topiramate and Migraine-Disorders

This systematic review focuses on chronic migraine patients with medication overuse headache using, respectively, topiramate, botulinum toxin type A, and human monoclonal antibodies targeting calcitonin gene-related peptide or its receptor.. A systematic search was conducted in the databases CENTRAL, MEDLINE, Embase and Web of Science until May 2022. We included randomized controlled trials reporting the outcomes of change in monthly headache/migraine days, ≥50% response rates and change in medication overuse status. Studies were excluded if response rates were not reported. Risk of bias assessment was performed using the Cochrane RoB2 tool. The quality of evidence for outcomes across included studies was evaluated according to the five factors outlined in Cochrane GRADE approach.. The initial search resulted in 1599 records. Following screening, 10 studies met our inclusion criteria, while seven studies with sufficient data were included in the meta-analysis. Studies assessing Botulinum toxin type A included 1139 patients and showed a mean reduction in headache frequency by 1.92 days per month compared to placebo (-1.92; 95% CI -2.68 to -1.16). Studies assessing human monoclonal antibodies included 1982 patients, and showed significant positive effect compared to placebo for all measured outcomes. The overall odds ratio for the ≥50% response rate was 2.90 (95% CI, 2.23 to 3.78). No significant difference was observed in the frequency of adverse effect for both Botulinum toxin type A and low dose of human monoclonal antibodies compared to placebo. There is currently insufficient evidence to determine the impact of topiramate in chronic migraine patients with medication overuse headache.. Botulinum toxin type A and human monoclonal antibodies targeting calcitonin gene-related peptide receptor were beneficial in reducing monthly migraine days and ≥50% response rate, but uncertainties remained for Botulinum toxin type A regarding response rate. The effect size for human monoclonal antibodies was greater with relatively lower drop-out rate. High-quality randomized trials are required to evaluate the effect of topiramate in chronic migraine patients with medication overuse headache.

Topics: Antibodies, Monoclonal; Botulinum Toxins, Type A; Calcitonin Gene-Related Peptide; Headache; Headache Disorders, Secondary; Humans; Migraine Disorders; Topiramate

While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative safety and efficacy of these drugs. We conducted a systematic review and network meta-analysis to facilitate comparison between drugs for migraine prophylaxis.. We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to August 13, 2022, for randomized trials of pharmacological treatments for migraine prophylaxis in adults. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist random-effects network meta-analysis and rated the certainty (quality) of evidence as either high, moderate, low, or very low using the GRADE approach.. We identified 74 eligible trials, reporting on 32,990 patients. We found high certainty evidence that monoclonal antibodies acting on the calcitonin gene related peptide or its receptor (CGRP(r)mAbs), gepants, and topiramate increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo. We found moderate certainty evidence that beta-blockers, valproate, and amitriptyline increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, and low certainty evidence that gabapentin may not be different from placebo. We found high certainty evidence that, compared to placebo, valproate and amitriptyline lead to substantial adverse events leading to discontinuation, moderate certainty evidence that topiramate, beta-blockers, and gabapentin increase adverse events leading to discontinuation, and moderate to high certainty evidence that (CGRP(r)mAbs) and gepants do not increase adverse events.. (CGRP(r)mAbs) have the best safety and efficacy profile of all drugs for migraine prophylaxis, followed closely by gepants.

Topics: Adult; Amitriptyline; Antibodies, Monoclonal; Calcitonin Gene-Related Peptide; Gabapentin; Humans; Migraine Disorders; Network Meta-Analysis; Topiramate; Valproic Acid

Due to the diverse mechanisms of action of antiseizure drugs, there has been a rise in prescriptions of these drugs for non-epileptic pathologies. One drug that is now being used for a variety of conditions is topiramate. This is a narrative review that used PubMed, Google Scholar, MEDLINE, and ScienceDirect to review literature on the clinical and pharmacologic properties of topiramate. Topiramate is a commonly prescribed second-generation antiseizure drug. The drug works through multiple pathways to prevent seizures. In this regard, topiramate blocks sodium and calcium voltage-gated channels, inhibits glutamate receptors, enhances gamma-aminobutyric acid (GABA) receptors, and inhibits carbonic anhydrase. Topiramate is approved by the Food and Drug Administration (FDA) for epilepsy treatment and migraine prophylaxis. Topiramate in combination with phentermine is also FDA-approved for weight loss in patients with a body mass index (BMI) > 30. The current target dosing for topiramate monotherapy is 400 mg/day and 100 mg/day to treat epilepsy and migraines, respectively. Commonly reported side effects include paresthesia, confusion, fatigue, dizziness, and change in taste. More uncommon and serious adverse effects can include acute glaucoma, metabolic acidosis, nephrolithiasis, hepatotoxicity, and teratogenicity. Related to a broad side effect profile, physicians prescribing this drug should routinely monitor for side effects and/or toxicity. The present investigation reviews various anti-seizure medications before summarizing indications of topiramate, off-label uses, pharmacodynamics, pharmacokinetics, adverse effects, and drug-drug interactions.

Topics: Anticonvulsants; Epilepsy; Fructose; Humans; Migraine Disorders; Topiramate

Although the association between CGRP and migraine disease is well-known and studied, therapies can target other pathways to minimize migraine symptoms. It is important to understand the role of these medications as options for migraine treatment and the varied mechanisms by which symptoms can be addressed. In the present investigation, the role of non-CGRP antagonist/non-triptan options for migraine disease therapy is reviewed, including NSAIDs, ß-blockers, calcium channel blockers, antidepressants, and antiepileptics. Pharmacologic therapies for both acute symptoms and prophylaxis are evaluated, and their adverse effects are compared.. At present, the Food and Drug Association has approved the beta-blockers propranolol and timolol and the anti-epileptic drugs topiramate and divalproex sodium for migraine prevention. Clinicians have other options for evidence-based treatment of episodic migraine attacks. Treatment decisions should consider contraindications, the effectiveness of alternatives, and potential side effects. NSAIDs are effective for the acute treatment of migraine exacerbations with caution for adverse effects such as gastrointestinal upset and renal symptoms. Beta-blockers are effective for migraine attack prophylaxis but are associated with dizziness and fatigue and are contraindicated in patients with certain co-morbidities, including asthma, congestive heart failure, and abnormal cardiac rhythms. Calcium channel blockers do not show enough evidence to be recommended as migraine attack prophylactic therapy. The anti-epileptic drugs topiramate and divalproex sodium and antidepressants venlafaxine and amitriptyline are effective for migraine exacerbation prophylaxis but have associated side effects. The decision for pharmacologic management should ultimately be made following consideration of risk vs. benefit and discussion between patient and physician.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Calcium Channel Blockers; Drug-Related Side Effects and Adverse Reactions; Humans; Migraine Disorders; Propranolol; Serotonin 5-HT1 Receptor Agonists; Topiramate; Tryptamines; Valproic Acid

Topiramate is a repurposed first-line treatment for migraine prophylaxis. The aim of this systematic review and meta-analysis is to critically re-appraise the existing evidence supporting the efficacy and tolerability of topiramate.. A systematic search in MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov was performed for trials of pharmacological treatment in migraine prophylaxis as of August 13, 2022, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Randomized controlled trials in adult patients that used topiramate for the prophylactic treatment of migraine, with placebo as active comparator, were included. Two reviewers independently screened the retrieved studies and extracted all data. Outcomes of interest were the 50% responder rates, the reduction in monthly migraine days, and adverse events leading to treatment discontinuation. Results were pooled and meta-analyzed, with sensitivity analysis based on the risk of bias of the studies, the monthly migraine days at baseline, and the previous use of other prophylactic treatments. Certainty evidence was judged according to the GRADE framework.. Eight out of 10,826 studies fulfilled the inclusion/exclusion criteria, accounting for 2,610 randomized patients. Six studies included patients with episodic migraine and two with chronic migraine. Topiramate dose ranged from 50 to 200 mg/day, and all studies included a placebo arm. There was a high certainty that topiramate: 1) increased the proportion of patients who achieved a 50% responder rate in monthly migraine days, compared to placebo [relative risk: 1.61 (95% confidence interval (CI): 1.29-2.01); absolute risk difference: 168 more per 1,000 (95% CI: 80 to 278 more)]; 2) was associated with 0.99 (95% CI: 1.41-0.58) fewer migraine days than placebo; 3) and had a higher proportion of patients with adverse events leading to treatment discontinuation [absolute risk difference 80 patients more per 1,000 (95% CI: 20 to 140 more patients)].. There is high-quality evidence of the efficacy of topiramate in the prophylaxis of migraine, albeit its use poses a risk of adverse events that may lead to treatment discontinuation, with a negative effect on patient satisfaction and adherence to care.

Topics: Adult; Headache; Humans; Migraine Disorders; Patient Satisfaction; Topiramate; Transcription Factors

Migraine is the world's second most common disabling disorder, affecting 15% of UK adults and costing the UK over £1.5 billion per year. Several costly new drugs have been approved by National Institute for Health and Care Excellence.. To assess the cost-effectiveness of drugs used to treat adults with chronic migraine.. We did a systematic review of placebo-controlled trials of preventive drugs for chronic migraine. We then assessed the cost-effectiveness of the currently prescribable drugs included in the review: Onabotulinum toxin A (BTA), Eptinezumab (100mg or 300mg), Fremanezumab (monthly or quarterly dose), Galcanezumab or Topiramate, each compared to placebo, and we evaluated them jointly. We developed a Markov (state-transition) model with a three-month cycle length to estimate the costs and quality-adjusted life years (QALYs) for the different medications from a UK NHS and Personal Social Services perspective. We used a two-year time horizon with a starting age of 30 years for the patient cohort. We estimated transition probabilities based on monthly headache days using a network meta-analysis (NMA) developed by us, and from published literature. We obtained costs from published sources and applied discount rates of 3.5% to both costs and outcomes.. Deterministic results suggest Topiramate was the least costly option and generated slightly more QALYs than the placebo, whereas Eptinezumab 300mg was the more costly option and generated the most QALYs. After excluding dominated options, the incremental cost-effectiveness ratio (ICER) between BTA and Topiramate was £68,000 per QALY gained and the ICER between Eptinezumab 300mg and BTA was not within plausible cost-effectiveness thresholds. The cost-effectiveness acceptability frontier showed that Topiramate is the most cost-effective medication for any amount the decision maker is willing-to-pay per QALY.. Among the various prophylactic medications for managing chronic migraine, only Topiramate was within typical cost-effectiveness threshold ranges. Further research is needed, ideally an economic evaluation alongside a randomised trial, to compare these newer, expensive CGRP MAbs with the cheaper oral medications.

Topics: Adult; Cost-Benefit Analysis; Decision Making; Headache; Humans; Migraine Disorders; Quality-Adjusted Life Years; Topiramate

Chronic migraine can be a profoundly disabling disorder that may be treated with preventive medications. However, uncertainty remains as to which preventive medication is the most effective. We present a network meta-analysis to determine the effectiveness and rank of preventive drugs for chronic migraine in adults.. We identified, reviewed, and extracted data from randomised controlled trials (RCTs) of preventive drugs for chronic migraine with at least 200 participants. Data were analysed using network meta-analysis.. We included 12 RCTs of six medications (Eptinezumab, Erenumab, Fremanezumab, Galcanezumab, Onabotulinumtoxin A, and Topiramate) compared to placebo or each other. All drugs effectively reduced monthly headache and migraine days compared with placebo. The most effective drug for monthly headache days was Eptinezumab 300mg, with a mean difference of -2.46 days, 95% Credible Interval (CrI): -3.23 to -1.69. On the Surface Under the Cumulative Ranking Area (SUCRA) analysis, the probability that Eptinezumab 300mg was ranked highest was 0.82. For monthly migraine days, the most effective medication was Fremanezumab-monthly, with a mean difference: -2.77 days, 95% CrI: -3.36 to -2.17, and 0.98 probability of being ranked the highest. All included drugs, except Topiramate, improved headache-related quality of life. No eligible studies were identified for the other common preventive oral medications such as Amitriptyline, Candesartan, and Propranolol. The main reasons were that the studies did not define chronic migraine, were undertaken before the definition of chronic migraine, or were too small.. All six medications were more effective than the placebo on monthly headache and migraine days. The absolute differences in the number of headache/migraine days are, at best, modest. No evidence was found to determine the relative effectiveness of the six included drugs with other oral preventive medications.. PROSPERO (number CRD42021265990).

Topics: Adult; Double-Blind Method; Headache; Humans; Migraine Disorders; Network Meta-Analysis; Topiramate; Treatment Outcome

This review provides an update on sex differences in chronic migraine (CM), with a focus on clinical characteristics, pathophysiology, and treatments.. Approximately 6.8-7.8% of all migraineurs have CM, with an estimated prevalence of 1.4-2.2% in the general population. The economic burden caused by CM, including medical costs and lost working ability, is threefold higher than that caused by episodic migraine (EM). Notably, the prevalence of migraine is affected by age and sex. Female migraineurs with CM experience higher levels of headache-related disability, including longer headache duration, higher frequency of attacks, and more severely impacted efficiency at work. Sex hormones, including estrogen, testosterone, and progesterone, contribute to the sexually dimorphic characteristics and prevalence of migraine in men and women. Recent neuroimaging studies have indicated that migraine may have a greater impact and cause greater dysfunction in the organization of resting-state functional networks in women. Accumulating evidence suggests that topiramate, Onabotulinumtoxin A and calcitonin gene-related peptide (CGRP) monoclonal antibodies are effective as the preventative treatments for CM. Recent evidence highlights a divergence in the characteristics of CM between male and female populations. The data comparing the treatment response for CM regarding sex are lacking.

Topics: Calcitonin Gene-Related Peptide; Female; Headache; Humans; Male; Migraine Disorders; Sex Characteristics; Topiramate

Topiramate-induced acute angle closure (TiAAC) is a potentially vision-threatening side effect of topiramate (TPM) use. The purpose of this article is to review demographic characteristics, clinical features, and management options of TiAAC. A systematic literature search of all reported cases and case series of TiAAC was conducted in the following search engines: PubMed, Web of Science, Google Scholar, Elsevier, and EBSCO. Seventy-three publications describing 77 cases were included. 58 (75.3%) patients were female, and the mean age was 34.88 ± 11.21 years (range, 7-57). The most commonly reported indication of TPM use was migraine headache (59.7%), and the mean duration from starting treatment until the onset of angle closure was 14.1 ± 31.5 days. All cases were managed by immediate cessation of TPM and topical therapy. In addition, systemic medications (carbonic anhydrase inhibitors, hyperosmotic agents, and steroids) were used in 51 patients (66.2%). A laser and/or surgical intervention was performed in 10 patients (13%). After commencement of treatment, the mean duration until the resolution of TiAAC was 3.9 ± 3.6 days (range, 1-18). The findings of our study present a summary of the current body of evidence provided by case reports and case series on TiAAC. In conclusion, the onset of angle closure following TPM use peaks at 2 weeks after initiating treatment, and in most cases, successful management can be achieved by discontinuing TPM and initiating appropriate medical therapy.

Topics: Acute Disease; Adult; Anticonvulsants; Female; Fructose; Glaucoma, Angle-Closure; Humans; Male; Middle Aged; Migraine Disorders; Topiramate; Young Adult

Multiple clinical trials with different exercise protocols have demonstrated efficacy in the management of migraine. However, there is no head-to-head comparison of efficacy between the different exercise interventions.. A systematic review and network meta-analysis was performed involving all clinical trials which determined the efficacy of exercise interventions in reducing the frequency of monthly migraine. Medical journal search engines included Web of Science, PubMed, and Scopus spanning all previous years up to July 30, 2022. Both aerobic and strength/resistance training protocols were included. The mean difference (MD, 95% confidence interval) in monthly migraine frequency from baseline to end-of-intervention between the active and control arms was used as an outcome measure. Efficacy evidence from direct and indirect comparisons was combined by conducting a random effects model network meta-analysis. The efficacy of the three exercise protocols was compared, i.e., moderate-intensity aerobic exercise, high-intensity aerobic exercise, and strength/resistance training. Studies that compared the efficacy of migraine medications (topiramate, amitriptyline) to exercise were included. Additionally, the risk of bias in all included studies was assessed by using the Cochrane Risk of Bias version 2 (RoB2).. There were 21 published clinical trials that involved a total of 1195 migraine patients with a mean age of 35 years and a female-to-male ratio of 6.7. There were 27 pairwise comparisons and 8 indirect comparisons. The rank of the interventions was as follows: strength training (MD = -3.55 [- 6.15, - 0.95]), high-intensity aerobic exercise (-3.13 [-5.28, -0.97]), moderate-intensity aerobic exercise (-2.18 [-3.25, -1.11]), topiramate (-0.98 [-4.16, 2.20]), placebo, amitriptyline (3.82 [- 1.03, 8.68]). The RoB2 assessment showed that 85% of the included studies demonstrated low risk of bias, while 15% indicated high risk of bias for intention-to-treat analysis. Sources of high risk of bias include randomization process and handling of missing outcome data.. Strength training exercise regimens demonstrated the highest efficacy in reducing migraine burden, followed by high-intensity aerobic exercise.

Topics: Adult; Amitriptyline; Exercise; Female; Humans; Male; Migraine Disorders; Network Meta-Analysis; Resistance Training; Topiramate

It is well-known that topiramate as a kind of antiepileptic drug has been proved effective for migraine prevention in North America and Europe. However, topiramate is still viewed as an off-label medication for migraine treatment in China, partly because of the limited evidence in Chinese patients. We summarize the effects of topiramate on the frequency, severity, quality-of-life, and adverse event among migraine patients, including children and adolescent in this review, so as to provide reference for Chinese doctors.

Topics: Adolescent; Anticonvulsants; Child; Fructose; Humans; Migraine Disorders; Quality of Life; Topiramate; Treatment Outcome

Botulinum neurotoxin A (BoNT-A) was the primary choice for preventive treatment of chronic migraine. Topiramate and acupuncture showed promising effect for chronic migraine, but their effectiveness relative to BoNT-A was rarely studied. We aimed to perform a network meta-analysis to compare the effectiveness and acceptability between topiramate, acupuncture, and BoNT-A.. We searched OVID Medline, Embase, the Cochrane register of controlled trials (CENTRAL), the Chinese Clinical Trial Register, and clinicaltrials.gov for randomized controlled trials (RCTs) that compared topiramate, acupuncture, and BoNT-A with any of them or placebo in the preventive treatment of chronic migraine. A network meta-analysis was performed by using a frequentist approach and a random-effects model. The primary outcomes were reduction in monthly headache days and monthly migraine days at week 12. Acceptability was defined as the number of dropouts owing to adverse events.. We included 15 RCTs (n = 2545). Eleven RCTs were at low risk of bias. The network meta-analyses (n = 2061) showed that acupuncture (2061 participants; standardized mean difference [SMD] -1.61, 95% CI: -2.35 to -0.87) and topiramate (582 participants; SMD -0.4, 95% CI: -0.75 to -0.04) ranked the most effective in the reduction of monthly headache days and migraine days, respectively; but they were not significantly superior over BoNT-A. Topiramate caused the most treatment-related adverse events and the highest rate of dropouts owing to adverse events.. Topiramate and acupuncture were not superior over BoNT-A; BoNT-A was still the primary preventive treatment of chronic migraine. Large-scale RCTs with direct comparison of these three treatments are warranted to verified the findings.

Topics: Acupuncture Therapy; Adult; Botulinum Toxins, Type A; Female; Humans; Migraine Disorders; Network Meta-Analysis; Topiramate

Monoclonal antibodies targeting the calcitonin gene-related peptide pathway (anti-CGRP mAbs) have shown promising efficacy in randomised clinical trials for the prevention of episodic and chronic migraine, but no head-to-head comparisons with established treatments are available. We aimed to examine absolute differences in benefit-risk ratios between anti-CGRP mAbs, topiramate and propranolol for the prevention of episodic migraine and between anti-CGRP mAbs, topiramate and onabotulinumtoxinA for the prevention of chronic migraine using a likelihood to help versus harm analysis.. The number of patients needed to be treated for a patient to achieve ≥ 50% reduction in migraine days (NNTB. All agents tested were more likely to be beneficial than harmful (likelihood to help versus harm > 1) with the exception of topiramate at 200 mg per day for the prevention of episodic migraine. Anti-CGRP mAbs in all tested doses had higher LHH values than propranolol or topiramate for episodic migraine and onabotulinumtoxinA or topiramate for chronic migraine prevention. Fremanezumab had the highest LHH ratio in episodic migraine and galcanezumab in chronic migraine.. This analysis showed that anti-CGRP mAbs exhibit a more favourable benefit-risk ratio than established treatments for episodic and chronic migraine. Head-to-head studies are needed to confirm these results.

Topics: Antibodies, Monoclonal; Botulinum Toxins, Type A; Calcitonin Gene-Related Peptide; Humans; Migraine Disorders; Propranolol; Protein Precursors; Topiramate; Treatment Outcome

Relative to migraine generally, chronic migraine (CM) imposes greater disability, healthcare utilization and socioeconomic burden. Six therapies currently possess a credible evidence base for prevention/suppression of CM. This review is intended to provide an assessment of their relative utility, defined as a blend of safety, tolerability and efficacy, focusing in particular on their safety and tolerability.Areas Covered: We discuss all six medications currently FDA-approved for migraine prevention which also specifically possess credible evidence of efficacy in treating CM. While we do address the efficacy of each, our primary emphasis involves assessment of safety and tolerability data derived from clinical trials and post-marketing experience.Expert Opinion: Recent research involving CM has led to the identification of highly targeted and typically well-tolerated therapies. For patients who experience obstacles to accessing these newer therapies, topiramate is available as an evidence-based alternative, but contraindications, drug-drug interactions and poor tolerability may limit or prevent its use. Although data to support such intervention presently is limited, clinically challenging CM cases may benefit from combination therapy. 'Real world' studies are needed to evaluate such polytherapy, along with studies intended to assess the long-term safety of the individual therapies and their use during pregnancy and breast-feeding.

Topics: Chronic Disease; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Migraine Disorders; Topiramate

The approval of monoclonal antibodies for prevention of migraine has revolutionized treatment for patients. Oral preventatives are still considered first line treatments as head-to-head trials comparing them with antibodies are lacking.. The main purpose of this study was to provide a comparative overview of the efficacy of three commonly prescribed migraine preventative medication classes. For this systematic review and meta-analysis, we searched the databases CENTRAL, EMBASE, and MEDLINE until 20 March 2020. We included RCTs reporting the 50% response rates for topiramate, Botulinum Toxin Type A and monoclonal antibodies against CGRP(r). Studies were excluded if response rates were not reported, treatment allocation was unclear, or if study quality was insufficient. Primary outcome measure were the 50% response rates. The pooled odds ratios with 95% confidence intervals were calculated with the random effects model. The study was registered at PROSPERO (CRD42020222880).. We identified 6552 reports. Thirty-two were eligible for our review. Studies assessing monoclonal antibodies included 13,302 patients and yielded pooled odds ratios for the 50% response rate of 2.30 (CI: 2.11-2.50). Topiramate had an overall effect estimate of 2.70 (CI: 1.97-3.69) with 1989 included patients and Botulinum Toxin Type A achieved 1.28 (CI: 0.98-1. 67) with 2472 patients included.. Topiramate, botulinum toxin type A and monoclonal antibodies showed higher odds ratios in achieving a 50% response rate compared to placebo. Topiramate numerically demonstrated the greatest effect size but also the highest drop-out rate.

Topics: Antibodies, Monoclonal; Botulinum Toxins, Type A; Calcitonin Gene-Related Peptide; Humans; Migraine Disorders; Topiramate

Head-to-head comparator trials between first-line oral migraine preventatives and the new monoclonal antibodies (mAbs) blocking the calcitonin gene-related peptide (CGRP) pathway have not been published to date.. This study aimed to indirectly compare the clinical efficacy and safety of mAbs against CGRP or its receptor (CGRPR) and topiramate in episodic migraine prophylaxis using meta-analysis.. We included controlled trials testing efficacy and safety of erenumab, galcanezumab, fremanezumab, eptinezumab, and topiramate in adults diagnosed with episodic migraine. We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from January 2000 to November 2020. We used the Risk of Bias 2 (RoB2) tool to assess the risk of bias and report pooled mean effects (mean difference and risk ratio) as estimated in a random effect model. For efficacy analysis, we determined the reduction of monthly migraine days (MMDs), reduction of days with acute medication (AMDs), and 50% responder rates (50% RR). For safety, we determined adverse events (AEs) occurring in ≥ 2% of study participants and the number of patients who discontinue treatment due to AEs (DAEs). The number needed to treat (NNT) and to harm (NNH) were estimated as well as the likelihood to help or harm (LLH).. We included 13 trials involving 7557 patients: three trials with erenumab, two trials with galcanezumab, two trials with fremanezumab, one trial with eptinezumab, and five trials with topiramate, for the prophylaxis of episodic migraine in adults. The placebo-subtracted reduction (pooled mean difference) of MMDs were - 1.55 (95% CI - 1.86 to - 1.24; active drug n = 3326 vs placebo n = 2219, 8 studies) for the CGRP(R) mAb and - 1.11 (95% CI - 1.62 to - 0.59; active drug n = 1032 vs placebo n = 543, 4 studies) for topiramate (p for subgroup difference = 0.15). 'Cognitive' and 'sensory & pain'-related adverse events occurred more often in patients treated with topiramate compared with those treated with a CGRP(R) mAb (p for subgroup difference 0.03 and < 0.001, respectively). Based on the 50% RR and DAE, the NNT, NNH, and LHH for the CGRP(R) mAbs were 6, 130, and 24.3:1, respectively. For topiramate, these values were 7, 9, and 1.8:1, respectively.. The efficacy of CGRP(R) mAbs to reduce migraine days does not differ from topiramate. However, the safety profile is in favor of the CGRP(R) mAbs, with a higher likelihood to help than to harm compared with topiramate. The diversity of endpoint determination and the heterogeneity between studies for some endpoints cause some limitations for this study.

Topics: Administration, Oral; Adult; Antibodies, Monoclonal; Calcitonin Gene-Related Peptide; Calcitonin Gene-Related Peptide Receptor Antagonists; Humans; Migraine Disorders; Topiramate; Treatment Outcome

Migraine is one of the most common neurologic disorders in children and adolescents. However, a quantitative comparison of multiple preventive pharmacologic treatments in the pediatric population is lacking.. To examine whether prophylactic pharmacologic treatments are more effective than placebo and whether there are differences between drugs regarding efficacy, safety, and acceptability.. Systematic review and network meta-analysis of studies in MEDLINE, Cochrane, Embase, and PsycINFO published through July 2, 2018.. Randomized clinical trials of prophylactic pharmacologic treatments in children and adolescents diagnosed as having episodic migraine were included. Abstract, title, and full-text screening were conducted independently by 4 reviewers.. Data extraction was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis network meta-analysis guidelines. Quality was assessed with the Cochrane Risk of Bias tool. Effect sizes, calculated as standardized mean differences for primary outcomes and risk ratios for discontinuation rates, were assessed in a random-effects model.. Primary outcomes were efficacy (ie, migraine frequency, number of migraine days, number of headache days, headache frequency, or headache index), safety (ie, treatment discontinuation owing to adverse events), and acceptability (ie, treatment discontinuation for any reason).. Twenty-three studies (2217 patients) were eligible for inclusion. Prophylactic pharmacologic treatments included antiepileptics, antidepressants, calcium channel blockers, antihypertensive agents, and food supplements. In the short term (<5 months), propranolol (standard mean difference, 0.60; 95% CI, 0.03-1.17) and topiramate (standard mean difference, 0.59; 95% CI, 0.03-1.15) were significantly more effective than placebo. However, the 95% prediction intervals for these medications contained the null effect. No significant long-term effects for migraine prophylaxis relative to placebo were found for any intervention.. Prophylactic pharmacologic treatments have little evidence supporting efficacy in pediatric migraine. Future research could (1) identify factors associated with individual responses to pharmacologic prophylaxis, (2) analyze fluctuations of migraine attack frequency over time and determine the most clinically relevant length of probable prophylactic treatment, and (3) identify nonpharmacologic targets for migraine prophylaxis.

Topics: Adolescent; Anticonvulsants; Antidepressive Agents; Antihypertensive Agents; Calcium Channel Blockers; Child; Dietary Supplements; Humans; Migraine Disorders; Propranolol; Topiramate; Vasodilator Agents

Migraine is highly prevalent and carries a significant personal, social and economic burden. It is the second cause of disability (years living with disability) worldwide and the first cause under 50 years of age. Chronic migraine (occurring for more than 15 days a month) and refractory migraine (treatment resistant), especially when there is also analgesic overuse, are the most disabling forms of migraine. These three disorders (chronic migraine, refractory migraine and medication overuse headache) are particularly difficult to treat. This article reviews their epidemiology, clinical presentation, diagnostic criteria, risk factors, comorbidities and social and personal impact. The therapeutic options available are discussed and focused on a multidisciplinary approach, non-pharmacological interventions treatment of comorbidities and avoiding analgesic overuse. Prophylactic treatments are mandatory and include the oral prophylactic treatments (topiramate), botulinum toxin type A and the novel monoclonal antibodies against calcitonin gene related peptide or its receptor, which are the first migraine preventive medicines developed specifically to target migraine pathogenesis. In refractory cases, multiple therapies are required including neurostimulation.. A enxaqueca é uma cefaleia muito prevalente na população com importantes custos pessoais, sociais e económicos e é a segunda causa a nível mundial de anos vividos com incapacidade. As suas variantes, crónica (aquela que ocorre mais de 15 dias por mês) e refratária (resistente ao tratamento), sobretudo quando se complicam de uso excessivo de analgésicos, embora mais raras, constituem as formas que causam maior incapacidade. Os autores revêm estes três tipos de cefaleias (enxaqueca refratária, enxaqueca crónica e cefaleia secundária a utilização excessiva de analgésicos) que constituem um grupo de cefaleias de difícil terapêutica. São revistos a epidemiologia, os aspetos clínicos, os critérios de diagnóstico, as comorbilidades, os fatores de agravamento e o impacto destas cefaleias sobre a qualidade de vida dos doentes. O tratamento de cada uma destas entidades é abordado, ressalvando a importância de uma abordagem abrangente, considerando o tratamento das comorbilidades, a utilidade de medidas não farmacológicas, o imperativo de evitar o abuso de analgésicos e a necessidade absoluta de tratamento profilático. São revistos os diferentes tratamentos profiláticos disponíveis (e a evidência científica da sua eficácia), tais como os fármacos preventivos orais (neuromodeladores como o topiramato), a toxina botulínica tipo A e os novos medicamentos preventivos para a enxaqueca (anticorpos monoclonais que atuam sobre o péptido relacionado com o gene da calcitonina ou o seu recetor, e que são os primeiros medicamentos preventivos desenvolvidos especificamente para atuar na fisiopatogenia da enxaqueca. Para os casos refratários são consideradas outras alternativas terapêuticas como a neuroestimulação.

Topics: Antibodies, Monoclonal; Anticonvulsants; Botulinum Toxins, Type A; Chronic Disease; Headache; Headache Disorders, Secondary; Humans; Migraine Disorders; Neuromuscular Agents; Topiramate

Chronic migraine is a disabling condition that is currently underdiagnosed and undertreated. In this narrative review, we discuss the future of chronic migraine management in relation to recent progress in evidence-based pharmacological treatment.. Patients with chronic migraine require prophylactic therapy to reduce the frequency of migraine attacks, but the only currently available evidence-based prophylactic treatment options for chronic migraine are topiramate and onabotulinumtoxinA. Improved prophylactic therapy is needed to reduce the high burden of chronic migraine in Italy. Monoclonal antibodies that target the calcitonin gene-related peptide (CGRP) pathway of migraine pathogenesis have been specifically developed for the prophylactic treatment of chronic migraine. These anti-CGRP/R monoclonal antibodies have demonstrated good efficacy and excellent tolerability in phase II and III clinical trials, and offer new hope to patients who are currently not taking any prophylactic therapy or not benefitting from their current treatment.. Treatment of chronic migraine is a dynamic and rapidly advancing area of research. New developments in this field have the potential to improve the diagnosis and provide more individualised treatments for this condition. Establishing a culture of prevention is essential for reducing the personal, social and economic burden of chronic migraine.

Topics: Antibodies, Monoclonal; Botulinum Toxins, Type A; Chronic Disease; Disabled Persons; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Topiramate

Headaches are a common source of pain and suffering. The study's purpose was to assess beta-blockers efficacy in preventing migraine and tension-type headache.. Cochrane Register of Controlled Trials; MEDLINE; EMBASE; ISI Web of Science, clinical trial registries, CNKI, Wanfang and CQVIP were searched through 21 August 2018, for randomized trials in which at least one comparison was a beta-blocker for the prevention of migraine or tension-type headache in adults. The primary outcome, headache frequency per month, was extracted in duplicate and pooled using random effects models.. This study included 108 randomized controlled trials, 50 placebo-controlled and 58 comparative effectiveness trials. Compared to placebo, propranolol reduced episodic migraine headaches by 1.5 headaches/month at 8 weeks (95% CI: -2.3 to -0.65) and was more likely to reduce headaches by 50% (RR: 1.4, 95% CI: 1.1-1.7). Trial Sequential Analysis (TSA) found that these outcomes were unlikely to be due to a Type I error. A network analysis suggested that beta-blocker's benefit for episodic migraines may be a class effect. Trials comparing beta-blockers to other interventions were largely single, underpowered trials. Propranolol was comparable to other medications known to be effective including flunarizine, topiramate and valproate. For chronic migraine, propranolol was more likely to reduce headaches by at least 50% (RR: 2.0, 95% CI: 1.0-4.3). There was only one trial of beta-blockers for tension-type headache.. There is high quality evidence that propranolol is better than placebo for episodic migraine headache. Other comparisons were underpowered, rated as low-quality based on only including single trials, making definitive conclusions about comparative effectiveness impossible. There were few trials examining beta-blocker effectiveness for chronic migraine or tension-type headache though there was limited evidence of benefit.. Prospero (ID: CRD42017050335).

Topics: Adrenergic beta-Antagonists; Adult; Clinical Trials as Topic; Female; Humans; Male; Migraine Disorders; Propranolol; Tension-Type Headache; Topiramate; Valproic Acid

Migraine is one of the most common neurological disorders in the general population. It affects 18% of women and 6% of men. In more than 50% of women migraineurs the occurrence of migraine attacks correlates strongly with the perimenstrual period. Menstrual migraine is highly debilitating, less responsive to therapy, and attacks are longer than those not correlated with menses. Menstrual migraine requires accurate evaluation and targeted therapy, that we aim to recommend in this review.. This review of the literature provides an overview of currently available pharmacological therapies (especially with triptans, anti-inflammatory drugs, hormonal strategies) and drugs in development (in particular those acting on calcitonin gene-related peptide) for the treatment of acute migraine attacks and the prophylaxis of menstrual migraine. The studies reviewed here were retrieved from the Medline database as of June 2017.. The treatment of menstrual migraine is highly complex. Accurate evaluation of its characteristics is prerequisite to selecting appropriate therapy. An integrated approach involving neurologists and gynecologists is essential for patient management and for continuous updating on new therapies under development.

Topics: Acute Disease; Calcitonin Gene-Related Peptide; Female; Fructose; Humans; Menstruation; Migraine Disorders; Serotonin Receptor Agonists; Sumatriptan; Topiramate; Tryptamines; Vasodilator Agents

Migraine is a disabling and prevalent condition that affects the pediatric and adolescent population. This review describes current acute and preventive migraine pharmacologic therapies for the pediatric and adolescent population.. Multiple pharmacotherapies that have been used in the treatment of acute headache and prevention in pediatric migraine are reviewed. There have been recent advances in the management of migraines among pediatric and adolescent patients, including US Food and Drug Administration approval of triptans for acute management in children as young as 6 years, and the first prospective, randomized, double-blind, placebo-controlled comparative study of preventive pharmacotherapy in pediatric migraine. A major challenge of evidence-based research in pediatric and adolescent migraine is the significant placebo effect.. Although progress is being made in the management of migraines among pediatric and adolescent patients, there remains much work to be done.

Topics: Adolescent; Adrenergic beta-Antagonists; Amitriptyline; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Calcium Channel Blockers; Child; Cognitive Behavioral Therapy; Dihydroergotamine; Dopamine Antagonists; Fluid Therapy; Glucocorticoids; Headache Disorders, Secondary; Humans; Magnesium; Migraine Disorders; Nerve Block; Topiramate; Tryptamines; Valproic Acid

This paper describes current non-antibody pharmacologic approaches to the prevention of migraine in adults. Preventive therapy should be considered for patients with migraine who routinely have more than 6 headache days per month or in other special circumstances. Choices for preventive therapy are based on patient preferences about side effects and evidence of efficacy. The evidence level and commonly used doses for selected categories of migraine preventive medication are reviewed, including antiepileptic drugs, antihypertensive drugs, and antidepressants. Propranolol, timolol, topiramate, and divalproex sodium are approved for migraine prevention by the US FDA. OnabotulinumtoxinA is approved for prevention of chronic migraine. Several off-label drugs, especially lisinopril, candesartan, and amitriptyline also have good evidence of benefit. The spectrum of response to preventive therapy varies; in general, complete cessation of headaches is uncommon, although there are "super-responders" to every therapy, as illustrated by patient reports of dramatic responses to treatment. Preventive treatment should be started at a low dose and doses increased slowly until therapeutic benefit is achieved or side effects preclude continued use.

Topics: Analgesics, Non-Narcotic; Anticonvulsants; Antidepressive Agents; Botulinum Toxins, Type A; Humans; Migraine Disorders; Primary Prevention; Topiramate

Although chronic migraine (CM) is a common disorder that severely impacts patient functioning and quality of life, it is usually underdiagnosed, and treatment responses often remain poor even after diagnosis. In addition, effective treatment options are limited due to the rarity of randomized controlled trials (RCTs) involving patients with CM. In the present review, we discuss updated pharmacological, non-pharmacological, and neurostimulation treatment options for CM.. Pharmacological treatments include both acute and preventive measures. While acute treatment options are similar between CM and episodic migraine (EM), preventive treatment with topiramate and botulinum toxin A exhibited efficacy in more than two RCTs. In addition, several studies have revealed that behavioral interventions such as cognitive behavioral therapy, biofeedback, and relaxation techniques are associated with significant improvements in symptoms. Thus, these treatment options are recommended for patients with CM, especially for refractory cases. Neurostimulation procedures, such as occipital stimulation, supraorbital transcutaneous stimulation, non-invasive vagal nerve stimulation, and transcranial direct current stimulation, have shown promising results in the treatment of CM. However, current studies on neurostimulation suffer from small sample size, no replication, or negative results. Although CM is less responsive to treatment compared to EM, recent advance in pharmacological, non-pharmacological, and neurostimulation treatments may provide more chance for successful treatment of CM.

Topics: Biofeedback, Psychology; Botulinum Toxins, Type A; Chronic Pain; Cognitive Behavioral Therapy; Electric Stimulation Therapy; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Quality of Life; Relaxation Therapy; Topiramate; Transcranial Direct Current Stimulation; Treatment Outcome; Vagus Nerve Stimulation

Mainly based on evidence of success in adults, various medications are commonly used to prevent pediatric migraines. Topiramate has been approved for migraine prevention in children as young as 12 years of age. In this meta-analysis, we aimed to assess the currently published data pertaining to the efficacy of topiramate for migraine prevention in patients less than 18 years of age.. We searched PubMed/Medline, Embase and the Cochrane Library (from inception to April 2017) for randomized controlled trials (RCTs) published in English. Two independent investigators performed data extraction and quality evaluation using the Cochrane Collaboration's tool. The data extracted were analyzed by Review Manager 5.3 software.. A total of four RCTs matching the inclusion criteria were included, with an aggregate of 465 patients. Of these patients, 329 were included in the topiramate group, and 136 were included in the placebo group. This meta-analysis revealed that compared with placebo, topiramate failed to decrease the number of patients experiencing a ≥ 50% relative reduction in headache frequency (n = 465, RR = 1.26, 95% CI = [0.94,1.67], Z = 1.55, P = 0.12) or the number of headache days (n = 465, MD = -0.77, 95% CI = [-2.31,0.76], Z = 0.99, P = 0.32) but did reduce PedMIDAS scores (n = 205, MD = -9.02, 95% CI = [-17.34, -0.70], Z = 2.13, P = 0.03). Higher rates of side effects and adverse events in the topiramate group than in the placebo group were observed in the included trials.. Topiramate may not achieve a more effective clinical trial endpoint than placebo in the prevention of migraines in patients less than 18 years of age, and topiramate may lead to more side effects or adverse events in the included patients.

Topics: Adolescent; Anticonvulsants; Child; Fructose; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Topiramate

Headaches in children are quite common; however, the study and characterization of headache disorders in the pediatric age group has historically been limited. Because of the lack of controlled studies on prophylactic treatment of headache disorders in this age group, the diagnosis of migraine rests on criteria similar those in adults. Likewise, data from adult studies is often inferred and applied to children. Although it appears that many preventives are safe in children, currently none are FDA or EMA approved for this age group. Consequently, many children who present to their primary care physicians with migraines do not receive any preventive therapy despite experiencing significant disability.. Controlled clinical trials investigating the use of preventive medications in children have suffered from high placebo response rates. The shorter duration of headaches and other characteristic features seen in children are such that designing randomized controlled trials in this age group is more problematic and limiting. Treatment practices vary widely, even among specialists, due to the absence of evidence-based guidelines from clinical trials. The Childhood and Adolescent Migraine Prevention Study (CHAMP) was developed to examine the effectiveness of two of the most widely prescribed preventive medications for pediatric migraine and help narrow this gap. To date, it has been the largest enrolling study of its kind within the pediatric migraine world; its results and implications will be discussed and considered here. The CHAMP trial was discontinued early on account of futility and exhibited that neither of two preventive medications for pediatric migraine was more effective than placebo in reducing the number of headache days over a period of 24 weeks. Subjects in the amitriptyline and topiramate groups had higher rates of adverse events than those who had received placebo.

Topics: Amitriptyline; Analgesics, Non-Narcotic; Child; Controlled Clinical Trials as Topic; Fructose; Headache Disorders; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate

In evidence-based guidelines published in 2000, topiramate was a third-tier migraine preventive with no scientific evidence of efficacy; recommendation for its use reflected consensus opinion and clinical experience. Its neurostabilizing activity, coupled with its favorable weight profile, made topiramate an attractive alternative to other migraine preventives that caused weight gain. When guidelines for migraine prevention in episodic migraine were published in 2012, topiramate was included as a first-line option based on double-blind, randomized controlled trials involving nearly 3000 patients. The scientific and clinical interest in topiramate has generated a large body of data from randomized controlled trials, meta-analyses, patient registries, cohort studies, and claims data analyses that have more fully characterized its role as a migraine preventive.. This article will review the profile of topiramate that has emerged out of the past decade of research and clinical use in migraine prophylaxis. It will also address the rationale for extended-release (XR) formulations in optimizing topiramate therapy in migraine.. Topiramate has activity at multiple molecular targets, which may account for why it is effective in migraine and most other, more specific, anticonvulsants are not. Based on randomized controlled trials, topiramate reduces migraine frequency and acute medication use, improves quality of life, and reduces disability in patients with episodic migraine and in those with chronic migraine with or without medication overuse headache. Its efficacy in chronic migraine is not improved by the addition of propranolol. Topiramate's ability to prevent progression from high-frequency episodic migraine to chronic migraine remains unclear. Consistent with clinicians' perceptions, migraineurs are more sensitive to topiramate-associated side effects than patients with epilepsy. Paresthesia is a common occurrence early in treatment but is rarely cause for terminating topiramate treatment. Cognitive problems occur much less frequently than paresthesia but are more troublesome in terms of treatment discontinuation. Cognitive complaints can often be managed by slowly increasing the topiramate dose in small increments to allow habituation. As with other carbonic anhydrase inhibitors, topiramate has metabolic effects that favor the development of metabolic acidosis and possibly renal stones. Because migraineurs have an increased risk of renal stones independent of topiramate exposure, clinicians should counsel all migraine patients to maintain hydration. Abrupt onset of blurring, other visual disturbances, and/or ocular pain following topiramate's initiation should be evaluated promptly since this may indicate rare but potentially sight-threatening idiosyncratic events. Postmarketing evidence has shown that first-trimester exposure to topiramate monotherapy is associated with increased occurrence of cleft lip with or without cleft palate (Pregnancy Category D). Even though topiramate's long half-life would seemingly support q.d. dosing, randomized controlled migraine trials used b.i.d. administration of immediate-release (IR) topiramate, which has more favorable plasma concentration-time profile (ie, lower peak concentrations and higher trough concentrations) than q.d. IR dosing. Given the sensitivity of migraineurs to topiramate-related adverse events, particularly cognitive effects, pharmacokinetic profiles should be considered when optimizing migraine outcomes. The extended-release (XR) formulations Qudexy

Topics: Central Nervous System Agents; Fructose; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Topiramate

A large number patients struggle with migraine which is classified as a chronic disorder. The relative efficacy, safety and tolerability of prophylactic medications for migraine play a key role in managing this disease.. We conducted an extensive literature search for popular prophylactic medications that are used for migraine patients. Pairwise meta-analysis and network meta-analysis (NMA) were carried out sequentially for determining the relative efficacy, safety and tolerability of prophylactic medications. Summary effect for migraine headache days, headache frequency, at least 50% reduction in headache attacks, all-adverse events, nausea, somnolence, dizziness, withdrawal and withdrawal due to adverse events were produced by synthesizing both direct and indirect evidence.. Patients with three interventions exhibited significantly less average migraine headache days compared with those treated by placebo (topiramate, propranolol, divalproex). Moreover, topiramate and valproate exhibited a significantly increased likelihood of at least 50% reduction in migraine headache attacks compared to placebo. Patients with topiramate and propranolol also exhibited significantly reduced headache frequency compared to those with placebo. On the other hand, patients with divalproex exhibited significantly higher risk of nausea compared to those with placebo, topiramate, propranolol, gabapentin and amitriptyline. Finally, divalproex was associated with an increased risk of withdrawal compared to placebo and propranolol.. Topiramate, propranolol and divalproex may be more efficacious than other prophylactic medications. Besides, the safety and tolerability of divalproex should be further verified by future studies.

Topics: Adult; Amines; Amitriptyline; Anticonvulsants; Cyclohexanecarboxylic Acids; Dizziness; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Migraine Disorders; Nausea; Pre-Exposure Prophylaxis; Propranolol; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome; Valproic Acid

Chronic migraine (CM) is a common and disabling disorder that remains underdiagnosed and poorly treated. Significant unmet therapeutic needs add to the burden of this disorder; even when CM is recognized, effective treatment options are limited and randomized controlled trials supporting the use of various preventive medications are sparse. In this review, we discuss the available options for CM treatment. Currently the only FDA-approved treatment for CM prevention is onabotulinumtoxinA. Two double-blind studies have demonstrated the efficacy of topiramate for CM prevention, but it is not FDA-approved for this indication. Treatments in development for migraine will also be reviewed. Advancements in the understanding of migraine pathogenesis have identified new targets for both acute and preventive treatment and have engendered the development of targeted and mechanism-based therapies. The need for more effective treatment for CM patients, which has long since been identified, is now being addressed. Several of the emerging treatments for migraine prevention are under investigation specifically for CM or high-frequency episodic migraine.

Topics: Animals; Botulinum Toxins, Type A; Chronic Disease; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate; Treatment Outcome

Antiepileptic drugs (AED) are often considered first line for monotherapy in treatment of patients with migraines, and also those with comorbid migraine and epilepsy. Topiramate, a newer generation AED, has broad mechanism of action and evidence of benefit in patients with either episodic or chronic migraine along with epilepsy, both generalized and focal.. Our goal is to review the relevant mechanisms of action along with any supportive evidence published to date on the use of topiramate (TPM) in patients with both migraine headache and epilepsy.. There has been very little published to date on the use of TPM in patients diagnosed with both disorders. Despite this, TPM has been adopted as first line therapy in this patient population. Future studies investigating the effectiveness of this treatment strategy are warranted in order to determine the most effective use of this medication in patients diagnosed with migraine headaches and epilepsy.

Topics: Databases, Bibliographic; Epilepsy; Female; Fructose; Humans; Male; Migraine Disorders; Neuroprotective Agents; Topiramate

Recurrent headache is common in children. Among them migraine is the most common disabling cause of primary headache. It causes serious disability in child's life and family. It causes negative impact on their quality of life. Clinical characteristic of migraine in children differ from adult. It may be shorter in duration and bifrontal or bitemporal in location in contrast to adult which is longer in duration and usually unilateral. It is less common before 3 years of age. Males are more affected before puberty. But after puberty females are predominantly affected. Intensity of pain is moderate to severe. There are some triggering factors. Positive family history usually present. Disability can be assessed by PedMIDAS scale in children and adolescents which is modified version of MIDAS scale for adult. Diagnosis of migraine usually clinical but evaluation should be done to exclude severe underlying secondary cause. Management consists of pharmacological and non pharmacological approach. Parental education, life style modification is the mainstay of management. Acute treatment consists of Acetaminophen, NSAIDs and Triptans. Among Triptans, Sumatriptan nasal spray is only found effective for children. Preventive therapy aims to decrease frequency and severity of headache. Flunarizine, Propranolol, Amitryptylline, Levetiracetam, Valproate, Topiramate are found effective in pediatric age group. Pediatrician should evaluate the child to exclude secondary cause of headache when indicated. They should have also proper knowledge and skills to manage a child having migraine to improve their quality of life and academic achievement.

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Female; Headache; Humans; Male; Migraine Disorders; Quality of Life; Topiramate

Topics: Adult; Anticonvulsants; Female; Fructose; Humans; Isoxazoles; Kidney Calculi; Migraine Disorders; Pseudotumor Cerebri; Topiramate; Zonisamide

Migraine is a complex and multifactorial brain disorder affecting approximately 18% of women and 5% of men in the United States, costing billions of dollars annually in direct and indirect healthcare costs and school and work absenteeism and presenteeism. Until this date, there have been no medications that were designed with the specific purpose to decrease the number of migraine attacks, which prompts a search for alternative interventions that could be valuable, such as acupuncture.. Acupuncture origins from ancient China and encompasses procedures that basically involve stimulation of anatomical points of the body.. This manuscript reviews large and well-designed trials of acupuncture for migraine prevention and also the effectiveness of acupuncture when tried against proven migraine preventative medications.. Acupuncture seems to be at least as effective as conventional drug preventative therapy for migraine and is safe, long lasting, and cost-effective. It is a complex intervention that may prompt lifestyle changes that could be valuable in patients' recovery.

Topics: Acupuncture Therapy; Female; Flunarizine; Fructose; Humans; Male; Migraine Disorders; Neuroprotective Agents; Randomized Controlled Trials as Topic; Time Factors; Topiramate

While it has been established that headaches in the pediatric age group are relatively common, the characterization of headache disorders and their treatment in this group has historically been limited. Due to the paucity of controlled studies on prophylaxis of the primary headache disorders in children, the diagnosis of migraine often rests on criteria similar to those used in adults. Data from adult studies are often extrapolated and applied to the pediatric patient. Although it appears that many prophylactic agents are safe, well tolerated and efficacious in children, currently only topiramate is FDA-approved for use in patients 12 years and over. As a result, despite often experiencing significant disability, many children who present to their physician with migraines do not receive preventive therapy. One-third of adolescents meet the criteria for warranting prophylactic therapy, yet few are offered a preventative medication. Moreover, controlled clinical trials investigating the use of both abortive and prophylactic medications in children have suffered from high placebo response rates. A diverse group of medications are used to prevent migraine attacks, including antidepressants, antiepileptics, antihistamines and antihypertensive agents, yet there still remains a serious lack of controlled studies on the pharmacological treatment of pediatric migraine.

Topics: Adolescent; Adult; Anticonvulsants; Antidepressive Agents; Antihypertensive Agents; Child; Fructose; Histamine Antagonists; Humans; Migraine Disorders; Research Design; Topiramate

Chronic migraine is a disease that affects 0.5-2.5% of the population, depending on the statistics that are analysed and the definition of chronic migraine that is used. It is extraordinarily disabling, since it does not allow the sufferer to carry out any of their scheduled personal, professional or social activities, and it has a great impact on the patients' quality of life, as measured on disability, quality of life and impact on daily activities scales. Yet, nowadays there are treatments that have proven to be effective in cases of chronic migraine, such as OnabotulinumtoxinA. It is a treatment that is well tolerated and with a high rate of efficacy. Yet it is not only a therapeutic tool, but in the world of headaches it has also opened up the doors to invasive treatments, to the learning of techniques and, in short, to placing headaches in referral units that are usually located in tertiary care hospitals. Furthermore, it has also helped to overcome the idea that patients with headache should be visited exclusively by primary care physicians or general neurologists. This is an opportunity to redefine the field of study and the care for headaches that must be seized. In the future, this is going to be complemented by novel treatments with neurostimulation and probably with monoclonal antibodies against the calcitonin gene-related peptide. A revolution has begun in our knowledge and capacity to act. It is our duty to give it the importance and usage it deserves both for our patients and for us as specialists.. Posicionamiento de las unidades de cefalea en el ambito de la neurologia: la importancia de la OnabotulinumtoxinA y otras terapias en el tratamiento de la cefalea.. La migraña cronica es una enfermedad que afecta al 0,5-2,5% de la poblacion segun las estadisticas que se analicen y la definicion de migraña cronica que se adopte. Es extraordinariamente incapacitante, ya que no permite realizar las actividades personales, profesionales o sociales programadas, y tiene un gran impacto sobre la calidad de vida de los pacientes, medido en escalas de discapacidad, calidad de vida e impacto en la actividad diaria. Sin embargo, actualmente se dispone de tratamientos que han demostrado eficacia en la migraña cronica, como la OnabotulinumtoxinA. Es un tratamiento bien tolerado y con una tasa de eficacia elevada. Pero no es solo una herramienta terapeutica, sino que ha abierto las puertas en el mundo de la cefalea a la realizacion de tratamientos invasivos, al aprendizaje de tecnicas y, en definitiva, a situar la cefalea en unidades de referencia ubicadas, habitualmente, en hospitales de tercer nivel. Ademas, ha ayudado a eliminar el concepto de que los pacientes con cefalea deben ser atendidos exclusivamente por medicos de atencion primaria o neurologos generales. Esta es una oportunidad que debe aprovecharse para redimensionar el campo del estudio y asistencia de la cefalea. En el futuro, esto va a complementarse con novedosos tratamientos con neuroestimulacion y, probablemente, con anticuerpos monoclonales contra el peptido relacionado con el gen de la calcitonina. Se ha iniciado una revolucion en nuestro conocimiento y capacidad de actuacion. Es nuestro deber darle la importancia y uso que se merecen tanto para nuestros pacientes como para nosotros como especialistas.

