DepressionDigital HealthNew MedicinesPsychedelic-Assisted Psychotherapy

Esketamine availability in Australia

Spravato is the brand name of esketamine, a glutamate receptor drug used for rapid depression treatment manufactured by Johnson & Johnson in the US. Esketamine contained within the standard pharmaceutical form of ketamine, which has traditionally been used at higher doses as an anaesthetic. The difference between Esketamine and Ketamine is that the latter contains the former. Pharmaceutical forms of ketamine contain two mirror-image molecules of itself called enantiomers (R-Ketamine and esKetamine – see below), the pharmaceutical industry has isolated one mirror image and shown some benefits of using that “enantiomer”¹.

esketamine enantiomer

If you would like to watch a short video of how esketamine may work have a look at the video below:

Current availability in Australia

Although Spravato was launched in the US at the beginning of March 2019 as of yet (January 2021) there are no licensed products in Australia, we will be continually updating this blog to chart its progress so if you are interested and would like alerts please follow us on social media or subscribe to this blog.

Future availability of esketamine in Australia

Although a license for esketamine, for psychiatric conditions in Australia is not yet present, off-label prescribing of ketamine for major depression is possible, but uncommon, given regulatory hurdles (esketamine is still classed as a Schedule 8 poison) and uncertainty around efficacy and safety.

The reason for caution is primarily the taboo surrounding “psychedelics” which has been spurred by the Royal Australian and New Zealand College of Psychiatrists (RANZCP) calling on medical practitioners to proceed with caution when treating patients with ketamine.

However, this RANZCP announcement was not out of the blue, it followed a small unsuccessful clinical trail² of Intranasal Esketamine for Treatment-resistant Depression which completed in 2016, which was ended prematurely because of unexpected side effects suffered by patients. It was found at the dose given, 100mg – over 10 sprays, more than twice the dose of any previous trial – their blood pressure shot up, they became uncoordinated and they suffered “unpleasant” psychotic-like effects. This is in light of other successful international trials seems to indicate not that the drug is ineffective, however, that the dosage range should be below this top threshold of between 50mg-100mg.

Who will be most likely to be prescribed esketamine?

It is likely when esketamine is licensed Australia, meaning it will be more easily prescribed, that people who will be most eligible to receive the medicine will be those that match the inclusion criteria of the initial clinical trial. The inclusion criteria for which includes:

  • At least a single-episode major depressive disorder (MDD) that lasted for a minimum of two years.
  • must have a MADRS total score of >=22
  • nonresponse to 2+ oral antidepressant treatments

Who will be LEAST likely to be prescribed esketamine?

Again, according to the original clinical trial patients who were excluded from use include:

  • previously not responded to ketamine in the past.
  • MDD with psychotic features, bipolar or related disorders, intellectual disability, autism spectrum disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder
  • homicidal ideation
  • history of moderate or severe substance or alcohol abuse
  • neurodegenerative disorder such as Alzheimer’s disease, vascular dementia, Parkinson’s disease)

Alternatives to esketamine

One alternative to esketamine is the original form of the medicine, ketamine. There are some clinicians administering the original drug form as ‘off-label’ treatment, below is a list of what is available in Australia:

  • Black Dog Institute – two studies running in Sydney, one in New Zealand and one in Gold Coast.

At these clinics Ketamine, is administered in a variety of ways: via an intravenous ketamine infusion (IV), an intramuscular injection (IM), a subcutaneous injection (SC), intranasally (NAS), sublingually(SL) and orally. Routes vary in the onset of action, bioavailability and clearing time through the system for each individual. While there is generally a predictable response based on past administration, it is possible that patient maybe experience variable physiological and subjective experiences with the same dose.

There are a variety of dosing protocols in practice. Much research and attention has been focused on the provision of 0.5mg/kg of ketamine by IV infusion over 45 minutes, in a repeated series consisting of 2/week for 3-4 weeks. Other described protocols include the provision of a single infusion, twice weekly, weekly or longer interval dosing as determined by patient need and response.

Another alternative is to investigate the use of other agents (often termed psychedelics) including psilocybin (magic mushrooms) or NDMA. The science surrounding these substance has progressed a long way in recent years, so much so that there is a petition to the organisation which regulates medicines in Australia the TGA to decriminalise their use.

Conclusion

In conclusion, it is now highly likely that in the near future that there will be dedicated esketamine clinics set up in Australia. If you are desperate to access the medicine now, possibly try access the medicine “off-label” (potentially very expensive as above) or try the Black Dog Institue, or wait till the end of the year…

Reference:

  1. Ketamine-related drug could be ‘watershed’ in treating depression, 2019,https://www.theguardian.com/society/2019/mar/08/new-ketamine-related-drug-could-be-watershed-in-treating-depression.
  2. A Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression (SUSTAIN-2):  https://www.australianclinicaltrials.gov.au/anzctr/trial/NCT02497287