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Commentary: Looking at Migraine Treatment in a Comprehensive Way, June 2024
Migraine care requires a comprehensive approach. Identifying and avoiding triggers is a key component of patient-directed self-care. For many migraine patients, preventive therapy can substantially improve their quality of life. Yet, even with the best migraine prevention plan, many patients experience occasional migraines and require therapy for acute symptom relief. When it comes to selecting therapies for acute migraine treatment, criteria include efficacy, fast action, long duration of action, low risk for rebound symptoms, minimal side effects, and patient safety. Prescription therapies and therapies used in a medical setting include new calcitonin gene-related peptide (CGRP) receptor antagonists as well as antihistamines, antiemetics, neuroleptics, and triptans that have been used for years.
A study published in The Journal of Headache and Pain in April 2024 examined migraine symptom relief with the use of Nurtec OTD (rimegepant), one of the recently approved CGRP receptor antagonists. This post hoc subgroup analysis of a large double-blind randomized phase 3 clinical trial included 1075 participants, of whom 538 took 75 mg rimegepant and 537 took placebo to treat a single migraine episode. According to the analysis, rimegepant outperformed placebo on measures of freedom from the most bothersome symptom, pain relief at 2 hours post-dose, ability to function normally at 2 hours post-dose, use of rescue medication within 24 hours post-dose, and sustained pain freedom up to 48 hours post-dose. Treatment-emergent adverse events were assessed using EEG, vital signs, and laboratory tests. There was no notable difference in the incidence of adverse events between the rimegepant group and the placebo group, and no drug-related adverse events were reported.
This result is similar to that of previous studies which have demonstrated the significant efficacy of CGRP receptor blockers on acute migraine symptoms, including pain, bothersome symptoms, and nausea when compared with placebo.1
A study published in the May 2024 issue of Pediatric Emergency Care examined the efficacy of prochlorperazine monotherapy or prochlorperazine combined with diphenhydramine for the treatment of acute migraine in the pediatric emergency department. This retrospective study included 1683 patients who were treated with either prochlorperazine monotherapy or diphenhydramine co-administered with prochlorperazine. The authors reported that the need for additional therapy, the 72-hour return visit rates, and the admission rates were equal for both groups. They reported that, overall, 13% of the patients required additional therapy, 16.7% were admitted, and 5.3% returned within 72 hours. Extrapyramidal side effects were reported in 2.4% of patients in the prochlorperazine group, while none of the patients in the prochlorperazine/diphenhydramine group reported extrapyramidal side effects. This difference in side-effect incidence should not be interpreted as a protective effect of diphenhydramine but could be an indication that adding diphenhydramine did not increase the risk for extrapyramidal side effects.
A study published in the April 2024 issue of Headache examined the efficacy of parenteral agents on acute migraine in the emergency room setting. The data analysis included 97 studies. The authors examined the efficacy of these medications and various combinations:
- •diphenhydramine (intravenous);
- •trimethobenzamide (intramuscular);
- •granisetron (intravenous);
- •valproate (intravenous);
- •neuroleptics (intravenous):
- ◦prochlorperazine,
- ◦chlorpromazine,
- ◦haloperidol,
- ◦droperidol,
- ◦methotrimeprazine; and
- •dihydroergotamine (intravenous, intramuscular, or subcutaneous);
- •ketorolac (intravenous); and
- •magnesium sulfate (intravenous).
Each of these therapies was shown to improve migraine symptoms. According to the authors, "the majority of the parenteral agents commonly available to treat patients with migraine headaches in emergency settings was shown to be effective in providing pain relief." They recommended combination therapy or monotherapy of either neuroleptics or metoclopramide as first-line treatment options for treating acute migraine pain and acknowledged that these therapies carry an increased risk for extrapyramidal side effects.
According to a study published in 2015 in Cephalgia, there were 1.2 million migraine visits to US emergency departments in 2010.2 With emerging preventive and acute treatments, it is possible that these numbers could decrease. However, the need for self-administration of acute migraine treatment and for migraine care in the emergency room setting is not likely to go away. The results regarding efficacy and safety of acute migraine therapies are encouraging, as patients who are experiencing migraine need acute therapy for distressing symptoms and do not always have many available options. Patients who can use prescription treatment may need to try a few different therapies before learning which acute migraine treatment is the most effective and which treatment causes the fewest side effects for them personally. Migraine patients who need care in the emergency room can experience speedy and effective relief with most available therapies.
Additional References
1. Pak K, Kim J, Lee GH, et al. Effectiveness of calcitonin gene-related peptide receptor antagonists for migraine treatment: a meta-analysis. Eur Neurol. 2022;85(3):195-201. doi: 10.1159/000521697 Source
2. Friedman BW, West J, Vinson DR, et al. Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia. 2015;35(4):301-309. doi: 10.1177/0333102414539055 Source
Migraine care requires a comprehensive approach. Identifying and avoiding triggers is a key component of patient-directed self-care. For many migraine patients, preventive therapy can substantially improve their quality of life. Yet, even with the best migraine prevention plan, many patients experience occasional migraines and require therapy for acute symptom relief. When it comes to selecting therapies for acute migraine treatment, criteria include efficacy, fast action, long duration of action, low risk for rebound symptoms, minimal side effects, and patient safety. Prescription therapies and therapies used in a medical setting include new calcitonin gene-related peptide (CGRP) receptor antagonists as well as antihistamines, antiemetics, neuroleptics, and triptans that have been used for years.
A study published in The Journal of Headache and Pain in April 2024 examined migraine symptom relief with the use of Nurtec OTD (rimegepant), one of the recently approved CGRP receptor antagonists. This post hoc subgroup analysis of a large double-blind randomized phase 3 clinical trial included 1075 participants, of whom 538 took 75 mg rimegepant and 537 took placebo to treat a single migraine episode. According to the analysis, rimegepant outperformed placebo on measures of freedom from the most bothersome symptom, pain relief at 2 hours post-dose, ability to function normally at 2 hours post-dose, use of rescue medication within 24 hours post-dose, and sustained pain freedom up to 48 hours post-dose. Treatment-emergent adverse events were assessed using EEG, vital signs, and laboratory tests. There was no notable difference in the incidence of adverse events between the rimegepant group and the placebo group, and no drug-related adverse events were reported.
