19011431

pubmed:Citation

6

This randomized, placebo-controlled, double-blind study was the first to evaluate the antidepressant efficacy, safety, and tolerability of an NR2B subunit-selective N-methyl-D-aspartate receptor antagonist, CP-101,606. Subjects had major depression, according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and a history of treatment refractoriness to least 1 adequate trial of a selective serotonin reuptake inhibitor. The study had 2 treatment periods. In period 1, subjects first received a 6-week open-label trial of paroxetine and a single-blind, intravenous placebo infusion. Period 1 nonresponders (n = 30) then received a randomized double-blind single infusion of CP-101,606 or placebo plus continued treatment with paroxetine for up to an additional 4 weeks (period 2). Depression severity was assessed using the Montgomery-Asberg Depression Rating Scale and 17-item Hamilton Depression Rating Scale. On the prespecified main outcome measure (change from baseline in the Montgomery-Asberg Depression Rating Scale total score at day 5 of period 2), CP-101,606 produced a greater decrease than did placebo (mean difference, 8.6; 80% confidence interval, -12.3 to -4.5) (P < 0.10). Hamilton Depression Rating Scale response rate was 60% for CP-101,606 versus 20% for placebo. Seventy-eight percent of CP-101,606-treated responders maintained response status for at least 1 week after the infusion. CP-101,606 was safe, generally well tolerated, and capable of producing an antidepressant response without also producing a dissociative reaction. Antagonism of the NR2B subtype of the N-methyl-D-aspartate receptor may be a fruitful target for the development of a new antidepressant with more robust effects and a faster onset compared with those currently available and capable of working when existing antidepressants do not.

eng

IM

MEDLINE

1533-712X

Electronic

NLM

631-7

pubmed-meshheading:19011431-Adult, pubmed-meshheading:19011431-Antidepressive Agents, pubmed-meshheading:19011431-Depressive Disorder, Major, pubmed-meshheading:19011431-Double-Blind Method, pubmed-meshheading:19011431-Drug Resistance, pubmed-meshheading:19011431-Excitatory Amino Acid Antagonists, pubmed-meshheading:19011431-Female, pubmed-meshheading:19011431-Humans, pubmed-meshheading:19011431-Infusions, Intravenous, pubmed-meshheading:19011431-Male, pubmed-meshheading:19011431-Middle Aged, pubmed-meshheading:19011431-Paroxetine, pubmed-meshheading:19011431-Piperidines, pubmed-meshheading:19011431-Psychiatric Status Rating Scales, pubmed-meshheading:19011431-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:19011431-Research Design, pubmed-meshheading:19011431-Serotonin Uptake Inhibitors, pubmed-meshheading:19011431-Severity of Illness Index, pubmed-meshheading:19011431-Time Factors, pubmed-meshheading:19011431-Treatment Failure, pubmed-meshheading:19011431-Young Adult

An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder.

Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't