Topiramate Treatment of Chronic Migraine: A Randomized, Placebo-Controlled Trial of Quality of Life and Other Efficacy Measures

Objective.— To define yet more clearly the utility of topiramate in the treatment of chronic migraine, we evaluated prespecified secondary endpoints from a recent randomized, double‐blind, placebo‐controlled, multicenter clinical trial. Background.— We previously reported that topiramate 100 mg per day produced a statistically significant reduction in mean monthly migraine/migrainous and migraine headache days compared with placebo treatment and that it was safe and generally well tolerated. Methods.— Variables analyzed included between‐treatment group differences in percent responders, change in the mean monthly rate of total headache days and headache‐free days, change in average and worst daily headache severity, change in the mean monthly use of acute headache medications, and absolute change and percent change in a headache index. Additional analyses included evaluation of changes in: the associated symptoms of photophobia, phonophobia, and nausea; Migraine‐Specific Quality of Life Questionnaire scores; Migraine Disability Assessment Scale scores; and Physician's and Subjects Global Impression of Change. Results.— The intent‐to‐treat population consisted of 306 patients (topiramate, n = 153; placebo, n = 153). Categorical responder rates of reductions in mean monthly migraine/migrainous days for topiramate‐ vs placebo‐treated subjects were as follows: for ≥25% reduction: 68.6% vs 51.6% (P = .005); ≥50%: 37.3% vs 28.8% (P = .093); and ≥75%: 15.0% vs 9.2% (P = .061). The decrease in mean monthly total headache days and headache‐free days for topiramate vs placebo treatment was 5.8 vs 4.7 days (P = .067). Compared with placebo, topiramate treatment resulted in statistically significant mean improvements in the Role Restrictive (P = .028) and Emotional Function (P = .036) domains of the Migraine‐Specific Quality of Life Questionnaire, in the worst daily severity of migraine (P = .016), severity of photophobia (P = .032), frequency of vomiting (P = .018), photophobia (P = .038), phonophobia (P = .010), unilateral pain (P = .015), pulsatile pain (P = .023), and pain worsened because of physical activity (P = .047). In addition, there were trends observed (favoring topiramate) in average daily severity of migraine (P = .077), acute headache medication use (P = .127), severity of nausea (P = .098), frequency of nausea (P = .166), the Role Preventive domain of the Migraine‐Specific Quality of Life Questionnaire (P = .061), and severity of phonophobia (P = .062). Conclusions.— In addition to significantly reducing mean monthly migraine/migrainous and migraine headache days, treatment of chronic migraine with topiramate was effective with regard to several traditionally important and clinically relevant secondary outcomes in migraine prevention trials. Treatment with topiramate was well tolerated and not associated with serious adverse events.     

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. METHODS: This was a randomized, placebo-controlled, parallel-group, multicenter study consisting of 16 weeks of double-blind treatment. Subjects aged 18 to 65 years with 15 or more headache days per month, at least half of which were migraine/migrainous headaches, were randomized 1:1 to either topiramate 100 mg/day or placebo. An initial dose of topiramate 25 mg/day (or placebo) was titrated upward in weekly increments of 25 mg/day to a maximum of 100 mg/day (or to the maximum tolerated dose). Concomitant preventive migraine treatment was not allowed, and acute headache medication use was not to exceed 4 days per week during the double-blind maintenance period. The primary efficacy endpoint was the change from baseline in the mean monthly number of migraine/migrainous days; the change in the mean monthly number of migraine days also was analyzed. A fixed sequence approach (ie, gatekeeper approach) using analysis of covariance was used to analyze the efficacy endpoints. Assessments of safety and tolerability included physical and neurologic examinations, clinical laboratory parameters, and spontaneous reports of clinical adverse events. RESULTS: The intent-to-treat population included 306 (topiramate, n = 153; placebo, n = 153) of 328 randomized subjects who provided at least 1 efficacy assessment; 55.8% of the topiramate group and 55.2% on placebo were trial completers. The mean final topiramate maintenance dose was 86.0 mg/day. The mean duration of therapy was 91.7 days for the topiramate group and 90.6 days for the placebo group. Topiramate treatment resulted in a statistically significant mean reduction of migraine/migrainous headache days (topiramate -6.4 vs placebo -4.7, P= .010) and migraine headache days relative to baseline (topiramate -5.6 vs placebo -4.1, P= .032). Treatment-emergent adverse events occurred in 132 (82.5%) and 113 (70.2%) of topiramate-treated and placebo-treated subjects, respectively, and were generally of mild or moderate severity. Most commonly reported adverse events in the topiramate group were paresthesia (n = 46, 28.8%), upper respiratory tract infection (n = 22, 13.8%), and fatigue (n = 19, 11.9%). The most common adverse events in the placebo group were upper respiratory tract infection (n = 20, 12.4%), fatigue (n = 16, 9.9%), and nausea (n = 13, 8.1%). Discontinuations due to adverse events occurred in 18 (10.9%) topiramate subjects and 10 (6.1%) placebo subjects. There were no serious adverse events or deaths. CONCLUSIONS: Topiramate treatment at daily doses of approximately 100 mg resulted in statistically significant improvements compared with placebo in mean monthly migraine/migrainous and migraine headache days. Topiramate is safe and generally well tolerated in this group of subjects with chronic migraine, a burdensome condition with important unmet treatment needs. Safety and tolerability of topiramate were consistent with experience in previous clinical trials involving the drug.     