This result is similar to that of previous studies which have demonstrated the significant efficacy of CGRP receptor blockers on acute migraine symptoms, including pain, bothersome symptoms, and nausea when compared with placebo.1
A study published in the May 2024 issue of Pediatric Emergency Care examined the efficacy of prochlorperazine monotherapy or prochlorperazine combined with diphenhydramine for the treatment of acute migraine in the pediatric emergency department. This retrospective study included 1683 patients who were treated with either prochlorperazine monotherapy or diphenhydramine co-administered with prochlorperazine. The authors reported that the need for additional therapy, the 72-hour return visit rates, and the admission rates were equal for both groups. They reported that, overall, 13% of the patients required additional therapy, 16.7% were admitted, and 5.3% returned within 72 hours. Extrapyramidal side effects were reported in 2.4% of patients in the prochlorperazine group, while none of the patients in the prochlorperazine/diphenhydramine group reported extrapyramidal side effects. This difference in side-effect incidence should not be interpreted as a protective effect of diphenhydramine but could be an indication that adding diphenhydramine did not increase the risk for extrapyramidal side effects.
A study published in the April 2024 issue of Headache examined the efficacy of parenteral agents on acute migraine in the emergency room setting. The data analysis included 97 studies. The authors examined the efficacy of these medications and various combinations:
- •diphenhydramine (intravenous);
- •trimethobenzamide (intramuscular);
- •granisetron (intravenous);
- •valproate (intravenous);
- •neuroleptics (intravenous):
- ◦prochlorperazine,
- ◦chlorpromazine,
- ◦haloperidol,
- ◦droperidol,
- ◦methotrimeprazine; and
- •dihydroergotamine (intravenous, intramuscular, or subcutaneous);
- •ketorolac (intravenous); and
- •magnesium sulfate (intravenous).
Each of these therapies was shown to improve migraine symptoms. According to the authors, "the majority of the parenteral agents commonly available to treat patients with migraine headaches in emergency settings was shown to be effective in providing pain relief." They recommended combination therapy or monotherapy of either neuroleptics or metoclopramide as first-line treatment options for treating acute migraine pain and acknowledged that these therapies carry an increased risk for extrapyramidal side effects.
According to a study published in 2015 in Cephalgia, there were 1.2 million migraine visits to US emergency departments in 2010.2 With emerging preventive and acute treatments, it is possible that these numbers could decrease. However, the need for self-administration of acute migraine treatment and for migraine care in the emergency room setting is not likely to go away. The results regarding efficacy and safety of acute migraine therapies are encouraging, as patients who are experiencing migraine need acute therapy for distressing symptoms and do not always have many available options. Patients who can use prescription treatment may need to try a few different therapies before learning which acute migraine treatment is the most effective and which treatment causes the fewest side effects for them personally. Migraine patients who need care in the emergency room can experience speedy and effective relief with most available therapies.
Additional References
1. Pak K, Kim J, Lee GH, et al. Effectiveness of calcitonin gene-related peptide receptor antagonists for migraine treatment: a meta-analysis. Eur Neurol. 2022;85(3):195-201. doi: 10.1159/000521697 Source
2. Friedman BW, West J, Vinson DR, et al. Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia. 2015;35(4):301-309. doi: 10.1177/0333102414539055 Source
Migraine care requires a comprehensive approach. Identifying and avoiding triggers is a key component of patient-directed self-care. For many migraine patients, preventive therapy can substantially improve their quality of life. Yet, even with the best migraine prevention plan, many patients experience occasional migraines and require therapy for acute symptom relief. When it comes to selecting therapies for acute migraine treatment, criteria include efficacy, fast action, long duration of action, low risk for rebound symptoms, minimal side effects, and patient safety. Prescription therapies and therapies used in a medical setting include new calcitonin gene-related peptide (CGRP) receptor antagonists as well as antihistamines, antiemetics, neuroleptics, and triptans that have been used for years.
A study published in The Journal of Headache and Pain in April 2024 examined migraine symptom relief with the use of Nurtec OTD (rimegepant), one of the recently approved CGRP receptor antagonists. This post hoc subgroup analysis of a large double-blind randomized phase 3 clinical trial included 1075 participants, of whom 538 took 75 mg rimegepant and 537 took placebo to treat a single migraine episode. According to the analysis, rimegepant outperformed placebo on measures of freedom from the most bothersome symptom, pain relief at 2 hours post-dose, ability to function normally at 2 hours post-dose, use of rescue medication within 24 hours post-dose, and sustained pain freedom up to 48 hours post-dose. Treatment-emergent adverse events were assessed using EEG, vital signs, and laboratory tests. There was no notable difference in the incidence of adverse events between the rimegepant group and the placebo group, and no drug-related adverse events were reported.
This result is similar to that of previous studies which have demonstrated the significant efficacy of CGRP receptor blockers on acute migraine symptoms, including pain, bothersome symptoms, and nausea when compared with placebo.1
A study published in the May 2024 issue of Pediatric Emergency Care examined the efficacy of prochlorperazine monotherapy or prochlorperazine combined with diphenhydramine for the treatment of acute migraine in the pediatric emergency department. This retrospective study included 1683 patients who were treated with either prochlorperazine monotherapy or diphenhydramine co-administered with prochlorperazine. The authors reported that the need for additional therapy, the 72-hour return visit rates, and the admission rates were equal for both groups. They reported that, overall, 13% of the patients required additional therapy, 16.7% were admitted, and 5.3% returned within 72 hours. Extrapyramidal side effects were reported in 2.4% of patients in the prochlorperazine group, while none of the patients in the prochlorperazine/diphenhydramine group reported extrapyramidal side effects. This difference in side-effect incidence should not be interpreted as a protective effect of diphenhydramine but could be an indication that adding diphenhydramine did not increase the risk for extrapyramidal side effects.
A study published in the April 2024 issue of Headache examined the efficacy of parenteral agents on acute migraine in the emergency room setting. The data analysis included 97 studies. The authors examined the efficacy of these medications and various combinations:
- •diphenhydramine (intravenous);
- •trimethobenzamide (intramuscular);
- •granisetron (intravenous);
- •valproate (intravenous);
- •neuroleptics (intravenous):
- ◦prochlorperazine,
- ◦chlorpromazine,
- ◦haloperidol,
- ◦droperidol,
- ◦methotrimeprazine; and
- •dihydroergotamine (intravenous, intramuscular, or subcutaneous);
- •ketorolac (intravenous); and
- •magnesium sulfate (intravenous).
Each of these therapies was shown to improve migraine symptoms. According to the authors, "the majority of the parenteral agents commonly available to treat patients with migraine headaches in emergency settings was shown to be effective in providing pain relief." They recommended combination therapy or monotherapy of either neuroleptics or metoclopramide as first-line treatment options for treating acute migraine pain and acknowledged that these therapies carry an increased risk for extrapyramidal side effects.
According to a study published in 2015 in Cephalgia, there were 1.2 million migraine visits to US emergency departments in 2010.2 With emerging preventive and acute treatments, it is possible that these numbers could decrease. However, the need for self-administration of acute migraine treatment and for migraine care in the emergency room setting is not likely to go away. The results regarding efficacy and safety of acute migraine therapies are encouraging, as patients who are experiencing migraine need acute therapy for distressing symptoms and do not always have many available options. Patients who can use prescription treatment may need to try a few different therapies before learning which acute migraine treatment is the most effective and which treatment causes the fewest side effects for them personally. Migraine patients who need care in the emergency room can experience speedy and effective relief with most available therapies.
