title: Neurocognitive effects of ketamine in treatment-resistant major depression: association with antidepressant response.
abstract: BACKGROUND
  The N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine has demonstrated rapid antidepressant effects in patients with treatment-resistant depression (TRD). Despite the promise of a novel and urgently needed treatment for refractory depression, concerns regarding potential adverse neurocognitive effects of ketamine remain.
  
  
  OBJECTIVE
  Although extensive research has been conducted in healthy volunteers, there is a paucity of studies examining the neurocognitive effects of ketamine in depressed patients. Therefore, the aims of the current study were to characterize the relationship between baseline neurocognition and antidepressant response to ketamine, measure the acute impact of ketamine on neurocognition, and investigate the relationship between acute neurocognitive effects of ketamine and antidepressant response.
  
  
  METHODS
  Neurocognitive functioning was assessed in 25 patients with TRD using a comprehensive battery: estimated premorbid intelligence quotient (IQ), current IQ, and tests from the MATRICS Consensus Cognitive Battery (MCCB). A subset of the MCCB was repeated immediately following a 40-min intravenous infusion of ketamine (0.5 mg/kg).
  
  
  RESULTS
  Patients who responded to ketamine 24 h following treatment had poorer baseline neurocognitive performance relative to nonresponders and, in particular, slower processing speed (F = 8.42; df = 23; p = 0.008). Ketamine was associated with selective impairments in memory recall, and the degree of cognitive change carried negative prognostic significance (e.g., negative cognitive effects immediately after ketamine predicted lower response rate at 24 h; Fisher's exact test two-sided p = 0.027).
  
  
  CONCLUSIONS
  Taken together, our findings suggest a potential baseline neurocognitive predictor of ketamine response and an inverse relationship between the cognitive effects of ketamine and antidepressant efficacy.
authors.affiliation: Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1230, New York, NY, 10029, USA, james.murrough@mssm.edu.
authors.forename: James W
authors.initials: JW
authors.lastname: Murrough
authors.forename: Le-Ben
authors.initials: LB
authors.lastname: Wan
authors.forename: Brian
authors.initials: B
authors.lastname: Iacoviello
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Collins
authors.forename: Carly
authors.initials: C
authors.lastname: Solon
authors.forename: Benjamin
authors.initials: B
authors.lastname: Glicksberg
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Perez
authors.forename: Sanjay J
authors.initials: SJ
authors.lastname: Mathew
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Charney
authors.forename: Dan V
authors.initials: DV
authors.lastname: Iosifescu
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Burdick
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