Effect of comorbid migraine on propranolol efficacy for painful TMD in a randomized controlled trial

Introduction The migraine-preventive drug propranolol is efficacious in reducing pain from temporomandibular disorder, suggesting potential modifying or mediating effects of comorbid migraine. Methods In this randomized controlled trial, myofascial temporomandibular disorder patients were treated with propranolol or placebo for 9 weeks. The primary endpoint was change in a facial pain index derived from daily symptom diaries. Linear and logistic regression models tested for a migraine × treatment-group interaction in reducing facial pain index. Counterfactual models explored changes in headache impact and heart rate as mediators of propranolol's efficacy. Results Propranolol's efficacy in reducing facial pain index was greater among the 104 migraineurs than the 95 non-migraineurs: For example, for the binary ≥ 30% reduction in facial pain index, odds ratios were 3.3 (95% confidence limits: 1.4, 8.1) versus 1.3 (0.5, 3.2), respectively, although the interaction was statistically non-significant (p = 0.139). Cumulative response curves confirmed greater efficacy for migraineurs than non-migraineurs (differences in area under the curve 26% and 6%, respectively; p = 0.081). While 9% of the treatment effect was mediated by reduced headache impact, 46% was mediated by reduced heart rate. Conclusions Propranolol was more efficacious in reducing temporomandibular disorder pain among migraineurs than non-migraineurs, with more of the effect mediated by reduced heart rate than by reduced headache impact. Study identification and registration SOPPRANO; NCT02437383; https://clinicaltrials.gov/ct2/show/NCT02437383