Slow-release ketamine tablet alleviates severe depression symptoms: Clinical trial

A new tablet form of ketamine has demonstrated potential in treating severe depression, providing an alternative to current clinic-based treatments that are often costly and inconvenient. Unlike the injectable and nasal spray versions, which necessitate two hours of medical supervision to monitor side effects, this slow-release tablet can be safely administered at home with minimal side effects.

The study was spearheaded by Professor Paul Glue from the University of Otago, in collaboration with researchers from UNSW Sydney and the Black Dog Institute (BDI). The trial, conducted across various research institutions in Australia and New Zealand, was a randomized-controlled trial aimed at evaluating the effectiveness of ketamine tablets for depression against a placebo.

In the trial, 168 patients with treatment-resistant depression were randomly assigned to one of five groups: four groups received different doses of ketamine, while one group received a placebo. The group that received the highest dose of ketamine, 180mg taken orally twice a week, showed the most significant improvement compared to the placebo group. The effectiveness was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), where a higher score indicates more severe depression symptoms.

The results were compelling: in the 180mg ketamine group, the MADRS score dropped by an average of 14 points from a baseline of 30, whereas the placebo group's average reduction was only 8 points. Other doses of ketamine (120mg, 60mg, and 30mg) also showed slightly better outcomes than the placebo.

These findings were published in Nature Medicine. Professor Colleen Loo, a clinical psychiatrist and researcher with UNSW and BDI, has previously worked on the injectable and nasal spray forms of ketamine for depression treatment. She finds these results promising for multiple reasons.

Firstly, the tablet form is much more convenient than existing treatments. Patients no longer need to visit a clinic for injections and subsequent monitoring, but can instead take the medication at home, akin to other antidepressant treatments. This reduces the logistical and financial burden on patients.

Secondly, the results challenge existing beliefs about ketamine's mechanism in treating depression. Some theories suggest that the dissociative effects, where patients experience altered reality and perception, are essential for the antidepressant effects of ketamine. These dissociative effects are similar to those in psychedelic-assisted therapies, which propose that altering brain circuitry can lead to new insights and help patients break free from depressive thought patterns. However, the slow-release tablet form of ketamine does not cause these dissociative effects, yet still shows efficacy in treating depression. This suggests that such altered perceptions may not be necessary for the drug’s antidepressant benefits.

The double-blind trial, where neither the administrators nor the participants knew who received ketamine or placebo, was the first to examine the effectiveness of this slow-release tablet form. However, it will likely take years and substantial financial investment in further trials before this treatment could be approved for clinical use.

Douglas Pharmaceuticals, the New Zealand company behind the drug, still needs to conduct more studies. The treatment has not yet been approved by the FDA in the United States or the TGA in Australia. If it manages to pass regulatory hurdles, the tablet form could make ketamine treatment for severe depression more convenient and affordable.

The next step involves conducting similar studies at multiple global sites with a larger patient pool to verify the reproducibility of these results. Future research could also compare the tablet form with other delivery methods, such as injections, which have shown strong efficacy so far.