Many studies have shown that ketamine is a promising treatment for people with major depression. However, figuring out how to safely administer the drug has been a challenge for researchers. One hopeful delivery method has been a nasal spray device due to 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 shows some unexpected issues with the nasal spray method. In particular, the study reveals the unpredictable nature of intranasal ketamine tolerance from one person to the next.
Lead author Professor Colleen Loo of the University of New South Wales (UNSW), who works at the Black Dog Institute, explains:
It is clear that the intranasal method of ketamine delivery is not as straightforward as it initially seemed. Many factors play a role in nasal spray ketamine treatment. The absorption varies between people and can fluctuate within an individual on any given day based on mucus levels in the nose and the specific application technique used.
The pilot study aimed to analyze the effectiveness of repeated doses of ketamine through an intranasal device in 10 volunteers with major depression prior to a larger randomized controlled trial.
Initially, participants received extensive training in appropriate self-management techniques before receiving either eight ketamine treatments or active control over a four-week period under study center supervision.
After observing each patient’s initial response to the nasal spray, the dosages were adjusted to include longer time intervals between sprays.
However, the study had to be interrupted after testing with five participants resulted in unexpected tolerability issues. Side effects included high blood pressure, psychotic effects, and motor incoordination that made it impossible for some participants to continue administering the spray themselves.
Professor Colleen Loo commented:
Intranasal ketamine delivery is very effective as it bypasses metabolic pathways and ketamine is quickly absorbed into the bloodstream. As our results show, this can lead to problems with high ketamine spikes in some people, which cause problematic side effects. Other recent studies have questioned whether changes in ketamine composition after metabolism to derivatives can actually have beneficial therapeutic effects. It remains unclear whether ketamine nasal sprays can be used safely to treat patients with major depression.
Previous research conducted by Loo over the past year has shown the success of ketamine’s antidepressant effects in the elderly when administered repeatedly in repeated doses that were individually adjusted and given by the subcutaneous method (injections under the skin):
Our previous research indicated that changing the dose on an individual patient basis was important. However, we wanted to see if a simpler, fixed-dose ketamine all-human approach, given by nasal spray, could work as well in this latest pilot. Further research is needed to determine the optimal ketamine dosage level for each specific application method before nasal sprays can be considered a viable treatment option.
Researchers are now recruiting participants for the world’s largest independent study of ketamine for the treatment of depression to determine the safety and effects of repeated dosing using subcutaneous injections.
This guest article appeared on PsychCentral.com: Ketamine Nasal Spray For Depression Encounters Problems and was originally published on Psych Central by Traci Pedersen.
Gálvez V., Li A., Huggins C. et al. Repeated Intranasal Ketamine For Treatment Resistant Depression – The Right Way To Go? Results of a randomized controlled pilot study. Journal of Psychopharmacology. 2018; 32 (4): 397- 407. doi: 10.1177 / 0269881118760660.
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