Family History of Alcohol Dependence and Initial Antidepressant Response to an N-methyl-D-aspartate Antagonist

Background: A 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. Methods: Twenty-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. Results: Subjects 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. Conclusions: A family history of alcohol dependence appears to predict a rapid initial antidepressant response to an NMDA receptor antagonist.