Prolonged-Release Ketamine Tablets: Potential Cure for Severe Depression

A novel tablet formulation of ketamine has demonstrated potential in the treatment of severe depression, providing a possible substitute for the current treatments provided in a clinic, which may be costly and inconvenient for certain patients (1^✔ ✔Trusted Source
Extended-release ketamine tablets for treatment-resistant depression: a randomized placebo-controlled phase 2 trial

Go to source). The prolonged-release tablet form, also known as extended-release tablet form, allows patients to safely take their medication at home without the need for medical supervision and has minimal side effects. It has advantages over the injectable and nasal spray alternatives which require clinicians to monitor patients for two hours until as the side effects diminish.

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What is Ketamine?

Ketamine is a chemical compound developed in the 1960s for its use as an anesthetic. It is also known to have hallucinogenic effects. This medication must be given in controlled and closely monitored clinical environments.

The Food and Drug Administration has approved ketamine as a sedative/analgesic and general anesthetic, and it is a low-cost dissociative drug.

Dissociative substances are a type of psychoactive drugs that create a feeling of separation from one's environment, physical self, and sense of self. These substances can result in intense episodes of distorted reality and changes in consciousness.

Earlier research studies had shown that small amounts of this drug could provide quick relief from depression for individuals with Major Depressive Disorder (MDD).

Recent studies show Ketamine has potential to be an effective treatment for severe depression, with no significant adverse effects when compared to electroconvulsive therapy, which is widely regarded as the benchmark treatment for depression (2^✔ ✔Trusted Source
Ketamine in tablet form shown to reduce symptoms of severe depression

Go to source).

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Objective and Details of the Clinical Trial

A randomized controlled trial was conducted by a team of scientists under the under the leadership of Professor Paul Glue from University of Otago. These scientists from UNSW Sydney and the affiliated Black Dog Institute (BDI) collaborated with colleagues from other research institutions in Australia and New Zealand to run this trial. The objective of the trial was to assess the efficacy of ketamine tablets in treating depression, in comparison to a placebo.

The scientists randomly assigned 168 patients with treatment-resistant depression into five groups: four received different doses of ketamine and one received a placebo.

The scientists found that patients who were administered the highest dose of ketamine, which is 180mg taken orally twice a week, showed the most favorable outcomes in comparison to those who received a placebo. The effectiveness of the treatment was evaluated based on the extent of reduction in the patient's MADRS score, which is an indicator of depression symptoms. A higher score on the MADRS scale indicates a more severe level of depression.

In the 180mg cohort, the mean decrease in MADRS score decreased by 14 points from a peak of 30. On the other hand, the placebo cohort experienced an average reduction of 8 points. In comparison, all other doses of ketamine (120mg, 60mg, and 30mg) exhibited marginally superior results compared to the placebo group.

The study details were presented in the journal, Nature Medicine.

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Encouraging Study Outcome

Professor Colleen Loo, a clinical psychiatrist and researcher affiliated with UNSW and BDI, has previously made significant contributions to studies involving the use of injectable and nasal spray forms of ketamine for treating depression.

She says, “The kind of results we’re seeing look as good as other ways of giving ketamine, and are fascinating for two reasons,”.

“First of all, there's the practical clinical reason that this is a way of administering ketamine to treat depression that's much easier to give. Rather than having to come to the clinic and have an injection and have medical monitoring for two hours, once or twice a week, this is much more convenient and allows patients to have their treatment at home, making it as convenient as other antidepressant medications.”

“It is also possible that some people may respond to one approach to treatment, such as the tablet, while others respond to another, such as the injection, so having more treatment approaches is very useful.”

“The second reason is that it challenges some beliefs about how ketamine works in helping people successfully overcome depression.”

Prof. Loo further states, “There's one school of thought that says what we call dissociative effects – where you're feeling a kind of altered reality and perception – are actually integral to the ability to improve the depression with ketamine,”.

“And that's very similar to the psychedelic assisted therapy model that says changing your brain circuit functioning in that very profound way gives you new insights that help you to break out of your way of thinking, and that this acute kind of dissociative altered reality experience is necessary for you to improve.”

“But with this tablet form you don't experience that because only a tiny amount is released into the bloodstream at a time, with ongoing slow release over days, and you don't experience the dissociation at all, and yet people are improving.”

“So it could be that the theory that you must have these altered reality perceptions to improve may not be correct.”

Next Steps Ahead

The double-blind study, in which the allocation of ketamine or placebo to each group was concealed from both trial administrators and patients, was the first to evaluate the efficacy of a prolonged-release tablet form of ketamine for treatment of depression. However, it may take several years and millions of dollars in additional trials before it is approved for clinical use.

Douglas Pharmaceuticals, the New Zealand-based company responsible for manufacturing the medication, is still required to conduct additional research. It is crucial to emphasize that the drug has not yet received approval from the FDA in the United States or the TGA in Australia.

Prof. Loo adds, “But if it does get through all those hoops and becomes an approved treatment, it certainly makes it much more convenient, not to mention cheaper, to use ketamine to treat severe depression.”

According to Prof. Loo, the subsequent steps involve conducting similar studies in numerous locations worldwide with a larger patient population to demonstrate the replicability of the findings. As an example, one potential study could examine the efficacy of ketamine in tablet form compared to other administration methods, particularly injection, which has thus far exhibited promising outcomes.

References:

1. Extended-release ketamine tablets for treatment-resistant depression: a randomized placebo-controlled phase 2 trial - (https://www.nature.com/articles/s41591-024-03063-x.pdf)
2. Ketamine in tablet form shown to reduce symptoms of severe depression - (https://www.unsw.edu.au/newsroom/news/2024/06/ketamine-tablet-reduce-severe-depression)

Source-Medindia