• Laura E Phelps, Nancy Brutsche, Jazmin R Moral, David A Luckenbaugh, Husseini K Manji, and Carlos A Zarate.
• Laboratory of Molecular Pathophysiology and Experimental Therapeutics, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health/DHHS, 10 Center Drive, Bethesda, MD 20892-1282, USA.
• Biol. Psychiatry. 2009 Jan 15; 65 (2): 181-4.

BackgroundA high rate of comorbidity exists between mood disorders and alcohol dependence. Furthermore, both ketamine, a dissociative anesthetic with a recently described rapid-onset antidepressant effect, and ethanol are N-methyl-D-aspartate (NMDA) receptor antagonists. Previous investigations of healthy individuals with a family history of alcohol dependence have found that these individuals have an attenuated response to ketamine's perceptual disturbance and dysphoric effects similar to that found in individuals with a self-reported history of alcohol dependence. This study investigated whether a family history of alcohol dependence influences ketamine's initial antidepressant effect.MethodsTwenty-six subjects with DSM-IV treatment-resistant major depression were given an open-label intravenous infusion of ketamine hydrochloride (.5 mg/kg) and rated using various depression scales at baseline, 40, 80, 120, and 230 min postinfusion. The primary outcome measure was Montgomery-Asberg Depression Rating Scale (MADRS) scores.ResultsSubjects with a family history of alcohol dependence showed significantly greater improvement in MADRS scores compared with subjects who had no family history of alcohol dependence.ConclusionsA family history of alcohol dependence appears to predict a rapid initial antidepressant response to an NMDA receptor antagonist.

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