Ketamines triumph over depression: clinical trial results

A recent trial shows that a low-cost version of ketamine effectively treats severe depression, with more than 20% of participants achieving full remission. The cost-effective treatment could revolutionize the treatment of depression, leading researchers to advocate for broader adoption supported by Medicare.

A recent double-blind trial revealed the promising effects of a low-cost version of ketamine in treating severe depression, compared to placebo.

In research published in British Journal of Psychiatry, researchers led by the University of New South Wales (UNSW Sydney) and affiliated Black Dog Institute found that more than one in five participants achieved full symptom remission after a month of fortnightly injections, while a third improved symptoms. by at least 50 percent. The study was a collaboration between six clinical mood disorders academic units in Australia and one in New Zealand and was funded by the Australian National Health and Medical Research Council (NHMRC).

For people with treatment-resistant depression, that is, those who have not benefited from different modes of psychotherapy, commonly prescribed antidepressants or electroconvulsive therapy, a 20% remission is actually very good, says lead researcher Professor Colleen Loo.

We found that in this trial, ketamine was clearly better than placebo, with 20% reporting that they no longer had clinical depression, compared to just 2% in the placebo group. This is a huge and very obvious difference and brings definitive evidence to the field that has only had smaller trials comparing ketamine to placebo.

Judgment Methodology

The researchers recruited 179 people with treatment-resistant depression. All received an injection of a generic form of ketamine, which is already widely available in Australia as an anesthesia and sedation medication, or placebo. Participants received two injections per week at a clinic where they were monitored for about two hours, while the acute dissociative and sedative effects generally wore off within the first hour. The treatment lasted one month and participants were asked to rate their mood at the end of the trial and one month later.

Being a double-blind trial, neither the participants nor the investigators administering the drug knew which patients received generic ketamine or placebo, to ensure that psychological biases were minimized. It is important to highlight that a placebo was chosen that also causes sedation, to improve the masking of the treatment. Midazolam is a sedative typically administered before general anesthesia, whereas in many previous studies the placebo was saline.

Because there are no subjective effects of saline, in previous studies it became obvious which people were receiving ketamine and which people were receiving placebo, says Prof. Loo.

When using midazolam, which is not a treatment for depression, but it makes you feel a little dizzy and so you have much less chance of knowing if you have received ketamine, which has similar acute effects.

Other features of the recent study that set it apart from previous studies included accepting people into the study who had previously received electroconvulsive therapy (ECT).

People receive ECT treatment for depression when all other treatments have been ineffective, says Prof.

Most studies exclude people who have had ECT because it is very difficult for a new treatment to work where ECT does not.

Another difference in this trial was that the drug was administered subcutaneously (injected into the skin) rather than via a drip, thus greatly reducing medical time and complexity. The study is also the world’s largest to date comparing generic ketamine with placebo in the treatment of severe depression.

Cost Efficiency of Generic Ketamine

In addition to the positive results, one of the notable benefits of using generic ketamine for treatment-resistant depression is that it is much cheaper than the patented S-ketamine nasal spray currently in use in Australia. While S-ketamine costs about $800 per dose, generic ketamine is a mere fraction of that, costing just $5, depending on the supplier and whether the hospital buys it in bulk. In addition to the cost of the medication, patients must pay for the medical care they receive to ensure their experience is safe, which at Black Dog Institute clinics amounts to $350 per session.

With S-ketamine nasal spray, you lose about $1,200 for each treatment by the time you pay for the medication and procedure, whereas for generic ketamine, you pay about $300-350 for the treatment, including the cost of the medicine. Prof. Loo says.

She adds that for both S-ketamine and generic ketamine treatments, the positive effects usually wear off after a few days or weeks, so continued treatment may be necessary depending on someone’s clinical situation. But the prohibitive costs of the drug and procedure make this proposition untenable for most Australians.

This is why we are applying for a Medicare item number to fund this treatment now, because it is a very powerful treatment.

And when you consider that many of these people can spend many months in the hospital, or be unable to work and are often quite suicidal, it’s quite profitable when you see how incredibly quickly and powerfully it works. We’ve seen people go back to work, study or leave the hospital because of this treatment in a matter of weeks.

Next, researchers will look at larger trials of generic ketamine over longer periods of time and refine the treatment’s safety monitoring.

Reference: Efficacy and Safety of a 4-Week Course of Repeated Subcutaneous Ketamine Injections for Treatment-Resistant Depression (KADS Study): Randomized Double-Blind Active-Controlled Trial by Colleen Loo, Nick Glozier, David Barton, Bernhard T. Baune, Natalie T. Mills, Paul Fitzgerald, Paul Glue, Shanthi Sarma, Veronica Galvez-Ortiz, Dusan Hadzi-Pavlovic, Angelo Alonzo, Vanessa Dong, Donel Martin, Stevan Nikolin, Philip B. Mitchell, Michael Berk, Gregory Carter, Maree Hackett, John Leyden, Sean Hood, Andrew A. Somogyi, Kyle Lapidus, Elizabeth Stratton, Kirsten Gainsford, Deepak Garg, Nicollette LR Thornton, Clia Fourrier, Karyn Richardson, Demi Rozakis, Anish Scaria, Cathrine Mihalopoulos, Mary Lou Chatterton, William M. McDonald , Philip Boyce, Paul E. Holtzheimer, F. Andrew Kozel, Patricio Riva-Posse, and Anthony Rodgers, July 14, 2023, The British Journal of Psychiatry.
DOI: 10.1192/bjp.2023.79

Funding: Australian National Health and Medical Research Council