A Comprehensive Guide to Ketamine
Explore the burgeoning potential of ketamine infusion therapy with our comprehensive guide, designed to shed light on its therapeutic applications.
Ketamine and esketamine are regulated differently in Australia, which influences how they are prescribed and delivered in clinical practice. Esketamine (Spravato) is approved by the Therapeutic Goods Administration (TGA) for treatment-resistant depression under a defined framework, while ketamine is used off-label by experienced clinicians based on established evidence and clinical guidelines.
A common question from patients and referrers exploring new treatments for depression is simple: If ketamine works, why isn’t it approved like esketamine (Spravato®)?
The answer lies not only in the science, but in how medications are regulated, funded, and brought to market in Australia. Understanding this distinction is essential when considering treatment options for treatment-resistant depression (TRD) and chronic pain.
Is ketamine legal in Australia?
Ketamine is legal in Australia. It is classified as a Schedule 8 controlled medication, meaning it can only be prescribed by authorised clinicians and must be administered within a regulated medical setting.
It is already approved for use in anaesthesia. However, when used for depression and chronic pain, ketamine is prescribed off-label — a common and accepted practice in medicine when supported by evidence and specialist oversight.
In practical terms, this means that ketamine can be prescribed for depression and chronic pain by appropriately trained clinicians, even though it is not formally approved for these specific indications.
What does “off-label” prescribing mean?
Off-label prescribing occurs when a medication is used for a condition outside its official regulatory approval. This is not unusual. Many widely accepted treatments in psychiatry and pain medicine are used off-label when there is sufficient clinical evidence to support their use.
In Australia, doctors are legally permitted to prescribe medications off-label provided they act in accordance with professional standards, obtain informed consent, and ensure appropriate monitoring. Ketamine for depression and chronic pain falls within this framework.
Why is esketamine TGA approved?
Esketamine (Spravato®) is approved by the Therapeutic Goods Administration for treatment-resistant depression because it has undergone the full regulatory approval process.
For a medication to receive TGA approval for a specific indication, a pharmaceutical company must submit a comprehensive application demonstrating safety, efficacy, and quality. This typically requires large-scale clinical trials — particularly Phase 3 randomised controlled trials — along with significant financial investment.
Esketamine is a patented medication developed specifically for depression and supported by multiple industry-funded studies. Its approval reflects the fact that it has successfully completed this regulatory pathway.
Why isn’t ketamine TGA approved for depression?
The absence of TGA approval for ketamine in depression and chronic pain is not due to a lack of evidence. Rather, it reflects the realities of the pharmaceutical and regulatory system.
Ketamine is an older, off-patent medication that is widely available and inexpensive. Because it cannot be exclusively marketed, there is little commercial incentive for pharmaceutical companies to invest in the large, costly trials required for regulatory approval.
In contrast, esketamine is a proprietary formulation. Its patent protection allows a company to justify the substantial financial investment needed to obtain approval.
As a result, regulatory status in this case reflects commercial viability rather than clinical superiority.
Is ketamine effective for depression?
Ketamine has been studied extensively over the past two decades in the treatment of depression, particularly in patients who have not responded to conventional therapies.
Clinical trials and meta-analyses consistently demonstrate that ketamine can produce rapid antidepressant effects, often within hours to days, along with meaningful reductions in suicidal ideation. Large-scale analyses have also shown that ketamine may be associated with greater effect sizes, faster onset of action and more durable effects compared to esketamine (Nikolin et al., 2023; Bahji et al., 2021).
This growing body of evidence has led to the widespread adoption of ketamine in specialist settings internationally, despite its off-label status.
What are the limitations of the esketamine evidence?
Esketamine is an effective treatment for many patients. However, its evidence base has been subject to ongoing discussion within the psychiatric community.
Some studies have demonstrated that while esketamine achieves statistical significance compared to placebo, the magnitude of improvement is modest in certain trials. There is also variability in response between patients, and much of the evidence comes from industry-sponsored research.
These considerations do not negate its clinical utility, but they highlight an important point: regulatory approval does not necessarily indicate superior effectiveness, only that a treatment has met the requirements of the approval process.
Can ketamine be prescribed for depression and chronic pain in Australia?
Yes. Ketamine can be prescribed for depression and chronic pain in Australia by specialist clinicians when it is clinically appropriate.
This typically occurs in structured settings such as:
· Specialist psychiatric and chronic pain services
· Interventional pain or mental health clinics
· Hospital-based programs
Treatment involves careful assessment, monitoring, and follow-up, consistent with best-practice clinical standards.
What is the real difference between ketamine and esketamine regulation?
The distinction between ketamine and esketamine is best understood as a difference in regulatory pathway rather than therapeutic category.
Esketamine is a standardised, TGA-approved product delivered via a nasal spray under a defined protocol. Ketamine, by contrast, is used off-label but offers greater flexibility in dosing and administration, most commonly via intravenous infusion.
Both treatments have demonstrated efficacy in treatment-resistant depression. The choice between them depends on a combination of clinical factors, patient preference, and treatment setting.
The key takeaway
Ketamine is legal in Australia and widely used in specialist practice for depression and chronic pain, despite not being TGA-approved for these indications. Esketamine is approved because it has undergone the formal regulatory process, supported by industry-funded trials.
Importantly, this difference reflects how medications are developed and approved — not necessarily which treatment is more effective.
As the field continues to evolve, treatment decisions are increasingly guided by clinical evidence, patient characteristics, and specialist expertise, rather than regulatory status alone.
References
Nikolin S, Rodgers A, Schwaab A, Bahji A, Zarate CA Jr, Vazquez G, Loo C. Ketamine for the treatment of major depression: A systematic review and meta-analysis. eClinicalMedicine. 2023;62:102127.
Bahji A, Vazquez GH, Zarate CA Jr. Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis. Journal of Affective Disorders. 2021;278:542–555.
Disclaimer
Anodyne is a specialised health service focused on patient centred and novel approaches for pain management and mental health treatments.
Any advice posted on our blog, website, or app is of a general nature and for informational purposes only. It is not intended to replace or substitute for any medical or other advice.
Anodyne makes no representations or warranties and expressly disclaim any and all liability concerning any treatment, action by, or effect on any person following the general information offered or provided within or through the blog, website, or app. If you have specific concerns or a situation arises in which you require medical advice, you should consult with an appropriately trained and qualified medical practitioner.
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