This randomized, double-blind, placebo-controlled, safety study (n=5) found that intranasal (IN) ketamine was not well tolerated at dosages leading up to 100mg. The absorption between patients varied up to two-fold.
Abstract
“Background: Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments.
Methods: This randomised, double-blind, placebo-controlled pilot study compared a 4-week course of eight treatments of 100 mg ketamine or 4.5 mg midazolam. Each treatment was given as 10 separate IN sprays, self-administered 5 min apart. The study was stopped early due to poor tolerability after five treatment-resistant depressed participants were included. Feasibility, safety (acute and cumulative), cognitive and efficacy outcomes were assessed. Plasma ketamine and norketamine concentrations were assayed after the first treatment.
Results: Significant acute cardiovascular, psychotomimetic and neurological side effects occurred at doses < 100 mg ketamine. No participants were able to self-administer all 10 ketamine sprays due to incoordination; treatment time occasionally had to be extended (>45 min) due to acute side effects. No hepatic, cognitive or urinary changes were observed after the treatment course in either group. There was an approximately two-fold variation in ketamine and norketamine plasma concentrations between ketamine participants. At course end, one participant had remitted in each of the ketamine and midazolam groups.
Conclusions: IN ketamine, with the drug formulation and delivery device used, was not a useful treatment approach in this study. Absorption was variable between individuals and acute tolerability was poor, requiring prolonged treatment administration time in some individuals. The drug formulation, the delivery device, the insufflation technique and individual patient factors play an important role in tolerability and efficacy when using IN ketamine for TRD.”
Authors: Verònica Gálvez, Adrienne Li, Christina Huggins, Paul Glue, Donel Martin, Andrew A. Somogyi, Angelo Alonzo, Anthony Rodgers, Philip B. Mitchell & Colleen K. Loo
Summary of Repeated intranasal ketamine for treatment-resistant depression – the way to go? Results from a pilot randomised controlled trial
Introduction
Evidence from 10 randomised controlled trials (RCTs) suggests that a single sub-anaesthetic dose of ketamine results in marked and rapid antidepressant effects, but that the benefit is often short-lived. Further, no prior published RCTs have compared the feasibility, safety or potential efficacy of repeated ketamine dosing to an active control treatment condition. Several recent RCTs have reported promising results using the intramuscular (IM) and subcutaneous (SC) routes, and the intranasal (IN) route is also gaining interest, as it has theoretical advantages over parenteral or oral routes. In a recent cross-over RCT, 50 mg of IN ketamine was administered to patients with chronic moderately severe treatment-resistant depression. The treatment effects were short-lived, and the ketamine dose was equivalent to 0.15 – 0.34 mg/kg of IV ketamine, which was lower than the 0.5 mg/kg used in most prior studies.
The current pilot RCT examined the feasibility and safety of repeated doses of IN ketamine for TRD. A fixed dose of 100 mg IN was used to approximate the previously used IV dosage of 0.5 mg/kg.
Study details
Compounds studied
Ketamine
Topics studied
Depression
Treatment-Resistant Depression
Study characteristics
Placebo-Controlled
Double-Blind
Randomized
Participants
5