mark in some trials. Conclusion: Preliminary evidence suggests IV ketamine as being safe and effective for the treatment of BD. Future studies should focus on investigating the effects of repeated acute and maintenance infusions using a randomized study design.