RT Journal
A1 Diazgranados N, Ibrahim L, Brutsche NE, et al
T1 A randomized add-on trial of an n-methyl-d-aspartate antagonist in treatment-resistant bipolar depression
JF Archives of General Psychiatry
JO Archives of General Psychiatry
YR 2010
FD August 1
VO 67
IS 8
SP 793
OP 802
DO 10.1001/archgenpsychiatry.2010.90
UL http://dx.doi.org/10.1001/archgenpsychiatry.2010.90
AB Context 
    Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects—for instance, within a few hours or days—would have an enormous impact on patient care and public health.Objective 
    To determine whether an N-methyl-D-aspartate–receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression.Design 
    A randomized, placebo-controlled, double-blind, crossover, add-on study conducted from October 2006 to June 2009.Setting 
    Mood Disorders Research Unit at the National Institute of Mental Health, Bethesda, Maryland.Patients 
    Eighteen subjects with DSM-IV bipolar depression (treatment-resistant).Interventions 
    Subjects maintained at therapeutic levels of lithium or valproate received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery-Asberg Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110, and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion.Main Outcome Measures 
    Change in Montgomery-Asberg Depression Rating Scale primary efficacy measure scores.Results 
    Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo (d = 0.52, 95% confidence interval [CI], 0.28-0.76); this improvement remained significant through day 3. The drug difference effect size was largest at day 2 (d = 0.80, 95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6% responded to placebo at some point during the trial. One subject receiving ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally well tolerated; the most common adverse effect was dissociative symptoms, only at the 40-minute point.Conclusion 
    In patients with treatment-resistant bipolar depression, robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist.Trial Registration 
    clinicaltrials.gov Identifier: NCT00088699