Many studies have shown ketamine to be a promising treatment for those suffering from severe depression, but figuring out how to safely administer the drug has been a challenge for researchers. One hopeful delivery method was a nasal spray device because of its ease-of-use and the fact that it is less invasive than other methods such as injection.
But a new Australian study published in the Journal of Psychopharmacology reveals some unexpected problems with the nasal spray method. In particular, the study shows the unpredictable nature of intranasal ketamine tolerance from one person to the next.
“It’s clear that the intranasal method of ketamine delivery is not as simple as it first seemed,” said lead author Professor Colleen Loo at the University of New South Wales (UNSW), who is based at Black Dog Institute.
“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.”
The pilot trial aimed to analyze the effectiveness of repeated doses of ketamine through an intranasal device amongst 10 volunteers with severe depression, ahead of a larger randomized controlled trial.
First, the participants were given extensive training in proper self-administration techniques before receiving either a course of eight ketamine treatments or an active control over a period of four weeks, under supervision at the study center.
Following the observation of each patients’ initial reaction to the nasal spray, the dosages were adjusted to include longer time intervals between sprays.
However, the trial had to be put on hold after testing with five participants resulted in unexpected problems with tolerability. Side effects included high blood pressure, psychotic-like effects, and motor incoordination which left some participants unable to continue to self-administer the spray.
“Intranasal ketamine delivery is very potent as it bypasses metabolic pathways, and ketamine is rapidly absorbed into the bloodstream,” said Loo. “But as our findings show, this can lead to problems with high peak levels of ketamine in some people causing problematic side effects.”
“Other recent studies have questioned whether changes to ketamine’s composition after being metabolised into derivative compounds may actually deliver useful therapeutic effects. It remains unclear whether ketamine nasal sprays can be safely relied upon as a treatment for patients with severe depression.”
Previous research led by Loo last year revealed the success of ketamine’s antidepressant effects in elderly patients when delivered in repeated doses, which were adjusted on an individual basis and given by the subcutaneous method (injections under the skin).
“Our prior research has shown that altering the dose on an individual patient basis was important. However, we wanted to see if a simpler approach using a set dose of ketamine for all people and administered by nasal spray could work just as well in this latest pilot,” said Loo.
“More research is needed to identify the optimal level of ketamine dosage for each specific application method before nasal sprays can be considered a feasible treatment option.”
The researchers are now recruiting participants for the world’s largest independent trial of ketamine to treat depression, to determine the safety and effects of repeated dosing using subcutaneous injections.
Source: University of New South Wales