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.
Phelps
Laura E
LE
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.
Brutsche
Nancy
N
Moral
Jazmin R
JR
Luckenbaugh
David A
DA
Manji
Husseini K
HK
Zarate
Carlos A
CA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000235:genetics*; D000928:Antidepressive Agents / Q000494:pharmacology*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005190:Family; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011569:Psychiatric Status Rating Scales; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine