Effect of comorbid migraine on propranolol efficacy for painful TMD in a randomized controlled trial.
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ABSTRACT: 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.
SUBMITTER: Tchivileva IE
PROVIDER: S-EPMC8166404 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Propranolol is a nonselective beta-adrenergic receptor antagonist. A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2b trial enrolled participants aged 18 to 65 years with temporomandibular disorder myalgia to evaluate efficacy and safety of propranolol compared with placebo in reducing facial pain. Participants were randomized 1:1 to either extended-release propranolol hydrochloride (60 mg, BID) or placebo. The primary endpoint was change in facial pain index (FPI = facial pain intensity multiplied by facial pain duration, divided by 100). Efficacy was analyzed as a mean change in FPI from randomization to week 9 and as the proportion of participants with ≥30% or ≥50% reductions in FPI at week 9. Regression models tested for treatment-group differences adjusting for study site, sex, race, and FPI at randomization. Of 299 participants screened, 200 were randomized; 199 had at least one postrandomization FPI measurement and were included in intention-to-treat analysis. At week 9, model-adjusted reductions in mean FPI did not differ significantly between treatment groups (-1.8, 95% CL: -6.2, 2.6; P = 0.41). However, the proportion with a ≥30% reduction in FPI was significantly greater for propranolol (69.0%) than placebo (52.6%), and the associated number-needed-to-treat was 6.1 (P = 0.03). Propranolol was likewise efficacious for a ≥50% reduction in FPI (number-needed-to-treat = 6.1, P = 0.03). Adverse event rates were similar between treatment groups, except for more frequent fatigue, dizziness, and sleep disorder in the propranolol group. Propranolol was not different from placebo in reducing mean FPI but was efficacious in achieving ≥30% and ≥50% FPI reductions after 9 weeks of treatment among temporomandibular disorder participants.
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Project description:IntroductionWith the development of new neuroimaging tools it has become possible to assess neurochemical alterations in patients experiencing chronic pain and to determine how these factors change during pharmacological treatment. The goal of this study was to examine the exact neurochemical mechanism underlying pregabalin treatment, utilizing magnetic resonance spectroscopy (1H-MRS), in a population of patients with painful diabetic polyneuropathy (PDN), with the overall aim to ultimately objectify the clinical effect of pregabalin.MethodsA double blind, randomized, placebo-controlled study was conducted. A total of 27 patients with PDN were enrolled in the study, of whom 13 received placebo treatment (control group) and 14 received pregabalin (intervention group). Pregabalin treatment consisted of stepwise dose escalation over the study period from 75 mg daily ultimately to 600 mg daily. 1H-MRS was performed at 3T on four regions of interest in the brain: the rostral anterior cingulate cortex (rACC), left and right thalamus and prefrontal cortex. The absolute concentrations of N-acetyl aspartate, glutamate, glutamine, gamma-amino-butyric-acid (GABA), glucose (Glc) and myo-inositol (mINS) were determined using LCModel.ResultsThe concentration of most neurometabolites in the placebo and pregabalin group did not significantly differ over time, with only a small significant difference in Glc level in the left thalamus (p = 0.049). Comparison of the effects of the different doses revealed significant differences for mINS in the rACC (baseline 2.42 ± 1.21 vs. 450 mg 1.58 ± 0.94; p = 0.022) and dorsolateral prefrontal cortex (75 mg 2.38 ± 0.89 vs. 450 mg 1.59 ± 0.85; p = 0.042) and also for GABA in the rACC (75 mg 0.53 ± 0.51 vs. 225 mg 0.28 ± 0.19; p = 0.014).ConclusionNo differences were found in metabolite concentrations between the placebo (control) and intervention groups, but some differences, although small, were found between the different doses.Trial registrationThis study is registered at ClinicalTrials.gov (NCT01180608).FundingLyrica Independent Investigator Research Award (LIIRA) 2010 (Pfizer) funded the study.
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Project description:Objectiveto investigate the efficacy and safety of a medicated plaster containing betamethasone valerate (BMV) 2.25 mg in patients with chronic elbow tendinopathy.Methodsrandomized, double-blind, placebo-controlled study with assignment 2:2:1:1 to BMV medicated plaster applied daily for 12 hours, daily for 24 hours or matched placebo. 62 patients aged ≥18 years with chronic lateral elbow tendinopathy were randomized. The primary efficacy variable was pain reduction (VAS) at day 28. Secondary objectives included summed pain intensity differences (SPID), overall treatment efficacy and tolerability.Resultsmean reduction in VAS pain score at day 28 was greater in both BMV medicated plaster groups, -39.35±27.69 mm for BMV12-h and -36.91±32.50 mm for BMV24-h, than with placebo, -20.20±27.32 mm. Considering the adjusted mean decreases, there was a statistically significant difference between BMV12-h and placebo (p=0.0110). Global pain relief (SPID) and overall treatment efficacy were significantly better with BMV. BMV and placebo plasters had similar local tolerability and there were few treatment-related adverse events.ConclusionsBMV plaster was significantly more effective than placebo at reducing pain in patients with chronic elbow tendinopathies. The BMV plaster was safe and well tolerated.
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Project description:Postural tachycardia syndrome (POTS) is a form of dysautonomia which presents with complex symptoms including orthostatic intolerance. Several medications are prescribed for POTS; however, the efficacy of sustained medical treatment has not been well-investigated. Here, we conducted a 2?×?2 factorial design, randomized, clinical trial of a 3-month medical treatment regimen in POTS patients. Patients were randomly allocated to 4 treatment groups (Group 1: propranolol; Group 2: bisoprolol; Group 3: propranolol + pyridostigmine; Group 4: bisoprolol + pyridostigmine). The orthostatic intolerance questionnaire (OIQ), Beck depression inventory-II (BDI-II), and short-form health survey (SF-36) were conducted at baseline, 1 and 3 months after treatment. Seventy-seven patients who completed the 3-month follow-up were analyzed. In total, every clinical score improved significantly after medical treatment. The OIQ score was significantly lower than that at baseline (18.5?±?6.7) after 1 month (12.5?±?4.5, P?<?0.01), which decreased further after 3 months (7.8?±?5.7, P?<?0.01). The OIQ score improvements were consistent across every treatment group. In the subgroup analysis of 59 patients who did not receive antidepressants, the BDI-II score significantly decreased after treatment, regardless of the regimen. Physical components of the SF-36 improved after 3 months in every group, while mental components improved only in Group 3. The amount of changes in each score was similar among groups throughout the comparisons. Sustained medical treatment is beneficial to POTS patients, not only for orthostatic intolerance symptoms but also for depression and diminished quality of life, even without prescriptions for antidepressants. The efficacy of each regimen in POTS patients was comparable. TRIAL REGISTRATION:NCT02171988.
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