Migraine Disorders: Lewis D

Lewis D, Ashwal S, Hershey A, Hirtz D, Yonker M, Silberstein S, Anonymous00323, Anonymous00324. · Division of Child Neurology, Department of Pediatrics, Children's Hospital of the King's Daughters, Eastern Virginia Medical School, Norfolk, USA. · Neurology. · Pubmed #15623677 No free full text.

Abstract: OBJECTIVE: To review evidence on the pharmacologic treatment of the child with migraine headache. METHODS: The authors reviewed, abstracted, and classified relevant literature. Recommendations were based on a four-tiered scheme of evidence classification. Treatment options were separated into medications for acute headache and preventive medications. RESULTS: The authors identified and reviewed 166 articles. For acute treatment, five agents were reviewed. Sumatriptan nasal spray and ibuprofen are effective and are well tolerated vs placebo. Acetaminophen is probably effective and is well tolerated vs placebo. Rizatriptan and zolmitriptan were safe and well tolerated but were not superior to placebo. For preventive therapy, 12 agents were evaluated. Flunarizine is probably effective. The data concerning cyproheptadine, amitriptyline, divalproex sodium, topiramate, and levetiracetam were insufficient. Conflicting data were found concerning propranolol and trazodone. Pizotifen, nimodipine, and clonidine did not show efficacy. CONCLUSIONS: For children (>age 6 years), ibuprofen is effective and acetaminophen is probably effective and either can be considered for the acute treatment of migraine. For adolescents (>12 years of age), sumatriptan nasal spray is effective and should be considered for the acute treatment of migraine. For preventive therapy, flunarizine is probably effective and can be considered, but is not available in the United States. There are conflicting or insufficient data to make any other recommendations for the preventive therapy of migraine in children and adolescents. For a clinical problem so prevalent in children and adolescents, there is a disappointing lack of evidence from controlled, randomized, and masked trials.

Brenner M, Oakley C, Lewis D. · Department of Pediatrics, Children's Hospital of The King's Daughters, Eastern Virginia Medical School, Norfolk, VA 23507, USA. · Curr Pain Headache Rep. · Pubmed #18765142 No free full text.

Abstract: Headache can be caused by primary entities (as in migraine or tension-type headache) or the pain may result from secondary causes, such as brain tumors, idiopathic intracranial hypertension, chronic meningitis, hydrocephalus, drug intoxications, paranasal sinus disease, or acute febrile illnesses (eg, influenza). To determine the nature of a child's headache, the evaluation begins with a thorough medical history, followed by methodic physical examination with measurement of vital signs and complete neurologic examination. The diagnosis of primary headache disorders such as migraine and tension-type rests principally on clinical criteria as set forth by the International Headache Society (http://www.i-h-s.org/). Clues to the presence and identification of secondary causes of headache are uncovered through this systematic process of history and physical examination. The performance of ancillary diagnostic testing rests upon information or concerns revealed during the history and physical examination.

Logan P, Loga P, Lewis D. · Royal Brisbane & Women's Hospital, Queensland, Australia [corrected] · Emerg Med J. · Pubmed #17384391 No free full text.

This publication has no abstract.

Lewis D, Paradiso E. · Division of Pediatric Neurology, Department of Pediatrics, Children's Hospital of the King's Daughters, Eastern Virginia Medical School, Norfolk, VA 23507-1972, USA. · Headache. · Pubmed #18052950 No free full text.

