Efficacy In Migraine Prevention Research Articles

VPAC1 and VPAC2 receptors mediate tactile hindpaw hypersensitivity and carotid artery dilatation induced by PACAP38 in a migraine relevant mouse model

BackgroundPituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide pivotal in migraine pathophysiology and is considered a promising new migraine drug target. Although intravenous PACAP triggers migraine attacks and a recent phase II trial with a PACAP-inhibiting antibody showed efficacy in migraine prevention, targeting the PACAP receptor PAC1 alone has been unsuccessful. The present study investigated the role of three PACAP receptors (PAC1, VPAC1 and VPAC2) in inducing migraine-relevant hypersensitivity in mice.MethodsHindpaw hypersensitivity was induced by repeated PACAP38 injections. Tactile sensitivity responses were quantified using von Frey filaments in three knockout (KO) mouse strains, each lacking one of the PACAP-receptors (Ntotal = 160). Additionally, ex vivo wire myography was used to assess vasoactivity of the carotid artery, and gene expression of PACAP receptors was examined by qPCR.ResultsPACAP38 induced hypersensitivity in WT controls (p < 0.01) that was diminished in VPAC1 and VPAC2 KO mice (p < 0.05). In contrast, PAC1 KO mice showed similar responses to WT controls (p > 0.05). Myograph experiments supported these findings showing diminished vasoactivity in VPAC1 and VPAC2 KO mice. We found no upregulation of the non-modified PACAP receptors in KO mice.ConclusionsThis study assessed all three PACAP receptors in a migraine mouse model and suggests a significant role of VPAC receptors in migraine pathophysiology. The lack of hypersensitivity reduction in PAC1 KO mice suggests the involvement of other PACAP receptors or compensatory mechanisms. The results indicate that targeting only individual PACAP receptors may not be an effective migraine treatment.

Effects of a Single Session of OnabotulinumtoxinA Therapy on Sleep Quality and Psychological Measures: Preliminary Findings in a Population of Chronic Migraineurs.

Chronic migraine is a burdensome condition, and onabotulinumtoxinA is revealed to be an effective therapy. Migraine shows a bidirectional relationship with sleep, but the effects of preventive therapies on sleep quality are poorly studied. This study aims to evaluate the effects of a single session of onabotulinumtoxinA on patients' sleep quality and correlates the results with measures of comorbid anxiety/depression. Patients completed self-administrable questionnaires about sleep quality (Pittsburgh Sleep Quality Index-PSQI) and psychological symptoms (Beck Depression Inventory, 2nd edition-BDI-II-and Hospital Anxiety and Depression Scale-HADS-subscales "a" and "d" for anxiety and depression, respectively), and reported migraine frequency at baseline and after 12 weeks. The 42 included patients showed a significant reduction in migraine days (from 20.6 ± 6.0 to 13.6 ± 6.2, p < 0.001), while no changes were observed in sleep quality (PSQI score from 11.0 ± 5.0 to 9.8 ± 4.6, p = 0.277) or psychological measures (BDI-II from 16.7 ± 10.2 to 15.7 ± 10.3, p = 0.678; HADS-a from 10.3 ± 4.8 to 9.3 ± 5.5, p = 0.492; and HADS-d from 7.2 ± 3.9 to 7.1 ± 5.0, p = 0.901). On the other hand, a strong correlation among PSQI, BDI-II, HADS-a, and HADS-d scores (p < 0.001, rho > 0.7) was found. Despite its efficacy in migraine prevention, a single session of onabotulinumtoxinA was not able to affect patients' sleep quality or their psychological symptoms.

Drug Safety in Episodic Migraine Management in Adults. Part 2: Preventive Treatments.

The aim of this review is to aid in decision-making when choosing safe and effective options for preventive migraine medications. In Part 2, we have compiled clinically relevant safety considerations for commonly used migraine prophylactic treatments. Preventive treatment of episodic migraine includes nonspecific and migraine-specific drugs. While medications from several pharmacological classes-such as anticonvulsants, beta-blockers, and antidepressants-have an established efficacy in migraine prevention, they are associated with a number of side effects. The safety of migraine-specific treatments such as anti-CGRP monoclonal antibodies and gepants are also discussed. This review highlights safety concerns of commonly used migraine prophylactic agents and offers suggestions on how to mitigate those risks.

Cerebral Blood Flow and Other Predictors of Responsiveness to Erenumab and Fremanezumab in Migraine-A Real-Life Study.

