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Monoclonal antibodies targeting the calcitonin gene-related peptide have been introduced into the therapeutic arsenal of migraine prophylaxis. Clinical trials report similar efficacy between them, and there is no evidence of switching to another one after failure. We aim to describe our experience in switching from erenumab to galcanezumab after therapeutic failure. We retrospectively reviewed 30 migraine patients who received monoclonal antibodies, with 15 of them switched after failure to achieve reduction in migraine days per month ≥30%. A ≥30% reduction in migraine days per month compared to baseline was observed in 8/15 (4/15 ≥ 50%) patients after switch. Some nonresponsive patients may benefit from switching between monoclonal antibodies with different therapeutic targets.

Aim: The efficacy of the drugs used for migraine prophylaxis remains unclear. At our headache polyclinic, when we observed the difference in prophylactic response especially in valproic acid (VA) treatment between genders, the response of male was found to be better than that of females so we wanted to document this difference by collecting data retrospectively Material and Method: 46 chronic migraine without aura patients with VA who were enrolled in our headache outpatient clinic between 2015 - 2018 were included in the study (29 male, 17 female). In these patients, after VA the frequency of montly attacks between sexes, changes in VAS (Visual analogue scale) scores, single VA prophylaxis and the addition of a second prophylaxis drug were evaluated. Results: None of the men needed an additional second drug while 11 of 17 women needed the addition of a second drug. There was no gender difference in monthly attack frequency before treatment, whereas monthly attack frequency after treatment with VA was found to be significantly lower in men ( before treatment; female 20,9±11,3 male 17,7±11,5, p>0.05) (after treatment; male 1,2±5,5 female 12,0±12,2, p0.05)(after treatment; female 4,4±2,8 male 2,3±2,8, p

Background Migraine is characterized by moderate to severe recurrent headache lasting for 4–72 h. Cortical hyperexcitability may play a crucial role in migraine onset. Therefore, antiepileptic drugs, such as levetiracetam, may be beneficial. Methods We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective studies that evaluated the efficacy of levetiracetam in migraine prophylaxis. Electronic databases, including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, were searched for articles on migraine prophylaxis and levetiracetam published before May 2020. The main outcomes were number of patients with >50% headache frequency reduction, frequency of headache, and headache severity. Results We identified 4 RCTs involving 192 patients and 4 prospective studies involving 85 patients. The overall data on number of patients with >50% headache frequency reduction, headache frequency, and headache severity were subjected to meta-analysis, which revealed significant differences between the levetiracetam and the placebo groups (risk ratio [RR] of number of patients with >50% headache frequency reduction = 0.46, 95% confidence interval [CI] = 0.35 to 0.61; weighted mean difference [WMD] of headache frequency per month = −3.78, 95% CI = −5.52 to −2.03; standard mean difference [SMD] of headache severity = −2.42, 95% CI = −4.47 to −0.37). Conclusion Our study indicated that levetiracetam can significantly reduce headache frequency and severity in adults and children. Thus, oral levetiracetam can be a therapeutic option for migraine prophylaxis, especially concerning with the adverse effects or teratogenicity of other preventive treatments.

Background: There is a need for effective, well tolerated and affordable drug for chronic migraine prophylaxis in low socioeconomic countries. Objective: To study the efficacy and safety of propranolol and sodium valproate (a food and drug administration approved and widely used treatment for prevention of migraine) as a prophylactic treatment in chronic migraine (CM) patients and to compare their efficacy and safety to each other. Methods: In this single center, open labeled clinical trial, 40 patients with CM were subdivided into two group: group 1 (n=20) treated with propranolol and group 2 (n=20) treated with sodium valproate. Patients maintained headache diaries over a 1-month baseline period and a 6- month active study period. The evaluation of the treatment was done after 3 and 6 months of the initiation of the treatment. The efficacy measures were evaluation of monthly attacks frequency and attacks severity using VAS of pain (visual analogue scale. Disability and impact of migraine were evaluated using Migraine assessment disability scale (MIDAS) and Headache Impact Test (HIT-6). Throughout the study, patients were monitored for any symptoms or signs of adverse effects. Results: Of 40 patients participated in this study (mean age, 33.48; females 72.5%). At the 6th month, the study was completed by 27 patients (propranolol; n=14 and sodium valproate; n=13). Between 55 and 62% of both groups reported more than 50% reduction in monthly attacks frequency. In both groups, there was significant reduction of VAS of pain scores. Both groups showed significant improvement of HIT-6 and MIDAS scores. Before the start of treatment, 85% to 100% of patients in both groups had severe MIDAS and HIT-6 scores. At the end of the study, only 35.7% of propranolol group and 30.8 of sodium valproate group showed severe MIDAS scores and 50% of propranolol group and 40% of sodium valproate group reported severe HIT-6 scores. 55% (n=11) of patients in propranolol reported AEs related to treatment compared to 75% (n=15) in the sodium valproate group. A higher proportion of patients discontinued the treatment because of AEs in Na valproate group compared to sodium valproate group with no statistically significant difference in between (20% vs. 5%, respectively). Conclusions: Propranolol and sodium valproate demonstrated similar efficacy and tolerability in the prophylactic treatment of CM.

