title: Is off-label repeat prescription of ketamine as a rapid antidepressant safe? Controversies, ethical concerns, and legal implications.
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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Addiction Management Service, Institute of Mental Health, 10 Buangkok Green Medical Park, 539 747, Singapore, Singapore. melvynzhangweibin@gmail.com.
authors.forename: Melvyn W
authors.initials: MW
authors.lastname: Zhang
authors.affiliation: School of Psychology, University of Queensland, Queensland, Australia.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Harris
authors.affiliation: Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Roger C
authors.initials: RC
authors.lastname: Ho
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy*; D003866:Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007649:Ketamine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D056687:Off-Label Use / Q000941:ethics / Q000331:legislation & jurisprudence; D012449:Safety
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine