In January, researchers from Houston's Ben Taub General Hospital announced their groundbreaking research into a new drug-based treatment for depression. It was, they said, ridding the clinically depressed of their symptoms within a matter of hours and showed a success rate of 70-90 per cent – making it one of the biggest medical developments since the advent of antidepressants in the late 1950s.
"Everything since then has been essentially incremental," said study leader Sanjay Mathew, associate professor of psychiatry and behavioural sciences at Baylor College of Medicine. "It's a completely different mechanism. And the focus is on really rapidly helping someone get out of a depressive episode."
This new mechanism isn't the result of a recently discovered chemical compound but the reapplication of an existing drug – ketamine. Used in both human and veterinary science as an anaesthetic agent, it's also taken recreationally among drug users who seek out its dissociative, euphoric and hallucinatory effects.
A completely separate class of medication to traditional antidepressants, which work on serotonin or adrenaline, ketamine works on the glutamate receptor system and presents an exciting paradigm shift in the treatment of depression.
The recent study is a follow-up to 2006 research conducted by the National Institute of Mental Health. With the success of these studies, researchers from the University of New South Wales' School of Psychiatry and the Black Dog Institute – in conjunction with clinical pharmacologists from The University of Adelaide and the University of Otago – have embarked on the first Australian investigation.
"When I read the studies I was bowled over by the incredible response to ketamine that was being reported. It was almost too good to be true," said study leader Professor Colleen Loo. "We thought, gee, if they're that fantastic we should really try and see for ourselves. What the conventional antidepressants were achieving in two-to-four weeks they were achieving in 24 hours, sometimes less. It was unbelievable."
Not only is the response time in stark contrast to drugs currently on the market, it's proving to be more effective in relieving participants of their depressive symptoms. Whereas traditional antidepressants can be a bit hit and miss with only 30-40 per cent of patients responding to the initial prescribed medication and dosage, ketamine studies are showing early success rates of more than double that. Though long-term effectiveness is yet to be established, the success rate and its relative speed is promising – especially for individuals presenting with severe depressive symptoms.
"One of the first things is that people can be really unwell. They can be suicidal or they're not eating or drinking and it's a problem if you can't turn them around for two-to-four weeks... If you have a treatment that can get people well quickly that is very beneficial," said Loo. "The other problem of waiting up to four weeks is that you're not sure how you're going to respond to the drug. You could take this one for four weeks and then you might have to take a different one and again you might have to wait four weeks to see if that's going to work before you try the next one. This can start to become quite drawn out and begin to discourage patients."
Another proposed benefit to the use of ketamine is the relative absence of serious side effects. Electroconvulsive therapy has so far been the only effective tool to help combat clinical depression in patients who haven't responded to medication. Though it's a viable treatment, studies show ECT can cause memory loss and other adverse cognitive effects. Because the ketamine study is looking at short-term, low-dose use the side effects are minimal, and there have even been reports of people who have failed with ECT responding to ketamine.
"What we are finding is that at the higher doses you can get transient psychonautic effects. I think this is what people who abuse it are looking for. You can feel a bit disassociated, a bit unreal, things look distorted and, at higher doses, you can actually start to have hallucinations," said Loo. "We're using lower doses than what people do who abuse so people aren't actually having hallucinations, they're getting that milder unreal feeling but these are transient and go away after half an hour or so. On the other side it can affect your blood pressure and heart rate so we monitor that very carefully. In the conditions where we do it we're looking at single doses, not the large number of repeated doses of people who abuse it."
Just as illicit drugs such as LSD, ecstasy and marijuana have been used in a medical context but remain dangerous in terms of recreational use so too is ketamine. Loo explains that they administer the drug intravenously in a hospital setting once a week over six weeks in order to carefully control both dose and rate, and he stresses that individuals who self-administer run the risk of more serious side effects.
"People aren't just sitting on a chair in a ward somewhere drinking something; it's under very careful, medically monitored conditions," she said. "You need to remember that ketamine is used as a full anaesthetic agent so it's not safe to just draw something and inject it into yourself at any old rate... You could end up increasing your heart rate to the point where you have a stroke."
With Australian trials underway since February, Dr Rosalyn Lai, a research fellow at The New South Wales Institute of Psychiatry and fellow study author, says the response has been promising.
"The results have been quite positive so far, we've had four people complete the trial so far, and of the four people who have gone through, all of them have achieved some level of response," she said. "What I mean by response is that they've had a drop of at least 50 per cent in their mood rating scores. It's been very, very exciting to see."
Loo adds that more investigation is in order before ketamine is ready for clinical use. Though that could be as soon as a few years away, she says researchers need to see if it has a long-lasting response before it can be marketed as a useful tool in the treatment of clinical depression. Even then, she doesn't foresee it replacing antidepressants currently on the market.
"In its current form ketamine needs to be given intravenously in a hospital setting under careful medical supervision, so it's a lot more complicated than giving someone a script and saying, 'Go home and take this pill.' Unless ketamine can be developed into a form that can be given safely orally and still be effective, and we're not there yet, I don't see it replacing antidepressants," she said. "It's my opinion that we don't need to replace A with B or C with D. Having a whole suite of treatment options, so that we have more to choose from, means we can better match the treatment to the clinical situation and the patient. I think that's to the advantage of everyone."