Introduction: OnabotulinumtoxinA (OBT-A) and monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway are two of the few treatments that ameliorate chronic migraine (CM) in randomized controlled trials and real-life studies. Separate clinical practice guidelines have been developed for the management of CM with OBT-A or CGRP-targeting mAbs. Areas covered: Considering the concomitant availability of OBT-A and CGRP-targeting mAbs as therapeutic treatment options, Italian migraine experts reviewed the evidence supporting the efficacy of OBT-A and CGRP-targeting mAbs in CM in order to rationalize the management of CM patients treated with OBT-A. Experts addressed everyday practice needs to shape the optimal pharmacological management by balancing adherence to regulatory indications, ethical considerations, and clinical expertise. Considering the remarkable challenge of improving the health and quality of life of patients with CM, even partial improvements may be clinically meaningful, particularly for those who are resistant or intolerant to oral migraine treatments. Expert opinion: In this collaborative effort, we propose a treatment algorithm that integrates the relevant aspects of managing patients with CM to provide ready-to-use practical guidance regarding the appropriate use of OBT-A.

Chronic migraine (CM) is a highly disabling primary headache. Botulinum toxin (onabotulinumtoxinA) is effective for treatment of CM, with ~ 50% of patients responding after 24 weeks. A response predictor would prevent unnecessary treatments. Inhibiting calcitonin gene related peptide (CGRP) release from trigeminal nociceptive fibres is one of the modes of acting discussed for onabotulinumtoxinA in CM. Therefore, we hypothesized that the response to triptans might predict response to onabotulinumtoxinA. Contrariwise, onabotulinumtoxinA treatment might affect triptan efficacy. 49 CM patients scheduled for their first onabotulinumtoxinA treatment were included. Before (T0) and three months after (T1) onabotulinumtoxinA treatment, patients rated triptan efficacy and indicated number of headache days/month. At T1, patients additionally rated onabotulinumtoxinA efficacy. Headache days/month were on average reduced by 7.1 ± 7.0 days from T0 to T1 (p

Background Migraine 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. Methods Analyses 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. Results Numbers 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. Conclusions Age (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 registrations EVOLVE-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.

Objective: The prevalence of migraine is higher in patients with gastrointestinal disorders. Possible underlying mechanisms could be increased intestinal permeability and systemic inflammation. Pro...

Introduction OnabotulinumtoxinA (BoNT-A) was proved effective and safe in chronic migraine (CM) prevention by the Phase III Research Evaluating Migraine Prophylaxis (PREEMPT) and Phase IV Chronic migraine OnabotulinuMtoxinA Prolonged Efficacy open-Label (COMPEL) trials over 1 and 2 years of treatment, respectively. Real-life studies highlighted BoNT-A sustained benefits up to 3 years of administration. Aim of this retrospective real-life study was observing within a 4-year timeframe the progress of a consecutive series of CM patients treated with BoNT-A and evaluating whether long-term quarterly treatment (up to 16 cycles) confirms the outcomes of previous studies over shorter periods of therapy. Methods One hundred nine chronic migraineurs were quarterly treated with BoNT-A according to the PREEMPT paradigm. Headache days and hours, analgesics intake and latency time together with disability were analysed at baseline, thereafter bi-annually up to 48 months. Patient responsiveness (improvement in monthly headache days and hours versus baseline) was computed at each study timepoint. Results A significant overall decrease from baseline to the 48-month assessment (p p Conclusions This study appears to reconfirm the benefits of long-lasting CM prevention with BoNT-A, thus supporting quarterly treatment with BoNT-A over several year.

Migraine is a common disabling neurological disorder which is characterised by a recurring headache associated with a variety of sensory and autonomic symptoms. The pathophysiology of migraine remains not entirely understood, although many mechanisms involving the central and peripheral nervous system are now becoming clear. In particular, it is widely accepted that migraine is associated with energy metabolic impairment of the brain. The purpose of this review is to present an updated overview of the energy metabolism involvement in the migraine pathophysiology. Several biochemical, morphological and magnetic resonance spectroscopy studies have confirmed the presence of energy production deficiency together with an increment of energy consumption in migraine patients. An increment of energy demand over a certain threshold creates metabolic and biochemical preconditions for the onset of the migraine attack. The defect of oxidative energy metabolism in migraine is generalized. It remains to be determined if the mitochondrial deficit in migraine is primary or secondary. Riboflavin and Co-Enzyme Q10, both physiologically implicated in mitochondrial respiratory chain functioning, are effective in migraine prophylaxis, supporting the hypothesis that improving brain energy metabolism may reduce the susceptibility to migraine.

Introduction Non-invasive vagus nerve stimulation (nVNS; gammaCore®) has the potential to prevent migraine days in patients with migraine on the basis of mechanistic rationale and pilot clinical data. Methods This multicentre study included a 4-week run-in period, a 12-week double-blind period of randomised treatment with nVNS or sham, and a 24-week open-label period of nVNS. Patients were to administer two 120-second stimulations bilaterally to the neck three times daily (6–8 hours apart). Results Of 477 enrolled patients, 332 comprised the intent-to-treat (ITT) population. Mean reductions in migraine days per month (primary outcome) were 2.26 for nVNS (n = 165; baseline, 7.9 days) and 1.80 for sham (n = 167; baseline, 8.1 days) ( p = 0.15). Results were similar across other outcomes. Upon observation of suboptimal adherence rates, post hoc analysis of patients with ≥ 67% adherence per month demonstrated significant differences between nVNS (n = 138) and sham (n = 140) for outcomes including reduction in migraine days (2.27 vs. 1.53; p = 0.043); therapeutic gains were greater in patients with aura than in those without aura. Most nVNS device-related adverse events were mild and transient, with application site discomfort being the most common. Conclusions Preventive nVNS treatment in episodic migraine was not superior to sham stimulation in the ITT population. The “sham” device inadvertently provided a level of active vagus nerve stimulation. Post hoc analysis showed significant effects of nVNS in treatment-adherent patients. Study identification and registration: PREMIUM; NCT02378844; https://clinicaltrials.gov/ct2/show/NCT02378844