Two center, randomized pilot study of migraine prophylaxis comparing paradigms using pre-emptive frovatriptan or daily topiramate: research and clinical implications

(Headache 2012;52:749‐764) Objective.— To compare the efficacy and clinical benefit of 2 paradigms of migraine prevention using pre‐emptive frovatriptan and daily topiramate. The study compares the paradigms of pre‐emptive use of frovatriptan, a drug approved for acute migraine, and the daily use of topiramate, a Federal Drug Administration‐approved and ‐accepted standard for migraine prophylaxis. Background.— Traditionally, preventive treatment of migraine required daily medication. However, recent studies suggest that pre‐emptive prophylaxis may be beneficial to those migraineurs who can predict an attack of migraine based on premonitory symptoms and treat during that phase. Methods.— A total of 76 adult subjects with a diagnosis of migraine were screened for the study. During a 1‐month baseline period, subjects demonstrated through a daily diary that they predicted at least 50% of migraine attacks during the premonitory phase and treated with their usual medication. Of these, 55 were randomized to either Group A (daily topiramate) or Group B (frovatriptan during premonitory symptoms); 44 completed the study. The treatment period lasted 2 months. The subjects answered the Migraine‐Specific Quality of Life Questionnaire at randomization, and at Weeks 4 and 8. The revised Patient Perception of Migraine Questionnaire was answered 24 hours after taking frovatriptan (Group A, for break‐through headaches; Group B, treatment during premonitory symptoms). Results.— The number of migraine attacks and headache days per month decreased significantly from baseline for both Groups A and B. Subjects in Group A had considerably more adverse events leading to study withdrawal than in Group B (18% vs 4%). Though this study was not powered to directly compare the efficacy of the 2 drugs, topiramate showed superiority over frovatriptan at Month 2 in reduction of headache days, which was a secondary end point in the study (P = .036). Conclusions.— This pilot study demonstrated that statistical benefit for reduction of headache days over baseline for both pre‐emptive frovatriptan and daily topiramate. Subjects utilizing pre‐emptive frovatriptan experienced fewer adverse events leading to study withdrawal. Subjects utilizing daily topiramate had fewer headache days at Month 2.     

The long-term effect of insomnia on primary headaches: a prospective population-based cohort study (HUNT-2 and HUNT-3)

(Headache 2011;51:570‐580) Objective.— Few prospective studies have evaluated the relationship between insomnia and headache. We aimed to analyze the influence of insomnia at baseline on the risk for headache 11 years later. Methods.— This longitudinal cohort study included subjects who participated in 2 consecutive surveys of the Nord‐Trøndelag Health Study (HUNT‐2 and HUNT‐3). Among the invited individuals aged 20 years or more in HUNT‐2 (n = 92,566) and HUNT‐3 (n = 94,194), a total of 26,197 completed the headache section of both surveys. A proxy insomnia diagnosis based on DSM‐IV at baseline and ICDH‐2‐based headache diagnoses at follow‐up were derived from questionnaires. Headache‐free individuals in HUNT‐2 (n = 15,268) were selected for analysis. The relative risks (RRs) for headache in insomniacs were calculated with logistic regression. Results.— The presence of baseline insomnia was associated with a 40% increased risk for headache in HUNT‐3 (RR = 1.4, 95% CI = 1.2‐1.7). Similar results were found for tension‐type headache (TTH), migraine, and non‐classified headache. Subjects with insomnia‐related working disability had a 60% increased headache risk (RR = 1.6, 95% CI = 1.3‐2.1). The RR was larger for migraine (RR = 2.0, 95% CI = 1.3‐3.1) than for TTH (RR = 1.5, 95% CI = 1.1‐2.1). Insomnia at baseline was related to headache frequency at follow‐up for both migraine (P trend = 0.02) and TTH (P trend < 0.001). Conclusion.— In headache‐free subjects, insomnia was associated with an increased risk of headache 11 years later. The association was particularly strong for chronic headache.     