Abstract: BACKGROUND: Basilar-type migraine (BM) is the most common migraine "variant," representing 3-19% of migraine in children.BMis characterized by attacks of dizziness, vertigo, visual disturbances, ataxia, and/or diplopia, followed by migraine headache. OBJECTIVE: The objective of this study is to assess the efficacy and safety of topiramate for prophylaxis of BM in children and adolescents (6-18 years). DESIGN: Outpatient, double-blind, parallel-group, dose comparison study with 2 phases: prerandomization (screening/washout and 4-week prospective baseline) and 12-week double blind (titration and maintenance). METHODS: Following consent and assent, subjects with BMs, as defined by the International Classification of Headache Disorders (second edition), and > or =4 migraines/month were randomized to receive either 25 mg per day or 100 mg per day of topiramate in a 1 : 1 ratio. RESULTS: Fourteen children (4 boys, 10 girls) completed the double-blind phase (7 in the 25-mg group and 7 in the 100-mg group). During the prospective baseline, the mean headache frequency of the combined group "all migraines" per month was 4.5/month (25 mg) and 4.8/month (100 mg). Average duration of migraine was 5.5 hours (25 mg) and 5.0 hours (100 mg) and average mean pain (5-point faces scale) was 3.3 for both (25 mg 100 mg). The reduction in median monthly migraine rate during the double-blind treatment phase relative to baseline was 2.9 (64.4%) and 3.6 (75.0%) for the 25-mg and 100-mg topiramate-treated groups, respectively (P < .001). The reduction in median monthly BM rate during the double-blind treatment phase relative to baseline was 2.5 (74.24%) and 2.3 (82.8%) for the 25-mg and 100-mg topiramate-treated groups, respectively. The overall reduction in BM attacks reduced from 2.84/month to 0.59/month (79.2%; P < .0042). Overall, 86% of patients responded with a greater than 50% reduction in migraine frequency (100%, 25 mg and 71%, 100 mg). Mean reduction in migraine duration was 18 minutes (25 mg) and 89 minutes (100 mg). There was no significant difference in migraine severity between the 2 groups. Parent Global Assessment was "very much" or "much improved" in 6 of 7 (25 mg) and 3 of 7 (100 mg) patients. Migraine disability as measured by PedMidas reduced from moderate to no disability (P < .001). There were no serious adverse events. CONCLUSIONS: Preventive therapy with topiramate resulted in reducing the overall migraine frequency and the frequency of attacks of BM at both 25 mg and 100 mg doses relative to the historical baseline and prospective baseline periods. The 2 treatment groups resulted in comparable outcomes.

Visser WH, Winner P, Strohmaier K, Klipfel M, Peng Y, McCarroll K, Cady R, Lewis D, Nett R, Anonymous00023. · Merck Research Laboratories, West Point, PA 19486, USA. · Headache. · Pubmed #15447698 No free full text.

Abstract: OBJECTIVE: To examine the short- and long-term efficacy and tolerability of rizatriptan 5 mg in adolescents with migraine. METHODS: Two studies were conducted in patients aged 12 to 17 years. The first study was a randomized, double-blind, placebo-controlled, single-attack study followed by a randomized, 1-year, open-label extension. The second study was a randomized, 1-year, open-label study. In the single-attack study, patients treated a moderate or severe migraine headache and up to two recurrences with rizatriptan 5-mg tablets (n = 234) or placebo (n = 242). Patients were instructed to use the study medication only on nonschool days. Headache severity, associated symptoms, and functional disability were assessed by the patient at 0.5, 1, 1.5, 2, 3, and 4 hours after the initial dose. In the 1-year studies, patients treated up to 6 migraine attacks per month with rizatriptan 5-mg tablets (n = 273), rizatriptan 5-mg wafers (n = 281), or standard care therapy (n = 132). Headache severity was assessed by the patient at 2 hours after the initial dose. In all studies, the primary efficacy measure was pain relief at 2 hours post dose. RESULTS: In the single-attack study, the proportion of patients with pain relief at 2 hours was not significantly different between rizatriptan 5 mg (68.2%) and placebo (68.8%). Fewer patients than expected (about 30%) treated their migraine attacks on the weekend. Among these patients, the proportion with pain relief at 2 hours was significantly higher in the rizatriptan group than in the placebo group (74% vs. 58%, P = 0.022). In the multiple-attack studies, pain relief at 2 hours was achieved in significantly more attacks treated with rizatriptan 5-mg tablet (77%) or with rizatriptan 5-mg wafer (77%) than with standard care (64%). Rizatriptan 5 mg was well tolerated in both the studies, with an adverse event profile not significantly different from that of placebo or standard care. CONCLUSIONS: Rizatriptan 5 mg was not more effective than placebo in the treatment of a single migraine attack in adolescents, but appeared to be more effective than standard care for treating multiple attacks occurring over 1 year in these patients. Rizatriptan 5 mg was well tolerated in adolescents during short-term and long-term use.

Winner P, Lewis D, Visser WH, Jiang K, Ahrens S, Evans JK, Anonymous00007. · Palm Beach Headache Center at Premiere Research Institute, West Palm Beach, Fla, USA. · Headache. · Pubmed #12005275 No free full text.