Liver and kidney role in detoxification and drug metabolism increases the risk of their poisonous injury. Topiramate (TMP) is an effective popular migraine prophylaxis that is accepted for utilize in adults and teenagers. Therefore, the target of this research is to estimate the potential toxic effects of TMP on liver and kidney in male mice. Thirty-two adult albino male mice were divided into four groups (

Background: Several drugs are used individually for migraine prophylaxis. Objective: The purpose of the present study was to compare the propranolol and amitriptyline as monotherapy for the prophylaxis of migraine. Methodology: This randomized control trial was conducted in headache clinic at Banghabandhu Sheikh Medical University (BSMMU), Dhaka, Bangladesh from July 2012 to June 2014 for a period of two (02) years. Migraine patients with or without aura of 16 to 50 years of age, patients not on any prophylactic medication were included for this study. Patients meeting all the criteria was randomized group A who were treated with Amitriptyline and group B who were treated with propranolol. Patients was followed for a three months period during which they was instructed to maintain a headache diary. The primary outcome evaluated was the proportion of patients in each group that achieved a 50% reduction in the number of days with headache. Result: A total 80 adult patients were selected. During 1st visit among the patients duration of pain 1 to 4 hours (2.5.0%), 5 to 8 hours (13.3%) 9 to 12 hours (35.0%) and above 13 hours (22.5%) in group A were recorded; however, in group B, duration of pain 1 to 4 hours 1(2.5), 5-8 hours 16(13.3%), 9-12 hours 19(47.5) and above 13 hours 4(10.0) (p>0.05). In group A, no adverse effect was found 26(65.0%), drowsiness 6 (15.0%), dryness of mouth 6(15.0%), constipation 2(5.0%), fatigue and bradycardia were not found. In group B, no adverse effect was found 29(72.5%), drowsiness, dryness of mouth and constipation were not found, fatigue and bradycardia were 7(17.5%) and 4(10.0%). Conclusion: In conclusion number of attack and headache before treatment gradually decrease in subsequent follow up in both groups. Journal of Current and Advance Medical Research 2019;6(2):77-82

Objective To study the efficacy and safety of lasmiditan for acute treatment of migraine in patients using migraine preventive medications. Background While lasmiditan has been proven to be an effective acute treatment for migraine, its effectiveness has not been examined when used concurrently with migraine preventives. Methods SAMURAI and SPARTAN were similarly designed, double-blind, phase 3, placebo-controlled studies of patients 18 years or older with 3 to 8 migraine attacks per month. Patients were randomized to treat a migraine attack with oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo. Migraine preventives were allowed as long as doses were stable for 3 months prior to screening and were unchanged during the study. Preventive medications with established or probable efficacy, as recommended by the American Academy of Neurology, the American Headache Society, and the European Headache Federation, plus botulinum toxin type A and candesartan, were included. Within the subgroups of patients using and not using preventive therapies, lasmiditan and placebo groups were analyzed for the outcome of pain-free at 2 h and other efficacy outcomes. The subgroups of patients using and not using preventive therapies were compared and interaction p-values were calculated for safety and efficacy outcomes. Results In these trials, 698 of 3981 patients (17.5%) used migraine preventive treatments. Among patients using preventives, all lasmiditan doses resulted in significantly more patients being pain-free at 2 h, compared to placebo (p

Background The Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials demonstrated efficacy/tolerability of onabotulinumtoxinA for headache prevention in adults with chronic migraine. This post hoc analysis assessed time of onset of onabotulinumtoxinA after the first treatment in total and responder populations and consistency weekly through five treatment cycles. Methods In the 24-week, double-blind, placebo-controlled phase of PREEMPT, individuals were randomized 1:1 to onabotulinumtoxinA (155-195 U) or placebo every 12 weeks for two cycles. The primary pooled efficacy variable was change in headache days per 28 days at week 24. We assessed change in headache and migraine/probable migraine (hereafter migraine) days/week compared with baseline week 4. Results Baseline mean (SD) headache days/week (week 4 of baseline) for onabotulinumtoxinA (n = 688) and placebo (n = 696) were similar (4.8 [1.6] vs. 4.8 [1.6] days/week, respectively), as were migraine days/week (4.6 [1.7] vs. 4.6 [1.7] days/week). The effect of onabotulinumtoxinA on change in headache and migraine days/week was significantly greater than placebo at week 1, persisting from week 3 after the first treatment (−1.6 [2.2] vs. −1.1 [2.2] headache days/week [ p Conclusions Treatment with onabotulinumtoxinA is associated with significant reductions in headache and migraine days/week at week 1, persisting after week 3, compared with placebo. Combined with earlier reports showing onabotulinumtoxinA treatment results in a persistent and progressive reduction in headache days over 56 weeks, it is suggested peak benefit may require multiple treatments. Trial registration number ClinicalTrials.gov: NCT00156910 and NCT00168428.