Topics: Acetylcholine Release Inhibitors; Antibodies, Monoclonal; Botulinum Toxins, Type A; Calcitonin; Cluster Headache; Electric Stimulation Therapy; Forecasting; Fructose; Headache Disorders; Hospital Units; Humans; Migraine Disorders; Nerve Block; Neuralgia; Neurology; Prevalence; Protein Precursors; Spain; Therapies, Investigational; Topiramate; United States

Anticonvulsants represent one of the main substance classes used for the preventive treatment of migraine. Efficacy has been demonstrated in randomized placebo-controlled trials for topiramate and valproic acid including divalproex sodium. In the case of topiramate, efficacy has recently been proven for chronic migraine and even medication overuse headache, questioning the established concept of medication withdrawal. However, preventive treatment with anticonvulsants is frequently hampered by side effects that occasionally require treatment discontinuation. In addition, these data indicate that some anticonvulsant drugs are effective in migraine, while a number are clearly not useful. Effective anticonvulsants, such as topiramate and valproate, target nociceptive trigeminovascular and trigeminothalamic dural pathways or mechanisms involved in cortical spreading depression. Dissecting out how the anticonvulsants that do not work differ mechanistically from those that do will almost certainly provide avenues through which one can develop new treatments to bring to patients with migraine.

Topics: Animals; Anticonvulsants; Cortical Spreading Depression; Fructose; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Topiramate; Valproic Acid

Chronic migraine is a frequent, severely disabling headache that often evolves from EM. Treatment should be individualized with consideration of the patient as a whole person rather than just the headaches. Many options have been used for acute and preventive pharmacologic management, although good scientific and clinical evidence is limited to a few options. Evidence supports the efficacy and tolerability of both topiramate and onabotulinumtoxinA for prevention of CM headaches. However, only onabotulinumtoxinA is approved by the FDA for preventive treatment of CM.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Botulinum Toxins, Type A; Female; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Serotonin 5-HT1 Receptor Agonists; Sumatriptan; Topiramate

To evaluate the currently published data pertaining to the efficacy and safety of topiramate for prophylaxis of classic and common migraine in pediatric patients.. The literature was identified via PubMed (through April 2013) and Iowa Drug Information System (through April 2013). References from identified articles were also reviewed.. Data were included from studies of efficacy and safety in pediatric patients experiencing migraine (with or without aura), as defined by the International Headache Society. Studies including patients with more specific types of migraine, such as basilar migraine, were excluded.. Eight publicatons were identified, including 3 randomized controlled trials (RCTs), a subgroup analysis, and 4 observational studies. These studies reported a decrease in headache frequency ranging from 63% to 100% for doses of 100 mg/d and 65% for 200 mg/d. Response to therapy, defined as ≥50% reduction in migraine rate, was also reported in 83% to 95% of patients receiving topiramate. Topiramate is generally well tolerated. Adverse effects were dose related and included paresthesias, weight loss, and cognitive adverse effects.. Topiramate is an effective and well-tolerated prophylactic therapy for use in pediatric migraine patients. Doses of 100 and 200 mg/d (1.47-2.0 mg/kg/d) effectively decrease the frequency of migraine headaches, with 100 mg/d providing optimal benefit-to-risk ratio. Additional randomized, double-blind, placebo-controlled studies are needed to determine the impact of the drug on quality-of-life outcomes, such as school function, and migraine severity and duration.

Topics: Child; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate; Treatment Outcome

Pseudotumor cerebri syndrome (PTCS) refers to the primary and secondary disorders that cause elevated intracranial pressure without an intracranial mass lesion, ventriculomegaly, or central nervous system infection or malignancy. Headache is the most frequent symptom of PTCS, but there is considerable overlap between the headache features of raised intracranial pressure and the headache features of primary headache disorders. We review headache subtypes that occur in PTCS, non-headache features that help distinguish PTCS from other headache types, changes to the diagnostic criteria for PTCS with and without papilledema, and headache treatment strategies as they apply to PTCS.

Topics: Acetazolamide; Back Pain; Diagnosis, Differential; Diuretics; Fructose; Furosemide; Headache Disorders; Humans; Intracranial Hypertension; Migraine Disorders; Neuroprotective Agents; Papilledema; Pseudotumor Cerebri; Tinnitus; Topiramate; Vision Disorders; Weight Reduction Programs

Migraine is a very common medical disorder characterized by attacks of moderate-severe headache, nausea and disability. Topiramate is an effective, popular prophylactic migraine treatment, which is approved for use in adults and adolescents. Due to its multiple mechanisms of action, topiramate has multiple potential safety issues, including systemic and CNS adverse events, which may complicate therapy.. This review evaluates common adverse events as seen in the pivotal trials of topiramate for migraine as well as those observed in postmarketing studies. These include weight loss, metabolic acidosis, renal calculi, acute angle closure glaucoma, visual distortions and cognitive slowing. Topiramate use during pregnancy is associated with an increased risk of cleft lip. This review highlights both common and unusual safety issues associated with topiramate use, including important drug interactions and a comparison with other migraine prophylactic agents.. Topiramate is highly effective in migraine prophylaxis but clinicians using the drug need to be aware of the potential for bothersome or serious adverse events. When treating with topiramate, use a slow titration to the goal dose of 100 mg or the lowest dose, which helps prevent migraine.

Topics: Adolescent; Adult; Animals; Anticonvulsants; Cleft Lip; Dose-Response Relationship, Drug; Drug Interactions; Female; Fructose; Humans; Infant, Newborn; Migraine Disorders; Pregnancy; Topiramate

Migraine is a complex disorder with many different manifestations. There has been an increasing interest in the association of migraine and vertigo. Many different terms have been developed to describe this concept, the more popular being vestibular migraine, migrainous vertigo, and migraine-associated vertigo. The most commonly cited diagnostic criteria are that of Neuhauser though this has yet to be included in the International Classification of Headache Disorders (2nd edition). At this time, there is a lack of consensus regarding migraine-related vertigo and its pathomechanism. Regardless, a few randomized controlled prospective studies have been performed to evaluate the efficacy of various medications. Topiramate has been shown to be effective for migraine-related vertigo. At this time there is no specific treatment for migraine-related dizziness outside of conventional migraine management. The genetics have yet to be fully realized though an autosomal dominant familial migraine vertigo disorder has been identified.

Topics: Animals; Comorbidity; Dizziness; Fructose; Genetic Predisposition to Disease; Humans; Kindling, Neurologic; Migraine Disorders; Models, Neurological; Nystagmus, Pathologic; Randomized Controlled Trials as Topic; Topiramate; Trigeminal Nerve; Vertigo; Vestibule, Labyrinth; Visual Perception

To report the case of a 32-year-old woman with abdominal migraine and present a literature review to evaluate abdominal migraine in adults, with particular regard to effective treatment.. A 32-year-old African American female presented with recurrent, severe abdominal pain. The patient had several previous admissions with similar symptoms and an extensive gastrointestinal workup in which findings were normal. Attacks of abdominal pain occurred despite treatment with analgesics and antiemetics. She had a family history of migraine headaches. A diagnosis of abdominal migraine was presumed and prophylactic therapy with topiramate 50 mg twice daily relieved the symptoms.. Most published cases of adult abdominal migraine describe females who had a long history of abdominal pain refractory to conventional therapies. The majority of patients had a strong family history of migraine and reported similar episodic abdominal pain. Patients responded to prophylactic migraine therapies, including calcium channel blockers, β-blockers, topiramate, and antihistamines; a few responded to abortive sumatriptan therapy.. Abdominal migraine should be considered a possible source of incurable abdominal pain in adults when accompanied by a complete gastrointestinal workup with normal results. We recommend a trial of topiramate as prophylactic therapy if abdominal migraine is the likely source of the pain.

Topics: Abdominal Pain; Adult; Analgesics; Anticonvulsants; Female; Fructose; Humans; Migraine Disorders; Topiramate

Some antiepileptic drugs but not others are useful in clinical practice for the prophylaxis of migraine. This might be explained by the variety of actions of these drugs in the central nervous system. The present review is part of an update of a Cochrane review first published in 2004, and previously updated (conclusions not changed) in 2007.. To describe and assess the evidence from controlled trials on the efficacy and tolerability of topiramate for preventing migraine attacks in adult patients with episodic migraine.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2012, Issue 12), PubMed/MEDLINE (1966 to 15 January 2013), MEDLINE In-Process (current week, 15 January 2013), and EMBASE (1974 to 15 January 2013) and handsearched Headache and Cephalalgia through January 2013.. Studies were required to be prospective, controlled trials of topiramate taken regularly to prevent the occurrence of migraine attacks, to improve migraine-related quality of life, or both.. Two review authors independently selected studies and extracted data. For headache frequency data, we calculated mean differences (MDs) between topiramate and comparator (placebo, active control, or topiramate in a different dose) for individual studies and pooled these across studies. For dichotomous data on responders (patients with ≥ 50% reduction in headache frequency), we calculated odds ratios (ORs) and, in select cases, risk ratios (RRs); we also calculated numbers needed to treat (NNTs). We calculated MDs for selected quality of life instruments. Finally, we summarised data on adverse events from placebo-controlled trials and calculated risk differences (RDs) and numbers needed to harm (NNHs).. Twenty papers describing 17 unique trials met the inclusion criteria. Analysis of data from nine trials (1737 participants) showed that topiramate reduced headache frequency by about 1.2 attacks per 28 days as compared to placebo (MD -1.20; 95% confidence interval (CI) -1.59 to -0.80). Data from nine trials (1190 participants) show that topiramate approximately doubled the proportion of responders relative to placebo (RR 2.02; 95% CI 1.57 to 2.60; NNT 4; 95% CI 3 to 6). Separate analysis of different topiramate doses produced similar MDs versus placebo at 50 mg (-0.95; 95% CI -1.95 to 0.04; three studies; 520 participants), 100 mg (-1.15; 95% CI -1.58 to -0.71; six studies; 1620 participants), and 200 mg (-0.94; 95% CI -1.53 to -0.36; five studies; 804 participants). All three doses significantly increased the proportion of responders relative to placebo; ORs were as follows: for 50 mg, 2.35 (95% CI 1.60 to 3.44; three studies; 519 participants); for 100 mg, 3.49 (95% CI 2.23 to 5.45; five studies; 852 participants); and for 200 mg, 2.49 (95% CI 1.61 to 3.87; six studies; 1025 participants). All three doses also significantly improved three or more domains of quality of life as compared to placebo. Meta-analysis of the three studies that included more than one dose of topiramate suggests that 200 mg is no more effective than 100 mg. With regard to mean headache frequency and/or responder rate, seven trials using active comparators found (a) no significant difference between topiramate and amitriptyline (one study, 330 participants); (b) no significant difference between topiramate and flunarizine (one study, 83 participants); (c) no significant difference between topiramate and propranolol (two studies, 342 participants); (d) no significant difference between topiramate and relaxation (one study, 61 participants); but (e) a slight significant advantage of topiramate over valproate (two studies, 120 participants). Relaxation improved migraine-specific quality of life significantly more than topiramate. In trials of topiramate against placebo, seven adverse events (AEs) were reported by at least three studies. These were usually mild and of a non-serious nature. Except for taste disturbance and weight loss, there were no significant differences in the frequency of AEs in general, or of the seven specific AEs, between placebo and topiramate 50 mg. AEs in general and all of the specific AEs except nausea were significantly more common on topiramate 100 mg tha. Meta-analysis demonstrates that topiramate in a 100 mg/day dosage is effective in reducing headache frequency and reasonably well-tolerated in adult patients with episodic migraine. This provides good evidence to support its use in routine clinical management. More studies designed specifically to compare the efficacy or safety of topiramate versus other interventions with proven efficacy in the prophylaxis of migraine are needed.

Topics: Adult; Anticonvulsants; Fructose; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Topiramate

Some antiepileptic drugs but not others are useful in clinical practice for the prophylaxis of migraine. This might be explained by the variety of actions of these drugs in the central nervous system. The present review is part of an update of a Cochrane review first published in 2004, and previously updated (conclusions not changed) in 2007.. To describe and assess the evidence from controlled trials on the efficacy and tolerability of valproate (valproic acid or sodium valproate or a combination of the two) for preventing migraine attacks in adult patients with episodic migraine.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2012, Issue 12), PubMed/MEDLINE (1966 to 15 January 2013), MEDLINE In-Process (current week, 15 January 2013), and EMBASE (1974 to 15 January 2013) and handsearched Headache and Cephalalgia through January 2013.. Studies were required to be prospective, controlled trials of valproate taken regularly to prevent the occurrence of migraine attacks, to improve migraine-related quality of life, or both.. Two review authors independently selected studies and extracted data. For headache frequency data, we calculated mean differences (MDs) between valproate and comparator (placebo, active control, or valproate in a different dose) for individual studies and pooled these across studies. For dichotomous data on responders (patients with ≥ 50% reduction in headache frequency), we calculated odds ratios (ORs) and, in select cases, risk ratios (RRs); we also calculated numbers needed to treat (NNTs). We calculated MDs for Migraine Disability Assessment (MIDAS) scores. We also summarised data on adverse events from placebo-controlled trials and calculated risk differences (RDs) and numbers needed to harm (NNHs).. Ten papers describing 10 unique trials met the inclusion criteria. Analysis of data from two trials (63 participants) showed that sodium valproate reduced headache frequency by approximately four headaches per 28 days as compared to placebo (MD -4.31; 95% confidence interval (CI) -8.32 to -0.30). Data from four trials (542 participants) showed that divalproex sodium (a stable combination of sodium valproate and valproic acid in a 1:1 molar ratio) more than doubled the proportion of responders relative to placebo (RR 2.18; 95% CI 1.28 to 3.72; NNT 4; 95% CI 2 to 11). One study of sodium valproate (34 participants) versus placebo supported the latter findings (RR for responders 2.83; 95% CI 1.27 to 6.31; NNT 3; 95% CI 2 to 9). There was no significant difference in the proportion of responders between sodium valproate versus flunarizine (one trial, 41 participants) or between divalproex sodium versus propranolol (one trial, 32 participants). Pooled analysis of post-treatment mean headache frequencies in two trials (88 participants) demonstrates a slight but significant advantage for topiramate 50 mg over valproate 400 mg (MD -0.90; 95% CI -1.58 to -0.22). For placebo-controlled trials of sodium valproate and divalproex sodium, NNHs for clinically important adverse events ranged from 7 to 14.. Valproate is effective in reducing headache frequency and is reasonably well tolerated in adult patients with episodic migraine.

Topics: Adult; Anticonvulsants; Flunarizine; Fructose; Humans; Migraine Disorders; Propranolol; Randomized Controlled Trials as Topic; Topiramate; Valproic Acid

Migraine is a common illness and migraine-related dizziness occurs in up to 3% of the population. Because the diagnosis is controversial and may be difficult, many patients go undiagnosed and untreated. This review summarizes current understanding of the taxonomy and diagnosis of vestibular migraine, the relation of vestibular migraine to labyrinthine disease, and the treatment of the condition in adults and children.. The categories of migraine accepted by the International Headache Society do not reflect the complex presentations of patients suspected of having vestibular migraine. In clinical practice and research, criteria are increasingly accepted that divide patients suspected of vestibular migraine into 'definite vestibular migraine' and 'probable vestibular migraine.' Because vertigo itself may trigger migraine, patients with vestibular migraine should be suspected of having vestibular end-organ disease until proven otherwise. Treatment remains controversial because of a notable lack of randomized controlled studies of vestibular migraine treatment.. For now, the best strategy for the treatment of suspected vestibular migraine patients is dietary/lifestyle modification, antinausea/antiemetics for acute vertigo, and preventive medication for patients who have continued disruptive symptoms. Patients with vestibular migraine should be monitored regularly for the development of latent audiovestibular end-organ disease.

Topics: Anticonvulsants; Benign Paroxysmal Positional Vertigo; Diagnosis, Differential; Diet; Fructose; Humans; Life Style; Meniere Disease; Migraine Disorders; Topiramate; Vertigo

AIM. To analyse the effectiveness of therapeutic exercise on migraines and tension-type headaches (TTH). MATERIALS AND METHODS. Electronic databases were used to search the literature for relevant articles. Eligibility criteria were: controlled randomised clinical trials (RCT), conducted on patients with migraine or TTH, in which the therapeutic intervention was based on therapeutic exercise, and the papers had been published in English and Spanish. Two independent reviewers performed the analysis of the methodological quality using the Delphi scale. RESULTS. Ten RCT were selected, seven of which offered good methodological quality. According to all the studies analysed, the intensity and frequency of pain diminished in comparison to the situation prior to establishing therapeutic exercise, and in five studies the effect was higher than in the control group. The qualitative analysis showed strong evidence of the absence of adverse events following the application of therapeutic exercise. Furthermore, strong evidence was also found of the effect of physiotherapeutic treatment, including therapeutic exercise, in lowering the intensity, frequency and duration of pain in patients with TTH. Limited evidence was also found of the effectiveness of aerobic exercise in patients with migraine, although it was not better than the effects derived from other forms of treatment. CONCLUSIONS. Results show that therapeutic exercise is a safe treatment that provides beneficial effects on migraines or TTH. Further RCT are required in the future with appropriate methodological designs to confirm these results.. Ejercicio terapeutico como tratamiento de las migrañas y cefaleas tensionales: revision sistematica de ensayos clinicos aleatorizados.. Objetivo. Analizar la efectividad que tiene el ejercicio terapeutico sobre las migrañas y las cefaleas de tipo tensional (CTT). Materiales y metodos. La busqueda de articulos se realizo utilizando bases de datos electronicas. Los criterios de inclusion fueron: estudios clinicos aleatorizados (ECA) controlados, realizados en pacientes con migrañas o CTT, donde la intervencion terapeutica se basara en ejercicio terapeutico y publicados en ingles y español. Dos revisores independientes realizaron el analisis de la calidad metodologica utilizando la escala Delphi. Resultados. Se seleccionaron 10 ECA, de los cuales siete presentaron una calidad metodologica buena. Segun todos los estudios analizados, el ejercicio terapeutico disminuyo la intensidad y frecuencia del dolor comparado con la situacion previa, y en cinco estudios el efecto fue mayor que en la comparativa con el grupo control. El analisis cualitativo muestra evidencia fuerte acerca de la ausencia de eventos adversos tras la aplicacion de ejercicio terapeutico. Ademas, se encontro evidencia fuerte acerca del efecto del tratamiento de fisioterapia, incluyendo el ejercicio terapeutico, para disminuir la intensidad, la frecuencia y la duracion del dolor en pacientes con CTT. Se observo evidencia limitada acerca de la efectividad del ejercicio aerobico sobre los pacientes con migraña sin ser superior el efecto al de otros tratamientos. Conclusiones. Los resultados muestran que el ejercicio terapeutico es un tratamiento seguro, que presenta efectos beneficiosos sobre las migrañas o las CTT. Es necesario que futuros ECA con diseños metodologicos adecuados confirmen estos resultados.

Topics: Acupuncture Therapy; Adult; Analgesics; Combined Modality Therapy; Evidence-Based Medicine; Exercise Movement Techniques; Female; Fructose; Humans; Male; Migraine Disorders; Neck Muscles; Pain Management; Physical Therapy Modalities; Randomized Controlled Trials as Topic; Relaxation Therapy; Research Design; Tension-Type Headache; Topiramate; Treatment Outcome

The classification of the International Headache Society (IHS) generally differentiates episodic from chronic headache. Chronic migraine is defined as headache on 15 and more days a month over more than 3 months and headache on 8 days or more fulfils the criteria for migraine or were triptan/ergot-responsive when thought to be migrainous in early stages of the attack. The prevalence of chronic migraine is estimated at 2-4 %. The quality of life is highly compromised in this condition and comorbidities are much more frequent compared to episodic migraine. Data from prospective randomized studies are scarce as most patients with chronic migraine were excluded from previous trials and only few studies were conducted for this condition. The efficacy for prophylactic treatment compared with placebo is proven for topiramate and onabotulinum toxin A.

Topics: Botulinum Toxins, Type A; Comorbidity; Cross-Sectional Studies; Fructose; Humans; Migraine Disorders; Prospective Studies; Randomized Controlled Trials as Topic; Recurrence; Topiramate

OBJECTIVE To assess the effectiveness of prophylactic headache treatment in children and adolescents. DATA SOURCES PubMed, EMBASE, Cochrane Database of Clinical Trials, and bibliography of retrieved articles through August 11, 2012. STUDY SELECTION Randomized trials of headache treatment among children and adolescents (<18 years old). INTERVENTION Any placebo-controlled trial or comparisons between 2 or more active medications. MAIN OUTCOME MEASURE Number of headaches per month. RESULTS Among 21 included trials, there were 13 placebo-controlled and 10 active comparator trials (2 also included placebo). Twenty trials focused on episodic migraines and 1 on chronic daily headaches. Drugs more effective than placebo for episodic migraines (<15 headaches per month) included topiramate (difference in headaches per month, -0.71; 95% CI, -1.19 to -0.24) and trazodone (-0.60; 95% CI, -1.09 to -0.11). Ineffective drugs included clonidine, flunarizine, pizotifen, propranolol, and valproate. A single trial of fluoxetine for chronic daily headaches found it ineffective. Patients given placebo experienced a significant (P = .03) decline in headaches, from 5.6 (95% CI, 4.52-6.77; Q = 8.14 [Cochran Q is a measure of the heterogeneity of the included studies]) to 2.9 headaches per month (95% CI, 1.66-4.08; Q = 4.72). Among the 10 active comparator trials, flunarizine was more effective than piracetam (difference in headaches per month, -2.20; 95% CI, -3.93 to -0.47) but no better than aspirin, dihydroergotamine, or propranolol. Propranolol was compared with valproate as well as behavioral treatment, and 2 studies compared different doses of topiramate; none of these trials showed significant differences. CONCLUSIONS Topiramate and trazodone have limited evidence supporting efficacy for episodic migraines. Placebo was effective in reducing headaches. Other commonly used drugs have no evidence supporting their use in children and adolescents. More research is needed.

Topics: Adolescent; Adrenergic beta-Antagonists; Analgesics; Anticonvulsants; Child; Child, Preschool; Comparative Effectiveness Research; Fructose; Headache; Headache Disorders; Humans; Migraine Disorders; Placebo Effect; Selective Serotonin Reuptake Inhibitors; Topiramate; Trazodone

We define chronic migraine as that clinical situation in which migraine attacks appear 15 or more days per month. Until recently, and in spite of its negative impact, patients with chronic migraine were excluded of the clinical trials. This manuscript revises the current treatment of chronic migraine. The first step should include the avoidance of potential precipitating/aggravating factors for chronic migraine, mainly analgesic overuse and the treatment of comorbid disorders, such as anxiety and depression. The symptomatic treatment should be based on the use of nonsteroidal anti-inflammatory agents and triptans (in this case < 10 days per month). It is necessary to avoid the use of combined analgesics, opioids and ergotamine-containing medications. Preventive treatment includes a 'transitional' treatment with nonsteroidal anti-inflammatory agents or steroids, while preventive treatment exerts its actions. Even though those medications efficacious in episodic migraine prevention are used, the only drugs with demonstrated efficacy in the preventive treatment of chronic migraine are topiramate and pericranial infiltrations of Onabotulinumtoxin A.

Topics: Amitriptyline; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Antihypertensive Agents; Anxiety; Barbiturates; Botulinum Toxins, Type A; Chronic Disease; Contraindications; Depression; Drug Combinations; Ergot Alkaloids; Fructose; Headache Disorders, Secondary; Humans; Migraine Disorders; Narcotics; Risk Factors; Topiramate; Tryptamines

Migraine is a chronic neurological disorder with episodic manifestations, progressive in some individuals. Preventive treatment is recommended for patients with frequent or disabling attacks. A sizeable proportion of migraineurs in need of preventive treatment does not significantly benefit from monotherapy. This short review evaluates the role of pharmacological polytherapy in migraine prevention.

Topics: Clinical Trials as Topic; Drug Therapy, Combination; Fructose; Humans; Migraine Disorders; Nortriptyline; Topiramate

Chronic migraine is defined in different ways. The most commonly used definition is headache on more than 15 days per month in patients with migraine. Chronic migraine is difficult to treat and requires a multidisciplinary approach. Only two pharmacological treatments have been shown to be effective in placebo-controlled randomized trials: topiramate and local injection of botulinum toxin. Both therapies are effective in patients with chronic migraine with and without medication overuse. Many other substances have been investigated in chronic daily headache. All trials were underpowered and, therefore, recommendations concerning possible efficacy are not possible.

Topics: Anticonvulsants; Botulinum Toxins, Type A; Chronic Disease; Fructose; Humans; Migraine Disorders; Topiramate

Migraine occurs in about 15% of the general population. Migraine is usually managed by medication, but some patients do not tolerate migraine medication due to side effects or prefer to avoid medication for other reasons. Non-pharmacological management is an alternative treatment option. We systematically reviewed randomized clinical trials (RCTs) on manual therapies for migraine. The RCTs suggest that massage therapy, physiotherapy, relaxation and chiropractic spinal manipulative therapy might be equally effective as propranolol and topiramate in the prophylactic management of migraine. However, the evaluated RCTs had many methodological shortcomings. Therefore, any firm conclusion will require future, well-conducted RCTs on manual therapies for migraine.

Topics: Anticonvulsants; Fructose; Humans; Manipulation, Chiropractic; Massage; Migraine Disorders; Musculoskeletal Manipulations; Physical Therapy Modalities; Propranolol; Randomized Controlled Trials as Topic; Relaxation Therapy; Topiramate; Treatment Outcome; Vasodilator Agents

Topics: Adolescent; Child; Chronic Disease; Evidence-Based Medicine; Female; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Randomized Controlled Trials as Topic; Topiramate

Three antiepileptic drugs (AEDs), valproic acid, gabapentin, and topiramate (TPM), are used frequently in the prophylactic treatment of migraines. In December 2008, the US Food and Drug Administration issued a warning suggesting that the use of all AEDs is associated with an increased risk of suicidal ideation and behavior. This warning has been received by the medical community with great skepticism, and the validity of the findings of the meta-analysis that led to its publication has been questioned because of various methodological problems. Yet, migraine by itself is associated with an increased risk of suicidal ideation and behavior as well as with an increased risk of psychiatric disorders that facilitate the development of suicidal behavior. Furthermore, TPM has been associated with psychiatric adverse events that potentially could result in suicidal ideation and behavior. In this article, we review data to determine whether the AEDs used in the prevention of migraine are associated with an increased risk of suicidality.

Topics: Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Drug Labeling; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Migraine Disorders; Risk Factors; Suicidal Ideation; Suicide; Topiramate; Treatment Outcome; United States; United States Food and Drug Administration; Valproic Acid

Migraine is a widespread disorder. Migraine patients experience worse health-related quality of life than the general population. The availability of effective and tolerable treatments for this disorder is an important medical need. This narrative review focuses on the clinical pharmacology of topiramate, an antiepileptic drug that was approved for the prophylaxis of migraine where it should act as a neuromodulator.. A PubMed database search (from 2000 to 24 January 2011) and a review of the human studies published on topiramate and migraine was conducted.. Topiramate is an important option for the prophylaxis of migraine and is of proven efficacy and tolerability. It has also been studied in chronic migraine with encouraging results, even in patients with medication overuse. However, in migraine prevention its efficacy is comparable to the other first-line drugs and there are no published trials with a superiority design which can establish topiramate's role in the available therapeutic armamentarium.

Topics: Anticonvulsants; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Fructose; Humans; Migraine Disorders; Time Factors; Topiramate

Migraine is a common neurological disease affecting about 12% of the population in Western Europe and North America, and causing a considerable burden both to migraineurs and to society. Severe, frequent and disabling migraine attacks, as well as those poorly responsive to acute care medication, require preventive treatment, which is often under-utilized. Antiepileptic drugs are used in the prevention of migraine. We performed a literature search of PubMed through June 2008 for controlled trials of antiepileptic drugs in the prevention of migraine. The search identified 70 papers for a full-text review. The majority of these papers referred to valproate and topiramate, and showed that these drugs are effective and well tolerated in migraine prevention and are suitable for first-line clinical use. On the other hand, acetazolamide, lamotrigine, oxcarbazepine and vigabatrin have been shown to be not effective and gabapentin requires further evaluation. For the rest of the antiepileptic drugs, no data from controlled trials are available.

Topics: Adult; Anticonvulsants; Child; Chronic Disease; Clinical Trials as Topic; Fructose; Humans; Migraine Disorders; Quality of Life; Topiramate; Valproic Acid

Although the triptan drugs provide effective relief from migraine for many patients, a substantial number of affected individuals are unresponsive to these compounds, and such therapy can also lead to a range of adverse effects. Telcagepant represents a new class of antimigraine drug-the calcitonin gene-related peptide receptor blockers. This compound exerts its effects by blocking receptors for the calcitonin-gene-related peptide at several sites in the trigeminal and central nervous systems, resulting in pain relief. Telcagepant does not cause vasoconstriction, a major limitation in the use of triptans. Comparisons with triptans in clinical trials for acute treatment of migraine attacks revealed clinical effects similar to those of triptans but better than those of placebo. Telcagepant might provide hope for those who have a poor response to, or are unable to use, older drugs. In patients who need prophylaxis because of frequent attacks of migraine, topiramate is a first-line drug for migraine prevention in many countries; it is generally safe and reasonably well tolerated. Data suggest that topiramate could aid reversion of chronic migraine to episodic migraine.

Topics: Anticonvulsants; Azepines; Calcitonin Gene-Related Peptide Receptor Antagonists; Fructose; Humans; Imidazoles; Migraine Disorders; Topiramate

Migraine is a very common disorder characterized by the combination of typical headache with associated autonomic symptoms and ranked by the WHO as number 19 among all diseases worldwide causing disability. Considerable progresses have been made in recent years to understand the pathophysiology of migraine, which has led to improved treatment options for the acute migraine attack as well as migraine prophylaxis. When headaches are frequent or particularly severe, prophylactic therapy should be considered, however preventive treatment is often insufficient to decrease migraine frequency substantially or is not well tolerated. The present paper summaries the possible drug treatment options which have the A level of evidence for effective preventive therapy of migraine. Summarises the evidences for the prophylactic migraine treatment, specially the role of the newly approved topiramate in the prophylaxis.

Topics: Evidence-Based Medicine; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate

To compare adverse drug reactions (ADRs) to topiramate in patients with migraine and patients with epilepsy, we systematically reviewed all published randomized controlled trials (RCTs) that compare topiramate monotherapy in epilepsy and migraine. We included four epilepsy RCTs (N = 1,179 patients; vs. active comparators) and six migraine RCTs (N = 1,723 patients; vs. placebo). Behavioral ADRs and headache were found only in the case of epilepsy, whereas cognitive complaints and alteration of taste were found only in the case of migraine. The risk ratios (RRs) for paresthesia in migraine vs. epilepsy trials were 2.5 (99% confidence interval (CI): 1.66-3.77) for 50 mg, 2.7 (99% CI: 1.80-3.97) for 100 mg, and 3.0 (99% CI: 1.95-4.56) for 200 mg. For ADR-related dropouts, the RR was 2.5 (95% CI: 2.03-2.98) for 50 mg but no different for the other doses. We conclude that when treated with the same doses of topiramate, migraineurs show different ADRs than patients with epilepsy and are more likely to drop out because of ADRs.

Topics: Drug-Related Side Effects and Adverse Reactions; Epilepsy; Fructose; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Risk Factors; Topiramate

The use of anticonvulsant drugs for the prevention of migraine in children and adolescents has been supported in the past.. To evaluate the available evidence for the efficacy and safety of anticonvulsants drugs in the prevention of migraine attacks in children and adolescents.. Studies were selected through a comprehensive literature search. We included all types of study designs (controlled and uncontrolled) due to the limited evidence. Monthly migraine frequency was used as the primary outcome measure in most of the studies. Studies were classified into levels of evidence according to their design.. Fourteen studies were included with a total of 939 patients. Topiramate (4 randomized controlled trials [RCT], two uncontrolled trials), sodium valproate/divalproex sodium (two RCTs, one uncontrolled trial, two retrospective chart reviews) levetiracetam and zonisamide (both only uncontrolled studies) are the anticonvulsants that have been reported in the literature. The findings show that valproate is not different from placebo and topiramate may not be different but further randomized trials are needed. All drugs were well tolerated in this age group with no serious events reported.. The use of anticonvulsants in the prevention of migraine in children and adolescents is not adequately supported by methodologically sound RCTs. More research is needed in the future to establish the efficacy and safety of specific agents.

Topics: Adolescent; Age Factors; Anticonvulsants; Child; Clinical Trials as Topic; Evidence-Based Medicine; Fructose; Humans; Migraine Disorders; Off-Label Use; Topiramate; Treatment Outcome; Valproic Acid

Migraine, according to the criteria of the International Headache Society, occurs in about 5 to 10% of children and adolescents. Pediatric migraine can cause a significant impact on quality of life. As stated by the American Academy of Neurology and Child Neurology Society's migraine guidelines, situations for prophylaxis consideration include recurring migraines that significantly interfere with daily activities, despite acute therapy; frequent headaches; contraindication, overuse, or failure of acute therapy; adverse reactions to acute therapy; cost of acute and preventive therapies; patient preferences; and presence of uncommon migraine conditions. Preventive therapy may be warranted in as many as 30% of young patients with migraine seen in tertiary headache centers. Headache related disability can be measured by scoring systems such as the Pediatric Migraine Disability Assessment Scale. Numerous medications have been studied to prevent migraines in children, including antihistamines, antidepressants, and antihypertensive agents. However, few high quality clinical trials actually demonstrate efficacy in this population. Recently, many studies dealt with the use of antiepileptic drugs in this indication but there is a paucity of placebo controlled studies. Both topiramate (TPM) and divalproex sodium have been studied in a randomized-controlled study. Only TPM showed efficacy, though, clearly, further controlled trials are needed to confirm these data. Besides unproven efficacy, adverse effects of valproic acid, such as weight gain, somnolence, and alopecia may limit its use. Additional studies are warranted before recommending levetiracetam (LVT), zonisamide (ZNS) and gabapentin (GBP) agents for migraine prophylaxis in children and adolescents.

Topics: Adolescent; Amines; Anticonvulsants; Child; Cyclohexanecarboxylic Acids; Drug Tolerance; Fructose; Gabapentin; gamma-Aminobutyric Acid; Headache; Humans; Levetiracetam; Migraine Disorders; Piracetam; Placebos; Retrospective Studies; Topiramate; Treatment Failure; Valproic Acid

In the US, it is estimated that up to 10% of men and 25% of women, particularly those aged 25-55 years, experience debilitating migraines, such that the condition presents an enormous economic burden for patients, health systems, employers and society. Migraine headache is a particularly prevalent condition associated with major reductions in patients' quality of life. From a payer perspective, the implementation of relevant programmes of migraine prophylaxis is highly desirable. Consistent evidence exists, from several randomized, controlled studies, of the efficacy of amitriptyline, divalproex sodium, propranolol, timolol and topiramate in migraine prophylaxis. Considering resource utilization, various studies suggest that migraine prophylaxis with antiepileptics, antidepressants, beta-blockers or calcium channel antagonists markedly reduces triptan use and visits to physician offices and emergency departments (EDs), without compromising quality of care or treatment outcomes. Over recent years, the effects of topiramate in reducing resource utilization in patients with migraine have been relatively widely studied. In US claims database analyses involving >4000 patients with migraine, topiramate significantly reduced triptan use by up to 20% in the 12-month period after starting treatment. Reductions were also noted in the numbers of ED visits, diagnostic procedures, hospital admissions and migraine-related hospitalization days. These long-term benefits of topiramate manifested without any increase in overall headache-related costs. Furthermore, in detailed modelling analyses based on UK and US data, topiramate-induced savings in acute medical services were estimated to offset about one-quarter of the monthly per patient cost of the topiramate regimen, which was shown to be a dominant cost-effective intervention relative to no preventive therapy: cost-effectiveness ratios were calculated as pound 5728 per quality-adjusted life-year (QALY) [2005 costings] and $US10 888 per QALY (2002 costings), respectively. Overall, there is a need to improve quality of care in migraine, and prophylactic therapy appears to be an effective option, particularly with respect to decreasing resource use and improving productivity. For both health-plan payers and employers, topiramate appears to be a cost-effective intervention for preventing migraine.

Topics: Adult; Cost of Illness; Costs and Cost Analysis; Databases, Factual; Efficiency; Female; Fructose; Humans; Male; Migraine Disorders; Quality of Life; Quality-Adjusted Life Years; Topiramate; United Kingdom; United States

Chronic migraine has been linked to the excessive use of acute headache medications. Medication overuse (MO) is commonly considered the most significant risk factor for the progression of migraine from an episodic to a chronic condition. Managing MO is a challenge. Discontinuation of the acute medication can result in withdrawal headache, nausea, vomiting and sleep disturbances. This review summarizes the results from two similarly designed, randomized, placebo-controlled, multicentre studies of chronic migraine conducted in the USA and European Union. Both studies demonstrate the efficacy and safety of the migraine preventive medication, topiramate, for the treatment of chronic migraine in patient populations both with and without MO. These studies may have important implications for the future of chronic migraine management, suggesting that detoxification prior to initiating prophylactic therapy may not be required in all patients if MO is present.

Topics: Analgesics; Anticonvulsants; Chronic Disease; Fructose; Humans; Migraine Disorders; Topiramate

Increasing evidence shows that migraine, typically considered as an episodic disease, is a chronic and, in some patients, progressive disorder. Among neuromodulators used for migraine prevention, topiramate has a high level of evidence-based efficacy. Through its wide range of mechanisms of action topiramate increases the activation threshold resulting in neuronal stabilization and thereby reducing cortical neurons hyperexcitability, which is believed to be an important electrophysiological feature underlying the pathogenesis of epilepsy and migraine. Recent studies show that migraineurs have subclinical structural brain changes and persistent alteration of pain perception, in some cases correlated with the duration of the disease and the frequency of attacks that might play a role in the transformation of episodic migraine to chronic forms. An early and prolonged preventive treatment might reduce the risk of such transformation. Recent evidence suggests that topiramate, by reducing migraine frequency and use of acute medication, may prevent the negative progression of migraine. Furthermore, two recently completed multicenter, randomised, placebo-controlled trials have shown that treatment with topiramate 100 mg/day is effective and well tolerated in patients already progressed to chronic migraine and difficult to treat conditions associated with medication-overuse. Topiramate seems to be a preventive treatment, which might be able to act at different levels of the migraine cycle: reduction of frequency in episodic migraine, prevention, and treatment of chronic migraine.

Topics: Anticonvulsants; Brain; Chronic Disease; Disease Progression; Fructose; Humans; Migraine Disorders; Neurons; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome

Migraine and epilepsy share several common characteristic clinical features, and epilepsy is a comorbid disorder of migraine. Clinical studies have shown that some antiepileptic drugs are effective for the preventive treatment of migraine. The rationale for the use of these antiepileptic drugs in migraine prophylaxis is the hypothesis that migraine and epilepsy have several common pathophysiological mechanisms. It has been suggested that in these 2 pathological conditions, an imbalance exists between excitatory glutamate-mediated transmission and inhibitory GABA-mediated transmission in cerebral tissues, mainly in specific brain areas. Moreover, it has been postulated that abnormal activation of some kinds of voltage-gated ionic channels has been postulated to have a key role in both migraine and epilepsy, especially when caused by a genetic abnormality. It has been found that cortical spreading depression is involved in the pathophysiological mechanism of epilepsy, in addition to the generation of migraine aura. Preventive antiepileptic drugs can be chosen for treatment after considering clinical efficacy- scientific evidence, side effects, and patients' specific personal conditions. Recently, scientific evidence was found to demonstrate efficacy of valproic acid and topiramate in the preventive treatment of migraine. These drugs can reduce the incidence of migraine attacks in the large clinical studies. Other new antiepileptic drugs can be tried in future clinical study.

Topics: Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Drug Administration Schedule; Fructose; Gabapentin; gamma-Aminobutyric Acid; Glutamates; Humans; Ion Channels; Migraine Disorders; Premedication; Synaptic Transmission; Topiramate; Valproic Acid

Topics: Adrenergic beta-Antagonists; Amitriptyline; Evidence-Based Medicine; Family Practice; Female; Fructose; Humans; Male; Migraine Disorders; Neuroprotective Agents; Pain Measurement; Practice Guidelines as Topic; Prognosis; Propranolol; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Severity of Illness Index; Timolol; Topiramate; Treatment Outcome

The term chronic daily headache refers to a heterogeneous group of headache disorders characterized by a frequency of headaches on > or = 15 days per month. Chronic migraine is a subtype of chronic daily headache. The prevalence of chronic migraine is approximately 1%. Baseline attack frequency and acute medication overuse have been identified as potential risk factors for the progression of migraine from an episodic disorder to a chronic condition. There is an unmet patient need for effective and safe treatments for patients with chronic migraine, but data from rigorous controlled trials are limited. Previous studies have demonstrated that topiramate is an effective and safe preventive treatment for episodic migraine. In addition, pilot studies have suggested the utility of topiramate for the prevention of chronic migraine. Two randomized, double-blind, placebo-controlled, multicenter trials investigating the efficacy and safety of topiramate in the treatment of patients with chronic migraine have recently been completed. This review presents comparative data from these 2 clinical trials, which suggest that topiramate at a dose of 100 mg daily is effective and generally well tolerated in chronic migraine.

Topics: Chronic Disease; Fructose; Headache Disorders; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Risk Factors; Topiramate; Treatment Outcome

According to the criteria of the International Headache Society, migraine occurs in approximately 5 to 10% of children. As many as 30% of young patients with migraine experience such frequent and disabling attacks, or have unsatisfactory results and/or experience adverse effects with pharmacologic treatment of acute migraine attack, that daily preventive medications are required. Many studies have investigated the use of antiepileptic drugs in this indication but there is a paucity of placebo-controlled studies. So far, in the setting of migraine with and without aura, only flunarizine and topiramate have proved their efficacy in more than one placebo-controlled study. Uncontrolled studies suggest the possible efficacy of valproic acid, gabapentin, levetiracetam, zonisamide, and magnesium in preventive therapy of childhood periodic syndromes. Most of antiepileptic drugs used in pediatric preventive therapy are well tolerated. The most common adverse events are asthenia and somnolence.

Topics: Anticonvulsants; Child; Flunarizine; Fructose; Humans; Migraine Disorders; Topiramate

Episodic migraine is a disabling painful disease that can affect the normal function of daily routine activities such as performance at work and school, and home and social relationships. In addition to the physical disability during migraine, between attacks many patients experience a condition referred to as interictal burden, which can present as pre-event worry about future attacks and can result in the anticipatory use and/or overuse of acute care medications. The overuse of medication can often lead to medication overuse headaches (MOHs) and chronic migraine. Unfortunately, patients, and even some physicians, are often unaware of this phenomenon. Therefore, it is important for knowledgeable physicians to raise awareness and to address the risks of medication overuse with their patients through effective communication. Future management of medication overuse should include detoxification and a comprehensive programme that includes the use of preventive medications such as sodium valproate (divalproex sodium) and topiramate in order to reduce dependency on acute care medication. Also, MOHs may be most effectively managed with the initiation of preventive treatment prior to detoxification, in addition to the decreased use of acute care medication. A long-term treatment plan, including behavioural therapy, migraine preventive medication and appropriate acute care therapy, may be optimal in treating patients with MOHs.

Topics: Communication; Fructose; Headache Disorders, Secondary; Humans; Medication Therapy Management; Migraine Disorders; Neuroprotective Agents; Patient Education as Topic; Physician-Patient Relations; Topiramate; Valproic Acid

Topiramate is an effective and generally well-tolerated migraine preventive therapy, as shown in three large, randomized, double-blind, placebo-controlled registration trials. Based upon efficacy/tolerability, topiramate 100 mg/day (50 mg BID) is the recommended target dose for most patients with migraine. To further assess the safety and tolerability of topiramate for migraine prevention, we analyzed safety data from 1,580 patients who participated in the three pivotal registration trials or an earlier pilot, randomized, double-blind, placebo-controlled trial.. The safety population consisted of all patients who took >or=1 dose of study medication during the double-blind phase (topiramate 50 mg/day [N = 235], 100 mg/day [N = 386], 200 mg/day [N = 514], or placebo [N = 445]). Safety assessments included adverse event (AE) reports, physical examination, and clinical laboratory tests.. Paresthesia was the most common topiramate-associated AE (35%, 51%, and 49% of patients receiving topiramate 50 mg/day, 100 mg/day, or 200 mg/day, respectively [6% on placebo]). The most common topiramate-associated AE were generally mild or moderate in severity and occurred at consistently higher rates during the titration period, compared with the maintenance period of the double-blind phase. AEs leading to withdrawal from the recommended dose of topiramate 100 mg/day included paresthesia (8%), fatigue (5%), nausea (2%), and difficulty with concentration (2%). Serious AEs were infrequent, occurring in 2% of 1,135 topiramate-treated patients and 3% of 445 placebo-treated patients. Patients on topiramate experienced significant decreases in mean body weight compared with placebo.. Topiramate is generally safe and reasonably well tolerated for the prevention of migraine in adults. The most common topiramate-associated AEs were mild or moderate in severity and occurred more frequently during titration to target doses.

Topics: Adolescent; Adult; Aged; Child; Drug Tolerance; Fructose; Humans; Middle Aged; Migraine Disorders; Neuroprotective Agents; Patient Selection; Randomized Controlled Trials as Topic; Safety; Topiramate

Pediatric migraine is a disabling condition, which can cause a significant impact on quality of life. Currently, no drugs have been approved by the FDA for its preventive treatment. Our aim was to review the medical literature concerning the efficacy and tolerability of topiramate in the prophylactic treatment of migraine in children and adolescents. A total of five papers were reviewed: two randomized controlled trials (RCTs), a post-hoc subset analysis of adolescents who had been included in three RCTs carried out on adults and two open studies. Topiramate has been proven to reduce headache frequency and the accompanying disability. The frequency of side effects varied considerably among studies, the most frequent being weight loss, anorexia, abdominal pain, difficulties in concentrating, sedation and paresthesia. Since these adverse events, although often transitory, may be distressing for the child, we strongly recommend to assess the disability caused by the migraine episodes before deciding to initiate a prophylactic treatment. Nevertheless, dropout rates due to side effects in the studies were very low.

Topics: Adolescent; Child; Female; Fructose; Humans; Male; Migraine Disorders; Neuroprotective Agents; Pediatrics; PubMed; Randomized Controlled Trials as Topic; Retrospective Studies; Topiramate

Topiramate (TPM; TOPAMAX) is a broad-spectrum antiepileptic drug (AED) that is approved in many world markets for preventing or reducing the frequency of epileptic seizures (as monotherapy or adjunctive therapy), and for the prophylaxis of migraine. TPM, a sulfamate derivative of the naturally occurring sugar D-fructose, possesses several pharmacodynamic properties that may contribute to its clinically useful attributes, and to its observed adverse effects. The sulfamate moiety is essential, but not sufficient, for its pharmacodynamic properties. In this review, we discuss the known pharmacodynamic and pharmacokinetic properties of TPM, as well as its various clinically beneficial and adverse effects.

Topics: Adult; Aged; Anti-Obesity Agents; Anticonvulsants; Female; Fructose; Humans; Hypoglycemic Agents; Ion Channel Gating; Migraine Disorders; Neuroprotective Agents; Neurotransmitter Agents; Pregnancy; Receptors, Presynaptic; Topiramate

Migraine and epilepsy share several clinical features, and epilepsy is a comorbid condition of migraine. Clinical studies have shown that some antiepileptic drugs are effective at preventing migraine attacks. A rationale for their use in migraine prophylaxis is the hypothesis that migraine and epilepsy share several common pathogenetic mechanisms. An imbalance between excitatory glutamate-mediated transmission and GABA-mediated inhibition in specific brain areas has been postulated in these two pathological conditions. Moreover, abnormal activation of voltage-operated ionic channels has been implicated in both migraine and epilepsy. Cortical spreading depression has been found to be involved in the pathophysiology of epilepsy, in addition to the generation of migraine aura.

Topics: Amines; Animals; Anticonvulsants; Cyclohexanecarboxylic Acids; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Migraine Disorders; Topiramate; Valproic Acid

The studies of different antiepileptic drugs (AEDs) in the prophylaxis of episodic migraine, cluster headache (CH) and chronic headache forms (chronic daily headache, transformed or chronic migraine, chronic tension-type headache) are reviewed. The main results from published trials are summarised - focusing on responder rates as reported in placebo-controlled, double-blind studies. Most common adverse events are also discussed. This review indicated that robust evidence supports the use of sodium valproate-divalproex and of topiramate (TPM) in the prophylaxis of migraine, while definitive conclusions about the real effects of other AEDs in migraine cannot be drawn. Overall, evidence of efficacy of different AEDs in chronic headache forms and in CH is still lacking, most studies being open-label, small-sample trials. Nevertheless, encouraging data from controlled trials are emerging for TPM in the treatment of chronic headache forms.

Topics: Anticonvulsants; Clinical Trials as Topic; Cluster Headache; Drug Resistance; Fructose; Headache Disorders; Humans; Migraine Disorders; Topiramate; Treatment Outcome; Valproic Acid

Within the last decades significant progress has been made in the understanding of the underlying pathophysiological mechanisms of migraine. There is a general agreement now that migraine is not only a vascular phenomenon but also a genetically determined heterogenic ion-channelopathy resulting in cortical-spreading-depression-like events, the temporary impairment of antinociceptive structures of the brainstem and the activation of the trigeminal-vascular system. The development and use of drugs targeting ion-channels and subsequently reducing cortical excitability appears as a promising avenue for both the acute treatment of migraine and migraine prevention. This review summarizes the current knowledge and evidence for GABAergic drugs in the treatment of migraine.

Topics: Acute Disease; Amines; Animals; Cyclohexanecarboxylic Acids; Fructose; GABA Agents; GABA Antagonists; Gabapentin; gamma-Aminobutyric Acid; Humans; Migraine Disorders; Neuroprotective Agents; Pregabalin; Receptors, GABA; Receptors, GABA-A; Receptors, GABA-B; Topiramate; Valproic Acid

The onset of a migraine attack is associated with the activation of the trigemino-vascular system. Early intervention with triptans, which inhibit this activation is an effective treatment for migraine attacks. To avoid a cutaneous allodynia it is necessary to introduce as soon as possible the treatment with triptans. Drugs useful in the migraine prophylaxis tend to reduce the neuronal excitability in different areas of the central nervous system. The new definition of a chronic migraine is presented. This chronic migraine is frequently the result of an overuse of triptans. The practical aspects of the therapy of this specific migraine are described.

Topics: Acute Disease; Adrenergic beta-Antagonists; Anticonvulsants; Chronic Disease; Fructose; Humans; Hyperalgesia; Migraine Disorders; Topiramate; Tryptamines

Topiramate is one of several antiepileptic drugs that are used in the prevention of migraine, but the only one licensed for use in the UK. Topiramate has an extensive evidence base provided by double-blind, placebo-controlled trials to show that it is a safe, effective and well tolerated drug in the management of migraine. It has also been shown to have a role in the management of chronic migraine, which represents a challenge to primary care clinicians as well as headache specialists. Studies have demonstrated that topiramate can also be effective in preventing migraine in childhood and adolescence, although this is unlicensed in the UK. It has been shown in models both in the US and the UK to offer a cost benefit when direct and indirect costs are evaluated by reducing work loss, improving quality of life and reducing the use of increasingly scarce health resources.

Topics: Anticonvulsants; Drug Interactions; Fructose; Humans; Migraine Disorders; Quality of Life; Topiramate; Treatment Outcome

Migraine is a costly, recurrent condition that affects 28 million individuals in the United States yet remains underdiagnosed and undertreated. In 2004, the U.S. Food and Drug Administration approved topiramate for the prevention of migraine in adults, joining three other agents with this indication: divalproex sodium, propranolol, and timolol. We evaluated the role of topiramate in the treatment of migraine based on published literature and our clinical experiences. A qualitative systematic search of the literature from January 1966-December 2004 was conducted by using MEDLINE, and other pertinent literature was reviewed. Three large, randomized, placebo-controlled trials of topiramate for migraine prevention in individuals experiencing 3-12 attacks/month have been published, as have several small studies and a comparator trial with propranolol. Based on the results of these studies, 100 mg/day is the optimum topiramate dosage in terms of efficacy and tolerability. Using that dosage, the number of migraine attacks/month decreased by approximately two. Several other secondary outcome measures were also significantly reduced including the number of days/month with migraine and the use of acute treatment/attack. Suboptimal efficacy was shown with 50 mg/day, whereas 200 mg/day caused considerably more tolerability issues. Paresthesia was dose related and the most common cause of attrition. Cognitive dysfunction and weight loss were also commonly reported. The reduction by two migraines/month demonstrated with topiramate in clinical trials is similar to the published results for other preventive agents, though most of those studies were small, antiquated, and poorly designed. In contrast, the topiramate trials enrolled a larger number of patients and closely adhered to the International Headache Society research recommendations, strengthening the quality of results. Topiramate 100 mg/day is an effective option in adults who require migraine prophylaxis. Although the published efficacy results of the various migraine preventive agents are comparable, the superior study design of the topiramate trials warrants consideration of topiramate as an agent of choice for migraine prevention. Future studies of any preventive agent should include more refined quality-of-life outcomes.

Topics: Fructose; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Topiramate

Topiramate is approved for the preventive treatment of migraine in several countries based on the results of three large randomised, double-blind studies that showed that this compound was significantly more effective than placebo in migraine prophylaxis. We review the results of two studies: one which pooled data from the three controlled double-blind trials using 100 mg/day of topiramate, and an open-label extension of two of these trials in which patients received different topiramate doses for an eight-month maintenance period. The overall results confirm that topiramate is effective in reducing migraine frequency, and has a satisfactory tolerability profile.

Topics: Double-Blind Method; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome

About 14% of adults in the UK have migraines. Drugs used in migraine prophylaxis include beta-blockers (e.g. propranolol), 5HT antagonists (e.g. pizotifen), antidepressants (e.g. amitriptyline), antiepileptics (e.g. sodium valproate) and NSAIDs. The antiepileptic topiramate (Topamax-Janssen-Cilag) is licensed for the prophylaxis of migraine headache in patients aged over 16 years. Here we discuss the place of topiramate in migraine prophylaxis.

Topics: Analgesics; Double-Blind Method; Drug Costs; Fructose; Humans; Meta-Analysis as Topic; Migraine Disorders; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome

Migraine is a chronic neurologic disorder with heterogeneous characteristics resulting in a range of symptom profiles, burden, and disability. Migraine affects nearly 12% of the adult population in occidental countries, imposing considerable economic and social losses. The pharmacologic treatment of migraine includes preventive and acute strategies. A better understanding of the migraine pathophysiology along with the discovery of novel molecular targets has lead to a growing number of upcoming therapeutic proposals. This review focuses on new and emerging agents for the treatment of migraine.

Topics: Fructose; Humans; Migraine Disorders; Topiramate

The purposes of this review were to assess the efficacy of topiramate as monotherapy for epilepsy and migraine prevention, describe how it should be used, and give clinical advice on how to manage the practical aspects of dosing, titration, and possible adverse events in these 2 indications.. We searched the PubMed and BIOSIS databases using the key words topiramate, epilepsy, and migraine from the year 1987 onward, and subsequently focused the search on larger controlled trial studies of topiramate as monotherapy.. Studies have evaluated the use of topiramate as monotherapy in the treatment of partial-onset and generalized seizures and in the prevention of migraine. In a randomized study, 75% of epilepsy patients treated with 400 mg/d topiramate remained seizure free at 1 year. Patients in the same study treated with a lower dose of topiramate (50 mg/d) also experienced notable seizure reductions, with 59% of patients free of seizures at 1 year. A comparison trial of topiramate (100 or 200 mg/d), valproate, and carbamazepine found that topiramate was associated with a similar time to first posttreatment seizure as the other 2 agents (P = NS). Trials of topiramate monotherapy in migraine prevention found that 100 mg/d was associated with a > or =50% reduction in monthly migraine frequency in 49% to 54% of patients. The migraine prevention trials typically used a starting dose of 25 mg/d, with weekly increases of 25 mg and an initial monotherapy target dose of 100 mg/d. The most common adverse events associated with topiramate are paresthesia, weight loss, and other centrally mediated symptoms, many of which may be ameliorated by proper titration and dosing and by good communication between physician and patient.. Data from controlled trials suggest that 100 mg/d topiramate as monotherapy is effective in the treatment of partial-onset and generalized seizures and in the prevention of migraine.

