A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression

Arch Gen Psychiatry. Author manuscript; available in PMC 2010 December 9.

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 MachadoVieira, MD, PhD, Husseini K. Manji, MD, FRCPC, and Carlos A. Zarate Jr, MD

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 …

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.

Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo.

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