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Ketamine tablet reduces symptoms of severe depression

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A new tablet form of ketamine has shown promise in treating severe depression, offering a potential alternative to expensive clinic-based treatments.

Unlike the injectable and nasal spray alternatives that require clinicians to monitor patients for two hours while side effects subside, the slow-release tablet form can be taken safely at home without medical supervision and with negligible side effects.

Professor Colleen Loo is clinical psychiatrist and researcher with UNSW Sydney and the Black Dog Institute (BDI).

Loo has previously contributed to research on the injectable and nasal spray versions of ketamine treatment for depression.

The researcher said: “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.”

Researchers from UNSW Sydney and BDI  collaborated with colleagues from other research institutions in Australia and New Zealand to run a randomised-controlled trial testing the effectiveness of ketamine tablets to treat depression compared with placebo.

The researchers randomly assigned 168 patients with treatment-resistant depression to one of five groups: four that received different strengths of ketamine, and one that received placebo.

Patients on the strongest dose of ketamine – at 180mg, taken orally twice a week – had the best results when compared to placebo, the researchers found.

Success was measured by the size of reduction in a patient’s MADRS score – a measure of depression symptoms, where the higher the score, the more serious the depression.

In the 180mg group, the average reduction in MADRS score dropped by 14 points from a high of 30.

In the placebo group, the average reduction was eight points.

All of the remaining doses of ketamine (120mg, 60mg and 30mg) had slightly better outcomes than placebo.

The findings challenge some beliefs about how ketamine works in helping people successfully overcome depression.

Prof Loo said: “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.”

The next step, said Prof Loo, is for the group to run similar studies in multiple sites around the world in larger numbers of patients to show that the results are reproducible.

One such study could look at how the tablet form of ketamine compares with other modes of delivery such as injection, which to date has shown strong results.

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