Total Headache Days Research Articles

Combined Prophylaxis of Chronic Migraine with OnabotulinumtoxinA and Anti-CGRP Antibodies

Objective: To evaluate the efficacy of adding large molecule anti-calcitonin gene-related peptide monoclonal antibodies (mAbs) to onabotulinumtoxinA (OBT-A) for chronic migraine prevention. Background: Chronic migraine (CM) is a highly prevalent, debilitating disorder that leads to personal, social, and economic burdens. Both OBT-A and mAbs are proven safe and effective in chronic migraine prevention. The use of combination therapy has not been formally studied but may prove more effective than either monotherapy alone in select patients. Methods: This is a retrospective chart review of patients with chronic migraine, treated with OBT-A, who received additional mAb preventative therapy. The primary endpoint was migraine headache days per month (MHD) after 3 months of combined therapy. Secondary endpoints included total headache days per month, headache intensity, disability level, and use of abortive medications. Results: Of 1503 patients reviewed, 133 met inclusion criteria. At 3 months of combined therapy, mean reduction of MHD from baseline was 6.2 (95% CI 4.91 to 7.49, p < 0.0001). Nearly 2/3rd of patients (60.9%) experienced ≥ 50% MHD reduction. Fewer patients reported high disability level (14.6% [17/126], compared to 29.4%) and high headache intensity (13.0% [16/119], compared to 51.3%) at 3 months (all p < 0.0001). A reduction in abortive medication doses needed and discontinuation of concomitant oral preventative medications was also noted in 15.8% and 6.8% of patients, respectively. Conclusions: Combined therapy with OBT-A and mAbs is well-tolerated, effective in further reducing migraine frequency, and may improve quality of life for patients with CM refractory to monotherapy.

Infrared Polarized Light Application in the Chronic Migraine Treatment: Safety and Effectiveness

The phase II study aimed to evaluate the safety and efficacy of non-invasive infrared polarized light device on patients with chronic migraine (CM). Forty patients aged between 18 and 60 years with a diagnosis of CM were included. Sociodemographic and clinical information were obtained by face-to-face interviews with the patients and they had migraine diary containing headache information before and monthly during 4 months of the treatment. Clinical data included age of migraine onset, duration of disease as years, total headache days per month, severity of headache assessed by visual analogue scale (VAS), number of painkillers used monthly, and impact of headache on patients' home, work and social life activities. Short form-36 (SF-36) was used to examine for the quality of life. Migraine therapy devices; both active and inactive, were given to the patients to use at home according to study protocol, double-blinded, randomized, sham-controlled trial. Statistical analysis was performed using the SAS University Edition 9.4 program. A total of 40 patients, 36 (90%) were female and t he mean age was 37.50 ± 9.77 years . The mean duration of migraine was 12.74 ± 9.55 years. Migraine therapy device was well tolerated without any side effects.

Efficacy of erenumab and factors predicting response after 3 months in treatment resistant chronic migraine: a clinical service evaluation

BackgroundCalcitonin gene-related peptide (CGRP) inhibitors have been developed as options for treatment of chronic and episodic migraine. We present our experience of the use of erenumab in a tertiary headache centre.MethodsThis was a prospective clinical audit of all patients commenced on erenumab following a locally agreed pathway and criteria over a consecutive period. Patients received monthly erenumab 140 mg for 3 months. Data were collected prospectively at baseline and 3 months follow up.ResultsOne hundred three patients were commenced on erenumab during the study period. Patients had tried a median of 7 previous prophylactics, including onabotulinum toxin A in 94%. At 3 months there was a reduction in median total (28 to 20, 29% reduction, p < 0.0001) and severe (15 to 5, 67% reduction, p < 0.0001) headache days. 39.8% of patients achieved at least a 30% reduction in total headache days; 61.8% of patients achieved at least a 50% reduction in severe headache days. Meeting either of these thresholds was considered a positive response, 68% of patients achieved this. Presence of daily headache pattern was negatively associated with response, (56% response vs. 90% without daily headache, p = 0.0003). There was no association between age, gender, presence of medication overuse or number of previously tried prophylactic treatments and response to erenumab. 43% of patients reported at least one adverse effect, most commonly constipation (26%); treatment was discontinued in 3 patients due to adverse effects.ConclusionsErenumab was an effective treatment for chronic migraine in this treatment resistant population over 3 months of follow up. Presence of daily headache predicted poorer response but there was still a significant positive response rate in this group.

