Ketamine for Depression is 'Not New or Radical' – So Why Hasn't Australia Caught Up?

In the United States, ketamine is having a bit of a moment. Since a nasally administered version of the drug called esketamine, or Spravato, was approved by the FDA for medicinal use in 2019, “ketamine clinics” have been cropping up across America. 

The anaesthetic and sometimes-hallucinogen has been approved for medical use across the world since the 1960s – but the recent FDA approval for Spravato, submitted by its Belgian-based manufacturer Janssen, came after recent contributions to a growing research base on its efficacy against treatment-resistant depression (TRD).

In the US, Sravato can only be administered in a clinical setting, by a doctor, and is only approved for people with depression that is otherwise treatment-resistant. The treatments at these so-called “ketamine clinics” are expensive, varying from $400 to $800 a session, but they are accessible in terms of their widespread availability. There are even virtual ketamine clinics now.

Spravato was approved in Australia in March 2021, by the Therapeutic Goods Administration (TGA), for medical use on patients with TRD. But the roll-out of clinical ketamine treatment here has been marred by widespread inaccessibility and high costs. As Spravato isn’t on Australia’s Pharmaceutical Benefits Scheme (PBS), treatments can cost from $300 to $1800 per week.

The manufacturer’s application to have Spravato listed under the PBS was rejected, for the second time, in July last year, with the Pharmaceutical Benefits Advisory Committee (PBAC) citing that there was “limited long-term safety data for esketamine, including data assessing the potential for developing dependence”, among a litany of concerns. 

Despite the submission’s input from “individuals, clinicians and organisations which highlighted the severe impact of TRD on daily life” and its inclusion of experience reports from individuals and clinicians, who described the treatments as “being able to restore hope to patients, when other options had failed”, the PBAC concluded that Spravato was not recommended for PBS listing. 

But Spravato is only one form of ketamine being researched.

Doctor Adam Bayes, a clinical academic scientist and senior research fellow at Sydney’s Black Dog institute, said that currently, in Australia, there were two main formulations of ketamine being studied and offered for treatment.

“Standard ketamine is two molecules, which are basically mirror-images, and that’s been around for decades as an anaesthetic. It’s 50 per cent (S)ketamine and 50 per cent (R)ketamine,” Dr Bayes told VICE.

“There’s Spravato, esketamine, which is the intranasal formulation, and a lot of research has been done on that. Then there’s racemic ketamine.”

Racemic ketamine has both (S)ketamine and (R)ketamine, and is administered intravenously. It’s this general formulation of ketamine that is simultaneously being researched and offered as a treatment at Black Dog.

Despite the lagging path to literal access, Australia has been a world leader in ketamine research, notably for the work done by Professor Colleen Loo, who led the first randomised control trials of the drug as a novel treatment for severe depression in the early 00s. Professor Loo is a clinical psychiatrist and Professor of Psychiatry at the University of New South Wales and at Black Dog, where she has led an ongoing research program into the use of ketamine to treat depression for the last decade. 

Dr Bayes said the Black Dog Institute had just completed the first Phase Three randomised control trials of racemic ketamine. The study, which is currently being peer reviewed ahead of publishing in The Lancet, looked at how racemic ketamine could be used in coordination with a patient’s usual antidepressants. 

“These studies are done in patients with treatment resistant depression, so basically these patients that have failed multiple trials of standard antidepressants, and that's generally the patient group that we're interested in with ketamine,” Dr. Bayes said.

“Generally, ketamine is added to an existing antidepressant. And there's been positive findings. When ketamine is compared to a placebo, there are higher rates of patients that go into remission and no longer have depression after receiving ketamine versus receiving the placebo.” 

In the study, patients with adult depression remained on whichever antidepressants were working for them, SSRIs or other, and had either ketamine or a placebo added in conjunction over a four-week period. 

The study was the first in the world to look at racemic ketamine on an adult population with treatment-resistant depression, and was held at seven sites aside from Black Dog.

“It’s a pretty important study,” Dr. Bayes said.

“It's been exciting because we're talking about a group of patients that have failed other treatments. And that’s why it's particularly important because these are patients that aren’t responding to standard treatments, and then when ketamine is added into an antidepressant, some of them will respond and get better. It's quite interesting.”

