Ketamine for bipolar depression: an updated systematic review
Farhan Fancy, Sipan Haikazian, Danica E. Johnson, David C J Chen-Li, Anastasia Levinta, M. I. Husain, Rodrigo B. Mansur, Joshua D. Rosenblat
Therapeutic Advances in Psychopharmacology 2023 DOI: 10.1177/20451253231202723 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Open-label Peer reviewed |
|---|---|
| Sample size | 235 |
| Population | Adults with bipolar depression |
| Intervention | esketamine |
| Dose | 0.5–0.75 mg/kg (intravenous ketamine), 28–84 mg (esketamine) |
| Topics | Depression Esketamine Ketamine |
| Citations | 23 |
| Key findings | 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.
Comparable studies
Other systematic reviews and meta-analyses on ketamine for depression, most cited first.