Additional References
1. Pak K, Kim J, Lee GH, et al. Effectiveness of calcitonin gene-related peptide receptor antagonists for migraine treatment: a meta-analysis. Eur Neurol. 2022;85(3):195-201. doi: 10.1159/000521697 Source
2. Friedman BW, West J, Vinson DR, et al. Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia. 2015;35(4):301-309. doi: 10.1177/0333102414539055 Source
Commentary: Diet and Lifestyle in Migraine, May 2024
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
Commentary: Migraine and Cardiovascular Risk, April 2024
A recent study, published in the March 2024 issue of Sleep Medicine, identified shift work as one of the risk factors for headache and migraine. The researchers conducted a meta-analysis, including seven studies and involving 422,869 participants. The authors defined shift work as characterized by individuals or teams working consecutively to exceed the standard 8-hour day. They reported that the pooled analysis revealed a significant association between shift work and an increased risk for headache. Specifically, they determined that "individuals working night shifts had a 44% higher risk of developing headaches and a higher incidence of migraines." The authors stated that this association did not establish any causal relationship, and they suggested that future research should investigate the impact of genetics or health behaviors, which could be considered shared risk factors.
An article that had been published in 2019 in Headache included two case reports detailing the effects of shift work on patients with migraine. The authors of the case reports stated that "in the two cases presented, shift work appeared to be associated with chronification of migraine and higher headache-related disability, despite optimal headache management and good patient adherence."[1] They observed that "a switch to only day shifts promoted transition to an episodic, less disabling pattern of migraine."[1] These publications both support the idea that, while patients may have an underlying predisposition to migraine, certain lifestyle factors can play a role in exacerbating symptoms.
Erenumab, one of the relatively new therapies for migraine, was found to have a potential link to worsening hypertension. According to an article published in February in Headache: The Journal of Head and Face Pain, there has not been evidence of hypertension in preclinical models or clinical trials, yet postmarketing data suggest that erenumab may be associated with hypertension. The authors conducted an observational retrospective cohort study that included 335 patients who had been seen at a tertiary headache or neurology department. At baseline, 20.9% (70/335) of patients had a prior diagnosis of hypertension. The researchers observed that 23.3% (78/335) of the patients were found to have worsening hypertension, and 13 patients of the 225 who continued on erenumab experienced an improvement in their blood pressure. The authors noted that there was no association between worsening hypertension and preexisting hypertension, sex, body mass index, or age, but patients with atrial fibrillation were more likely to develop worsening hypertension (odds ratio 4.9; 95% CI 1.12-21.4; P = .035).
Consideration of a relationship between hypertension and anti-calcitonin gene–related peptide migraine (CGRP) therapies has been found in other studies as well. Results of a retrospective study conducted at the University Hospital of Modena, to explore the rate of hypertension among patients treated with anti-CGRP monoclonal antibodies, were published in April 2024 in Neurological Sciences (published online November 6, 2023). Those authors reported that no significant increase in blood pressure was detected overall, yet 5.7% of the patients developed a significant increase in their blood pressure.[2] Specifically, the researchers reported that patients with preexisting hypertension were more likely to have a significant increase in blood pressure.[2] The study authors of the Neurological Sciences publication suggested that patients with preexisting hypertension should be cautiously monitored for signs of hypertension. A more recent publication noted that "CGRP is involved in the regulation of vasomotor tone under physiologic and pathologic conditions, including hypertension," which could explain these findings. As the two studies noted different underlying risk factors for hypertension for patients taking anti-CGRP migraine therapies, it is important to monitor patients for signs of hypertension regardless of their underlying cardiovascular status.
Migraine was also noted to potentially be associated with an increased risk for cerebrovascular disease and stroke among women who have underlying cardiovascular disease risk factors. According to a cross-sectional analysis whose results were published in Mayo Clinic Proceedings in May 2023, women with migraine were significantly more likely to have severe hot flashes compared with women without migraine.[3] Additionally, the authors stated that migraine was associated with a diagnosis of hypertension.[3]
Results of a secondary data analysis of a subset of 1954 women in the Coronary Artery Risk Development in Young Adults (CARDIA) study were published in the April 2024 issue of Menopause. After adjustment for age, race, estrogen use, oophorectomy, and hysterectomy, women with histories of migraine and persistent vasomotor symptoms were found to have a greater risk for cerebrovascular disease (hazard ratio [HR] 2.25; 95% CI 1.15-4.38), and stroke (HR 3.15; 95% CI 1.35-7.34), compared with women without migraine histories and with minimal vasomotor symptoms. After adjustment for cerebrovascular disease risk factors, the associations between migraine/vasomotor symptoms and cerebrovascular disease were attenuated (HR 1.51; 95% CI 0.73-3.10), and associations between migraine/vasomotor symptoms and stroke were similarly attenuated (HR 1.70; 95% CI 0.66-4.38). The authors of this research article concluded that migraine and persistent vasomotor symptoms are jointly associated with greater risk for cerebrovascular disease and stroke, particularly for women who already have traditional risk factors for cerebrovascular disease.
This new research brings the importance of managing migraine risk factors and symptoms to the forefront. Patients who experience migraine may have a higher risk for cerebrovascular disease. Minimizing migraine risk factors could potentially help reduce this risk for cerebrovascular disease for some patients, and effectively treating migraines may also play a role in reducing the risk for cerebrovascular disease. Some migraine therapies could worsen cardiovascular disease for some patients, however — particularly patients who already have underlying risk factors. Therefore, it is crucial for physicians to approach migraine care with a comprehensive strategy to reduce risk factors, assess underlying disease, and monitor for comorbidities.
Additional References
1. Sandoe CH, Sasikumar S, Lay C, Lawler V. The impact of shift work on migraine: A case series and narrative review. Headache. 2019;59:1631-1640. doi: 10.1111/head.13622 Source
2. Guerzoni S, Castro FL, Brovia D, Baraldi C, Pani L. Evaluation of the risk of hypertension in patients treated with anti-CGRP monoclonal antibodies in a real-life study. Neurol Sci. 2024;45:1661-1668. doi: 10.1007/s10072-023-07167-z Source
3. Faubion SS, Smith T, Thielen J, et al. Association of migraine and vasomotor symptoms. Mayo Clin Proc. 2023;98:701-712. doi: 10.1016/j.mayocp.2023.01.010 Source
A recent study, published in the March 2024 issue of Sleep Medicine, identified shift work as one of the risk factors for headache and migraine. The researchers conducted a meta-analysis, including seven studies and involving 422,869 participants. The authors defined shift work as characterized by individuals or teams working consecutively to exceed the standard 8-hour day. They reported that the pooled analysis revealed a significant association between shift work and an increased risk for headache. Specifically, they determined that "individuals working night shifts had a 44% higher risk of developing headaches and a higher incidence of migraines." The authors stated that this association did not establish any causal relationship, and they suggested that future research should investigate the impact of genetics or health behaviors, which could be considered shared risk factors.
