Ketamine: The Glutamatergic Antidepressant and Its Efficacy

  • Derek K. Tracy
  • Caroline Caddy
  • Sukhwinder S. Shergill


Ketamine, an uncompetitive glutamatergic NMDA antagonist, was first synthesised as an anaesthetic agent, though its unwanted induction of post-operative ‘dissociative’ states led to its gradual withdrawal from mainstream use. It has remained a common drug of abuse ever since, in the same class as the more powerful phencyclidine (‘PCP’ or ‘angel-dust’). However, as well as subjectively pleasurable perceptual changes and alterations to consciousness, data began to emerge of a positive effect upon depressed mood states. Of particular interest, such effects, where they occurred, were seen to develop far more rapidly than with ‘traditional’ antidepressants. Scientific trials of effectiveness have included work exploring ketamine as the sole medication, co-prescribing studies, and work looking at augmentation of ECT. Overall these early data are showing some interesting and exciting results, with general support for efficacy in all settings tested. However, significant challenges remain. Firstly, benefits derived tend to be temporary, with rapid relapse after several weeks, and there is a need to find a mechanism to sustain the drug effects. Secondly, most studies utilised intravenous administration, which carries an obvious clinical burden. Finally, the risks of dependency and ketamine-induced psychosis remain as yet uncertain. Nevertheless the societal burden of depression mandates further work on this compound, not least to better understand the mechanism of action of any therapeutic changes.


Major Depressive Disorder Suicidal Ideation Major Depressive Disorder Antidepressant Effect Bipolar Depression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors are grateful to David Baumeister and Luis Tojo for their assistance with the literature on illicit dissociative drugs more broadly.


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Copyright information

© Springer India 2016

Authors and Affiliations

  • Derek K. Tracy
    • 1
    • 2
  • Caroline Caddy
    • 2
  • Sukhwinder S. Shergill
    • 3
    • 2
  1. 1.Oxleas NHS Foundation TrustLondonUK
  2. 2.Cognition Schizophrenia and Imaging Laboratory, Department of Psychosis Studies, the Institute of PsychiatryKing’s College LondonLondonUK
  3. 3.South London and Maudsley, NHS Foundation TrustLondonUK

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