Topics: Anticonvulsants; Drug Therapy, Combination; Epilepsy; Fructose; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Topiramate

The role of preventive treatment in the management of migraine must be reassessed. Many patients who would benefit from preventive therapy do not receive it, and many might benefit from earlier and more aggressive use of preventive therapy. Physicians who treat migraine have long recognized that a subset of patients with episodic migraine evolve to chronic forms of the disorder that are difficult to treat and have a poor outcome. This article reviews the evidence for current and emerging prophylactic migraine treatment and raises the possibility that timely use of prophylactic treatment might modify or prevent the transformation to chronic migraine and the extreme disability that characterizes a small but significant subset of the migraine population. Along with aggressive treatment of the acute pain and other symptoms of migraine, prevention of progression to severe forms of this disorder will increasingly be a focus and goal of the treatment.

Topics: Anticonvulsants; Disease Management; Fructose; Humans; Migraine Disorders; Topiramate

When treating patients with migraine, clinicians should consider prescribing appropriate combinations of acute and preventive therapies. An effective migraine-preventive therapy should be prescribed to patients with frequent (> or = 2 migraines per month) or severe migraine. Topiramate has been shown to be an effective and generally well-tolerated migraine prophylaxis (preventive) therapy in adults, as demonstrated in several large, controlled trials. The most common adverse events in these trials were paresthesia, fatigue, anorexia, nausea, taste alteration, and diarrhea. Most adverse events were mild to moderate and transient in nature. Although patients should take migraine-preventive medications for approximately 2 to 3 months before evaluating effect, topiramate has shown efficacy as early as the first month of treatment. This article describes "real-world" approaches to using topiramate as a migraine-preventive therapy. Topiramate has received regulatory approval for the prophylaxis of migraine headache in adults in the United States and many other countries. The practical issues discussed in this article will enable clinicians to maximize the effectiveness while minimizing the side effects associated with this preventive agent.

Topics: Adult; Anticonvulsants; Fructose; Humans; Migraine Disorders; Topiramate

The efficacy of topiramate in migraine prevention (prophylaxis) was established in two multicenter, randomized, double-blind, placebo-controlled, pivotal trials. Topiramate has received regulatory approval for use in adults for migraine prophylaxis (prevention) in the US and numerous other countries, including France, Ireland, Switzerland, Brazil, Taiwan, Spain, and Australia. Treatment with 100 or 200 mg per day of topiramate was associated with significant reductions in the frequency of migraine headaches, number of migraine days, and use of acute medications. No increase in efficacy was observed between 100 and 200 mg per day of topiramate. Based on efficacy and tolerability, 100 mg per day of topiramate should be the initial target dose for most patients. The most common adverse events were paresthesia, fatigue, decreased appetite, nausea, diarrhea, weight decrease, and taste perversion. Topiramate is a first-line migraine preventive drug and should especially be considered as a preferred treatment for all patients who are concerned about gaining weight, who are currently overweight, or who have coexisting epilepsy.

Topics: Adolescent; Adult; Aged; Animals; Anticonvulsants; Double-Blind Method; Fructose; Humans; Middle Aged; Migraine Disorders; Multicenter Studies as Topic; Pilot Projects; Randomized Controlled Trials as Topic; Topiramate

Topiramate is a neuromodulatory compound with stabilizing properties that was initially introduced for the management of partial seizures. Topiramate has been demonstrated to modify several receptor-gated and voltage-sensitive ion channels, including voltage-activated Na+ and Ca2+ channels and non-NMDA receptors. These receptors have been implicated in the pathophysiology of both epilepsy and migraine. The pharmacological mechanisms of action for topiramate that may explain its antiepileptic and migraine preventive activities will be discussed in this review. In addition, the potential relationship between the molecular activities of topiramate and its efficacy in epilepsy and migraine prevention will be emphasized.

Topics: Animals; Anticonvulsants; Fructose; Humans; Ion Channels; Migraine Disorders; Seizures; Topiramate

To review recent advances in preventive headache treatment.. Migraine may be a progressive disorder. Aggressive treatment may stop progression. Propranolol, the beta-blocker, and the anticonvulsant topiramate are effective for migraine prevention. Feverfew, montelukast and acupuncture have not proven effective.. New drugs and other treatment strategies expand the spectrum of preventive migraine treatments.

Topics: Acupuncture Therapy; Adrenergic beta-Antagonists; Anticonvulsants; Disease Progression; Fructose; Humans; Migraine Disorders; Propranolol; Topiramate

This paper reviews results of placebo-controlled trials on topiramate (TPM) prophylaxis in migraine patients, and discusses issues regarding the use of this medication in clinical practice. Data from well conducted double-blind controlled trials and from a comparative trial show that TPM is effective against migraine, confirming the experience of physicians in various countries. Lack of major contraindications, high responder rate, good tolerability at the target dose (100 mg/day) following slow titration, and lack of weight gain make TPM one of the most effective and well accepted drugs for migraine prophylaxis.

Topics: Anticonvulsants; Clinical Trials as Topic; Fructose; Humans; Migraine Disorders; Topiramate

With more than 8 million sufferers in Germany alone, migraine is one of the most frequent medical disorders. Recent discoveries in the pathophysiology and genetics of headaches, as well as specific developments in pharmacology, have paved the way for a significant improvement in both acute migraine treatment and migraine prevention. Within the group of 5-HT(1B/D)-agonists (triptans), seven substances with 23 dosages and formulations have been approved in Germany that allow the customized treatment of migraine attacks. In addition, several new drugs such as valproic acid or topiramate are now available as drugs of first choice for migraine prevention, as well as the well established beta blockers, thus enabling the physician to tailor the preventative treatment according to the individual needs of the patient.

Topics: Adrenergic beta-Antagonists; Fructose; Germany; Humans; Migraine Disorders; Practice Guidelines as Topic; Practice Patterns, Physicians'; Serotonin Antagonists; Topiramate; Tryptamines; Valproic Acid

Topiramate has been shown to be effective as a preventive treatment for migraine in three large placebo-controlled, dose-ranging trials. Because the protocols were similar in design using the same primary and secondary endpoints, data from these studies were pooled to evaluate the consistency of efficacy, efficacy by gender and tolerability of topiramate 100 mg/day (n = 386) versus placebo (n = 372). Topiramate was superior to placebo as measured by the reduction in mean monthly migraine frequency, monthly migraine days and monthly migraine duration. The responder rates, defined as at least 50% reduction for the respective parameters, were significantly in favour of topiramate (p < 0.001), for example 46.3% of patients on topiramate achieved at least 50% reduction in monthly migraine period frequency compared with 22.8% on placebo (p < 0.001). Use of medication to treat the acute migraine attack was significantly reduced by topiramate compared with placebo (p < 0.001). The therapeutic effect was consistent throughout the different studies and independent of gender. The most common adverse effect was paraesthesia, mostly of mild-to-moderate severity. The findings confirm that, at a dose of 100 mg/day, topiramate is an effective and well-tolerated drug for migraine prevention.

Topics: Adolescent; Adult; Aged; Double-Blind Method; Drug Administration Schedule; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome

Topics: Adolescent; Adult; Aged; Anticonvulsants; Anxiety Disorders; Female; Fructose; Glaucoma, Angle-Closure; Humans; Male; Middle Aged; Migraine Disorders; Myopia; Pain; Personality Disorders; Topiramate; Weight Loss

The number of migraine treatments and our understanding of migraine pathophysiology are both increasing. Newer treatments focus on migraine prevention. Botulinum toxin (BTX) is a potent neurotoxin used primarily to treat diseases associated with increased muscle activity. Recently, BTX was found to have antinociceptive effects that are probably independent of its muscle-relaxant action. Clinical trials support the efficacy of BTX type A (and possibly also type B) in the treatment of migraine. The anticonvulsant topiramate was recently shown to be effective for migraine prevention. At the low doses used for this indication, cognitive side effects are not a major concern. Another new approach to migraine prevention is angiotensin type 1 (AT1) receptor blockade. The high tolerability of the AT1 receptor blocker candesartan warrants further studies to assess its role in migraine prevention.

Topics: Angiotensin Receptor Antagonists; Anti-Dyskinesia Agents; Botulinum Toxins; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Neurotransmitter Agents; Topiramate

Topics: Anticonvulsants; Botulinum Toxins; Calcitonin Gene-Related Peptide; Central Nervous System; Clinical Trials as Topic; Drug Design; Fructose; Humans; Indoles; Meta-Analysis as Topic; Migraine Disorders; Pain; Piperidines; Pyrrolidines; Serotonin Receptor Agonists; Signal Transduction; Sumatriptan; Topiramate; Triazoles; Trigeminal Nerve; Tryptamines; Vasodilation

In this paper we review new treatment options for migraine prevention. Because we focus on new drugs, some of the data we present herein were acquired in well design double blind, controlled studies, while the efficacy of other medication is supported only by open, uncontrolled trials (noted in the text wherever appropriate).

Topics: Analgesics; Angiotensin-Converting Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Antioxidants; Benzimidazoles; Biphenyl Compounds; Botulinum Toxins; Clonidine; Coenzymes; Fructose; Humans; Lisinopril; Migraine Disorders; Neuroprotective Agents; Petasites; Phytotherapy; Piperazines; Tetrazoles; Topiramate; Triazoles; Ubiquinone

Evidence is emerging on the physiological processes underlying episodic migraine and the rationale for preventive treatment. Objectives for preventive treatment include limiting future pain and disability and potentially modulating the course of disease progression. Many factors influence medication choice for patients such as migraine type, patient preference, co-existing conditions, and medication side effects. In this paper, frequently prescribed treatment options for migraine prevention are reviewed. Most headache preventive medications treat other medical disorders and are found serendipitously to be beneficial in migraine or other headache disorders. A new treatment option is topiramate, with proven safety and efficacy across the largest controlled migraine prevention trials conducted to date. New clinical information is enhancing patient care and enabling clinicians to ease the burden of migraine worldwide.

Topics: Amitriptyline; Fructose; Humans; Migraine Disorders; Propranolol; Topiramate; Valproic Acid

The mainstay of migraine treatment is pharmacotherapy. There have been numerous medications used to prevent migraine headaches, including b-blockers, calcium-channel blockers, anticonvulsants, and nonsteroidal anti-inflammatory drugs. Sodium valproate is the only antiepileptic drug approved by the Food and Drug Administration for migraine prevention. Newer antiepileptics, including gabapentin and topiramate, are being evaluated for their role in preventive therapy. The mechanism of action of antiepileptics is not fully understood, but they all share a common role in enhancing gamma-aminobutyric acid-mediated inhibition. This article reviews the role of anticonvulsants in preventive migraine therapy.

Topics: Acetates; Amines; Anticonvulsants; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Drug Approval; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Migraine Disorders; Recurrence; Topiramate; Treatment Outcome; Valproic Acid

To review recent advances in acute and preventive migraine treatment.. The number of migraine drugs continues to expand, allowing for more flexible and tolerable treatment plans. Two new triptans, frovatriptan and eletriptan, and a nasal formulation of zolmitriptan have been recently developed. Eletriptan is effective for acute migraine treatment and may have some pharmacologic and clinical advantages. Frovatriptan has a longer half-life and lower headache recurrence rates compared with other triptans. It may be useful for patients who have prolonged attacks and high headache recurrence rate. Zolmitriptan nasal spray has a rapid onset of action and high efficacy. It should be considered when patients have rapid-onset attacks, especially when associated with severe nausea or vomiting. The butyrophenone neuroleptic droperidol is very effective in aborting acute migraine attacks. Central nervous system side effects are common, however, and the ECG should be monitored. Botulinum toxin type A shows promise as a safe, tolerable and effective drug for migraine prevention, with the unique advantages of almost no systemic adverse events and a long interval between treatments. The anticonvulsant topiramate is effective for migraine prevention. Cognitive side effects are of less concern with the lower doses needed for migraine. The angiotensin converting enzyme receptor blocker candesartan appears to be effective and highly tolerable in the prevention of migraine, but needs to be further evaluated.. New drugs expand the spectrum of migraine treatment both for the acute attack and for prevention.

Topics: Angiotensin Receptor Antagonists; Anticonvulsants; Antipsychotic Agents; Botulinum Toxins, Type A; Carbazoles; Droperidol; Fructose; Humans; Indoles; Migraine Disorders; Neuromuscular Agents; Oxazolidinones; Pyrrolidines; Serotonin Receptor Agonists; Topiramate; Tryptamines

Topics: Acetates; Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Migraine Disorders; Topiramate; Valproic Acid

To evaluate the efficiency of topiramate (TPM), an antiepileptic medication (AEM) which possesses multiple mechanisms of action and good pharmacokinetics, in the different types of childhood epilepsy and to make an appraisal of its value in migraines, bipolar disorder, eating disorders and neuropathic pain, according to studies that have been published. To do so, we have made use of an analysis of the literature, together with a multi centre study conducted in Spain and personal casuistry.. We consider the percentage of seizure free patients and of patients who responded (reduction of 50% or above in the frequency of the seizures) in childhood epilepsy, partial epilepsy, generalized tonic clonic seizures, absence seizures, tonic seizures, patients with diverse types of seizures, juvenile myoclonic epilepsy, Lennox Gastaut syndrome, falling sickness and GTCS, West s syndrome and Dravet s syndrome. With monotherapy, in partial epilepsy, between 39 and 54% of patients treated were seizure free. TPM has also proved to be efficient in experiments with animals, as a neuroprotector, and in clinical trials, in type I bipolar disorder, eating disorders, neuropathic pain and migraine.. TPM is an AEM offering a wide therapeutic spectrum that has proved to be efficient in clinical trials, expansion phases and observational studies, as an associated drug in partial epilepsy, generalized epilepsy, Lennox Gastaut syndrome, West s syndrome and Dravet s syndrome. It has proved to be more efficient in monotherapy, in partial epilepsy, as a first line AEM. TPM has also proved to be useful in mood disorders, eating disorders, neuropathic pain and tremor in observational studies, although this efficiency has not been backed up by clinical trials. In migraine and in clinical trials TPM has shown its efficiency. Its neuroprotective effect opens up new therapeutic perspectives.

Topics: Animals; Anticonvulsants; Bipolar Disorder; Clinical Trials as Topic; Drug Interactions; Epilepsy; Feeding and Eating Disorders; Fructose; Humans; Migraine Disorders; Multicenter Studies as Topic; Neuroprotective Agents; Pain; Spain; Topiramate

To examine group differences in self-reported migraine days among youth who completed the Childhood and Adolescent Migraine Prevention (CHAMP) trial prior to its closure and explore the relationship between self-reported and "nosology-derived" (i.e., International Classification of Headache Disorders, 3rd edition [ICHD-3]) migraine days.. The CHAMP trial compared amitriptyline and topiramate to placebo for migraine prevention in youth and proposed to analyze change in migraine days as a secondary outcome. There is considerable variability in the field regarding what constitutes a "migraine day," how this is determined and reported in trials, and how consistent these measures are with diagnostic nosology.. CHAMP trial completers (N = 175) were randomized to receive amitriptyline (n = 77), topiramate (n = 63), or placebo (n = 35). Participants maintained daily headache diaries where they reported each day with headache and if they considered that headache to be a migraine. For each headache day, participants completed a symptom record and reported about symptoms such as pain location(s) and presence of nausea/vomiting or photophobia and phonophobia. We examined group differences in self-reported migraine days at trial completion (summed from trial weeks 20-24) compared to baseline. We also used an algorithm to determine whether participants' symptom reports met ICHD-3 criteria for migraine without aura, and examined the association between self-reported and "nosology-derived" migraine days.. Results showed no significant differences between groups in self-reported migraine days over the course of the trial. Self-reported and "nosology-derived" migraine days during the baseline and treatment phases were strongly associated (r's = 0.73 and 0.83, respectively; p's < 0.001).. Regardless of treatment, CHAMP trial completers showed clinically important reductions in self-reported migraine days over the course of the trial (about 3.8 days less). The strong association between self-reported and "nosology-derived" migraine days suggests youth with migraine can recognize a day with migraine and reliably report their headache features and symptoms. Greater rigor and transparency in the calculation and reporting of migraine days in trials is needed.

Topics: Adolescent; Amitriptyline; Child; Double-Blind Method; Fructose; Headache; Headache Disorders; Humans; Migraine Disorders; Outcome Assessment, Health Care; Self Report; Topiramate; Treatment Outcome

Atogepant, an oral calcitonin gene-related peptide receptor antagonist, and topiramate, a commonly used oral antiepileptic, are approved as preventive migraine treatments. Given the distinct mechanisms of action of these treatments, it is possible that they may be coprescribed for migraine. This open-label, single-center, 2-cohort, phase 1 trial evaluated the potential pharmacokinetic (PK) 2-way drug-drug interactions (DDIs), safety, and tolerability of atogepant and topiramate in healthy adults. Participants received atogepant 60 mg once daily and topiramate 100 mg twice daily. Cohort 1 (N = 28) evaluated the effect of topiramate on the PK of atogepant; cohort 2 (N = 25) evaluated the effect of atogepant on the PK of topiramate. Potential DDIs were assessed using geometric mean ratios and 90% confidence intervals calculated for maximum plasma drug concentration at steady state (C

Topics: Adult; Drug Interactions; Healthy Volunteers; Humans; Migraine Disorders; Topiramate

To investigate the impact of topiramate versus flunarizine on the non-headache symptoms (NHS) of migraine, and to observe the changes of dopamine (DA) and prolactin (PRL) before and after prophylactic treatment.. Sixty-six episodic migraine patients were enrolled and randomized 1:1 to receive either flunarizine or topiramate treatment. Clinical characteristics and NHS associated with migraine were investigated before and after prophylactic treatment. The DA and PRL levels were also determined before and after prophylactic treatment.. The NHS of migraine in the two groups were significantly better after treatment than before treatment in premonitory phase (PP), headache phase (HP), and resolution phase (RP). The NHS in the two groups had no significant difference in PP, HP, and RP before and after treatment. In the flunarizine group, the PRL content after treatment was significantly higher than that before treatment (. The two classical prophylactic drugs of migraine were significantly effective in treating the NHS of migraine, but there was no significant difference between the two drugs. The DA-PRL axis may be involved in the underlying mechanism of the flunarizine treatment for the NHS of migraine.

Topics: Dopamine; Flunarizine; Fructose; Headache; Humans; Migraine Disorders; Topiramate

The aim of the TOP-PRO-study, a double-blind randomized controlled trial, was to assess the efficacy (non-inferiority) and tolerability of propranolol compared to topiramate for the prevention of chronic migraine.. Except for topiramate, oral preventive treatment for chronic migraine lacks credible evidence.. Chronic migraine patients aged above 18 years and less than 65 years of age, not on any preventive treatment were randomly allocated to receive topiramate (100 mg/day) or propranolol (160 mg/day). The primary efficacy outcome was the mean change in migraine days per 28 days at the end of 24 weeks from baseline. A mean difference of 1.5 days per four weeks was chosen as the cut-off delta value. Multiple secondary efficacy outcomes and treatment emergent adverse events were also assessed.. As against the planned sample size of 244, only 175 patients could be enrolled before the spread of the corona virus disease-2019 pandemic and enforcement of lockdown in India. Of the 175 randomized patients, 95 (topiramate 46 and propranolol 49) completed the trial. The mean change in migraine days was -5.3 ± 1.2 vs -7.3 ± 1.1 days (p = 0.226) for topiramate and propranolol groups respectively. Propranolol was found to be non-inferior and not superior to topiramate (point estimate of -1.99 with a 95% confidence interval of -5.23 to 1.25 days). Multiple secondary outcomes also did not differ between the two groups. Intention to treat analysis of 175 patients and per-protocol analysis of 95 patients yielded concordant results. There was no significant difference in the incidence of adverse events between the two groups.. Propranolol (160mg/day) was non-inferior, non-superior to topiramate (100mg/day) for the preventive treatment of chronic migraine and had a comparable tolerability profile.Trial Registration: Clinical Trials Registry-India CTRI/2019/05/018997).

Topics: Aged; Communicable Disease Control; COVID-19; Double-Blind Method; Fructose; Humans; Migraine Disorders; Propranolol; Topiramate; Treatment Outcome

We compared the tolerability and efficacy of erenumab, a monoclonal antibody binding to the calcitonin gene-related peptide receptor, to topiramate for migraine prophylaxis in adults.. HER-MES was a 24-week, randomised, double-blind, double-dummy, controlled trial conducted in 82 sites in Germany. Patients with ≥4 migraine days per month and naïve to study drugs were randomly assigned (1:1) to either subcutaneous erenumab (70 or 140 mg/month) plus topiramate placebo (erenumab group) or oral topiramate at the individual dose with optimal efficacy (50-100 mg/day) plus erenumab placebo (topiramate group).The primary endpoint was medication discontinuation due to an adverse event during the double-blind phase. The proportion of patients that achieved ≥50% reduction from baseline in monthly migraine days during the last 3 months of the double-blind phase was a secondary endpoint.. Seven hundred and seventy-seven patients were randomised (from 22 February 2019 to 29 July, 2020) and 95.1% completed the study. In the erenumab group, 10.6% discontinued medication due to adverse events compared to 38.9% in the topiramate group (odds ratio, 0.19; 95% confidence interval 0.13-0.27;. Erenumab demonstrated a favourable tolerability and efficacy profile compared to topiramate.Trial registration: ClinicalTrials.gov NCT03828539, URL: https://clinicaltrials.gov/ct2/show/NCT03828539.

Topics: Adult; Antibodies, Monoclonal, Humanized; Calcitonin Gene-Related Peptide Receptor Antagonists; Double-Blind Method; Humans; Migraine Disorders; Topiramate; Treatment Outcome

Examine preventive medication adherence among youth with migraine.. Adherence (self-report, pill count, and blood serum drug levels) was assessed as an ancillary study that utilized data from 328 CHAMP Study participants (ages 8-17). CHAMP was a multisite trial of preventive medications. Participants completed a prospective headache diary during a six-month active treatment period during which youth took amitriptyline, topiramate, or placebo pill twice daily. Self-reported medication adherence was collected via daily diary. At monthly study visits, pill count measures were captured. At trial month 3 (trial midpoint) and 6 (end of active trial), blood serum drug levels were obtained. Self-report and pill count adherence percentages were calculated for the active trial period, at each monthly study visit, and in the days prior to participants' mid-trial blood draw. Percentages of nonzero drug levels were calculated to assess blood serum drug level data. Adherence measures were compared and assessed in context of several sociodemographic factors. Multiple regression analyses investigated medication adherence as a predictor of headache outcomes.. Self-report and pill count adherence rates were high (over 90%) and sustained over the course of the trial period. Serum drug level adherence rates were somewhat lower and decreased significantly (from 84% to 76%) across the trial period [t (198) = 3.23, p = .001]. Adherence measures did not predict headache days at trial end; trial midpoint serum drug levels predicted headache-related disability.. Youth with migraine can demonstrate and sustain relatively high levels of medication adherence over the course of a clinical trial.

Topics: Adolescent; Child; Headache; Humans; Medication Adherence; Migraine Disorders; Prospective Studies; Topiramate

To compare the efficacy and tolerability of combination treatment of topiramate and greater occipital nerve block to topiramate monotherapy in adult chronic migraine patients.. Options for the preventive treatment of chronic migraine are limited and costly. Combination treatments do not have an evidence base yet.. This was a parallel group, 3 arms with 1:1:1 allocation ratio randomized controlled study in consecutive adult chronic migraine patients attending Headache Clinic in a tertiary care hospital. Patients received either topiramate monotherapy 100 mg/day (group A), or topiramate plus greater occipital nerve block with 40 mg lidocaine (2%) and 80mg (2 ml) methylprednisolone as the first injection followed by monthly injections of lidocaine for the next 2 months (group B) or topiramate plus greater occipital nerve block with 40 mg lidocaine (2%) injections monthly for 3 months (group C). The primary endpoint was the mean change in monthly migraine days at Month 3. Multiple secondary endpoints were assessed that included among others, achievement of ≥50% reduction in mean monthly headache days compared to baseline at Month 3 and assessment for any adverse events.. One hundred and twenty-five patients were randomized; 41 to group A, 44 to group B, and 40 to group C. Efficacy assessments were done for 121 patients. Patients receiving combination treatment of topiramate and greater occipital nerve block with steroids and lidocaine and greater occipital nerve block with only lidocaine compared to topiramate monotherapy showed greater reductions in monthly migraine days at Month 3 (-9.6 vs -7.3 days; p = 0.003) and (-10.1 vs -7.3 days; p < 0.001) respectively. Greater proportion of patients in both the combination treatment groups (added greater occipital nerve block with and without steroid) achieved ≥50% reduction in mean monthly headache days [71.4% vs 39%; OR (95% CI) 3.9(1.6-9.8); p = 0.004] and [62.4% vs 39%; OR (95% CI) 2.7(1.1-6.7); p = 0.034] respectively, compared to those receiving topiramate monotherapy. Adverse effects between the groups were comparable although patients receiving combination treatment with added greater occipital nerve block reported transient adverse effects like post-injection dizziness, local site swelling, and pain. No serious adverse event was reported.. Combination treatments of topiramate with monthly injections of greater occipital nerve block were more effective in reducing monthly migraine days in chronic migraine than topiramate monotherapy at Month 3. Combination treatments were well tolerated.

Topics: Adult; Double-Blind Method; Fructose; Headache; Humans; Lidocaine; Migraine Disorders; Nerve Block; Topiramate; Treatment Outcome

The aim of this study was to evaluate the efficacy and safety of tiapride compared to topiramate as a prophylactic in chronic migraine.. The study was conducted under randomised and double blind conditions. A total of 56 patients aged 18-65 years with chronic migraine were assigned to two treatment arms: tiapride, 100 mg twice daily, or topiramate, 25 mg twice daily, for 12 weeks. The primary endpoint was the change in the monthly average number of migraine days. In addition, measurements were performed to determine the change in the monthly number of headache days, the percentage of subjects with >50% and >75% decrease in their monthly migraine days, and the change in headache impact as measured by the Headache Impact Test-6.. The intention-to-treat population included 39 subjects (tiapride = 21; topiramate = 18), 35 of whom (tiapride = 18; topiramate = 16) completed the trial. The tiapride group had a mean reduction of 7.2 ± 7.5 migraine days per month compared to 7.6 ± 5.8 for the topiramate group (p = 0.86). As with the other efficacy variables measured, no differences were found between the two groups. Adverse side effects were mild in both groups.. In patients with chronic migraine, tiapride was found to be an effective, safe and well-tolerated prophylactic treatment when compared to topiramate.. Comparación de la tiaprida y el topiramato en el tratamiento profiláctico de la migraña crónica: estudio piloto, aleatorizado y doble ciego.. Objetivo. Evaluar la eficacia y la seguridad de la tiaprida en comparación con el topiramato en la profilaxis de la migraña crónica. Pacientes y métodos. Es un estudio aleatorizado y doble ciego. Un total de 56 pacientes de 18 a 65 años con migraña crónica fueron asignados a dos brazos de tratamiento: tiaprida, 100 mg dos veces al día, o topiramato, 25 mg dos veces al día, durante 12 semanas. El criterio de valoración principal fue el cambio en el promedio mensual de días de migraña. Además, se midió el cambio en el número mensual de días de cefalea, el porcentaje de sujetos con disminución > 50% y > 75% de sus días de migraña mensual, y el cambio del impacto de la cefalea medido por el Headache Impact Test-6. Resultados. La población por intención de tratar incluyó a 39 sujetos (tiaprida = 21; topiramato = 18) y completaron el ensayo 35 participantes (tiaprida = 18; topiramato = 16). El grupo con tiaprida tuvo una reducción media de 7,2 ± 7,5 días con migrañas por mes en comparación con 7,6 ± 5,8 para el grupo con topiramato (p = 0,86). Al igual que en las otras variables de eficacia medidas, no hubo diferencias significativas entre ambos grupos. Los efectos adversos fueron leves en ambos grupos. Conclusión. En pacientes con migraña crónica, la tiaprida demostró ser un tratamiento profiláctico eficaz, seguro y bien tolerado, al compararla con el topiramato.

Topics: Double-Blind Method; Fructose; Headache; Humans; Migraine Disorders; Pilot Projects; Tiapride Hydrochloride; Topiramate; Treatment Outcome

Topics: Anticonvulsants; Double-Blind Method; Fructose; Humans; Migraine Disorders; Nerve Block; Topiramate; Treatment Outcome

HER-MES was the first head-to-head, phase 4 trial to assess the tolerability and effectiveness of erenumab against standard of care treatment (topiramate). This post hoc analysis compared the efficacy of erenumab with topiramate in patients who completed the trial on study medication.. Post hoc sensitivity analysis was performed using the full analysis set. Outcomes assessed included the proportion of patients with a ≥50% reduction in monthly migraine days (MMD) from baseline (50% responder rate), over the last 3 months (months 4, 5, and 6) of the double-blind treatment phase (DBTP), the 50% responder rate during the first month of the DBTP, and change from baseline in MMD during the DBTP. Multiple imputation was done for efficacy values of patients who discontinued study treatment.. Patients (N = 777) were randomly assigned (1:1) to either 70 or 140 mg/month erenumab (N = 389) or 50-100 mg/day topiramate (N = 388). Of these, 334 patients (85.9%) receiving erenumab, and 231 patients (59.5%) receiving topiramate completed the DBTP on study medication. Patients on study medication until the end of the DBTP received a mean dose of 119 mg/month for erenumab and 92 mg/day for topiramate. At month 1, a significantly greater proportion of patients receiving erenumab (39.2%) reported ≥50% reduction in MMD from baseline compared with those receiving topiramate (24.0%; p < 0.001). In the last 3 months, a significantly larger proportion of patients receiving erenumab (60.3%) achieved ≥50% reduction in MMD from baseline compared with those receiving topiramate (43.3%; p < 0.001). Patients receiving erenumab demonstrated significantly greater reductions in MMD during the last 3 months from baseline versus those receiving topiramate (- 6.13 vs - 4.90; 95% CI: - 1.87 to - 0.61; p < 0.001).. This post hoc analysis demonstrated significantly superior efficacy of erenumab versus topiramate in achieving a ≥50% reduction in MMD with an early onset of efficacy.. ClinicalTrials.gov NCT03828539 .

Topics: Antibodies, Monoclonal, Humanized; Double-Blind Method; Humans; Migraine Disorders; Topiramate; Treatment Outcome

Identify preventive medication treatment response trajectories among youth participating in the Childhood and Adolescent Migraine Prevention study.. Data were evaluated from 328 youth (ages 8-17). Childhood and Adolescent Migraine Prevention study participants completed headache diaries during a 28-day baseline period and a 168-day active treatment period during which youth took amitriptyline, topiramate, or placebo. Daily headache occurrence trajectories were established across baseline and active treatment periods using longitudinal hierarchical linear modeling. We tested potential treatment group differences. We also compared final models to trajectory findings from a clinical trial of cognitive behavioral therapy plus amitriptyline for youth with chronic migraine to test for reproducibility.. Daily headache occurrence showed stability across baseline. Active treatment models revealed decreases in headache frequency that were most notable early in the trial period. Baseline and active treatment models did not differ by treatment group and replicated trajectory cognitive behavioral therapy plus amitriptyline trial findings.. Replicating headache frequency trajectories across clinical trials provides strong evidence that youth can improve quickly. Given no effect for medication, we need to better understand what drives this clinically meaningful improvement. Results also suggest an expected trajectory of treatment response for use in designing and determining endpoints for future clinical trials.

Topics: Adolescent; Amitriptyline; Child; Double-Blind Method; Headache; Headache Disorders; Humans; Migraine Disorders; Reproducibility of Results; Topiramate; Treatment Outcome

To compare effectiveness of onabotulinumtoxinA and topiramate for chronic migraine (CM) prevention.. The efficacy* of onabotulinumtoxinA and topiramate has been established in placebo-controlled randomized clinical trials (*defined as the benefit of treatment under ideal conditions). The effectiveness* of the 2 preventive treatments, however, has not been established (*the benefit of treatment under real-world conditions, representing a blend of efficacy and tolerability).. In this multicenter, randomized, parallel-group, post-authorization, open-label prospective study (FORWARD; ClinicalTrials.gov, NCT02191579), we randomized adults with CM (1:1) to onabotulinumtoxinA 155 U every 12 weeks for 3 cycles or topiramate "immediate release" 50-100 mg/day to week 36. Primary outcome measure was proportion of patients achieving ≥50% reduction in headache days (weeks 29-32). Missing values were imputed using baseline observation carried forward (BOCF) methodology. After 12 weeks, patients initially randomized to topiramate could cross over to onabotulinumtoxinA treatment. We monitored and recorded all adverse events (AEs).. We enrolled 282 patients (onabotulinumtoxinA, n = 140; topiramate, n = 142) and 148 patients completed randomized treatment (onabotulinumtoxinA, n = 120 [86%]; topiramate, n = 28 [20%]). Primary reasons for withdrawal were ineffective treatment (onabotulinumtoxinA, n = 7 [5%]; topiramate, n = 27 [19%]) and AEs (onabotulinumtoxinA, n = 5 [4%]; topiramate, n = 72 [51%]). Eighty topiramate patients crossed over to onabotulinumtoxinA. In the BOCF analysis, a significantly higher proportion of patients randomized to onabotulinumtoxinA experienced ≥50% reduction in headache frequency compared with those randomized to topiramate (40% [56/140] vs 12% [17/142], respectively; adjusted OR, 4.9 [95% CI, 2.7-9.1]; P < .001). OnabotulinumtoxinA was superior to topiramate in meeting secondary endpoints. In a post hoc analysis using observed data, the 50% responder rates at week 12 were 45.6% for onabotulinumtoxinA (n = 125) and 29.4% for topiramate (n = 109) (P = .015). AEs were reported by 48% (105/220) of onabotulinumtoxinA and 79% (112/142) of topiramate patients. Results were similar in those who crossed over to onabotulinumtoxinA.. While using imputation methods of accounting for differences in discontinuation rates, we found onabotulinumtoxinA to have greater clinical utility than topiramate, largely because of tolerability issues associated with the latter and a relatively higher number of onabotulinumtoxinA patients remaining on treatment.

Topics: Adult; Botulinum Toxins, Type A; Cross-Over Studies; Female; Headache; Humans; Male; Middle Aged; Migraine Disorders; Topiramate; Treatment Outcome

Topiramate for the treatment of migraine prophylaxis may cause side effects such as cognitive dysfunction. We aimed to investigate the topiramate's efficacy in migraineours and effect on cognitive functions. 24 migraine patients (Group 1) and 24 healthy participants (Group 2) were included. In both groups event-related potentials P300 Latency, Amplitude and N200 Latency, Amplitude's were evaluated. Topiramate treatment was ordered to group 1. Two months after treatment, the same parameters were evaluated. Monthly number of attacks, painful days, analgesic-triptan use and VAS scores were compared before and 2 months after treatment. Evaluation between group 1 and group 2 showed no difference. Group1's before and after treatment values were compared; all parameters after treatment were statistically significantly better. Group 1's number of attacks in a month, the number of painful days in a month, VAS score, the number of analgesic use, the number of triptan use had all decreased after treatment. 100 mg topiramate was effective in the treatment of migraine. However, electrophysiological studies showed that cognitive functions are also affected adversely.

Topics: Adult; Anticonvulsants; Cognition; Evoked Potentials; Female; Humans; Male; Middle Aged; Migraine Disorders; Topiramate

To evaluate the efficacy of sucrose in the prevention of migraine attacks.. Two randomized double-blinded pilot trials were conducted, one in college students and one in adults. Migraineurs were randomized into two groups that each received an oral liquid: for students, sucrose 5 g/day (s-group; n = 12) or glucose 2.5 g/day (g-group; n = 10) for 3 months; and for adults, sucrose 5 g/day (s-group; n = 10) or fructose 2.5 g/day (f-group; n = 9) for 6 months. The primary endpoint was the frequency of migraine attacks per month, and the secondary endpoints were mean duration and severity of migraine per attack. Continuous measurements were described as mean ± standard deviation (SD). The overall significance of the effects between different groups was tested using repeated measures analysis of variance (RANOVA), and the efficacy was evaluated using an intent-to-treat analysis.. Migraine frequency in the students declined significantly in the g-group (mean reduction ± SD: 0.65 ± 0.71; P < .01), but not in the s-group (0.33 ± 2.02; P = .58). RANOVA results suggested that the secondary endpoints significantly declined over time (all P < .01) with no differences between the groups. In the adult trial, mixed-effects model analysis showed that both the primary and secondary endpoints significantly declined over time with no significant differences between the groups.. Long-term consumption of a 5-g dose of sucrose for adult migraineurs or a 2.5-g dose of glucose for college student migraineurs may be as effective as preventive treatments.

Topics: Adult; Double-Blind Method; Humans; Migraine Disorders; Pilot Projects; Sucrose; Topiramate; Treatment Outcome

Topics: Adolescent; Amitriptyline; Child; Female; Follow-Up Studies; Humans; Male; Migraine Disorders; Monitoring, Physiologic; Pain Measurement; Patient Safety; Placebos; Primary Prevention; Risk Assessment; Severity of Illness Index; Topiramate; Treatment Outcome

To investigate the effects of topiramate on choroidal thickness and anterior chamber parameters using optical coherence tomography in the treatment of patients with migraine.. A total of 22 eyes of 22 adults (12 females, 10 males) diagnosed with migraine and scheduled to topiramate treatment for pain control were recruited in this prospective study. Choroidal thickness (CT), anterior chamber depth (ACD), anterior chamber angle (ACA), spherical refractive equivalent (SphEq) and intraocular pressure (IOP) measurements were recorded at baseline (prior the topiramate therapy), first and second month visits for the statistical analysis. One-way ANOVA with repeated measures test was used for the statistical evaluation.. Mean age of the patients was 40.2 ± 6.5 years. Mean CT at central fovea was 324 ± 47 μm initially, 341 ± 45 μm in the first month and 344 ± 46 μm in the second month, thus first and second month measures were significantly higher than base values (p < 0.001). There was also a slight increase in IOP values among baseline (15.5 ± 2.4 mmHg) and follow-up visits (17.5 ± 2.6 mmHg, 19.0 ± 3.3 mmHg, respectively, ` p = 0.001). Baseline ACD (3.66 ± 0.22 mm) measures significantly decreased at the first month (3.63 ± 0.22 mm) and second month (3.62 ± 0.22 mm, p = 0.009). Also, a significant reduction was detected in the first (36.2 ± 4.9°) and second month (35.9 ± 5.1°) ACA measures comparing with baseline (39.1 ± 5.1°, p = 0.05). A significant myopic shift was determined in the first and second month SphEq values (-0.08 ± 0.6, -0.10 ± 0.6, respectively, p = 0.05).. The study revealed increased CT and altered anterior chamber parameters and IOP due to topiramate therapy. Therefore, the patients using topiramate should be carefully monitored by an ophthalmologist considering the possible side effects.

Topics: Adult; Analgesics, Non-Narcotic; Anterior Chamber; Choroid; Female; Fructose; Humans; Intraocular Pressure; Male; Middle Aged; Migraine Disorders; Topiramate

This study's objective was to evaluate the efficacy and tolerability of transcutaneous occipital nerve stimulation (tONS) in patients with migraine, and to explore whether different tONS frequencies influenced treatment effectiveness. This was a randomized, controlled trial of tONS for prevention of migraine. Patients were randomized to 1 of 5 therapeutic groups before treatment for 1 month. Groups A through C received tONS at different frequencies (2 Hz, 100 Hz, and 2/100 Hz), group D underwent sham tONS intervention, and group E received topiramate orally. The primary outcomes were the 50% responder rate and headache characteristics. A total of 110 patients completed the study. The 50% responder rate was significantly greater in the groups undergoing active tONS and topiramate, compared with sham-treated group. A significant reduction in headache intensity was noted in each test group compared with the sham group; the groups undergoing tONS at different frequencies did not differ significantly. From baseline to the 1-month treatment period, the tONS group with 100 Hz and topiramate group exhibited significant decreases in headache duration. We conclude that tONS therapy is a new promising approach for migraine prevention. It has infrequent and mild adverse events and may be effective among patients who prefer nonpharmacological treatment.. This article introduces a randomized, controlled trial to illustrate tONS as a new approach for prevention of migraine. It shows tONS is well tolerated and could be considered as a promising treatment for patients who prefer to nonpharmacological therapy.

Topics: Administration, Oral; Adolescent; Adult; Biophysics; Double-Blind Method; Female; Follow-Up Studies; Fructose; Headache; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Occipital Bone; Pain Measurement; Peripheral Nerves; Topiramate; Transcutaneous Electric Nerve Stimulation; Treatment Outcome; Young Adult

Migraine is included in the top-ten disabling diseases and conditions among the Western populations. Non-invasive neurostimulation, including the Cefaly® device, for the treatment of various types of pain is a relatively new field of interest. The aim of the present study was to explore the clinical experience with Cefaly® in a cohort of migraine patients previously refractory or intolerant to topiramate prophylaxis.. A prospective, multi-center clinical study was performed in patients diagnosed with episodic or chronic migraine with a previous failure to topiramate treatment requiring prevention with Cefaly® according to the treating physician's suggestion. A 1-month period of baseline observation was followed by a 3-month period of observation during the use of transcutaneous supraorbital nerve stimulation (t-SNS) with Cefaly® as the only preventive treatment.. A small but statistically significant decline was shown over time in the number of days with headache (HA), the number of days with HA with intensity ≥5/10, and the number of days with use of acute medication after 3 months (p < 0.001 for all of the three changes). Twenty-three patients (65.7%) expressed their satisfaction and intent to continue treatment with Cefaly®. Compliance was higher among satisfied subjects compared to non-satisfied subjects. None of the explored factors were significantly associated with the reason for the failure of topiramate.. Three-months of preventive treatment for episodic or chronic migraine with t-SNS proved to be an effective, safe and well tolerated option for the treatment of patients with migraine who were intolerant or did not respond to topiramate.. ClinicalTrials NCT03125525 . Registered 21 April 2017.

Topics: Adult; Biomedical Research; Chronic Disease; Fructose; Headache; Humans; Middle Aged; Migraine Disorders; Neuroprotective Agents; Pain; Patient Compliance; Prospective Studies; Topiramate; Transcutaneous Electric Nerve Stimulation; Treatment Failure; Treatment Outcome; Young Adult

The pathophysiology of pain in migraine is related to the activation of the trigeminovascular system by releasing vasoactive neuropeptides, the most important of which is calcitonin gene-related peptide (CGRP), which causes a neurogenic inflammation in the leptomeningeal vessels.. To study whether CGRP is increased in frequent episodic migraine and whether preventive treatment with topiramate or zonisamide modifies its levels.. We studied 28 patients with episodic migraine with or without aura, in accordance with the International Headache Society criteria, with a frequency of 4-14 days/month. Plasma levels of CGRP were determined in all the patients during an interictal period (> 72 hours without pain). Patients were divided at random into two treatment groups, one with 50 mg/day of topiramate and the other with 50 mg/day of zonisamide, for three months. At the end of the active period the CGRP level was analysed again. The control group consisted of nine healthy subjects.. CGRP was significantly higher in the episodic migraine group than in the control group (50.61 ± 22.5 pg/mL versus 34.96 ± 17.03 pg/mL; p = 0.037). After treatment with neuromodulators no significant differences were found in the level of CGRP (46.11 ± 24.2 pg/mL basal versus 47.5 ± 24.88 pg/mL post-treatment). Neither were any differences found on analysing the topiramate and zonisamide groups individually.. The plasma level of CGRP is increased in episodic migraine, and its levels are not modified by treatment with low doses of topiramate or zonisamide.. Migraña episodica frecuente y peptido relacionado con el gen de la calcitonina. Influencia del tratamiento con topiramato y zonisamida en los niveles del peptido.. Introduccion. La fisiopatologia del dolor en la migraña se relaciona con la activacion del sistema trigeminovascular por medio de la liberacion de neuropeptidos vasoactivos, y el mas importante es el peptido relacionado con el gen de la calcitonina (CGRP), que causa una inflamacion neurogena en los vasos leptomeningeos. Objetivo. Investigar si el CGRP esta incrementado en la migraña episodica frecuente y si el tratamiento preventivo con topiramato o zonisamida modifica sus niveles. Sujetos y metodos. Se estudiaron 28 pacientes con migraña episodica con o sin aura, cumpliendo los criterios de la Sociedad Internacional de Cefaleas, con una frecuencia de 4-14 dias/mes. En todos los pacientes se determinaron los niveles plasmaticos del CGRP durante un periodo intercritico (> 72 h sin dolor). Los pacientes se aleatorizaron en dos grupos de tratamiento, uno con 50 mg/dia de topiramato y otro con 50 mg/dia de zonisamida, durante tres meses. Al finalizar el periodo activo se analizo nuevamente el nivel del CGRP. El grupo control lo constituyeron nueve sujetos sanos. Resultados. El CGRP fue significativamente superior en el grupo de migraña episodica comparado con el grupo control (50,61 ± 22,5 pg/mL frente a 34,96 ± 17,03 pg/mL; p = 0,037). Despues del tratamiento con neuromoduladores no se hallaron diferencias significativas en el nivel de CGRP (46,11 ± 24,2 pg/mL basal frente a 47,5 ± 24,88 pg/mL postratamiento). Tampoco se hallaron diferencias al analizar los grupos de topiramato y zonisamida de forma individualizada. Conclusiones. El nivel plasmatico del CGRP esta incrementado en la migraña episodica y sus niveles no son modificados por el tratamiento con dosis bajas de topiramato o zonisamida.

Topics: Adult; Aged; Calcitonin Gene-Related Peptide; Female; Fructose; Humans; Isoxazoles; Male; Middle Aged; Migraine Disorders; Topiramate; Young Adult; Zonisamide

Migraine is the sixth most common cause of disability in the world. Preventive migraine treatment is used to reduce frequency, severity and duration of attacks and therefore lightens the burden on the patients' quality of life and reduces disability. Topiramate is one of the preventive migraine treatments of proven efficacy. The mechanism of action underlying the preventive effect of topiramate in migraine remains largely unknown. Using functional magnetic resonance imaging (fMRI) we examined the central effects of a single dose of topiramate (100mg) on trigeminal pain in humans, compared to placebo (mannitol). In this prospective, within subject, randomized, placebo-controlled and double-blind study, 23 healthy participants received a standardized nociceptive trigeminal stimulation and control stimuli whilst being in the scanner. No differences in the subjective intensity ratings of the painful stimuli were observed between topiramate and placebo sessions. In contrast, topiramate significantly decreased the activity in the thalamus and other pain processing areas. Additionally, topiramate increased functional coupling between the thalamus and several brain regions such as the bilateral precuneus, posterior cingulate cortex and secondary somatosensory cortex. These data suggest that topiramate exhibits modulating effects on nociceptive processing in thalamo-cortical networks during trigeminal pain and that the preventive effect of topiramate on frequent migraine is probably mediated by an effect on thalamo-cortical networks.

Topics: Adult; Double-Blind Method; Female; Fructose; Gyrus Cinguli; Humans; Magnetic Resonance Imaging; Male; Migraine Disorders; Neuroprotective Agents; Pain; Placebo Effect; Prospective Studies; Somatosensory Cortex; Thalamus; Topiramate; Young Adult

Chronic migraine (CM) is a prevalent and devastating disorder with limited therapeutic options. This study explored the efficacy of 10 mg/d flunarizine for CM prophylaxis as compared with 50 mg/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 8 weeks 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, 10 mg/d flunarizine is more effective than 50 mg/d topiramate for CM prophylaxis.

Topics: Adult; Anticonvulsants; Double-Blind Method; Female; Flunarizine; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Topiramate

Which medication, if any, to use to prevent the headache of pediatric migraine has not been established.. We conducted a randomized, double-blind, placebo-controlled trial of amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a 2:2:1 ratio to receive one of the medications or placebo. The primary outcome was a relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with the last 28 days of a 24-week trial. Secondary outcomes were headache-related disability, headache days, number of trial completers, and serious adverse events that emerged during treatment.. A total of 361 patients underwent randomization, and 328 were included in the primary efficacy analysis (132 in the amitriptyline group, 130 in the topiramate group, and 66 in the placebo group). The trial was concluded early for futility after a planned interim analysis. There were no significant between-group differences in the primary outcome, which occurred in 52% of the patients in the amitriptyline group, 55% of those in the topiramate group, and 61% of those in the placebo group (amitriptyline vs. placebo, P=0.26; topiramate vs. placebo, P=0.48; amitriptyline vs. topiramate, P=0.49). There were also no significant between-group differences in headache-related disability, headache days, or the percentage of patients who completed the 24-week treatment period. Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo, including fatigue (30% vs. 14%) and dry mouth (25% vs. 12%) in the amitriptyline group and paresthesia (31% vs. 8%) and weight loss (8% vs. 0%) in the topiramate group. Three patients in the amitriptyline group had serious adverse events of altered mood, and one patient in the topiramate group had a suicide attempt.. There were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent migraine with amitriptyline, topiramate, or placebo over a period of 24 weeks. The active drugs were associated with higher rates of adverse events. (Funded by the National Institutes of Health; CHAMP ClinicalTrials.gov number, NCT01581281 ).

Topics: Adolescent; Amitriptyline; Anticonvulsants; Child; Double-Blind Method; Fatigue; Female; Fructose; Humans; Linear Models; Male; Migraine Disorders; Paresthesia; Placebos; Topiramate; Treatment Failure; Xerostomia

This study investigated another type of carbonic anhydrase inhibitor and antiepileptic drug, zonisamide, in order to evaluate its potential effectiveness for migraine prophylaxis refractory to topiramate, and to assess intolerability to adverse events, paresthesia in particular. This is an open-labeled retrospective single center study. We included headache patients who met the requirement of migraine without aura and were refractory to topiramate. Patients were treated only with zonisamide 100 mg/day, directly switching from topiramate. Patients were monitored every month for three months. A positive response to treatment (responders) was defined as a 50% or greater reduction in headache days at three months after study commencement, compared with baseline. One hundred and twenty migraineurs who were refractory to topiramate were recruited. Compared with baseline, headache days with zonisamide showed a decrease, compared with baseline (P < 0.01). Two patients complained of adverse effects, such as paresthesia. These results suggest that zonisamide is effective for migraine prophylaxis refractory to topiramate, or intolerable patients due to topiramate-induced paresthesia.

Topics: Adult; Female; Fructose; Headache; Humans; Isoxazoles; Male; Middle Aged; Migraine Disorders; Paresthesia; Retrospective Studies; Topiramate; Treatment Outcome; Zonisamide

To compare efficacy and safety of topiramate (TPM) and propranolol for migraine prophylaxis in children.. In a parallel single-blinded randomized clinical trial, 5-15 y-old referred migraineurs to Pediatric Neurology Clinic of Shahid Sadoughi Medical Sciences University, Yazd, Iran from May through October 2011, were evaluated. Patients were distributed into two groups, 50 of whom were treated with 3 mg/kg/d of topiramate (TPM) and another group of 50, were treated with 1 mg/kg of propranolol for 3 mo. Primary endpoints were efficacy in reduction of monthly frequency, severity, duration and headache related disability. Secondary outcome was clinical side effects.. Fifty two girls and 48 boys with mean age of 10.34 ± 2.31 y were evaluated. Monthly frequency, severity and duration of headache decreased with TPM, from 13.88 ± 8.4 to 4.13 ± 2.26 attacks, from 6.32 ± 1.93 to 2.8 ± 2.12, and from 2.36 ± 1.72 to 0.56 ± 0.5 h, respectively. Monthly frequency, severity and duration of headache also decreased with propranolol from 16.2 ± 6.74 to 8.8 ± 4.55 attacks, from 6.1 ± 1.54 to 4.8 ± 1.6 and from 2.26 ± 1.26 to 1.35 ± 1.08 h, respectively. Pediatric Migraine Disability Assessment score reduced from 31.88 ± 9.72 to 9.26 ± 7.21 with TPM and from 33.08 ± 8.98 to 23.64 ± 9.88 with propranolol. Transient mild side effects were seen in 18 % of TPM and in 10 % of propranolol (P = 0.249) groups.. Topiramate is more effective than propranolol for pediatric migraine prophylaxis.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Female; Fructose; Humans; Male; Migraine Disorders; Propranolol; Single-Blind Method; Topiramate

Lack of habituation during repetitive stimulation is the most consistent interictal abnormality of cortical information processing observed in migraine. Preventive migraine treatments might act by stabilizing cortical excitability level and thus the habituation to external stimuli.. We examined the effects of preventive treatment with topiramate on migraineur's habituation to nociceptive stimulation. Scalp potentials were evoked by Nd-YAP Laser stimulation of the hand dorsum and supraorbital region in 13 patients with migraine without aura (MO) and 15 healthy volunteers (HV). The exam was repeated in MO before and after treatment.. We observed a lack of habituation and lower initial amplitudes in MO compared to HV. These abnormalities reached statistical significance for N1 LEPs component, generated in the secondary somatosensory cortex (SII), but not for N2/P2 complex, generated in the insula and anterior cingulated cortex (ACC). Topiramate normalized the N1 habituation pattern in MO, with a significant correlation between clinical effects and normalization of neurophysiological responses.. Our results indicate a modulating action of topiramate on cortical processing of sensorial stimuli, mainly regarding the sensory-discriminative component of pain, elaborated by SII, without a significant effect on the affective dimension of pain, in which the ACC has an important role.