Outcomes That Matter to Adolescents With Continuous Headache Due to Chronic Migraine and Their Parents: A Pilot Survey Study.

Children and adolescents with chronic migraine who have continuous headache may have high levels of headache-related disability but have largely been excluded from clinical trials. Understanding patient-valued treatment outcomes may facilitate future study design. The aim of this work was to identify patient-valued outcome measures for headache preventive treatments among adolescents with continuous headache due to chronic migraine and their parents. Adolescents with an International Classification of Headache Disorders, 3rd edition diagnosis of chronic migraine, who had continuous headache and who were being cared for at a tertiary pediatric headache clinic, and their parents were surveyed to query the value of treatment outcomes in the domains of headache frequency, intensity, functional impact, and associated symptoms. Individual outcomes and categories of outcomes were ranked in order of preference using weighted average rank. Results were rounded to the degree of precision with which they were measured. The survey was completed by 55 adolescents and 60 parents of adolescents with continuous headache due to chronic migraine. Mean age of adolescents was 16 (SD 1, range 12-17) years. Median adolescent-reported duration of continuous headache was 24 (interquartile range [IQR] 12-39) months, and adolescents had tried a median of 2 (IQR 0-5) preventive medications, only 13% of which were perceived as helpful. Overall, the most valued individual outcome measure among both adolescents and parents was a decrease in frequency of more severe headaches; however, outcomes reflecting headache intensity were most valued by adolescents, while outcomes reflecting functional impact were most valued by parents. More than 60% of adolescents felt that it was more important to measure decrease in frequency and intensity of headaches in terms of severe headaches/spikes rather than total headache days. Among associated symptoms, improvement in brain fog was most highly valued by both adolescents and parents. The results of this study provide important information about which preventive treatment outcomes are valued by adolescents with continuous headache due to chronic migraine and their parents. Results suggest that adolescents value a decrease in frequency of severe headaches over a decrease in frequency of headache days overall. Generalizability may be limited because the surveyed population was being cared for at a tertiary pediatric headache clinic and generally had headache disorders that were refractory to treatment. These results may help guide future trial design in this population with continuous headache due to chronic migraine.

Long-Term Effects of Self-Administered Transcranial Direct Current Stimulation in Episodic Migraine Prevention: Results of a Randomized Controlled Trial

Migraine is a multifactorial neurovascular disorder, which affects about 12% of the general population. In episodic migraine, the visual cortex revealed abnormal processing, most likely due to decreased preactivation level. Transcranial direct current stimulation (tDCS) is able to modify cortical excitability and might result in an alleviation of migraine occurrence if used repetitively. To test the hypothesis that self-administered anodal tDCS over the visual cortex significantly decreases the number of monthly migraine days in episodic migraine. The study was single-blind, randomized, and sham-controlled. Inclusion criteria were age 18-80 years and an ICHD-3 diagnosis of episodic migraine. Exclusion criteria were pregnancy, presence of a neurodegenerative disorder, a contraindication against MRI examinations, and less than two migraine days during the 28-day baseline period. Patients in whom the baseline period suggested chronic migraine were excluded. After baseline, participants applied daily either verum (anodal-1mA to 20 min) or sham tDCS (anodal-1mA to 30 sec) at Oz (reference Cz electrode) for 28 days. Headache diaries were used to record the number of migraine days at baseline, during the stimulation period, and during four subsequent 28-day periods. Twenty-eight patients were included; two were excluded after the baseline period because less than two migraine days occurred; three were excluded because their headache diaries suggested the diagnosis of chronic migraine. Twenty-three datasets were taken for further analysis. Compared to sham tDCS (n=12), verum tDCS (n=11) resulted in a lower number of migraine days (p=0.010) across all follow-up periods. We found no significant change in total headache days (p=0.165), anxiety (p=0.884), or depression scores (p=0.535). No serious adverse events occurred; minor side effects were similar in both groups. This study provides Class II evidence that self-administered anodal tDCS over the visual cortex in episodic migraine results in a significantly lower number of monthly migraine days. However, it has neither an immediate nor a long-term effect.

