Migraine ICYMI

Key clinical point: Combination therapy with two parenteral agents or monotherapy with either neuroleptics or metoclopramide can be considered as a first-line treatment option for the management of acute migraine pain in the emergency department (ED) settings.

Major finding: Combination therapy of two parenteral agents vs placebo was an effective treatment option in reducing pain intensity scores (mean difference −3.36; 95% CI −4.64 to −2.08) and increasing the rate of achievement of pain relief (risk ratio 2.83; 95% CI 1.74-4.61). Monotherapy with neuroleptics and metoclopramide also provided pain relief and helped patients achieve pain-free status prior to discharge from the ED but increased the risk for adverse events, especially akathisia.

Study details: This meta-analysis of 97 randomized controlled trials evaluated the effectiveness of various parenteral agents for pain relief in patients with acute migraine presenting to the ED.

Disclosures: This study was funded by the Emergency Medicine Research Group, Canada. The authors declared no conflicts of interest.

Source: Kirkland SW, Visser L, Meyer J, et al. The effectiveness of parenteral agents for pain reduction in patients with migraine presenting to emergency settings: A systematic review and network analysis. Headache. 2024;64(4):424-447. doi: 10.1111/head.14704 Source

Key clinical point: Combination therapy with two parenteral agents or monotherapy with either neuroleptics or metoclopramide can be considered as a first-line treatment option for the management of acute migraine pain in the emergency department (ED) settings.

Major finding: Combination therapy of two parenteral agents vs placebo was an effective treatment option in reducing pain intensity scores (mean difference −3.36; 95% CI −4.64 to −2.08) and increasing the rate of achievement of pain relief (risk ratio 2.83; 95% CI 1.74-4.61). Monotherapy with neuroleptics and metoclopramide also provided pain relief and helped patients achieve pain-free status prior to discharge from the ED but increased the risk for adverse events, especially akathisia.

Study details: This meta-analysis of 97 randomized controlled trials evaluated the effectiveness of various parenteral agents for pain relief in patients with acute migraine presenting to the ED.

Disclosures: This study was funded by the Emergency Medicine Research Group, Canada. The authors declared no conflicts of interest.

Source: Kirkland SW, Visser L, Meyer J, et al. The effectiveness of parenteral agents for pain reduction in patients with migraine presenting to emergency settings: A systematic review and network analysis. Headache. 2024;64(4):424-447. doi: 10.1111/head.14704 Source

Key clinical point: Combination therapy with two parenteral agents or monotherapy with either neuroleptics or metoclopramide can be considered as a first-line treatment option for the management of acute migraine pain in the emergency department (ED) settings.

Major finding: Combination therapy of two parenteral agents vs placebo was an effective treatment option in reducing pain intensity scores (mean difference −3.36; 95% CI −4.64 to −2.08) and increasing the rate of achievement of pain relief (risk ratio 2.83; 95% CI 1.74-4.61). Monotherapy with neuroleptics and metoclopramide also provided pain relief and helped patients achieve pain-free status prior to discharge from the ED but increased the risk for adverse events, especially akathisia.

Study details: This meta-analysis of 97 randomized controlled trials evaluated the effectiveness of various parenteral agents for pain relief in patients with acute migraine presenting to the ED.

Disclosures: This study was funded by the Emergency Medicine Research Group, Canada. The authors declared no conflicts of interest.

Source: Kirkland SW, Visser L, Meyer J, et al. The effectiveness of parenteral agents for pain reduction in patients with migraine presenting to emergency settings: A systematic review and network analysis. Headache. 2024;64(4):424-447. doi: 10.1111/head.14704 Source

Key clinical point: Women with migraine tend to exclusively breastfeed their infants for a shorter duration than those without migraine.

Major finding: There was no significant difference between the proportions of women with and without migraine who did not breastfeed their infants (adjusted odds ratio [aOR] 1.03; 95% CI 0.74-1.27), but the odds of exclusively breastfeeding infants for 6 months and more were 16% lower in women with vs without migraine (aOR 0.84; 95% CI 0.71-0.99; P = .033).

Study details: Findings are from a cross-sectional study including 5282 women (age 20-49 years) who had given birth in the last 5 years, of whom 862 (16.3%) had migraine.

Disclosures: The study did not receive any specific funding. Christine Lay declared receiving research support from and serving on ad boards for various sources. The other authors declared no conflicts of interest.

Source: Vyas MV, Lee N, Lay C. Association between migraine and exclusive breastfeeding: A cross-sectional study. Headache. 2024 (Apr 21). doi: 10.1111/head.14713 Source

Key clinical point: Women with migraine tend to exclusively breastfeed their infants for a shorter duration than those without migraine.

Major finding: There was no significant difference between the proportions of women with and without migraine who did not breastfeed their infants (adjusted odds ratio [aOR] 1.03; 95% CI 0.74-1.27), but the odds of exclusively breastfeeding infants for 6 months and more were 16% lower in women with vs without migraine (aOR 0.84; 95% CI 0.71-0.99; P = .033).

Study details: Findings are from a cross-sectional study including 5282 women (age 20-49 years) who had given birth in the last 5 years, of whom 862 (16.3%) had migraine.

Disclosures: The study did not receive any specific funding. Christine Lay declared receiving research support from and serving on ad boards for various sources. The other authors declared no conflicts of interest.

Source: Vyas MV, Lee N, Lay C. Association between migraine and exclusive breastfeeding: A cross-sectional study. Headache. 2024 (Apr 21). doi: 10.1111/head.14713 Source

Key clinical point: Women with migraine tend to exclusively breastfeed their infants for a shorter duration than those without migraine.

Major finding: There was no significant difference between the proportions of women with and without migraine who did not breastfeed their infants (adjusted odds ratio [aOR] 1.03; 95% CI 0.74-1.27), but the odds of exclusively breastfeeding infants for 6 months and more were 16% lower in women with vs without migraine (aOR 0.84; 95% CI 0.71-0.99; P = .033).

Study details: Findings are from a cross-sectional study including 5282 women (age 20-49 years) who had given birth in the last 5 years, of whom 862 (16.3%) had migraine.

Disclosures: The study did not receive any specific funding. Christine Lay declared receiving research support from and serving on ad boards for various sources. The other authors declared no conflicts of interest.

Source: Vyas MV, Lee N, Lay C. Association between migraine and exclusive breastfeeding: A cross-sectional study. Headache. 2024 (Apr 21). doi: 10.1111/head.14713 Source

Key clinical point: In patients with migraine, greater severity of photophobia is significantly associated with worse sleep-related outcomes, such as sleep quality (SQ), sleep disturbance (SDi), sleep onset latency (SOL), sleep-related impairment (SRI), and insomnia.

Major finding: Compared with patients with migraine and without photophobia, those with migraine and photophobia presented significantly poorer SQ (β 0.15; P < .001), longer SOL (β 0.10; P = .011), higher levels of SDi (β 0.12; P < .001) and SRI (β 0.08; P = .020), and a higher prevalence of insomnia (β 0.11; P = .005).

Study details: This cross-sectional observational study evaluated the association between photophobia and sleep-related outcomes in 852 patients with migraine using data from the American Registry for Migraine Research.

Disclosures: This study did not receive any specific funding. Some authors declared receiving compensation for consulting from, serving as consultants for, or having other ties with various sources.

Source: Sharp N, Burish MJ, Digre KB, et al. Photophobia is associated with lower sleep quality in individuals with migraine: Results from the American Registry for Migraine Research (ARMR). J Headache Pain. 2024;25:55. doi: 10.1186/s10194-024-01756-9 Source

Key clinical point: In patients with migraine, greater severity of photophobia is significantly associated with worse sleep-related outcomes, such as sleep quality (SQ), sleep disturbance (SDi), sleep onset latency (SOL), sleep-related impairment (SRI), and insomnia.

Major finding: Compared with patients with migraine and without photophobia, those with migraine and photophobia presented significantly poorer SQ (β 0.15; P < .001), longer SOL (β 0.10; P = .011), higher levels of SDi (β 0.12; P < .001) and SRI (β 0.08; P = .020), and a higher prevalence of insomnia (β 0.11; P = .005).

Study details: This cross-sectional observational study evaluated the association between photophobia and sleep-related outcomes in 852 patients with migraine using data from the American Registry for Migraine Research.

Disclosures: This study did not receive any specific funding. Some authors declared receiving compensation for consulting from, serving as consultants for, or having other ties with various sources.

