First 'gold-standard' trial of ketamine's anti-depressant effects launched

Clinical trial conducted in Australia and New Zealand will compare patients’ response to multiple doses of the drug with placebo

The first “gold standard” clinical trial of ketamine for the ongoing treatment of major depression was launched in Sydney on Tuesday and will involve seven research institutions and 200 patients from across Australia and New Zealand.

Several pilot studies have examined the effectiveness of ketamine for depression but these have typically been smaller studies testing a single dose of ketamine on acutely depressed patients.

These trials were necessary to establish whether the drug triggered a response in depressed patients and also to determine effective methods of administering it – for example, intravenously, nasally or subcutaneously.

But no trial has been conducted to see how people respond to ongoing treatment with multiple doses of the drug compared with a placebo until now. The randomised double-blind trial – the gold standard for clinical research – means neither the researchers nor patients know whether they will be receiving ketamine or a placebo. The trial will run for three years.

Prof Colleen Loo from the University of New South Wales, who is based at the Black Dog Institute in Sydney, is one of the study’s leaders and has been researching the use of ketamine to treat depression for more than five years.

“Existing studies show that if you give a single dose of ketamine to people with serious clinical depression, they do tend to get better – but that only lasts for a few days,” Loo said. “Feeling better for a few days is no good with a chronic disease like depression.

“What we now need to do is establish whether it can be used as an effective ongoing clinical treatment and, if so, who best responds to the treatment and what the treatment guidelines might be.

“It is not good enough to say that just because it has made people feel better in previous trials, when given one dose, that it is a safe and effective treatment long term.”

Loo said she was concerned that some clinicians were already prescribing ketamine to depressed patients. Currently, ketamine has only been approved by Australia’s Therapeutic Goods Administration for use as an anaesthetic but this does not prevent psychiatrists from prescribing it “off label” for depression.

“I know those doctors are running into problems because they call me for help, because what they are doing is entirely experimental and there is no evidence-based treatment protocol for them to follow,” Loo said.

“What happens is the patient responds to the ketamine, relapses after a few days, and so their doctor gives them another dose. As they get the treatment more and more it becomes less effective as people become resistant, so the doctor escalates the treatment. But after a while it just isn’t effective and the doctor is too scared to take their patient off the treatment in case it causes them to crash.

“It’s a big concern. We aren’t winging it in our trial. We will be very carefully monitoring people under a predefined treatment protocol.”

Long-term use and abuse of ketamine was associated with liver inflammation, destruction of the bladder lining, cognitive problems and other serious medical complications, she said.

The patients involved in Loo’s trial will receive the drug via a needle into subcutaneous tissue, like an insulin injection. They will also undergo blood, gene and biomarker testing to help researchers determine if there are factors that make patients more likely to respond.

Prof Ian Hickie, a psychiatrist and national mental health commissioner, said the study would help ketamine treatment move “out of the lab and into clinical practice”.

“To date, nobody has demonstrated that ketamine is a viable longterm treatment for depression,” he said.

“There are a lot of commercial clinics going down this road long before the benefits of sustained treatment have been proven.

“We need to be wary of competing commercial interests. There is a lot of interest in developing drugs based on the ketamine model worldwide, there are a lot of pending patents out there, and a lot of people investing money, time and effort with only evidence of the short-term benefits.”

As well as the Black Dog Institute and the University of NSW, other research centres involved in the trial include the University of Otago in New Zealand, Sir Charles Gairdner hospital in Perth, South Eastern Private hospital and Monash Alfred Psychiatry Research Centre in Victoria, the Brain and Mind Centre and Royal Prince Alfred hospital in Sydney, the University of Adelaide and the Royal Adelaide hospital.

Patients in NSW with major depression and who have not responded to other treatments, and who are interested in being involved in the trial, can contact Other sites will advertise for patients in the coming months.

For information and support in Australia call Lifeline on 13 11 14. In the UK, the Samaritans can be contacted on 116 123. Hotlines in other countries can be found here


Melissa Davey

The GuardianTramp

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