Tuesday, April 28April 14, 2020Free AccessBright White Light Therapy for the Treatment of Multiple Sclerosis (MS) Associated Fatigue: A Randomized, Controlled Trial (1813)Farrah Mateen, Andre Vogel, Tamara Kaplan, Gladia Hotan, Natalie Manalo, Sara Grundy, Kathryn Holroyd, Matthew Stauder, and Aleksandar VidenovicAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.1813 Letters to the Editor

The International Classification of Headache Disorders, 3 edition (beta version), may be reproduced freely for scientific, educational or clinical uses by institutions, societies or individuals. Otherwise, copyright belongs exclusively to the International Headache Society. Reproduction of any part or parts in any manner for commercial uses requires the Society’s permission, which will be granted on payment of a fee. Please contact the publisher at the address below. International Headache Society 2013. Applications for copyright permissions should be submitted to Sage Publications Ltd, 1 Oliver’s Yard, 55 City Road, London EC1Y 1SP, United Kingdom (tel: þ44 (0) 20 7324 8500; fax: þ44 (0) 207 324 8600) (www.sagepub.co.uk). Translations

Objective: To assess the efficacy and safety of adding propranolol to topiramate in chronic migraine subjects inadequately controlled with topiramate alone. Methods: This was a double-blind, placebo-controlled, randomized clinical trial conducted through the National Institute of Neurological Disorders and Stroke Clinical Research Collaboration, expected to randomize 250 chronic migraine subjects inadequately controlled (≥10 headaches/month) with topiramate (50–100 mg/day) to either propranolol LA (long acting) (240 mg/day) or placebo. Primary outcome was 28-day moderate to severe headache rate reduction at 6 months (weeks 16 to 24) compared with baseline (weeks −4 to 0). Results: A planned interim analysis was performed after 48 sites randomized 171 subjects. The data and safety monitoring board recommended ending the trial after determining that it would be highly unlikely for the combination to result in a significant reduction in 28-day headache rate compared with topiramate alone if all 250 subjects were randomized. No safety concerns were identified. At study closure, 191 subjects were randomized. The 6-month reduction in moderate to severe 28-day headache rate and total 28-day headache rate for combination therapy vs topiramate alone was not significantly different: 4.0 vs 4.5 days (moderate to severe 28-day headache rate; p = 0.57) and 6.2 vs 6.1 days (total 28-day headache rate; p = 0.91). Conclusions: This study does not provide evidence that the addition of propranolol LA to topiramate adds benefit when chronic migraine is inadequately controlled with topiramate alone. Classification of evidence: This study provides Class II evidence that propranolol LA, added to topiramate, is ineffective in chronic migraine patients who fail topiramate monotherapy.

The Clinical Trials Subcommittee of the International Headache Society published its first edition of the guidelines on controlled trials of drugs in tension-type headache in 1995. These aimed ‘to improve the quality of controlled clinical trials in tension-type headache’, because ‘good quality controlled trials are the only way to convincingly demonstrate the efficacy of a drug, and form the basis for international agreement on drug therapy’. The Committee published similar guidelines for clinical trials in migraine and cluster headache. Since 1995 several studies on the treatment of episodic and chronic tension-type headache have been published, providing new information on trial methodology for this disorder. Furthermore, the classification of the headaches, including tension-type headache, has been revised. These developments support the need for also revising the guidelines for drug treatments in tension-type headache. These Guidelines are intended to assist in the design of well-controlled clinical trials in tension-type headache.

The TSM trial evaluated the ability of Preventive Drug Therapy (PDT) and Behavioral Migraine Management (BMM) separately and combined to improve outcomes with Optimal Acute Therapy (OAT) in frequent migraine. Potential trial participants with frequent migraine (IHS migraine, minimum of 3 migraines/mo., significant migraine-related disability) completed a 5-week acute therapy (Triptans, NSAID, anti-emetic and, as needed, rescue medication) run-in. Ss with diary confirmed migraine frequency/disability despite acute therapy were randomized (N=232; 79% female; means, age = 38 migraines/mo.= 6.3, migraine days/mo= 8.1.) to the 4 experimental treatments. The four experimental treatments were: 1) OAT (social learning based education to maximize effective use of acute therapies) + Preventive Placebo (PL), 2) OAT + PDT (Propranolol LA (PR) to 240 mg/d. or, if ineffective or not tolerated, Nadalol (NA) to 120 mg./d.), 3) OAT + BMM (migraine education, relaxation, thermal biofeedback or stress-management, pain management) + PL, and 4) OAT + BMM + PDT. Migraine activity and medication use was monitored by hand-held computer diary throughout the 16 mo. trial. Quality-of-Life (Headache Disability Inventory; HDI & Migraine Specific Quality of Life; MSQL) measures were collected periodically (mo. 0,1, 3,5,7,10,13,16).. Mixed models analysis (N = 232) revealed all 4 treatments produced substantial improvements across all outcome measures (p < .001), but the 4 treatments also differed in effectiveness (p < .001). Only the addition of BMM + PDT significantly improved migraine activity (episodes/mo, migraine days/mo.) beyond OAT alone (p < .01). However, both BMM + PDT and BMM alone improved outcomes on Q-of-L (HDI, MSQL) beyond both OAT alone and OAT + PDT. BMM + PDT optimally improved all outcomes obtained with OAT. OAT alone may effectively control migraines in up to 50% of Ss, raising the possibility that effective early abortion of migraine reduces the probability of migraine on subsequent days.

Abstract Chronic tension-type headache (CTTH) has been hypothesized to arise from a central pain processing deficit. Research has found that individuals with frequent TTH and CTTH exhibit increased pericranial muscle tenderness and reduced cephalic pressure pain thresholds (PPTs), possibly implicating sensitization at the trigeminal nucleus. However, CTTH sufferers have also been found to exhibit reduced extracephalic PPTs in some studies, suggesting a higher order deficit in pain processing. The purpose of this study was to examine pressure and thermal pain sensitivity in frequent TTH and CTTH at both cephalic and extracephalic locations.

Cognitive-behavioral stress-management therapy (SMT) and tricyclic antidepressant medication (AMT) are each moderately effective in treating chronic tension-type headache CTTH. However, little information is available about moderators of treatment response. 203 patients (75% females; mean age 38) with an International Headache Society diagnosis of CTTH (mean 26 headache days per month) were randomized to one of four treatments [Placebo (PL), AMT, SMT + PL, SMT + AMT] and evaluated via clinical assessments, daily headache diary, and psychosocial testing for 8 months. 1Holroyd, K et al; JAMA, 2001 The 169 patients who completed treatment are the focus of this report. The primary outcome measures were the Headache Index (HI; average daily pain rating taken 4 times per day) and the Headache Disability Inventory (HDI) that assesses the impact of headaches on psychosocial and affective functioning. Hierarchial linear modeling (ARIMA model) was used to examine moderators of treatment response. AMT showed the greatest advantage over PL when headache activity (p < .001 HI) and disability (p = .013 HDI) was severe, and when a co-morbid mood (p = .047 HI; p < .001 HDI) or anxiety disorder (p = .027 HDI) was present. Similarly, CBT showed the greatest advantage over PL when headache activity (p = .003 HI) and disability (p < .001 HDI) was severe, and when a co-morbid anxiety disorder (p = .009 HDI) was present. Overall the relative effectiveness of the three active treatments were moderated by the pretreatment severity of headaches and headache-related disability.