Abstract: OBJECTIVE: To investigate the tolerability and efficacy of rizatriptan 5 mg in adolescent migraineurs. METHODS: Randomized, double-blind, placebo-controlled study. Patients aged 12 to 17 years received rizatriptan 5 mg (n = 149) or placebo (n = 147) for a moderate or severe headache and for up to two recurrences. Headache severity, presence or absence of associated symptoms, and functional disability were assessed over a 4-hour postdose period, and any adverse events were recorded. The primary efficacy measure was pain-free status at 2 hours postdose. RESULTS: Rizatriptan 5 mg was well tolerated. The most commonly reported adverse events (all with incidence of 5% or less) among patients receiving rizatriptan were dry mouth, dizziness, asthenia/fatigue, nausea, and somnolence. The percentage of patients pain-free at 2 hours was 32% for rizatriptan 5 mg versus 28% for placebo (P=.474). The percentage of patients with pain relief (reduction of predose pain intensity to mild or none) at 2 hours was 66% for rizatriptan versus 56% for placebo (P=.079). Placebo response rates were higher than those typically observed in previous studies of rizatriptan in adults. Compared with placebo, rizatriptan significantly improved functional disability at 1.5 and 2 hours, and nausea at 1 and 1.5 hours. Post hoc analysis showed a significant benefit of rizatriptan versus placebo in the percentage of patients who had pain relief when their migraine attacks were treated on weekends (65% versus 36%, P=.046) compared with weekdays (66% versus 61%, P=.365), and the weekend placebo response rate was similar to that seen in adults. CONCLUSIONS: Rizatriptan 5 mg was well tolerated and effective on some measures when used in adolescents for the treatment of a migraine attack.

Lewis D, Winner P, Saper J, Ness S, Polverejan E, Wang S, Kurland CL, Nye J, Yuen E, Eerdekens M, Ford L. · Department of Pediatrics, Children's Hospital of the King's Daughters, Eastern Virginia Medical School, 601 Children's Lane, Norfolk, VA 23507-1971, USA. · Pediatrics. · Pubmed #19255022 No free full text.

Abstract: OBJECTIVE: Currently, no drugs are Food and Drug Administration-approved for migraine prophylaxis in pediatric patients. The objective of this study was to evaluate the efficacy and safety of topiramate for migraine prevention in adolescents. METHODS: Adolescents (12-17 years of age) with a >/=6-month history of migraine were assigned randomly to receive 16 weeks of daily treatment with topiramate (50 or 100 mg/day) or placebo. The primary efficacy measure was the percent reduction in monthly migraine attacks, with the use of the 48-hour rule, from the prospective baseline period to the last 12 weeks of the double-blind phase. The 48-hour rule defined a single migraine episode as all recurrences of migraine symptoms within 48 hours after onset. Several secondary efficacy measures were evaluated, including the reduction from baseline in the monthly migraine day rate and the 50% responder rate. Safety and tolerability were also assessed. RESULTS: A total of 29 (83%) of 35 subjects treated with topiramate at 50 mg/day, 30 (86%) of 35 subjects treated with topiramate at 100 mg/day, and 26 (79.0%) of 33 placebo-treated subjects completed double-blind treatment. Topiramate at 100 mg/day, but not 50 mg/day, resulted in a statistically significant reduction in the monthly migraine attack rate from baseline versus placebo (median: 72.2% vs 44.4%) during the last 12 weeks of double-blind treatment. Topiramate at 100 mg/day, but not 50 mg/day, also resulted in a statistically significant reduction in the monthly migraine day rate from baseline versus placebo. The responder rate favored topiramate at 100 mg/day (83% vs 45% for placebo). Upper respiratory tract infection, paresthesia, and dizziness occurred more commonly in the topiramate groups than in the placebo group. CONCLUSIONS: The 100 mg/day topiramate group demonstrated efficacy in the prevention of migraine in pediatric subjects. Overall, topiramate treatment was safe and well tolerated.

Rothner AD, Wasiewski W, Winner P, Lewis D, Stankowski J. · Cleveland Clinic Foundation, Cleveland, OH, USA. · Headache. · Pubmed #16412157 No free full text.

