Double-Blind Trial Shows Low-Cost Subcutaneous Version of Ketamine Is Effective Over Placebo in Treating Treatment-Resistant Depression


Generic ketamine could cost as little as $5, which is significantly lower than the $800 per dose for the currently available S-ketamine nasal spray.

Depression is reported as the second leading global cause of disability. Failure to respond to 2 or more treatments is known as treatment-resistant depression (TRD). Ketamine is a novel, highly effective, and fast acting treatment for TRD. The 2 main formulations or routes of ketamine administration in previous antidepressant studies have been intravenous (IV) infusions and a commercially developed nasal spray.1

Not including the $350 session fee, the generic ketamine costs as little as $5 depending on the drug’s supplier. This is significantly less than the S-ketamine nasal spray currently in use in Australia, which costs $800 per dose. Additionally, it is important to note that the positive effects of treatment could wear off after a few days to a week, meaning that ongoing treatment would be a possibility depending on the individual’s situation.2

syringe needle

Image credit: weyo -

“With the S-ketamine nasal spray, you are out of pocket by about $1200 for every treatment by the time you pay for the drug and the procedure, whereas for generic ketamine, you're paying around $300-350 for the treatment including the drug cost,” said lead study author Colleen Loo, MBBS (Hons), FRANZCP, MD, a clinical psychiatrist and professor of psychiatry at the University of New South Wales and the Black Dog Institute In Sydney, Australia, in a press release. “If you consider that many of these people might spend many months in hospital, or be unable to work and are often quite suicidal, it’s quite cost effective when you see how incredibly quickly and powerfully it works.”2

For this study, patients received subcutaneous treatments over a 4-week treatment period, during which time study participants received twice-weekly treatments of either racemic ketamine or placebo, which was midazolam (Versed: Pfizer). In order to reduce potential biases, both the participants and researchers administering the drug were unaware which patients had received the ketamine or the placebo. Additionally, a placebo that causes sedation was chosen to improve treatment masking.

Participants were divided into 2 groups: cohort 1 and cohort 2. Cohort 1 had received fixed doses at 0.5 mg/kg ketamine and 0.025 mg/kg midazolam. For cohort 2, flexible response-guided dosing was used: for this dosing process, participants who had not improved by 50% from pretreatment baseline in MADRSW scores at sessions 2, 4, and 6, dosages would be escalated (0.6, 0.75, and 0.9 mg/kg ketamine and 0.03, 0.0375, and 0.045 mg/kg midazolam).1

The efficacy of ketamine was evident in cohort 2 (flexible doses) more than cohort 1 (fixed doses), due to the response-guided dose escalations (0.5 mg/kg to 0.9 mg/kg). Additionally, ketamine’s antidepressant effect in cohort 2 was not present until late in the 4-week period due to the gradual dosage increase. It is recommended that future protocols should utilize an individualized dose titration approach.

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

Limitations of this study included changing the original dosing protocol due to advice of the Data Safety Monitoring Board, resulting in lack of efficacy for the first 51 participants (out of 179) who had completed treatment. Further limitations include the study’s period of cessation due to the COVID-19 pandemic, as well as the study not being designed to evaluate the long-term effects of ketamine if it were to be continuously administered.1


1. Loo C, Glozier N, Barton D, et al. Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): Randomised double-blind active-controlled trial. The Brit Journ of Psych, 2023;1-9. doi:10.1192/bjp.2023.79

2. University of New South Wales. Ketamine effective for treatment-resistant depression: clinical trial. News release. July 13, 2023. Accessed on July 18, 2023.

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