Cognitive effects of onabotulinumtoxinA in chronic migraine

BackgroundChronic migraine is a disabling condition, often associated with comorbidities including cognitive dysfunction, anxiety and depression. It is unclear whether cognitive complaints are associated with the underlying migraine pathophysiological process...

Response Predictors in Chronic Migraine: Medication Overuse and Depressive Symptoms Negatively Impact Onabotulinumtoxin-A Treatment.

Background: Despite numerous studies that have investigated clinical, radiological, and biochemical response predictors, the clinical profile of those patients who might benefit from OnabotulinumtoxinA is still missing. The aim of the present study was to identify potential OnabotulinumtoxinA response predictors among several clinical characteristics and confirm OnabotulinumtoxinA efficacy and safety in chronic migraine (CM) prevention.Methods: The study was conducted at the Headache Center—Neurology Clinic—Spedali Civili Hospital of Brescia. Eighty-four consecutive CM patients were enrolled, with a mean age of 48 years (SD 9.7) and a mean disease duration of 10.1 years (SD 6.6). The mean reported headache-days frequency was 22.5 (SD 5.9) per month, while the mean number of severe headache-days was 15.2 (SD 8.9) with a mean monthly medication intake of 33.2 (SD 5.6). The clinical characteristics analyzed as potential response predictors were: gender, disease duration, migraine characteristics (location, side constancy, unilateral autonomic and neurovegetative symptoms), previous prophylactic treatments, add-on therapies, withdrawal therapies, psychiatric (anxiety and depression symptoms) comorbidities and medication overuse.Results: A significant reduction from baseline to 3, 6, 9, and 12 month treatment cycles in total headache days, high intensity headache days and triptans consumption per month was found. Depressive symptoms and medication overuse negatively predicted OnabotulinumtoxinA outcome.Conclusions: Our results confirm the efficacy and safety of OnabotulinumtoxinA in CM. Depressive comorbidity and medication overuse, among all clinical variables, were the only significant response predictors. Such findings provide interesting insights regarding patients selection for OnabotulinumtoxinA treatment as, with the introduction of anti calcitonin gene-related (CGRP) monoclonal antibodies, clinicians will have to thoroughly judge and tailor among the many available therapeutic options now available. Future research might be needed to confirm our findings, in particular for its therapeutic implications.

Neurophysiological correlates of clinical improvement after greater occipital nerve (GON) block in chronic migraine: relevance for chronic migraine pathophysiology

BackgroundTherapeutic management of Chronic Migraine (CM), often associated with Medication Overuse Headache (MOH), is chiefly empirical, as no biomarker predicting or correlating with clinical efficacy is available to address therapeutic choices. The present study searched for neurophysiological correlates of Greater Occipital Nerve Block (GON-B) effects in CM.MethodsWe recruited 17 CM women, of whom 12 with MOH, and 19 healthy volunteers (HV). Patients had no preventive treatment since at least 3 months. After a 30-day baseline, they received a bilateral betamethasone-lidocaine GON-B of which the therapeutic effect was assessed 1 month later. Habituation of visual evoked potentials (VEP) and intensity dependence of auditory evoked potentials (IDAP) were recorded before and 1 week after the GON-B.ResultsAt baseline, CM patients had a VEP habituation not different from HV, but a steeper IDAP value than HV (p = 0.01), suggestive of a lower serotonergic tone. GON-B significantly reduced the number of total headache days per month (− 34.9%; p = 0.003). Eight out 17CM patients reversed to episodic migraine and medication overuse resolved in 11 out of 12 patients. One week after the GON-B VEP habituation became lacking respect to baseline (p = 0.01) and to that of HV (p = 0.02) like in episodic migraine, while the IDAP slope significantly flattened (p < 0.0001). GON-B-induced reduction in headache days positively correlated with IDAP slope decrease (rho = 0.51, p = 0.03).ConclusionsGON-B may be effective in the treatment of CM, with or without MOH. The pre-treatment IDAP increase is compatible with a weak central serotonergic tone, which is strengthened after GON-B, suggesting that serotonergic mechanisms may play a role in CM and its reversion to episodic migraine. Since the degree of post-treatment IDAP decrease is correlated with clinical improvement, IDAP might be potentially useful as an early predictor of GON-B efficacy.

A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study).