Topics: Adult; Evoked Potentials, Somatosensory; Female; Fructose; Habituation, Psychophysiologic; Humans; Lasers; Male; Migraine Disorders; Neuroprotective Agents; Pain; Pain Threshold; Topiramate

Although topiramate is widely prescribed for epilepsy and migraine, there is no intravenous product. We have developed an injectable topiramate formulation in which the drug is solubilized in a cyclodextrin matrix, Captisol(®) (Ligand Pharmaceuticals, Inc., La Jolla, CA). Our long-term goal is to evaluate intravenous topiramate for the treatment of neonatal seizures. Prior to studies in newborns, we carried out an investigation of injectable topiramate's safety and pharmacokinetics in adult patients.. Twenty adult volunteers with epilepsy or migraine on stable, on maintenance topiramate therapy were given 25 mg of a stable-labeled intravenous topiramate over 10 min, followed by their usual oral doses. Vital signs were taken, electrocardiography studies (ECGs) were recorded, and the infusion sites were periodically examined prior to and up to 24 h after dosing. Blood samples were collected prior to administration and serially for 96 h thereafter. Plasma concentrations of both stable-labeled and regular topiramate were measured using liquid chromatography-mass spectrometry (LC-MS). Concentration-time data were analyzed using a noncompartmental approach with WinNonlin 5.2 (Pharsight Corporation, Mountain View, CA, U.S.A.).. Seven patients experienced one or more of the following minor adverse events including nausea and vomiting (1), tingling around the lips (1), paresthesia in the arms and legs (1), and a mild vasovagal response with intravenous catheter placement (1). Included in the adverse events were four patients with epilepsy who had seizures consistent with their histories. There were no changes in heart rate, blood pressure, or ECG results, and there were no infusion site reactions. Pharmacokinetic parameters (mean ± standard deviation [SD]) determined following the intravenous dose included absolute bioavailability: 110 ± 16%, distribution volume: 0.79 ± 0.22 L/kg, clearance: 2.03 ± 1.07 L/h, and elimination half-life: 27.6 ± 9.7 h. Distribution volume, half-life, and clearance were significantly altered by enzyme-inducing drugs.. A single 25-mg dose of intravenous topiramate caused minimal infusion site or systemic adverse effects in patients taking oral topiramate. Pharmacokinetic results show that oral topiramate is completely absorbed and that its steady-state elimination half-life is longer than previously assumed, which permits once or twice daily dosing even in the presence of enzyme-inducing drugs. The information from this study can inform the design of subsequent studies in adults, older children, and newborns, including controlled clinical trials intended to determine the efficacy and safety of intravenous topiramate for neonatal seizures.

Topics: Administration, Oral; Adult; Aged; Anticonvulsants; Blood Pressure; Electrocardiography; Epilepsy; Female; Fructose; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Migraine Disorders; Topiramate

Migraine is one of the most common health problems for children and adolescents. If not successfully treated, it can impact patients and families with significant disability due to loss of school, work, and social function. When headaches become frequent, it is essential to try to prevent the headaches. For children and adolescents, this is guided by extrapolation from adult studies, a limited number of small studies in children and adolescents and practitioner preference. The aim of the Childhood and Adolescent Migraine Prevention (CHAMP) study is to determine the most effective preventive agent to use in children and adolescents.. CHAMP is a double-blinded, placebo-controlled, multicenter, comparative effectiveness study of amitriptyline and topiramate for the prevention of episodic and chronic migraine, designed to mirror real-world practice, sponsored by the US National Institute of Neurological Disorders and Stroke/National Institutes of Health (U01NS076788). The study will recruit 675 subjects between the ages of 8 and 17 years old, inclusive, who have migraine with or without aura or chronic migraine as defined by the International Classification of Headache Disorders, 2nd Edition, with at least 4 headaches in the 28 days prior to randomization. The subjects will be randomized in a 2:2:1 (amitriptyline: topiramate: placebo) ratio. Doses are weight based and will be slowly titrated over an 8-week period to a target dose of 1 mg/kg of amitriptyline and 2 mg/kg of topiramate. The primary outcome will be a 50% reduction in headache frequency between the 28-day baseline and the final 28 days of treatment (weeks 20-24).. The goal of the CHAMP study is to obtain level 1 evidence for the effectiveness of amitriptyline and topiramate in the prevention of migraine in children and adolescents. If this study proves to be positive, it will provide information to the practicing physician as how to best prevent migraine in children and adolescents and subsequently improve the disability and outcomes.

Topics: Adolescent; Amitriptyline; Analgesics; Child; Comparative Effectiveness Research; Double-Blind Method; Female; Fructose; Humans; Male; Migraine Disorders; Research Design; Topiramate

To compare the efficacy and safety of topiramate with gabapentin in the prophylaxis of migraine patients.. A 12-week randomised open label control trial was conducted at the Department of Pharmacology and Therapeutics, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre (JPMC), Karachi from January to March 2011 involving 80 outpatients who had a history of migraine. The sample was divided into two equal groups. Primary efficacy measure was changed into mean monthly migraine frequency. Secondary efficacy measure included reduction in severity and average duration of an attack. Chi square test and paired t-test were used to analyse the data through SPSS 15.. Reduction in mean monthly migraine frequency (10.67 +/- 4.25 to 1.82 +/- 2.02) in the topiramate group was significantly greater compared with (11.97 +/- 4.452 to 2.73 +/- 2.59) that in the gabapentin group (p < 0.001). Reduction in severity from 6.60 +/- 2.122 to 1.03 +/- 0.92 in the topiramate group was also significantly greater compared with 6.93 +/- 1.90 to 1.18 +/- 1.01 in the gabapentin group (p < 0.001). Reduction in the average duration of attacks from 25.77 +/- 22.32 hours to 1.05 +/- 1.06 hours in the topiramate group was significantly greater compared with 22.20 +/- 20.72 to 1.08 +/- 1.40 hours in the gabapentin group (p < 0.001). Weight loss and numbness were common adverse effects in the topiramate group. Dizziness, weight gain and somnolence were reported in the gabapentin group.. Gabapentin appeared well tolerated in 30 (75%) patients compared to topiramate in 23(57.5%) patients. Both drugs were equally effective in migraine prophylaxis.

Topics: Adult; Amines; Analgesics; Cohort Studies; Cyclohexanecarboxylic Acids; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Topiramate; Treatment Outcome; Young Adult

Topiramate and onabotulinumtoxin A have proven to be effective in chronic migraine with or without medication abuse according to recent criteria of the International Headache Society's Headache Classification.. To show that flunarizine is as effective as topiramate in cases of chronic migraine without medication abuse.. We conducted a prospective, non-randomised, comparative study of two groups of patients paired by age and sex, with chronic migraine without abuse, who had been treated preventively for the first time with topiramate or flunarizine.. Forty patients treated with flunarizine were assigned a patient of their same sex and age who was being treated with topiramate. The mean rate of reduction in intense migraines in the topiramate group was 59% and in the flunarizine group, 58.5% (p = 0.9444); the responder rate at four months of treatment did not show any significant differences either, the figures being 75% for topiramate and 70% for flunarizine (p = 0.6236). The mean reduction of other headaches in the topiramate group was 57% and in the flunarizine group, 64% (p = 0.4261); the responder rate at four months of treatment was similar in the two groups: 76%. The percentage of dropouts from treatment was higher with topiramate (19.5%) than with flunarizine (10%) (p = 0.3493). No serious side effects occurred in either of the groups. In all, 78.9% of the patients who took topiramate said they were satisfied with the drug versus 75% of those in the flunarizine group (p = 0.7903).. Flunarizine proved to be as effective as topiramate in the treatment of chronic migraine without medication abuse.. Estudio comparativo de la efectividad del topiramato y la flunaricina en series independientes de pacientes con migraña cronica sin abuso de medicacion.. Introduccion. El topiramato y la onabotulinumtoxina A han mostrado ser eficaces en la migraña cronica con o sin abuso de farmacos segun los criterios recientes de la Clasificacion de Cefaleas de la Sociedad Internacional de Cefaleas. Objetivo. Demostrar que la flunaricina es tan efectiva como el topiramato en la migraña cronica sin abuso de farmacos. Pacientes y metodos. Estudio prospectivo, no aleatorizado, comparativo de dos grupos de pacientes con similar edad y sexo, con migraña cronica sin abuso, tratados preventivamente por primera vez con topiramato o flunaricina. Resultados. A 40 pacientes tratados con flunaricina se les asigno un paciente del mismo sexo y edad tratado con topiramato. La media de reduccion de las migrañas intensas en el grupo del topiramato fue del 59% y en el grupo de la flunaricina, del 58,5% (p = 0,9444); la tasa de respondedores al cuarto mes de tratamiento tampoco mostro diferencias significativas, ya que fue del 75% para el topiramato y del 70% para la flunaricina (p = 0,6236). La media de reduccion de otras cefaleas en el grupo del topiramato fue del 57%, y en el grupo de la flunaricina, del 64% (p = 0,4261); la tasa de respondedores al cuarto mes de tratamiento fue del 76%, similar en ambos grupos. El porcentaje de abandonos del tratamiento fue mayor con el topiramato (19,5%) que con la flunaricina (10%) (p = 0,3493). En ninguno de los dos grupos hubo efectos adversos graves. Un 78,9% de los pacientes que tomo topiramato presento satisfaccion con el farmaco frente al 75% del grupo de la flunaricina (p = 0,7903). Conclusion. La flunaricina mostro ser tan efectiva como el topiramato en el tratamiento de la migraña cronica sin abuso de farmacos.

Topics: Adult; Calcium Channel Blockers; Chronic Disease; Cognition Disorders; Fatigue; Female; Flunarizine; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Patient Dropouts; Patient Satisfaction; Prospective Studies; Topiramate; Treatment Outcome

Topiramate is a small molecule widely used for the treatment of epilepsy, migraine, bipolar disorders and alcoholism, and its availability as a generic formulation could significantly reduce the National Health Service expenditure. A generic formulation, available in Italy under the trademark Sincronil, recently showed superimposable blood levels, after oral administration to healthy volunteers, with the reference formulation. In the present study we report the results of an open label, parallel group, randomized, controlled study performed to evaluate the efficacy, tolerability and impact on disability of two different formulations of topiramate (Sincronil and Topamax) in patients with migraine without aura.. Sixty patients aged between 18 and 65 years, suffering from migraine without aura with an attack frequency of 3-15 attacks/month were enrolled and received, after a titration phase lasting 20 days, randomly either Sincronil or Topamax at the dose of 25 mg twice daily for 3 months.. Fifteen out of the 30 patients who were administered Sincronil reported an improvement in the clinical condition, with a decrease in the frequency of attacks at the 3rd month of treatment higher than 50% with respect to the run-in period, 9 reported their clinical condition as being substantially unchanged and 6 reported that they had suspended the treatment within the first 4 weeks of therapy due to side effects. Among the 24 patients who continued treatment up to the 3rd month, the frequency of attacks during the 3rd month of treatment was significantly decreased from 7 ± 3.6 to 3.7 ± 3.7 (P<0.0001), migraine severity was reduced from 2.5 ± 0.5 to 1.7 ± 0.7 (P<0.0005) and the MIDAS score was reduced from 14.3 ± 4.9 to 8.6 ± 5.5 (P<0.0001). Sixteen out of the 30 patients who were administered Topamax reported an improvement in the clinical condition with a reduction in the attack frequency at the 3rd month of treatment higher than 50% with respect to the run-in period, 10 reported a substantially unchanged clinical condition and 4 stopped the treatment within the first weeks due to side effects. Among the 26 patients who continued treatment up to the 3rd month, headache frequency during the 3rd month of treatment was significantly reduced, from 7.3 ± 2.6 to 3.5 ± 2.7 (P<0.0001), migraine severity decreased from 2.4 ± 0.6 to 1.6 ± 0.8 (P<0.0005) and the MIDAS score from 14.1 ± 4.2 to 6.8 ± 4.8 (P<0.0001).. In conclusion, in this study Topamax (reference product) and Sincronil (generic formulation) have proven therapeutically equivalent and both products were well tolerated.

Topics: Adolescent; Adult; Aged; Central Nervous System Agents; Chemistry, Pharmaceutical; Drugs, Generic; Female; Fructose; Humans; Italy; Male; Middle Aged; Migraine Disorders; Severity of Illness Index; Time Factors; Topiramate; Treatment Outcome; Young Adult

This study aimed to identify predictive factors of outcome in patients with chronic migraine (CM) treated with acupuncture or topiramate in a randomized controlled trial.. Sixty-six consecutive CM patients were treated with either acupuncture (n=33) or topiramate (n=33) in a 12-week period. Data on potential predictive factors were collected at baseline, and secondary data analysis was performed to identify factors associated with treatment response. Treatment prognosis was defined as the change in mean number of moderate/severe headache days per 4 weeks from the 4-week baseline periods.. The median change in mean number of moderate/severe headache days per 4 weeks for patients with higher baseline headache days (>20 d) was significantly greater than that for lower baseline headache days (≤ 20 d) (median ± interquartile range: -12 ± 2 vs. -10 ± 1 d, P=0.01) in acupuncture group. There was a greater change in mean number of moderate/severe headache days per 4 weeks for high moderate/severe headache days (>20 d) than in low days (≤ 20 d) (-12 ± 1 vs. -10 ± 2 d, P=0.015) in acupuncture group. patients with throbbing symptoms had better prognosis with acupuncture than those without throbbing (-12 ± 2 vs. -9.5 ± 2.5 d, P=0.004). Higher score (>5 points) in the general expectations for improvement predicted better response in both treatment groups (>5 vs. ≤ 5 points: -12 ± 2 vs. -9 ± 2 d for acupuncture group; -10 ± 3 vs. -7 ± 4 d for topiramate group; P<0.001).. Some variables can predict outcome in acupuncture or topiramate treatment of CM patients. Identifying predictors of prognosis of both treatments for CM may help improve outcomes in future work.

Topics: Acupuncture Therapy; Adult; Chronic Disease; Disability Evaluation; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Pain Measurement; Predictive Value of Tests; Prognosis; Surveys and Questionnaires; Topiramate; Treatment Outcome

The present study was performed to evaluate the efficacy of low-dose topiramate and compare it with sodium valproate that is prevalently prescribed as a migraine prophylaxis. This was a randomized, double-blind, parallel-group clinical trial on 56 patients who completed the course of study. Topiramate and valproate were administered at 50 mg/day and 400 mg/day, respectively, during the follow-up period. Frequency, intensity, duration, associated symptoms with headaches, analgesics use, as well as drugs' side effects were studied. Participants completed MIDAS and HIT-6 questionnaires before and after treatment. Frequency, intensity, and duration of migraine headaches as well as MIDAS score and symptomatic medications decreased significantly between repeated follow-up visits in both groups. Responder rate for patients treated with topiramate and valproate were 71.6% and 64.3%, respectively, and the difference between the two groups was not statistically significant. The reduction of headache severity in the topiramate group was significantly more than that in the valproate group (p = .027). During the study, no statistically significant reduction in associated symptoms with migraine were observed in both the groups. Topiramate dose of 50 mg/day with fewer side effects in comparison with its higher doses may be an appropriate substitution for first-line migraine prophylaxis such as valproate.

Topics: Adult; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fructose; Humans; Male; Migraine Disorders; Severity of Illness Index; Topiramate; Valproic Acid

A sizeable proportion of migraineurs in need of preventive therapy do not significantly benefit from monotherapy. The objective of the study is to conduct a randomized controlled trial testing whether combination therapy of topiramate and nortriptyline is useful in patients who had less than 50% decrease in headache frequency with the use of the single agents. Patients with episodic migraine were enrolled if they had less than 50% reduction in headache frequency after 8 weeks of using topiramate (TPM) (100 mg/day) or nortriptyline (NTP) (30 mg/day). They were randomized (blinded fashion) to have placebo added to their regimen, or to receive the second medication (combination therapy). Primary endpoint was decrease in number of headache days at 6 weeks, relative to baseline, comparing both groups. Secondary endpoint was proportion of patients with at least 50% reduction in headache frequency at 6 weeks relative to baseline. A total of 38 patients were randomized to receive combination therapy, while 30 continued on monotherapy (with placebo) (six drop outs in the combination group and three for each single drug group). For the primary endpoint, mean and standard deviation (SD) of reduction in headache frequency were 4.6 (1.9) for those in polytherapy, relative to 3.5 (2.3) for those in monotherapy. Differences were significant (p < 0.05]. Similarly, 78.3% of patients randomized to receive polytherapy had at least 50% headache reduction, as compared to 37% in monotherapy (p < 0.04). Finally we conclude that combination therapy (of TPM and NTP) is effective in patients with incomplete benefit using these agents in monotherapy.

Topics: Adult; Analgesics; Double-Blind Method; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Nortriptyline; Topiramate; Young Adult

To assess efficacy and tolerability of rizatriptan orally disintegrating tablet (ODT) for treatment of acute migraine in patients using topiramate for migraine prophylaxis.. There are limited data from prospective controlled trials demonstrating the benefit of triptans in patients who experience migraine attacks while taking prophylactic medication.. This was a worldwide, randomized, placebo-controlled, double-blind, multiple-attack study in adults with a >1-year history of migraine taking a stable dose of topiramate for migraine prophylaxis and experiencing ≥2 moderate/severe attacks per month. Participants treated 3 moderate/severe attacks in crossover fashion (2 with rizatriptan 10-mg ODT, 1 with placebo) following random assignment to 1 of 3 treatment sequences. The primary end point was 2-hour pain relief.. Two-hour pain relief was significantly greater with rizatriptan compared with placebo (55.0% vs 17.4%, P < .001). Response rates also favored rizatriptan for sustained pain relief from 2-24 hours (32.6% vs 11.1%, P < .001), 2-hour pain freedom (36.0% vs 6.5%, P < .001), normal functional ability at 2 hours (42.2% vs 12.7%, P < .001), and overall treatment satisfaction at 24 hours (60.8% vs 33.6%, P < .001). Few participants reported adverse experiences (16 [15.8%] with rizatriptan, 3 [3.2%] with placebo); none were serious.. Rizatriptan 10-mg ODT was superior to placebo at all pain end points for treatment of acute migraine in patients using topiramate for migraine prophylaxis. Rizatriptan was generally well tolerated in this population. These results are comparable with those from clinical trials in patients not using prophylaxis, suggesting that the use of topiramate does not affect the efficacy or tolerability of rizatriptan for acute migraine treatment.

Topics: Acute Disease; Adolescent; Adult; Aged; Disability Evaluation; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Pain Measurement; Prospective Studies; Serotonin Receptor Agonists; Severity of Illness Index; Time Factors; Topiramate; Treatment Outcome; Triazoles; Tryptamines; Young Adult

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.. 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.. 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).. 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).. 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.

Topics: Adolescent; Adult; Carbazoles; Costs and Cost Analysis; Drug Administration Schedule; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Pain Perception; Patient Satisfaction; Pilot Projects; Quality of Life; Serotonin Receptor Agonists; Single-Blind Method; Surveys and Questionnaires; Time Factors; Topiramate; Treatment Outcome; Tryptamines; Young Adult

The objective of this study was to observe the efficacy, safety, and side effects of a combination of flunarizine plus topiramate compared with either flunarizine and or toparamate alone for migraine prophylaxis.. Out of 150 patients with migraine recruited into the study and randomly assigned to one of three conditions, 126 completed the trial in their group: flunarizine (39), topiramate (44), and flunarizine plus topiramate (43). Patient information was assessed at enrollment and at follow-up visits at the end of months 1-3, 6, 9, and 12. The primary measure of efficacy reduction in mean monthly migraine frequency of at least 50% as compared with baseline. Secondary efficacy parameters included reduction in mean monthly migraine days and severity of headache. Side effects were compared in the three groups by recording adverse reactions and weight changes.. The proportion whose monthly headache frequency decreased more than 50% was 66.7% (26/39) in the flunarizine group, 72.7% (32/44) in the topiramate group and 76.7% (33/43) in the combination group, respectively (P=0.593). The mean monthly days and severity of headache in the three groups also declined and was more significant in the flunarizine plus topiramate group than in the flunarizine group and the topiramate group (P<0.05). In the flunarizine group, the average weight change was 0.6kg. Topiramate was associated with a mean weight loss was of -0.9kg in the topiramate group and -0.2kg in the flunarizine plus topiramate group.. Flunarizine, topiramate, and the combination of flunarizine with topiramate are all effective and have good tolerability in migraine prophylaxis. Adding topiramate to flunarizine may reduce the latter's impact on body weight.

Topics: Adolescent; Adult; Aged; Drug Therapy, Combination; Female; Flunarizine; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Prospective Studies; Topiramate; Treatment Outcome; Young Adult

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

Topics: Adolescent; Adult; Aged; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Propranolol; Topiramate; Treatment Outcome; Young Adult

The study sought to evaluate whether topiramate prevents development of chronic daily headache (CDH, ≥15 headache days per month) in adult subjects with high-frequency episodic migraine (HFEM, 9-14 migraine headache days/month). A secondary objective was to assess the efficacy of topiramate as preventive migraine treatment in this population.. This was a multicenter, randomized, double-blind, placebo-controlled study comparing topiramate 100 mg/day and placebo for 26 weeks. The primary efficacy variable was new-onset CDH at month 6. Secondary efficacy measures included migraine and headache days. Adverse events (AEs) were evaluated.. A total of 159 topiramate subjects and 171 placebo subjects were efficacy-evaluable. At month 6, 1.4% of topiramate subjects versus 2.3% of placebo subjects had CDH (p = .589). Compared with placebo, topiramate treatment was associated with statistically significant reductions in mean number of migraine days (6.6 vs. 5.3/28 days; p = .001) and headache days (6.6 vs 5.3/28 days; p = .001). Most commonly reported AEs in the topiramate versus placebo group included paresthesia (32.4% vs. 7.0%), fatigue (14.8% vs. 8.6%), dizziness (11.4% vs. 7.6%) and nausea (10.8% vs. 9.2%).. Topiramate 100 mg/day did not prevent the development of CDH at six months in subjects with HFEM. Topiramate was effective in reducing headache days and migraine headache days and generally well tolerated.

Topics: Adult; Double-Blind Method; Female; Fructose; Headache Disorders; Humans; Male; Migraine Disorders; Neuroprotective Agents; Topiramate; Treatment Outcome

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).. 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.. 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.. OnabotulinumtoxinA and topiramate demonstrated similar efficacy for subjects with CM as determined by Global Physician Assessment and supported by multiple secondary endpoint measures.

Topics: Adolescent; Adult; Aged; Botulinum Toxins, Type A; Chronic Disease; Double-Blind Method; Endpoint Determination; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuromuscular Agents; Neuroprotective Agents; Pilot Projects; Prospective Studies; Surveys and Questionnaires; Topiramate; Young Adult

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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Dose-Response Relationship, Drug; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Prospective Studies; Topiramate; Treatment Outcome; Valproic Acid; Young Adult

Topics: Adolescent; Child; Cognition Disorders; Double-Blind Method; Female; Fructose; Humans; Male; Migraine Disorders; Neuroprotective Agents; Neuropsychological Tests; Topiramate

Scientific evidence regarding exercise in migraine prophylaxis is required. Therefore this study aimed to evaluate the effects of exercise in migraine prevention.. In a randomized, controlled trial of adults with migraine, exercising for 40 minutes three times a week was compared to relaxation according to a recorded programme or daily topiramate use, which was slowly increased to the individual's highest tolerable dose (maximum 200 mg/day). The treatment period lasted for 3 months, and migraine status, quality of life, level of physical activity, and oxygen uptake were evaluated. The primary efficacy variable was the mean reduction of the frequency of migraine attacks during the final month of treatment compared with the baseline.. Ninety-one patients were randomized and included in the intention-to-treat analysis. The primary efficacy variable showed a mean reduction of 0.93 (95% confidence interval (CI) 0.31-1.54) attacks in the exercise group, 0.83 (95% CI 0.22-1.45) attacks in the relaxation group, and 0.97 (95% CI 0.36-1.58) attacks in the topiramate group. No significant difference was observed between the groups (p = 0.95).. Exercise may be an option for the prophylactic treatment of migraine in patients who do not benefit from or do not want to take daily medication.

Topics: Adult; Anticonvulsants; Exercise Therapy; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Motor Activity; Oxygen; Prospective Studies; Quality of Life; Relaxation Therapy; Topiramate; Treatment Outcome

The aim of this study was to investigate the efficacy and tolerability of acupuncture compared with topiramate treatment in chronic migraine (CM) prophylaxis.. A total of 66 consecutive and prospective CM patients were randomly divided into two treatment arms: 1) acupuncture group: acupuncture administered in 24 sessions over 12 weeks (n = 33); and 2) topiramate group: a 4-week titration, initiated at 25 mg/day and increased by 25 mg/day weekly to a maximum of 100 mg/day followed by an 8-week maintenance period (n = 33).. A significantly larger decrease in the mean monthly number of moderate/severe headache days (primary end point) from 20.2 ± 1.5 days to 9.8 ± 2.8 days was observed in the acupuncture group compared with 19.8 ± 1.7 days to 12.0 ± 4.1 days in the topiramate group (p < .01) Significant differences favoring acupuncture were also observed for all secondary efficacy variables. These significant differences still existed when we focused on those patients who were overusing acute medication. Adverse events occurred in 6% of acupuncture group and 66% of topiramate group.. We suggest that acupuncture could be considered a treatment option for CM patients willing to undergo this prophylactic treatment, even for those patients with medication overuse.

Topics: Acupuncture; Adult; Aged; Chronic Disease; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Pain; Pain Measurement; Topiramate; Treatment Outcome; Young Adult

To assess the efficacy of topiramate in reducing both the frequency and the severity of vertigo and headache attacks in patients with migrainous vertigo and to compare 50 and 100 mg/day doses of the drug.. Thirty patients diagnosed as definite migrainous vertigo were recruited in the study. Vertigo and headache frequency was determined as the monthly number of attacks whereas severity was determined by visual analog scales measured in millimeters from 0 to 100. Patients were randomized to either 50 or 100 mg/day topiramate for 6 months. Vertigo and headache frequency and severity were evaluated at the end of the study period.. Number of mothly vertigo attacks decreased significantly in the overall group after treatment (median from 5.5 to 1; P < .01). The same was true for monthly headache attacks (median from 4 to 1; P < .01). A statically significant improvement in vertigo severity was noted (median from 80 to 20 mm; P < .01). Headache severity showed significant improvement as well (median from 60 to 30 mm; P < .01). No statistically significant difference between high- and low-dose groups was present regarding efficacy (P > .05). Four patients in the high-dose group discontinued treatment at the end of the first month because of adverse effects.. In the overall group, topiramate was found to be effective in reducing the frequency and the severity of vertigo and headache attacks. Both doses of the drug were equally efficacious. The 50 mg/day dose seems to be appropriate as higher adverse effects were noted when 100 mg/day was used.

Topics: Adolescent; Adult; Anticonvulsants; Diagnostic Imaging; Disability Evaluation; Dose-Response Relationship, Drug; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neurologic Examination; Outcome Assessment, Health Care; Topiramate; Treatment Outcome; Vertigo; Young Adult

Data from the Prolonged Migraine Prevention (PROMPT) with Topiramate trial were evaluated post hoc to determine whether topiramate could prevent migraine auras, and whether its efficacy in preventing migraine headaches was similar in patients with (MA; n = 269) and without (MoA; n = 542) aura. Migraines and auras were recorded during prospective baseline, 6-month open-label (OL) topiramate and 6-month double-blind (DB), placebo-controlled phases. In the last 28 OL days, migraines without aura and migraine auras decreased by 43.1% and 54.1%, respectively, in MA patients. MoA patients experienced a 44.3% reduction in migraines. In the DB phase, increases in migraines with placebo vs. topiramate were similar to the full study, but were generally not statistically significant, probably due to lack of power in the subgroup analysis. Similarly, there were no statistically significant changes in number of auras between groups. Thus, topiramate appears to reduce migraine auras in parallel with headache reductions, which are similar in patients with and without aura.

Topics: Adolescent; Adult; Aged; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Migraine with Aura; Neuroprotective Agents; Topiramate; Treatment Outcome; Young Adult

The majority of patients with migraine headaches are treated in non-specialized institutions though data on treatment outcomes are largely derived from tertiary care centers. The current non-interventional study explores efficacy and tolerability outcomes of patients with episodic migraines receiving topiramate as preventive agent in a general practice setting. A total of 366 patients (87% female, mean age 41.8 +/- 11.6 years) were eligible for migraine prevention and treated with flexible dose topiramate for 6 months (core phase), and optionally for a total of 12 months (follow-up phase). Overall, 261 patients (77.7% of safety analysis set, SAF) completed the core phase. Reasons for discontinuation included adverse events (2.1%), lost to follow-up (1.8%), other reasons (1.5%), and end of therapy (0.3%) though in the majority of patients who discontinued no reasons were listed. The median daily dose at endpoint was 50 mg/day (range, 25-187.5 mg/day). The median days with migraine headaches decreased from 6.0 to 1.2 days (p < 0.001), median pain intensity score decreased from 17.0 to 3.2 points (p < 0.001). In women with reported menstruation-associated migraine, the median number of migraine attacks decreased from 4.0 to 0.9 (p < 0.001). Absenteeism as well as triptan use decreased significantly, and significant improvements in activities of daily living and quality of life were reported. The most frequently reported AEs were paraesthesia (4.2%) and nausea (3%). Results suggest that migraine prevention with topiramate in a general practice is generally well tolerated and associated with a significant improvement in migraine headaches and related functional impairment.

Topics: Absenteeism; Adolescent; Adult; Aged; Analgesics, Opioid; Drug Administration Schedule; Dysmenorrhea; Electronic Health Records; Family Practice; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Outcome Assessment, Health Care; Pain Measurement; Prospective Studies; Quality of Life; Surveys and Questionnaires; Time Factors; Topiramate; Young Adult

Topiramate is known to be efficacious in migraine prophylaxis, but its optimal dose has not been systematically studied in the Asian population. Here, we show that a fixed low dose of topiramate 25 mg/day is efficacious in migraine prophylaxis and also attest to advantages in terms of medication cost savings and more favourable side effect profile.

Topics: Adolescent; Adult; Anticonvulsants; Asian People; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Costs; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Outcome Assessment, Health Care; Paresthesia; Pilot Projects; Singapore; Topiramate; Treatment Outcome; Young Adult

Neuropsychologic data are presented from a randomized, double-blind, placebo-controlled, multicenter study with placebo, topiramate 50 mg/day, and topiramate 100 mg/day. The Cambridge Neuropsychological Test Automated Battery (CANTAB) and cognitive adverse events were used to evaluate neurocognitive effects of topiramate. Topiramate 100 mg/day vs placebo was associated with slight statistically significant score increases, indicating slowing, from baseline vs placebo in three CANTAB measures: five-choice reaction time (P = 0.028), pattern recognition memory mean correct latency (P = 0.027), and rapid visual information processing mean latency (P = 0.040). No other patterns related to topiramate treatment were observed in measurements of learning, memory, and visual information processing, except for potential improvement with topiramate 100 mg/day vs placebo in spatial span total errors (accuracy test) (P = 0.040). The most common cognitive and neuropsychiatric adverse events with a higher incidence in the topiramate 50 and 100 mg/day groups vs placebo were anorexia (9% and 11% vs 3%), insomnia (9% and 3% vs 3%), fatigue (6% and 9% vs 6%), and dizziness (6% and 9% vs 0%). Thus, topiramate 100 mg/day was associated with modest increases in psychomotor reaction times. Learning, memory, and executive function were unchanged. The tolerability profile, including cognitive adverse events, appeared to be acceptable.

Topics: Adolescent; Anorexia; Child; Cognition Disorders; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fructose; Humans; Male; Migraine Disorders; Neuroprotective Agents; Neuropsychological Tests; Reaction Time; Recognition, Psychology; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Space Perception; Topiramate; Visual Perception

Demographic and clinical variables were examined in a post hoc analysis of the PROlonged Migraine Prevention with Topiramate (PROMPT) study to determine potential contribution to relapse.. After a six-month open-label (OL) topiramate phase, patients were randomised to continue topiramate or switch to placebo in a six-month double-blind (DB) phase. 'Relapse' was investigated in terms of change in monthly migraine days after randomisation compared with the month before randomisation, and was analysed during the first ('initial relapse') and last month ('sustained relapse') of the DB phase. More than 40 potential predicting factors were entered into analyses of variance and covariance.. For initial relapse, variable-by-treatment interactions were significant for the Headache Impact Test (HIT-6) at DB baseline, and decline in acute medication intake or reporting of 'anxiety' in the OL phase. For sustained relapse, no statistically significant interactions were observed.. Relapse after topiramate discontinuation in migraine prophylaxis appears to be unaffected by patient characteristics or baseline migraine frequency.

Topics: Double-Blind Method; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Recurrence; Topiramate

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.. 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.. 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.. The 100 mg/day topiramate group demonstrated efficacy in the prevention of migraine in pediatric subjects. Overall, topiramate treatment was safe and well tolerated.

Topics: Adolescent; Adverse Drug Reaction Reporting Systems; Anticonvulsants; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Fructose; Humans; Male; Migraine Disorders; Topiramate

Topics: Adult; Autonomic Nerve Block; Botulinum Toxins, Type A; Female; Fructose; Humans; Longitudinal Studies; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Neurotoxins; Topiramate; Young Adult

The primary objective of this study was to compare the efficacy and tolerability of topiramate and amitriptyline in the prophylaxis of episodic migraine headache.. 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.. 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%).. 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.

Topics: Adult; Amitriptyline; Body Weight; Central Nervous System Agents; Disability Evaluation; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Patient Satisfaction; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Topiramate; Treatment Outcome; United States

Migraine, particularly migraine with aura, and increased body weight are independent risk factors for cardiovascular disease (CVD). The association of weight change and clinical markers of CVD risk was evaluated in subjects participating in a randomized double-blind, parallel-group study of migraine-preventive treatment comparing 100 mg/day of topiramate and amitriptyline. Individuals from both treatment groups were pooled and stratified into three groups. The 'major weight gain' group gained > or = 5% of their baseline body weight at the conclusion of the study; the 'major weight loss' group lost > or = 5% of their baseline body weight. The third group had < 5% of weight change. The influence of weight change in headache outcomes, as well as in markers of CVD (blood pressure, cholesterol, C-reactive protein), was assessed using analysis of covariance. Of 331 subjects, 52 (16%) experienced major weight gain and 56 (17%) experienced major weight loss. Weight change was not associated with differential efficacy for the treatment of headache. However, contrasted with those with major weight loss, those who gained weight experienced elevations in mean diastolic blood pressure (+2.5 vs. -1.2 mmHg), heart rate (+7.6 vs. -1.3 beats per minute), glycosylated haemoglobin (+0.09% vs. -0.04%), total cholesterol (+6.4 vs. -6.3 mg/dl), low-density lipoprotein cholesterol (+7.0 vs. -4.4 mg/dl) and triglycerides (+15.3 vs. -10.4 mg/dl) and an increase in high-sensitivity C-reactive protein (+1.8 vs. -1.9 mg/l). Both groups experienced decreases in systolic blood pressure (-4.0 vs. -1.3 mmHg) and high-density lipoprotein cholesterol (-3.7 vs. -0.8 mg/dl). Increased weight during migraine treatment is not associated with poor headache treatment outcomes, but is associated with deterioration of CVD risk markers.

Topics: Adult; Amitriptyline; Analgesics, Non-Narcotic; Biomarkers; Blood Pressure; Cardiovascular Diseases; Cholesterol, HDL; Double-Blind Method; Female; Fructose; Humans; Male; Migraine Disorders; Risk Factors; Topiramate; Weight Gain; Weight Loss

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.

Topics: Analgesics; Anticonvulsants; Disability Evaluation; Double-Blind Method; Fructose; Humans; Migraine Disorders; Outcome Assessment, Health Care; Photophobia; Placebos; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Topiramate; Treatment Outcome; Vomiting

To evaluate the effect of different migraine prophylaxis medications on subject responsiveness to almotriptan.. There is evidence supporting an increase of responsiveness of symptomatic medications for migraine attacks by some prophylactic treatments although this has not been probed.. A total of 345 patients (230 women, mean age 37.3) with episodic or chronic migraine were classified according to the prophylaxis they were taking in the following groups: (1) no prophylactic medication; (2) propranolol; (3) topiramate; (4) flunarizine. Decrease in Analogical Visual Scale and pain-free at 2 hours after almotriptan intake was assessed at 2 months. Side effects and discontinuation or treatment were also assessed.. Headache severity was reduced 4.2 in control group, 5.3 in propranolol group, 4.1 in topiramate group, and 4.0 in flunarizine group, whereas pain-free status was achieved in 37.3%, 48.7%, 36.1%, and 38.1% respectively. These two parameters were statistically significative between propranolol and control groups. Side effects were similar in all groups.. Our results displayed a higher efficacy of almotriptan in propranolol group and we hypothesized it may be due to a common mechanism of action at serotoninergic receptors.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Anticonvulsants; Calcium Channel Blockers; Drug Interactions; Drug Therapy, Combination; Female; Flunarizine; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Pain Measurement; Propranolol; Serotonin Receptor Agonists; Topiramate; Treatment Outcome; Tryptamines; Young Adult

Topiramate (TPM) is a new antiepileptic drug approved for the prevention of migraine headache. However its use is limited by treatment-emergent adverse events; in particular, therapy can exert profound impact on language function. In this investigation, we used functional magnetic resonance imaging (fMRI) to study the anatomofunctional correlates of language disturbances in TPM patients experiencing subjective cognitive impairment. Ten right-handed individuals receiving therapy (five with and five without language disfluency) and five matched healthy control subjects took part in this study. During fMRI subjects alternately rested and performed a word-generating task. The task comprised the silent generation of words beginning with a different input letter visually presented. The activation paradigm consisted of six activation blocks alternating with six baseline rest blocks. The main fMRI measure was the pattern activation of the prefrontal regions (Brodmann's areas 44, 45, and 46) in both left and right hemispheres. Patients receiving TPM (50-100 mg/day) significantly reduced mean monthly migraine frequency. However several differences in fMRI activation were evident in the subject group comparison. Notably, changes in brain activity were observed during the phonemic task in patients with language disturbances. It is likely that TPM therapy is associated with a "remapping" of the language cerebral network.

Topics: Adolescent; Adult; Anticonvulsants; Brain Mapping; Child; Female; Frontal Lobe; Fructose; Humans; Image Processing, Computer-Assisted; Language; Magnetic Resonance Imaging; Male; Middle Aged; Migraine Disorders; Neuropsychological Tests; Oxygen; Topiramate

Effectiveness of antidepressants and antiepileptic drugs has already been demonstrated for migraine prophylaxis as monotherapy. In the present study, the efficacy and tolerability of amitriptyline and topiramate combination is examined in the prevention of migraine attacks, in comparison to the monotherapy of each drug.. A total of 73 patients with migraine headache with or without aura are included in this single-center, double-blind, randomized, and controlled trial. Patients were assigned to receive topiramate alone, amitriptyline alone or a combination of these drugs. Frequency, duration and severity of migraine attacks, accompanied symptoms, depressive state, consumption of medications, side effects and patient satisfaction were evaluated.. All treatments resulted in significant improvements in all efficacy measures (p<0.001 for all comparisons). However, patients receiving combination treatment had higher patient satisfaction compared with other groups both at 8 and 12 weeks (p=0.006 and p<0.001, respectively). Patients receiving amitriptyline and combination treatments had better depression scores compared with the topiramate group. Combination group had fewer side effects with a less amount of amitriptyline consumption.. Amitriptyline and topiramate combination may be beneficial for patients with migraine and comorbid depression, particularly in terms of side effects and associated displeasure due to monotherapy.

Topics: Adult; Amitriptyline; Anticonvulsants; Antidepressive Agents, Tricyclic; Constipation; Disorders of Excessive Somnolence; Double-Blind Method; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Patient Satisfaction; Time Factors; Topiramate; Treatment Outcome; Weight Gain

To assess the efficacy and safety of low-dose topiramate in migraine prophylaxis vs propranolol.. A randomized, double-blind, clinical trial including 62 patients with frequent migraine headaches (> or = 3 attacks per month) was performed for a period of 8 weeks. The patients were randomly divided into two treatment groups - treated by topiramate 50 mg/day and propranolol 80 mg/day, respectively. The patients were assessed at 0, 4, and 8 weeks of the study. Results - The topiramate group showed a reduction in the mean (+/-SD) of monthly migraine frequency from 6.07 (+/-1.89) to 1.83 (+/-1.39) episodes per month, headache intensity from 7.1 (+/-1.45) to 3.67 (+/-2.1) based on the Visual Analog Scale, and headache duration from 16.37 (+/-7.26) to 6.23 (+/-5.22) hours (P < 0.001). In the patients treated with propranolol, the mean (+/-SD) of monthly headache frequency declined from 5.83 (+/-1.98) to 2.2 (+/-1.67) per month, headache intensity lessened from 6.43 (+/-1.6) to 4.13 (+/-1.94) and headache duration decreased from 15.10 (+/-6.84) to 7.27 (+/-6.46) h (P < 0.001).. This study demonstrated that both low-dose topiramate and propranolol could significantly reduce migraine headache frequency, intensity, and duration. However, compared with propranolol, low-dose topiramate showed better results.

Topics: Adrenergic beta-Antagonists; Adult; Anticonvulsants; Brain; Cerebral Arteries; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fructose; Humans; Male; Migraine Disorders; Propranolol; Secondary Prevention; Sex Characteristics; Topiramate; Treatment Outcome

Frequent migraine headaches can have a significant impact on disability, prompting the need for early recognition and treatment. The objective of this study is to compare the efficacy of topiramate and sodium valproate for the prevention of pediatric migraine, retrospectively. Mean monthly migraine frequency, intensity, and duration in the 28 patients treated with topiramate decreased from 15.3 +/- 10.1 to 4.4 +/- 5.5 episode, from 6.8 +/- 1 to 3.2 +/- 1, and from 10.2 +/- 9.4 to 2.4 +/- 3.1 hours, respectively. Headache disability improved with a reduction of Pediatric Migraine Disability Assessment score from 36 +/- 29.5 to 4.6 +/- 6.5 (P < .05). Similarly, mean monthly headache frequency, headache intensity, headache duration, and Pediatric Migraine Disability Assessment score in the 20 patients treated with sodium valproate decreased from 20.1 +/- 10.2 to 6.6 +/- 8.6, from 7.1 +/- 1 to 3.4 +/- 2.1, from 7 +/- 12 to 1.4 +/- 2.5 hours, and from 20.5 +/- 16.1 to 5.5 +/- 9.2, respectively (P < .05). In conclusion, valproate and topiramate seem to be able to manage successfully childhood migraine without substantial differences in efficacy.

Topics: Adolescent; Anticonvulsants; Child; Disability Evaluation; Double-Blind Method; Female; Follow-Up Studies; Fructose; Humans; Male; Migraine Disorders; Pediatrics; Topiramate; Treatment Outcome; Valproic Acid

Histamine has a selective affinity for H3 receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology.. To evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of topiramate.. Ninety patients with migraine were selected in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week) compared with oral administration of topiramate (100 mg daily dose). The variables studied were: headache intensity, frequency, duration, analgesic intake and Migraine Disability Assessment.. The data collected during the 12 weeks of treatment revealed that headache symptoms improved in both the histamine and topiramate groups, which was evident within the first month after the initiation of treatment, with statistically significant (p < 0.001) reductions in headache frequency (50%), Migraine Disability Assessment score (75%), intensity of pain (51%), duration of migraine attacks (45%), as well as in the use of rescue medication (52%).. The present study provides evidence of the efficacy of subcutaneously applied histamine and orally administered topiramate in migraine prophylaxis. Subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients.

Topics: Adolescent; Adult; Double-Blind Method; Female; Fructose; Histamine; Histamine Agonists; Humans; Injections, Subcutaneous; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Topiramate

Topics: Adult; Female; Fructose; Humans; Longitudinal Studies; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Pain Measurement; Time Factors; Topiramate

To test treatment combining a beta-blocker plus topiramate in migraine patients previously resistant to the two medications in monotherapy.. Those patients who had not responded to a beta-blocker and topiramate received combined treatment.. Fifty-eight patients (47 women, age 25-76 years) received the combined treatment. Thirty-three (57%) met criteria for chronic migraine/medication overuse headache, 18 (31%) for migraine without aura and seven (12%) with aura. Ten (17%) discontinued due to adverse events. Among the 48 patients who tolerated the combination, 36 (75%, 62% of the total series) showed response (>50% reduction in frequency), while 12 (25%) did not. The number of days with headache/month decreased from 15.1 to 6.5 (-57%). Sixteen (44% of responders) showed an excellent (>75%) response. Eighteen patients (38%) experienced a total of 26 adverse events (mild-moderate).. The combination of beta-blocker plus topiramate showed a benefit in around 60% of patients who had not previously responded to monotherapy. Adverse events led to discontinuation in one out of six patients. From these open results, it seems reasonable to recommend this combination, complementary in terms of mechanism of action, as a potential strategy in patients with refractory migraine.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Drug Therapy, Combination; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Nadolol; Neuroprotective Agents; Propranolol; Topiramate; Treatment Outcome

The usual recommended duration of preventive treatment for migraine is 3-6 months. Our aim was to explore how many patients attending a specialised clinic need prolonged preventive treatment for longer than one year. Eighty consecutive migraine patients who received preventive treatment with topiramate for 3 months with good response and tolerability were included in this observational study. All patients continued on topiramate until they had completed 6 months, when this drug was stopped. Topiramate was reintroduced if there was a worsening. Topiramate was kept for 6 more months and then discontinued again. Those patients whose headaches became worse after this second withdrawal received topiramate again and were followed-up for at least half a year. Headaches did not worsen after the first withdrawal at 6 months in 40 patients (50%), while they clearly worsened in the remaining 40 patients. At the end of the first year only two patients out of these 40 (5%) discontinued topiramate and did not notice an increase in headache frequency after two months. In conclusion, around half of the patients attending a specialised clinic due to frequent headache need preventive treatment for more than one year. Our data suggest that the current practice recommending periods of preventive treatment of 3-6 months should be reconsidered for many patients.

Topics: Adult; Aged; Female; Fructose; Humans; Longitudinal Studies; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Time Factors; Topiramate; Treatment Outcome

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

Topics: Adolescent; Adult; Aged; Anticonvulsants; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Topiramate; Treatment Outcome

We conducted this study to determine whether topiramate at 100 mg/d for the treatment of migraine headache is associated with improved productivity in the workplace.. Results were derived from two randomized, double-blind, placebo-controlled trials among migraineurs. The number of hours of absenteeism (A), presenteeism (P), and total lost productivity (TLP) (A + P) were calculated. Results were not adjusted for multiplicity.. A total of 325 (162 in the topiramate group and 163 in the placebo group) of 449 subjects were included. Per person mean monthly A rate was only significantly less for individuals within the topiramate group (1.0 hours per person) versus those in the placebo group (1.5 hours per person) for month 3 (P < 0.05). Per person mean P and TLP rates were significantly lower for individuals in the topiramate group versus those in the placebo group for months 1 through 5 (P < 0.05).. Findings suggest that topiramate, compared with placebo, is associated with decreased workplace presenteeism and TLP.

Topics: Absenteeism; Adolescent; Adult; Double-Blind Method; Efficiency; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Statistics, Nonparametric; Topiramate; Treatment Outcome

The aim was to evaluate whether preventive treatment with topiramate in patients with episodic migraine reduces the risk of developing chronic forms of headache.. Chronic forms of headache, including chronic migraine or medication overuse headache (MOH), are characterized by 15 or more headache days per month. Acute medication overuse has been shown to be a risk factor for developing chronic headache, but it is not known whether preventive treatment can reduce the risk of developing chronic forms of headache or the development of MOH.. Pooled data from 3 trials in patients with episodic migraine randomized either to treatment with 100 mg topiramate per day (n = 384) or with placebo (n = 372) were analyzed with regard to the number of headache days during a prospective 4-week baseline period and the individual final 4 weeks of each patient's treatment during the planned 26-week double-blind treatment period.. The number of headache days per month in the topiramate versus the placebo-treated groups was 7.3 +/- 3.0 versus 7.3 +/- 3.1 during baseline and 4.1 +/- 4.2 versus 5.6 +/- 4.9 during the final 4 weeks, respectively (P < .001). At the end of the study, 8 versus 16 patients fulfilled International Headache Society criteria of chronic headache (odds ratio: 2.11, P= .082). Moreover, a significantly lower number of patients receiving topiramate treatment reported an increase in headache days per month by the end of the study when compared to placebo (66 vs 88 patients, respectively; odds ratio: 1.49, P < .05). Finally, the number of days with usage of acute medication was significantly lower in the topiramate arm compared with placebo (3.3 +/- 3.7 vs 4.3 +/- 3.6, respectively; P < .001).. Preventive treatment with topiramate in patients with episodic migraine may reduce the risk of developing chronic forms of headache.

Topics: Adolescent; Adult; Aged; Child; Double-Blind Method; Female; Fructose; Headache Disorders; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Odds Ratio; Prospective Studies; Risk Factors; Topiramate; Treatment Outcome

Topics: Adult; Anticonvulsants; Chronic Disease; Female; Fructose; Humans; Male; Migraine Disorders; Topiramate

To assess the efficacy and safety of topiramate and lamotrigine for prophylaxis in patients with frequent migraine as compared to each other and to placebo.. Sixty patients with frequent migraine (more than 4 attacks per month) from the headache clinic at a tertiary referral centre in India were randomized to receive 50 mg topiramate/lamotrigine or matching placebo for 1 month each in 2 divided doses in 4 phases in a crossover manner with a washout period of 7 days in between. Primary efficacy measure was responder rate (50% decrease in mean migraine frequency/intensity). Secondary efficacy measures included reduction in mean monthly frequency, intensity, duration, rescue medication use, migraine associated symptoms, and adverse events.. Analysis was on intention to treat basis. Data were analyzed as correlated data. Generalized estimation equation was used to compute overall mean standard deviation and 95% confidence intervals for each of the outcome variables. Bonferroni's correction done for multiple comparisons. P value of < .017 was taken as significant.. Fifty-seven patients comprised the intent-to-treat population. Four patients withdrew from the study at various phases, none because of the side effects. Responder rate for frequency was significantly higher for topiramate versus placebo (63% vs 30%, P < .001), and versus lamotrigine (63% vs 46 %, P = .02). For intensity of headache also a responder rate of topiramate versus placebo (50% vs 10%, P < .001), and versus lamotrigine (50% vs 41%, P = .01) was observed. Topiramate showed statistically significant benefits (P < .017) in most of the secondary efficacy measures while lamotrigine was beneficial for reduction in headache frequency, and migraine associated symptoms. Adverse events were similar.. Low-dose topiramate is efficacious in migraine prophylaxis as compared to both placebo and lamotrigine. Lamotrigine in low doses might be beneficial for headache frequency; however, longer trials are required to establish its efficacy on the intensity and frequency of migraine.

Topics: Adolescent; Adult; Calcium Channel Blockers; Dose-Response Relationship, Drug; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Female; Fructose; Humans; Lamotrigine; Male; Middle Aged; Migraine Disorders; Topiramate; Triazines

The aim of this study was to evaluate the efficacy and tolerability of topiramate for the prevention of chronic migraine in a randomized, double-blind, placebo-controlled trial. Chronic migraine is a common form of disabling headache presenting in headache subspecialty practice. Preventive treatments are essential for chronic migraine management, although there are few or no controlled empirical trial data on their use in this patient population. Topiramate is approved for the prophylaxis of migraine headache in adults. Patients (18-65 years) who experienced chronic migraine (defined as > or =15 monthly migraine days) for > or =3 months prior to trial entry and had > or =12 migraine days during the 4-week (28-day) baseline phase were randomized to topiramate or placebo for a 16-week, double-blind trial. Topiramate was titrated (25 mg weekly) to a target dose of 100 mg/day, allowing dosing flexibility from 50 to 200 mg/day, according to patient need. Existing migraine preventive treatments, except for antiepileptic drugs, were continued throughout the trial. The primary efficacy measure was the change in number of migraine days from the 28-day baseline phase to the last 28 days of the double-blind phase in the intent-to-treat population, which consisted of all patients who received at least one dose of study medication and had one outcome assessment during the double-blind phase. Health-related quality of life was evaluated with the Migraine Specific Quality of Life Questionnaire (MSQ, Version 2.1), the Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires, and tolerability was assessed by adverse event (AE) reports and early trial discontinuations. Eighty-two patients were screened. Thirty-two patients in the intent-to-treat population (mean age 46 years; 75% female) received topiramate (mean modal dose +/- SD = 100 +/- 17 mg/day) and 27 patients received placebo. Mean (+/-SD) baseline number of migraine days per 4 weeks was 15.5 +/- 4.6 in the topiramate group and 16.4 +/- 4.4 in the placebo group. Most patients (78%) met the definition for acute medication overuse at baseline. The mean duration of treatment was 100 and 92 days for topiramate- and placebo-treated patients, respectively. Study completion rates for topiramate- and placebo-treated patients were 75% and 52%, respectively. Topiramate significantly reduced the mean number of monthly migraine days (+/-SD) by 3.5 +/- 6.3, compared with placebo (-0.2 +/- 4.7,

Topics: Adolescent; Aged; Anticonvulsants; Chronic Disease; Disability Evaluation; Double-Blind Method; Female; Fructose; Headache Disorders, Secondary; Humans; Male; Middle Aged; Migraine Disorders; Patient Satisfaction; Placebos; Topiramate; Treatment Outcome

We evaluated the efficacy and safety of topiramate for migraine prophylaxis among Chinese patients in a multicenter prospective observational study. We found that topiramate at low doses was effective in preventing migraine headache in Chinese patients and was generally well tolerated. There was no difference in baseline headache frequency or intensity between responders and nonresponders.

Topics: Adult; Asian People; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Observation; Prospective Studies; Time Factors; Topiramate

Migraineurs treated with topiramate often experience adverse effects, such as paresthesia, fatigue, memory difficulty, or taste perversion. To investigate correlations between side effects and drug efficacy, we analyzed for these in 133 migraineurs treated with topiramate (100 mg/day). A 4-week baseline screening phase preceded a 4-week titration period and a 20-week maintenance phase. A total of 118 patients were evaluated at 3 months and 89 patients at 6 months. Patients who developed paresthesia (n = 73) showed lower headache days than those who did not (n = 60) (P = 0.026 at 3 months, P = 0.002 at 6 months), and had a higher responder rate (3 months, 57.5% and 6 months, 65.8%) than those who did not develop paresthesia (3 months, 38.3% and 6 months, 41.7%). Moreover, retrospective analysis of patients that dropped out showed no survival bias between paresthesia and headache improvement. Other adverse effects were not found to correlate with drug efficacy. This study suggests that the development of paresthesia predicts a favorable response to topiramate in migraine prophylaxis.

Topics: Adult; Aged; Anticonvulsants; Female; Fructose; Headache; Humans; Male; Middle Aged; Migraine Disorders; Paresthesia; Predictive Value of Tests; Prospective Studies; Retrospective Studies; Time Factors; Topiramate; Treatment Outcome

Preventive therapy is aimed at reducing migraine frequency, but should also improve the much deteriorated quality of life of the migraneur. We aimed to evaluate the impact of preventive therapy with two widely employed drugs (topiramate and nadolol) on the quality of life of migraine patients. A population of consecutive migraineurs aged > or = 16 years, with frequent migraines, was selected prospectively for evaluation at baseline and after 16 weeks of therapy with nadolol or topiramate (40 mg and 100 mg daily, respectively) by generic and specific quality of life questionnaires (SF-36 and MSQOL) and by an anxiety and depression scale (HADS). Preventive therapy resulted in a statistically significant improvement in physical domains of the SF-36, whereas mental domains remained almost unchanged. Despite this improvement, all domains remained below the population norms. The HADS revealed a moderate depressive state at baseline that did not change with therapy. The MSQOL global score also revealed statistically significant improvement. Both drugs were similarly effective, although topiramate was superior on the role physical domain compared with nadolol. Preventive therapy with nadolol and topiramate significantly improves the quality of life of migraineurs, although additional efforts are needed to place them in a nearer-to-normal situation compared with the general population.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Anticonvulsants; Anxiety; Depression; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Nadolol; Quality of Life; Surveys and Questionnaires; Topiramate

The efficacy, safety and tolerability of topiramate has been demonstrated in three large multicenter, randomized, double-blind, placebo-controlled trials. To characterize the time course of adverse events (AEs) that led to treatment discontinuation in >/=2% of patients who received topiramate 100 mg/day during three pivotal, multicenter, randomized, double-blind, placebo-controlled, and 26-week trials. The pooled population comprised all randomized patients who reported safety data during the double-blind phase (topiramate 100 mg/day, n = 386; placebo n = 372), which consisted of a 4-week titration period and a 22-week maintenance period. Incidence, time to onset, and cumulative mean rate of AEs were assessed. Overall, AEs led to treatment discontinuation in 24.9% of patients receiving topiramate 100 mg/day and 11.0% receiving placebo (P < 0.001). AEs leading to discontinuation during the double-blind phase in > or =2% of patients included paresthesia (8.0% discontinued), any cognitive symptoms (7.3% discontinued), fatigue (4.7% discontinued), insomnia (3.4% discontinued), nausea (2.3% discontinued), loss of appetite, anxiety, and dizziness (2.1% discontinued because each AE). Most AEs began during the titration period. Paresthesia, any cognitive symptoms, nausea, and loss of appetite occurred at a higher rate in the topiramate group than in the placebo group (P < 0.01). AEs leading to discontinuation of topiramate are probably to occur during dose titration. If a patient has not experienced one of these AEs within the first 6 weeks of initiating topiramate 100 mg/day, these AEs are unlikely to occur.

