Psychopharmacology

, Volume 231, Issue 3, pp 481–488

Neurocognitive effects of ketamine in treatment-resistant major depression: association with antidepressant response

  • James W. Murrough
  • Le-Ben Wan
  • Brian Iacoviello
  • Katherine A. Collins
  • Carly Solon
  • Benjamin Glicksberg
  • Andrew M. Perez
  • Sanjay J. Mathew
  • Dennis S. Charney
  • Dan V. Iosifescu
  • Katherine E. Burdick
Original Investigation

DOI: 10.1007/s00213-013-3255-x

Cite this article as:
Murrough, J.W., Wan, LB., Iacoviello, B. et al. Psychopharmacology (2014) 231: 481. doi:10.1007/s00213-013-3255-x

Abstract

Rationale

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.

Objectives

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.

Keywords

Major depressive disorder Treatment-resistant depression Neurocognition Cognitive functioning Ketamine Antidepressant Glutamate N-methyl-d-aspartate 

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • James W. Murrough
    • 1
    • 2
    • 3
  • Le-Ben Wan
    • 1
  • Brian Iacoviello
    • 1
  • Katherine A. Collins
    • 2
  • Carly Solon
    • 4
  • Benjamin Glicksberg
    • 2
  • Andrew M. Perez
    • 5
  • Sanjay J. Mathew
    • 6
    • 7
  • Dennis S. Charney
    • 1
    • 2
    • 8
  • Dan V. Iosifescu
    • 1
    • 2
    • 3
  • Katherine E. Burdick
    • 2
    • 3
    • 4
  1. 1.Mood and Anxiety Disorders Program, Department of PsychiatryIcahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Department of NeuroscienceIcahn School of Medicine at Mount SinaiNew YorkUSA
  3. 3.Friedman Brain InstituteIcahn School of Medicine at Mount SinaiNew YorkUSA
  4. 4.Department of PsychiatryIcahn School of Medicine at Mount SinaiNew YorkUSA
  5. 5.Department of AnesthesiologyIcahn School of Medicine at Mount SinaiNew YorkUSA
  6. 6.Michael E. Debakey VA Medical CenterHoustonUSA
  7. 7.Menninger Department of Psychiatry and Behavioral SciencesBaylor College of MedicineHoustonUSA
  8. 8.Department of Pharmacology and Systems TherapeuticsIcahn School of Medicine at Mount SinaiNew YorkUSA