A multi-center double-blind pilot comparison of onabotulinumtoxinA and topiramate for the prophylactic treatment of chronic migraine

(Headache 2011;51:21‐32) Objective.— This multi‐center pilot study compared the efficacy of onabotulinumtoxinA with topiramate (a Food and Drug Administration approved and widely accepted treatment for prevention of migraine) in individuals with chronic migraine (CM). Methods.— A total of 59 subjects with CM were randomly assigned to one of 2 groups: Group 1 (n = 30) received topiramate plus placebo injections, Group 2 (n = 29) received onabotulinumtoxinA injections plus placebo tablets. Subjects maintained daily headache diaries over a 4‐week baseline period and a 12‐week active study period. The primary endpoint was the Physician Global Assessment, which measured the treatment responder rate and indicated improvement in both groups over 12 weeks. Secondary endpoints, measured at weeks 4 and 12, included headache days per month, migraine days, headache‐free days, days on acute medication, severity of headache episodes, Migraine Impact & Disability Assessment, Headache Impact Test, effectiveness of and satisfaction with current treatment on the amount of medication needed, and the frequency and severity of migraine symptoms. At 12 weeks subjects were re‐evaluated and tapered off oral study medications over a 2‐week time period. Subjects not reporting a >50% reduction of headache frequency at 12 weeks were invited to participate in a 12‐week open label extension study with onabotulinumtoxinA. Of these, 20 subjects, 9 from the Topiramate Group and 11 from the OnabotulinumtoxinA Group, volunteered for this extension from weeks 14 to 26. Results.— This study demonstrated positive benefit for both onabotulinumtoxinA and topiramate in subjects with CM. Overall, the results were statistically significant within groups but not between groups. By week 26, subjects had a reduction of headache days per month compared with baseline. This was a significant within‐group finding. Conclusion.— OnabotulinumtoxinA and topiramate demonstrated similar efficacy for subjects with CM as determined by Global Physician Assessment and supported by multiple secondary endpoint measures.     

Treatment outcomes of chronic post-traumatic headaches after mild head trauma in US soldiers: an observational study

(Headache 2011;51:932‐944) Background.— The effectiveness of medical therapies for chronic post‐traumatic headaches (PTHs) attributable to mild head trauma in military troops has not been established. Objective.— To determine the treatment outcomes of acute and prophylactic medical therapies prescribed for chronic PTHs after mild head trauma in US Army soldiers. Methods.— A retrospective cohort study was conducted with 100 soldiers undergoing treatment for chronic PTH at a single US Army neurology clinic. Headache frequency and Migraine Disability Assessment (MIDAS) scores were determined at the initial clinic visit and then again by phone 3 months after starting headache prophylactic medication. Response rates of headache abortive medications were also determined. Treatment outcomes were compared between subjects with blast‐related PTH and non‐blast PTH. Results.— Ninety‐nine of 100 subjects were male. Seventy‐seven of 100 subjects had blast PTH and 23/100 subjects had non‐blast PTH. Headache characteristics were similar for blast PTH and non‐blast PTH with 96% and 95%, respectively, resembling migraine. Headache frequency among all PTH subjects decreased from 17.1 days/month at baseline to 14.5 days/month at follow‐up (P = .009). Headache frequency decreased by 41% among non‐blast PTH compared to 9% among blast PTH. Fifty‐seven percent of non‐blast PTH subjects had a 50% or greater decline in headache frequency compared to 29% of blast PTH subjects (P = .023). A significant decline in headache frequency occurred in subjects treated with topiramate (n = 29, ?23%, P = .02) but not among those treated with a low‐dose tricyclic antidepressant (n = 48, ?12%, P = .23). Seventy percent of PTH subjects who used a triptan class medication experienced reliable headache relief within 2 hours compared to 42% of subjects using other headache abortive medications (P = .01). Triptan medications were effective for both blast PTH and non‐blast PTH (66% response rate vs 86% response rate, respectively; P = .20). Headache‐related disability, as measured by mean MIDAS scores, declined by 57% among all PTH subjects with no significant difference between blast PTH (?56%) and non‐blast PTH (?61%). Conclusions.— Triptan class medications are usually effective for aborting headaches in military troops with chronic PTH attributed to a concussion from a blast injury or non‐blast injury. Topiramate appears to be an effective headache prophylactic therapy in military troops with chronic PTH, whereas low doses of tricyclic antidepressants appear to have little efficacy. Chronic PTH triggered by a blast injury may be less responsive to commonly prescribed headache prophylactic medications compared to non‐blast PTH. These conclusions require validation by prospective, controlled clinical trials.     

Topiramate: a case series study in migraine prophylaxis

We reviewed the electronic records of 74 migraine patients treated with topiramate for more than 6 weeks. Twenty-four patients had episodic migraine and 50 had chronic (transformed) migraine. Most (81%) started treatment at 25 mg per day and reached a dose of 100 mg twice a day (mean dose on the last follow-up visit was 208 mg). The mean headache frequency decreased from 20.6 days to 13.6 days per month (P<0.0001) for all headaches (9.9-5.1 (P<0.0001) and 25.7-17.7 (P<0.001) for episodic migraine and chronic migraine, respectively). The percentage of patients whose headache frequency was reduced by > or =50% was 44.6% for all patients; 58.3 for episodic migraine and 38.0 for chronic migraine. For all patients mean headache severity (10-point scale) was reduced from 6.2 to 4.8 (P<0.0001). Patients on monotherapy (20%) and polytherapy (80%) had similar reductions in headache frequency. Adverse events were usually mild to moderate and were seen in 58.1% (paresthesias in 25%, cognitive difficulties 14.9%). Mean weight loss was 3.1 +/- 4 kg (3.8% of total body weight).     

