Ketamine Is a Proven Antidepressant, But Should We Use it?

For decades now, medical research has demonstrated the antidepressive effects of ketamine—which is a drug also associated with tranquillising horses and your mates at doofs. It's also an anaesthetic according to Australian law, but can technically be administered "off-label" as an experimental treatment.

One of the world's foremost experts in ketamine research, University of New South Wales Professor Colleen Loo, is leading the charge. She's currently running the world's largest trial of ketamine as an antidepressant and last week authored an accompanying report in academic journal Lancet Psychiatry exploring its associated health risks and side effects.

The Lancet study is crucial. For Loo and anyone else in the know, it's a given that ketamine is an effective antidepressant, so the next step is figuring out what that means in a clinical context. "The main point is we want everyone to be aware—members of the public, doctors, other clinicians—that there is potential for treatment but there are some potentially serious side effects with repeated use," she tells VICE.

To be clear, most patients living with depression and treated with ketamine report experiencing side effects. Which won't surprise anybody who has entered the k-hole. The most common of these side-effects were headaches, dizziness, dissociation, elevated blood pressure, and blurred vision. More severe risks included increased anxiety, agitation and irritability, euphoria, and delusional thinking.

The safety of long-term, repeated ketamine dosing, as is increasingly used in clinical practice, is therefore uncertain. Data on the safety of this practice, including long-term outcomes, is essential before ketamine can be used in clinical treatments.

Importantly, Loo and her team found that during most trials of ketamine as an antidepressant, these side effects weren't well-assessed or reported on. And almost all of the ketamine trials she assessed as part of her research were short term: patients received only one dose of ketamine in a single session, often experiencing brief but dramatic relief of their symptoms. The brevity of the drug's action is one of the reasons researchers have been perhaps too eager to focus on its apparently miraculous effects.

"People are so excited that they're jumping straight into using it in the clinic. And maybe without realising that it's not a straightforward step to move from giving a single dose to giving a repeated dose," she explains.

For this reason, most ketamine clinics are useless. If you want to treat your depression with ket, sign up to participate in an accredited study like Loo's or risk serious side effects that won't be monitored or mitigated. "Some patients think, 'Why bother going to a research study, I might as well just go to these clinics for 20 minutes rather than answering questions for four hours before treatment.' But the reason we do that is that the majority of our time is spent addressing safety issues," she says.

The risks associated with ketamine use seem significant, but Loo cautions that this all sounds much worse than it is. All drugs, accredited or not, have potential side effects—every patient who has medicated their depression will tell the same story about experimenting with various pills and dosages until something worked and ketamine is likely in a similar situation.

"Hundreds of thousands [of medications] are used safely. Not because they have no side effects but because we know what the side effects are and can give instructions about safety and monitoring. We need to try giving ketamine in different ways to test the effectiveness and at the same time test the safety and what safety monitoring is required."

Loo's already got some ideas as to what will and won't work. Key to her research is the finding that intravenously-administered ketamine creates more dissociative side effects than ketamine administered subcutaneously via a tiny needle not dissimilar to those used by diabetics to administer insulin. It's a vast difference: 36 percent of non-intravenous patient groups reported these side-effects, compared with 72 percent of patients from intravenous ketamine studies.

Given that depression affects hundreds of millions of people worldwide, many of whom have found existing medications to be unhelpful and even detrimental, Loo argues that we should be putting much more energy into ketamine research. With time, we'll be able to treat depression with ketamine outside of those experimental and dubiously-legal clinics.

"If you do it with careful supervision and monitoring, I believe ketamine can be given safely. But if you ask me what is the monitoring that needs to be done, the answer is that we don't yet know—and that's what we're working out."

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Colleen and the Black Dog Institute are actively recruiting for the world's largest trial of ketamine for depression in Sydney. Anyone interested in joining the trial can email ket.study@unsw.edu.au.