Neuroscience Bulletin

, Volume 32, Issue 6, pp 557–564 | Cite as

Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant

  • Weili Zhu
  • Zengbo Ding
  • Yinan Zhang
  • Jie Shi
  • Kenji Hashimoto
  • Lin Lu


Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Conventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hindered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive N-methyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fast-acting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression. However, its safety and toxicity remain a concern. In this review, we focus on the limitations of ketamine, including neurotoxicity, cognitive dysfunction, adverse events associated with mental status, psychotomimetic effects, cardiovascular events, and uropathic effects. Studies have shown that its safety and tolerability profiles are generally good at low doses and with short-term treatment in depressed patients. The adverse events associated with ketamine usually occur with very high doses that are administered for prolonged periods of time and can be relieved by cessation. The antidepressant actions of its two enantiomers, S-ketamine (esketamine) and R-ketamine, are also discussed. R-ketamine has greater antidepressant actions than S-ketamine, without ketamine-related side-effects. Future treatment strategies should consider using R-ketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term ketamine use.


Antidepressant Ketamine Fast-acting Depression Safety 



This article was supported by the National Natural Science Foundation of China (81371489) and by the Strategic Research Program for Brain Sciences from the Japan Agency for Medical Research and Development, AMED.


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Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer Science+Business Media Singapore 2016

Authors and Affiliations

  • Weili Zhu
    • 1
  • Zengbo Ding
    • 1
  • Yinan Zhang
    • 1
  • Jie Shi
    • 1
  • Kenji Hashimoto
    • 3
  • Lin Lu
    • 1
    • 2
  1. 1.National Institute on Drug Dependence, Beijing Key Laboratory of Drug DependencePeking UniversityBeijingChina
  2. 2.Institute of Mental Health/Peking University Sixth HospitalKey Laboratory of Mental HealthBeijingChina
  3. 3.Division of Clinical NeuroscienceChiba University Center for Forensic Mental HealthChibaJapan

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