Is off-label usage of ketamine as a rapid antidepressant safe? Controversies, ethical concerns, and legal implications

Zhang, Melvyn W., Harris, Keith M. and Ho, Roger C. (2016) Is off-label usage of ketamine as a rapid antidepressant safe? Controversies, ethical concerns, and legal implications. BMC Medical Ethics, 17 4: . doi:10.1186/s12910-016-0087-3

Author Zhang, Melvyn W.
Harris, Keith M.
Ho, Roger C.
Title Is off-label usage of ketamine as a rapid antidepressant safe? Controversies, ethical concerns, and legal implications
Journal name BMC Medical Ethics   Check publisher's open access policy
ISSN 1472-6939
Publication date 2016-01-14
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1186/s12910-016-0087-3
Open Access Status DOI
Volume 17
Issue 4
Total pages 8
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Subject 2910 Issues, ethics and legal aspects
3306 Health (social science)
2719 Health Policy
Abstract Background: Depressive disorders are a common form of psychiatric illness and cause significant disability. Regulation authorities, the medical profession and the public require high safety standards for antidepressants to protect vulnerable psychiatric patients. Ketamine is a dissociative anaesthetic and a derivative of a hallucinogen (phencyclidine). Its abuse is a major worldwide public health problem. Ketamine is a scheduled drug and its usage is restricted due to its abuse liability. Recent clinical trials have reported that ketamine use led to rapid antidepressant effects in patients suffering from treatment-resistant depression. However, various flaws in study designs, and possible biased reporting of results, may have influenced those findings. Further analyses of ketamine use are needed to ensure patient safety. Discussion: The use of ketamine in research and treatment of depressive disorders is controversial. Recently, mental health professionals raised ethical concerns about an ongoing ketamine trial in the UK. Also, a Canadian agency reviewed the existing evidence and did not recommend prescribing ketamine to treat depressive disorders. Findings obtained from tightly controlled research settings cannot be easily translated to clinical practice as substance abuse is commonly comorbid with depressive disorders. An effective antidepressant should reduce severity of depressive symptoms without liability problems. Although the US FDA has not approved the use of ketamine to treat depressive disorders, some psychiatrists offer off-label repeat prescription of ketamine. Prescribing ketamine for treating depressive disorders requires substantial empirical evidence. Clinicians should also consider research findings on ketamine abuse. Depressive disorders can be chronic conditions and the current evidence does not rule out the risk of substance abuse after repeat prescription of ketamine. Off-label ketamine use in treating depressive disorders may breach ethical and moral standards, especially in countries seriously affected by ketamine abuse. This article presents two real-world clinical vignettes which highlight ethical principles and theories, including autonomy, nonmaleficience, fidelity and consequentialism, as related to off-label ketamine use. Conclusion: We urge clinicians to minimise the risk of harming patients by considering the empirical evidence on ketamine properties and attempting all standard antidepressant therapies before considering the off-label use of ketamine.
Keyword Addiction
Off label
Treatment resistance
Rapid antidepressant
Substance use
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: HERDC Pre-Audit
School of Psychology Publications
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 18 Jan 2016, 23:37:34 EST by Keith Harris on behalf of School of Psychology