Background: Topiramate is an anti epileptic medication originally and one of the first line drugs for migraine prophylaxis.Objective: To assess outcome of Topiramate in migraine prophylaxis by evaluating reduction in frequency and/or severity of attacks and address most common adverse affect associated with it.Methods: A Descriptive, prospective hospital based study was conducted at Ibrahim Malik Hospital, National center of neurological disease and sciences within the period of October 2018 –May 2019. Data entered, cleaned, analyzed using SPSS version 25.0.Results: This study covered 32 study participants; the mean age (33 ± 10) years, with female predominance by 27 (84%).Nearly, half of them 15(47%) migraine triggered by weather changes, 13 (41%) menstruation. 17(53%) was suffering from headache > 24 months, and most of them 26(81%) used the OTC medications in the acute pain headache.Mean of frequency of attacks per month was reduce (6.1 base line to 3.2), in severity mean was (6.9 turn to 5). Reduction in Frequency of attacks there was significant in both number and severity (p value < 0.001) with no significant difference in (50 mg and 100mg dose). Concerning adverse effects 5(15.6%) didn’t complain of any, more than third 12(38%) experienced weight loss, 7(22%) both Abdominal/GIT symptoms and Dizziness, 5(16%) mood changes, 4(13%) both parathesia and decreased memory, 3(9%) both Anorexia and sleepiness.Conclusion: Topiramate is effective in reducing headache frequency and reasonably well tolerated in adult Sudanese patients with episodic migraine. This may provide good evidence to support its use in routine clinical management.

OBJECTIVE:to assess migraine outcome following twelve months treatment with erenumab and compare patients who underwent three months erenumab discontinuation following the first treatment cycle to those who continued monthly administrations.METHODS:this is a multicentric observational study in migraine patients in treatment with erenumab. Following a full 12 months treatment cycle (T12) patients could either continue or discontinue erenumab for at least three months. Patients who underwent treatment discontinuation were assessed following three months (T15) to decide whether to start re-treatment. Patients were then assessed following at T16 and T18.RESULTS:Thirty consecutive patients were enrolled. Nineteen patients underwent treatment suspension at T12 up to T15, whereas 11 continued phrophylaxis. At T15, patients who discontinued treatment documented significantly more migraine days (17.06±6.5 vs 4.8±2.5; p < 0.0001) and analgesics consumption (14.8±9.2 vs 4.6±2.5; p = 0.002), compared to those who continued treatment. Following re-treatment, at T16, patients who had previously undergone discontinuation documented a significant improvement in terms of migraine days (9.01±4.4 vs 17.06±6.5; p < 0.0001) and analgesics consumption (9.6±7.3 vs 14.8±9.2; p = 0.004). Such improvement was even greater at T18, comparable to T12.CONCLUSIONS:Following treatment discontinuation, a rapid migraine worsening was found, despite the high clinical response during treatment and at re-treatment, which might be secondary to an untimely interruption of a potentially disease modifying pharmacological intervention. Although clinical improvement was documented following retreatment, given the high frequency and degree of worsening during discontinuation, it seems plausible – even ethical – to re-evaluate current timing of discontinuation.CLASSIFICATION OF EVIDENCE:This study provides class III evidence that people with migraine discontinuing erenumab migraine prophylaxis after 12 months were more likely to have an increase in non-responder status and migraine days than those who continued treatment.

Purpose: Calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are new agents approved by the US Food and Drug Administration for preventive treatment of chronic migraine. Comparison between CGRPmAbs and previously approved Botulinum neurotoxin A (BoNT-A) will inform optimal preventive treatment of chronic migraine, but head-to-head trials are lacking. We therefore aimed to perform adjusted indirect comparison between CGRPmAbs and BoNT-A through a meta-analysis.Methods: OVID MEDLINE, EMBASE and the Cochrane central register of controlled trials, clinical registries, and government websites were searched from inception to September 2019. Randomized controlled trials comparing CGRPmAbs or BoNT-A with placebo in the preventive treatment of chronic migraine were included. The primary outcomes were headache days and migraine days measured at week 12. Data were synthesized by using a frequentist approach; and the treatments were ranked by P-score.Results: We included 10 trials (n = 4,678) after screening 1049 candidates. Six trials were with low risk of bias. Fremanezumab had an effect similar to BoNT-A in the reduction of headache days at week 12 (standard mean difference [SMD] 0.08, 95%CI -0.55 to -0.7). Galcanezumab reduced more migraine days than BoNT-A at week 12 (SMD, -0.94, 95%CI −1.24 to −0.63); fremanezumab showed similar findings (SMD, −0.55, 95%CI −0.85 to −0.24). Galcanezumab and fremanezumab had better effect in mitigating headache impact at week 12. CGRPmAbs and BoNT-A had similar adverse event rate.Conclusion: CGRPmAbs and BoNT-A had similar effect in the preventive treatment of chronic migraine. BoNT-A might be preferentially selected owing to its cost-effectiveness profiles. Further studies with direct comparison of the two treatments are warranted.

