can any body comment on the pros and cons of the research methodology

A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression
Nancy Diazgranados, MD, MS; Lobna Ibrahim, MD; Nancy E. Brutsche, MSN; Andrew Newberg, MD; Phillip Kronstein, MD; Sami Khalife, MD; William A. Kammerer, MD; Zenaide Quezado, MD; David A. Luckenbaugh, MA; Giacomo Salvadore, MD; Rodrigo Machado-Vieira, MD, PhD; Husseini K. Manji, MD, FRCPC; Carlos A. Zarate Jr, MD

Arch Gen Psychiatry. 2010;67(8):793-802. doi:10.1001/archgenpsychiatry.2010.90

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.


Super Moderator
Have you been asked to comment on the methodology of the paper as an assignment? We aren't really here to do that for you I'm afraid.