CNS Drugs

, Volume 26, Issue 3, pp 189–204

Ketamine for Treatment-Resistant Unipolar Depression

Current Evidence

Authors

    • Menninger Department of Psychiatry and Behavioral SciencesBaylor College of Medicine
    • Michael E. Debakey VA Medical Center
    • Department of PsychiatryMount Sinai School of Medicine
  • Asim Shah
    • Menninger Department of Psychiatry and Behavioral SciencesBaylor College of Medicine
  • Kyle Lapidus
    • Department of PsychiatryMount Sinai School of Medicine
  • Crystal Clark
    • Menninger Department of Psychiatry and Behavioral SciencesBaylor College of Medicine
    • Michael E. Debakey VA Medical Center
  • Noor Jarun
    • Menninger Department of Psychiatry and Behavioral SciencesBaylor College of Medicine
  • Britta Ostermeyer
    • Menninger Department of Psychiatry and Behavioral SciencesBaylor College of Medicine
  • James W. Murrough
    • Department of PsychiatryMount Sinai School of Medicine
    • Department of NeuroscienceMount Sinai School of Medicine
Leading Article

DOI: 10.2165/11599770-000000000-00000

Cite this article as:
Mathew, S.J., Shah, A., Lapidus, K. et al. CNS Drugs (2012) 26: 189. doi:10.2165/11599770-000000000-00000

Abstract

Currently available drugs for unipolar major depressive disorder (MDD), which target monoaminergic systems, have a delayed onset of action andsignificant limitations in efficacy. Antidepressants with primary pharmacological targets outside the monoamine system may offer the potential for more rapid activity with improved therapeutic benefit. The glutamate system has been scrutinized as a target for antidepressant drug discovery. The purpose of this article is to review emerging literature on the potential rapid-onset antidepressant properties of the glutamate NMDA receptor antagonist ketamine, an established anaesthetic agent. The pharmacology of ketamine and its enantiomer S-ketamine is reviewed, followed by examples of its clinical application in chronic, refractory pain conditions, which are commonly co-morbid with depression. The first generation of studies in patients with treatment-resistant depression (TRD) reported the safety and acute efficacy of a single subanaesthetic dose (0.5 mg/kg) of intravenous ketamine. A second generation of ketamine studies is focused on testing alternate routes of drug delivery, identifying methods to prevent relapse following resolution of depressive symptoms and understanding the neural basis for the putative antidepressant actions of ketamine. In addition to traditional depression rating endpoints, ongoing research is examining the impact of ketamine on neurocognition. Although the first clinical report in MDD was published in 2000, there is a paucity of adequately controlled double-blind trials, and limited clinical experience outside of research settings. Given the potential risks of ketamine, safety considerations will ultimately determine whether this old drug is successfully repositioned as a new therapy for TRD.

Copyright information

© Adis Data Information BV 2012