ObjectiveTo evaluate the efficacy and tolerability of single pulse transcranial magnetic stimulation (sTMS) for the preventive treatment of migraine.BackgroundsTMS was originally developed for the acute treatment of migraine with aura. Open label experience has suggested a preventive benefit. The objective of this trial was to evaluate the efficacy and tolerability of sTMS for migraine prevention.MethodsThe eNeura SpringTMS Post-Market Observational U.S. Study of Migraine (ESPOUSE) Study was a multicenter, prospective, open label, observational study. From December 2014 to March 2016, patients with migraine (n = 263) were consented to complete a 1-month baseline headache diary followed by 3 months of treatment. The treatment protocol consisted of preventive (four pulses twice daily) and acute (three pulses repeated up to three times for each attack) treatment. Patients reported daily headache status, medication use, and device use with a monthly headache diary. The primary endpoint, mean reduction of headache days compared to baseline, was measured over the 28-day period during weeks 9 to 12. The primary endpoint was compared to a statistically-derived placebo estimate (performance goal). Secondary endpoints included: 50% responder rate, acute headache medication consumption, HIT-6, and mean reduction in total headache days from baseline of any intensity.ResultsOf a total of 263 consented subjects, 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set. For the primary endpoint, there was a −2.75 ± 0.40 mean reduction of headache days from baseline (9.06 days) compared to the performance goal (−0.63 days) (p < 0.0001). The 50% responder rate of 46% (95% CI 37%, 56%) was also significantly higher (p < 0.0001) than the performance goal (20%). There was a reduction of −2.93 (5.24) days of acute medication use, headache impact measured by HIT-6, −3.1 (6.4) (p < 0.0001), and total headache days of any intensity −3.16 days (5.21) compared to the performance goal (−0.63 days) (p < 0.0001). The most common adverse events were lightheadedness (3.7%), tingling (3.2%), and tinnitus (3.2%). There were no serious adverse events.ConclusionsThis open label study suggests that sTMS may be an effective, well-tolerated treatment option for migraine prevention.Trial registration numberNCT02357381

Migraine patients exhibit an imbalance between feedback and feedforward visual signalling.

Event Abstract Back to Event Migraine patients exhibit an imbalance between feedback and feedforward visual signalling. Marco Lisicki1, 2*, Kevin D'Ostilio1, 2, Gianluca Coppola3, Alain Maertens De Noordhout1, 2, Vincenzo Parisi3, Jean Schoenen1, 2 and Delphine Magis1 1 Headache Research Unit. CHU de Liège, Belgium 2 University of Liège, Belgium 3 Fondazione G.B. Bietti (IRCCS), Italy Introduction The aim of this study was to investigate visually induced alpha/beta (feedback) and gamma (feedforward) power in episodic migraine without aura patients during or outside of an attack, and to compare the results to those of chronic migraine patients and healthy volunteers. Materials and Methods The study involved 20 healthy volunteers (mean age: 36.1 ± 11.4 years), 30 episodic migraine without aura patients recorded during a headache free interval (±72 hours) (mean age: 33.3 ± 11.9 years), 20 episodic migraine without aura patients recorded during a migraine attack (mean age: 32.7 ± 9.1 years), and 20 chronic migraine patients (mean age: 40.3 ± 12.7 years). Pattern reversal (3.1 reversals/second, 68’ squares) Visual Evoked Potentials (VEP) recordings were performed in the electrophysiology laboratory of the Headache Research Unit (Neurology Department, Centre Hospitalier Régional de la Citadelle, Liège, Belgium). Six hundred trials, each lasting 250ms, were continuously registered. After DC subtraction, epochs were band-pass filtered between 1 and 100 Hz. Artiefacted epochs were rejected (<6%). The Fast Fourier Transform was applied on each epoch to compute spectral decomposition. Log-transform of single-trial spectral power was performed before averaging. To estimate power, the area under the curve of activity at the peak and nearby surrounding frequencies (4 to 16 Hz for alpha/beta - feedback and 40 to 60 Hz for gamma - feedforward) was calculated for each individual. Fully automated electrophysiological analyses were performed using EEGLAB running in MATLAB (The MathWorks Inc.). Statistical analyses and graphs were performed in Prism version 6.00 for Windows (GraphPad Software, La Jolla, California, USA). The significance level for all tests was set at p<0.05. Results Mean number of monthly migraine days and total headache days were 5.5 ± 3.5 / 7.3 ± 4.1 for headache free episodic migraine patients, 5.9 ± 3.6 / 8.6 ± 6.6 for episodic migraine patients in the ictal period, and 15.8 ± 6.4 / 23.9 ± 5.7 for chronic migraineurs. Mean alpha/beta power was significantly higher in headache free episodic migraine patients compared to healthy volunteers. Conversely, gamma power was higher in ictal episodic migraine patients as well as in chronic migrainerus. A significant decrease in the feedback/feedforward (alpha/beta-to-gamma) ratio was found in both the ictal and chronic migraine groups with respect to the headache free group. This ratio was negatively correlated with the number of total monthly headache days (r= -0,33; p= 0,02). However, when considering only migraine-specific days, the same correlation did not reach statistical significance (r=-0,2496; p=0,08). Discussion Prior evidence has shown that feedforward volleys upcoming from visual afferents induce oscillations in the primary visual cortex in the gamma range. Conversely, feedback activity arriving from higher order visual areas (i.e. V2-V4) induces oscillatory activity within the alpha/beta frequency bands.(1,2) Our results show that, while an increased feedback activity (alpha/beta power) characterizes the visual responses of episodic migraine patients when they are headache free, elevated feedforward activity (gamma power) is the main feature found in patients during the ictal period and in chronic migraineurs. Given their physiological properties, a possible interpretation of our finding of increased visually induced alpha/beta-to-gamma ratio in headache free migraine patients is that feedback activity limits feedforward volleys during the inter-ictal period; a restraining feature that is lost during migraine attacks. Figure 1