Migraine is a common disease worldwide and migraine prevention is primarily currently based on pharmaceuticals. The mechanism of Vitamin B2 may positively contribute to migraine. This systematic review and meta-analysis aimed to evaluate the impact of Vitamin B2 supplementation on the days, duration, frequency, and pain score of the migraine attack.: The PRISMA guideline was used for the studying process. Five electronic databases, PubMed, Embase, Cochrane, CINAHL, and CEPS were searched from 1990 to March 2019. The search terms were Vitamin B2, migraine, and prophylactic. A meta-analysis was performed using Comprehensive Meta-Analysis (CMA) version.: Nine articles were included in systemic review and finally meta-analysis. Eight randomized controlled trials and one controlled clinical trial with 673 subjects were analyzed using meta-analysis. Vitamin B2 supplementation significantly decreased migraine days (A pooled analysis of available randomized controlled clinical trials demonstrated that Vitamin B2 400 mg/day for three months supplementation had significant effect on days, duration, frequency, and pain score of migraine attacks.

Migraine is a common disorder of the paediatric age group. Propranolol has been used in prophylaxis for migraine. The use of Sodium valproate in the prophylaxis of migraine is not known. It is postulated that it increases the level of GABA in the brain that will decrease events related to migraine in the cortex. All parents of the patient were advised to keep diaries for noting time, date, severity and duration of headache during the study period, which was for a period of 6 wks. The decreased frequency of headache more than in Group A was 68% and propranolol group was 68.89%. In group A(sodium valproate), patients showed a reduction in headache duration and 52% in Group B. 20% of them headache free in Group A and 18% in Group B. Decrease in the severity of headache in Group A was 52% while 50% in Group B. The mean headache frequency before and after treatment was reduced from 8 to 2.5 attacks per month in group A and from 8.2 to 2.6 in group B. The t-value is 11 for group A. Sodium valproate is more effective and safer in migraine prophylaxis as compared with propranolol.

Objectives Allodynia, the clinical marker of central sensitization, affects even simple daily living activities and increases the tendency for migraine to be more resistant to treatment and have a chronic course. Migraine that impairs quality of life can often be treated with variable pharmaceutical agents, but with various side effects. Transcranial direct current stimulation (tDCS) is a potential alternative treatment for migraine prophylaxis. Materials and methods Seventy-seven patients diagnosed with migraine (48 with allodynia and 29 without allodynia) were included in the study. Randomly, 41 of the 77 patients received sham stimulation and 36 patients underwent three sessions of anodal left primary motor cortex stimulation for 2 mA, 20 min. Migraine attack characteristics (frequency, severity, and duration) and analgesic drug use were followed with headache diaries for one month after the stimulation. Results After tDCS, migraine attack frequency (p = 0.021), the number of headache days (p = 0.005), duration of attacks (p = 0.008), and symptomatic analgesic drug use (p = 0.007) decreased in patients receiving active tDCS, compared to the sham group. The therapeutic gain of tDCS was calculated as 44% (95% confidence interval [CI]: 22-60%) for headache days and 76% (95% CI: 55-86) for headache duration. Response to tDCS treatment was higher in patients without allodynia (60% vs. 24%; p = 0.028) and allodynia came out as an independent predictor of response to tDCS with logistic regression analysis. Side effects were rare and similar to the sham group. Conclusions tDCS is a safe, efficacious, and fast method for migraine prophylaxis. However, the administration of tDCS before allodynia occurs, that is, before central sensitization develops, will provide increased responsiveness to the treatment. Significance tDCS is more effective before the development of allodynia, but it also improves the quality of life even after the development of allodynia.

Migraine is one of the leading causes of years lived with disability and considered to be a major global health concern. Pharmacological preventive treatment often causes side effects that limit the adherence to longer-term treatment regimens. Both experimental and clinical evidence suggests that positive expectations can modulate pain and analgesic treatment effects. However, the role of expectations in migraine prophylactic treatment has not systematically been investigated. Here, we examined the influence of treatment expectation before commencing pharmacological preventive treatment on its efficacy and tolerability in N = 134 episodic (30%) and chronic migraine (70%) patients in a prospective, longitudinal observational study over the course of 6 months. The migraine prophylaxis reduced the number of headache and migraine days with acceptable tolerability. Positive treatment expectation was associated with a generally lower number of headache and migraine days and a stronger reduction in headache days over the course of the treatment in chronic but not in episodic migraine patients. Moreover, patients with prior treatment showed a stronger reduction in headache days with higher expectation as compared to patients without prior experience. Our results underscore the relevance of further exploring the role of treatment expectation and its systematic modulation in patients with migraine and other pain conditions.

Introduction Migraine is one of the most common illnesses in the world, with severe economical and subjective implications. Nowadays specific and nonspecific drugs are used for migraine chronic therapy, but a portion of patients have no benefit from these administrations. CGRP receptor antagonists are a good preventive treatment for episodic and chronic migraine. Areas covered This article reviews both preclinical and clinical studies on eptinezumab as a potential preventive therapy for migraine, as well as pharmacokinetic and pharmacodynamic features. Thus, it summarizes safety and tolerability data based on human studies. Expert opinion Eptinezumab had good results in several trials, making this molecule a promising migraine preventive drug. Although preclinical and clinical studies showed a significant efficacy, there are no data on the use of Eptinezumab during pregnancy or breastfeeding. There are still some knowledge limits about its pharmacokinetics and metabolism. This is a matter of concern that should be addressed in future studies.

