Frederick G. Freitag

Migraine prevalence, disease burden, and the need for preventive therapy

Objectives: 1) To reassess the prevalence of migraine in the United States; 2) to assess patterns of migraine treatment in the population; and 3) to contrast current patterns of preventive treatment use with recommendations for use from an expert headache panel. Methods: A validated self-administered headache questionnaire was mailed to 120,000 US households, representative of the US population. Migraineurs were identified according to the criteria of the second edition of the International Classification of Headache Disorders. Guidelines for preventive medication use were developed by a panel of headache experts. Criteria for consider or offer prevention were based on headache frequency and impairment. Results: We assessed 162,576 individuals aged 12 years or older. The 1-year period prevalence for migraine was 11.7% (17.1% in women and 5.6% in men). Prevalence peaked in middle life and was lower in adolescents and those older than age 60 years. Of all migraineurs, 31.3% had an attack frequency of three or more per month, and 53.7% reported severe impairment or the need for bed rest. In total, 25.7% met criteria for “offer prevention,” and in an additional 13.1%, prevention should be considered. Just 13.0% reported current use of daily preventive migraine medication. Conclusions: Compared with previous studies, the epidemiologic profile of migraine has remained stable in the United States during the past 15 years. More than one in four migraineurs are candidates for preventive therapy, and a substantial proportion of those who might benefit from prevention do not receive it.

Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society

Objective: To provide updated evidence-based recommendations for the preventive treatment of migraine headache. The clinical question addressed was: What pharmacologic therapies are proven effective for migraine prevention? Methods: The authors analyzed published studies from June 1999 to May 2009 using a structured review process to classify the evidence relative to the efficacy of various medications available in the United States for migraine prevention. Results and Recommendations: The author panel reviewed 284 abstracts, which ultimately yielded 29 Class I or Class II articles that are reviewed herein. Divalproex sodium, sodium valproate, topiramate, metoprolol, propranolol, and timolol are effective for migraine prevention and should be offered to patients with migraine to reduce migraine attack frequency and severity (Level A). Frovatriptan is effective for prevention of menstrual migraine (Level A). Lamotrigine is ineffective for migraine prevention (Level A).

Efficacy and Safety of Topiramate for the Treatment of Chronic Migraine: A Randomized, Double-Blind, Placebo-Controlled Trial

Objective.—To evaluate the efficacy and safety of topiramate (100 mg/day) compared with placebo for the treatment of chronic migraine.

A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis

Objective To evaluate the efficacy and safety of extended-release divalproex sodium compared with placebo in prophylactic monotherapy treatment of migraine headache. Methods This was a double-blind, randomized, placebo-controlled, parallel-group study. Subjects with more than two migraine headache attacks during a 4-week baseline were randomly assigned in a 1:1 ratio at each center to receive either extended-release divalproex sodium or matching placebo once daily for 12 weeks. Subjects initiated treatment on 500 mg once daily for 1 week, and the dose was then increased to 1,000 mg once daily with an option, if intolerance occurred, to permanently decrease the dose to 500 mg during the second week. Reduction from baseline in 4-week migraine headache rate was the primary efficacy variable. Migraine headaches separated by a <24-hour headache-free interval were counted as single migraines in calculating migraine headache rates. Tolerance and safety were also evaluated. Results The mean reductions in 4-week migraine headache rate were 1.2 (from a baseline mean of 4.4) in the extended-release divalproex sodium group and 0.6 (from a baseline mean of 4.2) in the placebo group (p = 0.006); reductions with extended-release divalproex sodium were significantly greater than with placebo in all three 4-week segments of the treatment period. No significant differences were detected between treatment groups in either the overall incidence or in the incidence of any specific treatment-emergent adverse event; 8% of subjects treated with extended-release divalproex sodium and 9% of those treated with placebo discontinued for adverse events. Conclusion Extended-release divalproex sodium is an efficacious, well-tolerated, safe, and easy-to-use once-a-day prophylactic antimigraine medication.

Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society

OBJECTIVE To provide updated evidence-based recommendations for the preventive treatment of migraine headache. The clinical question addressed was: Are nonsteroidal anti-inflammatory drugs (NSAIDs) or other complementary treatments effective for migraine prevention? METHODS The authors analyzed published studies from June 1999 to May 2009 using a structured review process to classify the evidence relative to the efficacy of various medications for migraine prevention. RESULTS The author panel reviewed 284 abstracts, which ultimately yielded 49 Class I or Class II articles on migraine prevention; of these 49, 15 were classified as involving nontraditional therapies, NSAIDs, and other complementary therapies that are reviewed herein. RECOMMENDATIONS Petasites (butterbur) is effective for migraine prevention and should be offered to patients with migraine to reduce the frequency and severity of migraine attacks (Level A). Fenoprofen, ibuprofen, ketoprofen, naproxen, naproxen sodium, MIG-99 (feverfew), magnesium, riboflavin, and subcutaneous histamine are probably effective for migraine prevention (Level B). Treatments considered possibly effective are cyproheptadine, Co-Q10, estrogen, mefenamic acid, and flurbiprofen (Level C). Data are conflicting or inadequate to support or refute use of aspirin, indomethacin, omega-3, or hyperbaric oxygen for migraine prevention. Montelukast is established as probably ineffective for migraine prevention (Level B).

LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine.

Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY293558, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA) receptor antagonist, is effective in preclinical models of migraine. We therefore tested LY293558 in acute migraine. We conducted a randomized, triple-blind, parallel-group, double-dummy, multicentre trial of 1.2 mg/kg intravenous (IV) LY293558, 6 mg subcutaneous (SC) sumatriptan, or placebo in the treatment of acute migraine. The primary efficacy variable was the headache response rate, i.e. headache score improvement from moderate/severe at baseline to mild/none at 2 h. Of 45 enrolled patients, 44 patients (20M:24F; mean age ± SD = 40 ± 9 years) completed the study. Response rates were 69% for LY293558 (P = 0.017 vs. placebo), 86% for sumatriptan (P < 0.01 vs. placebo) and 25% for placebo. LY293558 and sumatriptan were superior to placebo (P < 0.01 for all comparisons) on all other measures of improvement in pain and migraine associated symptoms. Fifteen percent of patients who took LY293558 reported adverse events (AEs) (n = 2; one mild, one severe). Fifty-three percent of patients who took sumatriptan (n = 8; seven mild, one moderate) and 31% of those who received placebo reported AEs (n = 5; four mild, one severe). The efficacy and safety results of LY293558 in this small migraine proof of concept trial, together with supportive preclinical data, provide evidence for a potential role of nonvasoactive AMPA/KA antagonists in treating migraine. Larger trials are needed to further test the hypothesis.

Ibuprofen plus caffeine in the treatment of tension‐type headache

The effectiveness of caffeine as an adjuvant to ibuprofen has been documented in investigations of acute pain. Our objectives were to assess this agent in the treatment of tension‐type headache and to establish clinical trial methods capable of assessing this agent in comparison with various tension headache treatments. Stopwatch technology was used for measurement techniques.

Botulinum Toxin Type A in the treatment of chronic migraine without medication overuse.

Introduction.— Chronic migraine is a recent diagnostic term that has undergone evolution from its original description. Clinically it has been believed that medication overuse contributed to its development and would block attempts at prevention. Previous studies with Botulinum Toxin Type A have demonstrated that it is effective even in patients with medication overuse. This study undertakes to examine the effects of Botulinum Toxin Type A in the absence of medication overuse in patients with chronic migraine.

OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine

Objective: To assess the effects of treatment with onabotulinumtoxinA (Botox, Allergan, Inc., Irvine, CA) on health-related quality of life (HRQoL) and headache impact in adults with chronic migraine (CM). Methods: The Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program (PREEMPT 1 and 2) included a 24-week, double-blind phase (2 12-week cycles) followed by a 32-week, open-label phase (3 cycles). Thirty-one injections of 5U each (155 U of onabotulinumtoxinA or placebo) were administered to fixed sites. An additional 40 U could be administered “following the pain.” Prespecified analysis of headache impact (Headache Impact Test [HIT]–6) and HRQoL (Migraine-Specific Quality of Life Questionnaire v2.1 [MSQ]) assessments were performed. Because the studies were similar in design and did not notably differ in outcome, pooled results are presented here. Results: A total of 1,384 subjects were included in the pooled analyses (onabotulinumtoxinA, n = 688; placebo, n = 696). Baseline mean total HIT-6 and MSQ v2.1 scores were comparable between groups; 93.1% were severely impacted based on HIT-6 scores ≥60. At 24 weeks, in comparison with placebo, onabotulinumtoxinA treatment significantly reduced HIT-6 scores and the proportion of patients with HIT-6 scores in the severe range at all timepoints including week 24 (p < 0.001). OnabotulinumtoxinA treatment significantly improved all domains of the MSQ v2.1 at 24 weeks (p < 0.001). Conclusions: Treatment of CM with onabotulinumtoxinA is associated with significant and clinically meaningful reductions in headache impact and improvements in HRQoL. Classification of evidence: This study provides Class 1A evidence that onabotulinumtoxinA treatment reduces headache impact and improves HRQoL.

Evidence-based understanding of medication-overuse headache: Clinical implications

This article discusses the problem of medication‐overuse headache from a variety of perspectives, based on the best available evidence. This presentation clarifies the definition of the disorder, distinguishing it from alternative terminology, and describes its epidemiology, natural history, and clinical course. Antimigraine medications are believed to differ in their relative liability to contribute to the development of medication‐overuse headache. Patients most at risk of developing medication‐overuse headache need to be identified so that appropriate preventive measures can be initiated.