In the present study we explored the efficiency and safety of Cefaly® used in episodic and chronic migraine prevention, after a failed trial of topiramate. Significant changes in headache days, headache days with headaches ≥5/10, use of analgesics, a high percentage of satisfaction and intent to continue treatment with Cefaly®, a poor responder rate and a very low percentage of AEs and technical issues were found in patients under active treatment with Cefaly from the 4 weeks of baseline period (Month-1) to the 4 weeks prior to the last observation or the 3rd month of active treatment.
A trial dose of 200 mg topiramate, as suggested by some experts but not all, was not offered to our patients. This was due to a recent meta-analysis of three studies that had included more than one dose of topiramate and suggested that the 200 mg dose is no more effective than the 100 mg dose [15]. Up to the present (March 2017), Cefaly® is not reimburshed by insurance schedules as a migraine treatment in Greece though the recently approved (2015) device is frequently used after a failed trial of medical treatment - commonly topiramate. Therefore, this criterion for inclusion may represent not only the general clinical recommendations but also the actual clinical practice needs as well, in Greece and elsewhere.
An important limitation of this study was the lack of a control group and the small size of our sample. Future studies should randomise participants to a control group where stimulation current is thought to be too low to be efficacious vs. standard current. Or compare participants to 3 or 6 months receiving topiramate vs. stimulation use, in an open manner for those who have not tried topiramate. Headache location is not used as a criterion for management decisions in migraine and changes in location within the same attack or between attacks is common among migrainous patients. Because of this, data regarding location was not collected or analyzed in this small exploratory study [3]. However, future studies or meta-analyses might explore the response or the adverse events of Cefaly® in patients differentially grouped according to the usual location of their headache pain.
A comparable percentage (70.59%) of satisfied patients was found in the verum group of the prospective, multicentre, double-blinded, randomized and sham-controlled PREvention of MIgraine using CEfaly® (PREMICE) study, which enrolled migraine patients with at least 2 attacks per month [16]. In another recent survey, 46.6% of 2313 renters of Cefaly® chose to return the device, which implied that they were not satisfied [11]. That leaves a 53.4% of satisfied patients. The difference might be attributed, among other reasons, to the different selection criteria in the survey, where patients were included on the basis of their triptan use for their headaches [11].
At baseline, the mean (SD) number of days with HA, which was one of our measures of efficacy, was 8.9 (4.7) while a mean of 5.3 (2.4) of those HAs showed peak intensity ≥5/10, which was one of our measures of efficacy. Regarding our third measure of efficacy, patients used acute medication for a mean of 8.2 (4.6) days (e.g. paracetamol, NSAIDS, triptanes etc.). On the last evaluation (after the 3rd active treatment month of the trial), the means (SD) for those measures were 6.3 (3.5), 4.3 (1.8) and 4.4 (3.3), respectively. Regarding the days with HA, these findings represent a reduction of 29.2%. In PREMICE study, patients in the verum group showed a comparable reduction of 32.3% in the days with HA [16]. Regarding acute medication use, a reduction of 46.3% was noted in the present study, comparable to the respective 36.7% in the PREMICE study [16].
Results from longitudinal analysis with Linear Mixed Models showed statistically significant decline over time in the following: the number of days with HA and the number of days with HA with intensity ≥5/10 after 3 months (p = 0.007 and p < 0.001 respectively), the number of days with use of acute medication after 1 and 3 months (p = 0.022 and p < 0.001 respectively), the number of days the device was not used after 2 and 3 months (p = 0.043 and p < 0.001 respectively) and finally, for those who expressed satisfaction in comparison to those who did not express satisfaction (Figs. 1 and 2). This was an expected finding as it confirms that patients were satisfied when the device helped them. It also emphasizes the importance of a full 3-month trial of t-SNS before determining efficacy, as it has been suggested by the researchers of the PREMICE study, that the maximum reduction in migraine frequency occurred only after 3 months of treatment with Cefaly® [16].
The present study, due to the small size of our sample, does not qualify for any vigorous exploration of safety with Cefaly®. Nevertheless, around 1 in 3 patients mentioned an AE. This may seem contrasting to a much lower percentage of 4.3% for AEs in the aforementioned survey [11]. However, in our own definition for AEs we included any unpleasant local paresthesia of any intensity intending to explore the whole range of events during the Cefaly® trial.
Among our intention-to-treat population, AEs were the primary reason for topiramate failure (57.1%). In the present study, we specifically aimed to determine whether the primary reason for the failure of topiramate – lack of efficacy or AEs – might be related to the possible future response to Cefaly®. No factors of response to Cefaly® were significantly associated with the reason for topiramate failure. The absence of time correlation between satisfaction and AEs suggests that AEs of topiramate, as a reason for its discontinuation, could be a more organic and not individualised perceptional factor compared to the seemingly unaffected AEs and non-satisfaction from Cefaly®.
The subgroup of 6 patients with chronic migraine from our cohort showed a similar profile of satisfaction/intent to continue treatment compared to the patients with episodic migraine (66.7% vs. 65.5% respectively). In an addendum to the PREMICE study [16], an increased effect size in relation to the frequency of HAs is reported, suggesting a possibly more favorable response in this subgroup with debilitating migraine, which is something that we were unable to confirm.