Topics: Adult; Anorexia; Anticonvulsants; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Fatigue; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Nausea; Paresthesia; Patient Compliance; Placebos; Time; Time Factors; Topiramate; Withholding Treatment

A substantial proportion of the patient population with migraine headache should be considered for preventive treatment based on the frequency and disability associated with this disorder. Use of the anticonvulsant topiramate was previously examined in two large, double-blind, randomized, placebo-controlled clinical trials of a subset of patients who have 3 to 12 migraine episodes per month.. To better characterize the efficacy of topiramate for prevention of migraine, with or without aura, by pooling and analyzing data from the two large clinical trials.. The pooled intent-to-treat population included 937 patients receiving topiramate at one of three dosages (50 mg/d, 100 mg/d, 200 mg/d) or placebo. Outcome measures included change in mean monthly migraine frequency and categorical responder rate throughout the 26-week doubleblind phase.. At daily doses of 100 and 200 mg, topiramate was associated with significant reductions in mean monthly migraine frequency throughout the double-blind phase compared with placebo (P<.001). Significantly more patients treated with these topiramate doses exhibited high-percentage reductions in monthly migraine frequency (>/=50% [P<.001], >/=75% [P<.001], 100% [P=.049]) versus placebo. The most common adverse events included anorexia, cognitive deficits, diarrhea, fatigue, nausea, and paresthesia. Topiramate (100 mg/d, 200 mg/d) was associated with significant and sustained reductions in mean monthly migraine frequency beginning as early as 1 week into therapy.. Pooled efficacy data from two large, similarly designed, placebo-controlled migraine-prevention trials demonstrated that a statistically significant proportion of patients using topiramate met or exceeded two main outcome guidelines recommended by the International Headache Society (>/=50% and >/=75% reduction in frequency of monthly attacks). Based on efficacy and tolerability, topiramate at a dosage of 100 mg per day (50 mg twice daily) should be the target dosage for most patients with migraine.

Topics: Adolescent; Adult; Aged; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Topiramate

Recent theories about migraine pathogenesis have outlined an abnormal central processing of sensory signals, also suggested by an abnormal pattern of EEG hyper-synchronization under visual stimulation. The aim of the present study was to test the efficacy of topiramate and levetiracetam vs placebo in a double blind project observing the effects of the three treatments on the EEG synchronization in the alpha band under sustained flash stimulation.. Forty-five migraine without aura outpatients (MO) were selected and randomly assigned to 100mg topiramate, 1000 mg levetiracetam or placebo treatment. In addition, 24 non-migraine healthy controls were submitted to EEG analysis. The EEG was recorded by 19 channels: flash stimuli with a luminosity of 0.2J were delivered, in a frequency range from 3 to 30 Hz. We evaluated the phase synchronization index, that we previously applied in migraine, after EEG signals filtering in the alpha band. Our approach was based on the Hilbert transform.. Both levetiracetam and topiramate significantly decreased migraine frequency, compared with placebo. MO patients displayed increased alpha-band phase synchronization as an effect of stimulus frequency; on the other hand the stimuli had an overall desynchronizing effect on control subjects. The phase synchronization index separates the two stages, before and after the treatment, only for levetiracetam, at stimulus frequencies of 9, 18, 24 and 27 Hz.. An abnormal alpha band synchronization under visual stimuli was confirmed in migraine; this phenomenon was reversed by levetiracetam preventive treatment.. These results confirmed in humans the inhibiting action of levetiracetam on neuronal hyper-synchronization.

Topics: Adolescent; Adult; Algorithms; Alpha Rhythm; Brain Mapping; Cortical Synchronization; Double-Blind Method; Electroencephalography; Evoked Potentials, Visual; Female; Fructose; Humans; Levetiracetam; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Nootropic Agents; Photic Stimulation; Piracetam; Topiramate

Several large, randomized controlled trials have demonstrated the efficacy of topiramate in migraine prophylaxis in adults. However, there are limited data about the use of topiramate in migraine prophylaxis in children. We conducted this single-center, double-blind, placebo-controlled trial to evaluate the efficacy and safety of topiramate in the prophylaxis of migraine in children. A total of 44 children with migraine were randomized using random number tables to receive topiramate (n = 22) or placebo (n = 22). The total duration of treatment was 4 months, including a baseline period of 1 month during which topiramate was titrated weekly in 25-mg increments to 100 mg/d in 2 divided doses or to the maximum tolerated dose. The titration was followed by a 12-week maintenance phase during which topiramate was given in 2 divided doses. The primary outcome measures were the reduction in the mean migraine frequency and severity of headache. Secondary outcome measures included the number of times analgesics were required for a month for acute attacks and functional disability. Functional disability was measured by comparing school absenteeism and Pediatric Migraine Disability Assessment Scale (PedMIDAS). The decrease in mean (+/-SD) monthly migraine frequency from 16.14 (+/-9.35) at baseline to 4.27 (+/-1.95) at the end of the study in the topiramate group was significantly greater as compared with a decrease from 13.38 (+/-7.78) to 7.48 (+/-5.94) at the end of the study in the placebo group (P = .025). The difference in number of rescue medications used for topiramate and placebo was not statistically significant (P = .059). There was a statistically significant decrease in the PedMIDAS score from 50.66 (+/-32.1) to 10.42 (+/-6.39) at the end of the study in the topiramate group compared with a decrease from 42.66 (+/-27.5) to 23.7 (+/-19.1) at the end of 4 months in the placebo group (P = .003). The decrease in school absenteeism was significant with topiramate compared with placebo (P = .002). Weight loss, decreased concentration in school, sedation, and parasthesias were important side effects with topiramate. Most of these side effects were mild to moderate and were not significant enough to cause dropout from the study.

Topics: Adolescent; Analysis of Variance; Anticonvulsants; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fructose; Humans; Male; Migraine Disorders; Neurotransmitter Agents; Quality of Life; Topiramate

Topiramate is approved for the prophylaxis (prevention) of migraine headache in adults. The most common adverse events in the three pivotal, randomized, double-blind, placebo-controlled trials were paresthesia, fatigue, cognitive impairment, anorexia, nausea, and taste alteration. In these trials, topiramate 100 mg/d significantly improved Migraine-Specific Questionnaire (MSQ) scores versus placebo (p < 0.001). The MSQ measures how much migraine limits/interrupts daily performance. Pooled analyses of pivotal trial data were conducted to further assess how topiramate 100 mg/d affects daily activities and patient functioning.. Mean MSQ and Medical Outcome Study Short Form 36 (SF-36) change scores (baseline to each double-blind assessment point) were calculated for pooled intent-to-treat (ITT) patients. Additionally, pooled ITT patients receiving topiramate 100 mg/d or placebo were combined and divided into two responder groups according to percent reduction in monthly migraine frequency: < 50% responders or >or= 50% responders. Between-group differences were assessed using analysis of covariance.. Of 756 patients (mean age 39.8 years, 86% female), 384 received topiramate 100 mg/d and 372 placebo. Topiramate significantly improved all three MSQ domains throughout the double-blind phase versus placebo (p = 0.024 [week 8], p < 0.001 [weeks 16 and 26] for role prevention; p < 0.001 for role restriction and emotional function [all time points]). Topiramate 100 mg/d significantly improved SF-36 physical component scores (PCS) throughout the double-blind phase versus placebo (p < 0.001, all time points) and significantly improved mental component scores (MCS) at week 26 (p = 0.043). The greatest topiramate-associated improvements on SF-36 subscales were seen for bodily pain and general health perceptions (p < 0.05; weeks 8, 16, and 26), and physical functioning, vitality, role-physical, and social functioning (p < 0.05; weeks 16 and 26). Significantly greater improvements in all three MSQ domains, as well as the PCS and MCS of SF-36, were observed for >or= 50% responders versus < 50% responders (p < 0.001). Significantly greater percentages of topiramate-treated patients were >or= 50% responders versus placebo (46% versus 23%; p < 0.001).. Topiramate 100 mg/d significantly improved daily activities and patient functioning at all time points throughout the double-blind phase. Daily function and health status significantly improved for those achieving a >or= 50% migraine frequency reduction.

Topics: Activities of Daily Living; Adult; Chemoprevention; Double-Blind Method; Female; Fructose; Humans; Longitudinal Studies; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Placebos; Psychometrics; Quality of Life; Sickness Impact Profile; Surveys and Questionnaires; Time Factors; Topiramate; Treatment Outcome

Use of preventive therapy for migraine is often recommended for only 6-9 months, but no randomised, placebo-controlled trials have investigated migraine frequency after the end of prophylaxis. We assessed the effects of discontinuation of topiramate after a treatment period of 6 months.. 818 patients who have migraines were enrolled from 88 clinics in 21 countries. After a 4-8-week lead-in period, patients received topiramate in a 26-week open-label phase. Daily dose was increased from 25 mg to 100 mg in steps of 25 mg every week; the dose could be adjusted further in the range 50-200 mg/day, but was stable for the final 4 weeks. Patients were randomly assigned to continue this dose or switch to placebo for a 26-week double-blind phase. The primary endpoint was the difference in number of days with migraine during the last 4 weeks of the double-blind phase compared with the last 4 weeks of the open-label phase. Analysis was by intention to treat. This trial is registered with EudraCT, number 2005-000321-29.. 559 patients (68.3%) completed the open-label phase; 514 entered the double-blind phase and were assigned to topiramate (n=255) or placebo (n=259). The mean increase in number of migraine days was greater in the placebo group (1.19 days in 4 weeks, 95% CI 0.71 to 1.66; p<0.0001) than in the topiramate group (0.10, -0.36 to 0.56; p=0.5756; mean difference between groups -1.09, -1.75 to -0.43; p=0.0011) [corrected] Patients in the placebo group had a greater number of days on acute medication than did those in the topiramate group (mean difference between groups -0.95, -1.49 to -0.41; p=0.0007). Quality of life, as assessed by the MIDAS questionnaire, fell in the placebo group but remained stable in the topiramate group. Patients were more satisfied with the efficacy of topiramate than with that of placebo, whereas satisfaction with tolerability was similar in both treatment groups.. Sustained benefit was reported after discontinuation of topiramate, although number of migraine days did increase. These findings suggest that patients should be treated for 6 months, with the option to continue to 12 months in some patients.

Topics: Adolescent; Adult; Aged; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Quality of Life; Severity of Illness Index; Time Factors; Topiramate; Treatment Outcome

Topiramate and sodium valporate are anticonvulsants, demonstrated to be effective as monotherapy for migraine prevention in placebo-controlled trials.. To compare the relative efficacy of topiramate and sodium valporate in the prevention of migraine.. A 24-week, randomized, double-blind, crossover, clinical trial was conducted from October 2003 to September 2004. A total of 64 patients with migraine headache, aged 14 to 57 years, were randomly allocated to the 2 treatment groups. The first group received topiramate (25 mg daily increment over 1 week to 50 mg) for a total of 2 months. The second group received sodium valporate (200 mg daily increment over 1 week to 400 mg) for 2 months. Response to treatment was assessed at 0, 1, 8, 16, and 24 weeks after start of therapy.. Topiramate appeared to be equivalent in efficacy and safety to sodium valporate. A significant decrease in duration, monthly frequency, and intensity of headache occurred in both groups. Of the 32 patients treated with sodium valporate, the mean standard deviation (SD) of monthly migraine frequency decreased from 5.4 (2.5) to 4.0 (2.8) episode per month, headache intensity from 7.7 (1.2) to 5.8 (1.7) by visual analog scale (VAS), and headache duration from 21.3 (14.6) to 12.3 (10.7) hours (P < .001). Correspondingly, in the 32 patients treated with topiramate, the mean SD of monthly headache frequency decreased from 5.4 (2.0) to 3.2 (1.9) per month, headache intensity from 6.9 (1.2) to 3.7 (1.3), and headache duration from 17.3 (8.4) to 3.9 (2.7) hours (P < .001).. This study demonstrates that treatment with topiramate and sodium valporate both significantly reduce migraine headache. This effect of topiramate and sodium valporate has previously been shown to reduce migraine headache, and we postulate that treatment with topiramate and sodium valporate may have a similar benefit.

Topics: Adolescent; Adult; Cross-Over Studies; Double-Blind Method; Female; Fructose; GABA Agents; Humans; Male; Middle Aged; Migraine Disorders; Topiramate; Treatment Outcome; Valproic Acid

Assess the impact of migraine preventive therapy on patient-reported routine daily activities using the Migraine Specific Questionnaire (MSQ) and the Medical Outcomes Study Short Form-36 (SF-36) in patients with migraine who participated in a 26-week, randomized, double-blind, placebo-controlled trial of topiramate for migraine prevention.. Patients were required to have 3-12 migraines and < or = 15 headache days/month during the baseline phase. Patients who failed > 2 adequate regimens of migraine preventive therapy were excluded. MSQ and SF-36 data were collected at baseline, weeks 8, 16, and 26 from 469 patients receiving either topiramate 50, 100, or 200 mg/day or placebo. Patients entered a double-blind, 8-week titration period followed by an 18-week maintenance period. Two activity-related MSQ domains (Role Restrictive [RR] and Role Prevention [RP]) and two activity-related SF-36 domains (Role Physical [SF-36-RP] and Vitality [SF-36-VT]) were prospectively designated as the outcome measures. Changes in MSQ and SF-36 scores during the double-blind phase relative to prospective baseline scores were compared between topiramate- and placebo-treated groups. Specifically, a mixed-effect piecewise linear regression model was used to estimate average domain score over time, and areas under the domain-over-time curve (AUC) were compared using a 2-sided t-test, with multiplicity adjustment.. In the intent-to-treat population (N = 469), topiramate (all doses) significantly improved mean MSQ-RR domain scores versus placebo (topiramate 50 mg/day, p = 0.035; topiramate 100 mg/day; p < 0.001; topiramate 200 mg/day, p = 0.001). Topiramate-associated improvements in mean MSQ-RP domain scores were significant versus placebo only for topiramate 100 mg/day (p = 0.045). SF-36-RP and SF-36-VT domain scores improved (not significant versus placebo) for topiramate 100 and 200 mg/day. Changes in these MSQ and SF-36 domain scores significantly correlated with changes in mean monthly migraine frequency.. Improvements in patient-reported outcomes specific for migraine (measured by the MSQ) were significantly better for patients receiving topiramate than for those receiving placebo. Improvements in the prospectively selected MSQ and SF-36 domains were significantly correlated with the decrease in mean monthly migraine frequency observed with topiramate treatment.

Topics: Activities of Daily Living; Adolescent; Adult; Aged; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Models, Biological; Neuroprotective Agents; Placebos; Prospective Studies; ROC Curve; Surveys and Questionnaires; Topiramate

Chronic migraine (CM) is a disabling condition with not many treatment strategies available. Topiramate is effective in episodic migraine prevention, however little is known about its effect in CM. An open label study was performed. Sixty-four patients diagnosed with CM or probable CM according to the IHS diagnostic criteria were enrolled, 50 patients were available for analysis and an intention-to-treat methodology was applied. The primary endpoint considered was the number of patients with a decrease in headache frequency higher than 50%. The median dose was 100 mg, a reduction in frequency higher than 50% occurred in 33 patients (66%) and 14 (28%) presented a complete response, defined as a frequency reduction higher than 95%. The medication was well tolerated. The most common side effects found were weight loss, paraesthesias, nausea, cognitive dysfunction, fatigue, somnolence, insomnia and depression. Our findings suggest that topiramate is effective in CM prophylaxis.

Topics: Adult; Anticonvulsants; Brain; Chronic Disease; Cognition Disorders; Disorders of Excessive Somnolence; Female; Fructose; GABA-A Receptor Agonists; Humans; Ion Channels; Male; Middle Aged; Migraine Disorders; Nausea; Paresthesia; Receptors, GABA-A; Topiramate; Treatment Outcome

To assess the impact of topiramate on the daily activities of patients with migraine.. We performed a randomized, double-blind, placebo-controlled multicenter trial Initiated on March 1, 2001, and completed on April 4, 2002. Patient-reported data from the Migraine Specific Questionnaire (MSQ) and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) were collected at baseline and at weeks 8, 16, and 26 from an intent-to-treat population receiving either topiramate, 50, 100, or 200 mg/d, or placebo. Two activity-related MSQ domains (role restrictive [MSQ-RR] and role prevention [MSQ-RP]) and 2 activity-related SF-36 domains (role physical [SF36-RP] and vitality [SF36-VT]) were the prospectively designated secondary outcome measures. The changes in MSQ and SF-36 scores for each treatment group were calculated by measuring the area under the curve from week 8 (the beginning of the maintenance period) through week 26 of the double-blind phase, relative to the prospective baseline. A mixed-effect piecewise linear regression model was used to estimate average domain score over time.. Patients receiving topiramate, 100 or 200 mg/d, had significantly reduced mean monthly (28-day) migraine frequency (P = .008 and P < .001, respectively) compared with placebo, but not patients receiving topiramate, 50 mg/d (P = .48). Topiramate significantly improved mean MSQ-RR domain scores (50 mg/d [P = .02], 100 mg/d [P< .001], and 200 mg/d [P < .001]) and mean MSQ-RP domain scores (50 mg/d [P = .007], 100 mg/d [P = .001], and 200 mg/d [P= .002]) vs placebo. Topiramate, 100 and 200 mg/d, significantly improved mean SF36-RP domain scores vs placebo (P = .02). Topiramate (all doses) improved SF36-VT domain scores, although not significantly vs placebo. Changes in prospectively designated domain scores were significantly correlated with changes in mean monthly migraine frequency (P < or = .001 [MSQ domains], P < or = .002 [SF-36 domains]).. Patient-reported migraine-specific outcomes measured by the MSQ-RR and MSQ-RP domains improved significantly for those receiving topiramate (all doses) vs placebo. The SF36-RP domain scores improved significantly for patients receiving 100 or 200 mg/d of topiramate. Improvements in all 4 prospectively selected MSQ and SF-36 domains were significantly correlated with decreases in mean monthly migraine frequency.

Topics: Activities of Daily Living; Adolescent; Adult; Aged; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fructose; Humans; Linear Models; Male; Middle Aged; Migraine Disorders; Prospective Studies; Surveys and Questionnaires; Topiramate; Treatment Outcome

Topics: Adolescent; Adult; Aged; Child; Double-Blind Method; Fructose; Humans; Middle Aged; Migraine Disorders; Paresthesia; Topiramate

Five-three percent of the patients who suffer from migraine present severe incapacity and need rest in bed. If we add to this the incapacity produced by vertigo, then the quality of life of these patients is seriously affected. Migraine/Vertigo (MV) should be another criterion in the selection of preventive treatment even when other criteria are not fulfilled. Auditory symptoms may accompany MV. We treated 10 patients with Topiramate in an open trial, twice a day, with an average dose of 100 mg/day. The treatment period for these patients ranges between 6 and 16 months, with a mean of 9. As of today, all patients present no crisis. Regarding auditory symptoms, all the patients referred that they were stabilized. The effect began quickly, from the first month in most patients as it has been reported in other studies.

Topics: Adult; Aged; Female; Fructose; Hearing Disorders; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Topiramate; Vertigo

We present a prospective case series of 24 children diagnosed with migraine refractory to prophylactics and treated for 4 months with topiramate as the only prophylactic drug. At the final visit, the mean topiramate dose was 3.5 +/- 1.7 mg/kg/day. Nearly all patients (87.5%) reported a shorter duration of attacks, and the average pain intensity was rated as mild by 14 patients (58.3%). Eight (33.3%) patients had adverse events, none of which were serious. In our sample of pediatric patients, topiramate was effective for the prophylactic treatment of migraine in children. It was well tolerated at the doses used for titration and maintenance. Controlled trials are needed to verify the efficacy of topiramate for migraine in children.

Topics: Adolescent; Child; Female; Fructose; Humans; Male; Migraine Disorders; Neuroprotective Agents; Pain Measurement; Prospective Studies; Topiramate; Treatment Outcome

To assess changes in health-related quality of life (HRQoL) measures among patients receiving topiramate (TPM) 100 mg/d in two divided doses for migraine prevention in three randomized, double-blind, placebo-controlled, 26-week trials with similar protocols and study populations.. Migraine substantially impairs HRQoL and work productivity before, during, and after attacks. Approximately 50% of patients with migraine could be recommended for preventive therapies, yet only 3% to 5% of patients receive them. TPM is an effective and generally well-tolerated migraine prophylactic (preventive) therapy for adults, as demonstrated in several randomized, double-blind, placebo-controlled trials. The most common adverse events in double-blind, placebo-controlled studies of TPM in migraine prevention are paresthesia, fatigue, anorexia, nausea, taste alteration, and diarrhea.. The Migraine-Specific Questionnaire (MSQ, version 2.1) was used to assess the effect of TPM 100 mg/d on the functionality and HRQoL of randomized intent-to-treat (ITT) and study-completer populations pooled from three randomized, double-blind, placebo-controlled trials. MSQ scores (0 to 100, higher score indicates better functioning) were assessed for the following three domains: role restriction (examines the degree to which performance of daily activities is limited by migraine), role prevention (examines the degree to which performance of daily activities is interrupted by migraine), and emotional function (examines feelings of frustration and helplessness due to migraine). Between-group differences from baseline in mean MSQ domain scores for TPM 100 mg/d and placebo were compared using a mixed-effects model with piecewise linear regression. Effect sizes were calculated to estimate the magnitude of change in HRQoL that can be associated with TPM therapy.. TPM 100 mg/d significantly improved all three MSQ domains compared with placebo for both the ITT (TPM, n = 372; placebo, n = 362) and study-completer (TPM, n = 220; placebo, n = 216) populations (P < .001 for all three domains, both populations). Effect sizes for TPM 100 mg/d varied from 0.40 to 0.78, indicating that the changes in MSQ scores for TPM 100 mg/d were moderate and may be clinically significant.. TPM 100 mg/d has been shown to be effective in the prevention of migraine headache in adults. As the MSQ results from the three randomized, placebo-controlled trials indicate, HRQoL is significantly improved for up to 6 months following initiation of treatment.

Topics: Adolescent; Adult; Aged; Double-Blind Method; Female; Fructose; Health; Humans; Male; Middle Aged; Migraine Disorders; Quality of Life; Surveys and Questionnaires; Topiramate; Treatment Outcome

Small open-label and controlled trials suggest that the antiepileptic drug topiramate is effective for migraine prevention.. To assess the efficacy and safety of topiramate for migraine prevention in a large controlled trial.. A 26-week, randomized, double-blind, placebo-controlled study was conducted during outpatient treatment at 52 North American clinical centers. Patients were aged 12 to 65 years and had a 6-month history of migraine (International Headache Society criteria) and 3 to 12 migraines a month but no more than 15 headache days a month during a 28-day prospective baseline phase.. After a washout period, patients meeting entry criteria were randomized to topiramate (50, 100, or 200 mg/d) or placebo. Topiramate was titrated by 25 mg/wk for 8 weeks to the assigned or maximum tolerated dose, whichever was less. Patients continued receiving that dose for 18 weeks.. The primary efficacy measure was change from baseline in mean monthly migraine frequency. Secondary efficacy measures included responder rate (proportion of patients with > or =50% reduction in monthly migraine frequency), reductions in mean number of monthly migraine days, severity, duration, and days a month requiring rescue medication, and adverse events. The month of onset of preventive treatment action was assessed.. Of 483 patients randomized, 468 provided at least 1 postbaseline efficacy assessment and comprised the intent-to-treat population. Mean monthly migraine frequency decreased significantly for patients receiving topiramate at 100 mg/d (-2.1, P =.008) and topiramate at 200 mg/d (-2.4, P<.001) vs placebo (-1.1). Statistically significant reductions (P<.05) occurred within the first month with topiramate at 100 and 200 mg/d. The responder rate was significantly greater with topiramate at 50 mg/d (39%, P =.01), 100 mg/d (49%, P<.001), and 200 mg/d (47%, P<.001) vs placebo (23%). Reductions in migraine days were significant for the 100-mg/d (P =.003) and 200-mg/d (P<.001) topiramate groups. Rescue medication use was reduced in the 100-mg/d (P =.01) and 200-mg/d (P =.005) topiramate groups. Adverse events resulting in discontinuation in the topiramate groups included paresthesia, fatigue, and nausea.. Topiramate showed significant efficacy in migraine prevention within the first month of treatment, an effect maintained for the duration of the double-blind phase.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Double-Blind Method; Female; Fructose; Humans; Linear Models; Male; Middle Aged; Migraine Disorders; Topiramate; Weight Loss

Open-label trials and small controlled studies report topiramate's efficacy in migraine prevention.. To assess the efficacy and safety of topiramate as a migraine-preventive therapy.. A 26-week, randomized, double-blind, placebo-controlled study.. Outpatient treatment at 49 US clinical centers. Patients Patients were aged 12 to 65 years, had a 6-month International Headache Society migraine history, and experienced 3 to 12 migraines per month, but had 15 or fewer headache days per month during the 28-day baseline period.. Participants were randomized to placebo or topiramate, 50, 100, or 200 mg/d, titrated by 25 mg/wk to the assigned dose or as tolerated in 8 weeks; maintenance therapy continued for 18 weeks.. The primary efficacy assessment was a reduction in mean monthly migraine frequency across the 6-month treatment phase. Secondary end points were responder rate, time to onset of action, mean change in migraine days per month, and mean change in rescue medication days per month.. Four hundred eighty-seven patients were randomized, and 469 composed the intent-to-treat population. The mean +/- SD monthly migraine frequency decreased significantly for the 100-mg/d group (from 5.4 +/- 2.2 to 3.3 +/- 2.9; P <.001) and the 200-mg/d group (from 5.6 +/- 2.6 to 3.3 +/- 2.9; P <.001) vs the placebo group (from 5.6 +/- 2.3 to 4.6 +/- 3.0); improvements occurred within the first treatment month. Significantly more topiramate-treated patients (50 mg/d, 35.9% [P =.04]; 100 mg/d, 54.0% [P <.001]; and 200 mg/d, 52.3% [P <.001]) exhibited a 50% or more reduction in monthly migraine frequency than placebo-treated patients (22.6%). Adverse events included paresthesia, fatigue, nausea, anorexia, and taste per version.. Topiramate, 100 or 200 mg/d, was effective as a preventive therapy for patients with migraine.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Topiramate; Treatment Outcome

Topiramate (TPM) has shown efficacy in migraine prophylaxis in two large placebo-controlled, dose-ranging trials. We conducted a randomised, double-blind, multicentre trial to evaluate the efficacy and safety of two doses of topiramate vs placebo for migraine prophylaxis, with propranolol (PROP) as an active control. Subjects with episodic migraine with and without aura were randomised to TPM 100 mg/d, TPM 200 mg/d, PROP 160 mg/d (active control), or placebo. The primary efficacy measure was the change in mean monthly migraine frequency from the baseline phase relative to the double-blind treatment phase. Five hundred and seventy-five subjects were enrolled from 61 centres in 13 countries. TPM 100 mg/d was superior to placebo as measured by reduction in monthly migraine frequency, overall 50% responder rate, reduction in monthly migraine days, and reduction in the rate of daily rescue medication use. The TPM 100 mg/d and PROP groups were similar with respect to reductions in migraine frequency, responder rate, migraine days, and daily rescue medication usage. TPM 100 mg/d was better tolerated than TPM 200 mg/d, and was generally comparable to PROP. No unusual or unexpected safety risks emerged. These findings demonstrate that TPM 100 mg/d is effective in migraine prophylaxis. TPM 100 mg/d and PROP 160 mg/d exhibited similar efficacy profiles.

Topics: Adult; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Drug Evaluation; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Propranolol; Prospective Studies; Time Factors; Topiramate; Treatment Outcome; Vasodilator Agents

Migraine is a highly prevalent chronic neurologic disorder. Frequent headache attacks require prophylactic treatment, and side effects are limiting prescribing factors among traditional agents for migraine prophylaxis. Beta-blockers, antidepressants, calcium channel blockers, and anticonvulsants have been used since the 1960s, and their efficacy has been demonstrated in several controlled studies. However, weight gain commonly occurs with most of these drugs and makes adherence to treatment a troublesome issue for many patients. Topiramate is a new anticonvulsant with proven efficacy in migraine and other conditions, which reportedly confers weight loss in patients receiving doses up to 300 mg/day.. The aim of this study was to evaluate adherence, weight loss, tolerability, and response to topiramate in adult migraineurs receiving treatment in a tertiary care center.. During a 2,5-year period, all patients receiving topiramate for migraine were evaluated after 3 months of treatment. The parameters evaluated were adherence to treatment, frequency in reduction of attacks > 50%, the presence and amount of weight loss, and adverse events.. Among 175 patients included, 134 (76.6%) adhered to the regimen, whereas 4% interrupted before the 3-month evaluation and 19.4% did not return for follow-up. Among the 134 patients evaluated, 82 (61.2%) revealed headache-frequency reduction > 50%; 105 (78.4%) patients experienced weight loss (range 1-10 kg; average, 3.4 kg). The most frequent side effects were paresthesia (39.6%); emotional disturbances, including depression, irritability, and anxiety (17.9%); thinking impairment (12.7%); memory disturbances (12.7%); and altered taste (11.9%).. Despite methodologic limitations, we conclude that good adherence to topiramate in a "real-world" headache clinic occurred in most of the study participants. The majority of patients also experienced weight loss and reductions in headache frequency, with an acceptable side-effect profile.

Topics: Adult; Anticonvulsants; Body Weight; Female; Fructose; Humans; Male; Migraine Disorders; Topiramate

The objectives of this paper are to evaluate the efficacy and tolerability of topiramate, given at the dose of 100 mg/day, in the prophylactic treatment of migraine. The hypothesis that migraine is the result of a condition of neuronal hyperexcitability and the quest for drugs that are able to limit the number of crises justifies the attempt to utilise the new antiepileptic drugs in the prophylaxis of this pathology, which is so important due to its high prevalence and due to the high disability it causes. The study was randomised double-blind versus placebo, lasting 16 weeks, and was preceded by a run-in period of 4 weeks. One hundred and fifteen patients were randomly allocated to treatment with topiramate (TPM) or placebo: 35 patients completed the study in the TPM group and 37 patients in the placebo group. At the end of the double-blind phase of study, in the TPM group, we recorded a significant reduction in the frequency of migraine crises (from 5.26 at baseline to 2.60 in the last 4 weeks), a significant reduction in the quantity of symptomatic drugs taken as compared to the placebo control group (from 6.17+/-1.80 SD to 2.57+/-0.80) and a significant downward trend in the number of days of disability over the 16-week period of therapy. In the TPM group, side effects were transient and well tolerated. TPM has thus proven its efficacy and tolerability in the prophylaxis of migraine.

Topics: Adult; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Topiramate

The safety and efficacy of medications for preventive treatment of migraine is the subject of current concern and investigation in health care. Two single-center, double-blind, placebo-controlled studies were conducted to evaluate the efficacy and safety of topiramate for migraine prophylaxis. Seventy patients with a diagnosis of migraine were randomly assigned to topiramate-treated and placebo groups. The studies consisted of a 4-week baseline phase, a 6-8 week titration, and 8-12 weeks of maintenance. Topiramate was titrated from an initial dose of 25 mg/day to a target dose of 100 mg BID. The primary efficacy measure, the mean 28-day migraine frequency, was lower in topiramate-treated patients than in the placebo group (3.2 versus 3.8, P=.001). Similarly, topiramate treatment resulted in a significantly greater mean reduction in migraine frequency than did placebo (1.55 versus 0.47, P=.001) and a significantly higher responder rate (35.3% versus 8.3%, P=.008). Paresthesia was the most common side effect reported with topiramate treatment. Other topiramate-associated adverse events included altered taste, memory impairment, diarrhea, and appetite suppression/weight loss. The rates of discontinuation were similar for the topiramate group (n=10) and the placebo group (n=8). These results suggest that topiramate is effective and well tolerated in the preventive treatment of migraine headaches.

Topics: Adult; Body Mass Index; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Pilot Projects; Topiramate

The efficacy of current preventive migraine treatments is limited. In addition, tolerability problems are not infrequent.. To check our experience with topiramate in the treatment of patients with refractory migraine.. We offered treatment with topiramate to patients with the diagnosis of International Headache Society (IHS) migraine who had not responded to or tolerated beta-blockers, amitriptyline, flunarizine and/or valproate. This series is made up of 115 patients (88 women), between 16 and 81 years. Most of them (n=79) fulfilled the Silberstein et al. criteria for transformed migraine. The parameters analyzed were "response" (reduction in migraine frequency>50%), excellent response (>75%) and tolerability.. After 3 months, the maintenance doses of topiramate ranged from 25 to 400 mg, though most patients took 100 mg. Twenty-four (21%) patients withdrew due to adverse events, mostly cognitive difficulties, that had already occurred with doses as low as 25-50 mg, while 26 (23%) found topiramate ineffective. The remaining 65 (56%) patients responded, 34 with excellent response. Sixteen patients (10 obese) lost weight (3-13 kg).. Topiramate seems to be a good therapeutic option for about half of the patients with refractory migraine. In these patients response is usually excellent. Intolerance due to adverse events appears in one-fifth of the cases early and at low doses.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Spain; Topiramate

The purpose of this study was to evaluate the efficacy of topiramate in the treatment of chronic migraine. This was a double-blind, randomized, placebo controlled, parallel-group study. Patients suffering from chronic migraine with analgesic overuse were randomly assigned in a 1 : 1 ratio to receive topiramate or placebo. Following a baseline phase of eight weeks, the study drug was titrated in 25-mg increments over one week to 50 mg daily. Titration phase was followed by a 8-week maintenance phase. Number of days with headache during a 28-day period was the efficacy variable. At baseline, there was no difference in the number of days with headache between patients treated with topiramate and those treated with placebo (mean +/- SD: 20.9 +/- 3.2 and 20.8 +/- 3.2, respectively). During the last 4 week-maintenance phase, topiramate-treated patients experienced a significantly lower 28-day headache frequency in comparison to those treated with placebo (mean number of days with headache +/- SD: 8.1 +/- 8.1 vs. 20.6 +/- 3.4, P < 0.0007). Topiramate at low doses proved to be an effective therapeutic approach to reduce headache frequency in patients with chronic migraine and analgesic overuse.

Topics: Adult; Analgesics; Chi-Square Distribution; Chronic Disease; Confidence Intervals; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Multivariate Analysis; Odds Ratio; Topiramate

Migraine is a significant problem for many children. Topiramate has been suggested to be effective for the prophylaxis of migraine in adults, but has not yet been examined in children. The drug has been demonstrated to be safe and effective for childhood seizure disorders. The objective of this study was to demonstrate the safety and efficacy of topiramate for the prevention of pediatric migraine.. Children with frequent migraine were prescribed topiramate for headache prevention. Dosages, serum levels, and Serum Glutamic Oxalacetic Transaminase (SGOT) levels were monitored. Changes in frequency, severity, and duration of headaches were recorded and changes in headache-related disability using PedMIDAS also were measured.. Ninety-seven children were treated with topiramate, and 75 were reevaluated 88.7 +/- 35.7 days later, 41 were seen at a second follow-up, and 17 were seen at a third follow-up evaluation. The daily dose reached at second evaluation was 84.0 +/- 38.6 mg/day or 1.42 +/- 0.74 mg/kg/day. This corresponded to a mean serum level of 2.8 +/- 1.6 micro g/mL. The mean headache frequency was reduced from 16.5 +/- 10.0 to 11.6 +/- 10.2 days per month (P<0.001) with a further reduction to 9.4 +/- 8.4 days by the second follow-up (P<0.001). Severity and duration of headache also were reduced. Headache disability improved, with a reduction of Pediatric Migraine Disability Assessment score from 36.0 +/- 42.3 to 20.8 +/- 34.0 at the first follow-up (P<0.05), 19.1 +/- 22.0 at the second follow-up (P<0.005), and 10.9 +/- 16.9 at the third follow-up (P<0.001). Most patients tolerated topiramate well. The most common side effects reported were cognitive (12.5%), weight loss (5.6%), and sensory (2.8%).. Topiramate is potentially an effective prophylactic medication for children with frequent migraine.

Topics: Anticonvulsants; Aspartate Aminotransferases; Child; Fructose; Headache; Humans; Migraine Disorders; Prospective Studies; Recurrence; Topiramate; Treatment Outcome

Cortical spreading depolarization, the cause of migraine aura, is a short-lasting depolarization wave that moves across the brain cortex, transiently suppressing neuronal activity. Prophylactic treatments for migraine, such as topiramate or valproate, reduce the number of cortical spreading depression events in rodents.. To investigate whether cortical spreading depolarization with and without chronic treatment with topiramate or valproate affect the DNA methylation of the cortex.. Sprague-Dawley rats were intraperitoneally injected with saline, topiramate or valproate for four weeks when cortical spreading depolarization were induced and genome-wide DNA methylation was performed in the cortex of six rats per group.. The DNA methylation profile of the cortex was significantly modified after cortical spreading depolarization, with and without topiramate or valproate. Interestingly, topiramate reduced by almost 50% the number of differentially methylated regions, whereas valproate increased them by 17%, when comparing to the non-treated group after cortical spreading depolarization induction. The majority of the differentially methylated regions lay within intragenic regions, and the analyses of functional group over-representation retrieved several enriched functions, including functions related to protein processing in the cortical spreading depolarization without treatment group; functions related to metabolic processes in the cortical spreading depolarization with topiramate group; and functions related to synapse and ErbB, MAPK or retrograde endocannabinoid signaling in the cortical spreading depolarization with valproate group.. Our results may provide insights into the underlying physiological mechanisms of migraine with aura and emphasize the role of epigenetics in migraine susceptibility.

Topics: Animals; Cortical Spreading Depression; DNA Methylation; Migraine Disorders; Rats; Rats, Sprague-Dawley; Topiramate; Valproic Acid

Topics: Anticonvulsants; Child; Cholecalciferol; Dietary Supplements; Fructose; Humans; Migraine Disorders; Topiramate

Calcitonin gene-related peptide (CGRP) is involved in migraine pathophysiology and blood pressure regulation. Although clinical trials have established the cardio-cerebrovascular safety profile of anti-CGRP treatment, limited high-quality real-world evidence exists on its long-term effects on blood pressure (BP). To address this gap, we examined the safety of anti-CGRP treatment on BP in patients with migraine headache in the Veterans Health Administration (VHA).. We emulated a target trial of patients who initiated anti-CGRP treatment or topiramate for migraine prevention between May 17th, 2018 and February 28th, 2023. We calculated stabilized inverse probability weights to balance between groups and then used weighted linear mixed-effect models to estimate the systolic and diastolic BP changes over the study period. For patients without hypertension at baseline, we estimated the cumulative incidence of hypertension using Kaplan-Meier curve. We also used weight mixed-effect Poisson model to estimate the number of antihypertension medications for patients with hypertension at baseline.. This analysis included 69,589 patients and 554,437 blood pressure readings. of these, 18,880 patients received anti-CGRP treatment, and they were more likely to be women, have a chronic migraine diagnosis and higher healthcare utilization than those received topiramate. Among patients without hypertension at baseline, we found no significant differences in systolic BP changes over the four-year follow-up between anti-CGRP (slope [standard error, SE] = 0.48[0.06]) and topiramate treated patients (slope[SE] = 0.39[0.04]). The incidence of hypertension was similar for anti-CGRP and topiramate group (4.4 vs 4.3 per 100 person-years). Among patients with hypertension at baseline who initiated anti-CGRP treatment, we found a small but persistent effect on exacerbating hypertension during the first four years of treatment, as evidenced by a significant annual 3.7% increase in the number of antihypertensive medications prescribed (RR = 1.037, 95%CI 1.025-1.048).. Our findings suggest that anti-CGRP treatment is safe regarding blood pressure in patients without hypertension. However, for those with baseline hypertension, anti-CGRP treatment resulted in a small but persistent increase in the number of antihypertensives, indicating an exacerbation of hypertension. Future studies are needed to evaluate the cardio-cerebrovascular safety of anti-CGRP treatment beyond the first four years.

Topics: Blood Pressure; Calcitonin Gene-Related Peptide; Female; Humans; Hypertension; Male; Migraine Disorders; Topiramate

We present a case of presumed topiramate-induced retinopathy in a 58-year-old woman who presented with progressive, bilateral visual loss following a 3- to 4-year history of oral topiramate intake for migraine. She reported difficulty with light adaptation, hemeralopia, and color desaturation. Her best-corrected visual acuity was 1/60 (20/1200) in the right eye and 6/18 (20/60) in the left eye, and she performed poorly on Ishihara color plate testing. Anterior segment examination was normal; dilated funduscopy showed mild macular pigmentary changes. Optical coherence tomography revealed subtle thinning and reduced reflectivity of the subfoveal ellipsoid zone and interdigitation zone bilaterally, associated with increased foveal autofluorescence. Humphrey visual field 24-2 revealed central defects. Electrodiagnostic testing showed a reduced and delayed b-wave and a normal a-wave on photopic full-field electroretinogram (ERG), with normal scotopic responses; multifocal ERG revealed reduced responses in the inner 10° in both eyes. She underwent extensive investigations including whole-body computed tomography and positron emission tomography scan, magnetic resonance imaging of the brain, uveitis screening, retinal autoantibody testing, and genetic testing on the retinal dystrophy panel to rule-out other causes for her presentation, all of which were normal or negative.

Topics: Electroretinography; Female; Humans; Middle Aged; Migraine Disorders; Retina; Retinal Dystrophies; Topiramate

Migraine is the primary cause of headache in children. Most patients can be treated with lifestyle changes and acute attack prophylaxis. Prophylaxis should be considered when symptoms cause frequent school absenteeism, poor quality of life, recurring emergency room visits, and frequent analgesic use. We aimed to compare the efficacy and side effects of drugs used in migraine prophylaxis, chosen according to the clinical and/or demographic characteristics of the patients.. One hundred eighty-six patients aged 6-18 years were evaluated and who were diagnosed with migraine according to The International Classification of Headache Disorders, 3rd edition beta version (ICH-3β). Propranolol, topiramate, flunarizine, and cyproheptadine were given as prophylactic treatment. The Pediatric Migraine Disability Assessment Score (PedMIDAS) score, severity, duration, and frequency of the headache attacks were evaluated from the medical records and pre- and post-treatment values were compared.. The median age of the patients was 14 years (range, 6-18 years) and the mean duration of headache was 29.6 ± 21.02 months. The mean PedMIDAS score was 29.9 ± 21.2 before and 14.9 ± 12.5 after treatment. Most reduction in the frequency of attacks was observed in the topiramate group. All four drugs significantly reduced the PedMIDAS score. The most common side effect was palpitations.. Significant improvement was found in PedMIDAS scores in all drug groups. Topiramate was found to be the most effective drug in reducing the frequency of attacks. All four drugs in this study may be utilized for migraine prophylaxis in terms of effectiveness and safety.

Topics: Child; Drug-Related Side Effects and Adverse Reactions; Fructose; Headache; Humans; Infant; Migraine Disorders; Quality of Life; Topiramate

Topics: Antibodies, Monoclonal; Botulinum Toxins, Type A; Chronic Disease; Double-Blind Method; Humans; Migraine Disorders; Topiramate; Treatment Outcome; Valproic Acid

Episodic ataxia type 2 is an autosomal dominant channelopathy, caused by genetic variants in the voltage-dependent calcium channel a-1 subunit (CACNA1A), which is characterized by intermittent episodes of vertigo and ataxia. A slow progression of cerebellar signs is commonly observed in the course of the disease. Treatment with the carbonic anhydrase inhibitor acetazolamide is recommended.. We report the cases of two patients with EA-2 and migraine, linked to a novel CACNA1A mutation associated with disabling ictal and interictal disease, which did not respond to acetazolamide.. A 30-year-old woman and a 50-year-old man, who was a ski instructor, reported disabling episodes of rotatory vertigo and progressive interictal ataxia. In both cases, the disease progressed despite treatment with acetazolamide. The concomitant use of topiramate and 4-aminopyridine significantly reduced the frequency and severity of relapses and migraine and improved the interictal cerebellar progression in both cases.. We propose combined applications of topiramate and 4-aminopyridine in refractory cases and those with poor tolerance to acetazolamide and also in those with frequent associated migraine. The effectiveness of this combination of drugs for treating intermittent ataxic episodes and interictal signs in EA-2 has not been previously reported.

Topics: 4-Aminopyridine; Acetazolamide; Adult; Ataxia; Cerebellar Ataxia; Female; Humans; Male; Middle Aged; Migraine Disorders; Mutation; Nystagmus, Pathologic; Recurrence; Topiramate; Vertigo

The prophylactic treatment of migraine includes anticonvulsant drugs such as valproic acid and topiramate. However, these substances are often poorly tolerated by migraine patients. So far levetiracetam has hardly been studied as an episodic migraine prophylactic agent in adults.. To perform a prospective pilot study for the evaluation of the efficacy and tolerability of levetiracetam in the prophylactic treatment of episodic migraine.. Fifty patients with episodic migraine were enrolled in this prospective, open label study. After a baseline period of four weeks, patients received 1,000 mg (starting dose 500 mg) bid levetiracetam for 12 weeks. Migraine frequency and accompanying symptoms were recorded in a headache diary. The primary endpoint was the comparison of attack frequency during the baseline with attack frequency during the last four weeks of treatment (treatment period 3).. In the Intent-To-Treat analysis, 46% of the patients had a migraine reduction of more than 50% in the third period as compared to the baseline period. The mean number of migraine attacks decreased from 5.2 +/- 2.1 (baseline) to 3.4 +/- 2.7 (period 3). The most frequently reported side effects were somnolence, nausea, and weight gain; all were mild and transient. In a post-hoc comparison, responders to levetiracetam had significantly less migraine attacks at baseline and had significantly more often migraine with aura.. The data suggest that levetiracetam has some potential in the prophylactic treatment of episodic migraine which seems, however, to be not superior to that of other anticonvulsant drugs. Levetiracetam was well tolerated and showed better efficacy in patients with migraine with aura and in less affected migraine patients. A larger placebo-controlled, double-blind study in adults seems justified on the basis of these data.

Topics: Adult; Anticonvulsants; Double-Blind Method; Humans; Levetiracetam; Migraine Disorders; Migraine with Aura; Pilot Projects; Prospective Studies; Topiramate; Treatment Outcome; Valproic Acid

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Cholecalciferol; Dietary Supplements; Double-Blind Method; Fructose; Humans; Migraine Disorders; Prospective Studies; Topiramate; Treatment Outcome; Vitamin D

Gut microbial dysbiosis and gut-brain axis dysfunction have been implicated in the pathophysiology of migraine. However, it is unclear whether migraine-related cephalic allodynia could induce the alteration of gut microbial composition.. A classic migraine rat model was established by repeated dural infusions of inflammatory soup (IS). Periorbital mechanical threshold and nociception-related behaviors were used to evaluate IS-induced cephalic allodynia and the preventive effect of topiramate. The alterations in gut microbial composition and potential metabolic pathways were investigated based on the results of 16 S rRNA gene sequencing. Microbiota-related short-chain fatty acids and tryptophan metabolites were detected and quantified by mass spectrometry analysis.. Repeated dural IS infusions induced cephalic allodynia (decreased mechanical threshold), migraine-like behaviors (increased immobility time and reduced moving distance), and microbial composition alteration, which were ameliorated by the treatment of topiramate. Decreased Lactobacillus was the most prominent biomarker genus in the IS-induced alteration of microbial composition. Additionally, IS infusions also enhanced metabolic pathways of the gut microbiota in butanoate, propanoate, and tryptophan, while the increased tryptophan-related metabolites indole-3-acetamide and tryptophol in feces could be the indicators.. Inflammatory dural stimulation-induced cephalic allodynia causes the alterations of gut microbiota profile and microbial metabolic pathways.

Topics: Animals; Gastrointestinal Microbiome; Humans; Hyperalgesia; Migraine Disorders; Rats; Rats, Sprague-Dawley; Topiramate; Tryptophan

Topiramate has multiple pharmacological mechanisms that are efficient in treating epilepsy and migraine. Ginger has been established to have gingerols and shogaols that cause migraine relief. Moreover, Topiramate has many off-label uses. Thus, it was necessary to explore the possible neurotoxicity of Topiramate and the role of ginger oil in attenuating the Topiramate neurotoxicity. Male albino mice were orally gavaged with Topiramate, ginger oil (400 mg/kg), and Topiramate plus ginger oil with the same pattern for 28 days. Oxidative stress markers, acetylcholinesterase (AchE), gamma-aminobutyric acid (GABA), and tumor necrosis factor-alpha (TNF-α) were examined. Histopathological examination, immunohistochemical glial fibrillary acidic protein (GFAP), and Bax expression analysis were detected. The GABAAR subunits, Gabra1, Gabra3, and Gabra5 expression, were assessed by RT-qPCR. The investigation showed that Topiramate raised oxidative stress markers levels, neurotransmitters, TNF-α, and diminished glutathione (GSH). In addition, Topiramate exhibited various neuropathological alterations, strong Bax, and GFAP immune-reactivity in the cerebral cortex. At the same time, the results indicated that ginger oil had no neurotoxicity. The effect of Topiramate plus ginger oil alleviated the changes induced by Topiramate in the tested parameters. Both Topiramate and ginger oil upregulated the mRNA expression of gabra1 and gabra3, while their interaction markedly downregulated them. Therefore, it could be concluded that the Topiramate overdose could cause neurotoxicity, but the interaction with ginger oil may reduce Topiramate-induced neurotoxicity and should be taken in parallel.

Topics: Acetylcholinesterase; Animals; bcl-2-Associated X Protein; Brain; Glutathione; Male; Mice; Migraine Disorders; Oils, Volatile; Plant Extracts; Topiramate; Tumor Necrosis Factor-alpha; Zingiber officinale

The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the medications currently used for migraine prevention in Taiwan. The subcommittee assessed the results of recently published trials, meta-analyses, and guidelines. After expert panel discussions, the subcommittee reached a consensus on the preventive treatment of migraine in Taiwan, which includes recommendation levels, the strength of evidence, and essential prescription information (i.e., dosage and adverse effects) . The recent introduction of CGRP monoclonal antibodies has had a substantial effect on migraine treatment. Thus, the subcommittee updated the previous version of the treatment guideline published in 2017. Preventive medications for migraines can be divided into the following categories: ß-blockers, anticonvulsants, calcium channel blockers, antidepressants, onabotulinumtoxinA, anti-CGRP monoclonal antibodies, and complementary and alternative medicine. For episodic migraine prevention, propranolol, flunarizine, and topiramate are recommended as the first-line medications. Second-line medications for episodic migraine prevention include valproic acid, amitriptyline, and anti-CGRP monoclonal antibodies. Other treatment options could be used as third-line treatments. For chronic migraine prevention, topiramate, flunarizine, onabotulinumtoxinA, and anti-CGRP monoclonal antibodies are recommended as first-line therapies. Preventive medications for episodic migraine can also be used as second-line treatments for chronic migraine. For menstrual migraines, nonsteroidal anti-inflammatory drugs and triptans can be used for short-term prophylaxis. Indications for starting preventive treatment include a headache frequency of ≥4 days per month, profound disabilities, failure of or contraindication to acute therapies, a complicated migraine with debilitating (e.g., hemiplegic) auras, and migrainous brain infarction. The general principle for oral preventives is to "start low and go slow" while monitoring for adverse events and comorbid conditions. Physicians could consider gradually tapering the medications in patients with sustained improvement over 3 to 6 months in episodic migraine and 6 to 12 months in chronic migraine. Education about not overusing acute medications is also essential for all patients with migraine. Key words: migraine, preventive treatment, evidence-based medicine, guidelines, CGRP monoclonal antibodies, onabotulinumtoxinA, neuromodulation.

Topics: Antibodies, Monoclonal; Botulinum Toxins, Type A; Flunarizine; Headache; Humans; Migraine Disorders; Taiwan; Topiramate

Topics: Anxiety; Flunarizine; Humans; Migraine Disorders; Topiramate; Vertigo

To examine the hearing outcomes of patients with sudden sensorineural hearing loss (SSNHL) treated with oral and intratympanic (IT) steroid only or a combination of steroid and migraine treatment. Our hypothesis was that adjuvant migraine medications may improve outcomes in SSNHL.. A retrospective chart review at a tertiary otology center was conducted to identify patients with SSNHL who received oral steroid and IT dexamethasone injection(s) with or without migraine medications (a combination of nortriptyline and topiramate).. A total of 47 patients received oral steroid and IT dexamethasone injection(s) only, and 46 patients received oral steroid and IT dexamethasone injection(s) as well as migraine lifestyle changes plus a combination of nortriptyline and topiramate. There were no significant differences in demographics and baseline audiometric data between the two groups. Both groups demonstrated improvements in pure tone average (PTA) and hearing thresholds at 250 Hz and 8000 Hz posttreatment. However, compared to steroid-only group, the adjuvant migraine medications group had significantly greater improvements in hearing thresholds at the lower frequencies (250 Hz, 500 Hz, 1000 Hz). Patients in the latter cohort also had greater improvement in PTA (P = .01) and received fewer IT injections (P = .04) PTA improvement of ≥ 10 dB was observed in 36 patients (78%) in the adjuvant migraine medications group and 22 patients (46%) in the control group (P < .001).. In multimodal treatment of SSNHL, supplementing oral and IT steroid with migraine medications may result in greater improvements in lower frequency hearing thresholds and PTA. Furthermore, adjuvant migraine treatment can lead to decrease in number of IT injections, thus reducing procedure-related risks and complications.. 3 Laryngoscope, 131:E283-E288, 2021.

