title: Family history of alcohol dependence and antidepressant response to an N-methyl-D-aspartate antagonist in bipolar depression.
abstract: OBJECTIVE
  Both ketamine and ethanol are N-methyl-d-aspartate (NMDA) receptor antagonists. Ketamine has rapid antidepressant properties in major depressive disorder (MDD) as well as bipolar depression. In individuals with MDD, a positive family history of alcohol dependence (FHP) was associated with greater improvement in depressive symptoms after ketamine administration compared to individuals whose family history of alcohol dependence was negative (FHN). This study investigated whether FHP influences ketamine's antidepressant and perceptual effects in individuals with bipolar depression.
  
  
  METHODS
  A post hoc analysis was conducted on 33 subjects with DSM-IV bipolar disorder (BD) type I or II depression pooled from two previously published studies. All subjects had undergone a double-blind, randomized, crossover trial of a single intravenous infusion of ketamine (0.5 mg/kg) combined with lithium or valproate therapy. Subjects were rated at baseline; at 40, 80, 120, and 230 min; and at days 1, 2, 3, 7, 10, and 14 post-infusion. The primary outcome measure was Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Patients were categorized as FHP when they reported at least one first-degree relative with alcohol dependence. Measures of psychosis, dissociation, and dysphoria were also collected.
  
  
  RESULTS
  After ketamine infusion, subjects with FHP showed significantly greater improvement on MADRS scores than FHN subjects. In addition, patients with FHP had attenuated psychotomimetic and dissociative scores compared to FHN patients.
  
  
  CONCLUSIONS
  FHP appears to predict a more sustained antidepressant response to ketamine in individuals with BD. Family history of alcoholism may be an important consideration in the development of glutamatergic-based therapies for depression.
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Division of Intramural Research Program, Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.forename: Lobna
authors.initials: L
authors.lastname: Ibrahim
authors.forename: Nancy
authors.initials: N
authors.lastname: Brutsche
authors.forename: Jose
authors.initials: J
authors.lastname: Franco-Chaves
authors.forename: Daniel
authors.initials: D
authors.lastname: Mathews
authors.forename: Craig A
authors.initials: CA
authors.lastname: Marquardt
authors.forename: Christy
authors.initials: C
authors.lastname: Cassarly
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000150:complications* / Q000188:drug therapy / Q000523:psychology; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000150:complications* / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D014635:Valproic Acid; D007649:Ketamine