Headache & Migraine

Key clinical point: Increased dietary niacin intake may have a beneficial effect on migraine outcomes in adults with inadequate niacin consumption and the effect seems to peak in patients with adequate niacin intake, with the threshold level being approximately 21.0 mg/day.

Major finding: The risk for migraine was lower among adults in the higher (18.4-26.2 mg/day: odds ratio [OR] 0.78; P  =  .004, and ≥26.3 mg/day: OR 0.74; P  =  .006) vs lower (≤12.3 mg/day) quartile of daily niacin intake, with the risk of developing migraine reducing by 2.5% with every 1 mg increase in daily dietary niacin consumption (OR 0.975; P  =  .011) in those with dietary niacin intake of <21 mg/day, but no such association was observed in those with dietary niacin intake of ≥21 mg/day.

Study details: This was a cross-sectional study including 10,246 participants aged ≥20 years, of whom 20.1% experienced migraine.

Disclosures: This study was supported by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Liu H et al. Association between dietary niacin intake and migraine among american adults: National Health and Nutrition Examination Survey. Nutrients. 2022;14(15):3052 (Jul 25). Doi: 10.3390/nu14153052

Key clinical point: Increased dietary niacin intake may have a beneficial effect on migraine outcomes in adults with inadequate niacin consumption and the effect seems to peak in patients with adequate niacin intake, with the threshold level being approximately 21.0 mg/day.

Major finding: The risk for migraine was lower among adults in the higher (18.4-26.2 mg/day: odds ratio [OR] 0.78; P  =  .004, and ≥26.3 mg/day: OR 0.74; P  =  .006) vs lower (≤12.3 mg/day) quartile of daily niacin intake, with the risk of developing migraine reducing by 2.5% with every 1 mg increase in daily dietary niacin consumption (OR 0.975; P  =  .011) in those with dietary niacin intake of <21 mg/day, but no such association was observed in those with dietary niacin intake of ≥21 mg/day.

Study details: This was a cross-sectional study including 10,246 participants aged ≥20 years, of whom 20.1% experienced migraine.

Disclosures: This study was supported by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Liu H et al. Association between dietary niacin intake and migraine among american adults: National Health and Nutrition Examination Survey. Nutrients. 2022;14(15):3052 (Jul 25). Doi: 10.3390/nu14153052

Key clinical point: Increased dietary niacin intake may have a beneficial effect on migraine outcomes in adults with inadequate niacin consumption and the effect seems to peak in patients with adequate niacin intake, with the threshold level being approximately 21.0 mg/day.

Major finding: The risk for migraine was lower among adults in the higher (18.4-26.2 mg/day: odds ratio [OR] 0.78; P  =  .004, and ≥26.3 mg/day: OR 0.74; P  =  .006) vs lower (≤12.3 mg/day) quartile of daily niacin intake, with the risk of developing migraine reducing by 2.5% with every 1 mg increase in daily dietary niacin consumption (OR 0.975; P  =  .011) in those with dietary niacin intake of <21 mg/day, but no such association was observed in those with dietary niacin intake of ≥21 mg/day.

Study details: This was a cross-sectional study including 10,246 participants aged ≥20 years, of whom 20.1% experienced migraine.

Disclosures: This study was supported by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Liu H et al. Association between dietary niacin intake and migraine among american adults: National Health and Nutrition Examination Survey. Nutrients. 2022;14(15):3052 (Jul 25). Doi: 10.3390/nu14153052

Key clinical point: Soy isoflavones significantly reduced the frequency and duration of migraine attacks, clinical indices, and calcitonin gene-related peptide (CGRP) levels and improved the quality of life in women with migraine.

Major finding: At 8 weeks, soy isoflavones vs placebo significantly reduced migraine frequency (mean change [MC] −2.36 vs −0.43; P < .001) and duration of attacks (MC −2.50 vs −0.02; P < .001), Migraine Headache Index score (MC −10.46 vs −1.47; P < .001), and CGRP levels (MC −12.18 vs −8.62 ng/L; P  =  .002) and significantly improved migraine-specific quality-of-life score (MC 16.76 vs 2.52; P < .001). No adverse effects were reported.

Study details: Findings are from a phase 3 trial including 88 adult women with migraine who had not reached menopausal/perimenopausal age and were randomly assigned to receive 50 mg/day soy isoflavones or placebo supplementation for 8 weeks.

Disclosures: This study was supported by Isfahan University of Medical Sciences, Iran. The authors declared no conflicts of interest.

Source: Babapour M et al. Effect of soy isoflavones supplementation on migraine characteristics, mental status and calcitonin gene-related peptide (CGRP) levels in women with migraine: results of randomised controlled trial. Nutr J. 2022;21:50 (Jul 30). Doi: 10.1186/s12937-022-00802-z

Key clinical point: Soy isoflavones significantly reduced the frequency and duration of migraine attacks, clinical indices, and calcitonin gene-related peptide (CGRP) levels and improved the quality of life in women with migraine.

Major finding: At 8 weeks, soy isoflavones vs placebo significantly reduced migraine frequency (mean change [MC] −2.36 vs −0.43; P < .001) and duration of attacks (MC −2.50 vs −0.02; P < .001), Migraine Headache Index score (MC −10.46 vs −1.47; P < .001), and CGRP levels (MC −12.18 vs −8.62 ng/L; P  =  .002) and significantly improved migraine-specific quality-of-life score (MC 16.76 vs 2.52; P < .001). No adverse effects were reported.

Study details: Findings are from a phase 3 trial including 88 adult women with migraine who had not reached menopausal/perimenopausal age and were randomly assigned to receive 50 mg/day soy isoflavones or placebo supplementation for 8 weeks.

Disclosures: This study was supported by Isfahan University of Medical Sciences, Iran. The authors declared no conflicts of interest.

Source: Babapour M et al. Effect of soy isoflavones supplementation on migraine characteristics, mental status and calcitonin gene-related peptide (CGRP) levels in women with migraine: results of randomised controlled trial. Nutr J. 2022;21:50 (Jul 30). Doi: 10.1186/s12937-022-00802-z

Key clinical point: Soy isoflavones significantly reduced the frequency and duration of migraine attacks, clinical indices, and calcitonin gene-related peptide (CGRP) levels and improved the quality of life in women with migraine.

Major finding: At 8 weeks, soy isoflavones vs placebo significantly reduced migraine frequency (mean change [MC] −2.36 vs −0.43; P < .001) and duration of attacks (MC −2.50 vs −0.02; P < .001), Migraine Headache Index score (MC −10.46 vs −1.47; P < .001), and CGRP levels (MC −12.18 vs −8.62 ng/L; P  =  .002) and significantly improved migraine-specific quality-of-life score (MC 16.76 vs 2.52; P < .001). No adverse effects were reported.

Study details: Findings are from a phase 3 trial including 88 adult women with migraine who had not reached menopausal/perimenopausal age and were randomly assigned to receive 50 mg/day soy isoflavones or placebo supplementation for 8 weeks.

Disclosures: This study was supported by Isfahan University of Medical Sciences, Iran. The authors declared no conflicts of interest.