Topics: Administration, Oral; Adult; Aged; Dexamethasone; Drug Therapy, Combination; Female; Glucocorticoids; Hearing Loss, Sensorineural; Hearing Loss, Sudden; Humans; Injection, Intratympanic; Male; Middle Aged; Migraine Disorders; Nortriptyline; Retrospective Studies; Topiramate

Calcitonin gene-related peptide (CGRP) inhibitors were introduced in the United States (US) in 2018. To understand the changing patterns of preventive treatment following the introduction of these new agents, we must first characterize the patterns which preceded their introduction.. To characterize the burden, unmet need, and treatment patterns in patients with migraine initiating preventive migraine medications before the introduction of CGRP inhibitors in the US.. Between March 2016 and October 2017, we enrolled episodic (EM) and chronic migraine (CM) patients initiating or changing preventive treatment at primary care or neurology clinic visits in the US, in a real-world observational study using a prospective cohort design. At baseline and monthly thereafter for 6 months, we collected data from study sites and patients on migraine frequency, treatment modifications, migraine impact on functioning, and work productivity for a descriptive analysis of migraine patient experience and treatment patterns.. From the sample of 234 completers, 118 had EM (50.4%) and 116 had CM (49.6%). Mean age at enrollment was 41 years (SD = 12) and mean age at first migraine diagnosis was 22 years (SD = 11). Most participants were females (n = 204/234; 87.2%) and white (n = 178/234; 76.1%). The majority (n = 164/234; 70.1%) had not used preventive migraine treatment in the 5 years prior to enrollment (treatment naïve). At baseline, mean monthly migraine days were 9.6 days (SD = 5.0) for the preventive treatment naïve group and 12.4 days (SD = 7.0) for treatment experienced patients. The majority had severe Migraine Disability Assessment (Grade IV, total score ≥21), including 67.1% (n = 110/164) of the preventive treatment naïve and 77.1% (n = 54/70) of the preventive treatment experienced patients. Headache Impact Test total scores indicating severe impairment (score >59) occurred in 88.4% (n = 145/164) of the treatment naïve and 88.6% (n = 62/70) of treatment experienced patients. Mean work productivity loss as measured by the Work Productivity and Activity Impairment questionnaire in the subsample of employed patients was 53.3% loss. The most used acute medications at baseline were nonsteroidal anti-inflammatory agents (n = 124/234; 53.0%), acetaminophen-based products (n = 112/234; 47.9%), and triptans (n = 105/234; 44.9%). The most commonly initiated preventive treatments were topiramate (n = 100/234; 42.7%), tricyclic antidepressants (n = 39/234; 16.7%), beta-blockers (n = 26/234; 11.1%), and onabotulinumtoxinA (n = 24/234; 10.3%). Over the 6-month follow-up period, almost half of patients (n = 116/234, 49.6%) modified their preventive treatment and discontinued treatment (n = 88/312 total modifications; 28.2%) or modified their pattern of use by increasing, decreasing, or skipping doses (n = 224/312 total modifications; 71.8%), often without seeking medical advice. Avoiding side effects was the main reason reported among patients who discontinued (n = 52/88; 59.1%), decreased frequency or dose (n = 37/89; 41.6%), and skipped doses (n = 29/86; 33.7%). Perceived lack of efficacy was another frequent reason reported among those who discontinued (n = 20/88; 22.7%), decreased frequency or dose (n = 15/89; 16.9%), and skipped doses (n = 18/86; 20.9%). Despite initiation of preventive treatment and improvements observed in number of headache and migraine days, migraine patients continued to experience substantial disability, headache impact, and reduced productivity througho. Prior to 2018, the burden of migraine was high for patients initiating preventive treatments. Despite having more than 9 days of migraine per month on average, the majority (70.1%) of patients initiating prevention had been treatment naïve, indicating underuse of preventive treatments. The preventive treatments used in this study were poorly tolerated and were reported by patients to lack efficacy, resulting in suboptimal adherence. The high discontinuation rates suggest that the preventive medications being offered during the period of the study did not meet the treatment needs of patients. In addition, the decisions by about half of patients to alter their prescribed treatment plan without consulting their provider can pose substantial health risks. These findings pertain to the broad set of preventive treatments initiated in this study and do not support inferences about individual preventive treatments, due to limitations in sample size. These findings suggest the need for more effective and better tolerated preventive treatment options.

Topics: Acetaminophen; Adrenergic beta-Antagonists; Adult; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Antidepressive Agents, Tricyclic; Botulinum Toxins, Type A; Chronic Disease; Female; Follow-Up Studies; Humans; Male; Middle Aged; Migraine Disorders; Neuromuscular Agents; Outcome Assessment, Health Care; Serotonin 5-HT1 Receptor Agonists; Topiramate

Topics: Anticonvulsants; Fructose; Humans; Migraine Disorders; Topiramate; Treatment Outcome

To evaluate the efficacy of a multi-modal migraine prophylaxis therapy for patients with hyperacusis.. In a prospective cohort, patients with hyperacusis were treated with a multi-modal step-wise migraine prophylactic regimen (nortriptyline, verapamil, topiramate, or a combination thereof) as well as lifestyle and dietary modifications. Pre- and post-treatment average loudness discomfort level (LDL), hyperacusis discomfort level measured by a visual analogue scale (VAS), and scores on the modified Khalfa questionnaire for severity of hyperacusis were compared.. Twenty-two of the 25 patients (88%) reported subjective resolution of their symptoms following treatment. Post-treatment audiograms showed significant improvement in average LDL from 81.3 ± 3.2 dB to 86.4 ± 2.6 dB (. The majority of patients with hyperacusis demonstrated symptomatic improvement from migraine prophylaxis therapy, as indicated by self-reported and audiometric measures. Our findings indicate that, for some patients, hyperacusis may share a pathophysiologic basis with migraine disorder and may be successfully managed with multimodal migraine prophylaxis therapy.

Topics: Adrenergic Uptake Inhibitors; Adult; Aged; Anticonvulsants; Drug Therapy, Combination; Female; Follow-Up Studies; Hearing; Hearing Tests; Humans; Hyperacusis; Male; Middle Aged; Migraine Disorders; Nortriptyline; Prospective Studies; Quality of Life; Topiramate; Treatment Outcome; Vasodilator Agents; Verapamil; Visual Analog Scale; Young Adult

A 22-year-old female was admitted to our hospital due to acute onset of severe headache, confusion, and deterioration of consciousness. Results of initial examinations did not suggest cerebrovascular diseases, encephalitis, or nonconvulsive status epilepticus. Over the next several weeks, her level of consciousness fluctuated in parallel with the severity of headache. The electroencephalogram, recorded during a symptomatic episode, showed lack of posterior dominant rhythm, and the single-photon emission CT (SPECT) also revealed a decrease in cerebral blood flow predominantly in the occipital lobes. Administration of sodium valproate and topiramate, recommended as treatment for migraine, dramatically ameliorated her headache and consciousness. Although this was an adult-onset case, her symptoms and clinical course were similar with the diagnosis of ICHD-3-unlisted confusional migraine rather than other listed subtypes of migraine with aura. Further accumulation of similar adult-onset cases is necessary to clarify the nature of this illness.

Topics: Adult; Epilepsy; Female; Humans; Migraine Disorders; Topiramate; Valproic Acid; Young Adult

Vestibular migraine (VM) consists of recurrent episodes of vestibular symptoms that are accompanied by migraine in at least 50% of the episodes. The criteria of the Bárány Society include two diagnostic categories: "actual" vestibular migraine and probable vestibular migraine. There is a wide range of drugs that can be prescribed for the prophylactic treatment of VM, but recommendations for the selection of the most appropriate drug are currently lacking.. To measure the extent to which the prophylactic treatment of VM reduces vestibular symptoms, headache and the number of crises depending on the diagnostic category of the Bárány Society and the drug used for prophylaxis.. This is a multicenter prospective study. Patients with VM who presented to any of the participating centers and who subsequently met the VM criteria were prescribed one of the following types of prophylaxis: acetazolamide, amitriptyline, flunarizine, propranolol or topiramate. Patients were called back for a follow-up visit 5 weeks later. This allowed the intensity of vestibular symptoms, headache and the number of crises before and during treatment to be compared.. 31 Patients met the inclusion criteria. During the treatment, all the measured variables decreased significantly. In a visual analogue scale, the intensity of vestibular symptoms decreased by 45.8 points, the intensity of headache decreased by 47.8 points and patients suffered from 15.6 less monthly crises compared to the period before the treatment. No significant between-group differences were found when patients were divided based on their diagnostic category or the choice of prophylaxis prescribed to them.. The treatment of VM produces a reduction of symptoms and crises with no significant differences based on patients' diagnostic categories or the choice of prophylaxis prescribed to them.

Topics: Acetazolamide; Amitriptyline; Analgesics; Central Nervous System Agents; Flunarizine; Humans; Migraine Disorders; Propranolol; Prospective Studies; Topiramate; Vertigo; Vestibular Diseases

Topics: Adult; Anticonvulsants; Benign Paroxysmal Positional Vertigo; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Migraine Disorders; Nystagmus, Pathologic; Patient Positioning; Retrospective Studies; Topiramate; Vestibular Diseases

Topics: Aged; Anticonvulsants; Choroid; Choroidal Effusions; Female; Humans; Intraocular Pressure; Microscopy, Acoustic; Migraine Disorders; Topiramate

Given the lack of evidence on patients with medically refractory vestibular migraine, this study aimed to identify factors associated with pharmacotherapy failure and progression to botulinum toxin injection in vestibular migraine.. A retrospective cohort study was conducted on definite vestibular migraine patients from September 2015 to July 2019 who completed the Dizziness Handicap Inventory at least six weeks apart... The study comprised 47 patients (mean age = 50.2 ± 15.8 years), with a mean follow-up time of 6.0 ± 6.0 months. The mean pre-treatment Dizziness Handicap Inventory score was 57.5 ± 23.5, with a mean reduction of 17.3 ± 25.2 (p < 0.001) at last follow up. Oscillopsia (r = 0.458, p = 0.007), failure of first medication (r = 0.518, p = 0.001) and pre-treatment Dizziness Handicap Inventory question 15 (an emotional domain question) score (r = 0.364, p = 0.019) were the only variables significantly correlated with progression to botulinum toxin injection.. Motion hypersensitivity, failure of first medication, and fear of social stigmatisation suggest a decreased treatment response. These symptoms may require more aggressive treatment at an earlier stage.

Topics: Adult; Aged; Aged, 80 and over; Botulinum Toxins; Dizziness; Female; Humans; Injections; Male; Middle Aged; Migraine Disorders; Nortriptyline; Propranolol; Retrospective Studies; Risk Factors; Topiramate; Treatment Failure; Verapamil; Young Adult

Topiramate is the only oral preventative with level of evidence I for the treatment of chronic migraine.. To evaluate gray matter parameters, obtained with magnetic resonance imaging (MRI), as biomarkers of the response to topiramate in chronic migraine patients.. The sample was composed by 57 chronic migraine patients, screened for first time in a Headache Unit due to chronic migraine. MRI acquisitions were performed at a 3 T unit. Afterwards, topiramate preventive treatment began. Response and tolerability were evaluated after three months, defining response as at least 50% reduction in headache days per month. We included patients that tolerated topiramate. T1- and diffusion-weighted MRI were processed to obtain gray matter (68 cortical and 16 subcortical regions) descriptive parameters. A logistic regression model was employed for the predictive assessment.. Forty-two patients tolerated the treatment and were analyzed, responding 23 of them (54.7%). The final prediction model was built with gray matter parameters with significant results. In this model, higher left cuneus curvature and right insula area values were associated with a higher probability of response, while higher right inferior parietal cortex volume and left superior temporal gyrus area values were associated with a lower probability. The accuracy of the predictive model was 95%.. The gray matter parameters may be useful biomarkers of preventive treatment response with topiramate in chronic migraine.. Predicción de la respuesta al tratamiento preventivo en migraña crónica mediante la medición de la sustancia gris en resonancia magnética: estudio piloto.. Introducción. El topiramato es el único tratamiento preventivo oral con nivel de evidencia I para la migraña crónica. Objetivo. Evaluar los parámetros de la sustancia gris, obtenidos mediante resonancia magnética, como marcadores de respuesta al tratamiento con topiramato en pacientes con migraña crónica. Pacientes y métodos. La muestra se compuso de 57 pacientes con migraña crónica atendidos por primera vez en una unidad de cefaleas como consecuencia de migraña crónica, a los que se realizó una resonancia magnética de 3 T. Posteriormente, se inició el tratamiento preventivo con topiramato. Se evaluaron la respuesta y la tolerancia a los tres meses y se definió respuesta como disminución de al menos un 50% en el número de días de cefalea al mes. Mediante procesamiento de imágenes de resonancia magnética ponderadas en T1 y difusión, se obtuvieron los parámetros de la sustancia gris (68 estructuras corticales y 16 subcorticales). Se obtuvo un modelo de regresión logística para la valoración predictiva. Resultados. Se analizó a 42 pacientes que toleraron el tratamiento, con respuesta terapéutica en 23 de ellos (54,7%). El modelo final de predicción se construyó con parámetros de la sustancia gris con resultados significativos. En dicho modelo, a mayor curvatura del cúneo izquierdo y área de la ínsula derecha, mayor probabilidad de respuesta, y menor probabilidad a mayor volumen de la corteza inferior parietal derecha y área del giro temporal superior izquierdo. La precisión del modelo predictivo fue del 95%. Conclusión. Los parámetros de la sustancia gris pueden ser marcadores útiles de respuesta al tratamiento preventivo con topiramato en la migraña crónica.

Topics: Anticonvulsants; Brain; Cerebral Cortex; Gray Matter; Humans; Magnetic Resonance Imaging; Migraine Disorders; Pilot Projects; Topiramate

Topics: Botulinum Toxins, Type A; Humans; Injections, Intramuscular; Migraine Disorders; Neuromuscular Agents; Quality of Life; Topiramate

Migraine diagnosis is based on clinical aspects and is dependent on the experience of the attending physician. This study aimed to describe the patients journey profile until they start their experience in a tertiary headache center.. In a cross-sectional study, medical charts from migraine patients were reviewed to describe which treatments, procedures and follow-up strategies are performed until the first appointment with a headache specialist. Patients from both sexes, ≥18 years old, which came to their first visit from March to July 2017 were included. Sociodemographic information, headache characteristics, diagnostic methods previously used, clinical history, family history and the treatments previously used were assessed in the first appointment with a specialist. Patient Health Questionnaire-9 and General Anxiety Disorder-7 were also applied. Descriptive analyses were performed to describe the sample profile and statistical tests were used to evaluate factors associated with the type of migraine (chronic or episodic).. The sample consisted of 465 patients. On average, the pain started 17.1 (SD = 11.4) years before the first appointment with a headache specialist. Most of patients were classified as having chronic migraine (51.7%), with an average frequency of 15.5 (SD = 9.9) days per month. Regarding patients' journey until a specialist, most patients were submitted to laboratory tests (74.0%), cranial tomography (66.8%) and magnetic resonance imaging (66.8%) as diagnostic methods, and preventive drugs (70.2%) and acupuncture (61.0%) as treatments. After stratification by migraine type as episodic or chronic, patients with chronic migraine were submitted to more magnetic resonance imaging test, acupuncture, psychotherapy, used preventive drugs, and reported to have used topiramate without beneficial effects.. Brazilian patients with migraine experiment a long journey until getting to a headache specialist and are submitted to a great number of unnecessary exams, especially those with chronic migraine.

Topics: Acupuncture Therapy; Adolescent; Adult; Cross-Sectional Studies; Female; Headache; Humans; Male; Middle Aged; Migraine Disorders; Topiramate

Topics: Adult; Anticonvulsants; Clobetasol; Dermatitis; Drug Eruptions; Eating; Female; Glucocorticoids; Granuloma; Humans; Migraine Disorders; Skin; Skin Diseases; Topiramate; Treatment Outcome

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Drug Therapy, Combination; Female; Humans; Indomethacin; Male; Migraine Disorders; Topiramate

Limited population-based data are available on antiepileptic drug (AED) treatment patterns in women of childbearing age with epilepsy; the current population risk is not clear.. To examine the AED treatment patterns and identify differences in use of valproate sodium and topiramate by comorbidities among women of childbearing age with epilepsy.. A retrospective cohort study used a nationwide commercial database and supplemental Medicare as well as Medicaid insurance claims data to identify 46 767 women with epilepsy aged 15 to 44 years. The eligible study cohort was enrolled between January 1, 2009, and December 31, 2013. Data analysis was conducted from January 1, 2017, to February 22, 2018.. Cases required an International Classification of Diseases, Ninth Revision, Clinical Modification-coded epilepsy diagnosis with continuous medical and pharmacy enrollment. Incident cases required a baseline of 2 or more years without an epilepsy diagnosis or AED prescription before the index date. For both incident and prevalent cases, focal and generalized epilepsy cohorts were matched by age, payer type, and enrollment period and then compared.. Antiepileptic drug treatment pattern according to seizure type and comorbidities.. Of the 46 767 patients identified, there were 8003 incident cases (mean [SD] age, 27.3 [9.4] years) and 38 764 prevalent cases (mean [SD] age, 29.7 [9.0] years). Among 3219 women in the incident epilepsy group who received AEDs for 90 days or more, 3173 (98.6%) received monotherapy as first-line treatment; among 28 239 treated prevalent cases, 18 987 (67.2%) received monotherapy. In 3544 (44.3%) incident cases and 9480 (24.5%) prevalent cases, AED treatment was not documented during 180 days or more of follow-up after diagnosis. Valproate (incident: 35 [5.81%]; prevalent: 514 [13.1%]) and phenytoin (incident: 33 [5.48%]; prevalent: 178 [4.53%]) were more commonly used for generalized epilepsy and oxcarbazepine (incident: 53 [8.03%]; prevalent: 386 [9.89%]) was more often used for focal epilepsy. Levetiracetam (incident: focal, 267 [40.5%]; generalized, 271 [45.0%]; prevalent: focal, 794 [20.3%]; generalized, 871 [22.2%]), lamotrigine (incident: focal, 123 [18.6%]; generalized, 106 [17.6%]; prevalent: focal, 968 [24.8%]; generalized, 871 [22.2%]), and topiramate (incident: focal, 102 [15.5%]; generalized, 64 [10.6%]; prevalent: focal, 499 [12.8%]; generalized, 470 [12.0%]) were leading AEDs prescribed for both focal and generalized epilepsy. Valproate was more commonly prescribed for women with comorbid headache or migraine (incident: 53 of 1251 [4.2%]; prevalent: 839 of 8046 [10.4%]), mood disorder (incident: 63 of 860 [7.3%]; prevalent: 1110 of 6995 [15.9%]), and anxiety and dissociative disorders (incident: 57 of 881 [6.5%]; prevalent: 798 of 5912 [13.5%]). Topiramate was more likely prescribed for those with comorbid headache or migraine (incident: 335 of 1251 [26.8%]; prevalent: 2322 of 8046 [28.9%]).. Many women appear to be treated with valproate and topiramate despite known teratogenicity risks. Comorbidities may affect selecting certain AEDs despite their teratogenicity risks.

Topics: Adolescent; Adult; Anticonvulsants; Anxiety Disorders; Comorbidity; Dissociative Disorders; Epilepsies, Partial; Epilepsy, Generalized; Female; Headache Disorders; Humans; Lamotrigine; Levetiracetam; Mental Disorders; Migraine Disorders; Mood Disorders; Oxcarbazepine; Phenytoin; Retrospective Studies; Risk; Teratogens; Topiramate; Valproic Acid; Young Adult

Some variables have been proposed as predictors of efficacy of OnabotulinumtoxinA in chronic migraine patients, but data available are inconclusive. We aimed to analyse the influence of single nucleotide polymorphisms in the response to OnabotulinumtoxinA.. We included 156 female patients treated with OnabotulinumtoxinA accordingly to PREEMPT paradigm in three headache units. OnabotulinumtoxinA was offered to patients that had not responded to topiramate and at least one other preventative. Age at first procedure was 43.7 ± 11.8 years (16-74). Patients with a reduction of at least 50% in the number of migraine days after two OnabotulinumtoxinA procedures were considered as responders. We analysed 25 polymorphisms selected for their relevance regarding migraine pathophysiology and their association with migraine according to previously published genome-wide association studies. Genotyping was performed using KASP probes and a LightCycler-480 (Roche-Diagnostics). Allelic, genotypic frequencies and dominance/recesivity hypothesis of the allelic variants were compared between responders and non-responders by Fisher's exact test.. Response to treatment with OnabotulinumtoxinA was achieved in 120 patients (76,9%). Two polymorphisms showed differences: CALCA rs3781719, where allele C represents 26.9% in responders and 40.9% in non-responders (p = 0.007, OR = 3.11 (1.33-7.26)); and TRPV1 rs222749, where allele A represents 4.17% in responders and 12.5% in non-responders (p = 0.013, OR = 3.29 (1.28-8.43)). No significant differences in rest of polymorphisms or clinical or demographic variables were found.. Polymorphic variations of CALCA and TRPV1 genes might play a role as prognostic markers of efficacy of OnabotulinumtoxinA in chronic migraine female patients in our population.

Topics: Adolescent; Adult; Aged; Botulinum Toxins, Type A; Calcitonin Gene-Related Peptide; Chronic Disease; Female; Gene Frequency; Genome-Wide Association Study; Humans; Middle Aged; Migraine Disorders; Neuromuscular Agents; Polymorphism, Single Nucleotide; Prospective Studies; Topiramate; Treatment Outcome; TRPV Cation Channels; Young Adult

Topiramate, 2,3:4,5-di-O-isopropylidene-β-d-fructopyranose sulfamate, is a potent antiepileptic drug with a broad spectrum of activity. It is effective in both partial and generalized seizures. Topiramate was also found to have significant efficacy in migraine prevention with considerable reductions in the frequency of migraine headaches. The most common adverse events, which may accompany the use of topiramate, are paresthesia, fatigue, decreased appetite, nausea, diarrhea, weight decrease and taste perversion. The weight loss observed with the use of topiramate in obese, epileptic patients, afforded the approval of this drug as an anti-obesity medication. This action is thought to be based on the selective inhibition of mitochondrial carbonic anhydrase isoforms. This profile is prepared to discuss and explain physical characteristics, proprietary and nonproprietary names of topiramate. It also includes methods of preparation, thermal and spectral behavior and methods of analysis. Pharmacokinetics, metabolism, excretion and pharmacology together with its uses and applications are also discussed.

Topics: Anticonvulsants; Epilepsy; Humans; Migraine Disorders; Topiramate

Topics: Anticonvulsants; Female; Humans; Middle Aged; Migraine Disorders; Topiramate; Treatment Outcome; Vertigo; Vestibular Diseases

Background Nitric oxide (NO) has been heavily implicated in migraine. Nitroglycerin is a prototypic NO-donor, and triggers migraine in humans. However, nitroglycerin also induces oxidative/nitrosative stress and is a source of peroxynitrite - factors previously linked with migraine etiology. Soluble guanylyl cyclase (sGC) is the high affinity NO receptor in the body, and the aim of this study was to identify the precise role of sGC in acute and chronic migraine. Methods We developed a novel brain-bioavailable sGC stimulator (VL-102), and tested its hyperalgesic properties in mice. We also determined the effect of VL-102 on c-fos and calcitonin gene related peptide (CGRP) immunoreactivity within the trigeminovascular complex. In addition, we also tested the known sGC inhibitor, ODQ, within the chronic nitroglycerin migraine model. Results VL-102-evoked acute and chronic mechanical cephalic and hind-paw allodynia in a dose-dependent manner, which was blocked by the migraine medications sumatriptan, propranolol, and topiramate. In addition, VL-102 also increased c-fos and CGRP expressing cells within the trigeminovascular complex. Importantly, ODQ completely inhibited acute and chronic hyperalgesia induced by nitroglycerin. ODQ also blocked hyperalgesia already established by chronic nitroglycerin, implicating this pathway in migraine chronicity. Conclusions These results indicate that nitroglycerin causes migraine-related pain through stimulation of the sGC pathway, and that super-activation of this receptor may be an important component for the maintenance of chronic migraine. This work opens the possibility for negative sGC modulators as novel migraine therapies.

Topics: Adrenergic beta-Antagonists; Allosteric Regulation; Animals; Anticonvulsants; Calcitonin Gene-Related Peptide; Disease Models, Animal; Enzyme Inhibitors; Female; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Migraine Disorders; Molecular Targeted Therapy; Nitric Oxide; Nitric Oxide Donors; Nitroglycerin; Oxadiazoles; Propranolol; Proto-Oncogene Proteins c-fos; Quinoxalines; Serotonin 5-HT1 Receptor Agonists; Soluble Guanylyl Cyclase; Sumatriptan; Topiramate

Topics: Humans; Migraine Disorders; Migraine with Aura; Pyrazoles; Pyridones; Topiramate; Warfarin

Certain medications used for migraine prevention in adults do not perform the same way in children and adolescents and can actually cause harm.

Topics: Adolescent; Adult; Amitriptyline; Child; Humans; Migraine Disorders; Topiramate

To evaluate the change in quality of life (QOL) of patients with Meniere's disease (MD) after treatment with migraine prophylaxis therapy.. Patients with definite MD were given the Meniere's Disease Outcomes Questionnaire-Retrospective (MDOQ-R) after migraine prophylactic therapy to assess QOL. Changes in physical, emotional, and social parameters affected by MD were calculated, along with a global pre- and posttreatment QOL scores.. The MDOQ-R was given to 27 consecutive patients with definite MD. Patients who had at least an 18-month follow-up were included, resulting in 25 questionnaires. The mean change in QOL score was 25 ± 16 (range, -3 to 55), P = .02. Quality of life was improved in 23 (92%) of the respondents in every metric measured, unchanged in 1 (4%), and poorer in 1 (4%) of patients after migraine prophylaxis treatment.. Majority of MD patients who had all failed diuretic therapy responded positively to medications used for migraine prophylaxis, as indicated by a significant improvement in QOL. This study may further suggest a correlation between the pathophysiologic basis of disease in MD and vestibular migraine. Patients with MD may be successfully managed with medications intended to treat migraine.

Topics: Chemoprevention; Female; Fructose; Humans; Male; Meniere Disease; Middle Aged; Migraine Disorders; Nortriptyline; Patient Reported Outcome Measures; Psychotropic Drugs; Quality of Life; Risk Reduction Behavior; Surveys and Questionnaires; Topiramate; Vasodilator Agents; Verapamil

Background The impact of adverse events (AEs) of antiepileptic drugs (AEDs) have an impact on compliance and dropouts. We compared tolerability of AEs of AEDs among patients with migraine, epilepsy, or both. Methods Overall, 335 patients (epilepsy (n = 142), migraine (n = 131), and both (n = 62)), were evaluated with the Liverpool Adverse Events Profile (LAEP) to assess the magnitude, profile and occurrence rate of the AEs of valproate, topiramate, and lamotrigine. Results AEs were significantly more common with topiramate treatment (71.0%) and among migraineurs (69.5%), the latter being more prone to discontinue AEDs (46.6%). The profile of AEs with topiramate and valproate differed among groups. Moreover, treatment with both topiramate and valproate was associated, for all groups, with a worse tolerability profile compared to lamotrigine. Conclusion Our data suggest a specific drug and disease AE profile of AEDs. Specifically, migraineurs are the most affected by AEs, even though they receive very low dosages of AEDs. This finding might be considered a clinical implication of central sensitization mechanisms. Both the profile and tolerability of AEs, highly influencing quality of life, depended on the underlying conditions, and deeply impacted on treatment dropout. Therefore, before starting, switching or stopping AED treatment, all options need to be considered.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Child; Epilepsy; Female; Humans; Lamotrigine; Male; Middle Aged; Migraine Disorders; Topiramate; Valproic Acid; Young Adult

Topics: Adult; Central Nervous System Agents; Epilepsy; Fructose; Humans; Male; Mental Disorders; Migraine Disorders; Topiramate

Topics: Amitriptyline; Child; Fructose; Humans; Migraine Disorders; Topiramate

Topics: Adolescent; Amitriptyline; Child; Humans; Migraine Disorders; Obesity; Pediatric Obesity; Risk Factors; Screen Time; Sedentary Behavior; Topiramate

Topics: Adolescent; Adult; Age Factors; Amitriptyline; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Child; Drug Industry; Duodenal Ulcer; Female; France; Gastroesophageal Reflux; Humans; Male; Migraine Disorders; Pharmacovigilance; Phenytoin; Plasma Substitutes; Polygeline; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Sex Factors; Stomach Ulcer; Topiramate

The aim of this study is to present a case of 44 years old woman with topiramate induced metabolic acidosis and kidney stones.. The laboratory features of topiramate caused renal tubular acidosis in blood and urine during topiramate treatment, with correction of metabolic acidosis by potassium citrate, and after topiramate withdrawal are presented. Differential diagnosis of all possible causes of metabolic acidosis is discussed.. This study has shown that long-term topiramate administration could induce metabolic acidosis and consequently urholithiasis. Thus, we could recommend testing blood acid base balance, urinary pH and citrates in patients taking topiramate and suffering from kidney stones.

Topics: Acidosis; Adult; Anticonvulsants; Female; Fructose; Humans; Kidney Calculi; Migraine Disorders; Topiramate; Withholding Treatment

Topics: Adolescent; Adult; Canada; Child; Drug-Related Side Effects and Adverse Reactions; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Randomized Controlled Trials as Topic; Topiramate; Treatment Failure; United States; United States Food and Drug Administration

Topiramate is an anticonvulsant that is being increasingly used for a number of different off-label indications. Its inhibition of carbonic anhydrase isoenzymes can lead to metabolic acidosis, elevated urine pH, reduced urine citrate, and hypercalciuria, thereby creating a milieu that is ripe for calcium phosphate stone formation. In this review, we describe a case of topiramate-induced metabolic acidosis. We review the frequency of metabolic acidosis among children and adults, as well as the mechanism of hyperchloremic metabolic acidosis and renal tubular acidosis in topiramate users. Finally, we describe the long-term effects of topiramate-induced metabolic acidosis, including nephrolithiasis, nephrocalcinosis, and bone degradation. Patients who are prescribed topiramate should be carefully monitored for metabolic derangements, and they may benefit from alkali supplementation, or in extreme cases, discontinuation of the drug altogether.

Topics: Acidosis; Adult; Carbonic Anhydrase Inhibitors; Female; Fructose; Humans; Migraine Disorders; Topiramate

Topics: Anticonvulsants; Dose-Response Relationship, Drug; Female; Humans; Middle Aged; Migraine Disorders; Pemphigus, Benign Familial; Skin; Topiramate

Mal de debarquement syndrome (MdDS) is a balance disorder that typically starts after an extended exposure to passive motion, such as a boat or plane ride. Management is typically supportive (e.g. physical therapy), and symptoms that persist beyond 6 months have been described as unlikely to remit. This study was conducted to evaluate the response of patients with MdDS to management with migraine prophylaxis, including lifestyle changes and medical therapy.. Prospective review.. Ambulatory setting at a tertiary care medical center.. Clinical history, detailed questionnaires, and audiograms were used to diagnose patients with MdDS. Those patients with the diagnosis of the MdDS were placed on our institutional vestibular migraine management protocol. Treatment response was assessed with a quality-of-life (QOL) survey and visual analog scale.. Fifteen patients were diagnosed with MdDS, with a predominance of females (73%) and a mean age of 50 ± 13 years. Eleven patients (73%) responded well to management with a vestibular migraine protocol, which included lifestyle changes, as well as pharmacotherapy with verapamil, nortriptyline, topiramate, or a combination thereof. In comparison, a retrospective control group of 17 patients demonstrated a lower rate of improvement when treated with vestibular rehabilitation and physical therapy.. Management of MdDS as vestibular migraine can improve patients' symptoms and increase the QOL. Nearly all the patients suffering from MdDS had a personal or family history of migraine headaches or had signs or symptoms suggestive of atypical migraine.. 4 Laryngoscope, 127:1670-1675, 2017.

Topics: Adult; Aged; Drug Therapy, Combination; Female; Fructose; Genetic Predisposition to Disease; Humans; Male; Meniere Disease; Middle Aged; Migraine Disorders; Motion Sickness; Nortriptyline; Prospective Studies; Quality of Life; Topiramate; Travel; Travel-Related Illness; Verapamil; Visual Analog Scale

To investigate the accommodation function in topiramate users.. Case-control clinical study.. The participants included 16 controls and 22 patients using 100 mg/kg topiramate who were diagnosed with migraine according to the International Classification of Headache Disorders, second edition criteria.. One-minute dynamic measurements of refraction with accommodation stimuli of 0 D, 2 D, 2.5 D, 3 D, 4 D, and 5 D were obtained using the open field refractometer WAM-5500 in.. In most of the accommodation stimuli ranges (0 D, 2.5 D, 3 D, and 5 D), topiramate users had a significantly higher accommodative lag compared with controls (p = 0.028, p = 0.014, p = 0.011, and p = 0.011, respectively). The most important causes of accommodative lag were found to be accommodation stimulus and inclusion in the topiramate group (p < 0.001, R

Topics: Accommodation, Ocular; Adult; Anticonvulsants; Case-Control Studies; Dose-Response Relationship, Drug; Female; Fructose; Humans; Male; Migraine Disorders; Myopia; Prognosis; Refraction, Ocular; Topiramate; Vision Tests; Visual Acuity

Topics: Amitriptyline; Double-Blind Method; Fructose; Humans; Migraine Disorders; Topiramate; Treatment Outcome

To investigate the acute effects of topiramate on the anterior chamber angle (ACA) and choroidal thickness in patients with migraine.. This prospective study included 15 eyes of 15 patients with migraine who have been scheduled to start topiramate therapy. All patients underwent complete ophthalmic examination including measurement of the ACA and choroidal thickness using a spectral domain optical coherence tomography device (Optovue Inc.) and refractive status evaluation with an autorefractokeratometer (KR-8100; Topcon) at the baseline and 1 week after starting therapy. The patients were asked to report any pain or discomfort in their eyes during therapy at the follow-up visit.. None of the patients experienced pain or discomfort in their eyes. The mean ACA significantly decreased at the first week of the therapy compared with the baseline levels (40.34±7.06° and 36.89±6.87°, respectively) (P=0.001). However, the mean choroidal thickness increased from 277.33±95.60 μm at the baseline to 323.40±84.50 μm at the first week (P=0.01). There was a nonsignificant increase in the mean refractive error (from -0.25±0.54 diopter [D] at the baseline to -0.38±0.49 D after 1 week) (P=0.06).. Topiramate can acutely decrease the ACA and increase the choroidal thickness. Because these effects may be asymptomatic, patients with migraine who start this therapy should be warned to be closely followed up by an ophthalmologist.

Topics: Adult; Anterior Chamber; Choroid; Female; Fructose; Humans; Intraocular Pressure; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Pilot Projects; Prospective Studies; Refractive Errors; Tomography, Optical Coherence; Topiramate; Visual Acuity

The aims of this study were to assess (1) the magnitude and temporality of decreased urinary citrate excretion in patients just starting topiramate and (2) the effect of alkali replacement on topiramate-induced hypocitraturia.. Study 1 was a prospective, non-intervention study in which patients starting topiramate for headache remediation provided pre- and post-topiramate 24 h urine collections for measurement of urine citrate. Study 2 was a clinical comparative effectiveness study in which patients reporting to our stone clinic for kidney stones and who were treated with topiramate were prescribed alkali therapy. Pre- and post-alkali 24 h urinary citrate excretion was compared.. Data for 12 and 22 patients (studies 1 and 2 respectively) were evaluated. After starting topiramate, urinary citrate excretion dropped significantly by 30 days (P = 0.016) and 62% of patients had hypocitraturia (citrate <320 mg day(-1) ). At 60 days, urine citrate was even lower than at baseline (P = 0.0032) and 86% of patients had developed hypocitraturia. After starting alkali, urine citrate increased in stone-forming patients on topiramate (198 ± 120 to 408 ± 274 mg day(-1) ; P = 0.042 for difference). 85% of patients were hypocitraturic on topiramate alone vs. 40% after adding alkali. The increase in urinary citrate was greater in patients provided ≥ 90 mEq potassium citrate.. Our study is the first to provide clinical evidence that alkali therapy can raise urinary citrate excretion in patients who form kidney stones while being treated with topiramate. Clinicians should consider alkali therapy for reducing the kidney stone risk of patients benefitting from topiramate treatment for migraine headaches or other conditions.

Topics: Adult; Alkalies; Citric Acid; Female; Fructose; Humans; Kidney Calculi; Male; Middle Aged; Migraine Disorders; Potassium Citrate; Prospective Studies; Topiramate

Topiramate is an approved and effective drug in migraine prophylaxis. Paresthesia is the most commonly reported side effect. The primary objective of this study was to compare the frequency of topiramate-induced paresthesia in migraine headache to epileptic patients. Patients with migraine without aura and epilepsy were enrolled in this observational study. All cases were interviewed by telephone about their history of paresthesia. Confounding factors were controlled through logistic regression. The odds ratio of developing topiramate-induced paresthesia in migraine compared to epilepsy patients was 3.4. Three factors were independent contributors to developing topiramate-induced paresthesia: female sex (odds ratio 2.1), topiramate dosage (odds ratio 0.3) and duration of therapy. Our findings indicate an independent association between migraine and development of paresthesia. Migraineurs were more likely than epileptic patients to report paresthesia as topiramate adverse effects. Female sex, treatment duration and topiramate dosage contribute significantly to subsequent development of paresthesia.

Topics: Adolescent; Adult; Central Nervous System Agents; Child; Epilepsy; Female; Fructose; Humans; Logistic Models; Male; Middle Aged; Migraine Disorders; Odds Ratio; Paresthesia; Topiramate; Young Adult

We report a 34-years-old woman who presented with bilateral incongruous inferior visual field defects after the commencement of topiramate for management of migraine. Investigations did not reveal any underlying angle closure glaucoma, reported in current literature to be associated commonly with topiramate associated visual field defects. The changes in the peripheral visual fields gradually improved over several months after the medication was withdrawn. There were only minor changes persistent on the left side on a background of pre-existing myopia and keratoconus. Visual field deficits secondary to topiramate are more commonly attributed to angle closure glaucoma due to ciliochoroidal effusion syndrome. In such instance, the visual field defects are associated with considerable pain due to raised intra-ocular pressure. There have also been reports of visual scotomas due to retinal damage and maculopathy in patients taking topiramate. It is worthwhile to obtain a baseline perimetry in patients being considered for topiramate therapy in order to gauge any changes in their peripheral field of vision during the treatment. Changes in visual fields during the course of medication use and after cessation can be easily compared especially if there are other possible confounders such as refractive errors or a history of migraine.

Topics: Adult; Anticonvulsants; Female; Fructose; Humans; Migraine Disorders; Topiramate; Vision Disorders; Visual Fields

Prophylactic therapy response varies in migraine patients. The present study investigated the relationship between the resistance to the drugs commonly used in prophylactic therapy and the possible polymorphic variants of proteins involved in the metabolism of these drugs. Migraine patients with the MDR1 3435TT genotype exhibited a better treatment response to topiramate than migraine patients with the CC and CT genotypes (p=0.020). The MDR1 C3435T polymorphism was also found to be a higher risk factor for topiramate treatment failure in a comparison of the number of days with migraine (β2=1.152, p=0.015). However, there was no significant relationship between the treatment response to topiramate and either the CYP2D6 or CYP2C19 polymorphism, and there were no significant correlations between the treatment responses to amitriptyline, propranolol, and valproic acid and the MDR1, CYP2D6 and CYP2C19 gene polymorphisms. This is the first study to investigate the effect of the polymorphic variants on prophylactic therapy response in migraine patients.

Topics: Adult; Amitriptyline; ATP Binding Cassette Transporter, Subfamily B; Central Nervous System Agents; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Drug Resistance; Female; Fructose; Gene Frequency; Genetic Association Studies; Humans; Male; Migraine Disorders; Polymorphism, Genetic; Propranolol; Risk Factors; Topiramate; Treatment Outcome; Valproic Acid

The responses of different patients to the same drug may vary as a consequence of biologic, psychosocial, and genetic differences. The aim of this study was to identify clinical factors associated with a response to pharmacologic treatment in pediatric patients with migraine.. The medical files of patients with migraine attending the headache clinic of a tertiary pediatric medical center in 2010-2015 were reviewed. The children and parents (or only the parents if the child was very young) completed the International Headache Society-based questionnaire. Patients were treated with at least one of the following medications: propranolol, amitriptyline, topiramate. Response to treatment was rated as no change in migraine pattern (grade 1) or a decrease in migraine attack frequency per month by at least 50% (grade 2) or at least 75% (grade 3). The highest-grade response to any pharmacologic treatment was defined as the best clinical response.. The study group included 248 patients of mean age 12.71 ± 3.04 years. A grade 3 best clinical response was significantly associated with a positive maternal history of migraine, younger age at treatment onset, lower frequency of headache attacks per month, postpubertal children had a significantly lower rate of grade 3 response than prepubertal children (P < .05). Analysis of the association of overuse of medication and treatment response achieved a P value equal to .05.. Several background and clinical factors are identified that may predispose children with migraine to respond better to pharmacologic treatment. Clinicians who see children with migraine in a pediatric headache clinic setting should consider these factors before initiating a treatment program.

Topics: Adolescent; Age Factors; Amitriptyline; Central Nervous System Agents; Child; Child, Preschool; Cohort Studies; Comorbidity; Female; Follow-Up Studies; Fructose; Humans; Male; Mental Disorders; Migraine Disorders; Propranolol; Puberty; Tertiary Care Centers; Topiramate; Treatment Outcome

Topics: Brain; Cabergoline; Central Nervous System Agents; Child; Dopamine Agonists; Ergolines; Fructose; Humans; Male; Migraine Disorders; Pituitary Neoplasms; Prolactinoma; Topiramate

Migraine with aura is an established stroke risk factor, and excitatory mechanisms such as spreading depression (SD) are implicated in the pathogenesis of both migraine and stroke. Spontaneous SD waves originate within the peri-infarct tissue and exacerbate the metabolic mismatch during focal cerebral ischemia. Genetically enhanced SD susceptibility facilitates anoxic depolarizations and peri-infarct SDs and accelerates infarct growth, suggesting that susceptibility to SD is a critical determinant of vulnerability to ischemic injury. Because chronic treatment with migraine prophylactic drugs suppresses SD susceptibility, we tested whether migraine prophylaxis can also suppress ischemic depolarizations and improve stroke outcome.. We measured the cortical susceptibility to SD and ischemic depolarizations, and determined tissue and neurological outcomes after middle cerebral artery occlusion in wild-type and familial hemiplegic migraine type 1 knock-in mice treated with vehicle, topiramate or lamotrigine daily for 7 weeks or as a single dose shortly before testing.. Chronic treatment with topiramate or lamotrigine reduced the susceptibility to KCl-induced or electric stimulation-induced SDs as well as ischemic depolarizations in both wild-type and familial hemiplegic migraine type 1 mutant mice. Consequently, both tissue and neurological outcomes were improved. Notably, treatment with a single dose of either drug was ineffective.. These data underscore the importance of hyperexcitability as a mechanism for increased stroke risk in migraineurs, and suggest that migraine prophylaxis may not only prevent migraine attacks but also protect migraineurs against ischemic injury.

Topics: Animals; Anticonvulsants; Brain Ischemia; Calcium Channels, N-Type; Chemoprevention; Cortical Spreading Depression; Fructose; Gene Knock-In Techniques; Infarction, Middle Cerebral Artery; Lamotrigine; Mice; Migraine Disorders; Stroke; Topiramate; Triazines

In addition to headache, persons with chronic migraine (CM) experience multiple symptoms, both ictal and interictal, that may contribute to their suffering. Translating clinical trial results into practice requires assessment of the results' clinical meaningfulness. When examining treatment benefit in this disabled patient population, multiple headache-symptom measures should be considered to fully reflect clinical relevance. Currently, only onabotulinumtoxinA is approved specifically for headache prophylaxis in adults with CM. Topiramate is the only other therapeutic agent with double-blind, placebo-controlled evidence in this population. Herein we evaluate the clinical meaningfulness of onabotulinumtoxinA and topiramate as headache prophylaxis in CM by comparing primary endpoints from the placebo-controlled, double-blind phase of the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program and the topiramate clinical trial (frequency of headache days [primary endpoint in PREEMPT; secondary in topiramate trial] and migraine/migrainous days [primary in topiramate trial, or "migraine/probable-migraine days"; secondary in PREEMPT]). Additionally, outcome measures such as responder rates, health-related quality of life, discontinuation rates, safety, and tolerability profiles are important clinical considerations. The clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate. These data support these treatments as meaningful headache prophylaxis in adults with CM.. CM is a chronic pain condition. We sought to determine the clinical relevance of recent trials in this disabled population. Clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate, and support use of these treatments as meaningful headache prophylaxis in CM.

Topics: Adult; Botulinum Toxins, Type A; Chronic Disease; Clinical Trials as Topic; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Outcome Assessment, Health Care; Quality of Life; Time Factors; Topiramate; Treatment Outcome; Young Adult

Although ocular side effects of topiramate are common, neuroophthalmologic manifestations such as blepharospasm, myokymia and oculogyric crisis are scarcely reported.. We present a serie of 8 patients with migraine who developed eyelid myokymia after treatment with topiramate. We reviewed all patients with migraine treated with topiramate attending the headache outpatient clinic of our hospital from January 2008 to December 2012.. During the study period, a total of 140 patients with migraine were treated with topiramate in our headache clinic. Eight presented eyelid myokymia after beginning treatment with topiramate (5,7%). Topiramate was stopped and myokymia disappeared in all patients, it was prescribed again and eyelid myokymia reappeared with their previous characteristics in all patients.. Eyelid myokymia is an underreported side-effect of topiramate in patients with migraine, of unknown cause, so that in future, further studies are need to examine whether patients with migraine are predisposed or not to this adverse effect.

Topics: Adolescent; Adult; Eyelids; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Myokymia; Topiramate

The Food and Drug Administration recently approved topiramate for migraine prevention in adolescents. Given the well-established appetite-suppressant side effects of topiramate, as well as data suggesting a potential comorbidity between migraine and eating disorders, susceptible young migraine patients may be at a greater risk for the development or worsening of eating disorder symptoms with topiramate therapy. This case series comprises 7 adolescent patients in whom serious eating disorders developed or were exacerbated after the initiation of topiramate therapy. Clinical characteristics of these patients are highlighted. In addition, this case series provides guidelines for providers to use in assessing eating disorders before prescribing topiramate for migraine prevention in adolescents.

Topics: Adolescent; Disease Progression; Feeding and Eating Disorders; Female; Fructose; Humans; Migraine Disorders; Retrospective Studies; Topiramate

Evidence of the cost and effects of interventions for reducing the global burden of migraine remains scarce. Our objective was to estimate the population-level cost-effectiveness of evidence-based migraine interventions and their contributions towards reducing current burden in low- and middle-income countries.. Using a standard WHO approach to cost-effectiveness analysis (CHOICE), we modelled core set intervention strategies for migraine, taking account of coverage and efficacy as well as non-adherence. The setting was primary health care including pharmacies. We modelled 26 intervention strategies implemented during 10 years. These included first-line acute and prophylactic drugs, and the expected consequences of adding consumer-education and provider-training. Total population-level costs and effectiveness (healthy life years [HLY] gained) were combined to form average and incremental cost-effectiveness ratios. We executed runs of the model for the general populations of China, India, Russia and Zambia.. Of the strategies considered, acute treatment of attacks with acetylsalicylic acid (ASA) was by far the most cost-effective and generated a HLY for less than US$ 100. Adding educational actions increased annual costs by 1-2 US cents per capita of the population. Cost-effectiveness ratios then became slightly less favourable but still less than US$ 100 per HLY gained for ASA. An incremental cost of > US$ 10,000 would have to be paid per extra HLY by adding a triptan in a stepped-care treatment paradigm. For prophylaxis, amitriptyline was more cost-effective than propranolol or topiramate.. Self-management with simple analgesics was by far the most cost-effective strategy for migraine treatment in low- and middle-income countries and represents a highly efficient use of health resources. Consumer education and provider training are expected to accelerate progress towards desired levels of coverage and adherence, cost relatively little to implement, and can therefore be considered also economically attractive. Evidence-based interventions for migraine should have as much a claim on scarce health resources as those for other chronic, non-communicable conditions that impose a significant burden on societies.

Topics: Amitriptyline; China; Cost-Benefit Analysis; Fructose; Humans; Income; India; Medication Adherence; Migraine Disorders; Models, Economic; Propranolol; Russia; Self Care; Topiramate; Treatment Outcome; Zambia

We report a 49-year-old female migraineur who experienced paradoxical hyperphagia and concurrent intrusive food thoughts leading to rapid weight gain and a substantial increase in waist circumference. A significant reduction in migraine frequency was also observed during topiramate treatment, a widely used migraine prophylactic agent which is generally associated with weight loss. Withdrawal of topiramate saw appetite return to baseline levels, however, migraine frequency was again increased. Topiramate was reinitiated in combination with phentermine, a drug indicated for weight management, without reoccurrence of adverse effects. Migraine control was maintained and progressive weight loss ensued. Combination treatment with phentermine may be a useful strategy should other patients experience this adverse reaction while gaining therapeutic anti-migraine benefit from topiramate.

Topics: Appetite Depressants; Drug Therapy, Combination; Female; Fructose; Humans; Hyperphagia; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Phentermine; Topiramate; Weight Gain

Topics: Adult; Anticonvulsants; Fructose; Humans; Male; Migraine Disorders; Retinal Diseases; Tomography, Optical Coherence; Topiramate; Visual Acuity; Withholding Treatment

Topics: Betamethasone; Child; Chronic Disease; Female; Fructose; Humans; Migraine Disorders; Paroxysmal Hemicrania; Topiramate; Treatment Outcome

The trigeminovascular system has a pivotal role in the pathomechanism of migraine. The aim of the present study was to further develop existing models of migraine making them more suitable for testing the effects of compounds with presumed antimigraine activity in anaesthetised rats. Simultaneous recording of ongoing activity of spontaneously active neurons in the trigeminocervical complex as well as their discharges evoked by electrical stimulation of the dura mater via activation of A- and C-sensory fibres were carried out. Effects of sumatriptan, propranolol and topiramate were evaluated prior to and after application of a mixture containing inflammatory mediators on the dura. Propranolol (10 mg/kg s.c) and topiramate (30 mg/kg s.c.) resulted in a tendency to decrease the level of both spontaneous and evoked activity, while sumatriptan (1 mg/kg s.c.) did not exhibit any effect on recorded parameters. Application of an inflammatory soup to the dura mater boosted up spontaneous activity, which could be significantly attenuated by propranolol and topiramate but not by sumatriptan. In addition, all compounds prevented the delayed increase of spontaneous firing. In contrast to the ongoing activity, evoked responses were not augmented by inflammatory mediators. Nevertheless, inhibitory effect of propranolol and topiramate was evident when considering A- or C-fibre responses. Findings do not support the view that electrically evoked responses are useful for the measurement of trigeminal sensitization. It is proposed however, that inhibition of enhanced firing (immediate and/or delayed) evoked by inflammatory mediators as an endpoint have higher predictive validity regarding the clinical effectiveness of compounds.

Topics: Action Potentials; Animals; Blood Pressure; Disease Models, Animal; Electric Stimulation; Fructose; Heart Rate; Male; Migraine Disorders; Neurons; Neuroprotective Agents; Predictive Value of Tests; Propranolol; Rats; Rats, Wistar; Reaction Time; Sumatriptan; Topiramate; Trigeminal Nerve; Trigeminal Nuclei; Vasodilator Agents

We present a case of late acute myopia syndrome following discontinuation of treatment with a combination of sulphonamide drugs. To the best of our knowledge, this is the first reported case with such a presentation, and suggests that the pathophysiological basis for the acute myopia syndrome is a rapid decrease in serum carbonic anhydrase inhibitors levels which may lead to a rebound increase in the production of aqueous humor and accumulation of suprachoroidal fluid. It is further postulated that there may be a cumulative effect of sulphonamide drug use on carbonic anhydrase activity in the ciliary body epithelium of susceptible individuals.

Topics: Acute Disease; Adult; Anti-Infective Agents; Anticonvulsants; Drug Therapy, Combination; Female; Fructose; Humans; Intraocular Pressure; Migraine Disorders; Myopia; Pharyngitis; Topiramate; Trimethoprim, Sulfamethoxazole Drug Combination

Granuloma annulare (GA) is a relatively common, self-limiting condition that can be associated with disorders such as diabetes mellitus, malignancy, and thyroid disease, and with the use of some drugs. Topiramate is approved for the prevention of migraine. Its adverse effects include somnolence, fatigue, paresthesia, anorexia and weight loss, and other abnormalities.. We report a 50-year-old woman in whom topiramate at 50 mg/d was initiated in January 2010.. One month after starting topiramate, the patient presented with painless nodules on the left ankle, which later spread to the left leg. Histopathology of a punch biopsy revealed lymphohistiocytic infiltrate, collagen degeneration, and mucin deposition, all of which are characteristic of GA. Two weeks after the discontinuation of topiramate, the lesion resolved. Two years later, the patient resumed topiramate. Two weeks later, a new GA appeared in the same area and disappeared within a few weeks of discontinuation of the drug.. Associations between the use of topiramate and a GA-like reaction have been reported in recent years. Based on the present case, it would appear that an actual association between GA and topiramate is possible given that: (i) the GA appeared only after the initiation of topiramate; (ii) the GA resolved after the discontinuation of topiramate; (iii) the GA reappeared with the resumption of topiramate in the same area and with the same characteristics as previously; and (iv) the lesion healed after topiramate was suspended.

Topics: Anticonvulsants; Drug Eruptions; Female; Fructose; Granuloma Annulare; Humans; Middle Aged; Migraine Disorders; Topiramate

The prevalence of chronic headaches in children and adolescents is up to 2 % resulting in the beginning of the later typical headache careers of adults. The therapy for chronic migraine with botulinum toxin is now established in adults. However, there is only limited experience in the use of botulinum toxin in paediatric patients.. 10 patients aged 13 - 17 years who suffered from chronic migraine according to the IHS criteria were injected at 31 specific injection points of the head and neck muscles with a total amount of 150 IE of botulinum toxin A (Botox®) according to the approved scheme. The number of headache days per month over the following 9 months was recorded and side effects were retrospectively determined.. The responder rate (that is reduction of headache days per month more than 50 %) was 7/10 at three months after the injection. On average the number of headache days per month was reduced from 19.2 days to a minimum of 10.1 days. After three to six months the number of headache days increased again in all responders. Slight local side effects such as redness or temporary pain were observed in all patients, but severe side effects such as infections, fever, ptosis or allergic reactions did not occur.. This small case series shows that the therapy for chronic migraine with botulinum toxin A can also be effective and safe in adolescents. As many adolescents still suffer from headaches later as adults a link between neuropaediatricians and neurologists is justifiable. An early botulinum toxin therapy followed by the transition of the adolescents would be helpful.