IntroductionMonoclonal antibodies (mAbs) showed efficacy in migraine prevention. The aim of this study was to check if baseline clinical parameters and cerebral blood flow (CBF) measured by transcranial Doppler (TCD) may help predict mAbs efficacy.MethodsElectronic charts of migraineurs treated with erenumab or fremanezumab, with baseline TCD evaluations were collected, including data on migraine type, pain localization, monthly migraine days (MMD), medication overuse headache (MOH), mean blood flow velocity (Vm), and pulsatility index (PI) in cerebral arteries.ResultsA total of 123 patients were enrolled, mean age 38, 75 years, 87 with chronic migraine, 61 with MOH, 72 were good responders (GR), and reported ≥50% reduction in MMD, 43 ≥75% reduction in MMD. Baseline Vm values in MCAs were significantly lower in GR as compared with non-responders. MAbs responsiveness ≥50% was positively associated with unilateral pain localization (OR: 6.53, 95% CI: 2.01–23.93; p = 0.003) and HIT-6 score (OR: 1.14, 95% CI: 1.01–1.30; p = 0.036) whereas negatively associated with Vm in right MCA (OR: 0.96, 95% CI: 0.92–0.99; p = 0.012), and having no relatives with migraine (OR: 0.40, 95% CI: 0.16–0.95; p = 0.040).ConclusionsBaseline Vm in MCA is lower in mAbs GR as compared with non-responders which may reflect increased secretion of CGRP with further vasodilation in GR. Simple clinical features and baseline CBF in anterior circulation might help to predict the patient's responsiveness.

Erenumab in chronic migraine: Experience from a UK tertiary centre and comparison with other real-world evidence.

Background and purposeChronic migraine is a highly disabling primary headache disorder that is the most common diagnosis of patients seen at tertiary headache centres. Typical oral preventive therapies are associated with many limitations that impact their therapeutic utility. Erenumab was the first available calcitonin gene‐related peptide monoclonal antibody in the UK. It had proven efficacy in migraine prevention in clinical trials and limited real‐world data in tertiary settings.MethodsWe audited our first 92 patients (n = 73 females) with severely disabling chronic migraine who were given monthly erenumab 70 mg sc for 6 months between December 2018 and December 2019.ResultsAt 3 months, monthly migraine days were significantly reduced by a median of 4 days, and all other variables also showed significant improvement. The improvement was not affected by baseline analgesic use status. More than half of our patients experienced a clinically meaningful improvement in migraine days. No serious adverse events were reported.ConclusionsOur real‐world data with erenumab demonstrate it is effective and well tolerated in managing patients with chronic migraine in a tertiary care setting.

CGRP monoclonal antibodies early onset of efficacy following four weeks of treatment in chronic migraine

Various studies have documented a rapid onset of efficacy in migraine prevention for monoclonal antibodies targeting CGRP. Aim of the present study was to assess migraine outcome following the first 4 weeks of treatment in patients treated with erenumab 70 mg or galcanezumab 240 mg (loading dose).

Changes in Cerebral Blood Flow after Erenumab Treatment in Good and Non-Responders-A Pilot Study of Migraine Patients.

Erenumab showed efficacy in migraine prevention, however we cannot identify which patients to treat by predicting efficacy response. The aim of this study was to compare changes in cerebral blood flow (CBF) reflected by transcranial Doppler (TCD) in erenumab good responders (GR) and non-responders, in order to identify a parameter that could predict the treatment response. In this study, migraineurs treated with erenumab underwent clinical and TCD evaluations before and 6 weeks after the treatment, including data on migraine type, monthly migraine days (MMD), medication overuse headache (MOH) presence, mean blood flow velocity (Vm) and pulsatility index (PI) in cerebral arteries (CA). GR were defined as reporting ≥50% reduction in MMD. Thirty women were enrolled, of mean age 40.53 years, 20 with chronic migraine, 14 with MOH, and 19 were GR. Baseline Vm values in right CA and basilar artery (BA) were significantly lower in GR as compared with non-responders. Vm values in all arteries significantly increased after the treatment as compared with corresponding baseline values, but only in GR. A significant negative correlation was observed between baseline Vm in right CA and treatment effectiveness. Baseline Vm in right CA and basilar artery is reduced in erenumab GR as compared with non-responders. This asymmetry normalizes after the treatment with significant Vm increase in CA which may reflect CBF increase in GR only. Lower baseline Vm in right CA may predict erenumab efficacy; however, these results should be replicated in a larger cohort.