Source: Babapour M et al. Effect of soy isoflavones supplementation on migraine characteristics, mental status and calcitonin gene-related peptide (CGRP) levels in women with migraine: results of randomised controlled trial. Nutr J. 2022;21:50 (Jul 30). Doi: 10.1186/s12937-022-00802-z

Key clinical point: Patients with diabetes who were screened for diabetic retinopathy (DR) had a lower risk of having migraine; however, DR was not a protective marker of incident migraine.

Major finding: The prevalence of migraine was 17% lower in patients with vs without diabetes (odds ratio [OR] 0.83; 95% CI 0.81-0.85), with the risk being lower in patients with vs without DR (OR 0.69; 95% CI 0.65-0.72). The risk of developing migraine was significantly lower in patients with diabetes and DR level ranging between 1 and 4 compared with matched individuals without diabetes (hazard ratio [HR] 0.66; 95% CI 0.55-0.80), but the risk was independent of the presence of DR.

Study details: The data come from a cross-sectional study including patients with diabetes who attended DR screening (n = 205,970) and age- and sex-matched patients without diabetes (n = 1,003,170).

Disclosures: This study was funded by the The Velux Foundation, Denmark. The authors declared no competing interests.

Source: Vergmann AS et al. Investigation of the correlation between diabetic retinopathy and prevalent and incident migraine in a national cohort study. Sci Rep. 2022;12:12443 (Jul 20). Doi: 10.1038/s41598-022-16793-0

Key clinical point: Patients with diabetes who were screened for diabetic retinopathy (DR) had a lower risk of having migraine; however, DR was not a protective marker of incident migraine.

Major finding: The prevalence of migraine was 17% lower in patients with vs without diabetes (odds ratio [OR] 0.83; 95% CI 0.81-0.85), with the risk being lower in patients with vs without DR (OR 0.69; 95% CI 0.65-0.72). The risk of developing migraine was significantly lower in patients with diabetes and DR level ranging between 1 and 4 compared with matched individuals without diabetes (hazard ratio [HR] 0.66; 95% CI 0.55-0.80), but the risk was independent of the presence of DR.

Study details: The data come from a cross-sectional study including patients with diabetes who attended DR screening (n = 205,970) and age- and sex-matched patients without diabetes (n = 1,003,170).

Disclosures: This study was funded by the The Velux Foundation, Denmark. The authors declared no competing interests.

Source: Vergmann AS et al. Investigation of the correlation between diabetic retinopathy and prevalent and incident migraine in a national cohort study. Sci Rep. 2022;12:12443 (Jul 20). Doi: 10.1038/s41598-022-16793-0

Key clinical point: Patients with diabetes who were screened for diabetic retinopathy (DR) had a lower risk of having migraine; however, DR was not a protective marker of incident migraine.

Major finding: The prevalence of migraine was 17% lower in patients with vs without diabetes (odds ratio [OR] 0.83; 95% CI 0.81-0.85), with the risk being lower in patients with vs without DR (OR 0.69; 95% CI 0.65-0.72). The risk of developing migraine was significantly lower in patients with diabetes and DR level ranging between 1 and 4 compared with matched individuals without diabetes (hazard ratio [HR] 0.66; 95% CI 0.55-0.80), but the risk was independent of the presence of DR.

Study details: The data come from a cross-sectional study including patients with diabetes who attended DR screening (n = 205,970) and age- and sex-matched patients without diabetes (n = 1,003,170).

Disclosures: This study was funded by the The Velux Foundation, Denmark. The authors declared no competing interests.

Source: Vergmann AS et al. Investigation of the correlation between diabetic retinopathy and prevalent and incident migraine in a national cohort study. Sci Rep. 2022;12:12443 (Jul 20). Doi: 10.1038/s41598-022-16793-0

Key clinical point: Bariatric surgery significantly reduced the frequency of migraine attacks, headache severity, and improved the quality of life and disability in patients with chronic migraine and severe obesity.

Major finding: After a mean period of 7.5 ± 2.3 months, there was a significant reduction in the number of migraine attacks (20.9 to 8.3 days; P < .001), headache severity score (7.7 to 4.8; P < .001), Migraine-Specific Quality-of-Life score (44.6 to 26.8; P < .001), and Migraine Disability Assessment Scale score (64.4 to 25.5; P < .001) in patients with chronic migraine who underwent bariatric surgery.

Study details: Findings are from a prospective study including 60 patients with chronic migraine and severe obesity who were referred for bariatric surgery.

Disclosures: This study was supported by Isfahan University of Medical Sciences, Iran, and others. The authors declared no conflicts of interest.

Source: Etefagh HH et al. Bariatric surgery in migraine patients: CGRP level and weight loss. Obes Surg. 2022 (Aug 3). Doi: 10.1007/s11695-022-06218-2

Key clinical point: Bariatric surgery significantly reduced the frequency of migraine attacks, headache severity, and improved the quality of life and disability in patients with chronic migraine and severe obesity.

Major finding: After a mean period of 7.5 ± 2.3 months, there was a significant reduction in the number of migraine attacks (20.9 to 8.3 days; P < .001), headache severity score (7.7 to 4.8; P < .001), Migraine-Specific Quality-of-Life score (44.6 to 26.8; P < .001), and Migraine Disability Assessment Scale score (64.4 to 25.5; P < .001) in patients with chronic migraine who underwent bariatric surgery.

Study details: Findings are from a prospective study including 60 patients with chronic migraine and severe obesity who were referred for bariatric surgery.

Disclosures: This study was supported by Isfahan University of Medical Sciences, Iran, and others. The authors declared no conflicts of interest.

Source: Etefagh HH et al. Bariatric surgery in migraine patients: CGRP level and weight loss. Obes Surg. 2022 (Aug 3). Doi: 10.1007/s11695-022-06218-2

Key clinical point: Bariatric surgery significantly reduced the frequency of migraine attacks, headache severity, and improved the quality of life and disability in patients with chronic migraine and severe obesity.

Major finding: After a mean period of 7.5 ± 2.3 months, there was a significant reduction in the number of migraine attacks (20.9 to 8.3 days; P < .001), headache severity score (7.7 to 4.8; P < .001), Migraine-Specific Quality-of-Life score (44.6 to 26.8; P < .001), and Migraine Disability Assessment Scale score (64.4 to 25.5; P < .001) in patients with chronic migraine who underwent bariatric surgery.

Study details: Findings are from a prospective study including 60 patients with chronic migraine and severe obesity who were referred for bariatric surgery.

Disclosures: This study was supported by Isfahan University of Medical Sciences, Iran, and others. The authors declared no conflicts of interest.

Source: Etefagh HH et al. Bariatric surgery in migraine patients: CGRP level and weight loss. Obes Surg. 2022 (Aug 3). Doi: 10.1007/s11695-022-06218-2

Key clinical point: Once-monthly 120 mg galcanezumab was more effective than placebo in reducing total pain burden (TPB) in patients with chronic or episodic migraine who previously did not benefit from 2-4 categories of migraine preventive medication.

Major finding: At 3 months, galcanezumab vs placebo led to a significantly higher overall percentage change in TPB in patients with chronic (mean difference [MD] −40.4%; P < .001) or episodic (MD −53.1%; P < .001) migraine and significant reductions in monthly number, duration, and severity of migraine headache days in the overall population (all P < .001).