Objective To determine reversion rates from chronic migraine to episodic migraine during long-term erenumab treatment. Methods A daily headache diary was completed during the 12-week, double-blind treatment phase of a placebo-controlled trial comparing erenumab 70 mg, 140 mg, and placebo, and weeks 1–12, 21–24, 37–40, and 49–52 of the open-label treatment phase. Chronic migraine to episodic migraine reversion rates were assessed over the double-blind treatment phase; persistent reversion to episodic migraine over 24 weeks (double-blind treatment phase through the first 12 weeks in the open-label treatment phase), long-term persistent reversion to episodic migraine over 64 weeks (double-blind treatment phase plus open-label treatment phase); delayed reversion to episodic migraine through the first 12 weeks of the open-label treatment phase among patients remaining in chronic migraine during the double-blind treatment phase. Results In the double-blind treatment phase, 53.1% (95% confidence interval: 47.8–58.3) of 358 erenumab-treated completers had reversion to episodic migraine; monthly reversion rates to episodic migraine were typically higher among patients receiving 140 mg versus 70 mg. Among 181 completers (receiving erenumab for 64 weeks), 98 (54.1% [95% confidence interval: 46.6–61.6]) had reversion to episodic migraine during the double-blind treatment phase; of those, 96.9% (95% confidence interval: 91.3–99.4) had persistent reversion to episodic migraine, 96.8% (95% confidence interval: 91.1–99.3) of whom had long-term persistent reversion to episodic migraine. Delayed reversion to episodic migraine occurred in 36/83 (43.4% [95% confidence interval: 32.5–54.7]) patients; of these, 77.8% (95% confidence interval: 60.9–89.9) persisted in reversion through week 64. Conclusions Patients with reversion to episodic migraine at week 12 will likely persist as episodic migraine with longer-term erenumab; others may achieve delayed reversion to episodic migraine. Clinical trial registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02066415

BACKGROUND: Frequent migraine headaches are disabling and aeromedically disqualifying. Four new monoclonal antibody medications, targeting calcitonin gene-related peptide (CGRP), have been approved by the U.S. Food and Drug Administration (FDA) since 2018, with more expected in the coming years. These medications present new alternatives for the treatment of migraine unresponsive to other therapeutic and prophylactic agents.CASE REPORT: We present a case of a 45-yr-old commercial pilot who presented with migraine headaches increasing in frequency to 1315 per month in spite of the use of propranolol for prophylaxis and sumatriptan for abortive treatment of the headaches. Upon presentation, he was not flying due to his frequent headaches and he was started on monthly subcutaneous injections of fremanezumab. Following his second injection, his headaches stopped entirely, and he has continued on the medication and not experienced another migraine headache. He underwent an aeromedical neurology evaluation and consideration for Authorization of Special Issuance of Medical Certificate, which was granted by the Federal Aviation Administration (FAA).DISCUSSION: This is the first case to our knowledge of the successful use of an anti-CGRP monoclonal antibody medication in an active pilot. The pilot appears to be a super responder to the medication, having achieved complete remission of a nearly life-long condition. Though only a small portion of treated individuals will see this sort of response, these medications represent an effective additional option for migraine prophylaxis in the pilot population.Garber MA, Sirven JI, Roth RS, Hemphill JM. Migraine prophylaxis using novel monoclonal antibody injections in a commercial pilot. Aerosp Med Hum Perform. 2020; 91(10):824825.

Background There is interest in whether supplements, including vitamin D and marine omega-3 (n-3) fatty acids, may be effective migraine prophylaxis. However, few studies have evaluated whether vitamin D or n-3 fatty acid supplementation may reduce migraine frequency or severity. Methods Participants in the VITamin D and OmegA-3 TriaL (VITAL) were assigned to vitamin D3 (2000 IU/d) or marine n-3 fatty acid (1 g/d) supplementation in a 2-by-2 factorial design. Lifetime history of migraine was assessed a median of 4.6 years after the start of the trial. Individuals were asked to self-report changes in migraine frequency (no change, more frequent, or less frequent) and severity (no change, more severe, less severe) in the past 5 years. We used χ2 tests to compare proportions of individuals reporting changes in migraine frequency and severity between active and placebo groups. Results Among the 25,871 participants in VITAL, 1032 participants had a history of probable migraine and provided information on changes in migraine frequency and severity. The percentage of individuals reporting decreases in migraine frequency did not differ between active (69.0%) and placebo vitamin D (68.4%) (P value = 0.54) or between active (67.8%) and placebo n-3 fatty acid (69.6%) (P value = 0.82). Similarly, the percentage of individuals reporting decreases in migraine severity did not differ between active (64.1%) and placebo vitamin D (65.0%) (P value = 0.86) or between active (64.5%) and placebo n-3 fatty acid (64.5%) (P value = 0.96). Conclusions Neither vitamin D nor marine n-3 fatty acid supplementation, compared to placebo, affected migraine frequency or severity among middle-aged or older adults.