Source: Sharp N, Burish MJ, Digre KB, et al. Photophobia is associated with lower sleep quality in individuals with migraine: Results from the American Registry for Migraine Research (ARMR). J Headache Pain. 2024;25:55. doi: 10.1186/s10194-024-01756-9 Source

Key clinical point: In patients with migraine, greater severity of photophobia is significantly associated with worse sleep-related outcomes, such as sleep quality (SQ), sleep disturbance (SDi), sleep onset latency (SOL), sleep-related impairment (SRI), and insomnia.

Major finding: Compared with patients with migraine and without photophobia, those with migraine and photophobia presented significantly poorer SQ (β 0.15; P < .001), longer SOL (β 0.10; P = .011), higher levels of SDi (β 0.12; P < .001) and SRI (β 0.08; P = .020), and a higher prevalence of insomnia (β 0.11; P = .005).

Study details: This cross-sectional observational study evaluated the association between photophobia and sleep-related outcomes in 852 patients with migraine using data from the American Registry for Migraine Research.

Disclosures: This study did not receive any specific funding. Some authors declared receiving compensation for consulting from, serving as consultants for, or having other ties with various sources.

Source: Sharp N, Burish MJ, Digre KB, et al. Photophobia is associated with lower sleep quality in individuals with migraine: Results from the American Registry for Migraine Research (ARMR). J Headache Pain. 2024;25:55. doi: 10.1186/s10194-024-01756-9 Source

Key clinical point: Patients with migraine had an increased risk for vascular dementia (VaD), with the risk being significantly higher in those with chronic vs episodic migraine.

Major finding: Compared with individuals without migraine, patients with migraine had a 1.21-fold higher risk for VaD (adjusted hazard ratio [aHR] 1.21; 95% CI 1.17-1.25), with the cumulative incidence of migraine being significantly higher in patients with chronic vs episodic migraine (log-rank P < .001).

Study details: This 10-year retrospective population-based cohort study included 212,836 patients with migraine and 5,863,348 participants without migraine, of whom 3914 (1.8%) and 60,259 (1.0%), respectively, were diagnosed with VaD during the follow-up period.

Disclosures: This study was funded by a grant from the National Research Foundation, Republic of Korea, and others. The authors declared no conflicts of interest.

Source: Shin H, Ha WS, Kim J, et al. Association between migraine and the risk of vascular dementia: A nationwide longitudinal study in South Korea. PLoS One. 2024;19:e0300379. doi: 10.1371/journal.pone.0300379 Source

Key clinical point: Patients with migraine had an increased risk for vascular dementia (VaD), with the risk being significantly higher in those with chronic vs episodic migraine.

Major finding: Compared with individuals without migraine, patients with migraine had a 1.21-fold higher risk for VaD (adjusted hazard ratio [aHR] 1.21; 95% CI 1.17-1.25), with the cumulative incidence of migraine being significantly higher in patients with chronic vs episodic migraine (log-rank P < .001).

Study details: This 10-year retrospective population-based cohort study included 212,836 patients with migraine and 5,863,348 participants without migraine, of whom 3914 (1.8%) and 60,259 (1.0%), respectively, were diagnosed with VaD during the follow-up period.

Disclosures: This study was funded by a grant from the National Research Foundation, Republic of Korea, and others. The authors declared no conflicts of interest.

Source: Shin H, Ha WS, Kim J, et al. Association between migraine and the risk of vascular dementia: A nationwide longitudinal study in South Korea. PLoS One. 2024;19:e0300379. doi: 10.1371/journal.pone.0300379 Source

Key clinical point: Patients with migraine had an increased risk for vascular dementia (VaD), with the risk being significantly higher in those with chronic vs episodic migraine.

Major finding: Compared with individuals without migraine, patients with migraine had a 1.21-fold higher risk for VaD (adjusted hazard ratio [aHR] 1.21; 95% CI 1.17-1.25), with the cumulative incidence of migraine being significantly higher in patients with chronic vs episodic migraine (log-rank P < .001).

Study details: This 10-year retrospective population-based cohort study included 212,836 patients with migraine and 5,863,348 participants without migraine, of whom 3914 (1.8%) and 60,259 (1.0%), respectively, were diagnosed with VaD during the follow-up period.

Disclosures: This study was funded by a grant from the National Research Foundation, Republic of Korea, and others. The authors declared no conflicts of interest.

Source: Shin H, Ha WS, Kim J, et al. Association between migraine and the risk of vascular dementia: A nationwide longitudinal study in South Korea. PLoS One. 2024;19:e0300379. doi: 10.1371/journal.pone.0300379 Source

Outcomes of Acute and Preventive Migraine Therapy Based on Patient Sex

I previously have addressed myths about migraine as they pertain to men and women. When I found an interesting study recently published in Cephalalgia investigating the effectiveness of calcitonin gene-related peptide receptor (CGRP-R) antagonists (gepants) for acute care and prevention of episodic migraine and CGRP monoclonal antibodies for preventive treatment of episodic and chronic migraine in men and women, I thought I would discuss it here.

The study’s aim was to discern if patient sex contributed to outcomes in each specific treatment arm. Female sex hormones have been recognized as factors in promoting migraine, and women show increased severity, persistence, and comorbidity in migraine profiles, and increased prevalence of migraine relative to men.

Gepants used for acute therapy (ubrogepant, rimegepant, zavegepant) and preventive therapy (atogepant, rimegepant) were studied in this trial. Erenumab, fremanezumab, galcanezumab, and eptinezumab are monoclonal antibodies that either sit on the CGRP receptor (erenumab) or inactivate the CGRP ligand (fremanezumab, galcanezumab, and eptinezumab) and are used for migraine prevention. CGRP-based therapies are not effective in all patients and understanding which patient groups respond preferentially could reduce trial and error in treatment selection. The effectiveness of treatments targeting CGRP or the CGRP receptor may not be uniform in men and women, highlighting the need for further research and understanding of CGRP neurobiology in both sexes.

Key findings:

• In the trial by Porreca et al: In women, the 3 gepants approved by the FDA for the acute care of migraine (ubrogepant, rimegepant, zavegepant) produced a statistically significant drug effect for the 2-hour pain freedom (2h-PF) endpoint, with an average drug effect of 9.5% (CI: 7.4 to 11.6) and an average number needed to treat (NNT) of 11.
• Men did not show statistically significant effects with the acute use of gepants. The average drug effect was 2.8%, and the average NNT was 36.
• For both men and women, CGRP-targeting therapies for prevention of migraine (the 4 monoclonal antibodies) were equally effective; however, possible sex differences remain uncertain and need further study.
• In patients with chronic migraine, CGRP/CGRP-R antibodies were similarly effective in both men and women.
• For the 2-hour freedom from most bothersome symptom (2h-MBS) endpoint when gepants were given acutely, the effects were much better in women than men, with an average drug effect of 10.2% and an average NNT of 10.
• In men, these medications produced observed treatment effects on 2h-MBS with an average drug effect of 3.2% and an average NNT of 32.
• In men, 5 out of 12 estimates favored placebo over the active treatment, suggesting a treatment with little to no effect.
• The pooled treatment effects for women were 3 times as large, at 9.2% and 10.2%, respectively.
• The placebo response rates for 2 of the 3 ubrogepant studies and one of 2 zavegepant studies were higher in men than in women.

The study concludes that, while small molecule CGRP-R antagonists are dramatically effective for acute therapy of migraine in women, available data do not demonstrate effectiveness in men. The treatment effect was found to always favor active treatment numerically for both men and women for prevention of episodic and chronic migraine. The data highlight possible differential effects of CGRP-targeted therapies in different patient populations and the need for increased understanding of CGRP neurobiology in men and women. The study also emphasizes the need to understand which patient groups preferentially respond to CGRP-based therapies to reduce trial and error in treatment. Note that rimegepant data on prevention were not available for analysis at the time of the writing.

It would be interesting to perform a meta-analysis of multiple well-done, large, real-world studies to see if the same differences and similarities are found in men versus women for acute care of migraine and prevention of episodic and chronic migraine. I suspect that we would find that acute care results favor women but that some men do well.

The Effectiveness of Prednisolone for Treating Medication Overuse Headache

I often discuss medication overuse headache (MOH), as it is difficult to diagnose and treat, so I wanted to comment on another pertinent study. It is a post hoc analysis of the Registry for Load and Management of Medication Overuse Headache (RELEASE). The RELEASE trial is an ongoing, multicenter, observational, cohort study of MOH that has been conducted in Korea since April 2020. Findings were recently published in Headache by Lee et al.

