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

Summary & key facts

In a small, controlled study of 18 people with treatment-resistant major depression, a single intravenous dose of the NMDA receptor antagonist ketamine (0.5 mg/kg) produced rapid drops in depression scores. Improvement began within about 2 hours and remained statistically significant compared with placebo for up to 1 week. The study used a double-blind, placebo-controlled crossover design and measured symptoms with the 21-item Hamilton Depression Rating Scale.

Key facts:

• The study enrolled 18 adults with DSM-IV treatment-resistant major depression.
• Design: randomized, double-blind, placebo-controlled crossover trial with two test days one week apart.
• Dose: a single intravenous infusion of ketamine hydrochloride 0.5 mg/kg (vs placebo) after a 2-week drug-free period.
• Timing: antidepressant effects were seen within 110 minutes (about 2 hours) after infusion and remained significant for 1 week.
• Effect size on the primary depression measure was very large at 24 hours (d = 1.46; 95% CI, 0.91–2.01) and was moderate to large at 1 week (d = 0.68; 95% CI, 0.13–1.23).
• Response and remission rates the day after ketamine infusion (of 17 treated subjects): 71% met response criteria and 29% met remission criteria.
• Durability: 35% of subjects maintained a treatment response for at least 1 week after the single infusion.
• Outcome measure: changes were assessed using the 21-item Hamilton Depression Rating Scale at baseline, several times in the first 230 minutes, and at days 1, 2, 3, and 7.
• Limitations noted by the study: small sample size, a single-dose intervention, and follow-up limited to 1 week, so longer-term effects and safety were not addressed in this trial.

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