Nasal nirvana: ketamine for migraine relief

3 minute read

Internasal ketamine sprays could offer breath of fresh air for chronic migraines sufferers.

Ketamine nasal spray could be effective as a refractory migraine treatment, according to a small new study that found it mitigated headaches and reduced the use of painkillers. 

Currently, ketamine treatments for migraines are only administered intravenously, limiting the scope of patients who can be treated in outpatient settings. Intranasal ketamine could make the treatment more readily accessible for chronic migraine sufferers, but it is uncertain whether it can be used safely in this mode, according to the authors of the new BMJ study. 

This single-centre study of 170 patients found that 50% reported the internasal ketamine was “very effective” at alleviating their migraines, and another 40% found it “somewhat effective”. 

Participants had access to compounded 15-30mL formulations of 100mg/mL internasal ketamine, and used up to 20 sprays per day as needed.

When asked about the reason underpinning their ketamine use, 59% reported it was due to an incomplete response to acute painkillers, 23% reported beneficial improvements from previous ketamine usage and 13% reported an unsuccessful lidocaine infusion.  

Approximately 22% reported using intranasal ketamine for more than 15 days per month, 14% were daily users and 18% of the total group used at least 10 sprays on a day.  

On average, participants used the spray 10 days per month. Of these patients, more than one in three reported a “much better” quality of life while 43% reported their quality of life was “somewhat better”. Approximately 18% reported “no change”, while 4% believed their overall quality of life was “worse”.  

There was no difference in per-day spray use between daily and non-daily users. Those who reported it as “very effective” used ketamine more frequently, but the overall daily dose was the same between groups.  

“Overall, there was a decrease in pain intensity with more than 70% treatment response consistency, particularly in those reported as very effective. Almost three-quarters reported less use of acute medication when using intranasal ketamine,” the authors wrote.  

Three in four participants reported experiencing at least one side effect, with the most common being fatigue and blurry vision. Confusion, dissociation, vivid dreams and hallucinations were also recorded. 

Most subjects also had elevated alanine and aspartate transaminase, without changes in bilirubin levels, however these side effects were short-lasting and did not prompt any participants to discontinue their use of the nasal spray.  

It took around 28 minutes for the pain-relieving effects of the intranasal ketamine to kick in after each spray, but this varied greatly from patient to patient.

“This variation in onset may reflect the effect of ketamine (and its metabolites) and its pharmacokinetic property,” the authors wrote.   

The right dosage to balance safety and efficacy was unclear, however, the researchers noted excessive nasal sprays would likely “… enter the stomach and are not effectively absorbed, thus limiting the potential for significant overdosing in a single use”.  

The overlap between migraine symptoms and ketamine side effects and use of preventative medications in participants are barriers to evaluating the drug’s safety profile. The authors suggested that a large-scale placebo-controlled trial would be needed to further evaluate intranasal ketamine use.  

They concluded that the use of ketamine should only be considered for patients who feel the most severe and debilitating effects of migraines, and routine clinical visits, re-education about safe use and monitoring for signs of misuse are essential.  

BMJ 2023, online 30 May  

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