MOH is a secondary headache disorder that develops in patients with a preexisting primary headache when they overuse acute care headache medications of any type except gepants. This includes prescription medications such as triptans, ergots, butalbital-containing medications; opioids; aspirin; acetaminophen; any type of combination medication often containing caffeine; or a combination of medications. This condition significantly impacts patients’ quality of life and productivity, usually increasing the frequency of headaches per month and leading to higher healthcare-related costs.

Treating MOH is challenging due to the lack of high-quality drug trials specifically designed for MOH and doctor inexperience. Current evidence is based largely on subgroup analyses of drug trials for the treatment of chronic migraine that contain these patient types.

Withdrawal of acute care headache medications that are being overused has traditionally been considered an important aspect of MOH treatment, although this may be changing. Withdrawal symptoms, such as increased intensity of headache pain, frequency of headaches, and other symptoms like agitation and sleep disturbance, can prevent patients from discontinuing overused medications. Systemic corticosteroids are widely used to reduce these withdrawal headaches, but clinical trials are sparse and have failed to meet proper endpoints. Despite this, corticosteroids have shown potential benefits, such as decreasing withdrawal headaches, reducing the use of rescue medications, and lowering headache intensity at certain time points after treatment.

Given these findings, this published study hypothesized that prednisolone may play a role in converting MOH to non-MOH at 3 months after treatment. The objective was to evaluate the outcome of prednisolone therapy in reversing medication overuse at 3 months posttreatment in patients with MOH using prospective multicenter registry data. Prednisolone was prescribed to 59 out of 309 patients (19.1%) enrolled during this observational study period, with doses ranging from 10 to 40 mg/day for 5-14 days. Of these patients, 228 (73.8%) completed the 3-month follow-up period.

Key findings:

• The MOH reversal rates at 3 months postbaseline were 76% (31/41) in the prednisolone group and 57.8% (108/187) in the no prednisolone group (p = 0.034).
• The steroid effect remained significant (adjusted odds ratio, 2.78; 95% confidence interval 1.27-6.1, p = 0.010) after adjusting for the number of monthly headache days at baseline, mode of discontinuation of overused medication, use of early preventive medications, and the number of combined preventive medications.

The study had several strengths, including the multicenter collection of data, prospective follow-ups, and comprehensiveness of data acquisition. However, it also had significant limitations, such as the noninterventional, observational nature of the study, potential bias in steroid prescription (every doctor prescribed what they wanted), and heterogeneity in the patient population. Also, there were a variety of treatments, and they were not standardized. Further external validation may be necessary before generalizing the study results.

Despite these limitations, the results do suggest that prednisolone may be one part of a valid treatment option for patients with MOH. I suspect, if the proper studies are done, we will see that using a good preventive medication, with few adverse events, and with careful education of the patient, formal detoxification will not be necessary when treating many patients with MOH. This has been my experience with MOH treatment utilizing the newer anti-CGRP preventive medications, including the older monoclonal antibodies and the newer gepants.

Outcomes of Acute and Preventive Migraine Therapy Based on Patient Sex

I previously have addressed myths about migraine as they pertain to men and women. When I found an interesting study recently published in Cephalalgia investigating the effectiveness of calcitonin gene-related peptide receptor (CGRP-R) antagonists (gepants) for acute care and prevention of episodic migraine and CGRP monoclonal antibodies for preventive treatment of episodic and chronic migraine in men and women, I thought I would discuss it here.

The study’s aim was to discern if patient sex contributed to outcomes in each specific treatment arm. Female sex hormones have been recognized as factors in promoting migraine, and women show increased severity, persistence, and comorbidity in migraine profiles, and increased prevalence of migraine relative to men.

Gepants used for acute therapy (ubrogepant, rimegepant, zavegepant) and preventive therapy (atogepant, rimegepant) were studied in this trial. Erenumab, fremanezumab, galcanezumab, and eptinezumab are monoclonal antibodies that either sit on the CGRP receptor (erenumab) or inactivate the CGRP ligand (fremanezumab, galcanezumab, and eptinezumab) and are used for migraine prevention. CGRP-based therapies are not effective in all patients and understanding which patient groups respond preferentially could reduce trial and error in treatment selection. The effectiveness of treatments targeting CGRP or the CGRP receptor may not be uniform in men and women, highlighting the need for further research and understanding of CGRP neurobiology in both sexes.

Key findings:

• In the trial by Porreca et al: In women, the 3 gepants approved by the FDA for the acute care of migraine (ubrogepant, rimegepant, zavegepant) produced a statistically significant drug effect for the 2-hour pain freedom (2h-PF) endpoint, with an average drug effect of 9.5% (CI: 7.4 to 11.6) and an average number needed to treat (NNT) of 11.
• Men did not show statistically significant effects with the acute use of gepants. The average drug effect was 2.8%, and the average NNT was 36.
• For both men and women, CGRP-targeting therapies for prevention of migraine (the 4 monoclonal antibodies) were equally effective; however, possible sex differences remain uncertain and need further study.
• In patients with chronic migraine, CGRP/CGRP-R antibodies were similarly effective in both men and women.
• For the 2-hour freedom from most bothersome symptom (2h-MBS) endpoint when gepants were given acutely, the effects were much better in women than men, with an average drug effect of 10.2% and an average NNT of 10.
• In men, these medications produced observed treatment effects on 2h-MBS with an average drug effect of 3.2% and an average NNT of 32.
• In men, 5 out of 12 estimates favored placebo over the active treatment, suggesting a treatment with little to no effect.
• The pooled treatment effects for women were 3 times as large, at 9.2% and 10.2%, respectively.
• The placebo response rates for 2 of the 3 ubrogepant studies and one of 2 zavegepant studies were higher in men than in women.

The study concludes that, while small molecule CGRP-R antagonists are dramatically effective for acute therapy of migraine in women, available data do not demonstrate effectiveness in men. The treatment effect was found to always favor active treatment numerically for both men and women for prevention of episodic and chronic migraine. The data highlight possible differential effects of CGRP-targeted therapies in different patient populations and the need for increased understanding of CGRP neurobiology in men and women. The study also emphasizes the need to understand which patient groups preferentially respond to CGRP-based therapies to reduce trial and error in treatment. Note that rimegepant data on prevention were not available for analysis at the time of the writing.

It would be interesting to perform a meta-analysis of multiple well-done, large, real-world studies to see if the same differences and similarities are found in men versus women for acute care of migraine and prevention of episodic and chronic migraine. I suspect that we would find that acute care results favor women but that some men do well.

The Effectiveness of Prednisolone for Treating Medication Overuse Headache

I often discuss medication overuse headache (MOH), as it is difficult to diagnose and treat, so I wanted to comment on another pertinent study. It is a post hoc analysis of the Registry for Load and Management of Medication Overuse Headache (RELEASE). The RELEASE trial is an ongoing, multicenter, observational, cohort study of MOH that has been conducted in Korea since April 2020. Findings were recently published in Headache by Lee et al.

MOH is a secondary headache disorder that develops in patients with a preexisting primary headache when they overuse acute care headache medications of any type except gepants. This includes prescription medications such as triptans, ergots, butalbital-containing medications; opioids; aspirin; acetaminophen; any type of combination medication often containing caffeine; or a combination of medications. This condition significantly impacts patients’ quality of life and productivity, usually increasing the frequency of headaches per month and leading to higher healthcare-related costs.

Treating MOH is challenging due to the lack of high-quality drug trials specifically designed for MOH and doctor inexperience. Current evidence is based largely on subgroup analyses of drug trials for the treatment of chronic migraine that contain these patient types.

Withdrawal of acute care headache medications that are being overused has traditionally been considered an important aspect of MOH treatment, although this may be changing. Withdrawal symptoms, such as increased intensity of headache pain, frequency of headaches, and other symptoms like agitation and sleep disturbance, can prevent patients from discontinuing overused medications. Systemic corticosteroids are widely used to reduce these withdrawal headaches, but clinical trials are sparse and have failed to meet proper endpoints. Despite this, corticosteroids have shown potential benefits, such as decreasing withdrawal headaches, reducing the use of rescue medications, and lowering headache intensity at certain time points after treatment.

Given these findings, this published study hypothesized that prednisolone may play a role in converting MOH to non-MOH at 3 months after treatment. The objective was to evaluate the outcome of prednisolone therapy in reversing medication overuse at 3 months posttreatment in patients with MOH using prospective multicenter registry data. Prednisolone was prescribed to 59 out of 309 patients (19.1%) enrolled during this observational study period, with doses ranging from 10 to 40 mg/day for 5-14 days. Of these patients, 228 (73.8%) completed the 3-month follow-up period.

