Ketamine may offer hope to patients with treatment-resistant depression.

Professor Rupert McShane, a psychiatrist at the University of Oxford and Oxford Health NHS Foundation Trust Consultant, has called for the use of ketamine as an option for severe or very refractory depressed patients who are candidates for electroconvulsive therapy (ECT). Professor McShane leads his ECT and ketamine services in Oxfordshire and runs a memory clinic.

Depression is a long-term condition, and the most severe illnesses often require long-term treatment. ECT remains the most effective antidepressant, especially for severely depressed patients, with 70% of his UK patients treated with ECT reporting significant improvement in their condition after treatment. Despite these encouraging statistics and improvements in treatment since it was first introduced, the stigma surrounding ECT means that few patients are reluctant to undergo it, and this lack of enthusiasm is exacerbated by the reported side effects of long-term amnesia in some ECT patients.

Professor Rupert McShane

Based on the results of a new US study(1) conducted in patients without psychosis, Professor McShane confirms that ketamine is as effective as ECT with fewer long-term side effects than ECT and calls for the use of ketamine as an option for these patients.

A previous Swedish study (2) concluded that ECT is still a better option for elderly and psychotic-depressed patients, but standard-dose ketamine is preferable for younger patients without psychotic depression.

Ketamine is known to be addictive and cause severe bladder damage when used frequently at high doses without medical supervision, raising fears of a “ketamine epidemic.”

However, at lower doses and under medical supervision this does not occur, indicating that NHS trusts may start using off-label ketamine now. However, many are reluctant to do so without “clearance” from NICE, where there is no mention of ketamine in guidelines for treating depression.

Further progress

Pharmaceuticals and healthcare products have established new and innovative routes to circumvent this problem.
Regulatory Authority (MHRA), National Institute for Excellence in Medical Research (NICE), National Institute for Medical Research (NIHR), NHS England (NHSE) and Department of Health and Social Care through NHSE (DHSC) Drug Reuse Program. Given sufficient data, a scientific review of research conducted in this field, and incentives for pharmaceutical companies to apply for licenses, NICE could limit the use of the NHS to the intravenous use of ketamine in specialty clinics for patients being considered for ECT.

The NHS has 93 ECT clinics accredited by the Royal Psychiatric Association. This infrastructure is highly suitable for the administration of IV ketamine.

Professor McShane said:

“The highly controlled use of intravenous ketamine proposed in specialty clinics treating the most critically ill patients, combined with our experience at the Oxford Ketamine Clinic, is confident that this use, governed by NICE restrictions, is safe and an attractive option for some patients.”

Professor McShane presented this proposal at the next conference. British Society Psychopharmacology Conference in Manchester on July 23rd.

1 Anand et al 2023, New Engl J Med

2 Extra Strand 2022

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