Patient Preference for Early Onset of Efficacy in Migraine Prevention (1749)

Patient Preference for Early Onset of Efficacy in Migraine Prevention (1749)

Effect of age on pharmacokinetics, efficacy, and safety of galcanezumab treatment in adult patients with migraine: results from six phase 2 and phase 3 randomized clinical trials

BackgroundMigraine clinical profile may change with age, making it necessary to verify that migraine treatments are equally safe and effective in older patients. These analyses evaluated the effects of patient age on the pharmacokinetics (PK), efficacy, and safety of galcanezumab for prevention of migraine.MethodsAnalyses included efficacy data from three double-blind phase 3 clinical trials: two 6-month studies in episodic migraine (EVOLVE-1, EVOLVE-2: N = 1773) and one 3-month study in chronic migraine (REGAIN:N = 1113). Patients were randomized 2:1:1 to placebo, galcanezumab 120 mg, or galcanezumab 240 mg. Safety and PK data included additional phase 2 and phase 3 trials for a larger sample size of patients > 60 years (range = 18–65 for all studies). Subgroup analyses assessed efficacy measures, adverse event (AE) occurrence, and cardiovascular measurement changes by patient age group. Galcanezumab PK were evaluated using a population analysis approach, where age was examined as a potential covariate on apparent clearance (CL/F) and apparent volume of distribution (V/F) of galcanezumab.ResultsNumbers of baseline monthly migraine headache days were similar across age groups. There were no statistically significant treatment-by-age group interactions for any efficacy measures, except in episodic migraine studies where older patients appeared to have a larger reduction than younger patients in the number of monthly migraine headache days with acute medication use. Age (18–65) had a minimal effect on CL/F, and no effect on V/F. Galcanezumab-treated patients ≥60 years experienced no clinically meaningful increases in blood pressure and no increased frequency in treatment-emergent AEs, discontinuations due to AEs, serious adverse events (SAEs) overall, or cardiovascular SAEs, compared to age-matched placebo-treated patients.ConclusionsAge (up to 65 years) does not affect efficacy in migraine prevention and has no clinically meaningful influence on galcanezumab PK to warrant dose adjustment. Furthermore, older galcanezumab-treated patients experienced no increases in frequency of AEs or increases in blood pressure compared with age-matched placebo-treated patients.Trial registrationsEVOLVE-1 (NCT02614183, registered 23 November 2015), EVOLVE-2 (NCT02614196, 23 November 2015), REGAIN (NCT02614261, 23 November 2015), ART-01 (NCT01625988, 20 June 2012, ), I5Q-MC-CGAB (NCT02163993, 12 June 2014, ), I5Q-MC-CGAJ (NCT02614287, 23 November 2015, ), all retrospectively registered.

Gepants, calcitonin-gene-related peptide receptor antagonists: what could be their role in migraine treatment?

Migraine is the second leading cause of years lived with disability after back pain. Poor tolerability, contraindications, drug-drug interactions and efficacy limited to a subpopulation make new approaches necessary for the acute and preventive treatment of migraine. The study of the calcitonin-gene-related peptide (CGRP) pathway over the last decades is a good example of translational medicine leading to directed therapies for patients. After some of the first-generation CGRP receptor antagonists, gepants, were not fully developed because of hepatotoxicity, the second generation of gepants have shown efficacy, safety and tolerability in recent clinical trials. Both rimegepant and ubrogepant have published positive randomized placebo-controlled clinical trials data. Vazegepant is the first intranasal gepant for the acute treatment of migraine and has announced a positive phase II/III study. Daily rimegepant use has preliminary data to suggest efficacy. Atogepant has shown efficacy in migraine prevention in a phase II/III study. Most importantly, hepatotoxicity has not been reported in specifically designed phase I studies or long-term extension studies, with rimegepant or ubrogepant, or in a preventive study with atogepant. Given the preventive effect, it seems likely that gepants will not lead to medication overuse headache. They will likely have no cardiovascular warnings. Because of the particular benefit gepants may represent for these groups of patients, specific studies in patients with medication overuse headache, as well as those with comorbid cardiovascular diseases, would be of considerable interest.

Individualization of Migraine Prevention: A Randomized Controlled Trial of Psychophysical-based Prediction of Duloxetine Efficacy.