Key findings:

• The MOH reversal rates at 3 months postbaseline were 76% (31/41) in the prednisolone group and 57.8% (108/187) in the no prednisolone group (p = 0.034).
• The steroid effect remained significant (adjusted odds ratio, 2.78; 95% confidence interval 1.27-6.1, p = 0.010) after adjusting for the number of monthly headache days at baseline, mode of discontinuation of overused medication, use of early preventive medications, and the number of combined preventive medications.

The study had several strengths, including the multicenter collection of data, prospective follow-ups, and comprehensiveness of data acquisition. However, it also had significant limitations, such as the noninterventional, observational nature of the study, potential bias in steroid prescription (every doctor prescribed what they wanted), and heterogeneity in the patient population. Also, there were a variety of treatments, and they were not standardized. Further external validation may be necessary before generalizing the study results.

Despite these limitations, the results do suggest that prednisolone may be one part of a valid treatment option for patients with MOH. I suspect, if the proper studies are done, we will see that using a good preventive medication, with few adverse events, and with careful education of the patient, formal detoxification will not be necessary when treating many patients with MOH. This has been my experience with MOH treatment utilizing the newer anti-CGRP preventive medications, including the older monoclonal antibodies and the newer gepants.

Outcomes of Acute and Preventive Migraine Therapy Based on Patient Sex

I previously have addressed myths about migraine as they pertain to men and women. When I found an interesting study recently published in Cephalalgia investigating the effectiveness of calcitonin gene-related peptide receptor (CGRP-R) antagonists (gepants) for acute care and prevention of episodic migraine and CGRP monoclonal antibodies for preventive treatment of episodic and chronic migraine in men and women, I thought I would discuss it here.

The study’s aim was to discern if patient sex contributed to outcomes in each specific treatment arm. Female sex hormones have been recognized as factors in promoting migraine, and women show increased severity, persistence, and comorbidity in migraine profiles, and increased prevalence of migraine relative to men.

Gepants used for acute therapy (ubrogepant, rimegepant, zavegepant) and preventive therapy (atogepant, rimegepant) were studied in this trial. Erenumab, fremanezumab, galcanezumab, and eptinezumab are monoclonal antibodies that either sit on the CGRP receptor (erenumab) or inactivate the CGRP ligand (fremanezumab, galcanezumab, and eptinezumab) and are used for migraine prevention. CGRP-based therapies are not effective in all patients and understanding which patient groups respond preferentially could reduce trial and error in treatment selection. The effectiveness of treatments targeting CGRP or the CGRP receptor may not be uniform in men and women, highlighting the need for further research and understanding of CGRP neurobiology in both sexes.

Key findings:

• In the trial by Porreca et al: In women, the 3 gepants approved by the FDA for the acute care of migraine (ubrogepant, rimegepant, zavegepant) produced a statistically significant drug effect for the 2-hour pain freedom (2h-PF) endpoint, with an average drug effect of 9.5% (CI: 7.4 to 11.6) and an average number needed to treat (NNT) of 11.
• Men did not show statistically significant effects with the acute use of gepants. The average drug effect was 2.8%, and the average NNT was 36.
• For both men and women, CGRP-targeting therapies for prevention of migraine (the 4 monoclonal antibodies) were equally effective; however, possible sex differences remain uncertain and need further study.
• In patients with chronic migraine, CGRP/CGRP-R antibodies were similarly effective in both men and women.
• For the 2-hour freedom from most bothersome symptom (2h-MBS) endpoint when gepants were given acutely, the effects were much better in women than men, with an average drug effect of 10.2% and an average NNT of 10.
• In men, these medications produced observed treatment effects on 2h-MBS with an average drug effect of 3.2% and an average NNT of 32.
• In men, 5 out of 12 estimates favored placebo over the active treatment, suggesting a treatment with little to no effect.
• The pooled treatment effects for women were 3 times as large, at 9.2% and 10.2%, respectively.
• The placebo response rates for 2 of the 3 ubrogepant studies and one of 2 zavegepant studies were higher in men than in women.

The study concludes that, while small molecule CGRP-R antagonists are dramatically effective for acute therapy of migraine in women, available data do not demonstrate effectiveness in men. The treatment effect was found to always favor active treatment numerically for both men and women for prevention of episodic and chronic migraine. The data highlight possible differential effects of CGRP-targeted therapies in different patient populations and the need for increased understanding of CGRP neurobiology in men and women. The study also emphasizes the need to understand which patient groups preferentially respond to CGRP-based therapies to reduce trial and error in treatment. Note that rimegepant data on prevention were not available for analysis at the time of the writing.

It would be interesting to perform a meta-analysis of multiple well-done, large, real-world studies to see if the same differences and similarities are found in men versus women for acute care of migraine and prevention of episodic and chronic migraine. I suspect that we would find that acute care results favor women but that some men do well.

The Effectiveness of Prednisolone for Treating Medication Overuse Headache

I often discuss medication overuse headache (MOH), as it is difficult to diagnose and treat, so I wanted to comment on another pertinent study. It is a post hoc analysis of the Registry for Load and Management of Medication Overuse Headache (RELEASE). The RELEASE trial is an ongoing, multicenter, observational, cohort study of MOH that has been conducted in Korea since April 2020. Findings were recently published in Headache by Lee et al.

MOH is a secondary headache disorder that develops in patients with a preexisting primary headache when they overuse acute care headache medications of any type except gepants. This includes prescription medications such as triptans, ergots, butalbital-containing medications; opioids; aspirin; acetaminophen; any type of combination medication often containing caffeine; or a combination of medications. This condition significantly impacts patients’ quality of life and productivity, usually increasing the frequency of headaches per month and leading to higher healthcare-related costs.

Treating MOH is challenging due to the lack of high-quality drug trials specifically designed for MOH and doctor inexperience. Current evidence is based largely on subgroup analyses of drug trials for the treatment of chronic migraine that contain these patient types.

Withdrawal of acute care headache medications that are being overused has traditionally been considered an important aspect of MOH treatment, although this may be changing. Withdrawal symptoms, such as increased intensity of headache pain, frequency of headaches, and other symptoms like agitation and sleep disturbance, can prevent patients from discontinuing overused medications. Systemic corticosteroids are widely used to reduce these withdrawal headaches, but clinical trials are sparse and have failed to meet proper endpoints. Despite this, corticosteroids have shown potential benefits, such as decreasing withdrawal headaches, reducing the use of rescue medications, and lowering headache intensity at certain time points after treatment.

Given these findings, this published study hypothesized that prednisolone may play a role in converting MOH to non-MOH at 3 months after treatment. The objective was to evaluate the outcome of prednisolone therapy in reversing medication overuse at 3 months posttreatment in patients with MOH using prospective multicenter registry data. Prednisolone was prescribed to 59 out of 309 patients (19.1%) enrolled during this observational study period, with doses ranging from 10 to 40 mg/day for 5-14 days. Of these patients, 228 (73.8%) completed the 3-month follow-up period.

Key findings:

• The MOH reversal rates at 3 months postbaseline were 76% (31/41) in the prednisolone group and 57.8% (108/187) in the no prednisolone group (p = 0.034).
• The steroid effect remained significant (adjusted odds ratio, 2.78; 95% confidence interval 1.27-6.1, p = 0.010) after adjusting for the number of monthly headache days at baseline, mode of discontinuation of overused medication, use of early preventive medications, and the number of combined preventive medications.

The study had several strengths, including the multicenter collection of data, prospective follow-ups, and comprehensiveness of data acquisition. However, it also had significant limitations, such as the noninterventional, observational nature of the study, potential bias in steroid prescription (every doctor prescribed what they wanted), and heterogeneity in the patient population. Also, there were a variety of treatments, and they were not standardized. Further external validation may be necessary before generalizing the study results.

Despite these limitations, the results do suggest that prednisolone may be one part of a valid treatment option for patients with MOH. I suspect, if the proper studies are done, we will see that using a good preventive medication, with few adverse events, and with careful education of the patient, formal detoxification will not be necessary when treating many patients with MOH. This has been my experience with MOH treatment utilizing the newer anti-CGRP preventive medications, including the older monoclonal antibodies and the newer gepants.

Proton pump inhibitors (PPIs), which are used to control acid reflux, are associated with an increased risk for migraine and other severe headache types, new research showed. 

Using data from the National Health and Nutrition Examination Survey (NHANES), investigators conducted a cross-sectional analysis and found all types of acid-suppression therapy were associated with an increased risk for severe headache including migraine but that PPIs conferred the greatest risk.