The Impact of the Endovascular Treatment of Cerebral Aneurysms on Headaches.

The co-occurrence of headaches and cerebral aneurysms is common in clinical practice, although a clear causal relationship has not been ascertained. We aimed to investigate the impact of endovascular obliteration of aneurysms on headaches using a cross-sectional, prospective, open-label protocol. We also sought to characterize the preexisting headaches in patients harboring cerebral aneurysms using the International Classification of Headache Disorders criteria. A total of 33 patients were recruited into the study and underwent endovascular treatment for obliteration of their aneurysms. A standardized survey was administered before and 3 to 6 months after the procedure, documenting the HIT-6 scores as well as the headache frequency. The study cohort included 25 women and 8 men. In 61% of cases, the aneurysms were located in the posterior circulation. We achieved grade 0 or 1 obliteration of aneurysms in 100% of cases and there were no complications. The mean for HIT-6 scores were 52.3 at baseline and 49.6 postprocedure (student t test, P<0.047). The headache frequency measured as total headache days per month did not demonstrate statistical significance. Our data indicated that more than half of our cohort had preexisting headaches which fulfilled the criteria for a primary headache disorder. These individuals showed a more robust response to the intervention compared with the remainder of the group, although the P-value per se was not considered statistically significant due to the small sample size. Endovascular treatment of the aneurysms mitigates the headache-related disability.

Flunarizine versus topiramate for chronic migraine prophylaxis: a randomized trial.

Chronic migraine (CM) is a prevalent and devastating disorder with limited therapeutic options. This study explored the efficacy of 10mg/d flunarizine for CM prophylaxis as compared with 50mg/d topiramate. We conducted a prospective, randomized, open-label, blinded-endpoint trial. Patients with CM were randomized to flunarizine and topiramate treatment. The primary outcomes assessed were the reductions in the total numbers of headache days and migraine days after 8weeks of treatment. Secondary outcomes were reductions in the numbers of days of acute abortive medication intake and acute abortive medication tablets taken, and the 50% responder rate. Sixty-two subjects were randomized (n=31/group). Patients treated with flunarizine showed significant reductions in the numbers of total headache days (-4.9 vs -2.3, P=.012) and migraine days (-4.3 vs -1.4, P=.001) compared with those treated with topiramate. Patients treated with flunarizine also showed significant reductions in the numbers of days of acute abortive medication intake (-2.3 vs -0.2, P=.005) and acute abortive medication tablets taken (-4.6 vs -0.5, P=.005) and had a higher 50% responder rate in terms of total headache days (58.6% vs 25.9%, P=.013) and migraine days (75.9% vs 29.6%, P=.001), compared with topiramate-treated patients. Flunarizine was generally well tolerated and had a safety profile comparable to that of topiramate. Our results suggest that, in an 8-week study, 10mg/d flunarizine is more effective than 50mg/d topiramate for CM prophylaxis.

