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Does ketamine have a future as a mainstream antidepressant?

With the US FDA approving ketamine as a potential treatment for depression, we examine the future of the notorious party drug

Welcome to the Dazed Beauty Digital Spa. From the role of placebo in extreme wellness to the problem with our cannabis obsession, here we explore the complexities of the wellness industry and how it might evolve.

Few substances can boast a reputation quite like ketamine’s. Celebrated and reviled in equal measure, it’s known in most circles as a party drug – “k”, the horse tranquilliser, the bump that sends you wonky, slurring and stumbling around the dancefloor. As such, its double-life as a possible treatment for depression has led to either great amusement or grave scepticism.

Ketamine has long been an established anaesthetic, particularly for treating severe injuries thanks to its dissociative qualities – so established in fact, it’s included on the World Health Organisation’s “essential medicines” list, making it a must-have drug for any safe and effective health service. Yet in March of this year, the US FDA (Food and Drug Administration) approved a drug called esketamine – a form of ketamine administered via nasal spray – making it the first new antidepressant to be green-lit in the States in years. Almost a decade after studies into its potential began, there is a very real possibility ketamine could be about to go mainstream.

Dr Asim Shah MD, a professor at the Baylor College of Medicine in Houston, Texas, has been studying ketamine since 2010. The idea to do so, he explains, came from another research team on the East-Coast, who observed ketamine’s effect on patients when used as an anaesthetic. “People who were using ketamine were feeling euphoric, feeling happy,” he says. “So the idea came from there: why don’t we use it to treat depression.”

The first pilot study was carried out in 2012, with the basic aim of proving the drug’s potential to the FDA. It involved administering a small dose of ketamine via intravenous drip, and assessing the effects on mood against a series of depressive scales. “We found patients’ depression was alleviated for the next several days and in some cases few weeks.”

“Ketamine’s popularity as a party drug makes putting it on the market a loaded proposition.”

What struck Dr Shah and his team about ketamine was how quickly it took hold. Unlike a traditional antidepressant such as Prozac, which can take as long as four to six weeks to work, the mood-boosting impact of ketamine is felt within a few hours. Dr Shah sees this as a major breakthrough. “If you have response rates within hours then you may not need to hospitalise half of patients who are depressed and end up hospitalised,” he says. Depressive episodes are one of the leading causes of mental-health related hospital admissions, meaning patients are often kept under observation until they are no longer at risk to themselves. Ketamine’s fast response could see them treated and discharged in a fraction of the time, saving resources and potentially lives. “To me, that’s huge,” Dr Shah adds.

For the past four or five years, Dr Shah and his team have been experimenting with practical ways of administering ketamine, moving their focus away from the long-winded intravenous method and towards simpler applications. Due to the chemical makeup of ketamine, oral ingestion has proved tricky, but attempts using an intranasal spray have quickly proved promising. “We did the first trial of intranasal ketamine, twice a week, for four weeks, a total of eight sprays,” Dr Shah says. “We saw people improve tremendously – anywhere between 50 percent to 70 percent [of patients improved]. This is in contrast to a typical antidepressant which has an efficacy ratio is in the 40s.”

The research is beginning to bear fruit. In February, an FDA panel approved esketamine – a ketamine-based nasal spray marketed by Johnson & Johnson, who will sell the drug under the brand name Spravato. The drug is intended for “treatment-resistant” depression – for people who have already failed two antidepressants – and is to be taken in conjunction with the patient’s existing medication. It is being hailed by many as the biggest breakthrough in antidepressants in decades.

There are obvious implications to all of this. Ketamine’s popularity as a party drug makes putting it on the market a loaded proposition. Not only is it known to cause hallucinations and loss of memory, but its recreational use has also been linked to bladder damage, causing incontinence and in some extreme cases surgery. The drug is also considered addictive, or at least prone to “psychological dependence”, with regular users building up a tolerance and relying on it increasingly large doses.

“The problem will be the cost of ketamine. If it’s cheaper, it’ll be a game-changer.” – Dr Shah

With this in mind, the FDA have created a special distribution system for the drug, call REMS – Risk Evaluation and Mitigation Strategy. It means the physician prescribing the drug, the pharmacy issuing it and the patient receiving it all have to be on a register. Secondly, patients receiving the intranasal spray – which will only contain one dose – will be required to do so in the presence of their doctor, who then keep them under observation for two hours. This isn’t just to prevent substance abuse. The well-documented side-effects of ketamine, including sedation and dissociation – doctor-speak for the k-hole – mean patients are at increased risk in the immediate aftermath of taking the drug.

There has been some resistance in medical circles, from specialists who feel research into the drug has been inadequate and inconclusive. Of the 16 FDA panellists who voted on esketamine, two voted against it, citing concerns around the drug’s side effects and the possibility it could be abused. Another panellist (who went on to approve the treatment) described it as a “nasty drug”. As it stands though, the biggest thing getting in the way of ketamine becoming a fully mainstream antidepressant is cost. Prices will vary but as it stands one spray could cost as much as $900, meaning the full treatment of eight sprays a month will be near $7000, with access to the medicine depending on whether or not insurance companies view it as a legitimate option. “The problem will be the cost of ketamine,” Dr Shah adds. “If it’s cheaper, it’ll be a game-changer.”

In the UK doctors have been trialling ketamine since 2011, where it is offered “off label”, a term used when a drug is prescribed for something it hasn’t been legally approved to treat – in ketamine’s case it remains a legal anaesthetic in the UK, but not an approved antidepressant. There is only one designated treatment centre, at Warneford NHS hospital in Oxford, although several other clinics have trialled it as part of broader treatments. There is hope among some clinicians that Johnson & Johnson’s esketamine could be available in the UK in as little as 18 months, making it the first new antidepressant in the UK for 35 years, but this could be optimistic.

In the UK wariness remains as strong. A statement issued by the Royal College of Psychiatrists in 2016 said that despite trials showing “rapid improvement in mood after ketamine infusion,” significant gaps in knowledge of the drug meant “extensive research” was still required before it could be recommended.

Prescription ketamine is a little way off, yet the principle of what it has to offer remains massive. Countering depressive symptoms within hours, rather than weeks, addresses a previously untreatable window of time. Patients at immediate risk of harming themselves, who would previously have been hospitalised, may for the first time be offered fast-acting relief. Then there are the many patients who have found ketamine to be the first drug to make a difference, after years of trying with conventional antidepressants. Much remains unknown, particularly of its long-term safety and efficacy, but if any of these promises are realised then there’s every chance K could be capable of something truly special.