An article that had been published in 2019 in Headache included two case reports detailing the effects of shift work on patients with migraine. The authors of the case reports stated that "in the two cases presented, shift work appeared to be associated with chronification of migraine and higher headache-related disability, despite optimal headache management and good patient adherence."[1] They observed that "a switch to only day shifts promoted transition to an episodic, less disabling pattern of migraine."[1] These publications both support the idea that, while patients may have an underlying predisposition to migraine, certain lifestyle factors can play a role in exacerbating symptoms.
Erenumab, one of the relatively new therapies for migraine, was found to have a potential link to worsening hypertension. According to an article published in February in Headache: The Journal of Head and Face Pain, there has not been evidence of hypertension in preclinical models or clinical trials, yet postmarketing data suggest that erenumab may be associated with hypertension. The authors conducted an observational retrospective cohort study that included 335 patients who had been seen at a tertiary headache or neurology department. At baseline, 20.9% (70/335) of patients had a prior diagnosis of hypertension. The researchers observed that 23.3% (78/335) of the patients were found to have worsening hypertension, and 13 patients of the 225 who continued on erenumab experienced an improvement in their blood pressure. The authors noted that there was no association between worsening hypertension and preexisting hypertension, sex, body mass index, or age, but patients with atrial fibrillation were more likely to develop worsening hypertension (odds ratio 4.9; 95% CI 1.12-21.4; P = .035).
Consideration of a relationship between hypertension and anti-calcitonin gene–related peptide migraine (CGRP) therapies has been found in other studies as well. Results of a retrospective study conducted at the University Hospital of Modena, to explore the rate of hypertension among patients treated with anti-CGRP monoclonal antibodies, were published in April 2024 in Neurological Sciences (published online November 6, 2023). Those authors reported that no significant increase in blood pressure was detected overall, yet 5.7% of the patients developed a significant increase in their blood pressure.[2] Specifically, the researchers reported that patients with preexisting hypertension were more likely to have a significant increase in blood pressure.[2] The study authors of the Neurological Sciences publication suggested that patients with preexisting hypertension should be cautiously monitored for signs of hypertension. A more recent publication noted that "CGRP is involved in the regulation of vasomotor tone under physiologic and pathologic conditions, including hypertension," which could explain these findings. As the two studies noted different underlying risk factors for hypertension for patients taking anti-CGRP migraine therapies, it is important to monitor patients for signs of hypertension regardless of their underlying cardiovascular status.
Migraine was also noted to potentially be associated with an increased risk for cerebrovascular disease and stroke among women who have underlying cardiovascular disease risk factors. According to a cross-sectional analysis whose results were published in Mayo Clinic Proceedings in May 2023, women with migraine were significantly more likely to have severe hot flashes compared with women without migraine.[3] Additionally, the authors stated that migraine was associated with a diagnosis of hypertension.[3]
Results of a secondary data analysis of a subset of 1954 women in the Coronary Artery Risk Development in Young Adults (CARDIA) study were published in the April 2024 issue of Menopause. After adjustment for age, race, estrogen use, oophorectomy, and hysterectomy, women with histories of migraine and persistent vasomotor symptoms were found to have a greater risk for cerebrovascular disease (hazard ratio [HR] 2.25; 95% CI 1.15-4.38), and stroke (HR 3.15; 95% CI 1.35-7.34), compared with women without migraine histories and with minimal vasomotor symptoms. After adjustment for cerebrovascular disease risk factors, the associations between migraine/vasomotor symptoms and cerebrovascular disease were attenuated (HR 1.51; 95% CI 0.73-3.10), and associations between migraine/vasomotor symptoms and stroke were similarly attenuated (HR 1.70; 95% CI 0.66-4.38). The authors of this research article concluded that migraine and persistent vasomotor symptoms are jointly associated with greater risk for cerebrovascular disease and stroke, particularly for women who already have traditional risk factors for cerebrovascular disease.
This new research brings the importance of managing migraine risk factors and symptoms to the forefront. Patients who experience migraine may have a higher risk for cerebrovascular disease. Minimizing migraine risk factors could potentially help reduce this risk for cerebrovascular disease for some patients, and effectively treating migraines may also play a role in reducing the risk for cerebrovascular disease. Some migraine therapies could worsen cardiovascular disease for some patients, however — particularly patients who already have underlying risk factors. Therefore, it is crucial for physicians to approach migraine care with a comprehensive strategy to reduce risk factors, assess underlying disease, and monitor for comorbidities.
Additional References
1. Sandoe CH, Sasikumar S, Lay C, Lawler V. The impact of shift work on migraine: A case series and narrative review. Headache. 2019;59:1631-1640. doi: 10.1111/head.13622 Source
2. Guerzoni S, Castro FL, Brovia D, Baraldi C, Pani L. Evaluation of the risk of hypertension in patients treated with anti-CGRP monoclonal antibodies in a real-life study. Neurol Sci. 2024;45:1661-1668. doi: 10.1007/s10072-023-07167-z Source
3. Faubion SS, Smith T, Thielen J, et al. Association of migraine and vasomotor symptoms. Mayo Clin Proc. 2023;98:701-712. doi: 10.1016/j.mayocp.2023.01.010 Source
A recent study, published in the March 2024 issue of Sleep Medicine, identified shift work as one of the risk factors for headache and migraine. The researchers conducted a meta-analysis, including seven studies and involving 422,869 participants. The authors defined shift work as characterized by individuals or teams working consecutively to exceed the standard 8-hour day. They reported that the pooled analysis revealed a significant association between shift work and an increased risk for headache. Specifically, they determined that "individuals working night shifts had a 44% higher risk of developing headaches and a higher incidence of migraines." The authors stated that this association did not establish any causal relationship, and they suggested that future research should investigate the impact of genetics or health behaviors, which could be considered shared risk factors.
An article that had been published in 2019 in Headache included two case reports detailing the effects of shift work on patients with migraine. The authors of the case reports stated that "in the two cases presented, shift work appeared to be associated with chronification of migraine and higher headache-related disability, despite optimal headache management and good patient adherence."[1] They observed that "a switch to only day shifts promoted transition to an episodic, less disabling pattern of migraine."[1] These publications both support the idea that, while patients may have an underlying predisposition to migraine, certain lifestyle factors can play a role in exacerbating symptoms.
