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

Summary & key facts

Researchers combined about 20 high-quality clinical trials that randomly compared ketamine to placebo in adults with major depression, including people with treatment-resistant and bipolar depression. They found a single ketamine dose usually produced the biggest drop in depressive symptoms around 24 hours, and a measurable benefit often lasted up to about 7 days. When ketamine was given again in repeated sessions, the improvement could be kept for about 2 to 3 weeks. These results show ketamine can act very quickly for some people, especially those who did not get better with other antidepressants, but the benefits after one dose are usually short lived and more research is needed on long-term effects and safety.

Key facts:

• The researchers pooled results from about 20 randomized clinical trials of ketamine versus placebo in adults with major depression, using studies available up to February 2019.
• A single dose of ketamine produced the largest reduction in depressive symptoms about 24 hours after treatment.
• A significant antidepressant effect compared with placebo was still seen up to about 7 days after a single ketamine dose.
• In people whose depression did not respond to usual treatments, and in those who kept taking their regular antidepressant while receiving ketamine, benefits were seen for up to about 7 days.
• When ketamine was given repeatedly, trials showed sustained reductions in depression severity at about 2 to 3 weeks compared with placebo, indicating repeated dosing can maintain the initial improvement.
• The authors note that effects after a single ketamine dose are usually short lived and that more research is needed on how long benefits last, optimal dosing schedules, and long-term safety.

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 observed after single dosing.

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

Substances

Ketamine

Conditions & symptoms

Depression Lack of energy or motivation Sadness or low mood