Prophylaxis of migraine,transformed migraine,and cluster headache with topiramate

OBJECTIVE: To assess the efficacy and tolerability of topiramate for prophylaxis of migraine and cluster headache via a retrospective chart analysis. BACKGROUND: Topiramate has multiple mechanisms of action that could potentially contribute to migraine prophylaxis. We conducted a retrospective chart review to assess the efficacy of topiramate as add-on therapy in patients with transformed migraine or cluster headache, and as first-line therapy in patients with episodic migraine. METHODS: Patients diagnosed with transformed migraine, episodic migraine, or cluster headache, who received topiramate either as add-on therapy or monotherapy were selected via retrospective chart review. Patients had begun topiramate therapy at 25 mg/day for the first week and increased their dosage by 25 mg/week to a maximum of 200 mg/day. Topiramate was used as add-on therapy for patients with transformed migraine and cluster headache, and as a first-line monotherapy in patients with episodic migraine who had no previous prophylactic therapy. The outcome parameters examined included a mean 28-day migraine frequency, migraine severity, number of headache days/month, number of abortive medication tablets/month, patient global evaluation, and the MIDAS scale. RESULTS: One hundred seventy-eight patients (transformed migraine: n = 96; episodic migraine: n = 70; and cluster headache: n = 12) were included in the retrospective analysis. The mean dose of topiramate for all patients was 87.5 mg/day. For patients with transformed migraine, mean migraine frequency decreased from 6.3/28 days to 3.7 (P = 0.005). Mean severity decreased from 7.1 to 3.8 on a 10-point scale, with 10 representing the most severe pain (P = 0.003). The mean number of headache days/month decreased from 22.1 to 9.6 (P = 0.001), and the mean number of abortive medication tablets decreased from 28.7/month to 10.6 (P = 0.001). Patient global evaluation indicated substantial or moderate improvement in 53% of patients with transformed migraine who used topiramate as add-on therapy. Mean MIDAS scale values decreased from 90.2 to 24.9 (P< 0.0001). The 70 episodic migraine patients who were administered topiramate as first-line therapy exhibited a decrease in mean migraine frequency (5.8/28 days to 1.9, P = 0.001), while mean migraine severity decreased from 8.1 to 2.0 (P = 0.003). Sixty-one percent of patients reported marked improvement. Nine of the 12 cluster headache patients exhibited substantial or moderate improvement in symptoms, whereas three had no improvement. The most common adverse effects were paresthesias (12%), cognitive effects (11%), and dizziness (6%). Eight patients discontinued topiramate due to adverse effects; cognitive effects were the most common reason. No patient discontinued topiramate treatment due to lack of efficacy. Twelve percent of patients lost more than 5 lbs during treatment (a range of 5-120 lbs). CONCLUSION: For both patients with transformed migraine (add-on therapy) and patients with episodic migraine (first-line monotherapy), topiramate yielded significant reductions in migraine frequency, migraine severity, number of headache days/month, and use of abortive medications. Topiramate also appears to be well tolerated and useful in the adjunctive treatment of cluster headache. Prospective double-blind, placebo-controlled trials will be required to confirm our results.     

Evaluation of Carisbamate for the Treatment of Migraine in a Randomized, Double-Blind Trial

Objective.— This study explored the dose‐response relationship of carisbamate administered at doses of 100 mg per day, 300 mg per day, or 600 mg per day, in the prevention of migraine. Background.— Carisbamate ([S]‐2‐O‐carbamoyl‐1‐o‐chlorophenyl‐ethanol; RWJ 333369) is a new chemical entity being studied for efficacy as adjunctive therapy in partial onset epilepsy. Because some antiepileptic drugs are also efficacious in migraine, for example, topiramate and valproate sodium, we tested carisbamate in migraine prophylaxis. Design/Methods.— This was a double‐blind, placebo‐controlled trial, approximately 22‐week duration. The primary efficacy variable was the percent reduction from baseline through the double‐blind phase in average monthly migraine frequency using a 48‐hour rule. Patients were randomized 1 : 1 : 1 : 1 to treatment with carisbamate 100, 300, or 600 mg per day, or placebo. Migraine attacks were counted during a prospective 4‐week baseline period, which was followed by a 2‐week titration period, a 12‐week maintenance period, a 1‐week medication reduction period, and a 3‐week observation period. Patients had an established history of migraine, with or without aura, for at least 1 year and a 3‐month history of 3‐12 migraine attacks per month. Results.— Patients (n = 323) were predominantly women (85%) and white (89%); mean age was 41 years. There were no statistically significant differences between any of the carisbamate groups and placebo (P ≥ .6) for the median (range) percentage reduction from baseline to end point in average monthly migraine frequency (P value vs placebo): 37% (?250%, 100%) for placebo; 33% (?210%, 100%; P = .7) CRS 100 mg/day; 27% (?100%, 100%; P = .8) CRS 300 mg/day; and 35% (?87%, 100%; P = .6) CRS 600 mg/day. Results for secondary efficacy measures (responder rate, percent reduction in average monthly migraine frequency using the 24‐hour rule, and percent reduction in average monthly migraine days) were consistent (P ≥ .075). The proportion of patients discontinuing because of adverse events was similar for placebo and carisbamate‐treated patients (13% each). The most common (occurring in ≥5% of patients) treatment‐emergent adverse events in patients treated with carisbamate were fatigue (17%) and nasopharyngitis (13%). Fatigue appeared to be dose related. Conclusions.— Carisbamate was not more efficacious in migraine prophylaxis than placebo in this well‐controlled study that included a suitable population. However, carisbamate monotherapy was well tolerated at doses up to 600 mg per day.     

