Biological Psychiatry
Volume 47, Issue 4 , Pages 351-354, 15 February 2000

Antidepressant effects of ketamine in depressed patients

  • Robert M Berman

      Affiliations

    • Abraham Ribicoff Center Clinical Neuroscience Research Unit of the Connecticut Mental Health Center, New Haven, USA (RMB, GRH, DSC, JHK)
    • Affective Disorders Program of the Department of Psychiatry, West Haven Veteran Affairs Medical Center, West Haven , USA (RMB, AA, DAO, DSC, JHK)
    • the Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA (RMB, AC, AA, DAO, GRH, DSC, JHK)
    • Corresponding Author InformationAddress reprint requests to Robert M. Berman, M.D., Clinical Neuroscience Unit (Rm 360), Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06519
  • ,
  • Angela Cappiello

      Affiliations

    • the Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA (RMB, AC, AA, DAO, GRH, DSC, JHK)
  • ,
  • Amit Anand

      Affiliations

    • Affective Disorders Program of the Department of Psychiatry, West Haven Veteran Affairs Medical Center, West Haven , USA (RMB, AA, DAO, DSC, JHK)
    • the Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA (RMB, AC, AA, DAO, GRH, DSC, JHK)
  • ,
  • Dan A Oren

      Affiliations

    • Affective Disorders Program of the Department of Psychiatry, West Haven Veteran Affairs Medical Center, West Haven , USA (RMB, AA, DAO, DSC, JHK)
    • the Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA (RMB, AC, AA, DAO, GRH, DSC, JHK)
  • ,
  • George R Heninger

      Affiliations

    • Abraham Ribicoff Center Clinical Neuroscience Research Unit of the Connecticut Mental Health Center, New Haven, USA (RMB, GRH, DSC, JHK)
    • the Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA (RMB, AC, AA, DAO, GRH, DSC, JHK)
  • ,
  • Dennis S Charney

      Affiliations

    • Abraham Ribicoff Center Clinical Neuroscience Research Unit of the Connecticut Mental Health Center, New Haven, USA (RMB, GRH, DSC, JHK)
    • Affective Disorders Program of the Department of Psychiatry, West Haven Veteran Affairs Medical Center, West Haven , USA (RMB, AA, DAO, DSC, JHK)
    • the Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA (RMB, AC, AA, DAO, GRH, DSC, JHK)
  • ,
  • John H Krystal

      Affiliations

    • Abraham Ribicoff Center Clinical Neuroscience Research Unit of the Connecticut Mental Health Center, New Haven, USA (RMB, GRH, DSC, JHK)
    • Affective Disorders Program of the Department of Psychiatry, West Haven Veteran Affairs Medical Center, West Haven , USA (RMB, AA, DAO, DSC, JHK)
    • the Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA (RMB, AC, AA, DAO, GRH, DSC, JHK)

Received 1 April 1999; received in revised form 4 August 1999; accepted 12 August 1999.

Abstract 

Background: A growing body of preclinical research suggests that brain glutamate systems may be involved in the pathophysiology of major depression and the mechanism of action of antidepressants. This is the first placebo-controlled, double-blinded trial to assess the treatment effects of a single dose of an N-methyl-d-aspartate (NMDA) receptor antagonist in patients with depression.

Methods: Seven subjects with major depression completed 2 test days that involved intravenous treatment with ketamine hydrochloride (.5 mg/kg) or saline solutions under randomized, double-blind conditions.

Results: Subjects with depression evidenced significant improvement in depressive symptoms within 72 hours after ketamine but not placebo infusion (i.e., mean 25-item Hamilton Depression Rating Scale scores decreased by 14 ± SD 10 points vs. 0 ± 12 points, respectively during active and sham treatment).

Conclusions: These results suggest a potential role for NMDA receptor-modulating drugs in the treatment of depression.

Keywords:  Major depression, N-methyl-d-aspartate antagonist, excitatory amino acids, randomized clinical trial

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PII: S0006-3223(99)00230-9

Biological Psychiatry
Volume 47, Issue 4 , Pages 351-354, 15 February 2000