Topics: Adolescent; Adrenergic beta-Antagonists; Botulinum Toxins, Type A; Chronic Disease; Female; Fructose; Humans; Male; Metoprolol; Migraine Disorders; Neurology; Neuromuscular Agents; Neuroprotective Agents; Pediatrics; Retrospective Studies; Topiramate; Transcutaneous Electric Nerve Stimulation; Treatment Outcome

Additional medications are needed for inflammatory bowel disease (IBD) as existing therapies are incompletely effective and can be costly and toxic. Preclinical studies suggest that topiramate (an anticonvulsant) may have disease-modifying properties in IBD, but its efficacy in humans is unknown.. To evaluate whether topiramate use is associated with clinical benefit in IBD patients.. We conducted a retrospective cohort study using administrative claims data from the MarketScan databases. Persons with IBD were identified between 2000 and 2010. New users of topiramate were compared with users of other anticonvulsant and anti-migraine medications. The primary outcome was a new prescription for an oral steroid (≥14 days). Secondary outcomes included initiation of biologic agents, abdominal surgery, and hospitalization. Cox proportional hazard modeling was used to adjust for potential confounders.. We identified 773 new users of topiramate and 958 users of comparator drugs. After adjusting for potential confounders, topiramate use was not associated with the primary outcome of steroid prescriptions [hazard ratio (HR) 1.14, 95 % confidence interval (CI) 0.74, 1.73]. Results did not differ significantly by IBD subtype. There was no difference between topiramate users and users of comparator drugs with respect to post-exposure initiation of biologic agents (HR 0.93, 95 % CI 0.39, 2.19), abdominal surgery (HR 1.04, 95 % CI 0.17, 6.41), or hospitalization (HR 0.86, 95 % CI 0.62, 1.19).. In this large U.S. administrative claims study, topiramate use was not associated with markers of IBD flares. These results cast doubt on whether topiramate may be an effective adjunct to current IBD therapy.

Topics: Adult; Anticonvulsants; Bipolar Disorder; Child; Child, Preschool; Databases, Factual; Female; Follow-Up Studies; Fructose; Humans; Infant; Infant, Newborn; Inflammatory Bowel Diseases; Male; Middle Aged; Migraine Disorders; Peripheral Nervous System Diseases; Pharmacoepidemiology; Proportional Hazards Models; Retrospective Studies; Seizures; Topiramate; Treatment Outcome; Young Adult

Topics: Adolescent; Adult; Analgesics; Botulinum Toxins, Type A; Child; Drug Administration Schedule; Drug Overdose; France; Fructose; Headache Disorders; Headache Disorders, Secondary; Hospitalization; Humans; Incidence; Migraine Disorders; Prevalence; Recurrence; Topiramate; Transcutaneous Electric Nerve Stimulation

To evaluate fetal or neonatal outcomes (with a focus on major congenital anomalies) with use of topiramate monotherapy and to examine whether differences occurred in the reporting and patterns of these outcomes for pregnant women with and without epilepsy.. Spontaneous, postmarketing reports involving women who used topiramate monotherapy during pregnancy from 18 July 1995 (International Birth Date of topiramate) through 30 April 2011 were retrieved from the sponsor's (Janssen Research & Development, LLC) Global Medical Safety database. All formulations for topiramate, used as monotherapy, were selected for the analysis. Monotherapy was defined as any situation where no other AED was listed in the pregnancy case report, either as a suspect or concomitant medication, regardless of indication. Results were summarized descriptively.. A total of 1163 cases of women who used topiramate monotherapy during pregnancy (for any indication) were retrieved from the Global Medical Safety database. Since some women used topiramate for more than one indication, there were a total of 1199 reported indications for topiramate monotherapy, which were primarily for treatment of epilepsy (n=599), accounting for half of the indications, and migraine prophylaxis (n=240, 20.0%). Out of 1163 cases, pregnancy outcome was reported in 50.6% (n=589). Live birth was the most frequently reported outcome, regardless of indication (epilepsy, 78.8% [312/396]; prophylaxis of migraine, 59. 3% [48/81]; other indication, 64.4% [85/132]). Cleft lip or palate anomalies (epilepsy, n=15; migraine, n=2; other indication, n=4; and indication not reported, n=2), limb, hand, or other skeletal anomalies (epilepsy, n=13; migraine, n=2; other indication, n=0; and indication not reported, n=1), and respiratory or cardiovascular anomalies (epilepsy, n=12; migraine, n=1; other indication, n=1; and indication not reported, n=2) were the most often reported major fetal or neonatal anomalies. More reported major fetal or neonatal anomalies occurred in patients being treated for epilepsy (53/79 anomaly-indication pairs) compared with patients being treated for migraine prophylaxis (10/79 anomaly-indication pairs).. Although incidence rates cannot be calculated based on spontaneous adverse event reporting, this summary of reported pregnancy and neonatal outcomes with use of topiramate monotherapy suggests that the risk for major fetal or neonatal anomalies may differ based on the indication for topiramate.

Topics: Abnormalities, Drug-Induced; Adult; Adverse Drug Reaction Reporting Systems; Anticonvulsants; Epilepsy; Female; Fructose; Humans; Infant, Newborn; Migraine Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Topiramate

Topics: Anticonvulsants; Fructose; Humans; Migraine Disorders; Topiramate

Topics: Adult; Burning Mouth Syndrome; Female; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate

Topics: Adult; Anticonvulsants; Female; Fructose; Humans; Migraine Disorders; Myopia; Topiramate; Vision Disorders; Visual Acuity

Topics: Analgesics; Contraceptives, Oral, Hormonal; Counseling; Drug Interactions; Drug Therapy, Combination; Female; Fertility; Fructose; Humans; Migraine Disorders; Topiramate; Young Adult

Topics: Acute Disease; Adult; Anti-Inflammatory Agents; Anticonvulsants; Antihypertensive Agents; Female; Fructose; Glaucoma, Angle-Closure; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate; Treatment Outcome; Uveitis, Anterior

Topics: Adolescent; Age Factors; Child; Drug Approval; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate; United States; United States Food and Drug Administration

There is a need for an objective assessment scoring system to evaluate the effectiveness of prophylactic drugs in paediatric migraine, and the aim of this study was to evaluate the Paediatric Migraine Disability Assessment Score (PedMIDAS).. We recruited 88 children aged between 6 and 17 years of age with migraine. The 53 children in the treatment group were divided into three groups according to the prophylactic drug they received topiramate, flunarizine and propranolol and assessed using PedMIDAS before the start of treatment and 3 and 6 months after treatment. The 35 patients in the control group did not receive prophylactic treatment and were assessed with PedMIDAS on three occasions, 3 months apart.. Topiramate, propranolol and flunarizine treatments significantly decreased PedMIDASs and were shown to be effective in improving the patients' quality of life. Topiramate and propranolol were more effective than flunarizine. The number of days on analgesic treatment significantly decreased in the patients who had received topiramate and propranolol treatments (p < 0.05), but remained unchanged in the flunarizine prophylaxis group (p > 0.05).. The PedMIDAS scoring system is useful in evaluating the efficacy of prophylactic therapy in paediatric migraine. Topiramate and propranolol lowered the PedMIDASs better than flunarizine.

Topics: Adolescent; Child; Disability Evaluation; Flunarizine; Fructose; Humans; Migraine Disorders; Propranolol; Topiramate; Treatment Outcome

Topiramate is a drug which emerged from its anticonvulsant properties and now over the years is used for a wider range of indications, including migraine prophylaxis. We described a very rare case of topiramate induced acute onset myopia during use for migraine. It is the first reported case of its kind from Sri Lanka with only a handful of reported cases in world literature.. A 35-year-old Sri Lankan female presented with long standing history of intermittent headache with recent worsening. A diagnosis of migraine was made and due to poor response to other medication was initiated on topiramate. Two weeks later patient developed visual impairment which was finally attributed to topiramate. Following discontinuation of the drug, within 3 days the symptoms started to improve with full recovery in 10 days.. All clinicians should be aware of the potential ocular side effects of topiramate. Although relatively rare, prompt recognition is key to appropriate management.

Topics: Acute Disease; Adult; Female; Fructose; Humans; Migraine Disorders; Myopia; Recovery of Function; Risk Factors; Time Factors; Topiramate; Vision, Ocular

Patients with chronic migraine (CM) and medication abuse are difficult to treat, and have a greater tendency towards chronification and a poorer quality of life than those with other types of headache.. To evaluate whether the presence of medication abuse lowers the effectiveness of topiramate.. A series of patients with CM were grouped according to whether they met abuse criteria or not. They were advised to stop taking the drug that they were abusing. Treatment was adjusted to match their crises and preventive treatment with topiramate was established from the beginning. The number of days with headache and intense migraine in the previous month and at four months of treatment was evaluated.. In all, 262 patients with CM criteria were selected and 167 (63.7%) of them fulfilled abuse criteria. In both groups there was a significant reduction in the number of days with headache/month and number of migraine attacks/month at the fourth month of treatment with topiramate. The percentage of reduction in the number of days with headache/month in CM without abuse was 59.3 ± 36.1%, and with abuse, 48.7 ± 41.7% (p = 0.0574). The percentage of reduction in the number of days with intense migraine/month in CM without abuse was 61.2%, and with abuse, 50% (p = 0.0224). Response rate according to the number of days with headache/month in CM without abuse was 69%, and with abuse, 57%. Response rate according to the number of intense migraines/month in CM without abuse was 76.8%, and in CM with abuse, 61% (p = 0.0097).. Topiramate was effective in patients with CM with and without medication abuse, although effectiveness is lower in the latter case.. El abuso de farmacos en pacientes con migraña cronica influye en la efectividad del tratamiento preventivo con topiramato?. Introduccion. Los pacientes con migraña cronica (MC) y abuso de medicacion son dificiles de tratar y tienen peor calidad de vida que otros pacientes con migrañas. Objetivo. Valorar si la presencia de abuso de farmacos disminuye la efectividad del topiramato. Pacientes y metodos. Una serie de pacientes con MC fueron agrupados segun presentasen criterios de abuso o no abuso de farmacos. Se les aconsejo la supresion del farmaco del cual abusaban. Se ajusto el tratamiento de sus crisis y se inicio tratamiento preventivo desde el principio con topiramato. Se valoro el numero dias con cefalea y migrañas intensas en el mes previo y al cuarto mes de tratamiento. Resultados. Fueron seleccionados 262 pacientes con criterios de MC, y de ellos 167 (63,7%) cumplieron criterios de abuso. En ambos grupos hubo una reduccion significativa del numero de dias con cefalea/mes y numero de crisis de migraña/mes al cuarto mes de tratamiento con topiramato. Porcentaje de reduccion de dias con cefalea/mes en MC sin abuso, 59,3 ± 36,1%; y con abuso, 48,7 ± 41,7% (p = 0,0574). Porcentaje de reduccion de migrañas intensas/mes en MC sin abuso, 61,2%; y con abuso, 50% (p = 0,0224). Tasa de respondedores segun numero de dias con cefalea/mes en MC sin abuso, 69%; y con abuso, 57%. Tasa de respondedores segun numero de migrañas intensas/mes en MC sin abuso, 76,8%; y en MC con abuso, 61% (p = 0,0097). Conclusiones. El topiramato fue efectivo en pacientes con MC sin y con abuso de farmacos, aunque con menor efectividad en estos ultimos.

Topics: Adult; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Drug Interactions; Drug Overdose; Female; Fructose; Headache Disorders; Headache Disorders, Secondary; Humans; Male; Middle Aged; Migraine Disorders; Patient Satisfaction; Substance-Related Disorders; Topiramate; Treatment Outcome; Tryptamines; Young Adult

Topics: Adult; Female; Follow-Up Studies; Fructose; Gonioscopy; Humans; Migraine Disorders; Myopia; Neuroprotective Agents; Refraction, Ocular; Topiramate

Topics: Adult; Central Nervous System Agents; Female; Fibromyalgia; Fructose; Humans; Migraine Disorders; Pain Measurement; Topiramate; Treatment Outcome

Topics: Acute Disease; Adult; Female; Fructose; Glaucoma, Angle-Closure; Gonioscopy; Humans; Intraocular Pressure; Migraine Disorders; Neuroprotective Agents; Tonometry, Ocular; Topiramate; Visual Acuity; Withholding Treatment

A 34-year-old woman presented with new intermittent short lasing headache around the left eye accompanied with lacrimation. She suffered from anemia and visual disturbance due to thalassaemia beta heterotype and retinitis pigmentosa. She also had continual cephalalgia from about 9 years old, and was taking nonsteroidal anti-inflammatory drug almost every day. After the medical treatment, we diagnosed her headache as migraine without aura, medication overuse headache (MOH) and short lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). Triptan was effective for a migraine headache, but it was ineffective for attacks of SUNA, while topiramate dramatically reduced the SUNA attacks. A headache diary was effective to evaluate the clinical course and the effect of treatment for two different types of headaches by devising the approach to description. A migraine and MOH may coexist with SUNA, and our attention should be paid to the diagnosis and medical treatment in such cases.

Topics: Adult; Female; Fructose; Headache; Humans; Migraine Disorders; Substance-Related Disorders; Topiramate

Topiramate is an anticonvulsant agent effective in the prophylaxis of migraine, which also induces weight reduction by an unknown mechanism. We investigated the effect of topiramate on resting metabolic rate, anthropometric measurements, and body composition in patients with migraine independently from any intention to lose body weight. Forty patients (18-71 years old) with migraine were treated with 100 mg of topiramate/day over a period of 3 months. Anthropometric measurements, body fat proportions and resting metabolic rates of these patients were measured before and after treatment. At the end of 3 months, we detected mean 0.8 kg reduction in body weight and 0.3 kg/m(2) reduction in body mass index (BMI). Waist circumference decreased significantly (p = 0.01). Body fat ratio decreased (p = 0.016). Abdominal skinfold measurements decreased after treatment (p = 0.048); however, no difference was found in other regions (p > 0.05). We did not find a significant difference in resting metabolic rate (p > 0.05).These TPM-treated patients lost weight and had reduction in their mean BMI. It was seen that patients lost weight from body fat tissue and central area. We saw that TPM'S weight-reducing effect was independent from resting metaobolic rate. The weight-reducing effect of TPM may result from changes on the hypothalamus.

Topics: Adolescent; Adult; Aged; Basal Metabolism; Body Composition; Body Weight; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Prospective Studies; Topiramate; Treatment Outcome; Weight Loss

The purpose of this study is to present the first case of a pure 'topiramate maculopathy' without acute glaucoma and/or myopia, which form the classical syndrome.. Interventional/observational case report.. Institutional University Teaching Hospital.. A 22-year-old American female, after taking 100 mg of topiramate (Topamax®) a day for 6 days because of a migraine attack, complained of severe visual acuity deterioration of sudden onset in both eyes, regardless of distance (far or near), during the span of 1 day. A complete ocular examination was carried out. Best-corrected visual acuity (BCVA) in the right eye was hand motion and in the left eye was counting fingers. Cycloplegic refraction and pinhole did not improve the visual acuity of patient's eyes. The anterior chamber depth was normal in both eyes. Tonometry was 14 mmHg in both eyes. Fundus biomicroscopy disclosed a maculopathy with macular striae and a cellophane-like reflex. Optical coherence tomography (OCT) showed an undulating profile with congruent retinal folds and choroidal layers plicae. INTERVENTIONAL/OBSERVATION PROCEDURE: Immediate discontinuation of Topamax and steroid therapy.. BCVA, cycloplegic refraction, tonometry, fundus photography, and OCT. Three days after suspension of Topomax and steroid therapy the patient's BCVA was 6/6 in both eyes. Tonometry was 14 mmHg in both eyes. Fundus appearance and OCT features were nearly normal. After 2 years of follow-up, the patient's BCVA, tonometry, macula, and OCT are stable in both eyes. In conclusion, an isolated (unassociated with glaucoma and/or induced myopia) acute maculopathy, previously known as being part of a rare syndrome, has been identified, described, and documented.

Topics: Anticonvulsants; Diagnosis, Differential; Female; Fluorescein Angiography; Fructose; Fundus Oculi; Humans; Macula Lutea; Migraine Disorders; Retinal Diseases; Tomography, Optical Coherence; Topiramate; Young Adult

The purpose of this study was to compare the efficacy and tolerability of topiramate and flunarizine for the prophylaxis of pediatric migraines. A retrospective medical-record review of patients who underwent prophylaxis after receiving a diagnosis of migraine with aura and without aura was performed. Only patients who completed at least 3 months of treatment were included in the analysis. Response to treatment was assessed as the total number of headache days/month. Patients with more than 50% reduction in headache days/month were classified as responders. Responder rate, retention rate, and adverse-event rates were also calculated from all patients who started on the prophylaxis. Further analyses were performed using different patient groups with a cut-off age of 12 years. The responder rate was 80% (89/111 patients) for flunarizine and 81% (122/150 patients) for topiramate, based on a comparison among 261 patients. The retention rate was 67% for flunarizine and 63% for topiramate and the adverse-event rate was 6% for flunarizine and 10% for topiramate. The responder rate, the retention rate, and the adverse-event rate were not significantly different between flunarizine and topiramate. These findings were concordant between the preadolescent (6-12 years old) and adolescent (13-18 years old) groups. The efficacy and tolerability of topiramate were not inferior to those of flunarizine for the prophylaxis of pediatric migraines. These findings were observed in preadolescent and adolescent patients.

Topics: Analgesics; Child; Female; Flunarizine; Fructose; Humans; Male; Migraine Disorders; Retrospective Studies; Topiramate; Treatment Outcome

Patients with migraine headaches are frequently prescribed topiramate to treat their condition.. We present a case of bilateral acute angle-closure glaucoma occurring 2 days after topiramate therapy was increased for symptoms related to migraine.. Acute angle-closure glaucoma secondary to topiramate is an uncommon but serious adverse reaction that may result in severe morbidity such as permanent visual loss if not recognized in a timely manner. Treatment differs from primary acute angle-closure glaucoma in that discontinuation of topiramate is necessary for the glaucoma to resolve.

Topics: Acute Disease; Anticonvulsants; Female; Fructose; Glaucoma, Angle-Closure; Humans; Middle Aged; Migraine Disorders; Topiramate

We describe the case of a 47-year-old woman who came to the emergency department (ED) complaining of worse than typical migraine headache and blurry vision after recently doubling the dose of topiramate earlier that day. After complete neurologic and ophthalmologic evaluation, she was found to have elevated intraocular pressures and was diagnosed with topiramate-induced bilateral acute angleclosure glaucoma, which is a rare side effect of this commonly prescribed medication. She was treated with timolol, brimonide, and prednisolone drops to reduce intraocular pressure as well as cessation of topiramate and was discharged home. This report briefly discusses the clinical history, appropriate evaluation, differential diagnosis, and approach to secondary acute angle-closure glaucoma in the ED.

Topics: Emergency Service, Hospital; Female; Fructose; Glaucoma, Angle-Closure; Humans; Intraocular Pressure; Middle Aged; Migraine Disorders; Neuroprotective Agents; Topiramate

Topics: Anticonvulsants; Female; Fructose; Glaucoma, Angle-Closure; Humans; Middle Aged; Migraine Disorders; Myopia; Topiramate

Topiramate, which is used as an anticonvulsant and for migraine prophylaxis in children, causes oligohydrosis as a side-effect, but its effect on sweat chloride concentrations has not been studied systematically.. Twenty-one children receiving topiramate and 20 healthy controls with no signs or symptoms of pulmonary or gastrointestinal disease and a negative family history for cystic fibrosis (CF) underwent bilateral pilocarpine iontophoresis and sweat collection via Macroduct® system.. Adequate samples (>15 µl volume) were obtained from 17/19 topiramate subjects (89%), and 19/20 (95%) controls. The mean sweat chloride concentration was 37.7 ± 18.8 mmol/L for patients receiving topiramate, and 15.9 ± 6.9 mmol/L for controls (p = 0.0001). The mean sweat volume was 29.1 ± 17.4 µl for patients receiving topiramate, and 41.2 ± 17.5 µl for controls (p = 0.037). Overall 8/17 (47%) of patients on topiramate with a measurable sweat chloride had either an intermediate (>40 mmol/L but <60 mmol/L) or elevated (>60 mmol/L) sweat chloride test result, while 0/19 control subjects had elevated sweat chloride (p = 0.0008). Further analysis of the in vitro activity of topiramate on cultured human bronchial epithelial cells in modified Ussing chambers showed no differences in chloride conductance measured in cells exposed to 10 or 50 µg/ml of topiramate when compared to non-exposed cells.. This is the first report of a medication affecting sweat chloride values and shows that topiramate therapy can cause elevated sweat chloride concentrations in the absence of clinical manifestations of CF.

Topics: Adolescent; Analgesics; Anticonvulsants; Bronchi; Cells, Cultured; Child; Chlorides; Cystic Fibrosis; Female; Fructose; Humans; Iontophoresis; Male; Migraine Disorders; Pilocarpine; Sweat; Topiramate; Treatment Outcome

Neuromodulators such as topiramate (TPM) and divalproex sodium (DVS) are effective in the preventive treatment of migraine. Nonetheless, patients often discontinue their use due to side effects.. The study aims to determine whether the combination of lower doses of TPM and DVS may be useful for patients responsive to higher doses of the individual drugs but experiencing intolerable side effects.. This clinic-based study was conducted to evaluate a series of patients who experienced at least a 50% reduction in headache frequency after 6 weeks of treatment with either TPM 100 mg/day or DVS 750 mg/day, but suffered intolerable drug-related side effects. At that point, patients were switched to TPM (50 mg in the morning and 25 mg at night) plus DVS 500 mg/day (single dose) and reevaluated after 6 further weeks.. Thirty-eight patients were evaluated. Mean age was 37 years, and 84% were female. Of the 38, 17 (77.3%) initially were using TPM only, and 10 (62.5%) initially were using DVS only. After 6 weeks on combination therapy, 27 (62.9%) reported improved tolerability without any decrease in efficacy. Five patients who initially were using TPM only and six using DVS only failed to return for follow-up or were noncompliant with treatment due to persistent or worsening side effects.. This small, open-label study suggests that the combination of TPM and DVS in doses lower than those typically used for migraine prophylaxis may be an effective option for patients who benefited from higher doses of these same medications used as monotherapy but were unable to tolerate such treatment due to side effects.

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Enzyme Inhibitors; Female; Follow-Up Studies; Fructose; gamma-Glutamyltransferase; Humans; L-Lactate Dehydrogenase; Male; Migraine Disorders; Neuroprotective Agents; Retrospective Studies; Topiramate; Treatment Outcome; Valproic Acid

The aim of this article is to create awareness among medical colleagues regarding the severe ophthalmic side effects associated with topiramate use.. A case of severe acute bilateral angle closure glaucoma with visual blurring after oral topiramate therapy.. This case was successfully managed by discontinuing topiramate and by starting anti-glaucoma medication. Intraocular pressure, acute transient myopia, and anterior chamber depth were normalized.. It is important for clinicians to recognize these conditions and educate patients about these serious adverse effects when prescribing topiramate.

Topics: Adult; Female; Fructose; Glaucoma, Angle-Closure; Humans; Intraocular Pressure; Migraine Disorders; Topiramate; Treatment Outcome; Visual Acuity

Spreading Depression is the underlying patho physiological mechanism for the neurological symptoms of migraine aura and is thought to play a major role in triggering migraine. Therefore it seems reasonable to use the Spreading Depression as a pharmacological tool for anti migraine drugs. Drugs that are able to alter parameters of Spreading Depression should also influence appearance and course of migraine attacks. Concerning the classification on the different mechanisms of drug action, especially the retinal Spreading Depression is useful, due to the separation of vascular and neuronal effects. In this study we investigated substances from different classes of common anti migraine drugs on different parameters of the retinal spreading depression. The results are discussed according to the classification of the drug.

Topics: Animals; Barbiturates; Chickens; Cortical Spreading Depression; Disease Models, Animal; Fructose; In Vitro Techniques; Migraine Disorders; Neurons; Retina; Serotonin; Topiramate; Videotape Recording

Topics: Anti-Obesity Agents; Female; Follow-Up Studies; Fructose; Humans; Middle Aged; Migraine Disorders; Neuroprotective Agents; Obesity, Morbid; Topiramate; Treatment Outcome; Weight Loss

Topics: Female; Fructose; Humans; Male; Migraine Disorders; Propranolol; Topiramate

Topics: Adult; Female; Form Perception; Fructose; Humans; Illusions; Migraine Disorders; Neuroprotective Agents; Topiramate; Vision Disorders

The most common causes of chronic cough in nonsmokers are postnasal drip syndrome, asthma, and gastroesophageal reflux disease. Drugs are also important in the etiology of resistant cough. Most common drugs inducing cough are the ACE inhibitors. Many drugs other than ACE inhibitors can also cause dry cough and one among them is topiramate. It is a new generation, efficacy-proved antiepileptic drug that is used widely for migraine prophylaxis in many countries. Most common adverse events of topiramate are paresthesia, cognitive symptoms, fatigue, insomnia, nausea, loss of apetite, anxiety, and dizziness. There is only one case report about topiramate associated cough in the literature. The present report refers to a patient, presenting with cough who is on topiramate treatment for migraine prophylaxis.

Topics: Adult; Cough; Female; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate

Somnambulism (sleepwalking) is a disorder of arousal that falls under "parasomnia" group and is more common in children. These phenomena occur as primary sleep events or secondary to systemic disease or can be drug induced. Medications that can cause sleepwalking include neuroleptics, hypnotics, lithium, amitriptyline, and β-blockers. This report presents an unusual adverse effect of topiramate on sleep in a patient with migraine.

Topics: Adult; Female; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Somnambulism; Topiramate

Previous magnetoencephalographic (MEG) studies showed different P100m (where 'm' denotes the magnetic counterpart of P100 in conventional visual evoked potentials) responses between episodic migraine (EM) and chronic migraine (CM) interictally. This study investigated the changes of visual P100m in CM patients who remitted to EM from CM after treatment.. At baseline, 25 patients with CM were studied interictally. For each patient, 30 sequential blocks of 50 P100m responses were obtained by MEG. Sub-averaged amplitudes at blocks 2, 9, 16, 23 and 30 were further compared with that at block 1 to assess response habituation or potentiation (i.e. significant decrease or increase at either block vs block 1). The same study was repeated in those patients who remitted from CM to EM after topiramate treatment.. In total, 10 CM patients remitted to EM after treatment. In the follow-up study of these patients during the interictal stage, the P100m at block 1 decreased in amplitude from 53.6 ± 6.6 nAm before remission to 43.0 ± 5.1 nAm (p = 0.028), and the responses at subsequent blocks switched from habituation (amplitude block 30 < block 1 before remission, p = 0.011) to potentiation (block 2 > block 1, p = 0.028).. The pattern of P100m responses to consecutive stimulation changes with the transition from CM to EM. Visual cortex plasticity might be a potential biomarker reflecting clinical remission of CM.

Topics: Adult; Anticonvulsants; Chronic Disease; Evoked Potentials, Visual; Female; Follow-Up Studies; Fructose; Humans; Magnetoencephalography; Male; Migraine Disorders; Neuronal Plasticity; Remission Induction; Topiramate; Visual Cortex; Young Adult

Topics: Female; Fructose; Humans; Male; Migraine Disorders; Neuroprotective Agents; Topiramate

Topics: Adolescent; Child; Cohort Studies; Fructose; Humans; India; Male; Migraine Disorders; Topiramate

A 42-year old woman was referred for a metabolic evaluation after two episodes of kidney stones. Her laboratory results revealed a normal anion-gap metabolic acidosis, a marked hypocitraturia (0,6 mmol/24h; norm 1,6-4,5) and a urinary pH of 7,0 confirming renal tubular acidosis (RTA). We identified topiramate, our patient's medication for migraine, as the cause of the RTA. Topiramate, a carboanhydrase inhibitor leads to RTA of a mixed (proximal and distal) type and thus significantly increases the risk for kidney stones.

Topics: Acidosis; Acidosis, Renal Tubular; Adult; Anticonvulsants; Citric Acid; Diagnosis, Differential; Female; Fructose; Humans; Kidney Calculi; Migraine Disorders; Renal Colic; Topiramate

Topics: Adult; Analgesics; Female; Fructose; Humans; Migraine Disorders; Sexual Dysfunction, Physiological; Topiramate

Topiramate, a sulpha-based medication used in the treatment of migraine, has been documented as causing choroidal effusions, transient myopia and acute secondary angle closure glaucoma. We would like to report a case demonstrating these adverse effects and underscore the utility of ultrasound biomicroscopy in diagnosis and management.

Topics: Administration, Oral; Administration, Topical; Adult; Anticonvulsants; Female; Fructose; Glaucoma, Angle-Closure; Humans; Intraocular Pressure; Microscopy, Acoustic; Migraine Disorders; Prednisolone; Topiramate; Vision Disorders

Topics: Adrenergic beta-Antagonists; Anticonvulsants; Fructose; Humans; Migraine Disorders; Practice Guidelines as Topic; Topiramate; Valproic Acid

Topics: Adult; Analgesics; Drug Therapy, Combination; Encephalitis; Fructose; Humans; Male; Migraine Disorders; Topiramate; Valproic Acid

Chronic migraine is a common disabling condition. Severe migraine attacks should be treated with triptans, but these agents are contraindicated in patients with vascular problems and may not be effective or tolerated in around one third of the patients. New acute migraine therapies without vasoconstrictive activity and triptan-specific side effects are emerging. For the prophylaxis of chronic migraine, only topiramate and OnabotulinumtoxinA have been shown to be effective in placebo-controlled randomized trials, so novel therapeutic strategies are needed. The growing understanding of the pathophysiology of chronic migraine will contribute to the identification of new treatment targets.

Topics: Botulinum Toxins, Type A; Chronic Disease; Drug Design; Fructose; Humans; Migraine Disorders; Molecular Targeted Therapy; Neuromuscular Agents; Neuroprotective Agents; Topiramate; Tryptamines

Cortical spreading depression (CSD) is a key pathogenetic step in migraine with aura. Dysfunctions of voltage-dependent and receptor-operated channels have been implicated in the generation of CSD and in the pathophysiology of migraine. Although a known correlation exists between migraine and release of the calcitonin gene-related peptide (CGRP), the possibility that CGRP is involved in CSD has not been examined in detail. We analyzed the pharmacological mechanisms underlying CSD and investigated the possibility that endogenous CGRP contributes to this phenomenon. CSD was analyzed in rat neocortical slices by imaging of the intrinsic optical signal. CSD was measured as the percentage of the maximal surface of a cortical slice covered by the propagation of intrinsic optical signal changes during an induction episode. Reproducible CSD episodes were induced through repetitive elevations of extracellular potassium concentration. AMPA glutamate receptor antagonism did not inhibit CSD, whereas NMDA receptor antagonism did inhibit CSD. Blockade of voltage-dependent sodium channels by TTX also reduced CSD. CSD was also decreased by the antiepileptic drug topiramate, but not by carbamazepine. Interestingly, endogenous CGRP was released in the cortical tissue in a calcium-dependent manner during CSD, and three different CGRP receptor antagonists had a dose-dependent inhibitory effect on CSD, suggesting a critical role of CGRP in this phenomenon. Our findings show that both glutamate NMDA receptors and voltage-dependent sodium channels play roles in CSD. They also demonstrate that CGRP antagonism reduces CSD, supporting the possible use of drugs targeting central CGRP receptors as antimigraine agents.

Topics: Animals; Anticonvulsants; Calcitonin Gene-Related Peptide; Calcitonin Gene-Related Peptide Receptor Antagonists; Carbamazepine; Cerebral Cortex; Cortical Spreading Depression; Dose-Response Relationship, Drug; Fructose; Male; Migraine Disorders; Rats; Rats, Wistar; Receptors, AMPA; Receptors, Calcitonin Gene-Related Peptide; Receptors, N-Methyl-D-Aspartate; Topiramate; Voltage-Gated Sodium Channels

Patients with frequent episodic and chronic migraine, which is often complicated with drug abuse, are resistant to treatment. An objective of the study was to evaluate the efficacy and safety of topalepsin (topiramate) in the preventive treatment of migraine. Thirty patients with frequent episodic and chronic migraine were treated with topalepsin (100 mg daily) during 6 months. After treatment, there was a significant reduction in the number of days with headache and migraine attacks as well as their duration, severity of concomitant symptoms and amount of analgesics used by patients.

Topics: Adult; Analgesics; Anticonvulsants; Chronic Disease; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Topiramate; Treatment Outcome

To report a rare case of bilateral anterior uveitis with hypopyon formation following systemic topiramate use.. A 40-year-old woman with migraine headache who was under topiramate treatment referred with bilateral ocular pain and visual blurring. Physical examination disclosed shallow anterior chamber and high intraocular pressure in both eyes. Following discontinuation of topiramate a severe bilateral anterior uveitis with posterior synechiae and hypopyon developed.. Ocular inflammation resolved with systemic and topical steroid. Because of severe cataract and synechiae formation she underwent phacoemulsification/posterior chamber intraocular lens implantation and visual acuity of both eyes improved to 20/25.. Topiramate should be added to the list of drugs that may cause anterior uveitis and hypopyon formation.

Topics: Adult; Anticonvulsants; Cataract; Eye Pain; Female; Fructose; Glaucoma; Humans; Lens Implantation, Intraocular; Migraine Disorders; Ocular Hypertension; Phacoemulsification; Topiramate; Uveitis, Anterior; Visual Acuity

To determine the changes in refractive error, and the cornea, anterior chamber, and retina induced by topiramate.. The study included 76 eyes of 38 patients that began to use topiramate due to migraine. Following ophthalmological examination, all of the patients underwent central corneal thickness (CCT), anterior chamber volume (ACV), anterior chamber depth (ACD), and anterior chamber angle (ACA) measurement using a Scheimpflug camera, as well as macular thickness, retinal and retinal nerve fiber layer thickness (RNFLT) measurements using optical coherence tomography (OCT). These procedures were repeated 15, 30, and 90 days after the initiation of topiramate therapy.. The median refractive error value showed a statistically significant increase from -0.25 diopters (D) to -0.62 D at the 90th day follow-up (P < 0.001). Mean CCT was 570.56 µm before treatment and increased to 573.69 µm at the 15th day follow-up, 575.31 µm at the 30th day follow-up, and 574.56 µm at the 90th day follow-up; however, these changes were not statistically significant. Mean ACV, ACD, and ACA did not exhibit statistically significant changes. Mean retinal thickness (RT) increased during the treatment from 263.46 µm to 271.60 µm, which was not statistically significant. The initial mean RNFLT was 100.56 ± 15.36 µm and significantly increased to 110.2 ± 8.41 µm and 111.03 ± 14.59 µm at the 30th and 90th day follow-ups, respectively (P  =  0.01 and P  =  0.004, respectively).. During the 3-month follow-up of patients using topiramate 50 mg d(-1) significant myopic shift and an increase in RNFLT were observed. Further studies are warranted in order to assess the effects of topiramate when used long term and at higher doses.

Topics: Administration, Oral; Adolescent; Adult; Anterior Eye Segment; Female; Follow-Up Studies; Fructose; Humans; Intraocular Pressure; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Prospective Studies; Refractive Errors; Retina; Topiramate

Topics: Carbonic Anhydrase Inhibitors; Fructose; Humans; Migraine Disorders; Risk Factors; Topiramate; Urolithiasis

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.. 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.. 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.. Our findings support the use of zonisamide as an alternative therapy for migraine prevention in patients with good response, but poor tolerance to topiramate.

Topics: Adult; Anticonvulsants; Female; Follow-Up Studies; Fructose; Humans; Incidence; Isoxazoles; Middle Aged; Migraine Disorders; Mood Disorders; Paresthesia; Prospective Studies; Severity of Illness Index; Topiramate; Treatment Outcome; Zonisamide

Topics: Adult; Anticonvulsants; Biopsy; Brachial Plexus Neuritis; Drug Eruptions; Female; Foot Dermatoses; Fructose; Granuloma Annulare; Humans; Leg Dermatoses; Migraine Disorders; PUVA Therapy; Recurrence; Skin; Topiramate

A 23-year-old woman who was seen due to decreasing far visual acuity 24hours after starting treatment with topiramate. In the cycloplegic refraction, RE showed -4.25 and LE -4.50. Retinal striae could be seen in the macula of both eyes. The alterations ceased 48hours after the drug treatment was interrupted.. Drug induced acute myopia is an infrequent phenomenon, the aetiology of which is still not fully known.

Topics: Anticonvulsants; Female; Fructose; Humans; Macula Lutea; Migraine Disorders; Mydriatics; Myopia; Retinal Diseases; Topiramate; Young Adult

Antiepileptic drugs (AEDs) are commonly used for prevention of migraine headaches. Bone loss is a known complication, particularly associated with use of older AEDs. Topiramate is a newer AED, widely used for migraine prevention, but no evidence is currently available on its effect on bone metabolism. In a clinic-based pilot study, we evaluated bone health by examining biochemical and radiological markers of bone metabolism, in women with migraine. Osteopenia was noted in 53% of the patients and was associated with the duration of exposure to topiramate (P = .04).

Topics: Adult; Anticonvulsants; Bone and Bones; Bone Diseases, Metabolic; Cross-Sectional Studies; Female; Fructose; Humans; Middle Aged; Migraine Disorders; Pilot Projects; Sex Factors; Topiramate

The drop-out rate among patients receiving preventive treatment for migraine is higher than 30%. This situation is not very widely known and the risk factors that lead patients to drop out from treatment have yet to be identified.. To evaluate some of the factors that can predispose patients to drop out of preventive treatment.. We conducted a prospective study of patients suffering from migraine who required preventive treatment for the first time with one of what are considered the top three first-choice drugs, i.e. a beta-blocker (nadolol), a neuromodulator (topiramate) or a calcium antagonist (flunarizine). Two groups were established according to whether patients dropped out of treatment or not. Different demographic and clinical variables were analysed and compared in the two groups.. Of 800 patients with migraine who required preventive treatment for the first time, the drop-out rate was 19.7%. In the drop-out group, the variables 'age', 'number of seizures', 'number of seizures prior to preventive treatment' and 'side effects' showed significant differences with those from the group of patients who did not drop out of preventive treatment.. The drug used as preventive treatment, the side effects, a younger age and a lower number of seizures before starting the preventive treatment favoured higher drop-out rates. Whether the migraine was episodic or chronic, the presence of medication abuse and the drugs used to treat the seizures were not related with dropping out of preventive treatment.

Topics: Adrenergic beta-Antagonists; Adult; Anticonvulsants; Female; Flunarizine; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Nadolol; Neuroprotective Agents; Patient Dropouts; Patient Satisfaction; Prospective Studies; Risk Factors; Topiramate; Treatment Outcome; Young Adult

A 38-year-old woman with a 10-year history of migraine without aura was treated with topiramate (TPM) for increasing frequency of headache. Initially, TPM was prescribed at a dose of 25 mg per day for 7 days, and then the dose was increased to 50 mg per day. Three days later, the patient complained of blurry vision, redness, and pain in both eyes. On ophthalmological examination, the pupils were found to be mid-dilated, and her visual acuity with correction was 1.2 in both eyes. Slitlamp examination revealed conjunctival hyperemia, chemosis, and shallow anterior chambers. Intraocular pressure in the right eye was 35 mmHg, while that in the left eye was 36 mmHg. Gonioscopy showed angle closure in both eyes, and therefore, a diagnosis of bilateral angle-closure glaucoma was made. TPM was discontinued immediately, and antiglaucoma medications were started. Four days after the initiation of antiglaucoma treatment, conjunctival hyperemia and chemosis disappeared and intraocular pressure in the right and left eyes decreased to 8 mmHg and 7 mmHg, respectively. The treatment was discontinued on the 11th day. To the best of our knowledge, this is the first case of TPM-induced angle-closure glaucoma in Japan.

Topics: Adult; Anticonvulsants; Female; Fructose; Glaucoma, Angle-Closure; Humans; Migraine Disorders; Topiramate

The development of new agents for the preventive treatment of migraine is the greatest unmet need in the therapeutics of primary headaches. Topiramate, an anticonvulsant drug, is an effective anti-migraine preventive whose mechanism of action is not fully elucidated. Since glutamate plays a major role in migraine pathophysiology, the potential action of topiramate through glutamatergic mechanisms is of considerable interest.. Recordings of neurons in the trigeminocervical complex (TCC) and the ventroposteromedial thalamic nucleus (VPM) of anesthetized rats were made using electrophysiological techniques. The effects of intravenous or microiontophorezed topiramate on trigeminovascular activation of second- and third-order neurons in the trigeminothalamic pathway were characterized. The potential interactions of topiramate with the ionotropic glutamate receptors were studied using microiontophoresis.. Both intravenous and microiontophorized topiramate significantly inhibited trigeminovascular activity in the TCC and VPM. In both nuclei microiontophoretic application of topiramate significantly attenuated kainate receptor-evoked firing but had no effect on N-methyl-d-aspartic acid or α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor activation.. The data demonstrate for the first time that topiramate modulates trigeminovascular transmission within the trigeminothalamic pathway with the kainate receptor being a potential target. Understanding the mechanism of action of topiramate may help in the design of new medications for migraine prevention, with the data pointing to glutamate-kainate receptors as a fruitful target to pursue.

Topics: Action Potentials; Animals; Anticonvulsants; Drug Evaluation, Preclinical; Dura Mater; Excitatory Amino Acid Antagonists; Face; Fructose; Glutamic Acid; Injections, Intravenous; Iontophoresis; Male; Migraine Disorders; Nociceptive Pain; Nociceptors; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, Kainic Acid; Receptors, N-Methyl-D-Aspartate; Spinal Cord; Thalamic Nuclei; Topiramate; Trigeminal Nerve

Topics: Amitriptyline; Analgesics; Anticonvulsants; Antidepressive Agents, Tricyclic; Chronic Disease; Female; Fructose; Humans; Male; Migraine Disorders; Risk Factors; Topiramate; Tryptamines; Valproic Acid

Topics: Adult; Depression; Female; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate

The aim of this study was to measure differences in occipital cortex excitability in migraineurs before and after administration of topiramate. We have previously demonstrated occipital cortex hyperexcitability in migraine using an objective technique of magnetic suppression of perceptual accuracy (MSPA). We hypothesized that a neuromodulator such as topiramate would demonstrate differences in MSPA in migraine compared with baseline. Ten migraine patients were recruited. To assess inhibitory function MSPA was measured using the following protocol. Timed transcranial magnetic stimulation were delivered at interstimulus intervals (ISI) varying from 40 to 190 ms (eight stimulations at each ISI) at 60% stimulus intensity. Subjects were asked to report letters projected at a fixed luminance on the screen. Visual suppression was calculated based on the number of errors the subjects made using automated analysis. This procedure was repeated at a minimum of two different dosages of topiramate when it was titrated for optimal migraine control. The interim dose was that at which an improvement in headache frequency was first observed, and the optimal dose was that at which the patient had a ≥ 50% reduction in headache frequency, or had reached a 100-mg dose. The mean [standard error (s.e.)] level of letters reported correct at baseline at 100-ms ISI was 91.6 (3.4) compared with 48.5 (6.0) (P = 0.001) at an optimal dose of topiramate. Dose ranged from 50 to 100 mg; the average dose was 75 mg. The interim dose for most patients was 50 mg; the mean (s.e.) percentage of letters reported correct at interim was 75.9 (6.2) compared with baseline (P = 0.01). Mean number of headaches at baseline was 27 per month, compared with eight headaches per month at interim dose and four headaches per month at optimal dose. There was no significant correlation between mean change in frequency of headache and mean change in inhibition from baseline to optimal dose (0.04, P = 0.89). Topiramate modulates occipital cortex excitability in chronic migraine possibly via mechanisms of cortical inhibition. Since there was not a strong correlation between the degree of inhibition and reduction of migraine frequency, it would appear that topiramate did have an independent effect on cortical excitability that was not dependent on reduction in migraine frequency.

Topics: Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate; Transcranial Magnetic Stimulation; Visual Cortex; Visual Perception

Topiramate is a highly effective drug in migraine prophylaxis and is considered a first-line treatment. The evidence for the efficacy of topiramate is based upon the results of several large, randomized, double-blind, placebo-controlled trials. Adverse events (AEs) are common and require discontinuation of the treatment in about 20-25% of patients, but they are rarely severe. There are reviews regarding topiramate-related AEs representing a large number of patients treated in controlled trials. The most common AEs are weight loss, dizziness, somnolence, abnormal thinking, fatigue, ataxia, confusion, paresthesias, impaired concentration, nervousness, amnesia, and language difficulties. The development of cough has never been reported as an AE during topiramate prophylaxis for migraine. We present 3 cases in which the prophylactic treatment for migraine with topiramate was discontinued due to the onset of primary intractable coughing.

Topics: Adult; Anticonvulsants; Brain; Cough; Dose-Response Relationship, Drug; Female; Fructose; Humans; Iatrogenic Disease; Male; Middle Aged; Migraine Disorders; Topiramate

Topics: Acute Disease; Adolescent; Chemical and Drug Induced Liver Injury; Female; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate

Topics: Adult; Analgesics; Bipolar Disorder; Comorbidity; Female; Fructose; Humans; Migraine Disorders; Topiramate; Treatment Outcome

The trigeminal autonomic cephalalgias (TACs) and hemicrania continua (HC) share many clinical characteristics including unilateral pain and ipsilateral autonomic features. We report a patient with a history of migraine without aura who developed cluster headache and HC simultaneously. The distinctive clinical features and differential response profiles to various treatments indicates that they are distinct disorders. We then review previous reports of patients with coexisting TACs and HC and discuss the relationship between these families of primary headache disorders.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Brain; Calcium Channel Blockers; Cluster Headache; Comorbidity; Diagnosis, Differential; Disease Progression; Female; Fructose; Humans; Indomethacin; Migraine Disorders; Time Factors; Topiramate; Treatment Outcome; Trigeminal Autonomic Cephalalgias; Verapamil

Topiramate is an anticonvulsant agent effective in the prophylaxis of migraine, which also induces weight reduction by an unknown mechanism. We investigated the effect of topiramate on metabolic and endocrine parameters in patients with migraine independently of any intention to lose body weight. Six patients (26-61 years old, body mass indices [BMI] 20.9-32.1 kg/m(2)) with migraine were treated with an average dose of 100 mg topiramate/day over a period of 20 weeks. The following parameters were measured every 4-8 weeks: BMI, body fat proportion, waist and hip circumference, HOMA insulin resistance, fasting serum-/plasma concentrations of adiponectin, leptin, ghrelin, vascular endothelial growth factor (VEGF), cortisol, interleukin-6 and tumor necrosis factor (TNF)-alpha. Profound metabolic changes were observed for the whole treatment period. Compared with the baseline value, 20 weeks of treatment reduced the BMI by 7.2+/-1.4%, body fat proportion by 11.6+/-3.6%, waist circumference by 4.2+/-1.2%, leptin by 39.2+/-6.5% and HOMA insulin resistance by 37.3+/-5%, while adiponectin was increased by 69.9+/-17.3% (P<0.05, respectively). VEGF concentrations increased during the week 2-4 by 177.4+/-39.4% (P<0.05) followed by a continuous decrease. There were trends for a reduction in ghrelin concentration, whereas cortisol, interleukin-6 and TNF-alpha values were unchanged. In summary, in this small sample of migraine patients topiramate treatment was associated with increased insulin sensitivity, increased adiponectin concentration and a reduction of body fat in all treated patients. The role of increased VEGF concentrations prior to these metabolic changes is not clear and might, hypothetically, involve a centrally mediated effect of topiramate on body weight regulation.

Topics: Adiponectin; Adipose Tissue; Adult; Anti-Obesity Agents; Anticonvulsants; Body Mass Index; Cytokines; Female; Fructose; Hip; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Migraine Disorders; Prospective Studies; Topiramate; Vascular Endothelial Growth Factors; Waist Circumference; Weight Loss

To explore efficacy and safety outcomes of topiramate for episodic migraine prevention in community practice.. Open-label, multicenter, flexible-dose clinical trial consisting of a 4-week baseline phase, 24-week core phase and an optional 24-week follow-up phase in patients (18-80 years) with episodic migraine treated in community practices outside tertiary care centers.. The primary efficacy endpoint was the change in the number of migraine days/28 days (baseline vs. the last 4 weeks of core treatment) Secondary efficacy parameters included aspects of quality of life (QoL) and subjective patient ratings.. A total of 360 patients entered the core phase (ITT population); 37.6% (97 patients) discontinued prematurely, mainly due to adverse events (AEs; 23.6%). Mean topiramate dosage was 90 mg/day. Migraine days decreased from 8.30/28 days to 5.65/28 days and QoL (HIT-6 and MIDAS) was improved. Efficacy, tolerability and satisfaction were rated as 'good' or better by 56, 61 and 63% of patients, respectively. A total of 321 of 364 patients (88.2%) reported at least one treatment emergent AE, and the most common during the core phase were paraesthesia (46.4% of 364 patients), fatigue (17.0%), nausea (15.4%), dizziness (12.9%), viral infection (12.9%), weight decrease (12.6%) and impaired concentration (10.2%). Of 227 patients completing the core phase, 199 (88%) participated in the follow-up phase. A total of 187 patients received topiramate and 38 (20.3%) of these stopped treatment prematurely due to insufficient efficacy (6.4%), AEs (4.8%) or other reasons (10.2%). Reduction in migraine days and improvements in QoL (HIT-6) were maintained or improved (MIDAS) during follow-up, and 84% rated their satisfaction with topiramate therapy as 'good to very good'.. This community practice study showed that long-term treatment with topiramate in the prevention of episodic migraine was effective and well-tolerated, and it was associated with clinically relevant improvements in several aspects of QoL.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Follow-Up Studies; Fructose; Humans; Middle Aged; Migraine Disorders; Prospective Studies; Topiramate; Young Adult

Topiramate is an anticonvulsant medication that is widely used for migraine prophylaxis. Hypohidrosis and hyperthermia are 2 rare adverse effects of topiramate treatment, which have mainly occurred in pediatric epilepsy patients. Herein, we describe the first case of reversible hypohidrosis in an adult patient treated with topiramate for chronic migraine.

Topics: Adult; Anticonvulsants; Fever; Fluid Therapy; Fructose; Headache Disorders; Hot Temperature; Humans; Hypertension; Hypohidrosis; Infusions, Intravenous; Male; Migraine Disorders; Obesity, Morbid; Patient Education as Topic; Sleep Apnea Syndromes; Sweat Glands; Sweating; Topiramate; Treatment Outcome

Topiramate and nadolol with levels A and C of scientific evidence, respectively, would be indicated as preventive treatments of migraine. To date only one study of satisfaction has been carried out to compare the two pharmaceuticals.. To compare the effectiveness parameters in independent groups of patients treated preventively with one of the pharmaceuticals from the study.. From a database of 700 patients with migraine, those with episodic migraine and who had followed a course of preventive treatment, for the first time, with topiramate or nadolol were selected for the study. The effectiveness variables (reduction in the number of crises at four months of preventive treatment and responder rates) were analysed.. Altogether 208 patients with were included for treatment: 140 with topiramate (77.8% females; mean age, 37.9) and 68 with nadolol (69% females; mean age, 36.9). The mean number of crises in the month prior to treatment was: topiramate group, 6.3 +/- 2.6; nadolol group 5.3 +/- 2.0 (p = 0.0066). At four months after starting treatment: topiramate group, 2.69 +/- 2.6; nadolol group 2.6 +/- 2.2 (NS). The percentage of reduction in the number of migraines was 56.6% with topiramate and 51.6% with nadolol (NS). The responder rate (reduction in the frequency of crises by at least 50%) was 71.3% with topiramate versus 69% with nadolol (NS). The excellent response rate (reduction in crises by at least 75%) was 53.3% with topiramate versus 32.2% with nadolol (p = 0.0077). Adverse side effects were reported by 54% of patients treated with topiramate versus 30.8% of those treated with nadolol (p = 0.0015). The rate of satisfaction was 61% for the topiramate group and 71% for the group with nadolol (NS).. Both topiramate and nadolol proved to be effective in the preventive treatment of episodic migraine. Topiramate was found to be more effective than nadolol, although it was used in patients with a higher frequency of crises, and was not tolerated so well.

Topics: Adrenergic beta-Antagonists; Adult; Female; Fructose; Humans; Male; Migraine Disorders; Nadolol; Topiramate

Topics: Adult; Analgesics; Causality; Female; Fructose; Humans; Medicine; Migraine Disorders; Neurology; Prevalence; Self Medication; Stress, Psychological; Topiramate; Tryptamines

Topics: Amines; Cyclohexanecarboxylic Acids; Cyclohexanols; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Gonadal Steroid Hormones; Herbal Medicine; Hot Flashes; Humans; Menstrual Cycle; Menstruation Disturbances; Middle Aged; Migraine Disorders; Postmenopause; Topiramate; Venlafaxine Hydrochloride

Chronic migraine is an important public health problem. The aim of treatment should be to reduce migraine frequency and its negative impact on functioning, as well as to limit the use of acute medications. These goals may be accomplished by introducing effective prophylaxis. The aim of the present article is to critically review the published evidence on the pharmacological prophylaxis of chronic migraine, analysing published double-blind, placebo-controlled studies on adult patients. The results of the review indicate that tizanidine, gabapentin, valproic acid, and particularly topiramate are effective prophylactics against chronic migraine, with improvements in several endpoints that were significantly superior to those achieved by placebo. However, the different results found by different trials, as well as several methodological problems inherent in the trials, suggest the need for further research to provide clear indications from large, multicentre, controlled trials with homogeneous inclusion criteria and adequate endpoints.

Topics: Amines; Analgesics; Chronic Disease; Clonidine; Cyclohexanecarboxylic Acids; Diagnosis, Differential; Double-Blind Method; Fructose; GABA Agents; Gabapentin; gamma-Aminobutyric Acid; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Topiramate; Valproic Acid

A case of topiramate-induced myoclonus and acute psychosis in a patient taking the recommended dosage of topiramate for migraine prophylaxis is reported.. A 29-year-old Caucasian, wheelchair-bound woman with diplegic cerebral palsy and a history of migraines was admitted to the hospital after developing paranoid thoughts and episodes of myoclonus two weeks after an increase in her topiramate dosage (25 mg twice daily to 50 mg twice daily). Her physical examination upon admission was unremarkable, with the exception of a temperature of 38.2 degrees C. Diagnostic laboratory test values, including those of the cerebrospinal fluid, were within normal limits. During neurologic examination, arm jerking, lip smacking, and finger movements occurred spontaneously and unprovoked, and severe bilateral leg myoclonus with plantar stimulation was observed. The results of an ultrasound of her lower extremities and a computed tomography scan of the brain with and without contrast revealed no abnormalities. An electroencephalogram was taken and showed nothing unusual. After nonpharmacologic etiologies were ruled out, her topiramate dosage was decreased and discontinued over four days. Her mental status and myoclonus drastically improved. She was stable and discharged within 24 hours of topiramate discontinuation. Follow-up at six months revealed that her myoclonus had completely resolved. While she has experienced additional psychotic episodes, these were mild and appear to be related to her depression. Myoclonus has not returned.. A patient with cerebral palsy experienced myoclonus and acute psychosis after receiving a standard dosage of topiramate for migraine prophylaxis.

