A slow-release tablet form of ketamine has offered some relief to sufferers of severe depression in a new clinical trial run by the University of New South Wales (UNSW) and the Black Dog Institute (BDI).
Researchers randomly assigned 168 patients with treatment-resistant depression (TRD) to five different groups, four of which would receive varying strength of the ketamine treatment and a control group receiving a placebo.
Patients on the strongest dose (180mg taken twice a week) experienced the strongest impact from the medication when compared with placebo.
Rewiring the brain
About 30% of people diagnosed with major depressive disorder are considered 'treatment resistant', meaning conventional treatments and medications make little to no impact on their symptoms.
New research into psycho-active compounds like ketamine, MDMA and psilocybin has offered new pathways for treatment-resistant mental health disorders, including post-traumatic stress disorder, generalised anxiety, eating disorders and depression.
Those treated in this most recent study experienced statistically significant improvements in their depression scores, which were rated on the Montgomery–Åsberg Depression Rating Scale (MADRS).
In the 180mg group, the average reduction in MADRS scores was 14 points, with the highest a 30-point drop.
In the placebo group, the average reduction in scores was 8 points, with the other remaining ketamine dose groups all slightly exceeding the control group’s progress.
Overall, the study offered strong evidence that slow-release ketamine could be an effective treatment pathway for TRD, offering alternatives to clinic-based treatments like injectable and nasal spray alternatives that require clinicians to monitor patients for two hours while side effects subside.
Results offer multiple insights
“The kind of results we’re seeing look as good as other ways of giving ketamine and are fascinating for two reasons,” said Professor Colleen Loo, a clinical psychiatrist and researcher with UNSW and BDI.
“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 study offers additional insight into the mechanisms of ketamine’s effect on the brain as well.
“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,” Professor Loo explained.
“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.”
More research needed
The study was the first of its kind investigating a slow-release tablet form of ketamine to treat depression.
The next step will be to run similar studies in multiple sites around the world with larger patient groups to show the results are reproducible.
“Douglas Pharmaceuticals, which is the New Zealand company that has produced the drug, still needs to do further studies and it’s important to note this is not yet approved by the FDA in the US or the TGA here in Australia,” Professor Loo clarified.
“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.”