April 6, 2023

Can ketamine help treat depression?

alone on a park bench looking over water

Ketamine is typically used as an anaesthetic in hospitals and by vets. It’s also sometimes used as a ‘party drug’.

Lately, it’s been making headlines for a different reason, as research continues into the effectiveness of ketamine for treating depression.

Ketamine is a dissociative drug.

This means it acts on different chemicals in the brain to distort sight and hearing, which can result in someone feeling detached from reality.1

We know ketamine can help people with severe depression who haven't responded well to anti-depressant medications or other treatments.2, 3

But there are questions about its limitations.

Is it safe? How long do the effects last? And is this a long-term solution?

How does ketamine work for treating depression?

Ketamine works by targeting a key chemical in the brain called glutamate, which affects memory and learning. It’s also thought to affect brain cell growth and function.4

In some trials, ketamine rapidly reduced depression symptoms and provided relief for several days. This is a much faster response compared to other treatments.5

These trials show ketamine has the potential to relieve feelings of sadness, helplessness and even thoughts of suicide.5

Getting the dose and delivery right

Researchers have been trying to find the right dose of ketamine and the most effective way to give it, with clinical trials using either an intravenous drip, injection or a nasal spray.3

The results have been mixed.

A successful trial in New South Wales gave ketamine to older people by injection. This study had positive results, with 68.8% of participants experiencing remission of their symptoms.6

Another trial tested ketamine given through a nasal spray. But all five participants experienced severe side-effects and couldn’t use all their nasal spray because of a lack of coordination.7

The trial was cancelled, demonstrating more work still needs to be done in terms of understanding dosage and how it’s taken.7

What are the risks of ketamine?

Responses to ketamine treatment will vary from person to person.2

The side-effects people experienced during trials highlight some of the potential risks of ketamine – even under medical supervision.8

There are also concerns about people who might try to self-medicate by using illicit ketamine.

And as with any prescribed drug, such as opioid painkillers, there’s the risk people might use it in a way that’s different to how it’s been prescribed. The question of how to avoid unprescribed use within ketamine programs is still being explored.

Is it available in Australia?

Currently, ketamine (esketamine hydrochloride) in the form of a nasal spray is available for treatment-resistant depression in Australia.

But there’s strict eligibility conditions:

  • The patient must be an adult experiencing a major depressive disorder and has not responded adequately to at least two different antidepressants.
  • The nasal spray must be used along with a new antidepressant.
  • The spray must only be taken in the presence of a health professional.9

Access options are the decision of each state and territory, including who can prescribe and where it can be given.

If you are interested in accessing esketamine hydrochloride:

If you’re experiencing symptoms of depression, you can visit your local GP, or contact help and support services:

  1. Morgan CJA, Curran HV. Ketamine use: a review. Addiction [Internet]. 2012 [16.03.2023]; 107(1):[27-38 pp.].
  2. Alnefeesi Y, Chen-Li D, Krane E, Jawad MY, Rodrigues NB, Ceban F, et al. Real-world effectiveness of ketamine in treatment-resistant depression: A systematic review & meta-analysis. Journal of Psychiatric Research [Internet]. 2022 [20.03.2023]; 151:[693-709 pp.].
  3. Bahji A, Zarate CA, Vazquez GH.Efficacy and safety of racemic ketamine and esketamine for depression: a systematic review and meta-analysis. Expert Opinion on Drug Safety [Internet]. 2022 20.03.23]; 21(6):[853-66 pp.].
  4. Matveychuk D, Thomas RK, Swainson J, Khullar A, MacKay MA, Baker GB, et al. Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers. Ther Adv Psychopharmacol [Internet]. 2020 [17.03.2023]; 10:[2045125320916657 p.]. Available from:
  5. Xu Y, Hackett M, Carter G, Loo C, Gálvez V, Glozier N, et al. Effects of Low-Dose and Very Low-Dose Ketamine among Patients with Major Depression: a Systematic Review and Meta-Analysis. The international journal of neuropsychopharmacology [Internet]. 2016 [17.03.2023]; 19(4).
  6. George DM, Gálvez VMD, Martin DP, Kumar DB, Leyden JM, Hadzi-Pavlovic DBSC, et al. Pilot Randomized-Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment Resistant Depression. Am J Geriatr Psychiatry [Internet]. 2017 [17.03.2023]; 25(11):[1199-209 pp.].
  7. Gálvez V, Li A, Huggins C, Glue P, Martin D, Somogyi AA, et al. Repeated intranasal ketamine for treatment-resistant depression – the way to go? Results from a pilot randomised controlled trial. J Psychopharmacol [Internet]. 2018 [17.03.2023]; 32(4):[397-407 pp.].
  8. Short B, Fong J, Galvez V, Shelker W, Loo CK. Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry [Internet]. 2018 [20.03.2023]; 5(1):[65-78 pp.].
  9. Therapeutic Goods Administration. Spravato 2021 [20.03.2023].

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