Study details: Findings are from a post hoc analysis of a phase 3 trial, CONQUER, including 458 patients with chronic or episodic migraine who previously did not benefit from 2-4 categories of migraine preventive medication and were randomly assigned to receive galcanezumab or placebo.

Disclosures: This study was sponsored by Eli Lilly and Company. Four authors declared being current or former employees or stockholders of Eli Lilly. J Ailani reported ties with various sources, including Eli Lilly and Company.

Source: Ailani J et al. Effect of galcanezumab on total pain burden in patients who had previously not benefited from migraine preventive medication (CONQUER Trial): A post hoc analysis. Adv Ther. 2022 (Aug 5). Doi: 10.1007/s12325-022-02233-y

Key clinical point: Once-monthly 120 mg galcanezumab was more effective than placebo in reducing total pain burden (TPB) in patients with chronic or episodic migraine who previously did not benefit from 2-4 categories of migraine preventive medication.

Major finding: At 3 months, galcanezumab vs placebo led to a significantly higher overall percentage change in TPB in patients with chronic (mean difference [MD] −40.4%; P < .001) or episodic (MD −53.1%; P < .001) migraine and significant reductions in monthly number, duration, and severity of migraine headache days in the overall population (all P < .001).

Study details: Findings are from a post hoc analysis of a phase 3 trial, CONQUER, including 458 patients with chronic or episodic migraine who previously did not benefit from 2-4 categories of migraine preventive medication and were randomly assigned to receive galcanezumab or placebo.

Disclosures: This study was sponsored by Eli Lilly and Company. Four authors declared being current or former employees or stockholders of Eli Lilly. J Ailani reported ties with various sources, including Eli Lilly and Company.

Source: Ailani J et al. Effect of galcanezumab on total pain burden in patients who had previously not benefited from migraine preventive medication (CONQUER Trial): A post hoc analysis. Adv Ther. 2022 (Aug 5). Doi: 10.1007/s12325-022-02233-y

Key clinical point: Once-monthly 120 mg galcanezumab was more effective than placebo in reducing total pain burden (TPB) in patients with chronic or episodic migraine who previously did not benefit from 2-4 categories of migraine preventive medication.

Major finding: At 3 months, galcanezumab vs placebo led to a significantly higher overall percentage change in TPB in patients with chronic (mean difference [MD] −40.4%; P < .001) or episodic (MD −53.1%; P < .001) migraine and significant reductions in monthly number, duration, and severity of migraine headache days in the overall population (all P < .001).

Study details: Findings are from a post hoc analysis of a phase 3 trial, CONQUER, including 458 patients with chronic or episodic migraine who previously did not benefit from 2-4 categories of migraine preventive medication and were randomly assigned to receive galcanezumab or placebo.

Disclosures: This study was sponsored by Eli Lilly and Company. Four authors declared being current or former employees or stockholders of Eli Lilly. J Ailani reported ties with various sources, including Eli Lilly and Company.

Source: Ailani J et al. Effect of galcanezumab on total pain burden in patients who had previously not benefited from migraine preventive medication (CONQUER Trial): A post hoc analysis. Adv Ther. 2022 (Aug 5). Doi: 10.1007/s12325-022-02233-y

Key clinical point: A dose of 120 mg galcanezumab monthly was effective and well tolerated in patients with episodic migraine.

Major finding: The reduction in mean monthly migraine headache days (MMHD) over 3 months was significantly higher with galcanezumab vs placebo (least squares mean change −3.81 vs −1.99 days; P < .0001), with a higher proportion of patients receiving galcanezumab vs placebo achieving ≥50%, ≥75%, and 100% reductions in MMHD (all P < .0001). The occurrence of serious adverse events was low, with none leading to treatment discontinuation.

Study details: Findings are from the phase 3, PERSIST trial including 520 patients with episodic migraine who were randomly assigned to receive monthly 120 mg galcanezumab or placebo.

Disclosures: This study was funded by Eli Lilly and Company. J Zhuang reported being a full-time employee, and 8 authors reported receiving clinical research fees from Eli Lilly. S Yu reported serving as an associate editor for the Journal of Headache and Pain.

Source: Hu B et al. Galcanezumab in episodic migraine: The phase 3, randomized, double-blind, placebo-controlled PERSIST study. J Headache Pain. 2022;23:90 (Jul 28). Doi: 10.1186/s10194-022-01458-0

Key clinical point: A dose of 120 mg galcanezumab monthly was effective and well tolerated in patients with episodic migraine.

Major finding: The reduction in mean monthly migraine headache days (MMHD) over 3 months was significantly higher with galcanezumab vs placebo (least squares mean change −3.81 vs −1.99 days; P < .0001), with a higher proportion of patients receiving galcanezumab vs placebo achieving ≥50%, ≥75%, and 100% reductions in MMHD (all P < .0001). The occurrence of serious adverse events was low, with none leading to treatment discontinuation.

Study details: Findings are from the phase 3, PERSIST trial including 520 patients with episodic migraine who were randomly assigned to receive monthly 120 mg galcanezumab or placebo.

Disclosures: This study was funded by Eli Lilly and Company. J Zhuang reported being a full-time employee, and 8 authors reported receiving clinical research fees from Eli Lilly. S Yu reported serving as an associate editor for the Journal of Headache and Pain.

Source: Hu B et al. Galcanezumab in episodic migraine: The phase 3, randomized, double-blind, placebo-controlled PERSIST study. J Headache Pain. 2022;23:90 (Jul 28). Doi: 10.1186/s10194-022-01458-0

Key clinical point: A dose of 120 mg galcanezumab monthly was effective and well tolerated in patients with episodic migraine.

Major finding: The reduction in mean monthly migraine headache days (MMHD) over 3 months was significantly higher with galcanezumab vs placebo (least squares mean change −3.81 vs −1.99 days; P < .0001), with a higher proportion of patients receiving galcanezumab vs placebo achieving ≥50%, ≥75%, and 100% reductions in MMHD (all P < .0001). The occurrence of serious adverse events was low, with none leading to treatment discontinuation.

Study details: Findings are from the phase 3, PERSIST trial including 520 patients with episodic migraine who were randomly assigned to receive monthly 120 mg galcanezumab or placebo.

Disclosures: This study was funded by Eli Lilly and Company. J Zhuang reported being a full-time employee, and 8 authors reported receiving clinical research fees from Eli Lilly. S Yu reported serving as an associate editor for the Journal of Headache and Pain.

Source: Hu B et al. Galcanezumab in episodic migraine: The phase 3, randomized, double-blind, placebo-controlled PERSIST study. J Headache Pain. 2022;23:90 (Jul 28). Doi: 10.1186/s10194-022-01458-0

Migraine is a unique neurologic condition, in that a person can't prove they have it and there are few objective tools neurologists have to guide their diagnostic process. The recognition of the role of the vasoactive peptide calcitonin gene-related peptide (CGRP) in the 1990s changed the way many researchers and clinicians conceptualized migraine. Subsequent studies have used CGRP as a human model for migraine, and most recently pituitary adenylate cyclase–activating polypeptide 38 (PACAP-38) has also been recognized for its important role in migraine propagation. All of the existing data have been in adults, and no studies until now have specifically investigated the presence of these peptides in children with migraine.

