An antidepressant containing a form of the drug ketamine has been added to the Pharmaceutical Benefits Scheme (PBS), making it much cheaper for the estimated 30,000 Australians with treatment-resistant depression. This is when a patient has tried multiple forms of treatment for major depression - usually at least two antidepressant medications - without any improvement.
Authors
- Nial Wheate
Professor, School of Natural Sciences, Macquarie University
- Shoohb Alassadi
Associate Lecturer and Registered Pharmacist, University of Sydney
From May 1, a dose of Spravato (also known as esketamine hydrochloride) will cost $A31.60 and $7.70 for concession card holders.
However, unlike oral antidepressants, Spravato can't be taken at home. Here's how it works, and who it's expected to help.
What is Spravato?
The chemical ketamine is used as an anaesthetic . In this formulation it combines both the right-handed (designated "R") and left-handed (called "S") forms of the molecule.
This means they are mirror images of each other, similar to how your left hand is a mirror image of your right hand. The left- and right-hand forms can have different effects in the body.
Spravato contains only the left-handed version, giving the drug its generic name esketamine.
Spravato works by increasing the levels of glutamate in the brain. Glutamate is a key chemical messenger molecule that excites brain nerve cells, lifting and improving mood. It also plays a role in learning and forming memories.
How is it taken?
Spravato cannot be taken at home.
A patient can self-administer, but it must be done at a registered treatment facility, such as a hospital, under the supervision of medical staff so they can look out for blood pressure changes and monitor potential side effects.
The drug is provided as a single-use nasal spray . This application means it's absorbed directly through the nasal lining into the brain, so it starts to work within minutes.
Spravato must also be taken alongside an oral antidepressant . This will be a new one the patient hasn't tried before. In clinical trials, it was usually an SNRI or SSRI medication .
When a patient first starts on Spravato, they are given the spray twice a week in the first month . It is then administered once a week for the second month, and then weekly or fortnightly after that.
Once there are signs the medicine is working, treatment is continued for at least six months.
How effective is it?
Spravato was approved for sale in Australia based on clinical trial data from more than 1,600 patients who were administered the drug for a period of four weeks. Each was given either Spravato, or a nasal placebo, and an oral antidepressant.
Patients were given a starting dose of either 28 or 56mg, which could be then increased up to 84mg by their doctor.
By the end of the four weeks, a greater percentage of patients who were given Spravato were found to have had a meaningful response to the treatment when compared with patients who received the placebo. Patients who were taking Spravato were also found to relapse at a lower rate. For those who did relapse, it took the Spravato patients longer to relapse when compared with patients who took the placebo.
It is expected Spravato will benefit a wide range of patients. The clinical trials demonstrated effectiveness for men and women, people aged 18 to 64, and those from a range of different ethnic backgrounds.
Potential side effects
As with any medicine, Spravato may cause side effects , some of which can be serious. The most common include:
- dissociation (feeling disconnected from yourself or what is around you)
- dizziness
- nausea and vomiting
- drowsiness
- headache
- change in taste
- vertigo.
Because Spravato can potentially increase blood pressure, medical staff will monitor a patient before and after it is administered.
Usually, blood pressure spikes around 40 minutes after taking the drug, so a reading is taken around this time. After taking Spravato, if their blood pressure has stayed low, or it's dropping, the patient is given the all-clear to go home.
Due to the potential for this and other serious side effects, Spravato carries a black triangle warning. This means medical staff are encouraged to report any problem or side effect to the Therapeutic Goods Administration. A black triangle warning is generally used for new medicines or medicines that are being used in a new way.
Who will be eligible?
To be eligible for a prescription, a patient will need to have been diagnosed with treatment-resistant depression . In practice, this means they will have unsuccessfully tried at least two other antidepressant drugs first.
Australia's Therapeutic Goods Administration approved Spravato for use in Australia in 2021 , meaning it was available but not subsidised. Since then, the sponsoring company, Janssen-Cilag (an Australian subsidiary of the multinational Johnson & Johnson), applied to have it added to the PBS four times.
In December 2024 , the Pharmaceutical Benefits Advisory Committee recommended a PBS listing.
The new PBS listing, capping the price of a single treatment at $31.60, is a significant price drop. In 2023, single doses of branded Spravato were reported to cost anywhere between $500 and $900 .
However, patients may still have to pay hundreds of dollars for appointments at private clinics where Spravato can be administered. Public places are available but limited.
Spravato may be suitable for you if you've tried different antidepressants without success. If it is suitable for you, then your doctor can discuss the next steps.
If this article has raised issues for you, or if you're concerned about someone you know, call Lifeline on 13 11 14.
Nial Wheate in the past has received funding from the ACT Cancer Council, Tenovus Scotland, Medical Research Scotland, Scottish Crucible, and the Scottish Universities Life Sciences Alliance. He is a fellow of the Royal Australian Chemical Institute. Nial is the chief scientific officer of Vaihea Skincare LLC, a director of SetDose Pty Ltd (a medical device company) and was previously a Standards Australia panel member for sunscreen agents. He is a member of the Haleon Australia Pty Ltd Pain Advisory Board. Nial regularly consults to industry on issues to do with medicine risk assessments, manufacturing, design and testing.
Shoohb Alassadi does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