Zonisamide for migraine prophylaxis in topiramate-intolerant patients: an observational study

(Headache 2011;51:287‐291) Background.— Zonisamide, a sulfonamide analog, is an antiepileptic drug with mechanisms of action similar to topiramate. Because of its pharmacodynamic and pharmacokinetics profiles, zonisamide is also potentially suitable for migraine prevention. Methods.— Tolerability and effectiveness of zonisamide for migraine prophylaxis in patients with a good response to topiramate, but interrupting it for intolerable side effects, were evaluated in 34 patients. After a 1‐month period of wash‐out, patients were treated with zonisamide (up to a 100 mg/day dosage) for 6 consecutive months. Results.— Zonisamide was well tolerated, only 4 (12%) patients reported transient and tolerable side effects. Mean number of days with headache per month was reduced from 14.9 ± 5.3 during the wash‐out period to 2.5 ± 0.6 after 6 months of zonisamide (P < .001). We observed a significant reduction in headache severity and disability, as assessed by visual analog scale and migraine disability assessment scale. Finally, when compared with the 1‐month period prior to starting zonisamide, a reduced use of analgesics was recorded at the end of the follow‐up. Conclusion.— Our findings support the use of zonisamide as an alternative therapy for migraine prevention in patients with good response, but poor tolerance to topiramate.     

Topiramate vs divalproex sodium in the preventive treatment of migraine: a prospective "real-world" study

(Headache 2011;51:554‐558) Background and objectives.— Certain neuromodulators, most notably topiramate (TPM) and divalproex sodium (DVP), are effective preventive agents for migraine. Published data from head‐to‐head studies comparing TPM and DVP are not available. The purpose of this study was to compare TPM and DVP for the prophyaxis of migraine in a “real‐world” setting. Methods.— At 2 centers and over a period of 12 months we prospectively evaluated and treated a consecutive series of migraine patients. At baseline all were experiencing less than 15 headache days/month, and we treated all patients requiring prophylactic therapy with either TPM or DVP. We evaluated adherence, headache frequency (HF) and tolerability after 3 months of treatment. TPM treatment was initiated at 25 mg daily and increased every 10 days (25 mg) to a target of 150 mg/day (2 divided doses/day). Treatment with DVP was initiated at 250 mg daily and sequentially titrated up to 500 mg twice daily. All patients were naïve to the use of TPM and DVP. Results.— One hundred and twenty patients (104 women and 16 men of ages 18 to 68, mean 41.2 years) were included. Topiramate selectively was prescribed to 69 patients and DVP selectively to 51. Baseline HF for both groups was similar (8 ± 4 headache days/month). By intention to treat analysis at 3 months, 40 (58%) of patients initially treated with TPM and 26 (51%) of those initially treated with DVP experienced a reduction in HF of >50% (P = NS). Ten patients (14.5%) initially treated with TPM and 8 (15.7%) initially treated with DVP did not return for follow up or were begun on alternative prophylactic therapy. The most common side effects manifested by TPM patients were weight loss (50% of those who completed the treatment period), paresthesia (48%), and cognitive disturbances (20%), whereas DVP patients who completed the treatment period reported weight gain, hair loss, and gastrointestinal symptoms (approximately 24% for each). The mean doses achieved by those completing the study were 140 mg/day for TPM and 890 mg/day for DVP. Conclusions.— Although any conclusions from this investigation necessarily are limited because of our study's open‐label nonrandomized design, these results suggest that TPM and DVP are reasonably effective and generally well tolerated when used to treat a “real‐world” population of episodic migraineurs who require prophylaxis.     

Topiramate for migraine prevention in adolescents: a pooled analysis of efficacy and safety

