Dataset Information

A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression.

ABSTRACT:

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.

SUBMITTER: Diazgranados N

PROVIDER: S-EPMC3000408 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression.

Diazgranados Nancy N Ibrahim Lobna L Brutsche Nancy E NE Newberg Andrew A Kronstein Phillip P Khalife Sami S Kammerer William A WA Quezado Zenaide Z Luckenbaugh David A DA Salvadore Giacomo G Machado-Vieira Rodrigo R Manji Husseini K HK Zarate Carlos A CA

Archives of general psychiatry 20100801 8

<h4>Context</h4>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.<h4>Objective</h4>To determine whether an N-methyl-D-aspartate-receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression.<h4>Design</h4>A randomized, placebo-controlled, double-blind, cros ...[more]

PMID: 20679587

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Dataset Information

A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression.

Context

Objective

Design

Setting

Interventions

Main outcome measures

Results

Conclusion

Publications

A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression.

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