May 28, 2018

Research: ketamine treatment for depression

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Typically used as an anaesthetic in hospitals, and used by a small number of Australians as a ‘party drug’, ketamine has been making headlines in recent years for a different reason.

Ongoing research has some mental health practitioners, and depression sufferers, very excited about ketamine’s potential to address treatment-resistant depression; but the recent cancellation of a trial also raises some red flags about who it will work for, and how it should be administered.

Ketamine trials

Ketamine has been found in some trials to rapidly reduce the symptoms of depression and provide relief for up to several days; this contrasts with most other treatments that do not produce the same quick response.1 It works by targeting a key signalling chemical in the brain called glutamate, and is thought to also affect brain cell growth and function.2

The participants involved in ketamine trials are typically suffering from severe depression and haven’t responded to other therapies. These trials have shown that ketamine has the potential to relieve feelings of sadness, helplessness and even suicidal ideation without creating a mood-elevating effect.1

But while ketamine is providing promising short-term outcomes for some individuals, these trials also reinforce the existing evidence on the unpredictability of ketamine as a treatment. And that ketamine as a long-term solution for depression still needs to be assessed.

Right dose and delivery

Most researchers are trying to uncover the right dose of ketamine, and the most effective way to administer it, but to date results have been mixed. Ketamine has been administered through an intravenous drip, injections, and as a nasal spray. A successful trial conducted in New South Wales administered ketamine to older people in the form of an injection under the skin. This study produced positive outcomes, with 68.8% of participants experiencing remission during the trial.3

After earlier promising results, another trial testing the effectiveness of ketamine administered as a nasal spray was established. However, it found all five patients experienced quite severe side-effects. These effects resulted in participants being unable to self-administer all their nasal spray due to a lack of coordination, and the trial was cancelled. These results highlight the uncertainty surrounding the appropriate dosage, and how it is administered, to enable the safe use of ketamine.4

Many of the trials have been too small to provide conclusive evidence on the effectiveness and safety of ketamine as a treatment.

It has been suggested that a trial with larger numbers, and which looks at both the risks and benefits of a taking a longer course of ketamine, should be undertaken.1 A 200-participant trial currently being conducted in Australia and New Zealand will hopefully start to answer these questions.2

Risks of ketamine as a treatment

The unanticipated side-effects that have occurred during the administration of ketamine highlight the potential harm of the drug – even under medical supervision. This further raises concerns about people who try to self-medicate, or access off-label ketamine treatments before the evidence is in.

The potential effects of ketamine administered at different dosages is still unknown. What we do know about ketamine, predominantly from research on recreational users, is that there is the potential for individuals to experience negative short-term and long-term effects.

Short-term effects can range from feeling relaxed and happy, to hallucinations, clumsiness, slurred speech, anxiety and vomiting; the long-term effects of ketamine can result in headaches, dependence and ketamine bladder syndrome where sufferers may experience incontinence and ulcers in the bladder.5

There is also the potential for people to use prescribed ketamine as a recreational drug, as people have with prescribed opioid painkillers. The question of how to avoid recreational use within therapeutic prescribed ketamine programs are still being explored.

More research needed

The allure of ketamine’s potential as an anti-depressant is strong – and it’s not the only drug of hope currently being researched for people who suffer from depression, especially depression that has not responded to other drugs or treatments. Studies into the potential positive effects of LSD and psilocybin (magic mushrooms), used in particular settings with appropriate participants, also warrant further research.

But as the science remains unproven, we need to be careful to let the research catch up with the hype.

  1. Hackett, M, et al.2016. 'Effects of Low-Dose and Very Low-Dose Ketamine among Patients with Major Depression: a Systematic Review and Meta-Analysis', International Journal Of Neuropsychopharmacology, vol. 19, no. 4.
  2. Black Dog Institute 2017, World’s largest trial of ketamine to treat depression begins.
  3. George, D et al. 2017. 'Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment-Resistant Depression', The American Journal of Geriatric Psychiatry, vol. 25, pp. 1199-1209.
  4. Gálvez, V, et al. 2018. 'Repeated intranasal ketamine for treatment-resistant depression - the way to go? Results from a pilot randomised controlled trial', Journal of Psychopharmacology, vol. 32, no. 4, pp. 397-407.
  5. Alcohol and Drug Foundation. 2018. Ketamine - Drug facts.

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