OBJECTIVE: To characterize the efficacy and safety of topiramate for migraine prevention in adolescents from 3 randomized, 26-week, double-blind, placebo-controlled trials. BACKGROUND: Limited information is available regarding the efficacy and safety of prophylactic medications for treatment of adolescent migraine, a significant health problem. In studies that included adults and children, topiramate 100 and 200 mg/day were effective and generally well-tolerated in the prevention of migraine headache. METHODS: We performed a post hoc subset analysis of the efficacy and safety data from the 51 patients, ages 12-17 years, enrolled in 3 pivotal trials of topiramate for migraine prophylaxis. RESULTS: Daily treatment with topiramate 50, 100, and 200 mg for 26 weeks reduced monthly migraine frequency from baseline 46% (P= .07), 63% (P= .02), and 65% (P= .04), respectively, compared with placebo (16%). Similarly, topiramate reduced both the monthly mean number of migraine days (1, 4, and 5 days for topiramate 50, 100, and 200 mg/day, respectively, vs 1 day for placebo) and percentage of days during which acute migraine medications were administered (59%, 54%, and 67% for topiramate 50, 100, and 200 mg/day, respectively, vs 42% for placebo), although the treatment differences did not reach nominal statistical significance. Topiramate 200 mg/day did not appear to offer greater efficacy than 100 mg/day. Treatment was generally well-tolerated, although adverse events were most frequent in the 200 mg/day dose group. CONCLUSIONS: This post hoc subset analysis suggests that topiramate 100 and 200 mg/day, and possibly 50 mg/day, administered prophylactically for 26 weeks may reduce migraine in adolescents.     

Self-reported comorbid pains in severe headaches or migraines in a US national sample

Aims.— To compare prevalence of self‐reported comorbid temporomandibular joint muscle disorder‐type, neck, back, and joint pains in people with severe headache or migraine; and analyze these self‐reported pains in the 2000‐2005 US National Health Interview Survey by gender and age for non‐Hispanic whites, Hispanics, and non‐Hispanic blacks (African Americans). Methods.— National Health Interview Survey data included information on gender, age, race, ethnicity, health status, and common pain types: severe headache or migraine, temporomandibular joint muscle disorder‐type, neck, and low back in the last 3 months, as well as prior‐month joint pains. Analyses included survey prevalence estimation and survey logistic regression to obtain odds ratios and 95% confidence intervals. Results.— The study included 189,967 adults: 48% males, 52% females; 73% white, 12% Hispanic, and 11% black. Of the entire sample, 29,712 (15%) reported severe headache or migraine, and 19,228 (64%) had severe headache or migraine with at least 1 comorbid pain. Two or more comorbid pains were reported in 10,200 (33%), with no gender difference, and with Hispanics (n = 1847 or 32%) and blacks (n = 1301 or 30%) less likely to report 2 or more comorbid pains than whites (n = 6747 or 34%) (odds ratio = 0.91, P = .032; OR = 0.82, P < .001, respectively). This group also reported significantly lower ratings of self‐rated health (P < .001). Differences in type of comorbid pain by age patterns were found. Conclusions.— Severe headache or migraine is often associated with other common pains, seldom existing alone. Two or more comorbid pains are common, similarly affecting gender and racial/ethnic groups.     

Topiramate for Migraine Prevention in a Naturalistic Setting: Results From an Open Label, Flexible Dose Study

Background.— Headaches are one of the most common neurological symptoms and migraines are the most common primary headache disorder. The global prevalence of migraines is around 10% and the condition is associated with a high burden of disease. Despite an abundance of good quality evidence, only 1 in 5 of patients who fulfill the criteria for preventive migraine therapy are appropriately treated. Data on patient outcomes with preventive medication derive mostly from specialized academic centers, which contrasts with normal clinical practice where the majority of patients are treated outside tertiary care centers. Objective.— To explore tolerability, safety and efficacy outcomes of patients receiving topiramate for migraine prevention in a naturalistic setting. Methods.— After a 4‐week prospective baseline, patients with a diagnosis of migraine according to International Headache Society criteria and eligible for migraine prevention were treated with flexible dosing of topiramate for 24 weeks (core phase), and optionally for a total of 48 weeks. The primary safety analysis included adverse events (AEs) during the core phase. For the main efficacy measures, the absolute changes from baseline to end of core phase as well as last follow‐up visit were calculated for migraine days per 4 weeks, migraine attacks per 4 weeks, mean maximum visual analogue scale of migraine headache per 4 weeks and mean maximum pain intensity of migraine headache (4‐point scale) per 4 weeks. In addition, changes in individual quality of life aspects were captured. Results.— The intention‐to‐treat population (ITT) consisted of 161 patients (90.7% female, mean age 45.7 ± 11.1 years). Topiramate median dose was 45.7 mg/day at endpoint. Some 74.1% of patients reported treatment emergent AEs, most frequently paresthesias (18.4%) and nausea (12.4%). Some 20.0% of patients withdrew from the study due to AEs. The mean number of migraine days per 4 week decreased from 6.2 ± 3.9 days at baseline to 3.9 ± 3.5 days at last core visit (P < .001). Mean maximum pain intensity per 4 week changed from 7.0 ± 2.3 at baseline to 4.7 ± 3.2 at last visit core phase (P < .001). Consumption of triptans and analgesics reduced during the course of the core phase (P < .005). Fifty‐one percent of all patients experienced at least a 50% reduction in migraine days during the core phase. Conclusion.— Topiramate used for migraine prevention in non‐academic institutions is generally safe, well tolerated and results in good control of migraine headaches and improvement in several aspects of quality of life.     

