Ketamine tablets help reduce side-effects in depression sufferers

The growing use of ketamine to ease depression has been boosted by research that found giving the drug in slow-release tablet form reduced side-effects from taking it via the nose or blood.

Patients who received an oral formulation of the medication largely avoided problems such as sedation, raised blood pressure and dissociation, an international group of scientists concluded.

Ketamine, long used medically as an anaesthetic and recreationally by clubbers, has attracted increasing interest from mental health professionals and employers as a therapy for depression that is hard to alleviate by other means.

The new research suggests a tablet could be a much simpler way for patients to use the drug, said Prof Paul Glue, a co-author of the paper, which was published in Nature Medicine on Monday.  

“Injectable or intranasal ketamine has to be given in clinics, requiring patients to remain there for two hours or so to recover from side-effects, and to allow safety monitoring,” said Glue, an expert in psychological medicine at New Zealand’s Otago university. “Potentially, extended release ketamine tablets could permit patients to dose themselves at home, have less time in clinic and experience few or no side-effects.”

The scientists analysed a new ketamine tablet called R-107 developed by New Zealand’s Douglas Pharmaceuticals. Its slower release of the drug means less ketamine makes it into the bloodstream because it is mostly broken down in the liver, but the treatment still works because the breakdown products have an antidepressant effect.

The scientists found that 43 per cent of 168 depression patients who received R-107 twice weekly relapsed after 13 weeks, compared with 71 per cent in the placebo group. The ketamine tablet group experienced no changes of blood pressure and only minimal reports of sedation and dissociation, according to Glue and his fellow researchers from Australia, New Zealand, Singapore, Taiwan and the UK.

The findings are the latest contributions to expanding research into the effectiveness of oral ketamine treatments.

The study may help resolve a financial deterrent to the take-up of ketamine as an alternative to other ways of dealing with medication-resistant depression, such as electroconvulsive therapy. Both the nasal treatment and the clinical set-up needed to administer the drug intravenously are expensive.

The research underlines the “impressive antidepressant effect of ketamine” and suggested it could be delivered in a “much more convenient and acceptable form”, said Dr Paul Keedwell, a consultant psychiatrist and fellow of the UK’s Royal College of Psychiatrists.

The likely large differences in the way individuals absorb and break down ketamine means further work will be needed to deduce the ideal dosing regime, said Keedwell, who was not involved in the study.

“Their results suggest that many will continue to do well with longer-term treatment, provided higher doses are used, but more research is needed with higher numbers of patients,” he said.