Finding an effective preventive agent for the individual migraineur is often long and frustrating. An individual-specific, efficacy-predicting tool would be invaluable in directing, shortening, and improving this process. As the serotonin-norepinephrine reuptake inhibitor duloxetine is a pain modulator, we hypothesized that pronociceptivity will directly predict drug efficacy, so that the more pronociceptive the patient is, the more efficacious the drug. Therefore, we used psychophysical pain measures to predict duloxetine efficacy in migraine prevention. Fifty-five migraineurs participated: 27 received duloxetine and 28 nonactive placebo. Responses to painful stimuli, conditioned pain modulation, and temporal summation of pain were measured before treatment. Treatment outcome measures included changes in attack frequency, migraine days, pain levels, and a reported self-estimate of migraine improvement at weeks 4 and 5. To examine treatment effects, the outcome measures were compared with pretreatment levels. Treatment by the psychophysical-predictor effect on treatment outcome was examined in separate regression models. Duloxetine was more efficacious than placebo in migraine prevention, as indicated by the patient's estimation of migraine improvement (duloxetine: 52.3±30.4%; placebo: 26.0±27.3%; P=0.001). Further, this measure, in the duloxetine group, was predicted by higher pretreatment pain ratings for tonic heat pain (P=0.012); greater pain sensitivity at baseline predicted greater percent of migraine improvement in duloxetine (r=0.47; P=0.013), but not in placebo (r=-0.36; P=0.060). Our results suggest how personalized medicine can be applied to designing appropriate migraine prevention treatment. Psychophysical testing can reveal and characterize pronociceptive migraineurs, who seem to be more likely than non-pronociceptive ones to benefit from migraine prevention with serotonin-norepinephrine reuptake inhibitors.

Topiramate: Comprehensive profile.

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.

Therapeutic role of melatonin in migraine prophylaxis: A systematic review.

BackgroundMelatonin is the “clock factor” generated from pineal gland dominating regular circadian rhythm in humans. Migraine is one of the most severe and debilitating primary headache disorders. Thus far, many diseases have been found to associate with melatonin, including the migraine. Therefore, melatonin's therapeutic potential for migraine is drawing attention.ObjectivesThe aim of this study is to offer a systematic review of extant data of melatonin in migraine prophylaxis and to provide clinical implications and specific recommendations for future studies.Data sources and study methodsA systematic research was conducted in September 2018 by using PubMed and Google Scholar databases to search for science literature published after 1988.ResultsIn all, 7 eligible articles were identified, including 4 randomized controlled studies and 3 observational studies. Due to high heterogeneities and limited number of studies, meta-analysis was not feasible, and only systematic review was performed. The results show that present evidence cannot claim melatonin's effectiveness according to the conflicting outcomes; however, the two negative outcomes of melatonin not different from placebo and melatonin inferior to amitriptyline are possible under-powering because of methodological, pharmacological, and therapeutic shortcomings. Observational studies also support melatonin's efficacy in migraine. As a result, melatonin is very likely to benefit migraine in prophylaxis and may have a similar effectiveness to other main preventive medications. Immediate-release melatonin 3 mg was established as effective, melatonin receptor agonist (Agomelatine) 25 mg and prolonged-release melatonin 4 mg were observed efficacious in observational studies. Melatonin displayed ineffective in the 2-month trial; thus, 3 months or more may be an enough duration for migraine therapy. Despite melatonin being generally safe, emerging literature is illustrating that a few severe adverse effects can be caused by melatonin, for example, liver injuries, reproductive system dysfunctions, and detrimental immunostimulation.ConclusionsMelatonin is very likely to be a promising alternative for migraine prophylaxis. Current literature examining melatonin's efficacy in migraine prevention is growing, but still limited. Future studies of perfect design in methodology, pharmacology, and therapeutics are needed to achieve a deeper awareness of melatonin's role in migraine as well as more studies to explore the safety issues of melatonin medicine.

Safety profile of a special butterbur extract from Petasites hybridus in migraine prevention with emphasis on the liver

Background: Butterbur supplements are available in the USA and Canada and are commonly used for treating migraines. Petadolex, a special butterbur extract from Petasites hybridus, is a natural herbal product and the only butterbur extract with proven clinical efficacy in migraine prevention. The Complimentary Migraine Guidelines of the AAN mention butterbur as level A recommendation for the prevention of chronic episodic migraine. However, these guidelines have been retired. Methods: We review suspected serious liver cases, pyrrolizidine alkaloids, regulatory issues, preclinical and clinical data of the special butterbur extract Petadolex. Results: The RUCAM (Roussel Uclaf Causality Assessment Method) test found no probable relationship between the butterbur root extract Petadolex® and cases of serious liver injury. Two cases of non-serious reversible liver enzyme elevations were rated as probably related to Petadolex®. The safety is supported by preclinical data in animals as well as in-vitro toxicology experiments. In addition, Petadolexis free of detectable levels of pyrrolizidine alkaloids. Conclusion: There is no evidence that the special butterbur root extract Petadolex poses a substantial risk of liver injury for patients.