Elsewhere in Australia, Orygn’s Study of Ketamine for Youth Depression (SKY-D) is still ongoing, after receiving an extension due to recruiting issues during COVID-19. 

The trial’s principal investigator, professor Chris Davey, said while it was too early in the trial to determine results, ketamine’s efficacy was “not new or radical”.

“The first study was published in 2000. So, that's 23 years later. It often frustrates me that it gets talked about as being such a new treatment, and experimental, and there's been 23 years of evidence now,” Davey told VICE.

“We're a bit slow on the uptake in Australia. There are plenty of clinics in the US and Europe. It's not that new or that radical. I think time has come to offer it in a controlled and considered way, and to make it more available to people.”

In Australia, ketamine still hasn’t been approved for clinical use for depression. As Davey told VICE, it has been “well and truly out of patent”, so it’s “highly unlikely” someone would apply to the government to get it approved to be used for depression.

“Generally, the only people who apply for approval are drug companies, it can take millions of dollars and paperwork and reports to get it submitted, and so it might not be properly approved for treatment of depression unless there are people with the time and resources to put an application in,” Davey said.

But, Davey said, one of the things that could make ketamine more affordable was if there was a Medicare item covering the cost of patients coming into the hospital to get the treatment.

Dr Bayes said he hoped Black Dog’s forthcoming research would help compel the case for getting ketamine treatments covered under Medicare.

“There are some major barriers, but I think over time, certainly as the evidence base is accumulating, I expect there will be more centres where ketamine is available. And I do think, in terms of the Medicare item number, that's something that that Black Dog is interested in getting up.”

But despite the evidence base, and its long-studied efficacy, there could be a number of years before ketamine treatment is actually accessible to those who need it.

Davey said that this was one of his primary concerns.

“An important thing to me is to provide ketamine treatment to people who really need it, who otherwise couldn't access it. I think it’s one of the things that's happening with treatments like ketamine, and I think we'll see it with psychedelic treatments, when they are able to prescribe psilocybin and MDMA.” 

“My theory is they’ll only be available to wealthy people – they’ll be the only people who are able to afford the treatments.”

“To digress, with psilocybin and MDMA, they’re taken in eight hour sessions with two therapists with you the whole time, so I don’t know how that’s going to be funded.”

Even if a patient can afford ketamine treatment, Dr Bayes said, accessibility in terms of distance was another massive barrier.

“The reality is that there aren't that many clinics at the moment. There are certain specialist centres and hospitals that do have a ketamine service but there aren't a lot around. For people in rural or remote areas, that's going to be very difficult for them to access, because it does require coming in to receive the treatment. Each treatment, you have to actually physically be in the clinic for it to be administered because it’s a schedule 8 drug.”

Both Davey and Dr Bayes expressed hope for the future. Davey works at a Melbourne hospital, which he said was rolling out a free, twice-a-week, intravenous ketamine treatment clinic that will be available for free to people in the mental health services.

“We’ll only be able to do it in a limited sort of way,” said Davey. “It’ll be pretty hard to even access as people have to have already made it into mental health services, which isn’t that easy, unfortunately, with the way mental health services are funded.”

Ultimately, despite the excitement and hope generated around a new treatment, without government intervention, these treatments remain inaccessible to large swathes of the population.

When Spravato was relisted for back in 2022, a flurry of articles surfaced, with esketamine users expressing sentiments like “it saved my life” and, "I feel more well than I ever have", as they joined the plea for the medicine to be acknowledged, and made affordable.

But, as seems to often be the case, Australia is lagging behind. All despite a mental health crisis that only worsens amid our other crises, like the rising cost of living and a bitter and restrictive housing market. While new research is paving the way for better treatment, the people who need it most are shut out. 

“These newer treatments are really only accessible to people in the private systems, people who can afford to access, which is not the way – mental illness and depression is much more common in people who are from lower socioeconomic groups, or people who are least able to access them,” said Davey.

“It’s really hard getting new treatments going, especially in the hospital setting, and in mental health, people aren’t really open to it.” 

“But there’s been a lot of evidence coming out from really reputable scientists for years now. It’s not this new-fangled, risky thing.”

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