Abstract: OBJECTIVE: The objective of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy and tolerability of the zolmitriptan conventional tablet at three different doses for the treatment of a single migraine attack in adolescents. BACKGROUND: Preliminary data from an open-label study suggested that the zolmitriptan conventional tablet could be effective in the treatment of acute migraine in adolescent patients. Methods: Migraine patients aged 12 to 17 years (n = 850) were randomized to receive zolmitriptan 2.5, 5, or 10 mg, or placebo for treatment of a single migraine attack. Patients recorded migraine headache intensity before and after treatment using a 4-point scale. RESULTS: There was no statistically significant improvement between zolmitriptan 10 mg (2 x 5 mg tablet) and placebo for the primary efficacy variable, headache response at 2 hours, nor any of the secondary variables tested. Two-hour headache response rates were 54%, 53%, and 57% for zolmitriptan 10, 5, and 2.5 mg, respectively, and 58% for placebo. Two-hour pain-free rates were 25%, 19%, and 23% for zolmitriptan 10, 5, and 2.5 mg, respectively, and 20% for placebo. Zolmitriptan was well tolerated, with a tolerability profile similar to the pattern seen in adults. CONCLUSION: The similar efficacy between zolmitriptan and placebo appears to be the result of the high placebo response rate. This is a recognized issue in pediatric migraine studies and there is an ongoing debate on ways to address this problem. Since this study was initiated, there has been some debate on the appropriateness of the 2-hour endpoint for response rates in adolescent studies, given the shorter duration of headache pain in adolescents compared with adults. Furthermore, accurate information regarding the timeliness of treatment and reporting of headache-related information by adolescents is difficult.

Hershey AD, Winner P, Kabbouche MA, Gladstein J, Yonker M, Lewis D, Pearlman E, Linder SL, Rothner AD, Powers SW. · Division of Neurology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. · Headache. · Pubmed #16324160 No free full text.

Abstract: OBJECTIVE: To evaluate the sensitivity of the new International Classification of Headache Disorders-2nd edition (ICHD-II) criteria in the diagnosis of childhood migraine and to propose specific criteria for the diagnosis of childhood migraine. BACKGROUND: In 2004, ICHD-II was adopted by the International Headache Society. The prior version had been criticized for its lack of sensitivity in diagnosing childhood headaches. ICHD-II is felt to be an improvement as it provides for some differences between pediatric and adult migraine diagnosis in its footnotes, however, has yet to be validated. Clinically, it is the impression of many pediatric headache specialists that children's migraines are of shorter duration, tend to be bilateral rather than unilateral, and that children more often report either photophobia or phonophobia, rather than both. METHODS: The characteristics of headache in 260 patients, ages 18 and under, clinically diagnosed with migraine at two large pediatric headache centers were compiled using standard intake questionnaires. Inter-rater reliability in clinical diagnosis was determined by consensus of the clinical diagnosis. These data were analyzed applying the International Classification of Headache Disorders-1st edition (ICHD-I) and ICHD-II criteria for migraine to determine sensitivity of migraine diagnosis in comparison with clinical impression. Each headache characteristic in ICHD-II was analyzed individually to determine its effect on sensitivity of diagnosis. RESULTS: 183/260 patients (70.4%) met ICHD-I criteria. 161/260 patients (61.9%) met the ICHD-II criteria with a 4- to 72-hour range. When the footnoted allowance of ICHD-II for short duration (2 hours) was utilized, 187/260 patients (71.9%) met criteria, while this improved to 192/260 patients (73.9%) with 1-hour duration. If duration was excluded, 210/260 patients (80.8%) met criteria. The most common reasons for patients not meeting the standard criteria were the requirement of unilateral location, headache duration and number of associated symptoms. Based on these observations, modified criteria were empirically derived and the sensitivity increased to 84.4%. Data were reanalyzed using the criteria of focal head pain, either bilateral or unilateral, shortened duration, and modified associated symptoms, which resulted in an improved sensitivity in migraine diagnosis of 84.4%. CONCLUSIONS: Modification of ICHD-II criteria to include bilateral headache, headache duration of 1 to 72 hours, and nausea and/or vomiting plus two of five other associated symptoms (photophobia, phonophobia, difficulty thinking, lightheadedness, or fatigue), in addition to the usual description of moderate to severe pain of a throbbing or pulsating nature worsening or limiting physical activity, improved sensitivity of migraine diagnosis to 84.4%.