P 111 Clinical trials in neurological disorders causing vertigo

The German Center for Vertigo and Balance Disorders (DSGZ) is an interdisciplinary center for research and treatment of vertigo, balance and ocular motor disorders. The long-term aim is to establish a patient-oriented research institution that is networked with all involved disciplines and methods. This includes also the establishment of a study infrastructure for prospective multicenter clinical trials. With this abstract we would like to give an overview over the current clinical trials conducted in collaborations with other investigational sites throughout Germany. During the last 20 years vestibular migraine has been identified as a distinct type of migraine with the leading symptom of vertigo. These attacks lasting minutes to hours, have considerable impact on quality of life, and can result in economical and social losses. The trial drug metoprolol with proven efficacy in migraine prevention is commonly used in the treatment of vestibular migraine. So far its indication in vestibular migraine is only based on expert opinion. The aim of the PROVEMIG study (a double-blind, placebo-controlled trial) is to demonstrate the superiority of metoprolol succinate treatment regarding the number of vertigo attacks and the number of headache attacks per month compared to placebo in patients with vestibular migraine. The leading symptom of vestibular paroxysmia (VP) are spontaneous recurrent attacks of rotatory or postural vertigo lasting seconds to a few minutes sometimes with accompanying symptoms like tinnitus or hypoacusis. The high frequency as well as the unpredictability of these vertigo attacks result in strong impact on quality of life. Based on the pathophysiological concept of neurovascular compression as for trigeminus neuralgia the sodium channel blocker Carbamazepin (CBZ) is used as off-label therapy for patients with VP. The purpose of the VesPa study is to demonstrate within a controlled clinical trial that CBZ is efficacious in reducing the frequency, duration and severity of vertigo attacks, the number of vertigo per month and improving quality of life in patients with VP. Benign peripheral paroxysmal positional vertigo (BPPV) is characterized by short but intense attacks of rotatory vertigo induced by changes in the position of the head or body, accompanied oscillopsia, nausea and vomiting. Furthermore, nearly 50 percent of these patients also experience a relapse of BPPV. Retrospective studies revealed that patients with BPPV show decreased vitamin D levels. The goal of the [email protected] study is to investigate the efficacy of vitamin D in reducing the amount of patients with one or more recurrences of BPPV. Interested study sites are welcome to contact the clinical study center of the DSGZ at http://ifb.klinikum.uni-muenchen.de/de/Studienzentrum or [email protected].

Spotlight on Anti-CGRP Monoclonal Antibodies in Migraine: The Clinical Evidence to Date.

Migraine, a common neurovascular brain disorder, represents a severe and widespread health problem; along with medication‐induced (medication‐overuse) headache, it is the third‐leading cause of disability worldwide. Currently, its therapeutic management remains unsatisfactory for several reasons; up to 40% of migraineurs are eligible for prophylactic treatment, but there are issues of efficacy, safety, and adherence. In recent years the evidence on the role of calcitonin gene‐related peptide (CGRP) in migraine pathophysiology has been consolidated, so new and promising treatments for migraine pain and its possible prevention have been developed. The following review reports the results of the clinical trials conducted so far with each of the new monoclonal antibodies targeting CGRP or its receptor, with particular reference to safety, tolerance, and efficacy in migraine prevention. Moreover, the pharmacological characterization and further developments of each monoclonal antibody are reported, based on current knowledge.

Anti-CGRP monoclonal antibodies in migraine: current perspectives.

