Researchers at Oxford Health NHS Foundation Trust and the University of Oxford have carried out the first UK study of the use of intravenous ketamine infusions in a clinical trial at the Warnedford Hospital. They report their findings in the Journal of Psychopharmacology.
“Ketamine is a promising new antidepressant which works in a different way to existing antidepressants. We wanted to see whether it would be safe if given repeatedly, and whether it would be practical in an NHS setting. We especially wanted to check that repeated infusions didn’t cause cognitive problems,” explains principal investigator Dr Rupert McShane, a consultant psychiatrist at Oxford Health and a researcher in Oxford University’s Department of Psychiatry.
The researchers confirmed that ketamine has a rapid antidepressant effect in some patients with severe depression who have not responded to other treatments. Although many patients relapsed within a day or two, 29% had benefits which lasted at least three weeks and 15% took over two months to relapse.
Dr McShane says: “We’ve seen remarkable changes in people who’ve had severe depression for many years that no other treatment has touched. It’s very moving to witness. Patients often comment that that the flow of their thinking seems suddenly freer. For some, even a brief experience of response helps them to realise that they can get better and this gives hope.”
Ketamine did not cause cognitive or bladder side effects when given on up to 6 occasions, although some people did experience other side effects such as anxiety during the infusion or being sick. The team has now given over 400 infusions to 45 patients who did not experience significant side effects. Researchers are exploring ways to maintain the effect. The study was funded by National Institute for Health Research.
In the Oxford study, 28 patients with treatment-resistant depression were treated over three weeks. They received either three or six ketamine infusions lasting 40 minutes in the recovery room of a routine ECT clinic at the Warneford hospital, part of Oxford Health NHS Foundation Trust. Memory tests were carried out a few days after the final infusion. Patients reported their mood symptoms daily via text or email.
The antidepressant response sometimes took a second ketamine infusion to become apparent. Three days after the last infusion, the depression scores had halved in 29% of the patients. In those that responded to the treatment, the duration of benefit varied widely, lasting between 25 days and 8 months (median 2.3 months).
Andrew Farmery commented: “Ketamine is an anaesthetic drug which is little used in the UK these days outside veterinary practice, hence it being best known on the street as a ‘horse tranquiliser’. We understand quite well how it works as an anaesthetic by blocking glutamate receptors in the brain, but its mechanism of action when given in almost imperceptibly low doses to these severely depressed patients is more complex. It is likely that it works at the genomic level by switching on genes which have a biological effect which persists long after the drug has disappeared from the system. What was remarkable in our patients was the speed in which an effect was seen (most classical antidepressants and electroconvulsive therapy take up to six weeks to have an effect, if at all), and so this could be a lifesaving therapy for acutely suicidal patients”.
Ketamine is also used as a recreational drug or drug of abuse, and is to be reclassified as a Class B banned substance by the Home Office. However, the doses used are very different. When used on the street at a level of several grams a day, severe bladder problems occur and cognitive function is impaired. The dose used in this study was no more than 80 mg (80 thousandths of a gram) every week in the controlled and closely monitored setting of an NHS hospital.
The report is co-authored by Peter R Diamond, Andrew D Farmery, Stephanie Atkinson, Jag Haldar, Nicola Williams, Phil J Cowen, John R Geddes and Rupert McShane. They now plan to build up clinical experience with ketamine in a small number of carefully monitored patients.
Dr McShane concluded: “By trying different infusion regimes and adding other licensed drugs, we hope to find simple ways to prolong its dramatic effect.”