title: 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.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD 20892, USA. zaratec@mail.nih.gov
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
authors.forename: Daniel
authors.initials: D
authors.lastname: Mathews
authors.forename: Lobna
authors.initials: L
authors.lastname: Ibrahim
authors.forename: Jose Franco
authors.initials: JF
authors.lastname: Chaves
authors.forename: Craig
authors.initials: C
authors.lastname: Marquardt
authors.forename: Immaculata
authors.initials: I
authors.lastname: Ukoh
authors.forename: Libby
authors.initials: L
authors.lastname: Jolkovsky
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Brutsche
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
mesh_terms: D000928:Antidepressive Agents / Q000097:blood / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000097:blood / Q000627:therapeutic use*; D011725:Pyridines / Q000097:blood / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: C585977:AZD6765; D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D010627:Phenethylamines; D011725:Pyridines; D016194:Receptors, N-Methyl-D-Aspartate