This study aimed to describe the demographic and clinical characteristics of migraineurs prescribed ≥1 migraine prophylactic therapy, and to analyze their therapeutic pathways, healthcare resource consumption, and related costs.This retrospective analysis was based on administrative databases from two regions and three local health units in Italy. Adult patients with ≥1 discharge diagnosis for migraine or ≥1 prescription for migraine-specific drugs, or ≥1 emergency room visit for migraine from 1 January 2010 to 31 December 2016 were included if they had received ≥1 migraine prophylactic therapy between 1 January 2011 and 31 December 2015 (enrollment period). The first date of the last migraine prophylactic treatment was considered as the index date (ID). Patients were characterized 1-year prior ID and followed-up for 1 year afterwards.Of the 166,362 identified migraineurs, 32,794 (mean age: 45.9 ± 13.9 years, 19.2% male) who received migraine prophylaxis were included in the analysis. At ID, 31,629 patients had received 1 prophylactic treatment with antidepressants (51.2%), neuromodulators (28.1%), beta blockers (12.4%), other migraine preparations (7.8%), and botulinum toxin A (0.5%). Focusing on patients with one prophylactic treatment at ID, 85.4% did not have any previous therapeutic failures whereas 14.6% had ≥1 previous failure. During follow-up, 5% of patients made a therapeutic switch after a mean period of 103.4 ± 97.9 days. Total mean annual cost for patients receiving migraine prophylaxis was 1193.64€ during characterization and 1303.86€ during follow-up periods.This real-world study gave insights on the characterization of migraineurs and patterns of prophylaxis utilization in Italian clinical settings, showing an underuse of prophylactic agents.

Despite the available prophylactic and acute drugs for migraine management, this disabling disorder remains undertreated especially among pediatrics. In this review, the authors aim at assessing the preventive role cinnarizine plays in treating migraine based on previously published studies.Randomized clinical trials, randomized controlled trials, non-randomized open-label trials, and retrospective studies concerning cinnarizine in migraine prevention in children and adults were reviewed. Especial attention was given to the response rate, migraine characteristics, and tolerability.The majority of reviewed trials demonstrated that cinnarizine is comparable to the conventional drugs used in migraine prophylaxis. However, most of the reviewed studies were limited by a non-controlled open-label design. Due to poor planning and possibility of high placebo responses, particularly in children and adolescents, the interpretation of open-label studies' results should be done cautiously. The evidence shows that cinnarizine's effectiveness was more promising in pediatric migraineurs and adults with migraine-associated vertigo such as vestibular migraine. Therefore, while the efficacy of cinnarizine cannot be dismissed, before reaching a definite conclusion on its effectiveness, it is necessary to do further high-quality RCTs among both children and adults.

Seit Anfang der 1970er-Jahre wird die progressive Muskelrelaxation (PMR) nach Jacobson in der Migraneprophylaxe eingesetzt. Hintergrund ist die Annahme, dass Migranepatienten eine erhohte autonome Aktivierung aufweisen, der man mit systematischer Entspannung entgegensteuern kann. Entspannungsverfahren reduzieren neben dem Aktivierungsniveau auch die zentrale Schmerzverarbeitung, auserdem bewirken entspannende Strategien eine Aktivierung in schmerzhemmenden Strukturen im periaquaduktalen Grau. Metaanalysen zeigen, dass die PMR ebenso wirksam ist wie medikamentose Verfahren. Ein guter Effekt stellt sich nur dann ein, wenn regelmasig taglich mindestens 5–25 min geubt wird und ein Transfer der Ubungen in den Alltag erfolgt. Diese Ubersicht fasst die empirischen Belege fur die Wirksamkeit von PMR bei Migrane kritisch zusammen. Es wird ein Mangel insbesondere an aktuellen Studien zur Thematik festgestellt. In einer eigenen Studie mit 50 Migranepatienten und 46 gesunden Kontrollen konnte neben der klinischen Wirksamkeit auch eine Anderung der kortikalen Aufmerksamkeitszuwendung bei der Messung der kontingenten negativen Variation („contingent negative variation“ [CNV]) nachgewiesen werden. Die zuvor erhohte CNV-Amplitude normalisierte sich bei regelmasiger Anwendung der PMR bei Migranepatienten. Mit der Ubersicht uber PMR-Studien zur Migraneprophylaxe und mit der eigenen Studie kann gezeigt werden, dass PMR ein effektives nichtmedikamentoses Verfahren zur Migraneprophylaxe ist und dass neben den klinischen Effekten auch nachweisbare Anderungen der kortikalen Reizverarbeitung im Sinne einer Normalisierung bewirkt werden konnen.

Background: Migraine hampers child's life through school absence, limitation of home and social activities. The goal of prophylactic (preventive) therapy is to reduce headache frequency, headache days, and headache severity with minimum side effects. Objective: To evaluate the efficacy and tolerability of levetiracetam compared to flunarizine as prophylactic treatment of Migraine in children. Methods: This prospective study was carried out in the outpatient department of a tertiary care hospital in Bangladesh. A total of 105 children aged 6-15 years, diagnosed as migraine without aura, were enrolled. Patients were treated with flunarizine or levetiracetam for three months. Headache disabilities were evaluated at baseline and at the end of three months. Results: In flunarizine group, 54 children and in levetiracetam group, 51 children were enrolled. Among them thirty nine children in flunarizine group and 36 children in levetiracetam group completed the study. Headache frequency, headache days, VAS (Visual Analogue Scale) score and PedMIDAS (Paediatric Migraine Disability Assessment Score) score were evaluated at baseline and during the follow up. After three months, headache frequency, headache days, pain severity (Visual Analogue Scale score) reduced significantly compared to baseline (p

To compare the cost of adverse events (AEs) associated with preventive treatment of migraine with fremanezumab, versus erenumab, galcanezumab, and onabotulinumtoxinA. A probabilistic modeling analy...