Pediatric migraine is unique in a number of ways. Children with migraine present less unilaterally, the duration of their attacks is typically shorter, and the associated symptoms can often be more prominent than the headache pain during an attack. There are unique pediatric migraine subtypes that are exceptionally rare in adults, such as periodic paralysis attacks and abdominal migraine. For this reason, it is not entirely clear whether the same biomarkers of disease in adults would also be present in the pediatric population.

In the study by Liu and colleagues, the investigators enrolled 76 pediatric patients with migraine (the diagnosis was confirmed by at least two neurologists). Patients were excluded if there was any analgesic medication use over the past 2 months; if there was concern for secondary headache; or any underlying mood disorders, congenital disease, or other major medical conditions. An additional 77 controls were matched for age and sex. Blood was collected from all participants after an 8-hour fast to avoid collecting after potentially ingesting a food trigger. Blood samples were obtained during an ictal period (within 8 hours of a migraine attack) as well as interictally (not taken if the participant had a migraine attack within the past 24 hours).

The plasma CGRP and PACAP-38 levels were significantly higher in pediatric patients with migraine than in those without a migraine history, in both the ictal state and the interictal state. Among patients with migraine, there was a nonsignificant trend toward a higher CGRP level in the ictal phase, and no difference in these phases with PACAP-38. There was no difference in the CGRP or PACAP-38 levels between participants with and those without aura. When different aura groups were compared (with the participants separated on the basis of a history of motor vs vision vs sensory aura), no difference was seen among the different aura groups. Binary logistic regression testing and analysis of variance also showed that CGRP and PACAP-38 are independent risk factors for pediatric migraine, and specific levels of each were associated with an 11 and a 13 times increased risk, respectively.

Biomarker testing is still not clinically performed for migraine either in adults or children. This is primarily due to cost and the fact that most commercially available laboratories do not currently offer these tests. The results above do shed additional light on migraine pathogenesis and indicate that the phenotypic differences seen in pediatric migraine are less likely related to differences in brain function in children.

Levetiracetam is a commonly used antiepileptic medication. Prior studies have investigated the use of this medication for migraine, both acutely and preventively. Other antiepileptic medications have been shown to be very effective for both of these indications. Topiramate and valproic acid are both commonly used for migraine: topiramate primarily preventively and valproic acid both for prevention and, commonly in its intravenous form, for acute treatment. Levetiracetam is currently not commonly used for migraine, although some institutions will use the intravenous formulation for severe refractory status migrainosus.

Evers and colleagues investigated the open label use of levetiracetam for migraine prevention at a dose of 1000 mg twice daily in a small population of 50 persons. The study participants were started at a dose of 500 mg twice daily for 4 weeks, then increased to 1000 mg twice daily for a total of 12 weeks. The primary endpoint was migraine attack frequency during the last 4 weeks of treatment.

A 50% reduction in headache frequency was seen in 46% of the enrolled participants. The most common reported side effects were sedation, nausea, and weight gain, as well as cognitive change (five patients dropped out of the study owing to intolerance of the treatment). A post hoc comparison between the patients with and without response to levetiracetam revealed that those who responded were those with a less refractory history — they had tried fewer medications and were using fewer acute medications as well.

The antiepileptic class of preventive migraine medications is notorious for issues with tolerance. Among the antiepileptic medications, levetiracetam is commonly used but also commonly stopped owing to mood and cognitive complaints. Although the researchers here do show early evidence for a moderate amount of efficacy for treating migraine, the fact that there are now more migraine-specific preventive medications that are better tolerated and overall more efficacious make choosing levetiracetam for prevention less necessary.

Now that there are multiple classes of migraine-specific acute medications, the outstanding question remains: What are the potential benefits and drawbacks for the use of triptans compared with the oral CGRP receptor antagonists (gepants)? Most obviously, triptan medications are contraindicated in patients with significant vascular risk factors; however, what is not known is whether some of the other adverse events associated with triptans are more or less prominent with gepant use. Lee and colleagues conducted a meta-analysis of 15 studies to review this data.

A previous meta-analysis demonstrated that oral CGRP receptor antagonists are more effective than placebo, but less effective than triptans against acute migraine. The most common intolerances for gepants are nausea, somnolence, and dry mouth, but the safety and tolerability of gepants have not been compared with that of triptans. These authors pooled the data on five gepant medications (BI44370TA, MK-3207, rimegepant, telcagepant, and ubrogepant). The primary outcome was incidence of treatment-related adverse events and the secondary outcome was the incidence of the specific intolerances of diarrhea, dizziness, dry mouth, fatigue, nausea, paresthesia, somnolence, upper abdominal pain, and vomiting.

Compared with placebo, the relative risk for any adverse event was found to be low, at 1.15, and the relative risk for treatment-related adverse events was only slightly higher, at 1.18. Gepants were found to be significantly more associated with an increased risk for fatigue, nausea, and somnolence vs placebo. Compared with triptans, the CGRP antagonists were associated with significantly less treatment-related adverse events as well as any adverse event. There was no significant difference in the incidence of diarrhea, nausea, and vomiting between the two groups.

This study helps elucidate some of the differences between the two classes of migraine-specific acute medications. As noted above, a prior meta-analysis did reveal some benefits with the triptan class, specifically better effectiveness. When choosing a better-tolerated medication for your patients, you may want to consider a gepant; when considering a stronger or more potent option, you might stick with a triptan.

Migraine is a unique neurologic condition, in that a person can't prove they have it and there are few objective tools neurologists have to guide their diagnostic process. The recognition of the role of the vasoactive peptide calcitonin gene-related peptide (CGRP) in the 1990s changed the way many researchers and clinicians conceptualized migraine. Subsequent studies have used CGRP as a human model for migraine, and most recently pituitary adenylate cyclase–activating polypeptide 38 (PACAP-38) has also been recognized for its important role in migraine propagation. All of the existing data have been in adults, and no studies until now have specifically investigated the presence of these peptides in children with migraine.

Pediatric migraine is unique in a number of ways. Children with migraine present less unilaterally, the duration of their attacks is typically shorter, and the associated symptoms can often be more prominent than the headache pain during an attack. There are unique pediatric migraine subtypes that are exceptionally rare in adults, such as periodic paralysis attacks and abdominal migraine. For this reason, it is not entirely clear whether the same biomarkers of disease in adults would also be present in the pediatric population.

In the study by Liu and colleagues, the investigators enrolled 76 pediatric patients with migraine (the diagnosis was confirmed by at least two neurologists). Patients were excluded if there was any analgesic medication use over the past 2 months; if there was concern for secondary headache; or any underlying mood disorders, congenital disease, or other major medical conditions. An additional 77 controls were matched for age and sex. Blood was collected from all participants after an 8-hour fast to avoid collecting after potentially ingesting a food trigger. Blood samples were obtained during an ictal period (within 8 hours of a migraine attack) as well as interictally (not taken if the participant had a migraine attack within the past 24 hours).

