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.
Key Words
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Article info
Publication history
Published online: December 03, 2012
Accepted:
October 16,
2012
Received in revised form:
September 6,
2012
Received:
July 27,
2012
Identification
Copyright
Published by Elsevier Inc.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Exploiting N-Methyl-D-Aspartate Channel Blockade for a Rapid Antidepressant Response in Major Depressive DisorderBiological PsychiatryVol. 74Issue 4
- PreviewIn the August 15 issue of this journal, two articles provide additional clinical support for the possibility of obtaining a rapid antidepressant response using pharmacologic means (1,2). In fact, the already documented antidepressant effect of the N-methyl-D-aspartate (NMDA) channel blocker ketamine using a quarter of its anesthetic dose can be qualified as immediate because it is often detectable within an hour or two, when the mild psychotomimetic effects of this agent have generally dissipated.
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