Erenumab, one of the relatively new therapies for migraine, was found to have a potential link to worsening hypertension. According to an article published in February in Headache: The Journal of Head and Face Pain, there has not been evidence of hypertension in preclinical models or clinical trials, yet postmarketing data suggest that erenumab may be associated with hypertension. The authors conducted an observational retrospective cohort study that included 335 patients who had been seen at a tertiary headache or neurology department. At baseline, 20.9% (70/335) of patients had a prior diagnosis of hypertension. The researchers observed that 23.3% (78/335) of the patients were found to have worsening hypertension, and 13 patients of the 225 who continued on erenumab experienced an improvement in their blood pressure. The authors noted that there was no association between worsening hypertension and preexisting hypertension, sex, body mass index, or age, but patients with atrial fibrillation were more likely to develop worsening hypertension (odds ratio 4.9; 95% CI 1.12-21.4; P = .035).
Consideration of a relationship between hypertension and anti-calcitonin gene–related peptide migraine (CGRP) therapies has been found in other studies as well. Results of a retrospective study conducted at the University Hospital of Modena, to explore the rate of hypertension among patients treated with anti-CGRP monoclonal antibodies, were published in April 2024 in Neurological Sciences (published online November 6, 2023). Those authors reported that no significant increase in blood pressure was detected overall, yet 5.7% of the patients developed a significant increase in their blood pressure.[2] Specifically, the researchers reported that patients with preexisting hypertension were more likely to have a significant increase in blood pressure.[2] The study authors of the Neurological Sciences publication suggested that patients with preexisting hypertension should be cautiously monitored for signs of hypertension. A more recent publication noted that "CGRP is involved in the regulation of vasomotor tone under physiologic and pathologic conditions, including hypertension," which could explain these findings. As the two studies noted different underlying risk factors for hypertension for patients taking anti-CGRP migraine therapies, it is important to monitor patients for signs of hypertension regardless of their underlying cardiovascular status.
Migraine was also noted to potentially be associated with an increased risk for cerebrovascular disease and stroke among women who have underlying cardiovascular disease risk factors. According to a cross-sectional analysis whose results were published in Mayo Clinic Proceedings in May 2023, women with migraine were significantly more likely to have severe hot flashes compared with women without migraine.[3] Additionally, the authors stated that migraine was associated with a diagnosis of hypertension.[3]
Results of a secondary data analysis of a subset of 1954 women in the Coronary Artery Risk Development in Young Adults (CARDIA) study were published in the April 2024 issue of Menopause. After adjustment for age, race, estrogen use, oophorectomy, and hysterectomy, women with histories of migraine and persistent vasomotor symptoms were found to have a greater risk for cerebrovascular disease (hazard ratio [HR] 2.25; 95% CI 1.15-4.38), and stroke (HR 3.15; 95% CI 1.35-7.34), compared with women without migraine histories and with minimal vasomotor symptoms. After adjustment for cerebrovascular disease risk factors, the associations between migraine/vasomotor symptoms and cerebrovascular disease were attenuated (HR 1.51; 95% CI 0.73-3.10), and associations between migraine/vasomotor symptoms and stroke were similarly attenuated (HR 1.70; 95% CI 0.66-4.38). The authors of this research article concluded that migraine and persistent vasomotor symptoms are jointly associated with greater risk for cerebrovascular disease and stroke, particularly for women who already have traditional risk factors for cerebrovascular disease.
This new research brings the importance of managing migraine risk factors and symptoms to the forefront. Patients who experience migraine may have a higher risk for cerebrovascular disease. Minimizing migraine risk factors could potentially help reduce this risk for cerebrovascular disease for some patients, and effectively treating migraines may also play a role in reducing the risk for cerebrovascular disease. Some migraine therapies could worsen cardiovascular disease for some patients, however — particularly patients who already have underlying risk factors. Therefore, it is crucial for physicians to approach migraine care with a comprehensive strategy to reduce risk factors, assess underlying disease, and monitor for comorbidities.
Additional References
1. Sandoe CH, Sasikumar S, Lay C, Lawler V. The impact of shift work on migraine: A case series and narrative review. Headache. 2019;59:1631-1640. doi: 10.1111/head.13622 Source
2. Guerzoni S, Castro FL, Brovia D, Baraldi C, Pani L. Evaluation of the risk of hypertension in patients treated with anti-CGRP monoclonal antibodies in a real-life study. Neurol Sci. 2024;45:1661-1668. doi: 10.1007/s10072-023-07167-z Source
3. Faubion SS, Smith T, Thielen J, et al. Association of migraine and vasomotor symptoms. Mayo Clin Proc. 2023;98:701-712. doi: 10.1016/j.mayocp.2023.01.010 Source
Commentary: Comorbidities in Migraine, March 2024
Additionally, several recently published reviews have examined the risks of comorbidities that are not neurologic or cardiovascular, such as allergies, inflammatory bowel disease, obesity, and diabetes. Although these types of associations are not inherently obvious in terms of migraine pathophysiology, determining whether there is a link may help shed a light on some contributing factors that could play a role in migraine or in the comorbid disorders.
Authors of a study published in the January 2024 issue of the European Journal of Medical Research sought to examine the relationship between allergic rhinitis and migraine. They noted that several studies, as well as a statement from the American Migraine Prevalence and Prevention Study, published in 2013, reported an increased frequency of migraines in patients with allergic rhinitis. The researchers used data extracted from the UK Biobank, comprising 25,486 patients diagnosed with allergic rhinitis and 87,097 controls and 8547 migraine cases and 176,107 controls. They performed statistical analysis using bidirectional two-sample Mendelian randomization with publicly available summary-level statistics of large genome-wide association studies to estimate the possible causal effects. The researchers did not find any clear causal or genetic association between allergic rhinitis and migraine risk. However, the lack of causation between migraine and allergic rhinitis does not contradict previous studies that point to the prevalence of comorbidity of the two conditions. It's also important to note that congestion is a known migraine trigger, and the results of the study do not contradict that relationship. Given the variability of results from different research studies, the authors suggested that more research is warranted to help untangle the complex association between allergic rhinitis and migraine.
Inflammatory bowel disease (IBD) is another condition with a higher prevalence in patients who have migraine. A January 2024 article in Scientific Reports described the results of a nationwide population-based study that was conducted using data from the Korean National Health Insurance Service database. This study included 10,131,193 individuals. The researchers found that the risk for development of IBD in patients with migraine was significantly higher, by 1.3 times, compared with the general population. These results are similar to previous studies, such as a meta-analysis published in May 2023 in the International Journal of Preventive Medicine, which reported a pooled prevalence of migraine in IBD cases of 19%, with 1.5-fold higher odds of developing migraine in IBD cases when compared with controls.[3] These studies were both aimed at examining epidemiologic data rather than uncovering a physiologic or genetic cause of the link, and neither study described an explanation for this connection.
