Ketamine for bipolar depression: an updated systematic review

Farhan Fancy; Sipan Haikazian; Danica E Johnson; David C J Chen-Li; Anastasia Levinta; Muhammad I Husain; Rodrigo B Mansur; Joshua D Rosenblat

doi:10.1177/20451253231202723

Ketamine for bipolar depression: an updated systematic review

Ther Adv Psychopharmacol. 2023 Sep 26:13:20451253231202723. doi: 10.1177/20451253231202723. eCollection 2023.

Authors

Farhan Fancy^{1

2}, Sipan Haikazian^{1

2}, Danica E Johnson^{1

2}, David C J Chen-Li^{1

2}, Anastasia Levinta^{1

3}, Muhammad I Husain^{2

3

4

5}, Rodrigo B Mansur^{1

2

3}, Joshua D Rosenblat^{3

6

4

7}

Affiliations

¹ Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
² Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
³ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁴ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
⁵ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
⁶ Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, 399 Bathurst Street, Toronto, ON M5T 2S8, Canada.
⁷ Braxia Scientific, Braxia Health, Canadian Rapid Treatment Centre of Excellence, Mississauga, ON, Canada.

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.

Keywords: bipolar depression; depression; ketamine; suicide; systematic review.