Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial.
BACKGROUND
Currently, no pharmacological treatments for bipolar depression exist that exert rapid (within hours) antidepressant or antisuicidal effects. We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment-resistant bipolar depression. The present study sought to replicate this finding in an independent sample.


METHODS
In this double-blind, randomized, crossover, placebo-controlled study, 15 subjects with DSM-IV bipolar I or II depression maintained on therapeutic levels of lithium or valproate received a single intravenous infusion of either ketamine hydrochloride (.5 mg/kg) or placebo on 2 test days 2 weeks apart. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale, which was used to rate overall depressive symptoms at baseline; at 40, 80, 110, and 230 minutes postinfusion; and on days 1, 2, 3, 7, 10, and 14 postinfusion.


RESULTS
Within 40 minutes, depressive symptoms, as well as suicidal ideation, significantly improved in subjects receiving ketamine compared with placebo (d = .89, 95% confidence interval = .61-1.16, and .98, 95% confidence interval = .64-1.33, respectively); this improvement remained significant through day 3. Seventy-nine percent of subjects responded to ketamine and 0% responded to placebo at some point during the trial. The most common side effect was dissociative symptoms, which occurred only at the 40-minute time point.


CONCLUSIONS
This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response. In addition, we found that ketamine rapidly improved suicidal ideation in these patients.
Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, Maryland, USA. zaratec@mail.nih.gov
Carlos A
CA
Zarate
Nancy E
NE
Brutsche
Lobna
L
Ibrahim
Jose
J
Franco-Chaves
Nancy
N
Diazgranados
Anibal
A
Cravchik
Jessica
J
Selter
Craig A
CA
Marquardt
Victoria
V
Liberty
David A
DA
Luckenbaugh
D000328:Adult; D001714:Bipolar Disorder / Q000188:drug therapy*; D018592:Cross-Over Studies; D003863:Depression / Q000188:drug therapy*; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D059020:Suicidal Ideation; D016896:Treatment Outcome
D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine