Study on High Dose Topical Mepyramine for Erythomyalgia
I came across a study that may be useful for those suffering erythomyalgia. The paper is on the use of 20% mepyramine cream (technically an antihistamine but it has sodium channel blocking properties) on patients whose causes were either NaV1.7 mutations or unknown. All patients had severe, poorly controlled erythomyalgia despite being on a number of medications. It's only 8 patients but the results were promising.
The second link is a data table showing the improvement in pain and shortened duration of erythomyalgia episodes each patient experienced. Link 3 is to pictures showing the visual difference. It includes one young girl whose family applied the cream to one limb and not the other in order to show the stark difference mepyramine had on her. Prior to the cream, her pain was 7 out of 10 despite being on multiple medications like morphine, fentanyl, and sodium channel blockers like mexiletine. She responded particularly well and went down to a 1 out of 10. Link 4 is to a list of all the medications the patients were on prior to trying the cream.
https://pmc.ncbi.nlm.nih.gov/articles/PMC12740923/
https://pmc.ncbi.nlm.nih.gov/articles/PMC12740923/table/tab3/
https://pmc.ncbi.nlm.nih.gov/articles/PMC12740923/figure/fig7/
https://pmc.ncbi.nlm.nih.gov/articles/PMC12740923/table/tab4/
20% mepyramine is a lot higher than the 2% found in normal commercial formulations . The researchers said doses tried before the study of around 2-5% were ineffective. The unconventionally high dose means it's something a doctor would have to order made through a compounding pharmacy. If any of your doctors believe this is worthwhile for you to try, I hope it works out for you. The lack of controls is regrettable, but given the many medications tried on these patients before without success and the ability to visually confirm the difference the cream had, it is unlikely the findings can be attributed to placebo.
Some selective quotes:
"In this study, we demonstrate that mepyramine, a compound previously shown to alleviate pain in animal models, effectively targets hNav1.7 channels carrying PEM-associated gain-of-function mutations, providing substantial pain relief in PEM patients. Using voltage-clamp recordings in human embryonic kidney (HEK) 293 cells, we demonstrated that mepyramine inhibits hNav1.7 channels carrying three distinct PEM mutations, I848T, L858F, and L1267V, which differentially affect the gating properties of hNav1.7. Importantly, mepyramine’s efficacy was consistent regardless of how these mutations altered channel activation or inactivation properties. To evaluate its clinical potential, we administered a high-dose topical formulation of mepyramine to a group of PEM patients suffering from severe pain that was unresponsive to conventional analgesics, including cases with identified SCN9A mutations. This treatment rapidly and durably reduced burning pain and erythema, providing meaningful relief for patients who had not responded to, or could not tolerate, previous therapies. These results suggest that mepyramine can inhibit PEM-associated Nav1.7 channel mutants and may offer a new therapeutic approach for PEM patients."
"The selection of the 20% concentration was based on preliminary data indicating that lower concentrations (2–5%) were ineffective and failed to provide adequate analgesia in patients with PEM"
"The patient reported a rapid decrease in NPRS score from 7/10 at baseline to 1/10, along with the complete disappearance of erythema and redness following the topical application of mepyramine (Figures 6, 7B,C and Table 3). The MCID indicated much relief, with an 85% reduction in pain. Noticeable relief was observed within 5–10 min of applying and rubbing the mepyramine cream and lasted for at least 3–4 h. The frequency of the attacks was also drastically reduced, and when they did occur, the duration was shortened to 10 min after mepyramine treatment compared to 30 min at baseline. No school absenteeism was observed during treatment, and the 9-year-old girl was able to resume cross-country activities."