According to a new pilot study in resistant depression, ketamine by the nasal route is accompanied by very large variations in dose which is the cause of significant side effects.
Two recent analyzes show that ketamine, a common anesthetic, is revolutionizing the treatment of severe and resistant depression. Intravenous ketamine indeed reduces suicidal ideation within a few hours, while it takes 2 to 3 weeks to observe a response with a classic antidepressant.
However, the infusion cannot constitute a long-term treatment and other routes of administration have been tested such as the subcutaneous route or the nasal route.
Poor nasal results
The nasal route is easier to use and less invasive than infusions. It was touted by a recent promotional campaign in the press but does not appear to be the promising way to deliver ketamine to patients with resistant depression.
Unlike previous trials, a new study reveals the random nature of patient-to-patient tolerance of nasal ketamine. The results are published today in the Journal of Psychopharmacology.
A strong variation in absorption
“It’s clear that delivering ketamine through the nose is not as attractive as it first seemed,” said lead author Professor Colleen Loo of the Black Dog Institute. “There are many factors that go into treatment with intranasal ketamine: Absorption varies from person to person and can vary from day to day depending on the condition of the nasal mucosa and of the administration technique used ”.
A pilot test stopped prematurely
The pilot trial aimed to test the feasibility of repeated doses of intranasal ketamine in 10 patients with severe depression, before a larger randomized controlled trial. The participants were all trained in intranasal self-administration before receiving eight treatments with ketamine or a placebo over a four-week period. After the first reactions, the dosage was adjusted to space the time intervals between sprays.
The study had to be stopped prematurely after five participants due to unexpected safety issues. Side effects included high blood pressure, pseudo-psychotic effects, and impaired motor coordination which prevented some participants from continuing to self-administer the aerosol.
Dosage adjustment is necessary
“The intranasal administration of ketamine is very potent because it bypasses the metabolic pathways, and ketamine is rapidly absorbed into the bloodstream,” Professor Loo said. “But as our results show, it can lead to problems with high levels of ketamine in some people causing problematic side effects.”
A first study conducted by Professor Loo last year showed the rapidity and extent of the antidepressant effects of ketamine in elderly patients when it was administered subcutaneously in repeated and individually adjusted doses.
“More studies are needed to identify the optimal dosage level of ketamine for each administration before the nasal route can be considered a valid treatment option.”
The right dose and the right way of administration have yet to be found for ketamine.
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