Like most medical professional bodies, the Royal Australian and New Zealand College of Psychiatrists (RANZCP) publishes research journals, in this case, two: the Australian and New Zealand Journal of Psychiatry (ANZJP) and Australasian Psychiatry (AP). They are absolutely conventional in the material they publish I don't know where these rank among the 350 or so psychiatric journals published throughout the world, certainly not anywhere near the top tier. With rare exceptions, their articles are almost exclusively oriented toward what they call the "biomedical model" of mental disorder. Once again, this model doesn't exist but that's another story; what counts is their intense reluctance to publish anything considered critical of mainstream psychiatry.

For example, I recently submitted a short and mildly-worded paper to AP on the refusal of the NSW and Qld governments to allow the UN Subcommittee for the Prevention of Torture to inspect their "places of detention," as they are required to do under the Convention Against Torture. One of the reviews said only: "Crude, anti-psychiatry diatribe that lacks logic, balance, examples, or solutions." Why is that person a reviewer, or why would the editor send it to the author? Who knows but it says a lot about the general attitude among the mainstream (the paper is now approved for publication). So imagine the surprise all round when this week's AP included a critical paper on the process which led to the approval of the drug esketamine [1]. As with everything in psychiatry, there's a lot of background that the general public will never know, and that's the important stuff.

When I did my anaesthetics term as a hospital resident, half a century ago, ketamine had just been released. It was the first "dissociative anaesthetic" meaning it didn't actually put people to sleep, just put them in a peculiar state of detachment or dissociation during which they didn't respond to pain. It was good because anaesthetics for seriously ill people are dangerous, so this meant that people with, for example, major burns could have skin grafts performed without running the risk of their blood pressure plummeting. But it was scary stuff because patients were in a wierd mental state for many hours after and needed very careful nursing. As a junior resident, I wasn't allowed to use ketamine, which was fine by me.

I didn't hear of it again for many years until I had a patient, a truck driver who had suffered severe crush injuries to his leg in a roll-over. He was left with chronic nerve pain and couldn't work and, of course, got fairly severely depressed. He was slowly getting better when the pain people heard ketamine was being used for chronic neuritic pain and decided to give him a try. He was sent south and had three IV infusions over a couple of weeks, and came back feeling great. The pain was still there, but he didn't care, he felt detached from it.

He also told me that half the patients in the very expensive private hospital were scammers, there was nothing wrong with them, they just wanted the drug. It was hugely popular with the dance/rave crowd because, mixed with amphetamines, they could stay up all night, completely out of their heads, and carry on like idiots. They knew it as "Special K," and I soon learned there was a massive black market in it. It's addictive (or course) but not as dangerous as drugs like morphine or methamphetamine. It's now classed as a psychotomimetic, meaning a drug that mimics the effects of psychosis, i.e. people are completely out of their heads, all sensations are changed, no pain, nothing matters. It can go wrong, of course, but they don't care about that.

But, as the unfortunate truck driver soon realised, the effects didn't last. After a few weeks of limping around in some sort of happy daze, he crashed. Badly. Another trip down south, another course (at a cost in excess of $40,000 each time), same thing happened. Eventually, with all the disruption to family life, long air trips and so on, he stopped going but the industry has thrived and, like all successful industries, it looks for new fields to conquer. And what better than psychiatry which, as everybody knows, is a therapeutic mess. In no time, the purveyors of chemical bliss zeroed in on depression, the latest and, we are told over and over, greatest of all epidemics.

It's important to remember that the real money in the ketamine industry is not in the drug itself, although that's hugely profitable because it's off patent and is now made in India (Indian pharmaceutical companies are world standard, most of the medicines you take come from India). The real money is in all the drama of bringing the patient in for the day and setting up an IV infusion, at anything up to $2,000 a day. That's very good money but, as only insurers will pay that, another company had the brilliant idea of developing a nasal spray so patients can just give themselves a blast at home. In January 2019, Janssen-Cilag, a Belgian research and manufacturing company now owned by the huge American corporation, Johnson and Johnson, applied to the Therapeutic Goods Administration (TGA) to list esketamine, a slightly different version of ketamine, as a nasal spray for "treatment resistant depression" (now known as TRD, alongside MDD, ADHD, OCD, ODD, BAD and the rest). The definition is "has failed to respond adequately to two different antidepressants," which, for psychiatrists who deal with a lot of chronic pain (as I did) means practically all the patients who come through the door. GPs will have prescribed 3, 4 or 5 antidepressants before they refer the patients. After a few months, Janssen's application was rejected as the TGA wasn't convinced ketamine was either safe or effective.