A Double-Blind Comparison of OnabotulinumtoxinA (BOTOX®) and Topiramate (TOPAMAX®) for the Prophylactic Treatment of Chronic Migraine: A Pilot Study

Background.— There is a need for effective prophylactic therapy for chronic migraine (CM) that has minimal side effects. Objective.— To compare the efficacy and safety of onabotulinumtoxinA (BOTOX^®, Allergan, Inc., Irvine, CA) and topiramate (TOPAMAX^®, Ortho‐McNeil, Titusville, NJ) prophylactic treatment in patients with CM. Methods.— In this single‐center, double‐blind trial, patients with CM received either onabotulinumtoxinA, maximum 200 units (U) at baseline and month 3 (100 U fixed‐site and 100 U follow‐the‐pain), plus an oral placebo, or topiramate, 4‐week titration to 100 mg/day with option for additional 4‐week titration to 200 mg/day, plus placebo saline injections. OnabotulinumtoxinA or placebo saline injection was administered at baseline and month 3 only, while topiramate oral treatment or oral placebo was continued through the end of the study. The primary endpoint was treatment responder rate assessed using Physician Global Assessment 9‐point scale (+4 = clearance of signs and symptoms and ?4 = very marked worsening [about 100% worse]). Secondary endpoints included the change from baseline in the number of headache (HA)/migraine days per month (HA diary), and HA disability measured using Headache Impact Test (HIT‐6), HA diary, Migraine Disability Assessment (MIDAS) questionnaire, and Migraine Impact Questionnaire (MIQ). The overall study duration was approximately 10.5 months, which included a 4‐week screening period and a 2‐week optional final safety visit. Follow‐up visits for assessments occurred at months 1, 3, 6, and 9. Adverse events (AEs) were documented. Results.— Of 60 patients randomized to treatment (mean age, 36.8 ± 10.3 years; 90% female), 36 completed the study at the end of the 9 months of active treatment (onabotulinumtoxinA, 19/30 [63.3%]; topiramate, 17/30 [56.7%]). In the topiramate group, 7/29 (24.1%) discontinued study because of treatment‐related AEs vs 2/26 (7.7%) in the onabotulinumtoxinA group. Between 68% and 83% of patients for both onabotulinumtoxinA and topiramate groups reported at least a slight (25%) improvement in migraine; response to treatment was assessed using Physician Global Assessment at months 1, 3, 6, and 9. Most patients in both groups reported moderate to marked improvements at all time points. No significant between‐group differences were observed, except for marked improvement at month 9 (onabotulinumtoxinA, 27.3% vs topiramate, 60.9%, P = .0234, chi‐square). In both groups, HA/migraine days decreased and MIDAS and HIT‐6 scores improved. Patient‐reported quality of life measures assessed using MIQ after treatment with onabotulinumtoxinA paralleled those seen after treatment with topiramate in most respects. At month 9, 40.9% and 42.9% of patients in the onabotulinumtoxinA and topiramate groups, respectively, reported ≥50% reduction in HA/migraine days. Forty‐one treatment‐related AEs were reported in 18 onabotulinumtoxinA‐treated patients vs 87 in 25 topiramate‐treated patients, and 2.7% of patients in the onabotulinumtoxinA group and 24.1% of patients in the topiramate group reported AEs that required permanent discontinuation of study treatment. Conclusions.— OnabotulinumtoxinA and topiramate demonstrated similar efficacy in the prophylactic treatment of CM. Patients receiving onabotulinumtoxinA had fewer AEs and discontinuations.     

Memantine in the Preventive Treatment of Refractory Migraine

Objectives.— To assess the efficacy and tolerability of memantine (MEM) in the preventive treatment of refractory migraine. Background.— Glutamate is of importance in migraine pathophysiology and may be related to progression from episodic to chronic mirgraine. Furthermore, individuals with chronic pain often report cognitive problems. MEM has the potential to address both issues, justifying this pilot study. Methods.— We included subjects with refractory migraine (episodic migraine with 8‐14 days of headache per month or transformed migraine, who had previously failed at least 2 trials of adequate preventive therapy). Other preventive drugs were allowed if the patient had been on a stable dose for more than 30 days. MEM dose ranged from 10 mg to 20 mg per day. The treatment phase lasted 3 months. The primary endpoint was number of days with headache at month 3. Cognitive performance was assessed with the trail making tests A and B (TMT‐A and B). Statistical analyses were performed on the intent‐to‐treat (ITT) population, using data subjected to the last observation carried forward algorithm. We also conducted per protocol analyses. Results.— In the ITT population (n = 28), monthly headache frequency was reduced from 21.8 days at baseline to 16.1 (P < .01) at 3 months. The mean number of days with severe pain was reduced from 7.8 to 3.2 at 3 months (P < .01). The mean disability scores were significantly reduced at 3 months, compared with baseline (36.6 vs 54.9, P < .01). There was a significant reduction in the time to complete TMT‐A at termination vs baseline (28.4 vs 23.2, P = .02) and also TMT‐B (70.1 vs 50.4, P = .04). Side effects were present in 37.5% of the patients; 5.5% dropped out the study because of poor tolerability. Most adverse events were mild. Conclusion.— This study offers preliminary evidence for the use of MEM in the prevention of refractory migraine. Double‐blind studies are now required.     

