A randomized trial of a low-trapping nonselective N-methyl-D-aspartate channel blocker in major depression.

Abstract

BACKGROUND:

The high-affinity N-methyl-D-aspartate (NMDA) antagonist ketamine exerts rapid antidepressant effects but has psychotomimetic properties. AZD6765 is a low-trapping NMDA channel blocker with low rates of associated psychotomimetic effects. This study investigated whether AZD6765 could produce rapid antidepressant effects in subjects with treatment-resistant major depressive disorder (MDD).

METHODS:

In this double-blind, randomized, crossover, placebo-controlled study, 22 subjects with DSM-IV treatment-resistant MDD received a single infusion of either AZD6765 (150 mg) or placebo on 2 test days 1 week apart. The primary outcome measure was the Montgomery-Åsberg Depression Rating Scale, which was used to rate overall depressive symptoms at baseline and 60, 80, 110, and 230 min postinfusion and on Days 1, 2, 3, and 7 postinfusion. Several secondary outcome measures were also used, including the Hamilton Depression Rating Scale.

RESULTS:

Within 80 min, Montgomery-Åsberg Depression Rating Scale scores significantly improved in subjects receiving AZD6765 compared with placebo; this improvement remained significant only through 110 min (d = .40). On the Hamilton Depression Rating Scale, a drug difference was found at 80 and 110 min and at Day 2 (d = .49). Overall, 32% of subjects responded to AZD6765, and 15% responded to placebo at some point during the trial. No difference was observed between the groups with regard to psychotomimetic or dissociative adverse effects.

CONCLUSIONS:

In patients with treatment-resistant MDD, a single intravenous dose of the low-trapping NMDA channel blocker AZD6765 was associated with rapid but short-lived antidepressant effects; no psychotomimetic effects were observed.

• Authors: Carlos A Zarate Jr, Daniel Mathews, Lobna Ibrahim, Jose Franco Chaves, Craig Marquardt, Immaculata Ukoh, Libby Jolkovsky, Nancy E Brutsche, Mark A Smith, David A Luckenbaugh
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 74 Issue 4 Pg. 257-64 (Aug 15 2013) ISSN: 1873-2402 [Electronic] United States
• PMID: 23206319 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Intramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• AZD6765
• Antidepressive Agents
• Excitatory Amino Acid Antagonists
• Phenethylamines
• Pyridines
• Receptors, N-Methyl-D-Aspartate

Topics

• Antidepressive Agents (blood, therapeutic use)
• Depressive Disorder, Major (drug therapy)
• Double-Blind Method
• Excitatory Amino Acid Antagonists (blood, therapeutic use)
• Female
• Humans
• Male
• Middle Aged
• Phenethylamines (blood, therapeutic use)
• Pyridines (blood, therapeutic use)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)