In this guest blog, Drs Barrie and Matthew Phillips reflect on their experience using aminophylline, a drug that has been used for decades in respiratory and cardiovascular medicine, in the treatment of migraine attacks.
My son and I recently published a short article about migraine, which was called “Aminophylline in Pain and Migraine” and published in December 2023 in the journal Pain Management.
The article featured an old drug, aminophylline, which we proposed might be very useful in the treatment of migraine attacks. This proposal was based on a previous small study that I performed along with another colleague at the time in British Columbia, Canada, when I was working as a general internist (I have since retired). The study, published in the Canadian Journal of General Internal Medicine in 2012, examined the impact of aminophylline in people with severe migraine attacks.
During my time as an internist, I had a lot of experience with aminophylline while performing cardiac exercise stress tests on people with heart disease. We often administered a drug called dipyridamole, which would dilate the coronary arteries around the heart. However, the dipyridamole would create a severe, migraine-like headache in 20% of our patients, which we could easily abolish with a low dose of intravenous aminophylline. We did this so often that I didn’t think more of it at the time.
Years later, I wondered if aminophylline might help people with migraine, so my colleague and I performed the 2012 study mentioned above in 21 patients who attended our emergency department with severe, unremitting migraine attacks. We would administer a low dose (100 mg) of intravenous aminophylline over 20-30 minutes. The effect of the aminophylline was striking, with roughly 80% of the patients experiencing rapid, usually complete pain relief by the end of the infusion. This was only a small pilot study, but we found aminophylline abolished some very severe migraine attacks, which were so intense that people attended our emergency department to obtain relief. Notably, these headaches were unresponsive to most migraine drugs. We did not notice any significant adverse effects in our 21 patients.
I had hoped that other doctors would try the drug and confirm our findings since then, but in the 10 years since this study was published, I have not seen any other studies that have tried to corroborate (or refute) our findings. I wanted to increase awareness of the potential for aminophylline in migraine, so I wrote up the recent article in Pain Management along with my son, who also happens to be a neurologist and researcher at Waikato Hospital, Hamilton, New Zealand. He helped conceptualize and articulate the ideas in the article, which was important.
As to how aminophylline works in migraine, its mechanism is not well understood. However, it may act by inhibiting a molecule called adenosine, which is elevated in the blood during a migraine attack. When adenosine levels are high, they activate receptors on cells that produce pain. However, when adenosine levels are lower, they activate different receptors, leading to pain relief. Hence, the concentration of adenosine may be critical in determining whether it produces pain or pain relief, and aminophylline can regulate the concentration of adenosine.
More studies will be required to assess whether or not aminophylline can be useful for the treatment of migraine. The results in our short study in 2012 were dramatic, but the study was not designed as a randomized controlled trial, which is the best kind of study to determine whether a drug (or any other intervention) is effective or not.
I think there is great potential for low-dose aminophylline in the treatment of migraine attacks, so I hope that work in this area continues. I am especially pleased that my son and I could write a paper together. My mother suffered from chronic severe migraine headaches every month or so, and I suspect she would have been pleased by our efforts.
Further reading
- Phillips, BL, Phillips, MCL. Aminophylline in pain and migraine. Pain Manag. Published ahead of print (2023). https://doi.org/10.2217/pmt-2023-0076
- Kenyon M, Phillips B, DeWit C. Personal observation: intravenous aminophylline treatment for migraine. CJGIM. 7, 129–130 (2012). https://www.utpjournals.press/doi/abs/10.22374/cjgim.v7i4.124