“It’s important to note that many people do need acid-reducing medications to manage acid reflux or other conditions, and people with migraine or severe headache who are taking these drugs or supplements should talk with their doctors about whether they should continue,” lead author Margaret Slavin, PhD, of the University of Maryland in College Park, said in a press release. 

The findings were published online  in Neurology Clinical Practice. 
 

New Look at Old Data

Previous research has shown that headache is listed among the most common adverse reactions in adults taking PPIs and histamine receptor agonists (H2RAs), which include cimetidine, famotidine, and nizatidine.

Other large studies of health databases have shown increased headache risk within a week of PPI exposure.

To compare the risk from PPIs versus H2RAs and other generics, researchers analyzed data from the NHANES for those who used PPIs, H2RAs, and generic antacids to learn more about the potential link between acid-suppression therapy and headache.

They used survey data from 1999 to 2004, the only years the NHANES included a question about migraine and other headache during the past 3 months. 

Investigators analyzed data for 11,800 participants aged 20 years or older who used prescription drugs, over-the-counter medications, and nutritional supplements during the past month. 

Participants who used acid-suppressing medications had an increased risk for migraine or severe headache versus those who did not use these agents. Investigators found PPIs were tied to a 70% increased risk, while H2RAs and antacids were associated with 40% and 30% higher risks, respectively. Use of any type of acid-suppression therapy was tied to a 47% increased risk for severe headache.
 

Magnesium a Risk Factor?

While magnesium supplements are sometimes prescribed as a “natural” headache prevention therapy to prevent migraine and other headache types, the investigators noted they were surprised to find individuals taking H2RAs who met the dietary reference intake for magnesium had a nearly threefold increased risk for migraine or severe headache (odds ratio, 2.80; 95% CI, 1.02-1.45; P = .025).

However, there was no association between magnesium and the other acid-reducing medications. 

The study’s limitations included the use of a single question to identify migraine or severe headache, which may have resulted in some misclassification of the outcome. The authors also pointed out that dietary and drug-intake data may be subject to recall bias. 

“These results suggest that there is a need for more intentionally designed prospective work to inform the extent to which associations between migraine and acid-suppression therapy are merely detecting comorbidities or to what extent migraine is an adverse event associated with the medications,” the authors wrote. 

There was no targeted funding. Disclosures are noted in the original article.

A version of this article appeared on Medscape.com.

Proton pump inhibitors (PPIs), which are used to control acid reflux, are associated with an increased risk for migraine and other severe headache types, new research showed. 

Using data from the National Health and Nutrition Examination Survey (NHANES), investigators conducted a cross-sectional analysis and found all types of acid-suppression therapy were associated with an increased risk for severe headache including migraine but that PPIs conferred the greatest risk.

“It’s important to note that many people do need acid-reducing medications to manage acid reflux or other conditions, and people with migraine or severe headache who are taking these drugs or supplements should talk with their doctors about whether they should continue,” lead author Margaret Slavin, PhD, of the University of Maryland in College Park, said in a press release. 

The findings were published online  in Neurology Clinical Practice. 
 

New Look at Old Data

Previous research has shown that headache is listed among the most common adverse reactions in adults taking PPIs and histamine receptor agonists (H2RAs), which include cimetidine, famotidine, and nizatidine.

Other large studies of health databases have shown increased headache risk within a week of PPI exposure.

To compare the risk from PPIs versus H2RAs and other generics, researchers analyzed data from the NHANES for those who used PPIs, H2RAs, and generic antacids to learn more about the potential link between acid-suppression therapy and headache.

They used survey data from 1999 to 2004, the only years the NHANES included a question about migraine and other headache during the past 3 months. 

Investigators analyzed data for 11,800 participants aged 20 years or older who used prescription drugs, over-the-counter medications, and nutritional supplements during the past month. 

Participants who used acid-suppressing medications had an increased risk for migraine or severe headache versus those who did not use these agents. Investigators found PPIs were tied to a 70% increased risk, while H2RAs and antacids were associated with 40% and 30% higher risks, respectively. Use of any type of acid-suppression therapy was tied to a 47% increased risk for severe headache.
 

Magnesium a Risk Factor?

While magnesium supplements are sometimes prescribed as a “natural” headache prevention therapy to prevent migraine and other headache types, the investigators noted they were surprised to find individuals taking H2RAs who met the dietary reference intake for magnesium had a nearly threefold increased risk for migraine or severe headache (odds ratio, 2.80; 95% CI, 1.02-1.45; P = .025).

However, there was no association between magnesium and the other acid-reducing medications. 

The study’s limitations included the use of a single question to identify migraine or severe headache, which may have resulted in some misclassification of the outcome. The authors also pointed out that dietary and drug-intake data may be subject to recall bias. 

“These results suggest that there is a need for more intentionally designed prospective work to inform the extent to which associations between migraine and acid-suppression therapy are merely detecting comorbidities or to what extent migraine is an adverse event associated with the medications,” the authors wrote. 

There was no targeted funding. Disclosures are noted in the original article.

A version of this article appeared on Medscape.com.

Proton pump inhibitors (PPIs), which are used to control acid reflux, are associated with an increased risk for migraine and other severe headache types, new research showed. 

Using data from the National Health and Nutrition Examination Survey (NHANES), investigators conducted a cross-sectional analysis and found all types of acid-suppression therapy were associated with an increased risk for severe headache including migraine but that PPIs conferred the greatest risk.

“It’s important to note that many people do need acid-reducing medications to manage acid reflux or other conditions, and people with migraine or severe headache who are taking these drugs or supplements should talk with their doctors about whether they should continue,” lead author Margaret Slavin, PhD, of the University of Maryland in College Park, said in a press release. 

The findings were published online  in Neurology Clinical Practice. 
 

New Look at Old Data

Previous research has shown that headache is listed among the most common adverse reactions in adults taking PPIs and histamine receptor agonists (H2RAs), which include cimetidine, famotidine, and nizatidine.

Other large studies of health databases have shown increased headache risk within a week of PPI exposure.

To compare the risk from PPIs versus H2RAs and other generics, researchers analyzed data from the NHANES for those who used PPIs, H2RAs, and generic antacids to learn more about the potential link between acid-suppression therapy and headache.

They used survey data from 1999 to 2004, the only years the NHANES included a question about migraine and other headache during the past 3 months. 

Investigators analyzed data for 11,800 participants aged 20 years or older who used prescription drugs, over-the-counter medications, and nutritional supplements during the past month. 

Participants who used acid-suppressing medications had an increased risk for migraine or severe headache versus those who did not use these agents. Investigators found PPIs were tied to a 70% increased risk, while H2RAs and antacids were associated with 40% and 30% higher risks, respectively. Use of any type of acid-suppression therapy was tied to a 47% increased risk for severe headache.
 

Magnesium a Risk Factor?

While magnesium supplements are sometimes prescribed as a “natural” headache prevention therapy to prevent migraine and other headache types, the investigators noted they were surprised to find individuals taking H2RAs who met the dietary reference intake for magnesium had a nearly threefold increased risk for migraine or severe headache (odds ratio, 2.80; 95% CI, 1.02-1.45; P = .025).

However, there was no association between magnesium and the other acid-reducing medications. 

The study’s limitations included the use of a single question to identify migraine or severe headache, which may have resulted in some misclassification of the outcome. The authors also pointed out that dietary and drug-intake data may be subject to recall bias. 

“These results suggest that there is a need for more intentionally designed prospective work to inform the extent to which associations between migraine and acid-suppression therapy are merely detecting comorbidities or to what extent migraine is an adverse event associated with the medications,” the authors wrote. 

There was no targeted funding. Disclosures are noted in the original article.

A version of this article appeared on Medscape.com.

Migraine and other headache types are common ailments, and there are many stereotypes and stigmas associated with these conditions. One of the prevailing beliefs about headaches and migraines is that they are linked with internalizing mental health conditions — anxiety and depression. These associations can affect pediatric migraine patients and their parents in complicated ways, potentially hindering adequate diagnosis and treatment. Results of a recent prospective study, published in the journal Headache, provided results that challenge the widespread belief that people who have migraines have a higher-than-average rate of internalizing mental health disorders. The authors provided a discussion and data to explain that their initial hypothesis of a relationship between migraine and mental health was disproven. The study included 123 participants age 8-18 years who had been previously diagnosed with migraine. The patients, who were seen in a pediatric neurology clinic, completed headache questionnaires and validated measures of anxiety and depressive symptoms. The final analysis showed no significant association between migraines or headaches with anxiety or depression.