Migraine headaches and suicide attempt

(Headache 2012;52:723‐731) Background.— Previous cross‐sectional studies reported an increased risk of suicide attempt in persons with migraine headache, which was sustained when psychiatric comorbidity was statistically controlled. Objective.— To estimate the risk of suicide attempt in persons with migraine vs controls with no history of severe headache, using prospective data and validated diagnostic assessment. To examine the specificity of the migraine‐suicide attempt risk by comparing it to the risk associated with non‐migraine headache of comparable severity and disability. Methods.— A cohort of persons with migraine (n = 496), non‐migraine severe headaches (n = 151), and controls with no history of severe headache (n = 539) was randomly selected from the general community, assessed in 1997 and reassessed 2 years later. Results.— Persons with migraine had an increased risk of suicide attempt during the 2‐year follow‐up period, compared with controls. Odds ratio, adjusted for sex, psychiatric disorder, and previous history of suicide attempt at baseline was 4.43 (95% confidence interval [CI] 1.93, 10.2). Persons with non‐migraine headache of comparable intensity and disability also had an increased risk of suicide attempt, compared to controls: odds ratio, adjusted for the same covariates, was 6.20 (95% CI 2.40, 16.0). The difference between the 2 estimates was not significant. In the entire sample, headache severity at baseline predicted suicide attempt: a difference of 1 standard deviation (SD) in pain score increased the risk of suicide attempt by 79%, adjusting for sex and psychiatric disorders. Conclusions.— The results suggest the possibility that pain severity might account in part for the increased risk of suicide attempt associated with migraine.     

Frovatriptan as preemptive treatment for fasting-induced migraine

Objective.— To examine frovatriptan's efficacy as preemptive treatment for fasting‐induced migraine. Background.— Fasting is a common migraine trigger that cannot always be avoided. The development of a short‐term preemptive approach would be of benefit. Because of its longer half‐life, frovatriptan has been effectively used for short‐term daily use to prevent menstrually related migraines and might prove useful in the prevention of fasting‐induced migraine. Methods.— This was a double‐blind, placebo‐controlled, randomized, parallel‐group trial. Subjects.— With a history of fasting‐induced episodic migraine were randomly assigned to receive either frovatriptan (5.0 mg) or placebo (ratio 1:1). Subjects.— Took a single dose of study medication at the start of their 20‐hour fast. Information about headache intensity, associated symptoms, and use of rescue medication was captured at defined time points from the start of the fast through 20 hours post‐fast. Results.— Of the 75 subjects screened, 74 subjects were randomized and 71 subjects completed the study. Demographic characteristics of the placebo and frovatriptan treatment groups were not statistically different. Thirty‐three subjects received active drug. Twelve (36.4%) developed a headache between 6 and 20 hours after the start of the fast (1/33 mild, 11/33 moderate or severe). In the placebo group, 18/34 (52.9%) developed a headache (4/34 mild, 14/34 moderate or severe). The difference between the 2 treatment groups did not achieve statistical significance; Pearson chi‐square, P = .172. Kaplan‐Meier survival analysis showed no difference between the 2 treatment groups with respect to the time of onset of headache of any intensity (log rank, P = .264) and for the time of onset of a moderate or severe intensity (log rank, P = .634). Conclusion.— More subjects on placebo developed a headache than those on frovatriptan. Perhaps because of the small number of subjects involved, the differences in headache incidences observed did not achieve statistical significance.     

Retracted: Prevalence and Burden of Headache Disorders: A Comparative Regional Study in China

Background.— Since the early 1990s, no study has been undertaken examining the prevalence and burden of headache disorders in China. Objective.— We conducted a one‐year survey on the prevalence and burden of primary headache in the Chinese provinces of Guangdong and Guangxi. Our study also evaluated the factors behind similarities and differences affecting prevalence in the 2 regions of study. Methods.— Random samples of 372 local residents in Guangdong and 182 local residents in Guangxi aged 18‐65 years were invited to a face‐to‐face interview. Results.— The one‐year prevalence of primary headache was 22.6% (84/372) in Guangdong and 41.2% (75/182) in Guangxi. The prevalence of migraine (14.3%, n = 26) in Guangxi was higher than prevalence of migraine (8.3%, n = 31) in Guangdong (P = .03). The ratio of headache cost and household income was 2.1% in Guangdong and 3.7% in Guangxi, the ratio in Guangdong was less than that in Guangxi (P = .001). The diagnostic confirmation rate of migraine was low. No migraineur used triptans drugs to treat migraine in either region. Conclusion.— Migraine prevalence was higher in the lower‐income region that also contains a higher proportion of ethnic minorities. Although there was no difference of headache cost between the 2 regions, the headache populations in the lower‐income region would relatively suffer a greater financial burden if taking the economic differences between the 2 regions into account. The improvement of diagnostic and therapeutic levels for the treatment of headache, especially migraine, in the 2 regions may be a matter of urgency.