Efficacy of continuous theta burst stimulation of the primary motor cortex in reducing migraine frequency: A preliminary open-label study

BackgroundTheta burst stimulation is a type of pattern-specific repetitive transcranial magnetic stimulation that requires less stimulation time and lower intensity to induce long-lasting effects comparable to those of other repetitive transcranial magnetic stimulation protocols. This pilot study investigated whether continuous theta burst stimulation (cTBS) on the primary motor cortex reduced headache frequency in patients with migraine. MethodsNine patients with migraine were recruited into our study. All patients received 20 cTBS sessions (bursts of 3 50-Hz TMS pulses at 200-ms intervals for 40 seconds), administered every weekday for 4 consecutive weeks. All patients kept headache diaries for 4 weeks before stimulation (baseline; T1), during stimulation (T2), and 4 weeks after stimulation (T3). The primary outcome measures were the changes of total headache and migraine days from baseline (Wilcoxon signed-rank test; T2 and T3 vs. T1). ResultsThe number of total headache days was reduced at T2 and T3 compared with T1 [9.4 ± 6.2 days (p = 0.024) and 8.7 ± 10.1 days (p = 0.012) vs. 13.4 ± 10.1 days]. The number of migraine days was also reduced at T2 and T3 compared with T1 [2.9 ± 2.7 days (p = 0.021) and 1.0 ± 1.6 days (p = 0.008) vs. 8.6 ± 8.7 days]. ConclusionOur results indicate that cTBS on the primary motor cortex might reduce the number of total headache and migraine days in patients with migraine. However, large-scale randomized controlled trials are necessary to further validate the findings.

Transcutaneous Supraorbital Nerve Stimulation (t-SNS) with the Cefaly® Device for Migraine Prevention: A Review of the Available Data.

So far, among the different non-invasive neurostimulation methods, only transcutaneous supraorbital nerve stimulation (t-SNS) with the Cefaly® (Cefaly Technology sprl, Herstal, Belgium) device has randomized controlled trial-based evidence for safety and efficacy and obtained American Food and Drug Administration approval for the prevention of episodic migraine. In a double-blinded, randomized, sham-controlled trial on 67 episodic migraine patients (mean pre-treatment migraine days/month: 6.9), the 50% responder rate after 3 months was significantly higher in the active group (38.2%) than in the sham group (12.1%); attack frequency and total headache days were also significantly reduced, but not headache severity. Acute anti-migraine drug intake was reduced by 36.7% in the active group. Statistical sub-analysis suggested that t-SNS was more effective in patients with a higher attack frequency. In a large survey on 2313 Cefaly users about safety and satisfaction only 4.3% of subjects reported side effects, all of which were minor and fully reversible, the most frequent being intolerance to the paresthesia feeling and the most severe an allergic skin reaction to the electrode gel. The efficacy/safety ratio of the Cefaly device was therefore most favorable, especially when compared to preventive anti-migraine drugs. The therapeutic efficacy of t-SNS with Cefaly with low-frequency migraine (≤5 attacks/month) was recently confirmed in an open randomized trial. No published data are available in chronic migraine. According to preliminary results of a fluorodeoxyglucose-positron emission tomography study, Cefaly might exert its effect in migraine by increasing activity in crucial areas of the limbic system and salience matrix such as orbitofrontal and anterior cingulate cortices.Electronic supplementary materialThe online version of this article (doi:10.1007/s40122-015-0039-5) contains supplementary material, which is available to authorized users.

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

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. 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. 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. 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 > or =25% reduction: 68.6% vs 51.6% (P = .005); > or =50%: 37.3% vs 28.8% (P = .093); and > or =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). 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.