Why does this matter? Stigma can prevent patients and parents from seeking care if parents feel that they will be judged as bad parents for contributing to their children's anxiety, depression, headaches, and migraines. In fact, beyond mental health stigma, children who have migraine can be blamed for having an unhealthy lifestyle.^[1] While advice to get enough sleep, eat healthy, and stay active is worthwhile, there can be an implication that pediatric migraine patients are causing their migraines by living an unhealthy lifestyle.^[1] Additionally, the implication that parents are not properly taking care of their children's health can inhibit an accurate symptom history. Releasing pediatric migraine patients and their parents from myths about migraines and headaches can be a beneficial component of doctor-patient communication regarding migraine care.

It is possible that dietary adjustments or supplements could help improve migraine frequency and severity. Maintaining a healthy diet is a frequent recommendation for people who have headaches, but it can be frustrating for patients to receive general recommendations to follow a healthy lifestyle. Specific direction regarding which foods to avoid and which foods to add to a diet can be helpful for patients as they try to navigate the challenge of adopting migraine-friendly lifestyle changes.

Eicosapentaenoic acid (EPA) is one of the omega-3 fatty acids. A recent study, with results published in Brain, Behavior, and Immunity, examined the effects of EPA on migraines. The 12-week randomized, double-blind, placebo-controlled trial included 70 participants who had been diagnosed with episodic migraine. Participants were randomly assigned to either EPA (2 g fish oil with 1.8 g of EPA/day) or placebo (2 g soybean oil/day). Migraine frequency and severity were assessed using standardized scales. According to the authors, the high-dose-EPA group had significantly reduced migraine frequency and severity, fewer number of days using acute treatment, reduced migraine-associated disability, improved anxiety and depression, and improved quality of life in comparison to the placebo group. The EPA group did not experience notable adverse events.To provide a sense of scale regarding dietary EPA, 3 oz of cooked wild salmon has 0.35 g of EPA, 3 oz of cooked shrimp has 0.2 g of EPA, and 3 oz of light canned tuna has 0.02 g of EPA.^[2] Thus, it's important to note that the amount of EPA used in this study was higher than what would be expected of dietary EPA.

An observational prospective study published in Scientific Reports examined the effects of dietary phytochemical index (DPI) on migraine. DPI is defined as the proportion of daily energy intake derived from foods rich in phytochemicals. Consumption of phytochemical-rich foods has been associated with cardiovascular and metabolic diseases prevention in various populations. These foods include fruits, vegetables, whole grains, seeds, nuts, and legumes. The study included 265 adults age 20-50 who had a diagnosis of migraine. Participants were asked to fill out a questionnaire, which was used to evaluate their diet in the preceding year, and they were asked to complete a diary to track their migraine symptoms. The results showed an inverse relationship between DPI index and migraine frequency. Participants who had the highest DPI had the lowest migraine frequency.^[3] While the authors found the results to be statistically significant, they did not point to a cause and effect. Migraine-associated symptoms such as nausea can have an effect on dietary choices, so patients who experience migraine symptoms may avoid certain foods before, during, or after a migraine episode. They also may consistently avoid foods that they have experienced as migraine triggers.

Diet and lifestyle can have an effect on migraine frequency, severity, and overall migraine-associated quality of life. Beyond general recommendations, however, it is not yet well established which foods or supplements could potentially help alleviate migraines. Advice to maintain a healthy lifestyle is definitely worthwhile for migraine patients, but it is important to avoid conveying blame or stigma when it comes to communication about the effect of lifestyle on migraine. This is especially important for pediatric migraine patients because the stigma extends beyond children to parents and could potentially interfere with clear communication and adequate care.

Additional References

1. Gelfand AA, Irwin SL. Lifestyle advice for pediatric migraine: Blaming the patient, or evidence based? Semin Neurol. 2020;40:277-285. doi: 10.1055/s-0040-1708868 Source

2. National Institutes of Health. Office of Dietary Supplements. Omega-3 fatty acids. Updated February 15, 2023. Source

3. Hamedi-Shahraki S, Jowshan M-R, Zolghadrpour M-A, et al. Dietary phytochemical index is favorably associated with oxidative stress status and cardiovascular risk factors in adults with obesity. Sci Rep. 2023;13:7035. doi: 10.1038/s41598-023-34064-4 Source

Migraine and other headache types are common ailments, and there are many stereotypes and stigmas associated with these conditions. One of the prevailing beliefs about headaches and migraines is that they are linked with internalizing mental health conditions — anxiety and depression. These associations can affect pediatric migraine patients and their parents in complicated ways, potentially hindering adequate diagnosis and treatment. Results of a recent prospective study, published in the journal Headache, provided results that challenge the widespread belief that people who have migraines have a higher-than-average rate of internalizing mental health disorders. The authors provided a discussion and data to explain that their initial hypothesis of a relationship between migraine and mental health was disproven. The study included 123 participants age 8-18 years who had been previously diagnosed with migraine. The patients, who were seen in a pediatric neurology clinic, completed headache questionnaires and validated measures of anxiety and depressive symptoms. The final analysis showed no significant association between migraines or headaches with anxiety or depression.

Why does this matter? Stigma can prevent patients and parents from seeking care if parents feel that they will be judged as bad parents for contributing to their children's anxiety, depression, headaches, and migraines. In fact, beyond mental health stigma, children who have migraine can be blamed for having an unhealthy lifestyle.^[1] While advice to get enough sleep, eat healthy, and stay active is worthwhile, there can be an implication that pediatric migraine patients are causing their migraines by living an unhealthy lifestyle.^[1] Additionally, the implication that parents are not properly taking care of their children's health can inhibit an accurate symptom history. Releasing pediatric migraine patients and their parents from myths about migraines and headaches can be a beneficial component of doctor-patient communication regarding migraine care.

It is possible that dietary adjustments or supplements could help improve migraine frequency and severity. Maintaining a healthy diet is a frequent recommendation for people who have headaches, but it can be frustrating for patients to receive general recommendations to follow a healthy lifestyle. Specific direction regarding which foods to avoid and which foods to add to a diet can be helpful for patients as they try to navigate the challenge of adopting migraine-friendly lifestyle changes.

Eicosapentaenoic acid (EPA) is one of the omega-3 fatty acids. A recent study, with results published in Brain, Behavior, and Immunity, examined the effects of EPA on migraines. The 12-week randomized, double-blind, placebo-controlled trial included 70 participants who had been diagnosed with episodic migraine. Participants were randomly assigned to either EPA (2 g fish oil with 1.8 g of EPA/day) or placebo (2 g soybean oil/day). Migraine frequency and severity were assessed using standardized scales. According to the authors, the high-dose-EPA group had significantly reduced migraine frequency and severity, fewer number of days using acute treatment, reduced migraine-associated disability, improved anxiety and depression, and improved quality of life in comparison to the placebo group. The EPA group did not experience notable adverse events.To provide a sense of scale regarding dietary EPA, 3 oz of cooked wild salmon has 0.35 g of EPA, 3 oz of cooked shrimp has 0.2 g of EPA, and 3 oz of light canned tuna has 0.02 g of EPA.^[2] Thus, it's important to note that the amount of EPA used in this study was higher than what would be expected of dietary EPA.

An observational prospective study published in Scientific Reports examined the effects of dietary phytochemical index (DPI) on migraine. DPI is defined as the proportion of daily energy intake derived from foods rich in phytochemicals. Consumption of phytochemical-rich foods has been associated with cardiovascular and metabolic diseases prevention in various populations. These foods include fruits, vegetables, whole grains, seeds, nuts, and legumes. The study included 265 adults age 20-50 who had a diagnosis of migraine. Participants were asked to fill out a questionnaire, which was used to evaluate their diet in the preceding year, and they were asked to complete a diary to track their migraine symptoms. The results showed an inverse relationship between DPI index and migraine frequency. Participants who had the highest DPI had the lowest migraine frequency.^[3] While the authors found the results to be statistically significant, they did not point to a cause and effect. Migraine-associated symptoms such as nausea can have an effect on dietary choices, so patients who experience migraine symptoms may avoid certain foods before, during, or after a migraine episode. They also may consistently avoid foods that they have experienced as migraine triggers.

Diet and lifestyle can have an effect on migraine frequency, severity, and overall migraine-associated quality of life. Beyond general recommendations, however, it is not yet well established which foods or supplements could potentially help alleviate migraines. Advice to maintain a healthy lifestyle is definitely worthwhile for migraine patients, but it is important to avoid conveying blame or stigma when it comes to communication about the effect of lifestyle on migraine. This is especially important for pediatric migraine patients because the stigma extends beyond children to parents and could potentially interfere with clear communication and adequate care.