Migraine is a highly disabling neurological pain disorder in which management is frequently problematic. Most abortive and preventative treatments employed are classically non-specific, and their efficacy and safety and tolerability are often unsatisfactory. Mechanism-based therapies are, therefore, needed. Calcitonin gene-related peptide (CGRP) is recognized as crucial in the pathophysiology of migraine, and new compounds that target the peptide have been increasingly explored in recent years. First tested were CGRP receptor antagonists; they proved effective in acute migraine treatment in several trials, but were discontinued due to liver toxicity in long-term administration. Monoclonal antibodies against CGRP (LY2951742, ALD-403, and LBR-101/TEV-48125) or its receptor (AMG334) were subsequently developed. As reviewed in this study, numerous phase 1 and 2 trials and preliminary results of phase 3 trials have shown a good safety/tolerability profile and efficacy in migraine prevention, especially in high frequent episodic and chronic forms. Being macromolecules, these mAbs are not suitable for oral administration; however, their intravenous or subcutaneous delivery can be performed at relatively low frequency-every month or even quarterly-which enhances patients' compliance. Although not all migraineurs respond to this treatment, and longer administration periods will be needed to assess long-term effects, the results so far obtained are extraordinarily promising. The future introduction of mAbs on the market will probably represent a turning point for prevention similar to that represented by triptans for abortive treatment in migraine.

A randomized, double-blinded, placebo-controlled, crossover, add-on study of CoEnzyme Q10 in the prevention of pediatric and adolescent migraine

To evaluate the efficacy of Coenzyme Q10 (CoQ10) supplementation in the prevention of migraine in children using a placebo-controlled, double-blinded, crossover, add-on trial. CoQ10 has been demonstrated to have efficacy in migraine prevention in adults but lacks pediatric research with more rigorous methodology. CoQ10 has been observed to be deficient in a significant number of children and adolescents presenting to tertiary headache centers. CoQ10 has the potential to modify both the inflammatory changes that occur during recurrent migraine and the alteration of mitochondrial function. A deficit of CoQ10 could thus affect the response to treatment and clinical characteristics of migraine in children and adults. One-hundred-and-twenty children and adolescents with migraine headache were randomized in a crossover, double-blind, placebo-controlled, randomized, add-on study to receive a placebo or CoQ10 (100 mg) supplement for 224 days. Data for 76 patients were available at the crossover point and 50 were analysed at the endpoint. Response to treatment, overall headache improvement, and headache disability were assessed. Both the placebo and CoQ10 groups showed reduced migraine frequency [F(1, 60)=15.68, p<0.001], severity [F(1, 54)=8.09, p=0.006], and duration [F(1, 45)=6.27, p=0.016] over time. CoQ10 treated patients had a significantly greater improvement in frequency from subject reported baseline starting within 4 weeks of initiation. No group differences comparing the first 4 weeks of treatment with the last 4 weeks of treatment were found in migraine frequency [F(1, 60)=2.34, p>0.05], severity [F(1, 54)=0.06, p>0.05], or duration [F(1, 45)=0.14, p>0.05]. Overall, results of the study demonstrate that children and adolescents with migraine improved over time with multidisciplinary, standardized treatment regardless of supplementation with CoQ10 or placebo. There was no difference in headache outcomes between the CoQ10 and placebo groups at day 224. Due to the improvements seen in weeks 1-4, CoQ10 may lead to earlier improvement in headache severity, but given the sample size this conclusion warrants further investigation with a larger sample.

Papel de los neuromoduladores en el tratamiento preventivo de la migraña

More than one quarter of patients who consult due to migraine need preventive treatment. At least half of these patients do not respond or cannot tolerate classical preventatives: beta-blockers, flunarizine or amitriptyline.To analyse the role of new antiepileptics (neuromodulators) in migraine prevention.Critical review of clinical trials carried out with antiepileptics for the treatment of migraine. Topiramate has demonstrated clear efficacy in the prevention of migraine with and without aura, including chronic migraine with and without analgesic overuse, although it is not tolerated by one fifth of patients. Valproic acid also has a demonstrated efficacy in the preventive treatment of migraine with and without aura, but its tolerability profile and the possibility of serious adverse events oblige us to prescribe this neuromodulator for refractory patients. Gabapentin shows a mild efficacy, clearly lower than that of topiramate and valproate. Lamotrigine is the treatment of choice in the prevention of migraine aura, but is not efficacious in the treatment of headache. Levetiracetam has shown some efficacy in open studies in migraine prevention, both in adults and children. Zonisamide has demonstrated good efficacy and tolerability in patients refractory to topiramate and shows a prolonged half life, which improves compliance. The remaining antipileptics have not shown efficacy.Topiramate and valproic acid have demonstrated efficacy in migraine prevention. Lamotrigine is efficacious for the treatment of migraine aura. Even though new studies are necessary, zonisamide could be a good option for the preventive treatment of migraine.

Topiramate in migraine prevention: evidence-based medicine from clinical trials

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.