Objectives: To evaluate the efficacy of a multi-modal migraine prophylaxis therapy for patients with hyperacusis. Methods: 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. Results: 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 ( P < .001), indicating increased sound tolerability. The VAS discomfort level also showed significant improvement from a pre-treatment average of 7.7 ± 1.1 to 3.7 ± 1.6 post-treatment ( P < .001). There was also significant improvement in the average total score on modified Khalfa questionnaire (32.2 ± 3.6 vs 22.0 ± 5.7, P < .001). Conclusions: 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.

Purpose The present study aimed to determine the effects of combined supplementation of Coenzyme Q10 with L-carnitine on mitochondrial metabolic disorders marker and migraine symptoms among migraine patients. Methods A total of 56 men and women, between 20–40 years of age with migraine headache, participated in this randomized, double-blind, placebo-controlled, parallel study. The subjects were randomly assigned to receive either 30 mg/day Coenzyme Q10 and 500 mg/day L-carnitine at the same time and/or placebo tablets for 8 weeks. The measurements were completed at the beginning and end of the study. The primary outcome was severity of headache attacks. The secondary outcomes included duration, frequency of headache attacks, the headache diary results (HDR), and serum levels of lactate. Results A significant reduction was obtained in serum levels of lactate (−2.28 mg/dl, 95% CI: −3.65, −0.90; p = 0.002), severity (−3.03, 95% CI: −3.65, −2.40; p ≤ 0.001), duration (−7.67, 95% CI: −11.47, −3.90; p ≤ 0.001), frequency (−5.42, 95% CI: −7.31, −3.53; p ≤ 0.001) and HDR (−103.03, 95% CI: −145.76, −60.29; p ≤ 0.001) after 8 weeks. Conclusion This double-blind parallel study provides evidences supporting the beneficial effects of Coenzyme Q10 and L-carnitine supplements on serum levels of lactate and migraine symptoms. Trial registration IRCT20121216011763N21.

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.

Jitka Pokladnikova,1,2 Petra Maresova,3 Josef Dolejs,3 A-La Park,4 Bo Wang,5 Xin Guan,5Frantisek Musil1 1Czech-Chinese Centre for Traditional Chinese Medicine, University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic; 2Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic; 3Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic; 4Personal Social Services Research Unit, Department of Health Policy, London School of Economics and Political Science, London, UK; 5Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China Background: Acupuncture has become a viable option for migraine prophylaxis in Europe; however, despite its wide use, more data on the short- and long-term cost-effectiveness are needed when considering the perspectives of a paying third-party, the patient, and of society in general. The aim was to evaluate the cost and effectiveness of adjuvant acupuncture to pharmacologic treatment vs pharmacologic treatment alone in migraine patients after a 3-month acupuncture course and a 6-month follow-up from all perspectives.Methods: The study involved an open-label randomized clinical trial of patients receiving acupuncture (n=42), and a waiting list control group (n=44). The number of migraine days during the last 28 days, as well as direct and indirect costs were considered. The trial was registered under DRKS00009803.Results: The total cost per patient reached €696 vs €285 after 3 months of acupuncture and €66 vs €132 in the acupuncture and control groups after a 6-month follow-up, respectively (P=0.071). The trends observed in effectiveness and costs from all perspectives are discussed.Conclusion: The inclusion of acupuncture in health care results beneficial mainly for its observed trend in reduced losses of productivity and income, with the latter often exceeding the costs of acupuncture treatment. As such, acupuncture may be recommended as an adjuvant treatment in migraine prophylaxis to standard pharmacotherapy. Keywords: acupuncture, cost, effectiveness, migraine, prophylaxis, Traditional Chinese Medicine

Background Patients with migraine often also suffer from gastrointestinal disorders such as irritable bowel syndrome, inflammatory bowel disease or celiac disease. All these diseases share increased intestinal permeability ("leaky gut") and thus increased inflammatory activity. There is an increase in proinflammatoric cytokines in the serum, which in turn can trigger migraine attacks. Probiotics can have a positive effect on the intestinal epithelium and reduce inflammatory activity. A first uncontrolled, small study of 39 migraineurs showed a decrease in the rate of attacks under the daily intake of a probiotic. Method In an uncontrolled observational study, the influence of a specially formulated multispecies probiotic on the frequency of migraine attacks and the intensity of migraine-associated complaints was recorded. The self-assessment of 1,020 patients was evaluated. Results Over the treatment period of 8 weeks, the number of headache days was reduced from 2 to 1.4 days per week. The headache intensity decreased from 5.1 to 2.1 points (0 = not present to 6 = very intensive). The migraine-associated complaints were reduced and the use of painkillers halved. All results were statistically significant (p ≤ 0.001). Conclusion It can be suggested that this multispecies probiotic formulation has a positive influence on intensity and frequency of migraine attacks. However, randomized, placebo-controlled trials are required for further confirmation.