Topics: Adult; Anticonvulsants; Cerebral Palsy; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Fructose; Humans; Migraine Disorders; Myoclonus; Psychoses, Substance-Induced; Topiramate

To assess the clinical characteristics of patients with migraine.. The medical records of 76 patients diagnosed with migraine were reviewed using the ICHD-II 2004 diagnosis criteria. The patients were classified into three age groups: 3-6 yr olds (group I), 7-12 yr olds (group II), and 13-17 yr olds (group III).. Migraine was the most common cause of headache in the patients of present pediatric neurology outpatient clinic (57.1%, 76/133). The mean age of patients was 11.08 ± 3.27 (3.25-17) yrs. The number of girls as the age increased (groups II and III). The mean headache attacks rate was 2.5 ± 1.5 per wk, which resulted in worsening of school performance (n = 26, 34.2%). In the majority of patients (n = 54, 71.1%), there was a family history of migraine or headache in the close relatives. Prophylaxis was found effective for all given medications (flunarizine: 46/54, propranolol: 19/21, topiramate: 10/10, sodium valproate: 1/1).. These findings indicate that: (a) migraine is the most frequent cause of headache in pediatric patients, (b) it has negative effects on school performance and daily activities, (c) the family history is important for making the diagnosis and (d) prophylaxis is significantly effective.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Female; Flunarizine; Fructose; Humans; Male; Migraine Disorders; Prevalence; Propranolol; Risk Factors; Topiramate; Turkey; Valproic Acid; Vasodilator Agents

Topics: Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Randomized Controlled Trials as Topic; Recurrence; Topiramate

Topiramate (TPM) is generally recognized efficacious and safe in migraine prevention. A significant proportion of patients undergoing TPM administration may show weight loss. In epileptic subjects, high body mass index (BMI) was found to be predictive of weight loss under TPM therapy. We therefore aimed to study whether common clinical determinants may be associated to TPM weigh loss in migraine patients. In our clinical series, high BMI was not found a predictor of weight loss under TPM treatment. Unknown genetic and environmental factors that may determine the courses of weight loss under TPM therapy are still do be identified.

Topics: Adult; Body Mass Index; Female; Fructose; Humans; Linear Models; Male; Migraine Disorders; Prospective Studies; Topiramate; Weight Loss

The surgical treatment of migraine headache is a recent innovation that has broadened the potential patient population who may benefit from craniofacial surgical techniques to millions of affected adults. However, the population at risk in the pediatric age group has not been clearly established. The present retrospective review was performed to provide demographic information of the adolescent migraine in a major children's hospital. This information is essential before considering surgical treatment of migraine in this age group.. Five hundred eighty-eight charts of patients aged 12 to 18 years who presented to the pediatric neurology clinic with headache in 2006 were retrospectively reviewed to evaluate for the diagnosis of migraine. Data collected included headache location, frequency, duration, intensity, associated migraine symptoms, and headache precipitants, as well as the response to medical treatment.. Two hundred ten (36%) of 588 patients had the diagnosis of migraine headache, and 51 patients (24%) were considered refractory to the medical treatment offered. In 101 of the 210 migraine patients, anatomic location of the headaches could be identified. Thirty-nine children (19%) with refractory migraines (mean age, 14.7 years [SD, 0.3 years]) reported definitive migraine triggers.. A significant percentage of pediatric patients with migraine headache remain refractory to medical treatment. At present, there is no good treatment regimen for migraine headaches in the pediatric population. We believe that surgical treatment of migraine headaches may be a realistic option for these patients.

Topics: Adolescent; Amitriptyline; Analgesics, Non-Narcotic; Biofeedback, Psychology; Child; Female; Follow-Up Studies; Fructose; Humans; Male; Migraine Disorders; Neuroprotective Agents; Recurrence; Retrospective Studies; Tension-Type Headache; Time Factors; Topiramate; Vasodilator Agents; Verapamil

To determine the pattern of headache-related resource utilization and costs before and after initiation of preventive migraine treatment with topiramate in a sample of a large managed-care population.. This study was a retrospective, longitudinal, cohort study analysis of medical and pharmacy claims using The HealthCore Integrated Research Network Database. Patients were required to have had at least one pharmacy claim for topiramate between 7/1/00 and 11/30/04, and at least 12 dosage units dispensed of any combination of acute migraine treatments (triptan, ergotamine, or ergotamine combination) during the 6-month period preceding the first pharmacy claim for topiramate (the index date). Headache-related inpatient and outpatient resource utilizations were compared pre-index vs. post-index period 1 (months 1-6) and pre-index vs. post-index period 2 (months 7-12). Statistical analyses included McNemar tests for categorical variables and paired t-tests for continuous variables.. A total of 3246 patients met the inclusion criteria. The mean (+/- SD) age was 44 +/- 10 years and 88% were female. From pre- to post-index period 2, outpatient visits significantly decreased by 30% (p < 0.0001), diagnostic procedures decreased by 74% (p = 0.0013), emergency room (ER) visits decreased by 27% (p < 0.0001), and abortive prescriptions decreased by 25% (p < 0.0001). No significant differences were found in mean number of hospitalization days. Total headache-related inpatient costs and outpatient costs decreased (p < 0.01) during post-index period 2 (43 and 46%, respectively). Headache-related pharmacy costs increased from pre- to post-index period 2.. Topiramate treatment for migraine prevention was associated with significantly lower healthcare resource use (ER visits, diagnostics, acute treatment) in the first 6 months of treatment, with continuing decreases, including physician office visits, during the second 6 months of treatment.. Since this study is a claims-based analysis there is the potential introduction of non-claims identifiable factors that might influence resource use such as lifestyle modifications and over-the-counter medications. In addition, adherence to topiramate treatment was not accounted for in this study. Nonetheless, this study provides important insights into the benefit of preventive migraine treatment in actual clinical practice.

Topics: Adult; Cohort Studies; Female; Fructose; Health Care Costs; Health Care Rationing; Humans; Longitudinal Studies; Male; Managed Care Programs; Middle Aged; Migraine Disorders; Retrospective Studies; Topiramate

This study aims to perform a descriptive analysis of the usage patterns of migraine prophylactic medications by various neurologists in our setting.. The first preventive treatment prescribed for migraine in patients not associated to other diagnoses of primary headache was recorded in three outpatient neurology clinics and one headache specific clinic.. A total of 235 prophylactic treatments out of 669 patients were initiated. The patients were aged 37 +/- 12 years (mean +/- standard deviation) and 84.45% were women. Migraines with aura accounted for 18.9% of migraines. By order of frequency, the prophylactic treatments administered were topiramate (43%), beta-blockers (18%), flunaricine (17%), amitriptyline (14%), selective serotonin reputake inhibitors (6%) and others (2%). Beta-blockers and flunaricine were used much more frequently in men (29.7% and 27% versus 15.9% and 14.4%, respectively) and antidepressants were used more in women (21.87% versus 5.4%). The most frequently used antidepressant was amitriptyline, and its use increases with the age of the patient, it being the most frequently used treatment in over 60-year-old patient group.. At present, topiramate has become the first preventive treatment option for migraine in our setting, especially in young women. There is greater variability in the choice of an alternative treatment. Amitriptyline is the first choice within the antidepressants and is almost exclusively prescribed in women with migraine and elderly age.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Ambulatory Care Facilities; Antidepressive Agents; Calcium Channel Blockers; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Topiramate; Young Adult

Topics: Adrenergic beta-Agonists; Anticonvulsants; Fructose; Humans; Magnesium; Migraine Disorders; Phytotherapy; Propranolol; Riboflavin; Topiramate

About 5-10% of school-age children manifest migraine headaches. Treatment options for pediatric migraine are limited. Topiramate is approved for migraine prophylaxis in adults, but its use in children is limited. We retrospectively reviewed the records of 37 patients, i.e., 22 (60%) girls and 15 (40%) boys (mean age, 14 years; range, 7.3-20.5 years), diagnosed with migraine without aura in 30 (81%), with aura in four (11%), and abdominal, ophthalmoplegic, and catamenial in one each. The mean follow-up was 12 +/- 5 months standard deviation (S.D.). Clinical response was qualified as excellent, good, no change, or worse. Numbers of headaches per month were 15 +/- 7 S.D. prior to treatment and 3 +/- 3.4 S.D. (P < 0.001) after treatment. An excellent or good response (>50% migraine reduction) was attained in 28 patients (76%). Ten (27%) patients exhibited adverse effects. Patients taking >2 mg/kg/day were more likely to demonstrate side effects. The mean dose for patients without adverse effects was 1.27 +/- 0.7 mg/kg/day S.D. Those who reported adverse effects were taking a mean dose of 2.8 +/- 1.5 mg/kg/day S.D. This study demonstrated that topiramate is an effective, safe alternative for the prophylaxis of pediatric migraine. An acceptable risk/benefit maintenance dose was < or =2 mg/kg/day.

Topics: Adolescent; Analgesics; Child; Female; Follow-Up Studies; Fructose; Humans; Male; Migraine Disorders; Migraine with Aura; Migraine without Aura; Retrospective Studies; Topiramate; Treatment Outcome; Young Adult

Topiramate (TPM) is a antiepileptic drug that has multiple mechanisms of action. It is effective as a monotherapy for migraine prophylaxis. Unfortunately, TPM can frequently cause adverse effects, such as cognitive dysfunction. The present study examines the neuropsychological and neurophysiological effects of TPM in 35 consecutive migraine patients above 18years of age. The TPM dose was started at 25mg/day and increased by 25mg/week, until reaching the maximum dose of 50mg twice daily in the fourth week. Patients were evaluated for development of side effects of the medication and for its effectiveness on migraine. The Wechsler memory scale was used for neuropsychological evaluation and cognitive evoked potentials were used for neurophysiologic evaluations. Analyses of repeated measures show that visual analog scale pain values, as well as migraine attack frequency and headache duration, were decreased significantly during the study. The amplitudes and latencies of P300 did not change. The results of this study show that 100mg TPM is effective in the prevention of migraine headache and in reducing severity of attacks. Patients' cognitive complaints are frequent in the first month and decrease in the following month. Despite these complaints, only the attention section of the visual memory section of the Wechsler memory scale was affected - other sections were not affected. Also, P300 study did not reflect changes appropriate to these cognitive complaints.

Topics: Adolescent; Adult; Anticonvulsants; Cerebral Cortex; Event-Related Potentials, P300; Female; Follow-Up Studies; Fructose; Humans; Male; Memory; Middle Aged; Migraine Disorders; Neuropsychological Tests; Pain Measurement; Reaction Time; Retrospective Studies; Topiramate; Young Adult

To propose minimal important differences (MID) for the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1). To our knowledge (to date), no published MID values exist for the MSQ v2.1 in any population. Analyses were performed on data from two pivotal clinical trials of topiramate for migraine prevention (n = 916), as well as from the QualityMetric National Headache Survey (n = 1016). Analyses included both distribution- and anchor-based MID techniques as well as group- and individual-level MID values. Group-level anchor-based MID values ranged from 3.2 [Role Restrictive domain (RR)] to 7.5 [Emotional Functioning domain (EF)], setting the minimum level of appropriate MID (which can also aid with power analysis). Individual-level distribution-based MID values resulted in highly similar estimates from two large databases: median MID of 8.5 for RR, 9.2 for Role Preventive (RP) and 12.0 for EF. Finally, individual-level anchor-based MID values ranged from 5.0 (RR and RP domains) to 10.6 (EF). For group-level purposes of calculating power for future studies, an MID of 3.2, 4.6 and 7.5 for RR, RP and EF is recommended. For within-group analyses for analysing clinical trial efficacy of each patient's change with responder analyses, 5 points is necessary for RR. For RP and EF, ranges are recommended: 5.0 to 7.9 for RP and 8.0 to 10.6 for EF. These latter two domains tend to have more error in the MID, and thus a sensitivity analysis with both ends of the range should be used to confirm significant differences in responder analyses.

Topics: Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Quality of Life; Randomized Controlled Trials as Topic; Reproducibility of Results; Surveys and Questionnaires; Topiramate

Topics: Adult; Anticonvulsants; Female; Fructose; Humans; Migraine Disorders; REM Sleep Behavior Disorder; Topiramate

The efficacy of topiramate in the preventive treatment of migraine is well demonstrated. Clinical trials indicate that the dose of 100 mg/daily is the ideal in terms of efficacy, but doses as low as 50 mg/ daily show some efficacy, which could improve its tolerability in some patients.. To analyse the behaviour of the different doses of topiramate in daily clinical practice.. Patients with frequent migraine with or without aura episodes who received topiramate in our clinic were treated in a homogeneous way. Initially they were given 50 mg/daily (usually as a nocturnal dose), after increasing the dose in 2-3 weeks. The efficacy was evaluated after 6-8 weeks. If no response (decrease in frequency by at least 50%) was observed the dose of topiramate was increased (25 mg/week) up to 100 mg/daily, The patients were seen at least once every 3 months.. This series includes 182 patients. Globally, 75% of the patients responded, 14% did not respond and 11% did not tolerate the drug. One-quarter of patients (44 cases) responded to low doses, while 92 patients (51%) responded to the 100 mg/dose. Tolerability slightly decreased on increasing the dose.. These data indicate that one-quarter of the patients respond to low doses in daily clinical practice, though about half of these patients will need doses of 100 mg/day. Given the higher tolerability of low doses, we recommend trying first low doses before giving higher doses, which will be necessary in half of the patients.

Topics: Adult; Aged; Anticonvulsants; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Topiramate; Treatment Outcome; Young Adult

SUNCT Syndrome (short-lasting unilateral neuralgiform headache with conjuntival injection and tearing) combines neuralgic, migraineus and autonomic headaches, three of four primary ones described in the International Classification of the IHS (International Headache Society). This work describes a paediatric case evaluated under MIDAS score in which a new therapeutic approach with topiramate (TPM) was used.

Topics: Adolescent; Conjunctiva; Fructose; Humans; Male; Migraine Disorders; Neuralgia; Syndrome; Tears; Topiramate

Posterior ischemic optic neuropathy (PION) is an uncommon form of optic nerve ischemia that results from damage to the intraorbital, intracanalicular, or intracranial optic nerve. It has been reported perioperatively, in association with systemic vasculitis, and in the nonsurgical setting with no identifiable cause. Review of the literature reveals only 2 patients with PION associated with migraine in a single report. We report a patient who developed PION in the setting of a migraine headache without any other identifiable risk factors.

Topics: Adult; Female; Fructose; Humans; Migraine Disorders; Optic Neuropathy, Ischemic; Topiramate

Topics: Adult; Anticonvulsants; Dose-Response Relationship, Drug; Female; Fructose; Hallucinations; Humans; Migraine Disorders; Topiramate

Topics: Anticonvulsants; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Placebos; Sexual Dysfunctions, Psychological; Topiramate

The aim of this study was to describe persistence with migraine prophylactic treatment and acute migraine medication utilization in patients prescribed migraine prophylaxis.. For this retrospective cohort study, the Health Core Integrated Research Database provided pharmacy/medical claims data from 5 commercial health insurance plans (ie, excluding Medicare and Medicaid) on adult patients with migraine. Eligible patients had >or=1 pharmacy claim for a migraine prophylactic medication between July 1, 2000, and May 31, 2005, and >or=12 U of any combination of acute treatment (serotonin receptor agonist [triptan], ergotamine, or ergotamine combination) dispensed during the 180-day period preceding a first pharmacy claim for a prophylactic medication (index date). The prophylactic medication identified at index date was used for categorizing patients into 1 of 4 cohorts: amitriptyline, propranolol/timolol, divalproex sodium, or topiramate (reference). Kaplan-Meier curves were used for evaluating unadjusted risk for discontinuation over time, and a multivariate Cox proportional hazards model was developed to analyze factors associated with discontinuation of prophylactic medication.. A total of 12,783 patients met the inclusion criteria and were included in the analysis (amitriptyline, 3749; propranolol/timolol, 2718; divalproex sodium, 1644; and topiramate, 4672). The mean (SD) ages were not significantly different across cohorts (43.9 [11.3], 42.0 [11.1], 43.1 [11.3], and 43.9 [10.6] years, respectively). The mean duration of treatment was significantly longer (131 [184] days) with topiramate compared with amitriptyline (94 [152] days), propranolol/ timolol (119 [180] days), and divalproex sodium (109 [158] days) (P < 0.001, P = 0.005, and P<0.001,respectively). The risks for discontinuing prophylactic treatment were 23%, 6%, and 11% higher with amitriptyline, propranolol/timolol, and divalproex sodium, respectively, compared with topiramate (P<0.001, P = 0.024, and P <0.001). Patients prescribed topiramate had a higher mean consumption rate of triptans preindex; postindex, decreases in triptan use were observed in all cohorts, although the magnitude of the decrease was greatest in patients prescribed topiramate compared with the other cohorts.. In this study, prescription of topiramate was associated with greater persistence with prophylactic treatment than the other prophylactic drugs. Furthermore, greater reductions in acute treatment utilization, particularly triptans, were observed among patients prescribed topiramate compared with the other prophylactic cohorts.

Topics: Adult; Age Factors; Amitriptyline; Cohort Studies; Databases, Factual; Dose-Response Relationship, Drug; Drug Prescriptions; Drug Therapy, Combination; Drug Utilization Review; Female; Fructose; Humans; Kaplan-Meier Estimate; Male; Managed Care Programs; Medication Adherence; Middle Aged; Migraine Disorders; Proportional Hazards Models; Propranolol; Retrospective Studies; Sex Factors; Time Factors; Timolol; Topiramate; Valproic Acid

Topiramate (TPM) therapies for epilepsy or migraine are long-time therapies with unknown mechanisms and special side effects. TPM influences cholesterol (TC) and lipoprotein serum levels. In addition, TPM may cause uric acid (UA) stone formation.. Serum UA, TC, and triglyceride (TG) levels were measured in 53 migraine patients receiving TPM and in 44 age- and sex-matched controls. Compared with controls, patients on TPM showed significantly higher UA and nonsignificantly higher TC and TG values. We recorded pre- and posttreatment levels of UA, TC, and TG levels in 23 patients.. We found increased serum levels of UA with TPM use (P < .01). There was a significant and positive correlation between serum UA levels and male gender (P < .01).The changes in serum UA levels before and after TPM treatment differed significantly (P < .01).. Our results suggest a need for monitoring serum UA levels in patients receiving TPM. We should perhaps prescribe a low-UA diet and advice to drink much more water in these patients.

Topics: Adult; Cholesterol, HDL; Cholesterol, LDL; Female; Fructose; Humans; Hyperuricemia; Lipids; Male; Middle Aged; Migraine Disorders; Topiramate; Triglycerides; Uric Acid

Language disturbances have been previously described as word-finding difficulties in epileptic patients. These disturbances have been recently reported in migraineurs in treatment with topiramate but they have never been defined and assessed in these patients with the aid of neuropsychological testing.. To verify the occurrence of language disturbances as a side effect of topiramate treatment in episodic and chronic migraine patients.. Language disturbances were recorded on the basis of spontaneous reports of 30 migraine patients treated with topiramate and 2 control groups (20 patients treated with other prophylactic drugs and 20 patients without prophylactic treatment) and were explored with neuropsychological tests. Psychiatric comorbidity was assessed using Zung Anxiety and Depression Scales.. Language disturbances were referred by 26.7% (n=8) of patients during topiramate treatment but by none of the patients in the 2 control groups. All patients in the topiramate group had a worse performance on all tests compared to patients of the 2 control groups. Moreover, in the topiramate group, patients with referred language disturbances had higher scores for all neuropsychological test variables, indicative of a worse performance. Some language functions (Trail Making Tests A and B) seemed to be influenced by the concomitant presence of psychiatric comorbidities, particularly anxiety and depression.. It can be hypothesized that a disorder such as migraine, which involves numerous cortical and subcortical circuits implicated in the transmission and behavioral and emotional processing of pain, represents a facilitated substrate for the occurrence of language disturbances due to topiramate. This could be the expression of a more generalized impairment of cognitive processing. These aspects should be investigated in prospective studies involving larger migraine patient samples.

Topics: Adult; Analysis of Variance; Female; Fructose; Humans; Language Disorders; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Neuropsychological Tests; Psychiatric Status Rating Scales; Topiramate

Few data are available on cognitive and psychiatric effects of topiramate (TPM) monotherapy in migraine. Twenty patients affected by migraine were treated with TPM monotherapy. At the same time, twenty control subjects were selected. A comprehensive neuropsychological and behavioural battery of tests were performed at baseline (T0), at titration (T1) and in maintenance period (T2). Topiramate serum levels were also investigated at T1 and T2. On comparison with the control group, no cognitive and psychiatric differences were detected at baseline. A significant reduction of word fluency score (P < 0.05) was evident after TPM treatment, both at T1 and T2. No patient developed psychiatric adverse events. TPM induced an impairment of verbal fluency and no psychiatric adverse events, demonstrating selective negative cognitive profile in migraine therapy. Slow titration, low doses, lack of previous psychiatric disorders and/or familial history may explain our data.

Topics: Adult; Anticonvulsants; Cognition; Female; Fructose; Humans; Male; Mental Disorders; Middle Aged; Migraine Disorders; Neuropsychological Tests; Psychometrics; Topiramate; Treatment Outcome; Verbal Behavior

We studied the excitability of the visual and motor cortex in 36 patients with frequent migraine without aura (30 women, mean age 38.6 +/- 10.0 years) before and after treatment with topiramate (100 mg/day) using transcranial magnetic stimulation. Treatment with topiramate resulted in reduction of both headache frequency (12.0 +/- 1.3 to 5.8 +/- 3.2 migraine days per month; P = 0.004) and cortical excitability: motor cortex thresholds increased on the right side from 43.8 +/- 7.5% to 47.7 +/- 9.2% (P = 0.049) and on the left side from 43.4 +/- 7.0% to 47.2 +/- 9.6% (P = 0.047), and phosphene thresholds increased from 58.9 +/- 11.1% to 71.2 +/- 11.2% (P = 0.0001). Reduction of headache frequency correlated inversely with an increase of visual thresholds and did not correlate with motor thresholds. The effect of topiramate in migraine prevention is complex and can not be explained simply by inhibition of cortical excitability.

Topics: Adolescent; Adult; Aged; Cerebral Cortex; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Motor Cortex; Prospective Studies; Time Factors; Topiramate; Transcranial Magnetic Stimulation; Visual Cortex

To provide prospective, longitudinal evidence of the effects of topiramate, an antiepileptic medication prescribed for migraine headaches, on stone-risk factors, specifically as pertaining to dosing and rapidity of onset.. Patients scheduled to begin topiramate therapy were recruited to participate in the study. Enrolled subjects collected a pretreatment 24-hour urine specimen with subsequent 24-hour urine specimens collected 5 days after beginning topiramate and after each dose escalation.. Six subjects enrolled in the study, 4 of whom completed two additional urine collections after initiating topiramate therapy. The pretreatment urine collections of the 4 subjects with additional samples revealed the following mean (range) values: urine volume 1550 (1300 to 1900) mL, pH 6.75 (6 to 7), creatinine 1436.3 (1196 to 1590) mg/day, calcium 305.8 (209 to 423) mg/day, and citrate 606.8 (290 to 860) mg/day. Five days after initiation of topiramate, mean calcium decreased to 211.5 mg/day (31% decrease), and mean citrate decreased to 398 (99 to 804) mg/day, an average decrease of 39.8% (6.5% to 65.9%) per patient. After a dose escalation, calcium increased to 286.8 mg/day, but citrate decreased further to 209 (119 to 353) mg/day, an average decrease of 65.1% (57.9% to 71.7%) per patient from pretreatment levels.. Topiramate therapy induces a profound decrease in urinary citrate levels, equivalent to the levels seen in distal renal tubular acidosis. Citrate levels decrease quickly after the start of topiramate therapy and continue to decrease with escalating doses.

Topics: Adult; Anticonvulsants; Calcium; Citric Acid; Creatinine; Dose-Response Relationship, Drug; Female; Fructose; Humans; Middle Aged; Migraine Disorders; Topiramate; Urinary Calculi

Topics: Adolescent; Anticonvulsants; Antihypertensive Agents; Drug Therapy, Combination; Female; Fructose; Glaucoma, Angle-Closure; Humans; Intraocular Pressure; Migraine Disorders; Papilledema; Pseudotumor Cerebri; Topiramate

Topics: Dose-Response Relationship, Drug; Fructose; GABA Agents; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate; Valproic Acid

Topics: Adult; Aggression; Akathisia, Drug-Induced; Anticonvulsants; Bipolar Disorder; Brain; Dose-Response Relationship, Drug; Female; Flunarizine; Fructose; Humans; Migraine Disorders; Mood Disorders; Topiramate; Withholding Treatment

To describe the dose-concentration relationship of a continuous intravenous infusion of valproic acid (VPA) in pediatric patients when a dosing protocol is used.. Retrospective and concurrent chart review.. Tertiary care, 473-bed, academic medical center with a 120-bed, dedicated children's hospital.. Twenty-six pediatric patients (< 18 yrs old) who received VPA according to the protocol for continuous intravenous infusions between January 1, 2004, and March 31, 2006, identified by using a pharmacy order-entry system.. Patient demographics, VPA treatment regimens, clinical responses, and safety data were recorded and analyzed. Median patient age was 8.5 years (range 1.4-16 yrs). Approximately two thirds received VPA for seizures, and one third for migraines. Patients were given a mean +/- SD VPA loading dose of 28.5 +/- 5.2 mg/kg followed by a continuous infusion rate of 1 +/- 0.2 mg/kg/hour. Mean +/- SD serum concentration measured 4.5 +/- 1.6 hours after the loading dose was 83.3 +/- 22.8 microg/ml. Steady-state concentration at 23.3 +/- 3.0 hours after the start of the continuous infusion was 80.0 +/- 26.0 microg/ml. Postload and steady-state serum concentrations were within the target concentration of 50-100 microg/ml in 77% and 69% of patients, respectively. On further analysis, when the target range was expanded to 50-125 microg/ml (125 microg/ml was deemed acceptable if no adverse effects were noted), 89% and 92% of patients, respectively, had postload and steady-state VPA serum concentrations within this range. The response rate was excellent, with nearly 85% of patients achieving a complete or partial response to therapy. Adverse effects were generally mild and uncommon.. The continuous-infusion protocol permitted rapid intravenous loading of VPA in pediatric patients while minimizing adverse events and achieving concentrations in the upper region of the therapeutic range.

Topics: Administration, Oral; Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Therapy, Combination; Drug Utilization Review; Female; Fructose; Hallucinations; Humans; Hyperammonemia; Infusions, Intravenous; Male; Medical Records; Metabolic Clearance Rate; Migraine Disorders; Phenobarbital; Phenytoin; Retrospective Studies; Seizures; Topiramate; Treatment Outcome; Valproic Acid

To evaluate the medical resource utilization and overall cost of care among patients treated with topiramate (TPM) for migraine prevention in a commercially insured population. Background.-Preventive migraine therapy with TPM significantly reduces the frequency of migraine attacks. Limited data exist on the real-world health care consumption associated with TPM therapy for migraine prevention.. Data were obtained from a large geographically diverse integrated medical and pharmacy claims database representative of the commercially insured population. The date of the first TPM claim between July 2000 and December 2003 was considered the index date. Patients needed at least 1 triptan prescription (Rx) claim during the 6-month preindex period, and > or =2 TPM Rx claims in the 12 months following index TPM Rx to be included in the analysis. Headache-related inpatient and outpatient resource use were compared: preindex vs postindex period 1 (months 1-6) and preindex vs postindex period 2 (months 7-12). Subgroup analyses were conducted based on the triptan consumption during the 6-month preindex period: Cohort L (low triptan users) with < or =36 triptan doses, and Cohort H (high triptan users) with >36 triptan doses.. The sample included 2645 plan members (1778 patients in Cohort L, and 867 patients in Cohort H). TPM utilization was associated with significantly less triptan utilization in the first (34.8 quantity dispensed; 7.5% decrease) and second (30.2; 19.6% decrease) follow-up periods compared to the preindex period (37.6; both P < .0001). In postindex period 1, there was a 46% decrease in emergency department (ED) visits, 39% decrease in diagnostic procedures (eg, CT scans and MRIs), and a 33% decrease in hospital admission; physician office visits were unchanged. In postindex period 2, there was a 46% decrease in ED visits, 72% decrease in diagnostic procedures, 61% decrease in hospital admissions, and a 35% decrease in physician office visits. Decreases in resource use were observed in both cohorts L and H. Mean +/- SD total headache-related cost was $2118 +/- $3406 per patient in the preperiod, versus $2450 +/- $3318 in follow-up period 1 and $2009 +/- $3136 in follow-up period 2.. In this sample of patients from a diverse set of health plans receiving TPM, significant decreases in resource use were observed within 6 months of TPM initiation, and this trend continued in follow-up period 2. Although there was an initial increase in total headache-related cost upon introduction of TPM (follow-up period 1), the cost in follow-up period 2 was lower than in the preindex period, suggesting that benefits of long-term treatment with TPM can be achieved without increasing total cost.

Topics: Adult; Cohort Studies; Cost of Illness; Costs and Cost Analysis; Databases, Factual; Dose-Response Relationship, Drug; Female; Fructose; Humans; Insurance Claim Review; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Pharmaceutical Services; Retrospective Studies; Topiramate

Topics: Adult; Female; Fructose; Humans; Middle Aged; Migraine Disorders; Motion Sickness; Neuroprotective Agents; Topiramate

Topiramate, an antiepileptic medication, has been widely used since its recent indication for migraine prophylaxis. We report a case of bilateral angle-closure glaucoma and acute myopia in a 44-year-old woman on oral topiramate therapy initiation for migraine prophylaxis. Intraocular pressure was 31 mmHg right and 32 mmHg left, myopia was 4 diopters. Topiramate was interrupted and general and local hypotensive treatment begun and rapidly stopped after improvement. Iridotomy was also performed. Fifteen days later, complete resolution was observed on ophthalmologic examination: anterior chambers were deep, myopia fully regressed, intraocular pressure returned to normal, and the visual field was complete. This new case prompts discussion on current reports in the literature and French drug monitoring database cases in this context.

Topics: Adult; Anticonvulsants; Female; Fructose; Glaucoma, Angle-Closure; Humans; Intraocular Pressure; Iridectomy; Migraine Disorders; Myopia; Topiramate; Treatment Outcome

Routine clinical practice data are useful for payers and formulary decision makers to make sound decisions regarding coverage policy. Based on a literature search, there has been scant research into topiramate prescribing patterns among Medicaid patients.. The aim of this study was to describe diagnoses, demographic characteristics, additional co-existing diagnoses, and dosing among Medicaid patients prescribed topiramate.. This descriptive, retrospective database analysis used data from South Carolina (SC) and Texas (TX) ambulatory Medicaid claims dated October 1, 2003, to December 31, 2004. Patients whose data were eligible for inclusion in the study were enrolled in Medicaid during the study period, had >or=2 topiramate prescriptions, were aged <65 years, and had evidence of a topiramate treatment-related diagnosis (possible diagnoses were identified through literature search and drug compendiums). Four cohorts were defined: (1) epilepsy only; (2) migraine only; (3) epilepsy and migraine; and (4) nonepilepsy/nonmigraine. Demographic characteristics, diagnoses, comorbidities, and daily dose of topiramate were summarized using descriptive statistics. The initial study analysis (period 1) was a 180-day window comprising the 90 days before and after the first available topiramate prescription claim was filed. A second, 360-day analysis (period 2) was completed comprising the 180 days before and after the index topiramate prescription date.. In the 180-day analysis, 2216 SC and 4766 TX Medicaid patients met the selection criteria. Cohort classification percentages were 32.3% and 39.6% (epilepsy only), 29.7% and 16.4% (migraine only), 10.7% and 9.2% (epilepsy and migraine), and 27.3% and 34.9% (nonepilepsy/nonmigraine) for SC and TX, respectively. Mean (SD) ages were 29.9 (15.9) (SC) and 27.1 (16.1) (TX) years. In the nonepilepsy/nonmigraine cohort, the most common diagnoses were bipolar disorder and depression. The median daily doses in the epilepsy-only cohort were 175 mg/d in the SC group and 200 mg/d in the TX group. In the migraine-only cohort, the median daily dose was 100 mg/d in SC and TX. Results for the 360-day analysis were similar.. In this descriptive study using data from 2 Medicaid populations, the majority of patients using topiramate had a diagnosis of epilepsy and/or migraine. Median dosages ranged from 175 to 200 mg/d in patients with epilepsy and 100 mg/d in those with migraine. Depression was a common comorbidity in the migraine cohort and the nonepilepsy/nonmigraine cohort.

Topics: Adolescent; Adult; Child; Comorbidity; Databases as Topic; Drug Utilization; Epilepsy; Female; Fructose; Humans; Male; Medicaid; Middle Aged; Migraine Disorders; Retrospective Studies; South Carolina; Texas; Topiramate

Topics: Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate; Treatment Outcome

The effect of topiramate prophylaxis on medication use and medical resource use for migraine patients was studied.. Medical and pharmacy claims from a commercially insured population were analyzed from July 1, 1999, to March 31, 2004. The study sample included patients with at least one physician encounter or facility claim with a diagnosis of migraine at any point during the study's time frame. Patients either were naive to drugs labeled for migraine prophylaxis or had switched to topiramate from another drug labeled for migraine prophylaxis. The date of topiramate initiation was between January 1, 2000, and September 30, 2003; topiramate initiation was the index date. Demographic and clinical characteristics were evaluated. Migraine-related medication use and resource use were compared between the pre- and postindex periods.. Of the 1749 patients analyzed, 90.2% were female. Neurologists wrote 54% of the index prescriptions. The mean +/- S.D. topiramate dosage was 98 +/- 65 mg/day. Statistically significant decreases occurred in the proportion of patients using drugs not labeled for migraine prophylaxis, nonopioid analgesics, nonsteroidal antiinflammatory drugs, and headache and migraine relief medications (p < 0.05). There was a 44.9% reduction in emergency room services, 53.2% reduction in migraine- related diagnostic procedures, and 57.1% reduction in migraine-related hospitalization days. Encounter claims for physicians' office visits did not change significantly.. Migraine patients within commercially insured health plans incurred substantial resource use. Within six months following initiation of topiramate preventive therapy, reductions in acute migraine medication and medical resource use were observed among this population of migraine sufferers.

Topics: Adolescent; Adult; Aged; Cohort Studies; Drug Utilization; Emergency Service, Hospital; Female; Follow-Up Studies; Fructose; Health Resources; Hospitalization; Humans; Male; Middle Aged; Migraine Disorders; Topiramate

Migraine is a common disorder with a relatively high burden of disease from the perspective of both society and the individual patient. Optimizing the use of prophylactic treatment may decrease the frequency and severity of attacks thus reducing the burden of disease. In this regard, topiramate has been found to be as effective as propranolol in the prevention of migraine attacks. In the present study, a cost-minimization analysis was performed. Monthly preventive medication cost and price per migraine attack reduced were used as measures. In comparison with propranolol and flunarizine, topiramate was identified as being the most costly option for migraine prophylaxis with a monthly drug cost of USD 24.97-45.04 as compared with propranolol (USD 1.72-6.87) and flunarizine (USD 6.09-12.18). Current treatment options would appear to offer better value for money in achieving effective migraine prophylaxis unless additional benefits can be identified for topiramate in this patient group.

Topics: Cost-Benefit Analysis; Dose-Response Relationship, Drug; Fructose; Humans; Meta-Analysis as Topic; Migraine Disorders; Neuroprotective Agents; Randomized Controlled Trials as Topic; Topiramate

Migraine headaches are common and among the most disabling nonfatal conditions of humankind. They are frequently misdiagnosed, which may lead to undertreatment. Patients often self-diagnose and self-medicate, resulting in inadequate treatment. Consequently, patients may take additional doses, trying to gain relief with inappropriate medications. Rebound can ensue. With adequate treatment, a patient's condition and quality of life may improve considerably. Patient education is extremely important to help patients identify appropriate self-care measures, such as identification of triggering events and coping with the chronic nature of their condition. This case study presents a patient who began experiencing migraines following a neck injury. His headaches became more frequent, and ergotamine and caffeine (Cafergot) suppositories were prescribed. When he presented, he was experiencing daily headaches and using daily ergotamine and caffeine suppositories. He was using the emergency department (ED) frequently because of severe headaches. Cervical spasm was recognized as his trigger, and the ergotamine and caffeine suppositories were discontinued. After 3 days of severe headaches, his rebound ceased. He reverted back to episodic migraines, which he treated with zolmitriptan (Zomig) nasal spray, which was effective. His cervical spasm was treated with botulinum toxin type A (Botox), with excellent results. He has maintained reasonable headache control for 2 years.

Topics: Acupuncture Therapy; Administration, Rectal; Adult; Caffeine; Combined Modality Therapy; Drug Combinations; Ergotamine; Fructose; Humans; Male; Manipulation, Chiropractic; Middle Aged; Migraine Disorders; Neuroprotective Agents; Oxazolidinones; Serotonin Receptor Agonists; Severity of Illness Index; Topiramate; Tryptamines; Vasoconstrictor Agents

The purpose of this report is to describe acute myopia as an ocular adverse reaction to topiramate (Topamax, Ortho-McNeil, Raritan, NJ) and discuss the importance of recognizing this syndrome.. Retrospective case report and brief review of the literature.. A 27-year-old female patient developed decreased vision in both eyes due to acute myopia 2 weeks of after initiating therapy with topiramate. Emergency department evaluation revealed visual acuities of 20/400 right eye and 20/200 left eye. Intraocular pressures were 33 mm Hg right eye and 26 mm Hg left eye. The anterior chambers were shallow. Retinal striae were present in the maculae. The patient stated no previous need for optical correction. However, after initiating treatment with topiramate, she refracted to approximately -5.00 D bilaterally. Ultrasound testing revealed that the patient had suprachoroidal effusions in both eyes. The symptoms and clinical findings resolved completely with discontinuation of topiramate, administration of topical atropine 1% and prednisolone acetate 1%.. An acute myopic shift may be the presenting sign of an idiosyncratic drug reaction that can include secondary bilateral angle closure glaucoma. This condition can occur in patients who do not have a history of anterior chamber abnormalities. Recognizing this condition and discontinuing the use of the causative drug may prevent angle closure and associated vision loss.

Topics: Adult; Diagnosis, Differential; Female; Follow-Up Studies; Fructose; Glaucoma, Angle-Closure; Humans; Intraocular Pressure; Migraine Disorders; Myopia; Neuroprotective Agents; Ophthalmoscopy; Refraction, Ocular; Retrospective Studies; Severity of Illness Index; Tomography, Optical Coherence; Topiramate

Topics: Adult; Follow-Up Studies; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Quality of Life; Severity of Illness Index; Time Factors; Topiramate; Treatment Outcome

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Female; Fructose; Functional Laterality; Headache; Humans; Indomethacin; Male; Middle Aged; Migraine Disorders; Topiramate

Six migraine patients experienced significant topiramate-related cognitive and language dysfunction that improved with donepezil treatment and allowed uninterrupted topiramate use. These patients represent the first report of topiramate-related cognitive and language dysfunction that improved with a cholinesterase inhibitor. Although, the mechanism responsible for this effect is uncertain, cholinesterase inhibition resulting in cholinergic augmentation and enhanced cognition probably account for some if not most of the improvement.

Topics: Adult; Cholinesterase Inhibitors; Cognition Disorders; Donepezil; Female; Fructose; Humans; Indans; Language Disorders; Male; Middle Aged; Migraine Disorders; Piperidines; Topiramate; Treatment Outcome

Topics: Blood-Brain Barrier; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome

Two patients are reported who developed palinopsia while taking topiramate for migraine prevention which resolved or decreased in frequency or duration on lower doses, but recurred or increased in frequency or duration on higher doses. Both patients had complete resolution of palinopsia when topiramate was discontinued. A third patient is described who developed the "Alice in Wonderland" syndrome about 1 week after starting topiramate for migraine prevention with complete resolution of symptoms about 1 month after stopping. Topiramate use may cause palinopsia and may be associated with the Alice in Wonderland syndrome through an unknown mechanism.

Topics: Adult; Afterimage; Anticonvulsants; Body Image; Female; Fructose; Humans; Middle Aged; Migraine Disorders; Perceptual Distortion; Topiramate

Topics: Adrenergic beta-Antagonists; Fructose; Germany; Humans; Migraine Disorders; Practice Guidelines as Topic; Practice Patterns, Physicians'; Serotonin Antagonists; Topiramate; Tryptamines; Valproic Acid

Topics: Anticonvulsants; Female; Fructose; Humans; Middle Aged; Migraine Disorders; Multiple Sclerosis; Obsessive-Compulsive Disorder; Topiramate

Topics: Acidosis, Renal Tubular; Anticonvulsants; Carbonic Anhydrases; Female; Fructose; Humans; Kidney; Middle Aged; Migraine Disorders; Models, Biological; Topiramate

Topics: Analgesics; Anticonvulsants; Botulinum Toxins, Type A; Chronic Disease; Clinical Trials as Topic; Drug Therapy, Combination; Fructose; Humans; Migraine Disorders; Topiramate

Acute transient myopia with shallowing of the anterior chamber is a rare idiosyncratic response to many systemic and topical medications, including sulfonamides. Several such cases have been reported in the past, but are less frequently reported in recent times. We report a case of acute progressive myopia and bilateral angle closure due to Topiramate--a drug used for epilepsy and migraine prophylaxis.

Topics: Adult; Anterior Chamber; Female; Follow-Up Studies; Fructose; Glaucoma, Angle-Closure; Humans; Intraocular Pressure; Migraine Disorders; Myopia; Neuroprotective Agents; Refraction, Ocular; Topiramate; Ultrasonography

To investigate the associations between interictal pattern glare, visual stress, and visual triggers of migraine.. There has been relatively little research on the visual stimuli that can trigger migraine episodes. This is surprising, since if practitioners can obviate such triggers, then some attacks may be prevented. The existing literature suggests that patients who are prone to visually triggered migraines report more illusions on viewing striped patterns ("pattern glare") and that colored filters may be an effective intervention for these people.. Headache symptoms and headache triggers were investigated in migraine and control groups in 2 separate experiments. In one experiment, we also determined, for each participant, pattern glare, whether it was reduced by colored filters and, if so, what the optimum color of filter was. Color vision was also assessed with the D15 test.. People with migraine saw significantly more illusions on viewing each striped pattern and experienced greater pattern glare. They were also more likely to select a colored filter to aid visual comfort, particularly colors in the blue-to-green sector of the spectrum. Color vision was impaired subtly but significantly in migraine. Principal component analyses grouped common headache triggers into 5 broadly equal components: food, visual triggers, alcohol, stress and tiredness, and the environment. In a second analysis, the overall number of illusions seen in striped patterns was associated with visual triggers while pattern glare, use of colored filters, and interictal light sensitivity together formed a sixth component interpreted as visual stress.. It is suggested that clinicians should ask migraine patients whether visual stimuli trigger their migraine, about interictal visual symptoms, and use the pattern glare test to ensure that those who may benefit from optometric interventions are appropriately managed.

Topics: Acute Disease; Adult; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Pilot Projects; Secondary Prevention; Serotonin Antagonists; Topiramate; Tryptamines

Topics: Adult; Female; Fructose; Headache; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Sexual Dysfunctions, Psychological; Topiramate

The aim of this study was to assess the cost-effectiveness of topiramate vs. no preventive treatment in the UK. Model inputs included baseline migraine frequency, treatment discontinuation and response, preventive and acute medical cost per attack [2005 GBP ( pound)] and gain in health utility. Outcomes included monthly migraines averted, acute and preventive treatment costs and cost per quality-adjusted life year (QALY). Topiramate was associated with 1.8 fewer monthly migraines and a QALY gain of 0.0384. The incremental cost of topiramate vs. no preventive treatment was about 10 UK pounds per migraine averted and 5700 UK pounds per QALY. Results are sensitive to baseline monthly migraine frequency, triptan use rate and the gain in utility. Incorporating savings from reduced work loss (about 36 UK pounds per month) suggests that topiramate would be cost saving compared with no preventive treatment. This analysis suggests that topiramate is a cost-effective treatment for migraine prevention compared with no preventive treatment.

Topics: Adult; Cost-Benefit Analysis; Decision Support Techniques; Fructose; Humans; Migraine Disorders; Models, Economic; Neuroprotective Agents; Quality of Life; Quality-Adjusted Life Years; Topiramate; United Kingdom

Topics: Adolescent; Child; Electroencephalography; Female; Fructose; Humans; Male; Migraine Disorders; Topiramate; Ultrasonography, Doppler, Transcranial

A previously published decision-analytic model assessing the clinical and economic consequences of topiramate versus no preventive treatment in migraineurs was updated with new published literature and unpublished clinical trial data. The model captured baseline migraine days, treatment discontinuation, treatment response (i.e., > or = 75%, 50%-74%, and < 50% reduction in migraine frequency), hours of disability, cost of preventive therapy, cost of acute treatment (pharmacy and medical service), and wages. Topiramate was associated with 29 fewer migraine-days and 78 fewer hours of disability per year, compared with no preventive treatment. The incremental cost per migraine-day averted for topiramate versus no preventive treatment was dollar 29 when only direct medical costs were considered and dollar 2 when total costs were included. Model results were sensitive to baseline migraine-days, response probability, and probability of an attack being treated with a triptan. Topiramate may be a cost-effective treatment for the prevention of migraine.

Topics: Cost-Benefit Analysis; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate; United States

Topiramate is the second antiepileptic drug, after valproate, to be approved by the FDA for prevention of migraine. There is no evidence that it is more effective than a beta-blocker for this indication, and it is much more expensive. Topiramate can cause cognitive impairment and weight loss. No studies have compared it to valproate for this indication.

Topics: Anticonvulsants; Cognition Disorders; Fructose; Humans; Migraine Disorders; Topiramate; Weight Loss

Topics: Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fructose; Humans; Incidence; Migraine Disorders; Pregnancy; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Topiramate; Treatment Outcome

Open-label studies and three large and controlled trials had demostrated the efficacy of topiramate in migraine prophylaxis.. The objective of this study was to assess the effectiveness and tolerability of topiramate in patients not previously treated with any prophylactic drug.. Patients selection was made on sequential patients attending our outpatient clinic. Patients were adults diagnosed of either transformed migraine or migraine with a frequency of more than four migraine attacks per month. Topiramate was started at 25 mg and titrated in 4 weeks by weekly increments of 25 mg, up to 100 mg/day. Patients were then followed up for a 12-week maintenance phase. Efficacy was assessed by change in mean monthly migraine attack frequency from baseline. Additional assessments included responder rates, mean number of migraine days and global impression by a seven-point improvement scale.. Mean monthly migraine attacks decreased significantly from baseline (from 5.2 +/- 2.6 to 2.1 +/- 2.2; p < 0.0001). Sixty-nine percent of patients were considered responders and mean reduction rate in migraine was 55.6 %. Topiramare was overall well tolerated. Twentyfive (28.4 %) patients stopped treatment due to adverse events. The most common adverse events were paresthesia, weight loss and cognitive effects. Some grade of satisfaction was reported by 55 % of patients at the end of the study.. This naturalistic study confirms clinical trial data that 100 mg/day is an effective target dose for patients with migraine and presents the possible beneficial effect in transformed migraine.

Topics: Adolescent; Adult; Aged; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Topiramate

Topics: Calcium Channel Blockers; Flunarizine; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Topiramate

Patients whose migraines are frequent, cause disruptions of daily routines, or are unresponsive to acute treatment are primary candidates for preventive migraine therapy. This cost-effectiveness model assesses the clinical and economic impact of topiramate (TPM) therapy versus no preventive treatment for migraine headache in the United States.. Despite significant progress in treatment options, the economic burden of migraine to patients, employers, health systems, and society is substantial. Treatment strategies for migraine are directed toward managing acute episodes. However, preventive therapy should be used for patients with frequent migraine attacks (>2 per month) or those experiencing attacks that disrupt daily routines.. Data for the model were obtained from the published literature and pooled results of two randomized, double-blinded, placebo-controlled trials of TPM in migraine prevention. Model inputs included baseline migraine frequency (the base case assumed 6 per month, consistent with the average rate in the TPM trials), treatment discontinuation (including discontinuation due to adverse events), treatment response (ie, > or = 75%, 50% to 75%, and <50% reduction in migraine frequency), cost of preventive therapy (TPM plus physician visits for medication titration), cost of acute treatment per attack (including pharmacy and medical service costs), hours of disability per attack, hourly wage, and quality-of-life (utility) weights. Model outcomes included the number of migraines averted, disability hours, total cost of acute and preventive treatment, and lost wages. Results were expressed as cost per migraine averted and cost per quality-adjusted life years (QALY). All costs were stated as 2002 U.S. dollars. We also conducted sensitivity analyses to assess the robustness of model findings with respect to variation in key parameters.. We estimated that the use of TPM would prevent 1.85 migraines per patient and almost 5 hours of disability per month versus no preventive treatment. Resulting savings in cost of acute treatment (dollar 27) and work loss (dollar 51) offset 68% of the expected monthly cost of TPM (dollar 113). The incremental cost per migraine averted was dollar 19, while the incremental cost per QALY was estimated to be dollar 10,888 (dollar 26,191 when indirect costs were excluded from the analysis). Model results were sensitive to baseline migraine rate and gain in health utility from migraine prevention.. Economic savings associated with reduced migraine frequency offset approximately two thirds of the cost of preventive TPM therapy. The cost-effectiveness of TPM depends on utility gains associated with a reduced frequency of migraine headaches, which is the subject of ongoing research. However, results from our model suggest that the use of TPM in prevention of migraine may offer reasonable value for money relative to many well-accepted medical interventions.

Topics: Cost-Benefit Analysis; Decision Trees; Economics, Pharmaceutical; Fructose; Humans; Migraine Disorders; Models, Econometric; Randomized Controlled Trials as Topic; Topiramate; United States

Topics: Acute Disease; Administration, Oral; Anticonvulsants; Female; Fructose; Functional Laterality; Glaucoma, Angle-Closure; Humans; Middle Aged; Migraine Disorders; Topiramate

Topics: Adult; Anticonvulsants; Carbonic Anhydrase Inhibitors; Chronic Disease; Dose-Response Relationship, Drug; Erectile Dysfunction; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Nitric Oxide; Penile Erection; Regional Blood Flow; Sex Characteristics; Sexual Dysfunction, Physiological; Topiramate

Assessment of health-related quality of life (QOL) has become increasingly common in clinical trials. Because QOL has multiple dimensions and is assessed repeatedly over time, multiple comparisons and missing data must be addressed in the design and analysis of these trials. While the development of an analysis plan will be a continuous process, described here are three critical phases in the ideal development of a statistical analysis plan for the QOL component of a clinical trial: concept, initial design, and final analysis plans. A clinical trial designed to evaluate a new therapy for the prevention of migraines was used to illustrate the critical decisions that are made during the design and analysis phases of a trial that incorporates QOL in the assessment procedure. Specifically addressed are clearly defining goals and objectives, endpoints, multiple comparisons, analysis of longitudinal data with dropout, and estimation of power.

Topics: Fructose; Humans; Migraine Disorders; Models, Statistical; Quality of Life; Randomized Controlled Trials as Topic; Topiramate

Topics: Administration, Intranasal; Botulinum Toxins, Type A; Fructose; Heart Septal Defects, Atrial; Humans; Migraine Disorders; Neuromuscular Agents; Neuroprotective Agents; Oxazolidinones; Serotonin Receptor Agonists; Sleep Bruxism; Topiramate; Tryptamines

Frequent migraine attacks require prophylactic treatment. Anticonvulsants have been suggested due to the progressive knowledge that cortical hyperexcitability is involved in migraine pathophysiology. Topiramate is one of these drugs and its efficacy has been demonstrated in several studies. The aim of this study is to evaluate the adherence and response to topiramate in migraineurs under treatment in a tertiary center. During a 2-year period, all of the patients receiving topiramate for migraine were evaluated after 3 months. The parameters evaluated were adherence to treatment, frequency reduction of attacks >50% and adverse events. Among 175 patients included, 134 (76.6%) returned. Among the 134 patients evaluated, 82 (61.2%) revealed frequency reduction >50% and 105 (78.4%) patients presented weight loss (average 3.4Kg). The most frequent side effects were paresthesias (39.6%); emotional disturbances (including depression, irritability and anxiety) in 17,9%; thinking impairment (12.7%); memory disturbances (12.7%) and altered taste (11.9%). Despite methodological limitations we concluded that adherence to its use and efficacy occurred in most of the patients. In addition, the side effect profile was acceptable. Further controlled studies are necessary to confirm these observations.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Cohort Studies; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Patient Compliance; Topiramate; Treatment Outcome

The importance of evidence-based medicine is often underestimated when migraine preventive treatments are chosen. Evidence from large, well-conducted, placebo-controlled trials of sufficient duration should be given particular consideration when evaluating the efficacy, tolerability and safety of a medication for a broad range of patients. Pizotifen, propranolol, flunarizine, amitriptyline, divalproex sodium and topiramate have all been evaluated for efficacy in migraine prevention in double-blind, placebo-controlled trials. The largest clinical programme in migraine prevention, studying these or any other agents, was comprised of 2 pivotal trials, as well as other studies, evaluating topiramate for preventive therapy in migraine. Results from these trials indicated that topiramate (100 mg/day) has proven safety and efficacy in migraine prevention. Response rates were high, and onset of action usually occurred within the first month of treatment. Therefore, topiramate has demonstrated safety and represents an effective option in the prevention of migraine, as supported by extensive clinical research.

Topics: Evidence-Based Medicine; Fructose; Humans; Migraine Disorders; Neuroprotective Agents; Randomized Controlled Trials as Topic; Topiramate

Topics: Adult; Fructose; Humans; Male; Migraine Disorders; Somnambulism; Topiramate

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).

Topics: Adolescent; Adult; Child; Dose-Response Relationship, Drug; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Neuroprotective Agents; Preventive Medicine; Topiramate; Treatment Outcome

To assess the efficacy and tolerability of topiramate for prophylaxis of migraine and cluster headache via a retrospective chart analysis.. 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.. 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.. 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).. 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.

Topics: Adult; Aged; Anticonvulsants; Chronic Disease; Cluster Headache; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Recurrence; Retrospective Studies; Topiramate; Treatment Outcome

Topiramate, a broad-spectrum anticonvulsant with multiple mechanisms of action, may be effective in preventing migraine headaches. We report the results of a retrospective chart review of patients treated with topiramate for prophylaxis of migraine.. Patients with a diagnosis of migraine who had at least one follow-up visit after > or =4 weeks on topiramate were eligible; 69 patients (56 women and 13 men) aged 18 to 68 years met these criteria. Charts were reviewed for frequency of mild or moderate/severe headaches at the start of topiramate (baseline) and at all subsequent visits up to 24 weeks.. The 28-day frequency of moderate/severe migraines declined significantly from baseline to end of treatment (10.6 +/- 8.4 to 7.4 +/- 7.7, respectively; P = 0.0004), whereas that of mild headaches did not demonstrate a significant change (from 11.8 +/- 8.9 to 11.0 +/- 10.0). Among the 38 patients who had not responded previously to >or =9 preventive medications, the monthly frequency of moderate/severe (but not mild) headaches decreased significantly from baseline to end of treatment. Patients who previously had not responded to <9 prior medications experienced significant declines in both mild and moderate/severe headaches. The most common adverse events were paresthesias, drowsiness, diarrhea, decreased appetite, and weight loss. Twenty-seven patients discontinued topiramate therapy, 20 as a result of adverse events and 7 due to lack of response.. Topiramate may be effective in reducing the frequency of both mild and moderate/severe migraine headaches. In particular, topiramate may offer relief to patients with moderate/severe migraines who do not respond to other treatments.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Female; Fructose; Humans; Male; Middle Aged; Migraine Disorders; Retrospective Studies; Topiramate; Treatment Outcome

Topics: Anticonvulsants; Fructose; Glaucoma; Humans; Migraine Disorders; Topiramate; Vision Disorders; Visual Fields

Topics: Adult; Anticonvulsants; Female; Fructose; Hallucinations; Headache; Humans; Migraine Disorders; Psychoses, Substance-Induced; Topiramate