The process of applying is difficult, as I learned some years ago. I was seeing a lot of people who were stuck on antidepressants and couldn't get off them. As we all know, this is because, like all psychiatric drugs, antidepressants are highly addictive. They also cause massive weight gain (30-50% increase in weight is common with these drugs) and seriously suppress sexual interest, among many other side effects, so people like to get off them. Trouble is, they can't. Every time they stop the drugs, they get severe withdrawal effects including intense physical and mental agitation, insomnia, bizarre sensations in the body and head and so on. However, psychiatry turns this around: "Oh no, that's not withdrawal effects, our drugs aren't addictive. That's your mental disease coming back, quick, try another antidepressant." That's why people have been taking them for 25 years or more and have tried half a dozen. So I thought it would be a good idea to be able to import smaller sized tablets so people could withdraw safely. Turns out it wasn't such a good idea.

My plan was to deal with an approved manufacturer (there are hundreds in India) to bring in two smaller doses for a couple of antidepressants, say 5mg and 10mg for a drug whose smallest tablet was 30mg. That way, we could set up proper tapering packs for people to withdraw safely. No way. Each preparation of each dose requires a new application, even if it's an approved drug from an approved manufacturer who is already exporting it to Australia. Each application requires all the massive amount of material on manufacturing, testing, safety reports from here, there and everywhere, accompanied by a fee. The fee for each dose for each tablet is $150,000. So licences for two smaller doses for three different drugs would have cost $900,000, which is why there are no tapering packs in Australia. This was about five years ago, I don't know what it costs now. Anyway, back to esketamine.

Undeterred, Janssen submitted a bit more material and, after a total of twenty-one months, that too was rejected as insufficient. But the Therapeutic Goods Act has an escape hatch. They were able to appeal to the minister for health, then the entirely useless Greg Hunt. In five weeks, a letter arrived at the TGA from the minister's office telling them to approve esketamine as nasal spray for "treatment-resistant depression." As the paper reveals, between 2016-2020, Janssen-Cilag donated $166,955 to the Liberal/National parties, and $197,400 to the ALP. There could easily have been more as most donations to political parties are anonymous.

Their nasal spray, trade-named Spravato, is now for sale in Australia. A prescription for two single-use sprays, each containing 28mg of esketamine, costs $784.12, or nearly $400 each. For people who want to misuse the drug (and there are already tens of thousands of ravers doing just that), that's probably not too expensive. However, the cost of a pack of three sprays (total 84mg) of the same drug in India today is... wait for it.... Rupees 316, that's $5.76 or under $2.00 each [2]. Given the cost of the packaging and transport and marketing and so on, the actual cost of the drug would be about 20c per spray. At that price, a night on the town is much cheaper than a beer. I'm sure somebody will wake up to this shortly and start to import it, so we can expect a massive increase in the numbers of people addicted to this unpredictable drug. Meantime, the private hospitals are making a killing from their "dedicated programs" to provide the miracle treatment for TRD. And the suicide rates just go up and up.

Well, folks, wasn't that a lovely story. It's heartwarming to know that the minister, a career politician who knows nothing about medicine, can, in just five weeks, override the various committees of experts in the TGA who spent not far off two years dredging through reams of reports and decided the drug wasn't safe or worthwhile. Since then, of course, the British NICE, their equivalent of TGA, agreed it wasn't justified and declined to authorise it. So if you want it in Australia, all you have to do is log in to Dr Google who will give you a little list of symptoms of chronic depression to memorise, and the names of a couple of antidepressants that weren't any use, and off you go to the local clinic. Then, after a quick stop at the pharmacy, you can head off to that really big music festival for a weekend smashed out of your mind. Fun fun fun.

All of this comes about just because psychiatry has no model of mental disorder that tells us what depression is and how to manage it. The idea that it is "a chemical imbalance of the brain" is pure ideology [3]. I was going to say something about the role of pressure groups in getting these drugs approved but all this has made me too depressed so that will have to wait. I think I'll have a nice cup of tea and go for a walk in the garden to see how my tomatoes are going. At midnight last Saturday, we were woken by a caterwauling from the garden. A couple of dingoes had come up from the creek and were serenading the moon about 50m down the slope. They must have got bored with their music because next morning, I found they had chewed through some of my irrigation pipes. The little dears.

References:

1. Lugg, W (2023) The parable of the TGA approval of esketamine in Australia. Australasian Psychiatry, doi: 10.1177/10398562231156475

2. Esketamine nasal spray Spravato. Treatment: antidepressant. Link at:

https://www.indiamart.com/proddetail/esketamine-spravato-nasal-spray-24702735848.html

3. McLaren N (2013). Psychiatry as Ideology. Ethical Human Psychology and Psychiatry 15: 7-18.

PS. I will be turning on subscriptions when I work out how to do it. Fees are in USD because.