Ketamine Nasal Spray Might Relieve Chronic Migraines

Ketamine has previously been shown to be effective when used intravenously for headache disorders such as cluster headaches and migraines, but it is not clear if ketamine could be used safely for chronic migraines that are resistant to treatment. 

To investigate, the researchers retrospectively reviewed the outcomes of those who were given nasal ketamine spray for chronic refractory migraines between January and February 2020 at a specialist headache center. 242 people were identified as being prescribed a nasal ketamine spray during the time frame, 169 of which agreed to participate and be interviewed. The participants had an average age of 44 years old, and 80% were women. 

67.5% of the participants reported having daily headaches, and close to 85% of the participants reported trying more than three types of preventive drugs, and they currently used 2 of those. 59% of the participants wanted to use the ketamine nasal spray due to partial response to painkillers, 31% for prevention, 22.5% had previous benefit from intravenous ketamine, and 13% due to failure of intravenous lidocaine treatments. 

25% were offered the ketamine nasal spray before treatment with intravenous ketamine infusion, 28% were offered after intravenous ketamine infusion, and 47% never received intravenous ketamine. Overall the participants reported using the ketamine nasal spray 6 times over an average of 10 days per month. 49% reported that the nasal spray was very effective, 39.5% said it was somewhat effective, and 35.5% reported that their quality of life was much better. 

When the participants compared the ketamine nasal spray with other pain-relieving drugs 43% said that it was much better and 29.5% reported that it was somewhat better. Close to three-quarters of the participants reported using fewer pain relievers when using the nasal spray, and at the time of the conclusion interview, 65% of the participants were still using the ketamine nasal spray. 

74% of the participants reported experiencing at least one side effect when using the ketamine nasal spray with the most common effect being fatigue and double/blurred vision, which was followed by cognitive effects such as confusion, dissociation, vivid dream, and hallucinations. However, these side effects were reported to be mostly temporary. 

The findings of this study may not be widely applicable as the study was based on a single headache center and it was comprised primarily of young White women. Additionally, the ketamine nasal spray was used alongside other medications making it difficult to assess the benefits of the spray alone. 

It was also noted that a safe dose has yet to be determined in the absence of clinical guidelines, and at the time of writing the spray had not been approved for use for headaches or pain. Furthermore, it was also noted that dependency is a potential drawback, highlighting that their study showed 23 participants used the spray daily and 37 participants used it more than 15 days per month. 

“[This] should be addressed carefully and individually, as some may respond only to repeated [intranasal] ketamine while some may overuse it,” they caution. “Clinicians should only consider the use of a potentially addictive medication such as ketamine for significantly disabled patients with migraine,” they advise.

Despite this, the researchers conclude: “This retrospective study suggests that [intranasal] ketamine may offer a pain-relieving effect with limited [side effects] for [refractory chronic migraine] in the outpatient setting,” but further clinical trials are needed to confirm the findings.