The plasma CGRP and PACAP-38 levels were significantly higher in pediatric patients with migraine than in those without a migraine history, in both the ictal state and the interictal state. Among patients with migraine, there was a nonsignificant trend toward a higher CGRP level in the ictal phase, and no difference in these phases with PACAP-38. There was no difference in the CGRP or PACAP-38 levels between participants with and those without aura. When different aura groups were compared (with the participants separated on the basis of a history of motor vs vision vs sensory aura), no difference was seen among the different aura groups. Binary logistic regression testing and analysis of variance also showed that CGRP and PACAP-38 are independent risk factors for pediatric migraine, and specific levels of each were associated with an 11 and a 13 times increased risk, respectively.

Biomarker testing is still not clinically performed for migraine either in adults or children. This is primarily due to cost and the fact that most commercially available laboratories do not currently offer these tests. The results above do shed additional light on migraine pathogenesis and indicate that the phenotypic differences seen in pediatric migraine are less likely related to differences in brain function in children.

Levetiracetam is a commonly used antiepileptic medication. Prior studies have investigated the use of this medication for migraine, both acutely and preventively. Other antiepileptic medications have been shown to be very effective for both of these indications. Topiramate and valproic acid are both commonly used for migraine: topiramate primarily preventively and valproic acid both for prevention and, commonly in its intravenous form, for acute treatment. Levetiracetam is currently not commonly used for migraine, although some institutions will use the intravenous formulation for severe refractory status migrainosus.

Evers and colleagues investigated the open label use of levetiracetam for migraine prevention at a dose of 1000 mg twice daily in a small population of 50 persons. The study participants were started at a dose of 500 mg twice daily for 4 weeks, then increased to 1000 mg twice daily for a total of 12 weeks. The primary endpoint was migraine attack frequency during the last 4 weeks of treatment.

A 50% reduction in headache frequency was seen in 46% of the enrolled participants. The most common reported side effects were sedation, nausea, and weight gain, as well as cognitive change (five patients dropped out of the study owing to intolerance of the treatment). A post hoc comparison between the patients with and without response to levetiracetam revealed that those who responded were those with a less refractory history — they had tried fewer medications and were using fewer acute medications as well.

The antiepileptic class of preventive migraine medications is notorious for issues with tolerance. Among the antiepileptic medications, levetiracetam is commonly used but also commonly stopped owing to mood and cognitive complaints. Although the researchers here do show early evidence for a moderate amount of efficacy for treating migraine, the fact that there are now more migraine-specific preventive medications that are better tolerated and overall more efficacious make choosing levetiracetam for prevention less necessary.

Now that there are multiple classes of migraine-specific acute medications, the outstanding question remains: What are the potential benefits and drawbacks for the use of triptans compared with the oral CGRP receptor antagonists (gepants)? Most obviously, triptan medications are contraindicated in patients with significant vascular risk factors; however, what is not known is whether some of the other adverse events associated with triptans are more or less prominent with gepant use. Lee and colleagues conducted a meta-analysis of 15 studies to review this data.

A previous meta-analysis demonstrated that oral CGRP receptor antagonists are more effective than placebo, but less effective than triptans against acute migraine. The most common intolerances for gepants are nausea, somnolence, and dry mouth, but the safety and tolerability of gepants have not been compared with that of triptans. These authors pooled the data on five gepant medications (BI44370TA, MK-3207, rimegepant, telcagepant, and ubrogepant). The primary outcome was incidence of treatment-related adverse events and the secondary outcome was the incidence of the specific intolerances of diarrhea, dizziness, dry mouth, fatigue, nausea, paresthesia, somnolence, upper abdominal pain, and vomiting.

Compared with placebo, the relative risk for any adverse event was found to be low, at 1.15, and the relative risk for treatment-related adverse events was only slightly higher, at 1.18. Gepants were found to be significantly more associated with an increased risk for fatigue, nausea, and somnolence vs placebo. Compared with triptans, the CGRP antagonists were associated with significantly less treatment-related adverse events as well as any adverse event. There was no significant difference in the incidence of diarrhea, nausea, and vomiting between the two groups.

This study helps elucidate some of the differences between the two classes of migraine-specific acute medications. As noted above, a prior meta-analysis did reveal some benefits with the triptan class, specifically better effectiveness. When choosing a better-tolerated medication for your patients, you may want to consider a gepant; when considering a stronger or more potent option, you might stick with a triptan.

Migraine is a unique neurologic condition, in that a person can't prove they have it and there are few objective tools neurologists have to guide their diagnostic process. The recognition of the role of the vasoactive peptide calcitonin gene-related peptide (CGRP) in the 1990s changed the way many researchers and clinicians conceptualized migraine. Subsequent studies have used CGRP as a human model for migraine, and most recently pituitary adenylate cyclase–activating polypeptide 38 (PACAP-38) has also been recognized for its important role in migraine propagation. All of the existing data have been in adults, and no studies until now have specifically investigated the presence of these peptides in children with migraine.

Pediatric migraine is unique in a number of ways. Children with migraine present less unilaterally, the duration of their attacks is typically shorter, and the associated symptoms can often be more prominent than the headache pain during an attack. There are unique pediatric migraine subtypes that are exceptionally rare in adults, such as periodic paralysis attacks and abdominal migraine. For this reason, it is not entirely clear whether the same biomarkers of disease in adults would also be present in the pediatric population.

In the study by Liu and colleagues, the investigators enrolled 76 pediatric patients with migraine (the diagnosis was confirmed by at least two neurologists). Patients were excluded if there was any analgesic medication use over the past 2 months; if there was concern for secondary headache; or any underlying mood disorders, congenital disease, or other major medical conditions. An additional 77 controls were matched for age and sex. Blood was collected from all participants after an 8-hour fast to avoid collecting after potentially ingesting a food trigger. Blood samples were obtained during an ictal period (within 8 hours of a migraine attack) as well as interictally (not taken if the participant had a migraine attack within the past 24 hours).

The plasma CGRP and PACAP-38 levels were significantly higher in pediatric patients with migraine than in those without a migraine history, in both the ictal state and the interictal state. Among patients with migraine, there was a nonsignificant trend toward a higher CGRP level in the ictal phase, and no difference in these phases with PACAP-38. There was no difference in the CGRP or PACAP-38 levels between participants with and those without aura. When different aura groups were compared (with the participants separated on the basis of a history of motor vs vision vs sensory aura), no difference was seen among the different aura groups. Binary logistic regression testing and analysis of variance also showed that CGRP and PACAP-38 are independent risk factors for pediatric migraine, and specific levels of each were associated with an 11 and a 13 times increased risk, respectively.

Biomarker testing is still not clinically performed for migraine either in adults or children. This is primarily due to cost and the fact that most commercially available laboratories do not currently offer these tests. The results above do shed additional light on migraine pathogenesis and indicate that the phenotypic differences seen in pediatric migraine are less likely related to differences in brain function in children.

Levetiracetam is a commonly used antiepileptic medication. Prior studies have investigated the use of this medication for migraine, both acutely and preventively. Other antiepileptic medications have been shown to be very effective for both of these indications. Topiramate and valproic acid are both commonly used for migraine: topiramate primarily preventively and valproic acid both for prevention and, commonly in its intravenous form, for acute treatment. Levetiracetam is currently not commonly used for migraine, although some institutions will use the intravenous formulation for severe refractory status migrainosus.

