A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression

Summary & key facts

In a small randomized, double-blind trial, a single intravenous dose of the NMDA-receptor antagonist ketamine (0.5 mg/kg over 40 minutes) produced fast and strong antidepressant effects in people with treatment-resistant major depression. Improvement began within about 2 hours and remained statistically significant for 1 week after the infusion. The study tested 18 patients who had not responded to at least two prior antidepressant trials. The results show rapid, short-term benefit but come from a small study with only one dose and follow-up limited to 1 week.

Key facts:

• Study design: randomized, double-blind, placebo-controlled crossover trial with 18 subjects who had treatment-resistant major depressive disorder.
• Dose and administration: ketamine 0.5 mg/kg given intravenously over 40 minutes, versus saline placebo, with the two infusions 1 week apart.
• Onset and duration: significant antidepressant effects were seen within 110 minutes (about 2 hours) after infusion and remained significant through 7 days postinfusion.
• Effect sizes: at 24 hours the drug difference had a very large effect size (d = 1.46; 95% CI, 0.91–2.01). At 1 week the effect size was moderate to large (d = 0.68; 95% CI, 0.13–1.23).
• Clinical response and remission: of 17 subjects who received ketamine, 71% met response criteria the day after infusion and 29% met remission criteria that day; 35% of subjects maintained response for at least 1 week.
• Limitations: the trial was small (18 people), used a single ketamine infusion, and followed patients for only 1 week, so longer-term benefits and risks were not assessed in this study.

Abstract

Robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist; onset occurred within 2 hours postinfusion and continued to remain significant for 1 week.

Topics

Neurotransmitter Receptor Influence on Behavior Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Alternative medicine Anesthesia Antidepressant Confidence interval Crossover study Depression (economics) Economics Hippocampus Internal medicine Ketamine Ketamine hydrochloride Macroeconomics Medicine Mood Pathology Placebo Psychiatry Psychology Randomized controlled trial

Substances

Ketamine

Conditions & symptoms

Depression Lack of energy or motivation Poor sleep Sadness or low mood