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expert reaction to ketamine for treatment-resistant depression

Researchers have published a review of the ethical considerations in off-label ketamine use for severe, treatment-resistant depression, in the Lancet Psychiatry.

These comments accompanied a briefing.


Prof. Allan Young, Chair of the Psychopharmacology Special Committee, Royal College of Psychiatrists, said:

“Preliminary data suggests that Ketamine may be a safe and effective treatment for severe depression and suicidal feelings.  Any research that explores how depression can be alleviated is to be greatly welcomed as severe depression is a common and costly disorder. However, any benefits and harms will need to be continually appraised.

“Despite clinical trials showing rapid improvement in mood after ketamine infusion, there are still significant gaps in our knowledge about dosage levels, treatment protocols and the effectiveness and safety of long term use. Before ketamine can be recommended for use in clinical practice, extensive research is required to understand how to optimally use ketamine for treating depression. The Royal College of Psychiatrists has concerns for patient safety; and hence recommends mental health practitioners to proceed with caution when treating patients with ketamine.”


Dr Michael Bloomfield, Clinical Lecturer in General Psychiatry and Honorary Senior Clinical Research Fellow, Division of Psychiatry, UCL, said:

“Whilst common, depression in severe forms can be a potentially life-threatening illness. There is increasing evidence that ketamine may be helpful for people with severe depression when other treatments are not working. However, more research is needed to establish the role of ketamine in standard treatment. This new paper, calling for more research and a centralised register is therefore very welcome.”


Dr Paul Keedwell, Consultant Psychiatrist and Honorary Senior Research Fellow, Cardiff University and Visiting Researcher at King’s College London’s Institute of Psychiatry, Psychology & Neuroscience, said:

“The effectiveness of low dose intravenous ketamine in the treatment of depression is one of the most exciting discoveries in psychiatry for years. Small doses have a dramatic and rapid effect on depression symptoms in many people who were previously resistant to treatment. The effect peaks at one day and can persist for a couple of weeks. Ketamine has also been shown to reduce acute suicide risk.

“However, more research is needed and having a registry allows researchers to share new findings, positive or negative. For example, one challenge is to determine how to prolong any positive effects, perhaps through multiple dosing, or by adding other drugs.  Also, to bring its use from lab to clinic, more acceptable and practical modes of administration might be equally effective. Finally, ketamine might be used more routinely in non-treatment-resistant depression, to accelerate improvement in combination with more conventional antidepressants.

“Checks might need to be made for any history of ketamine or other drug dependence in individuals before commencing this treatment, although so far studies have not revealed any addictive potential with the small doses given for depression treatment. They are much less than the amounts used to get high.”


* ‘Ketamine treatment for depression: opportunities for clinical innovation and ethical foresight’ by Singh et al. will be published in The Lancet Psychiatry Wednesday 5th April. 


Declared interests

Dr Keedwell: “I have no conflicts of interest.”

Others: No declarations received

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