Evers and colleagues investigated the open label use of levetiracetam for migraine prevention at a dose of 1000 mg twice daily in a small population of 50 persons. The study participants were started at a dose of 500 mg twice daily for 4 weeks, then increased to 1000 mg twice daily for a total of 12 weeks. The primary endpoint was migraine attack frequency during the last 4 weeks of treatment.

A 50% reduction in headache frequency was seen in 46% of the enrolled participants. The most common reported side effects were sedation, nausea, and weight gain, as well as cognitive change (five patients dropped out of the study owing to intolerance of the treatment). A post hoc comparison between the patients with and without response to levetiracetam revealed that those who responded were those with a less refractory history — they had tried fewer medications and were using fewer acute medications as well.

The antiepileptic class of preventive migraine medications is notorious for issues with tolerance. Among the antiepileptic medications, levetiracetam is commonly used but also commonly stopped owing to mood and cognitive complaints. Although the researchers here do show early evidence for a moderate amount of efficacy for treating migraine, the fact that there are now more migraine-specific preventive medications that are better tolerated and overall more efficacious make choosing levetiracetam for prevention less necessary.

Now that there are multiple classes of migraine-specific acute medications, the outstanding question remains: What are the potential benefits and drawbacks for the use of triptans compared with the oral CGRP receptor antagonists (gepants)? Most obviously, triptan medications are contraindicated in patients with significant vascular risk factors; however, what is not known is whether some of the other adverse events associated with triptans are more or less prominent with gepant use. Lee and colleagues conducted a meta-analysis of 15 studies to review this data.

A previous meta-analysis demonstrated that oral CGRP receptor antagonists are more effective than placebo, but less effective than triptans against acute migraine. The most common intolerances for gepants are nausea, somnolence, and dry mouth, but the safety and tolerability of gepants have not been compared with that of triptans. These authors pooled the data on five gepant medications (BI44370TA, MK-3207, rimegepant, telcagepant, and ubrogepant). The primary outcome was incidence of treatment-related adverse events and the secondary outcome was the incidence of the specific intolerances of diarrhea, dizziness, dry mouth, fatigue, nausea, paresthesia, somnolence, upper abdominal pain, and vomiting.

Compared with placebo, the relative risk for any adverse event was found to be low, at 1.15, and the relative risk for treatment-related adverse events was only slightly higher, at 1.18. Gepants were found to be significantly more associated with an increased risk for fatigue, nausea, and somnolence vs placebo. Compared with triptans, the CGRP antagonists were associated with significantly less treatment-related adverse events as well as any adverse event. There was no significant difference in the incidence of diarrhea, nausea, and vomiting between the two groups.

This study helps elucidate some of the differences between the two classes of migraine-specific acute medications. As noted above, a prior meta-analysis did reveal some benefits with the triptan class, specifically better effectiveness. When choosing a better-tolerated medication for your patients, you may want to consider a gepant; when considering a stronger or more potent option, you might stick with a triptan.

This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener from the faculty of medicine at the University of Duisburg-Essen in Germany.

Usually in this video series, I report on interesting scientific studies in the field of neurology published in the last month. But I have to admit, June was a lousy month for new science in neurology. Therefore, this month I’d like to take a different approach and tell you about a very interesting, old drug.

We are celebrating the 125th anniversary of aspirin. Aspirin was first synthesized in Wuppertal, Germany, a city which is only 40 km from my location, by Felix Hoffmann. Hoffmann was searching for a new drug for his father who suffered from severe joint pain, and the available drugs at that time had terrible adverse events. This prompted him to work on a new drug, which was later called aspirin acetylsalicylic acid.

Aspirin has been used very successfully to the present day as therapy for joint pain or arthritis. But as you know, it’s also effective in headaches, in particular, tension-type headache. I think it’s one of the most used drugs in the world for the treatment of acute migraine attacks.

It’s also available in some European countries in intravenous form for the treatment of severe migraine attacks or in the emergency room, and it’s as effective as subcutaneous sumatriptan. It’s also an effective migraine preventive drug in a dose of 300 mg/d.
 

Discovering aspirin’s antiplatelet activity

There was an interesting observation by a dentist in the 1930s, who noted bleeding when he extracted teeth in people who took aspirin for joint pain. When he started to ask his patients about possible bleeding complications and vascular events, he observed that people who took aspirin didn’t have coronary myocardial infarctions.

It took a long time for people to discover that aspirin is not only a pain medication but also an antiplatelet agent. The first randomized study that showed that aspirin is effective in secondary prevention after myocardial infarction was published in 1974 in The New England Journal of Medicine. In 1980, aspirin was approved by the U.S. Food and Drug Administration for the secondary prevention of stroke and in 1984 for secondary prevention after myocardial infarction.

A history of efficacy

Aspirin also has a proven role in the secondary prevention of transient ischemic attack and ischemic stroke. Given early, it reduces the risk for a recurrent vascular event by 50% and long-term, compared with placebo, by 20%.

Interestingly, the doses are different in different areas of the world. In the United States, it’s either 81 mg or 325 mg. In Europe, it’s usually 100 mg. Until a few years ago, there was no single trial which used 100 mg of aspirin, compared with placebo for the secondary prevention of stroke.

If we look at dual antiplatelet therapy, the combination of aspirin and clopidogrel was not superior to aspirin alone or clopidogrel alone for long-term prevention, but the combination of dipyridamole and aspirin and the combination of cilostazol and aspirin were superior to aspirin alone for secondary stroke prevention. Short-term, within the first 30 days, the combination of aspirin and clopidogrel and the combination of ticagrelor and aspirin is superior to monotherapy but also have an increased risk for bleeding.

People with atrial fibrillation or embolic strokes need to be anticoagulated, but the addition of aspirin to anticoagulation does not increase efficacy, it only increases the risk for bleeding.

In people above the age of 75 years who have to take aspirin, there is an increased risk for upper gastrointestinal bleeding. These patients should, in addition, receive proton pump inhibitors.

The use of aspirin for the primary prevention of vascular events was promoted for almost 50 years all over the world, but in the last 5 years, a number of randomized trials clearly showed that aspirin is not effective, compared with placebo, in the primary prevention of vascular event stroke, myocardial infarction, and vascular death. It only increases the risk for bleeding.

So it’s a clear separation. Aspirin should not be used for primary prevention of vascular events, but it should be used in basically everyone who doesn’t have contraindications for secondary prevention of vascular events and vascular death.

Ladies and gentlemen, a drug that is 125 years old is also still one of the most used and affordable drugs all around the world. It’s highly effective and has only a small risk for major bleeding complications. It’s really time to celebrate aspirin for this achievement.

Dr. Diener is professor, department of neurology, Stroke Center-Headache Center, University Duisburg-Essen (Germany). A complete list of his financial disclosures is available at the link below.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener from the faculty of medicine at the University of Duisburg-Essen in Germany.

Usually in this video series, I report on interesting scientific studies in the field of neurology published in the last month. But I have to admit, June was a lousy month for new science in neurology. Therefore, this month I’d like to take a different approach and tell you about a very interesting, old drug.