Additional References

1. Gelfand AA, Irwin SL. Lifestyle advice for pediatric migraine: Blaming the patient, or evidence based? Semin Neurol. 2020;40:277-285. doi: 10.1055/s-0040-1708868 Source

2. National Institutes of Health. Office of Dietary Supplements. Omega-3 fatty acids. Updated February 15, 2023. Source

3. Hamedi-Shahraki S, Jowshan M-R, Zolghadrpour M-A, et al. Dietary phytochemical index is favorably associated with oxidative stress status and cardiovascular risk factors in adults with obesity. Sci Rep. 2023;13:7035. doi: 10.1038/s41598-023-34064-4 Source

Migraine and other headache types are common ailments, and there are many stereotypes and stigmas associated with these conditions. One of the prevailing beliefs about headaches and migraines is that they are linked with internalizing mental health conditions — anxiety and depression. These associations can affect pediatric migraine patients and their parents in complicated ways, potentially hindering adequate diagnosis and treatment. Results of a recent prospective study, published in the journal Headache, provided results that challenge the widespread belief that people who have migraines have a higher-than-average rate of internalizing mental health disorders. The authors provided a discussion and data to explain that their initial hypothesis of a relationship between migraine and mental health was disproven. The study included 123 participants age 8-18 years who had been previously diagnosed with migraine. The patients, who were seen in a pediatric neurology clinic, completed headache questionnaires and validated measures of anxiety and depressive symptoms. The final analysis showed no significant association between migraines or headaches with anxiety or depression.

Why does this matter? Stigma can prevent patients and parents from seeking care if parents feel that they will be judged as bad parents for contributing to their children's anxiety, depression, headaches, and migraines. In fact, beyond mental health stigma, children who have migraine can be blamed for having an unhealthy lifestyle.^[1] While advice to get enough sleep, eat healthy, and stay active is worthwhile, there can be an implication that pediatric migraine patients are causing their migraines by living an unhealthy lifestyle.^[1] Additionally, the implication that parents are not properly taking care of their children's health can inhibit an accurate symptom history. Releasing pediatric migraine patients and their parents from myths about migraines and headaches can be a beneficial component of doctor-patient communication regarding migraine care.

It is possible that dietary adjustments or supplements could help improve migraine frequency and severity. Maintaining a healthy diet is a frequent recommendation for people who have headaches, but it can be frustrating for patients to receive general recommendations to follow a healthy lifestyle. Specific direction regarding which foods to avoid and which foods to add to a diet can be helpful for patients as they try to navigate the challenge of adopting migraine-friendly lifestyle changes.

Eicosapentaenoic acid (EPA) is one of the omega-3 fatty acids. A recent study, with results published in Brain, Behavior, and Immunity, examined the effects of EPA on migraines. The 12-week randomized, double-blind, placebo-controlled trial included 70 participants who had been diagnosed with episodic migraine. Participants were randomly assigned to either EPA (2 g fish oil with 1.8 g of EPA/day) or placebo (2 g soybean oil/day). Migraine frequency and severity were assessed using standardized scales. According to the authors, the high-dose-EPA group had significantly reduced migraine frequency and severity, fewer number of days using acute treatment, reduced migraine-associated disability, improved anxiety and depression, and improved quality of life in comparison to the placebo group. The EPA group did not experience notable adverse events.To provide a sense of scale regarding dietary EPA, 3 oz of cooked wild salmon has 0.35 g of EPA, 3 oz of cooked shrimp has 0.2 g of EPA, and 3 oz of light canned tuna has 0.02 g of EPA.^[2] Thus, it's important to note that the amount of EPA used in this study was higher than what would be expected of dietary EPA.

An observational prospective study published in Scientific Reports examined the effects of dietary phytochemical index (DPI) on migraine. DPI is defined as the proportion of daily energy intake derived from foods rich in phytochemicals. Consumption of phytochemical-rich foods has been associated with cardiovascular and metabolic diseases prevention in various populations. These foods include fruits, vegetables, whole grains, seeds, nuts, and legumes. The study included 265 adults age 20-50 who had a diagnosis of migraine. Participants were asked to fill out a questionnaire, which was used to evaluate their diet in the preceding year, and they were asked to complete a diary to track their migraine symptoms. The results showed an inverse relationship between DPI index and migraine frequency. Participants who had the highest DPI had the lowest migraine frequency.^[3] While the authors found the results to be statistically significant, they did not point to a cause and effect. Migraine-associated symptoms such as nausea can have an effect on dietary choices, so patients who experience migraine symptoms may avoid certain foods before, during, or after a migraine episode. They also may consistently avoid foods that they have experienced as migraine triggers.

Diet and lifestyle can have an effect on migraine frequency, severity, and overall migraine-associated quality of life. Beyond general recommendations, however, it is not yet well established which foods or supplements could potentially help alleviate migraines. Advice to maintain a healthy lifestyle is definitely worthwhile for migraine patients, but it is important to avoid conveying blame or stigma when it comes to communication about the effect of lifestyle on migraine. This is especially important for pediatric migraine patients because the stigma extends beyond children to parents and could potentially interfere with clear communication and adequate care.

Additional References

1. Gelfand AA, Irwin SL. Lifestyle advice for pediatric migraine: Blaming the patient, or evidence based? Semin Neurol. 2020;40:277-285. doi: 10.1055/s-0040-1708868 Source

2. National Institutes of Health. Office of Dietary Supplements. Omega-3 fatty acids. Updated February 15, 2023. Source

3. Hamedi-Shahraki S, Jowshan M-R, Zolghadrpour M-A, et al. Dietary phytochemical index is favorably associated with oxidative stress status and cardiovascular risk factors in adults with obesity. Sci Rep. 2023;13:7035. doi: 10.1038/s41598-023-34064-4 Source

Key clinical point: Anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAb) showed superior efficacy to botulinum toxin A (BoNT-A) in reducing the migraine burden in patients with chronic migraine (CM).

Major finding: Anti-CGRP mAbs vs BoNT-A led to significant reductions in mean Headache Impact Test-6 and Allodynia Symptoms Checklist-12 scores at 6 months (mean change −11.1 vs −3.2 points, P < .0001; and −5.2 vs −0.5 points, P = .0056, respectively) and 12 months (mean change −11.4 vs −3.6 points, P = .0042; and −6.0 vs −0.9 points, P = .0011, respectively).

Study details: This exploratory analysis of the real-world effectiveness of anti-CGRP mAb vs BoNT-A included 126 patients with CM who were treated with anti-CGRP mAb (n = 36) or BoNT-A (n = 90).

Disclosures: The study was supported by the Italian Ministry of Health. Some authors declared receiving funding, travel grants, honoraria, or personal fees for participation in advisory boards, speaker panels, and clinical investigation studies from various sources.

Source: Montisano DA, Giossi R, Canella M, et al. Reducing the impact of headache and allodynia score in chronic migraine: An exploratory analysis from the Real-world Effectiveness of Anti-CGRP Monoclonal Antibodies Compared to Onabotulinum Toxin A (RAMO) Study. Toxins. 2024;16(4):178. doi: 10.3390/toxins16040178 Source

Key clinical point: Anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAb) showed superior efficacy to botulinum toxin A (BoNT-A) in reducing the migraine burden in patients with chronic migraine (CM).

Major finding: Anti-CGRP mAbs vs BoNT-A led to significant reductions in mean Headache Impact Test-6 and Allodynia Symptoms Checklist-12 scores at 6 months (mean change −11.1 vs −3.2 points, P < .0001; and −5.2 vs −0.5 points, P = .0056, respectively) and 12 months (mean change −11.4 vs −3.6 points, P = .0042; and −6.0 vs −0.9 points, P = .0011, respectively).

Study details: This exploratory analysis of the real-world effectiveness of anti-CGRP mAb vs BoNT-A included 126 patients with CM who were treated with anti-CGRP mAb (n = 36) or BoNT-A (n = 90).

Disclosures: The study was supported by the Italian Ministry of Health. Some authors declared receiving funding, travel grants, honoraria, or personal fees for participation in advisory boards, speaker panels, and clinical investigation studies from various sources.