Topiramate versus amitriptyline in migraine prevention: A 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority trial in adult migraineurs

Objective: The primary objective of this study was to compare the efficacy and tolerability of topiramate and amitriptyline in the prophylaxis of episodic migraine headache. Methods: This was a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority study. Adults with 3 to 12 migraines per month were randomized in a 1:1 ratio to receive an initial dose of 25 mg/d of either topiramate or amitriptyline, subsequently titrated to a maximum of 100 mg/d (or the maximum tolerated dose). The primary efficacy outcome was the change from prospective baseline in the mean monthly number of migraine episodes. Secondary efficacy variables included changes from the prospective baseline phase to the end of the double-blind phase in the mean monthly (28-day) rate of days with migraine, mean monthly rate of days with headache (migraine and nonmigraine), mean monthly rate of acute abortive medication use, mean monthly migraine duration, and mean monthly migraine severity. Additional secondary efficacy variables included changes in the mean monthly severity of migraine-associated symptoms (photophobia, phonophobia, and nausea), change in the mean monthly frequency f migraine-associated vomiting, and response rates (based on monthly migraine days and total headache days). The Migraine-Specific Quality of Life Questionnaire (MSQ) and the Weight Satisfaction Scale Questionnaire, which measures subjective satisfaction with current weight, were administered. Treatment-emergent adverse events (TEAEs) were monitored through the end of double-blind treatment. Results: The intent-to-treat population included 331 subjects (172 topiramate, 159 amitriptyline; 84.9% female; 84.6% white; mean [SD] age, 38.8 [11.0] years; mean weight, 77.1 [20.1] kg) who provided at least 1 efficacy assessment. The least squares mean (LSM) change from baseline in the mean monthly number of migraine episodes was not significantly different between the topiramate and amitriptyline groups (-2.6 and -2.7, respectively; 95% CI, -0.6 to 0.7). There were no significant differences between treatment groups in any of the prespecified secondary outcome measures. Subjects receiving topiramate had a significantly greater improvement in mean functional disability scores during migraine attacks compared with amitriptyline (LSM change: -0.33 vs -0.19; 95% CI, -0.3 to 0.0; P = 0.040) and in the role function-restrictive, role function-preventive, and emotional function domains of the MSQ ( P = 0.012, P = 0.014, and P = 0.029, respectively). Subjects receiving topiramate had a mean weight loss of 2.4 kg, compared with a mean weight gain of 2.4 kg in subjects receiving amitriptyline. Subjects in the topiramate group reported an overall improvement from baseline in weight satisfaction, whereas the amitriptyline group reported an overall deterioration in weight satisfaction ( P < 0.001, topiramate vs amitriptyline). TEAEs of mild or moderate severity were reported in 118 subjects (66.7%) in the topiramate group and 112 subjects (66.3%) in the amitriptyline group. Among the most common TEAEs (reported in ±5% of subjects during the double-blind phase) in the topiramate group were paresthesia (29.9%), fatigue (16.9%), somnolence (11.9%), hypoesthesia (10.7%), and nausea (10.2%). The most commonly reported TEAEs in the amitriptyline group were dry mouth (35.5%), fatigue (24.3%), somnolence (17.8%), weight increase (13.6%), dizziness (10.7%), and sinusitis (10.7%). Conclusions: In this noninferiority study, topiramate was at least as effective as amitriptyline in terms of reducing the rate of mean monthly migraine episodes and all prespecified secondary efficacy end points. Topiramate was associated with improvement in some quality-of-life indicators compared with amitriptyline and was associated with weight loss and improved weight satisfaction.

Botulinum Toxin Type A in the Treatment of Chronic Migraine Without Medication Overuse

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. Double-blind placebo-controlled randomized trial of Botulinum Toxin Type A 100 units administered in a fixed dose and site paradigm. In total, 86 patients were enrolled. A total of 60 patients were randomized and 41 patients were treated with the study medication or placebo. Five patients failed to complete the study, which lasted 4 months after the study medication was injected. Botulinum Toxin Type A was statistically superior to placebo for the primary endpoint of reduction in migraine headache episodes. Six patients on Botulinum Toxin Type A compared with 3 patients on Placebo had at least a 50% reduction in their migraine episodes. Active treatment was superior to placebo for the secondary endpoints of total headache days, headache index, and quality of life measures. It showed numerical superiority to placebo for acute medication use and Migraine Disability Assessment Scores. Adverse events were rare and similar in both treatment groups. The use of Botulinum Toxin Type A may be an effective treatment for chronic migraine when the patient does not have concomitant medication overuse. It was well tolerated in this trial.

Fear Assessment: Cost-Benefit Analysis and the Pricing of Fear and Anxiety

Fear Assessment: Cost-Benefit Analysis and the Pricing of Fear and Anxiety