The TGA won’t label it, and Medicare won’t create an item number for off-label treatments, leaving patients on a costly merry-go-round.
The lack of a Medicare item number for off-label use of ketamine for treatment-resistant depression is wasting government money and blocking access for patients in desperate need, says ketamine expert Professor Colleen Loo.
In March 2021 the TGA registered nasal spray Spravato (esketamine hydrochloride) for use in adults who had not responded to at least two different antidepressants. After a limited rollout as part of a carefully controlled early access program across the country, its use by psychiatrists has increased with about 30 sites accredited by July 2022.
Esketamine is a patented, more potent, “s” form of ketamine which can be administered nasally.
Ketamine itself is off-patent and is on-label only for anaesthetic and sedation use. Its off-patent status makes it far cheaper than its newer offshoot.
Esketamine is not listed on the PBS. The July 2022 submission to the PBAC from sponsor Janssen-Cilag P/L was rejected because the PBAC “considered that for most patients, esketamine should be initiated after additional treatment options that have longer-term safety and effectiveness data and are more established in clinical practice (for example, combination therapy, augmentation with lithium or other agents and physical treatments such as ECT and rTMS) have been trialled or at least considered”.
That means the cost for patients is considerable, varying according to the dose and treatment schedule, and could be from $300 per week up to $1800 per week.
Ketamine, by contrast, is off-patent and therefore costs about $5 a vial, according to Professor Loo, a ketamine research pioneer with UNSW Sydney and the Black Dog Institute.
“Ketamine is still off-label and for the foreseeable future, it will remain off-label because labelling is not just an issue of the evidence base,” she told TMR.
“It’s an issue of having a commercial sponsor. Only a commercial sponsor can put up a labelling application to the TGA.
“Here is the block. Because it’s off-patent, ketamine is generically available for $5 per dose and anyone can produce it. It doesn’t make sense for any commercial sponsor to put up the cost and take all the risks of being a sponsor for a label for treatment-resistant depression.”
But where the rubber hits the road, she says, is when you want a Medicare item number reimbursement for the treatment procedure itself.
“Ketamine, although it’s technically a drug, it’s not a medication like other medications in psychiatry, where I see a patient in my rooms, I write a script and then off they go to a chemist and they take it themselves at home,” said Professor Loo.
“Ketamine requires a two-hour treatment process where we need to measure your blood pressure beforehand, monitor you carefully with line-of-sight monitoring, usually by nurse. We need to actually deliver the treatment, measure your blood pressure for some time afterwards, we need to make sure that you’re fit for discharge.
“The central parts to the treatment are the drug, but the other one is the treatment procedure, which is the same regardless of what drug you’re using, whether you’re using the patented nasal spray or the off-patent, generic drug.
“That incurs certain costs, because you need to have a certain number of nursing staff etc. So this clearly is going to become costly, and that’s a major barrier for patients.
“At the moment, patients are out of pocket for that treatment cost.
“Where the off-label thing becomes a problem is that when you apply to Medicare for an item number, they will say that they can’t give you an item number for a treatment that is off-label.”
It’s a wicked problem Professor Loo can’t see an end to, barring personal intervention from Health Minister Mark Butler.
“This is a systems issue,” she said. “It is such a pity, because ketamine is an amazing treatment for treatment-resistant depression.
“A number of things have happened in the last 12 months. The RANZCP has issued a clinical memorandum that it’s appropriate to use both Spravato and also ketamine [for treatment resistant depression].
“Both have got an evidence base for effectiveness and safety in treatment resistant depression,” she said.
“I see patients where they often fail to respond to five to 10 medications, they’re failed to respond to transcranial magnetic stimulation. And I would say, I think you would do really well with ketamine, but they say, I can’t afford it.
“Often, they end up having ECT, which is a very good treatment, but my concerns as a clinician are that it’s the cost-access issue that is determining treatment, not clinical need.
“The irony is it probably costs Medicare and the health funds more [for ECT] than a treatment of ketamine. And it’s very sad for the patient where that is not the recommended treatment in that scenario.”
So, for the sake of either allowing on-label use without the backing of a sponsor, or assigning a Medicare item number without on-label registration, not only are patients missing out on arguably the most appropriate treatment, but the government is paying over the odds.
“It is a wicked problem,” said Professor Loo. “The issue of off-label use is not in itself a problem, because [psychiatrists] are doing it all the time.
“But then you come to Medicare funding – which also means private health fund funding, because they follow Medicare – which then determines patient access to treatment.
“To be frank, the federal government would actually save money. When you look at the huge effect size of how much better people get – from being chronically depressed, unable to work or study or even suicidal, and in some cases, ending their lives, to being completely well and able to work, function and get on with things.
“When you look at that, plus the relatively small cost per treatment, if you use the $5 ketamine plus the $300 treatment process, ironically, Medicare, by funding this, would probably save the federal government money. But there is no one body that brings it all together – the TGA say it’s not their problem, and Medicare says it’s not theirs.”
The Department of Health and Aged Care was contacted for comment on this story last week but has not responded.
