According to a new pilot study in the resistant depression, the ketamine by the nasal route is accompanied by very strong variations of doses which is at the origin of important side effects.
Two recent analyzes show that ketamine, a common anesthetic, is revolutionizing the treatment of severe and resistant depression. Intravenous ketamine actually reduces suicidal ideation in a few hours, whereas it takes 2-3 weeks to see a response with a classic antidepressant.
But the infusion can not be a long-term treatment and other routes of administration have been tested such as the subcutaneous route or the nasal route.
Bad nasal results
The nasal route is easier to use and less invasive than infusions. It has been touted by a recent press promotion campaign but does not appear to be the promising way to deliver ketamine to patients suffering from resistant depression.
Unlike previous trials, a new study reveals the random nature of the tolerance of ketamine nasally from one patient to another. The results are published today in the Journal of Psychopharmacology.
A strong variation of absorption
"It is clear that the delivery of nasal ketamine is not as interesting as it seemed at first," said lead author Colleen Loo of the Black Dog Institute. "Many factors come into play in intranasal ketamine treatments: absorption varies from one person to another and can vary from day to day depending on the condition of the nasal mucosa and of the technique of administration used.
A pilot test stopped prematurely
The pilot trial was designed to test the feasibility of repeat doses of intranasal ketamine in 10 patients with severe depression prior to a larger randomized controlled trial. Participants were all trained in intra-nasal self-administration before receiving eight ketamine or placebo treatments 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 because of unexpected problems of tolerance. Side effects included high blood pressure, pseudo-psychotic effects, and motor coordination disorders that prevented some participants from continuing to self-administer the aerosol.
Dose adaptation is necessary
"Intranasal administration of ketamine is very powerful because it bypasses the metabolic pathways, and ketamine is rapidly absorbed into the bloodstream," said Professor Loo. "But as our results show, this 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 importance of the antidepressant effects of ketamine in elderly patients when it was administered subcutaneously in repeated doses and adjusted individually.
"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 good administration are still to be found for ketamine.