Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial

Summary & key facts

Researchers tested low-dose ketamine in 41 people whose depression had not improved with other treatments. One ketamine infusion eased symptoms more than a comparison drug within 24 hours. When people later received six ketamine infusions over two weeks, about 60% had their depression scores drop by half, usually after about three treatments. Those who improved kept that benefit with once-weekly infusions, but did not get extra improvement. The study suggests repeated ketamine can build up and prolong antidepressant effects, but the trial was small and parts of it were not blinded, so more research is needed to know the best way to use ketamine safely.

Key facts:

• Forty-one people with depression that had not responded to other treatments took part in the study.
• The trial first compared one low dose of ketamine to a comparison drug that can mimic some side effects; ketamine reduced depressive symptoms more at 24 hours.
• After symptoms returned, participants received six ketamine infusions over two weeks (three infusions per week).
• About 60% of people met the study's response rule — their depression scores dropped by half — after the repeated infusions.
• On average, people needed about three infusions before they reached that level of improvement.
• People who responded and then got once-weekly maintenance infusions kept their improvement, but did not get further gains.
• The researchers reported that repeated infusions had a cumulative effect and roughly doubled the number of people who responded compared with a single infusion.
• The study was small, done at one site, and the repeated and maintenance treatments were not given blind, so more research is needed to confirm the best dosing and long-term safety.

Abstract

OBJECTIVE: Subanesthetic ketamine doses have been shown to have rapid yet transient antidepressant effects in patients with treatment-resistant depression, which may be prolonged by repeated administration. The purpose of this study was to evaluate the antidepressant effects of a single ketamine infusion, a series of repeated ketamine infusions, and prolongation of response with maintenance infusions. METHODS: Forty-one participants with treatment-resistant depression completed a single-site randomized double-blind crossover comparison of single infusions of ketamine and midazolam (an active placebo control). After relapse of depressive symptoms, participants received a course of six open-label ketamine infusions administered thrice weekly over 2 weeks. Responders, classified as those participants who had a ≥50% decrease in their scores on the Montgomery-Åsberg Depression Rating Scale (MADRS), received four additional infusions administered once weekly (maintenance phase). RESULTS: Compared with midazolam, a single ketamine infusion elicited a significantly greater reduction in depressive symptoms at the primary efficacy endpoint (24 hours postinfusion). Linear mixed models revealed cumulative antidepressant effects with repeated infusions and doubling of the antidepressant response rate. Fifty-nine percent of participants met response criteria after repeated infusions, with a median of three infusions required before achieving response. Participants had no further change in MADRS scores during weekly maintenance infusions. CONCLUSIONS: Repeated ketamine infusions have cumulative and sustained antidepressant effects. Reductions in depressive symptoms were maintained among responders through once-weekly infusions. These findings provide novel data on efficacious administration strategies for ketamine in patients with treatment-resistant depression. Future studies should further expand on optimizing administration to better translate the use of ketamine into clinical settings.

Topics

Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Alternative medicine Anesthesia Antidepressant Cognition Crossover study Depression (economics) Economics Hippocampus Internal medicine Ketamine Macroeconomics Major depressive disorder Mathematics Medicine Midazolam Pathology Placebo Psychiatry Randomized controlled trial Repeated measures design Sedation Statistics Treatment-resistant depression

Substances

Ketamine

Conditions & symptoms

Depression Lack of energy or motivation Sadness or low mood