A Mendelian randomization study published in May 2023 in Headache investigated potential genetic links between migraine and IBD. As with the January 2024 European Journal of Medical Research study that was done to search for a genetic association between migraine and allergic rhinitis, the authors stated that there was no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease.[4] Although the evidence doesn't point to a causal relationship, it's important to note that diet plays a role in migraine management, and diet is especially important in managing IBD. Consideration of dietary factors could be beneficial for preventing symptoms — and is even more important for avoiding exacerbation of symptoms.
A high body mass index (BMI) is correlated with migraine. A study published in January 2024 in BMC Geriatrics analyzed data from people who participated in the National Health and Nutrition Examination Survey between 1999 and 2004 by the Centers for Disease Control and the National Center for Health Statistics, comprising a total of 31,126 participants. The researchers found a linear association between BMI and migraine. They also noted that increased BMI was related to a significantly higher risk for migraine in the group with diabetes, but this positive relationship between BMI and migraine seemed to be smaller in the group without diabetes. The authors considered inflammation associated with obesity as a possible contributing factor for this link but acknowledged that the pathophysiologic mechanism is unknown and suggested that there is a high likelihood of confounding factors. Given that diabetes and obesity are both correlated with an increased risk for vascular disease and migraine is associated with a slight increase in cardiovascular risk, it could be especially important to identify these comorbidities in individual patients.
Migraine is common, and many comorbidities have been verified with population studies. Although there are some explanations for the links between migraine and vascular or neurologic conditions, the cause of associations between migraine and other conditions is not known. Some theories that have begun to be investigated include inflammation and genetics. Eventually, further research and understanding of contributing factors could potentially provide explanations that may help in diagnosing migraine or associated disorders at an early stage — and might even be used to help guide treatment.
Additional References
1. Ashina M, Katsarava Z, Do TP, et al. Migraine: Epidemiology and systems of care. Lancet. 2021;397:1485-1495. doi: 10.1016/S0140-6736(20)32160-7 Source
2. Burch RC, Buse DC, Lipton RB. Migraine: Epidemiology, burden, and comorbidity. Neurol Clin. 2019;37:631-649. doi: 10.1016/j.ncl.2019.06.001 Source
3. Olfati H, Mirmosayyeb O, Hosseinabadi AM, Ghajarzadeh M. The prevalence of migraine in inflammatory bowel disease, a systematic review and meta-analysis. Int J Prev Med. 2023;14:66. doi: 10.4103/ijpvm.ijpvm_413_21 Source
4. Welander NZ, Rukh G, Rask-Andersen M, Harder AV, et al and International Headache Genetics Consortium. Migraine, inflammatory bowel disease and celiac disease: A Mendelian randomization study. Headache. 2023;63:642-651. doi: 10.1111/head.14470 Source
Additionally, several recently published reviews have examined the risks of comorbidities that are not neurologic or cardiovascular, such as allergies, inflammatory bowel disease, obesity, and diabetes. Although these types of associations are not inherently obvious in terms of migraine pathophysiology, determining whether there is a link may help shed a light on some contributing factors that could play a role in migraine or in the comorbid disorders.
Authors of a study published in the January 2024 issue of the European Journal of Medical Research sought to examine the relationship between allergic rhinitis and migraine. They noted that several studies, as well as a statement from the American Migraine Prevalence and Prevention Study, published in 2013, reported an increased frequency of migraines in patients with allergic rhinitis. The researchers used data extracted from the UK Biobank, comprising 25,486 patients diagnosed with allergic rhinitis and 87,097 controls and 8547 migraine cases and 176,107 controls. They performed statistical analysis using bidirectional two-sample Mendelian randomization with publicly available summary-level statistics of large genome-wide association studies to estimate the possible causal effects. The researchers did not find any clear causal or genetic association between allergic rhinitis and migraine risk. However, the lack of causation between migraine and allergic rhinitis does not contradict previous studies that point to the prevalence of comorbidity of the two conditions. It's also important to note that congestion is a known migraine trigger, and the results of the study do not contradict that relationship. Given the variability of results from different research studies, the authors suggested that more research is warranted to help untangle the complex association between allergic rhinitis and migraine.
Inflammatory bowel disease (IBD) is another condition with a higher prevalence in patients who have migraine. A January 2024 article in Scientific Reports described the results of a nationwide population-based study that was conducted using data from the Korean National Health Insurance Service database. This study included 10,131,193 individuals. The researchers found that the risk for development of IBD in patients with migraine was significantly higher, by 1.3 times, compared with the general population. These results are similar to previous studies, such as a meta-analysis published in May 2023 in the International Journal of Preventive Medicine, which reported a pooled prevalence of migraine in IBD cases of 19%, with 1.5-fold higher odds of developing migraine in IBD cases when compared with controls.[3] These studies were both aimed at examining epidemiologic data rather than uncovering a physiologic or genetic cause of the link, and neither study described an explanation for this connection.
A Mendelian randomization study published in May 2023 in Headache investigated potential genetic links between migraine and IBD. As with the January 2024 European Journal of Medical Research study that was done to search for a genetic association between migraine and allergic rhinitis, the authors stated that there was no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease.[4] Although the evidence doesn't point to a causal relationship, it's important to note that diet plays a role in migraine management, and diet is especially important in managing IBD. Consideration of dietary factors could be beneficial for preventing symptoms — and is even more important for avoiding exacerbation of symptoms.
A high body mass index (BMI) is correlated with migraine. A study published in January 2024 in BMC Geriatrics analyzed data from people who participated in the National Health and Nutrition Examination Survey between 1999 and 2004 by the Centers for Disease Control and the National Center for Health Statistics, comprising a total of 31,126 participants. The researchers found a linear association between BMI and migraine. They also noted that increased BMI was related to a significantly higher risk for migraine in the group with diabetes, but this positive relationship between BMI and migraine seemed to be smaller in the group without diabetes. The authors considered inflammation associated with obesity as a possible contributing factor for this link but acknowledged that the pathophysiologic mechanism is unknown and suggested that there is a high likelihood of confounding factors. Given that diabetes and obesity are both correlated with an increased risk for vascular disease and migraine is associated with a slight increase in cardiovascular risk, it could be especially important to identify these comorbidities in individual patients.
Migraine is common, and many comorbidities have been verified with population studies. Although there are some explanations for the links between migraine and vascular or neurologic conditions, the cause of associations between migraine and other conditions is not known. Some theories that have begun to be investigated include inflammation and genetics. Eventually, further research and understanding of contributing factors could potentially provide explanations that may help in diagnosing migraine or associated disorders at an early stage — and might even be used to help guide treatment.
