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Prevention and Management of Common Adverse Effects of Ketamine and Esketamine in Patients with Mood Disorders

  • Therapy in Practice
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Abstract

The emerging roles of ketamine and esketamine as effective rapid-acting antidepressants hold promise for patients suffering from treatment-resistant depression and/or major depressive disorder with suicidality. Practitioner familiarity with common tolerability/safety concerns along with pragmatic prevention and management strategies are needed to reduce patient burden and improve the acceptability and accessibility of these treatments. The most common treatment-emergent adverse events associated with ketamine/esketamine are dissociation, anxiety, nausea, increased blood pressure, and headache. The majority of side effects are mild, transient, dose dependent, and attenuate with subsequent treatments. Patient selection, baseline physical and psychiatric assessments, and an appropriate setting are critical first steps in the prevention and mitigation of adverse events. Patient education and supportive interventions play central roles in the prevention and management of select adverse events. Severe and/or clinically significant adverse effects may necessitate the judicious use of adjunctive medications. Moreover, practitioners must remain vigilant to the potential for abuse liability and long-term adverse events, for which there are insufficient data. This article succinctly reviews common treatment-emergent adverse events of ketamine and esketamine within the context of mood disorders, and provides practical suggestions for prevention and management at point-of-care.

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Authors and Affiliations

  1. Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada

    Felicia Ceban, Joshua D. Rosenblat, Yena Lee, Nelson B. Rodrigues, Hartej Gill, Mehala Subramaniapillai, Flora Nasri, Leanna M. W. Lui, Orly Lipsitz, Rodrigo B. Mansur & Roger S. McIntyre

  2. Braxia Health, Mississauga, ON, Canada

    Joshua D. Rosenblat, Kevin Kratiuk, Nelson B. Rodrigues, Hartej Gill, Mehala Subramaniapillai, Orly Lipsitz, Anil Kumar, Edmond H. Chau & Roger S. McIntyre

  3. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Joshua D. Rosenblat, Rodrigo B. Mansur & Roger S. McIntyre

  4. Department of Pharmacology, University of Toronto, Toronto, ON, Canada

    Joshua D. Rosenblat & Roger S. McIntyre

  5. Department of Psychiatry, College of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea

    Jung Goo Lee

  6. Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea

    Jung Goo Lee

  7. Department of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea

    Jung Goo Lee

  8. Key Laboratory of Cognition and Personality, Faculty of Psychology, Ministry of Education, Southwest University, Chongqing, People’s Republic of China

    Bing Cao

  9. Department of Affective Disorders, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou Medical University, Guangzhou, People’s Republic of China

    Kangguang Lin

  10. Laboratory of Emotion and Cognition, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou Medical University, Guangzhou, People’s Republic of China

    Kangguang Lin

  11. Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Roger C. Ho

  12. Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore

    Roger C. Ho

  13. Department of Psychiatry, University of Alberta, Edmonton, AB, Canada

    Jennifer Swainson

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  1. Felicia Ceban
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  2. Joshua D. Rosenblat
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  19. Roger S. McIntyre
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Corresponding author

Correspondence to Roger S. McIntyre.

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This research did not receive any grants or funding.

Conflict of interest

RSM has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation; speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp. JDR is the medical director of Braxia Health (a fully owned subsidiary of Braxia Scientific Corp.) and the Chief Medical and Scientific Officer of Braxia Scientific Corp, which provides ketamine and esketamine treatment for depression; he has received research grant support from the American Psychiatric Association, the American Society of Psychopharmacology, the Canadian Cancer Society, the Canadian Psychiatric Association, the Joseph M. West Family Memorial Fund, the Timeposters Fellowship, the University Health Network Centre for Mental Health, and the University of Toronto and speaking, consultation, or research fees from Allergan, COMPASS, Janssen, Lundbeck, and Sunovion. JS has received speaker/consultation fees from Bausch Health, CCRN, Eisai, ICPME, Lundbeck, Janssen, Otsuka, and Sunovion; she is on the Medical Advisory Board for the Newly Institute, which uses ketamine for psychedelic psychotherapy. RCH has received research grant support from the National Medical Research Council of Singapore, National Parks Board of Singapore, and the National University of Singapore; and speaker/consultation fees from Lundbeck, Janssen, Pfizer, and Otsuka. YL has received personal fees from Braxia Scientific Corp. LMWL is a contractor to Braxia Scientific Corp. All other authors have no disclosures to report.

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FC, RSM, and JDR drafted the manuscript. All authors provided clinical expertise and/or conducted critical revision for important intellectual content, and approved the final manuscript.

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Ceban, F., Rosenblat, J.D., Kratiuk, K. et al. Prevention and Management of Common Adverse Effects of Ketamine and Esketamine in Patients with Mood Disorders. CNS Drugs 35, 925–934 (2021). https://doi.org/10.1007/s40263-021-00846-5

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