We are celebrating the 125th anniversary of aspirin. Aspirin was first synthesized in Wuppertal, Germany, a city which is only 40 km from my location, by Felix Hoffmann. Hoffmann was searching for a new drug for his father who suffered from severe joint pain, and the available drugs at that time had terrible adverse events. This prompted him to work on a new drug, which was later called aspirin acetylsalicylic acid.

Aspirin has been used very successfully to the present day as therapy for joint pain or arthritis. But as you know, it’s also effective in headaches, in particular, tension-type headache. I think it’s one of the most used drugs in the world for the treatment of acute migraine attacks.

It’s also available in some European countries in intravenous form for the treatment of severe migraine attacks or in the emergency room, and it’s as effective as subcutaneous sumatriptan. It’s also an effective migraine preventive drug in a dose of 300 mg/d.
 

Discovering aspirin’s antiplatelet activity

There was an interesting observation by a dentist in the 1930s, who noted bleeding when he extracted teeth in people who took aspirin for joint pain. When he started to ask his patients about possible bleeding complications and vascular events, he observed that people who took aspirin didn’t have coronary myocardial infarctions.

It took a long time for people to discover that aspirin is not only a pain medication but also an antiplatelet agent. The first randomized study that showed that aspirin is effective in secondary prevention after myocardial infarction was published in 1974 in The New England Journal of Medicine. In 1980, aspirin was approved by the U.S. Food and Drug Administration for the secondary prevention of stroke and in 1984 for secondary prevention after myocardial infarction.

A history of efficacy

Aspirin also has a proven role in the secondary prevention of transient ischemic attack and ischemic stroke. Given early, it reduces the risk for a recurrent vascular event by 50% and long-term, compared with placebo, by 20%.

Interestingly, the doses are different in different areas of the world. In the United States, it’s either 81 mg or 325 mg. In Europe, it’s usually 100 mg. Until a few years ago, there was no single trial which used 100 mg of aspirin, compared with placebo for the secondary prevention of stroke.

If we look at dual antiplatelet therapy, the combination of aspirin and clopidogrel was not superior to aspirin alone or clopidogrel alone for long-term prevention, but the combination of dipyridamole and aspirin and the combination of cilostazol and aspirin were superior to aspirin alone for secondary stroke prevention. Short-term, within the first 30 days, the combination of aspirin and clopidogrel and the combination of ticagrelor and aspirin is superior to monotherapy but also have an increased risk for bleeding.

People with atrial fibrillation or embolic strokes need to be anticoagulated, but the addition of aspirin to anticoagulation does not increase efficacy, it only increases the risk for bleeding.

In people above the age of 75 years who have to take aspirin, there is an increased risk for upper gastrointestinal bleeding. These patients should, in addition, receive proton pump inhibitors.

The use of aspirin for the primary prevention of vascular events was promoted for almost 50 years all over the world, but in the last 5 years, a number of randomized trials clearly showed that aspirin is not effective, compared with placebo, in the primary prevention of vascular event stroke, myocardial infarction, and vascular death. It only increases the risk for bleeding.

So it’s a clear separation. Aspirin should not be used for primary prevention of vascular events, but it should be used in basically everyone who doesn’t have contraindications for secondary prevention of vascular events and vascular death.

Ladies and gentlemen, a drug that is 125 years old is also still one of the most used and affordable drugs all around the world. It’s highly effective and has only a small risk for major bleeding complications. It’s really time to celebrate aspirin for this achievement.

Dr. Diener is professor, department of neurology, Stroke Center-Headache Center, University Duisburg-Essen (Germany). A complete list of his financial disclosures is available at the link below.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Dear colleagues, I am Christoph Diener from the faculty of medicine at the University of Duisburg-Essen in Germany.

Usually in this video series, I report on interesting scientific studies in the field of neurology published in the last month. But I have to admit, June was a lousy month for new science in neurology. Therefore, this month I’d like to take a different approach and tell you about a very interesting, old drug.

We are celebrating the 125th anniversary of aspirin. Aspirin was first synthesized in Wuppertal, Germany, a city which is only 40 km from my location, by Felix Hoffmann. Hoffmann was searching for a new drug for his father who suffered from severe joint pain, and the available drugs at that time had terrible adverse events. This prompted him to work on a new drug, which was later called aspirin acetylsalicylic acid.

Aspirin has been used very successfully to the present day as therapy for joint pain or arthritis. But as you know, it’s also effective in headaches, in particular, tension-type headache. I think it’s one of the most used drugs in the world for the treatment of acute migraine attacks.

It’s also available in some European countries in intravenous form for the treatment of severe migraine attacks or in the emergency room, and it’s as effective as subcutaneous sumatriptan. It’s also an effective migraine preventive drug in a dose of 300 mg/d.
 

Discovering aspirin’s antiplatelet activity

There was an interesting observation by a dentist in the 1930s, who noted bleeding when he extracted teeth in people who took aspirin for joint pain. When he started to ask his patients about possible bleeding complications and vascular events, he observed that people who took aspirin didn’t have coronary myocardial infarctions.

It took a long time for people to discover that aspirin is not only a pain medication but also an antiplatelet agent. The first randomized study that showed that aspirin is effective in secondary prevention after myocardial infarction was published in 1974 in The New England Journal of Medicine. In 1980, aspirin was approved by the U.S. Food and Drug Administration for the secondary prevention of stroke and in 1984 for secondary prevention after myocardial infarction.

A history of efficacy

Aspirin also has a proven role in the secondary prevention of transient ischemic attack and ischemic stroke. Given early, it reduces the risk for a recurrent vascular event by 50% and long-term, compared with placebo, by 20%.

Interestingly, the doses are different in different areas of the world. In the United States, it’s either 81 mg or 325 mg. In Europe, it’s usually 100 mg. Until a few years ago, there was no single trial which used 100 mg of aspirin, compared with placebo for the secondary prevention of stroke.

If we look at dual antiplatelet therapy, the combination of aspirin and clopidogrel was not superior to aspirin alone or clopidogrel alone for long-term prevention, but the combination of dipyridamole and aspirin and the combination of cilostazol and aspirin were superior to aspirin alone for secondary stroke prevention. Short-term, within the first 30 days, the combination of aspirin and clopidogrel and the combination of ticagrelor and aspirin is superior to monotherapy but also have an increased risk for bleeding.

People with atrial fibrillation or embolic strokes need to be anticoagulated, but the addition of aspirin to anticoagulation does not increase efficacy, it only increases the risk for bleeding.

In people above the age of 75 years who have to take aspirin, there is an increased risk for upper gastrointestinal bleeding. These patients should, in addition, receive proton pump inhibitors.

The use of aspirin for the primary prevention of vascular events was promoted for almost 50 years all over the world, but in the last 5 years, a number of randomized trials clearly showed that aspirin is not effective, compared with placebo, in the primary prevention of vascular event stroke, myocardial infarction, and vascular death. It only increases the risk for bleeding.

So it’s a clear separation. Aspirin should not be used for primary prevention of vascular events, but it should be used in basically everyone who doesn’t have contraindications for secondary prevention of vascular events and vascular death.

Ladies and gentlemen, a drug that is 125 years old is also still one of the most used and affordable drugs all around the world. It’s highly effective and has only a small risk for major bleeding complications. It’s really time to celebrate aspirin for this achievement.

