Side Effects Stop Small Study of Repeated Intranasal Ketamine

March 28, 2018
nasal spray

Researchers testing repeated doses of intranasal ketamine in patients with treatment-resistant depression stopped their small pilot study early because of acute side effects in participants, including high blood pressure, psychotic-like effects, and motor incoordination.

They published their findings online in the Journal of Psychopharmacology.

“It's clear that the intranasal method of ketamine delivery is not as simple as it first seemed,” said lead author Colleen Loo, MD, a University of New South Wales professor based at Black Dog Institute, Sydney, Australia. “Many factors are at play when it comes to nasal spray ketamine treatments. Absorption will vary between people and can fluctuate on any given day within an individual based on such things as mucous levels in the nose and the specific application technique used.”

Why Not Make Ketamine a First-line Treatment?

Colleen Loo, MD
     Colleen Loo, MD

The study aimed to test the feasibility, safety, and potential efficacy of repeated doses of intranasal ketamine in 10 patients with treatment-resistant depression. A larger, randomized controlled trial was to follow.

Participants received extensive training on self-administration of the nasal spray and then were randomized to 8 treatments of either intranasal ketamine or midazolam over 4 weeks. Each treatment consisted of 10 separate intranasal sprays self-administered 5 minutes apart. Following initial reactions—some of which prevented participants from self-administering the sprays, researchers extended the time between sprays.

After testing with 5 participants, researchers opted to halt the study because of poor tolerability.

Ketamine Quickly Eases Depression, But Questions Remain

“Intranasal ketamine delivery is very potent as it bypasses metabolic pathways, and ketamine is rapidly absorbed into the bloodstream,” Dr. Loo said. “But as our findings show, this can lead to problems with high peak levels of ketamine in some people causing problematic side effects.”

“It remains unclear whether ketamine nasal sprays can be safely relied upon as a treatment for patients with severe depression,” she added.

—Jolynn Tumolo


Gálvez V, Li A, Huggins C, et al. Repeated intranasal ketamine for treatment-resistant depression - the way to go? Results from a pilot randomised controlled trial. Journal of Psychopharmacology. 2018 March 1;[Epub ahead of print].

Study casts doubt on ketamine nasal sprays for depression [press release]. Sydney, Australia: University of New South Wales; March 22, 2018.


Since Ketamine is administered IV usually, and generally without side effects, looks like the problem with this pilot study is that THE DOSE WAS TOO HIGH. Why did the subjects have to INHALE KETAMINE TEN TIMES PER TREATMENT? Why not just 1 to 2 inhalations?  The problem of this NEGATIVE result is that it makes it much less likely that Ketamine is a viable treatment for depression when PSYCHOSIS becomes a significant side effect. High blood pressure and motor incoordination can be addressed but PSYCHOSIS is a HUGE negative factor for Ketamine treatment. I would like to know WHAT DOSE WAS USED so we can avoid this in clinical practice.