Additional References
1. Ashina M, Katsarava Z, Do TP, et al. Migraine: Epidemiology and systems of care. Lancet. 2021;397:1485-1495. doi: 10.1016/S0140-6736(20)32160-7 Source
2. Burch RC, Buse DC, Lipton RB. Migraine: Epidemiology, burden, and comorbidity. Neurol Clin. 2019;37:631-649. doi: 10.1016/j.ncl.2019.06.001 Source
3. Olfati H, Mirmosayyeb O, Hosseinabadi AM, Ghajarzadeh M. The prevalence of migraine in inflammatory bowel disease, a systematic review and meta-analysis. Int J Prev Med. 2023;14:66. doi: 10.4103/ijpvm.ijpvm_413_21 Source
4. Welander NZ, Rukh G, Rask-Andersen M, Harder AV, et al and International Headache Genetics Consortium. Migraine, inflammatory bowel disease and celiac disease: A Mendelian randomization study. Headache. 2023;63:642-651. doi: 10.1111/head.14470 Source
Additionally, several recently published reviews have examined the risks of comorbidities that are not neurologic or cardiovascular, such as allergies, inflammatory bowel disease, obesity, and diabetes. Although these types of associations are not inherently obvious in terms of migraine pathophysiology, determining whether there is a link may help shed a light on some contributing factors that could play a role in migraine or in the comorbid disorders.
Authors of a study published in the January 2024 issue of the European Journal of Medical Research sought to examine the relationship between allergic rhinitis and migraine. They noted that several studies, as well as a statement from the American Migraine Prevalence and Prevention Study, published in 2013, reported an increased frequency of migraines in patients with allergic rhinitis. The researchers used data extracted from the UK Biobank, comprising 25,486 patients diagnosed with allergic rhinitis and 87,097 controls and 8547 migraine cases and 176,107 controls. They performed statistical analysis using bidirectional two-sample Mendelian randomization with publicly available summary-level statistics of large genome-wide association studies to estimate the possible causal effects. The researchers did not find any clear causal or genetic association between allergic rhinitis and migraine risk. However, the lack of causation between migraine and allergic rhinitis does not contradict previous studies that point to the prevalence of comorbidity of the two conditions. It's also important to note that congestion is a known migraine trigger, and the results of the study do not contradict that relationship. Given the variability of results from different research studies, the authors suggested that more research is warranted to help untangle the complex association between allergic rhinitis and migraine.
Inflammatory bowel disease (IBD) is another condition with a higher prevalence in patients who have migraine. A January 2024 article in Scientific Reports described the results of a nationwide population-based study that was conducted using data from the Korean National Health Insurance Service database. This study included 10,131,193 individuals. The researchers found that the risk for development of IBD in patients with migraine was significantly higher, by 1.3 times, compared with the general population. These results are similar to previous studies, such as a meta-analysis published in May 2023 in the International Journal of Preventive Medicine, which reported a pooled prevalence of migraine in IBD cases of 19%, with 1.5-fold higher odds of developing migraine in IBD cases when compared with controls.[3] These studies were both aimed at examining epidemiologic data rather than uncovering a physiologic or genetic cause of the link, and neither study described an explanation for this connection.
A Mendelian randomization study published in May 2023 in Headache investigated potential genetic links between migraine and IBD. As with the January 2024 European Journal of Medical Research study that was done to search for a genetic association between migraine and allergic rhinitis, the authors stated that there was no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease.[4] Although the evidence doesn't point to a causal relationship, it's important to note that diet plays a role in migraine management, and diet is especially important in managing IBD. Consideration of dietary factors could be beneficial for preventing symptoms — and is even more important for avoiding exacerbation of symptoms.
A high body mass index (BMI) is correlated with migraine. A study published in January 2024 in BMC Geriatrics analyzed data from people who participated in the National Health and Nutrition Examination Survey between 1999 and 2004 by the Centers for Disease Control and the National Center for Health Statistics, comprising a total of 31,126 participants. The researchers found a linear association between BMI and migraine. They also noted that increased BMI was related to a significantly higher risk for migraine in the group with diabetes, but this positive relationship between BMI and migraine seemed to be smaller in the group without diabetes. The authors considered inflammation associated with obesity as a possible contributing factor for this link but acknowledged that the pathophysiologic mechanism is unknown and suggested that there is a high likelihood of confounding factors. Given that diabetes and obesity are both correlated with an increased risk for vascular disease and migraine is associated with a slight increase in cardiovascular risk, it could be especially important to identify these comorbidities in individual patients.
Migraine is common, and many comorbidities have been verified with population studies. Although there are some explanations for the links between migraine and vascular or neurologic conditions, the cause of associations between migraine and other conditions is not known. Some theories that have begun to be investigated include inflammation and genetics. Eventually, further research and understanding of contributing factors could potentially provide explanations that may help in diagnosing migraine or associated disorders at an early stage — and might even be used to help guide treatment.
Additional References
1. Ashina M, Katsarava Z, Do TP, et al. Migraine: Epidemiology and systems of care. Lancet. 2021;397:1485-1495. doi: 10.1016/S0140-6736(20)32160-7 Source
2. Burch RC, Buse DC, Lipton RB. Migraine: Epidemiology, burden, and comorbidity. Neurol Clin. 2019;37:631-649. doi: 10.1016/j.ncl.2019.06.001 Source
3. Olfati H, Mirmosayyeb O, Hosseinabadi AM, Ghajarzadeh M. The prevalence of migraine in inflammatory bowel disease, a systematic review and meta-analysis. Int J Prev Med. 2023;14:66. doi: 10.4103/ijpvm.ijpvm_413_21 Source
4. Welander NZ, Rukh G, Rask-Andersen M, Harder AV, et al and International Headache Genetics Consortium. Migraine, inflammatory bowel disease and celiac disease: A Mendelian randomization study. Headache. 2023;63:642-651. doi: 10.1111/head.14470 Source
Commentary: Gut Microbiota and CGRP in Migraine, February 2024
The authors of a study published in the December 2023 issue of the Scandinavian Journal of Gastroenterology analyzed data to examine the potential link between gut microbiota and migraine. According to the statistical analysis, the researchers found that "a greater abundance of genus Lactobacillus was associated with a higher risk of migraine and a higher abundance of family Prevotellaceae was related to a decreased risk of migraine." Furthermore, they noted that these gut microbial patterns could be due to a genetic predisposition. The authors suggested that stool sampling could potentially be helpful in the diagnosis of migraine, and that measures to modify gut microbiota in the context of migraine therapy could be identified with future research.
While it is not clear whether migraine is a cause or effect of these alterations, or whether there is another confounding variable, the idea of using diet as a means of reducing migraine risk would be appealing for many patients. This offers hope, but it also leaves a window open for exaggeration and excessive reliance on certain foods or supplements before reliable links are established.
Further examining the genetic factors that might play a role in migraine, a large Korean data analysis published in the December 2023 issue of Epidemiology and Health described a link between migraine and Parkinson's disease. The researchers included 214,193 patients with migraine and 5,879,711 individuals without migraine. According to the statistical analysis, the patients who had migraine with aura showed a 1.35-fold higher risk for Parkinson's disease than individuals without migraine. However, the researchers did not note a statistically significant difference between the risk for Parkinson's disease among patients who had migraine without aura and individuals without migraine.