Dr. Diener is professor, department of neurology, Stroke Center-Headache Center, University Duisburg-Essen (Germany). A complete list of his financial disclosures is available at the link below.

A version of this article first appeared on Medscape.com.

Key clinical point: External concurrent occipital and trigeminal neurostimulation (eCOT-NS) was well tolerated, safe, and an effective treatment that provided fast and durable relief and freedom from pain in patients with migraine with or without aura.

Major finding: A significantly higher proportion of patients in the active vs sham eCOT-NS arm reported pain relief after 2 hours of treatment initiation (60% vs 37%; P  =  .018), freedom from pain at 2 hours after treatment initiation without any rescue medication (46% vs 12%; P < .001), and improvement in their most bothersome symptom (81% vs 60%; P  =  .047). No serious adverse events were reported.

Study details: Findings are from the RIME study, a randomized, double-blind, sham-controlled study including 187 adults with migraine with or without aura who were randomly assigned to receive active (n = 94) or sham (n = 93) eCOT-NS.

Disclosures: This study was supported by Neurolief Ltd. Several authors reported receiving research grants or honoraria or serving as consultants or advisory board members for various sources, including Neurolief Ltd.

Source: Tepper SJ et al. Migraine treatment with external concurrent occipital and trigeminal neurostimulation—A randomized controlled trial. Headache. 2022 (Jun 24). Doi:  10.1111/head.14350

Key clinical point: External concurrent occipital and trigeminal neurostimulation (eCOT-NS) was well tolerated, safe, and an effective treatment that provided fast and durable relief and freedom from pain in patients with migraine with or without aura.

Major finding: A significantly higher proportion of patients in the active vs sham eCOT-NS arm reported pain relief after 2 hours of treatment initiation (60% vs 37%; P  =  .018), freedom from pain at 2 hours after treatment initiation without any rescue medication (46% vs 12%; P < .001), and improvement in their most bothersome symptom (81% vs 60%; P  =  .047). No serious adverse events were reported.

Study details: Findings are from the RIME study, a randomized, double-blind, sham-controlled study including 187 adults with migraine with or without aura who were randomly assigned to receive active (n = 94) or sham (n = 93) eCOT-NS.

Disclosures: This study was supported by Neurolief Ltd. Several authors reported receiving research grants or honoraria or serving as consultants or advisory board members for various sources, including Neurolief Ltd.

Source: Tepper SJ et al. Migraine treatment with external concurrent occipital and trigeminal neurostimulation—A randomized controlled trial. Headache. 2022 (Jun 24). Doi:  10.1111/head.14350

Key clinical point: External concurrent occipital and trigeminal neurostimulation (eCOT-NS) was well tolerated, safe, and an effective treatment that provided fast and durable relief and freedom from pain in patients with migraine with or without aura.

Major finding: A significantly higher proportion of patients in the active vs sham eCOT-NS arm reported pain relief after 2 hours of treatment initiation (60% vs 37%; P  =  .018), freedom from pain at 2 hours after treatment initiation without any rescue medication (46% vs 12%; P < .001), and improvement in their most bothersome symptom (81% vs 60%; P  =  .047). No serious adverse events were reported.

Study details: Findings are from the RIME study, a randomized, double-blind, sham-controlled study including 187 adults with migraine with or without aura who were randomly assigned to receive active (n = 94) or sham (n = 93) eCOT-NS.

Disclosures: This study was supported by Neurolief Ltd. Several authors reported receiving research grants or honoraria or serving as consultants or advisory board members for various sources, including Neurolief Ltd.

Source: Tepper SJ et al. Migraine treatment with external concurrent occipital and trigeminal neurostimulation—A randomized controlled trial. Headache. 2022 (Jun 24). Doi:  10.1111/head.14350

Key clinical point: Vitamin D3 (5000 IU daily) supplementation as an adjuvant therapy to topiramate was well tolerated and safe, and an effective strategy for pediatric migraine prophylaxis.

Major finding: After 16 weeks of treatment, the monthly headache frequency (6.23 vs 9.79 attacks/month; P  =  .01) and disability from headache score (17.56 vs 25.18; P  =  .04) were significantly lower in the vitamin D3 supplementation vs placebo group, with >50% decrease in the monthly headache attack frequency being reported by a significantly higher proportion of patients receiving vitamin D3 supplementation vs placebo (75.0% vs 53.5%; P  =  .01) and no serious adverse events being reported.

Study details: The findings are from a double-blind, prospective case-control study including 60 children and adolescents (aged 5-14 years) with migraine who were randomly assigned to receive topiramate with vitamin D3 supplementation or placebo.

Disclosures: This study did not receive any financial support. The authors declared no competing interests.

Source: Elmala MK et al. The impact of vitamin D₃ supplementation to topiramate therapy on pediatric migraine prophylaxis. J Child Neurol. 2022 (Jun 22). Doi: 10.1177/08830738221092882

Key clinical point: Vitamin D3 (5000 IU daily) supplementation as an adjuvant therapy to topiramate was well tolerated and safe, and an effective strategy for pediatric migraine prophylaxis.

Major finding: After 16 weeks of treatment, the monthly headache frequency (6.23 vs 9.79 attacks/month; P  =  .01) and disability from headache score (17.56 vs 25.18; P  =  .04) were significantly lower in the vitamin D3 supplementation vs placebo group, with >50% decrease in the monthly headache attack frequency being reported by a significantly higher proportion of patients receiving vitamin D3 supplementation vs placebo (75.0% vs 53.5%; P  =  .01) and no serious adverse events being reported.

Study details: The findings are from a double-blind, prospective case-control study including 60 children and adolescents (aged 5-14 years) with migraine who were randomly assigned to receive topiramate with vitamin D3 supplementation or placebo.

Disclosures: This study did not receive any financial support. The authors declared no competing interests.

Source: Elmala MK et al. The impact of vitamin D₃ supplementation to topiramate therapy on pediatric migraine prophylaxis. J Child Neurol. 2022 (Jun 22). Doi: 10.1177/08830738221092882

Key clinical point: Vitamin D3 (5000 IU daily) supplementation as an adjuvant therapy to topiramate was well tolerated and safe, and an effective strategy for pediatric migraine prophylaxis.

Major finding: After 16 weeks of treatment, the monthly headache frequency (6.23 vs 9.79 attacks/month; P  =  .01) and disability from headache score (17.56 vs 25.18; P  =  .04) were significantly lower in the vitamin D3 supplementation vs placebo group, with >50% decrease in the monthly headache attack frequency being reported by a significantly higher proportion of patients receiving vitamin D3 supplementation vs placebo (75.0% vs 53.5%; P  =  .01) and no serious adverse events being reported.

Study details: The findings are from a double-blind, prospective case-control study including 60 children and adolescents (aged 5-14 years) with migraine who were randomly assigned to receive topiramate with vitamin D3 supplementation or placebo.

Disclosures: This study did not receive any financial support. The authors declared no competing interests.

Source: Elmala MK et al. The impact of vitamin D₃ supplementation to topiramate therapy on pediatric migraine prophylaxis. J Child Neurol. 2022 (Jun 22). Doi: 10.1177/08830738221092882