Efficacy and safety of racemic ketamine and esketamine for depression: a systematic review and meta-analysis

Summary & key facts

Researchers combined results from 36 trials that tested racemic ketamine or esketamine for major depression in about 2,900 people. They found that people given any form of ketamine were about twice as likely to have a clear treatment response and were more likely to reach remission than people given placebo. Symptom scores also fell by a medium-to-large amount after ketamine. Overall, people did not leave treatment more often when they got ketamine, and there was not a clear increase in the total number of side effects, although one measure suggested a possible rise in dropouts from side effects. The studies were generally high quality, but results did vary between trials, so some uncertainty remains.

Key facts:

• The review included 36 randomized trials with about 2,900 participants who had unipolar or bipolar major depression.
• Nine trials used esketamine and the rest used racemic ketamine.
• People who received any form of ketamine were about twice as likely to show a clear treatment response compared with placebo.
• People who received ketamine were about 60% more likely to reach remission of their depression symptoms than those given placebo.
• Depression symptom scores showed a medium-to-large improvement after ketamine compared with placebo.
• There was no overall increase in people leaving the studies early when they received ketamine.
• Dropouts specifically due to side effects were possibly higher with ketamine, but this finding was uncertain.
• The overall study quality was rated high, but results varied across trials, which adds uncertainty to how large and consistent the benefits are.

Abstract

BACKGROUND: Racemic ketamine and esketamine have demonstrated rapid antidepressant effects. We aimed to review the efficacy and safety of racemic and esketamine for depression. RESEARCH DESIGN AND METHODS: We conducted a PRISMA-guided review for relevant randomized controlled trials of racemic or esketamine for unipolar or bipolar major depression from database inception through 2021. We conducted random-effects meta-analyses using pooled rate ratios (RRs) and Cohen's standardized mean differences (d) with their 95% confidence intervals (CI). RESULTS: We found 36 studies (2903 participants, 57% female, 45.1 +/- 7.0 years). Nine trials used esketamine, while the rest used racemic ketamine. The overall study quality was high. Treatment with any form of ketamine was associated with improved response (RR=2.14; 95% CI, 1.72-2.66; I2=65%), remission (RR=1.64; 95% CI, 1.33-2.02; I2=39%), and depression severity (d=-0.63; 95% CI, -0.80 to -0.45; I2=78%) against placebo. Overall, there was no association between treatment with any form of ketamine and retention in treatment (RR=1.00; 95% CI, 0.99-1.01; I2<1%), dropouts due to adverse events (RR=1.56; 95% CI, 1.00-2.45; I2<1%), or the overall number of adverse events reported per participant (OR=2.14; 95% CI, 0.82-5.60; I2=62%) against placebo. CONCLUSIONS: Ketamine and esketamine are effective, safe, and acceptable treatments for individuals living with depression.

Topics

Bipolar Disorder and Treatment Digital Mental Health Interventions Treatment of Major Depression

Categories

Health Sciences Medicine Pharmacology

Tags

Adverse effect Alternative medicine Amygdala Anesthesia Confidence interval Depression (economics) Economics Internal medicine Ketamine Macroeconomics Major depressive disorder Medicine Meta-analysis Pathology Placebo Randomized controlled trial Relative risk

Substances

Ketamine

Conditions & symptoms

Depression Lack of energy or motivation Sadness or low mood