Typically administered intravenously, ketamine is already used as a last-resort treatment for depression when standard antidepressant drugs and therapy have proven ineffective. However, its availability is limited due to the need for clinic supervision, and a ketamine-like nasal spray was recently rejected by the NHS.

The recent trial, conducted by researchers from King's College London, tested an extended-release formulation of ketamine designed to release the drug gradually over a 10-hour period. The aim was to enhance treatment efficacy and minimize side effects such as dissociation, high blood pressure, rapid heart rate, and numbness. The extended-release feature is expected to reduce the drug's abuse potential as well.

The innovative trial design involved all 231 participants being initially given the new ketamine formulation for five days to identify "treatment responders." Of these, the 168 patients who showed a significant reduction in symptoms entered the second phase of the trial. They were randomly assigned to either continue taking ketamine tablets or receive a placebo.

The results revealed a notable difference in relapse rates, with 71% of patients from the placebo group experiencing relapse after 13 weeks compared to 43% of those who received the ketamine tablets twice weekly. Importantly, the patients on ketamine did not experience significant changes in blood pressure and reported minimal drowsiness. However, higher doses of ketamine were associated with feelings of dissociation and dizziness. One suicide occurred in the treatment group, but it was attributed to the patient's underlying illness rather than the treatment itself.

Prof Allan Young of King's College London, one of the co-authors of the findings, emphasized the clinically meaningful effect observed during the trial. He described the effect size as gratifyingly large, although further research is needed to confirm these findings on a larger scale.

While the results provide promising prospects for millions of people living with chronic depression, who have shown resistance to conventional medications, experts caution that further investigation is required to determine the ideal dosing regime and long-term safety of oral ketamine. Dr Rupert McShane, a consultant psychiatrist at Oxford Health NHS trust, expressed optimism about finding a ketamine formulation that mimics the benefits of intravenous ketamine while ensuring safety in the long run.

The trial's success in highlighting the impressive antidepressant effect of ketamine in a convenient slow-release tablet form is a significant step forward. However, it remains unclear whether ketamine treatments will be suitable for a wider population or if they will continue to be reserved for severe cases of depression. Dr Paul Keedwell, a consultant psychiatrist, believes that this uncertainty can be addressed through further research and clinical trials.

The findings of this groundbreaking trial have been published in the prestigious journal Nature Medicine, garnering attention from the medical community and offering a glimmer of hope for improved treatment options for individuals battling depression.