Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials

Summary & key facts

This meta-analysis combined 20 randomized clinical trials up to February 22, 2019, and found that a single dose of ketamine produced rapid antidepressant effects that were strongest at 24 hours and that these effects were still detectable up to 7 days. The analysis also found that repeated ketamine doses helped maintain the initial benefit, with significant reductions in depression scores after 2–3 weeks of repeated treatment. The results came from adults with major depression (unipolar or bipolar) and used standard depression rating scales compared to placebo or an active placebo.

Key facts:

• The meta-analysis included 20 randomized controlled trials of ketamine for major depression, searched through February 22, 2019.
• The largest effect after a single ketamine dose was at 24 hours: standardized mean difference (SMD) = −0.89 (95% CI −1.24 to −0.53), p < 0.00001.
• A single ketamine dose showed a significant difference from controls for up to 7 days after treatment.
• In treatment-resistant depression (TRD), single-dose ketamine showed significant effects versus controls for up to 7 days.
• When ketamine was given in addition to ongoing antidepressant treatment, significant effects versus controls were seen up to 7 days; when ketamine was used alone (monotherapy), there was no significant difference at 7 days.
• Repeated ketamine administration maintained initial antidepressant effects. At 2–3 weeks of repeated dosing, depression scores were significantly lower versus placebo with SMD = −0.70 (95% CI −1.15 to −0.25) or SMD = −0.81 (95% CI −1.41 to
• Outcomes were measured with validated depression scales such as the Hamilton Depression Rating Scale (HDRS) and the Montgomery–Åsberg Depression Rating Scale (MADRS).

Abstract

Our meta-analysis revealed rapid and robust antidepressant effects of single-dose ketamine in patients with treatment-resistant depression (TRD). By pooling data from RCTs, we showed for the first time that repeated ketamine administration is effective in sustaining initial antidepressant effects ob …

Topics

Mental Health Research Topics Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Amygdala Anesthesia Antidepressant Clinical trial Cochrane Library Depression (economics) Dosing Economics Hippocampus Internal medicine Ketamine Law Macroeconomics Major depressive disorder Medicine MEDLINE Meta-analysis Political science Randomized controlled trial Treatment-resistant depression