Source: Montisano DA, Giossi R, Canella M, et al. Reducing the impact of headache and allodynia score in chronic migraine: An exploratory analysis from the Real-world Effectiveness of Anti-CGRP Monoclonal Antibodies Compared to Onabotulinum Toxin A (RAMO) Study. Toxins. 2024;16(4):178. doi: 10.3390/toxins16040178 Source

Key clinical point: Anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAb) showed superior efficacy to botulinum toxin A (BoNT-A) in reducing the migraine burden in patients with chronic migraine (CM).

Major finding: Anti-CGRP mAbs vs BoNT-A led to significant reductions in mean Headache Impact Test-6 and Allodynia Symptoms Checklist-12 scores at 6 months (mean change −11.1 vs −3.2 points, P < .0001; and −5.2 vs −0.5 points, P = .0056, respectively) and 12 months (mean change −11.4 vs −3.6 points, P = .0042; and −6.0 vs −0.9 points, P = .0011, respectively).

Study details: This exploratory analysis of the real-world effectiveness of anti-CGRP mAb vs BoNT-A included 126 patients with CM who were treated with anti-CGRP mAb (n = 36) or BoNT-A (n = 90).

Disclosures: The study was supported by the Italian Ministry of Health. Some authors declared receiving funding, travel grants, honoraria, or personal fees for participation in advisory boards, speaker panels, and clinical investigation studies from various sources.

Source: Montisano DA, Giossi R, Canella M, et al. Reducing the impact of headache and allodynia score in chronic migraine: An exploratory analysis from the Real-world Effectiveness of Anti-CGRP Monoclonal Antibodies Compared to Onabotulinum Toxin A (RAMO) Study. Toxins. 2024;16(4):178. doi: 10.3390/toxins16040178 Source

Key clinical point: Contrary to common beliefs, neither anxiety nor depressive symptoms were associated with migraine-related outcomes in children and adolescents.

Major finding: Headache frequency and migraine-related disability had no significant association with anxiety (headache frequency P = .639; migraine-related disability P = .470) and depressive symptoms (headache frequency P = .209; migraine-related disability P = .796) at baseline. Similarly, no significant association was observed between longitudinal changes in anxiety and depressive symptoms and migraine-related outcomes.

Study details: Findings are from a prospective clinical cohort study including 123 children and adolescents with migraine who responded to a headache questionnaire and were assessed for anxiety and depressive symptoms.

Disclosures: This study was supported by the Program of Undergraduate Research Experience, University of Calgary, Canada, and others. Serena Laura Orr declared receiving royalties and research funding from various sources and serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation. The other authors declared no conflicts of interest.

Source: Rizvi BA, Kuziek J, Cho LY, et al. Anxiety and depressive symptoms and migraine-related outcomes in children and adolescents. Headache. 2024 (Apr 6). doi: 10.1111/head.14701 Source

Key clinical point: Contrary to common beliefs, neither anxiety nor depressive symptoms were associated with migraine-related outcomes in children and adolescents.

Major finding: Headache frequency and migraine-related disability had no significant association with anxiety (headache frequency P = .639; migraine-related disability P = .470) and depressive symptoms (headache frequency P = .209; migraine-related disability P = .796) at baseline. Similarly, no significant association was observed between longitudinal changes in anxiety and depressive symptoms and migraine-related outcomes.

Study details: Findings are from a prospective clinical cohort study including 123 children and adolescents with migraine who responded to a headache questionnaire and were assessed for anxiety and depressive symptoms.

Disclosures: This study was supported by the Program of Undergraduate Research Experience, University of Calgary, Canada, and others. Serena Laura Orr declared receiving royalties and research funding from various sources and serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation. The other authors declared no conflicts of interest.

Source: Rizvi BA, Kuziek J, Cho LY, et al. Anxiety and depressive symptoms and migraine-related outcomes in children and adolescents. Headache. 2024 (Apr 6). doi: 10.1111/head.14701 Source

Key clinical point: Contrary to common beliefs, neither anxiety nor depressive symptoms were associated with migraine-related outcomes in children and adolescents.

Major finding: Headache frequency and migraine-related disability had no significant association with anxiety (headache frequency P = .639; migraine-related disability P = .470) and depressive symptoms (headache frequency P = .209; migraine-related disability P = .796) at baseline. Similarly, no significant association was observed between longitudinal changes in anxiety and depressive symptoms and migraine-related outcomes.

Study details: Findings are from a prospective clinical cohort study including 123 children and adolescents with migraine who responded to a headache questionnaire and were assessed for anxiety and depressive symptoms.

Disclosures: This study was supported by the Program of Undergraduate Research Experience, University of Calgary, Canada, and others. Serena Laura Orr declared receiving royalties and research funding from various sources and serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation. The other authors declared no conflicts of interest.

Source: Rizvi BA, Kuziek J, Cho LY, et al. Anxiety and depressive symptoms and migraine-related outcomes in children and adolescents. Headache. 2024 (Apr 6). doi: 10.1111/head.14701 Source

Key clinical point: Treatment with a combination of anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) and onabotulinumtoxinA (onabot) was more effective than monotherapy with either anti-CGRP alone or onabot in reducing monthly migraine days (MMD) in patients with chronic migraine.

Major finding: Initiating therapy with either anti-CGRP mAbs or onabot significantly reduced the median MMD from 30 to 15 days, which further decreased to 8 days after initiating dual therapy with anti-CGRP mAb and onabot (both P < .0001). Overall, 68% of patients receiving dual therapy achieved 50% or greater reduction in MMD.

Study details: This real-world retrospective chart review included 423 patients with chronic migraine (age ≥ 18 years) who received monotherapy with either anti-CGRP mAb or onabot (n = 229) followed by dual therapy (concurrent treatment with anti-CGRP mAb and onabot; n = 194) for at least three consecutive months.

Disclosures: This study was funded by a Cleveland Clinic institutional grant. The authors declared no conflicts of interest.

Source: Salim A, Hennessy E, Sonneborn C, et al. Synergism of anti-CGRP monoclonal antibodies and onabotulinumtoxinA in the treatment of chronic migraine: A real-world retrospective chart review. CNS Drugs. 2024 (Apr 7). doi: 10.1007/s40263-024-01086-z  Source

Key clinical point: Treatment with a combination of anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) and onabotulinumtoxinA (onabot) was more effective than monotherapy with either anti-CGRP alone or onabot in reducing monthly migraine days (MMD) in patients with chronic migraine.

Major finding: Initiating therapy with either anti-CGRP mAbs or onabot significantly reduced the median MMD from 30 to 15 days, which further decreased to 8 days after initiating dual therapy with anti-CGRP mAb and onabot (both P < .0001). Overall, 68% of patients receiving dual therapy achieved 50% or greater reduction in MMD.

Study details: This real-world retrospective chart review included 423 patients with chronic migraine (age ≥ 18 years) who received monotherapy with either anti-CGRP mAb or onabot (n = 229) followed by dual therapy (concurrent treatment with anti-CGRP mAb and onabot; n = 194) for at least three consecutive months.

Disclosures: This study was funded by a Cleveland Clinic institutional grant. The authors declared no conflicts of interest.

Source: Salim A, Hennessy E, Sonneborn C, et al. Synergism of anti-CGRP monoclonal antibodies and onabotulinumtoxinA in the treatment of chronic migraine: A real-world retrospective chart review. CNS Drugs. 2024 (Apr 7). doi: 10.1007/s40263-024-01086-z  Source

Key clinical point: Treatment with a combination of anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAb) and onabotulinumtoxinA (onabot) was more effective than monotherapy with either anti-CGRP alone or onabot in reducing monthly migraine days (MMD) in patients with chronic migraine.

Major finding: Initiating therapy with either anti-CGRP mAbs or onabot significantly reduced the median MMD from 30 to 15 days, which further decreased to 8 days after initiating dual therapy with anti-CGRP mAb and onabot (both P < .0001). Overall, 68% of patients receiving dual therapy achieved 50% or greater reduction in MMD.

Study details: This real-world retrospective chart review included 423 patients with chronic migraine (age ≥ 18 years) who received monotherapy with either anti-CGRP mAb or onabot (n = 229) followed by dual therapy (concurrent treatment with anti-CGRP mAb and onabot; n = 194) for at least three consecutive months.

Disclosures: This study was funded by a Cleveland Clinic institutional grant. The authors declared no conflicts of interest.

Source: Salim A, Hennessy E, Sonneborn C, et al. Synergism of anti-CGRP monoclonal antibodies and onabotulinumtoxinA in the treatment of chronic migraine: A real-world retrospective chart review. CNS Drugs. 2024 (Apr 7). doi: 10.1007/s40263-024-01086-z  Source