A low-cost version of ketamine has shown promising results in its treatment of resistant depression in a double-blind trial.
Researchers at the University of New South Wales (UNSW) Sydney and the affiliated Black Dog Institute have found that more than one in five participants achieved total remission from their symptoms after a month of bi-weekly injections of generic ketamine.
One-third of the 179 participants had symptoms improve by at least 50%.
The study, published today in the British Journal of Psychiatry, was a collaboration between six academic clinical mood disorder units in Australia and one in New Zealand and was funded by the Australian National Health and Medical Research Council (NHMRC).
Lead researcher Professor Colleen Loo stated: “For people with treatment-resistant depression – so those who have not benefitted from different modes of talk therapy, commonly prescribed antidepressants, or electroconvulsive therapy – 20%remission is actually quite good.
“We found that in this trial, ketamine was clearly better than the placebo – with 20% reporting they no longer had clinical depression compared with only 2% in the placebo group. This is a huge and very obvious difference and brings definitive evidence to the field which only had past smaller trials that compared ketamine with placebo.”
How did the trial work?
For the trial, participants were given two injections a week of either a generic form of ketamine or a placebo and were monitored for around two hours while acute dissociative and sedative effects wore off.
The treatment was given over a month period and participants were assessed at the end of the trial and a month following the completion of the trail.
The trial used the placebo Midazolam which also causes sedation to improve treatment masking. Midazolam is a sedative normally administered before a general anaesthetic, while in many previous studies, the placebo was saline.
“Because there are no subjective effects from the saline, in previous studies it became obvious which people were receiving the ketamine and which people received placebo,” Professor Loo stated.
“In using midazolam – which is not a treatment for depression, but does make you feel a bit woozy and out of it – you have much less chance of knowing whether you have received ketamine, which has similar acute effects.”
Other features of the recent trial that set it apart from past studies included accepting people into the trial who had previously received electroconvulsive therapy (ECT).
“People are recommended ECT treatment for their depression when all other treatments have been ineffective,” Prof. Loo says.
“Most studies exclude people who have had ECT because it is very hard for a new treatment to work where ECT has not.”
Additionally, the drug was delivered subcutaneously rather than by drip, thus greatly reducing time and medical complexity.
Improving patient access
The researchers emphasise that one of the key benefits of using generic ketamine for treatment-resistant depression is that it is much more affordable than the patented S-ketamine nasal spray which costs around AUD$800 per dose.
The generic ketamine can cost as little as $5, and, patients need to pay for the medical care they receive to ensure their experience is safe, which costs $350 per session at the Black Dog Institute.
Professor Loo stated: “With the S-ketamine nasal spray, you are out of pocket by about $1200 for every treatment by the time you pay for the drug and the procedure, whereas for generic ketamine, you’re paying around $300-350 for the treatment including the drug cost.”
Loo also emphasised that for both S-ketamine and generic ketamine treatments, the positive effects often wear off after a few days to weeks, so ongoing treatment may be required, depending on someone’s clinical situation. However, the prohibitive costs of the drug and procedure make this an unsustainable proposition for most Australians.
“This is why we’re applying for a Medicare item number to fund this treatment now, because it’s such a powerful treatment,” Loo said.
“And if you consider that many of these people might spend many months in hospital, or be unable to work and are often quite suicidal, it’s quite cost-effective when you see how incredibly quickly and powerfully it works. We’ve seen people go back to work, or study, or leave hospital because of this treatment in a matter of weeks.”
The researchers will next be looking at larger trials of generic ketamine over longer periods, and refining the safety monitoring of treatment.