They also examined other factors, and noted that among individuals with migraine, those who had preexisting dyslipidemia had a higher risk for Parkinson's disease than those who did not have dyslipidemia. Other factors that were not correlated with an association between migraine and Parkinson's disease included cardiovascular risk factors, hypertension, diabetes, smoking status, and high body mass index.
The study authors noted that factors associated with the activity of calcitonin gene-related peptide (CGRP), which is known to play a significant role in the pathophysiology of migraine, could play a role in the link between migraine and Parkinson's disease. They pointed to previous studies that found evidence of elevated CGRP levels in the cerebrospinal fluid of patients with Parkinson's disease as possible evidence of a pathophysiologic link.
An earlier commentary, published in the April 2020 issue of Headache, suggested an implication of CGRP antagonists in the development of neurodegenerative disorders such as Parkinson's disease. The commentary authors noted that previous research correlated midlife migraine to late-life parkinsonism, suggesting a conceivable common pathology, which could include a genetic or environmental predisposition.[1] They also noted that studies suggest a possible link between CGRP and multiple system atrophy, a parkinsonian disorder.[1] They considered the possibility that one of the ways that CGRP could contribute to these disorders is through its role in the recruitment of inflammatory mediators, which can alter the function of nicotinic receptors in the dopaminergic system in Parkinson's disease pathogenesis.[2]
Recent research published in the December 2023 issue of Headache suggests that CGRP responsiveness in migraine therapy could be mediated by genetics. The study included 198 patients who had been typed for genes involved in CGRP signaling or pharmacologic response and were given genetic and polygenic risk scores. Responders were defined as patients who experienced ≥ 50% reduction in migraine days per month at 5.7-month follow-up.
The analysis revealed an association between nonresponder status and rs12615320-G in RAMP1, a gene that encodes a component of high-affinity CGRP receptors, which increased the risk for nonresponder status. The researchers also identified an association between nonresponder status and rs4680-A in COMT, a gene that has been associated with lower COMT enzymatic activity, chronic pain/fibromyalgia, and a "worrier" phenotype. Nonresponders also had a lower mean genetic risk score than responders. These genetic associations could help identify which patients would be most likely to benefit from anti-CGRP therapies.
Given that CGRP responsiveness may have a genetic component, it is possible that one of the contributors to the link between migraine and Parkinson's disease could lie in patients' genetic predisposition to CGRP activity. Yet, the association between these two common conditions is not thoroughly established, and the role of CGRP in the pathogenesis of Parkinson's disease is not fully validated. Nevertheless, the new developments in treatments that modify CGRP activity could have implications beyond migraine.
Additional References
1. Alexoudi A, Deftereos S. CGRP antagonists: side effects and potential Parkinson's disease development. Headache. 2020;60:789-790. doi: 10.1111/head.13770 Source
2. Blumenfeld A, Durham PL, Feoktistov A, et al. Hypervigilance, allostatic load, and migraine prevention: Antibodies to CGRP or receptor. Neurol Ther. 2021;10:469-497. doi:10.1007/s40120-021-00250-7 Source
The authors of a study published in the December 2023 issue of the Scandinavian Journal of Gastroenterology analyzed data to examine the potential link between gut microbiota and migraine. According to the statistical analysis, the researchers found that "a greater abundance of genus Lactobacillus was associated with a higher risk of migraine and a higher abundance of family Prevotellaceae was related to a decreased risk of migraine." Furthermore, they noted that these gut microbial patterns could be due to a genetic predisposition. The authors suggested that stool sampling could potentially be helpful in the diagnosis of migraine, and that measures to modify gut microbiota in the context of migraine therapy could be identified with future research.
While it is not clear whether migraine is a cause or effect of these alterations, or whether there is another confounding variable, the idea of using diet as a means of reducing migraine risk would be appealing for many patients. This offers hope, but it also leaves a window open for exaggeration and excessive reliance on certain foods or supplements before reliable links are established.
Further examining the genetic factors that might play a role in migraine, a large Korean data analysis published in the December 2023 issue of Epidemiology and Health described a link between migraine and Parkinson's disease. The researchers included 214,193 patients with migraine and 5,879,711 individuals without migraine. According to the statistical analysis, the patients who had migraine with aura showed a 1.35-fold higher risk for Parkinson's disease than individuals without migraine. However, the researchers did not note a statistically significant difference between the risk for Parkinson's disease among patients who had migraine without aura and individuals without migraine.
They also examined other factors, and noted that among individuals with migraine, those who had preexisting dyslipidemia had a higher risk for Parkinson's disease than those who did not have dyslipidemia. Other factors that were not correlated with an association between migraine and Parkinson's disease included cardiovascular risk factors, hypertension, diabetes, smoking status, and high body mass index.
The study authors noted that factors associated with the activity of calcitonin gene-related peptide (CGRP), which is known to play a significant role in the pathophysiology of migraine, could play a role in the link between migraine and Parkinson's disease. They pointed to previous studies that found evidence of elevated CGRP levels in the cerebrospinal fluid of patients with Parkinson's disease as possible evidence of a pathophysiologic link.
An earlier commentary, published in the April 2020 issue of Headache, suggested an implication of CGRP antagonists in the development of neurodegenerative disorders such as Parkinson's disease. The commentary authors noted that previous research correlated midlife migraine to late-life parkinsonism, suggesting a conceivable common pathology, which could include a genetic or environmental predisposition.[1] They also noted that studies suggest a possible link between CGRP and multiple system atrophy, a parkinsonian disorder.[1] They considered the possibility that one of the ways that CGRP could contribute to these disorders is through its role in the recruitment of inflammatory mediators, which can alter the function of nicotinic receptors in the dopaminergic system in Parkinson's disease pathogenesis.[2]
Recent research published in the December 2023 issue of Headache suggests that CGRP responsiveness in migraine therapy could be mediated by genetics. The study included 198 patients who had been typed for genes involved in CGRP signaling or pharmacologic response and were given genetic and polygenic risk scores. Responders were defined as patients who experienced ≥ 50% reduction in migraine days per month at 5.7-month follow-up.
The analysis revealed an association between nonresponder status and rs12615320-G in RAMP1, a gene that encodes a component of high-affinity CGRP receptors, which increased the risk for nonresponder status. The researchers also identified an association between nonresponder status and rs4680-A in COMT, a gene that has been associated with lower COMT enzymatic activity, chronic pain/fibromyalgia, and a "worrier" phenotype. Nonresponders also had a lower mean genetic risk score than responders. These genetic associations could help identify which patients would be most likely to benefit from anti-CGRP therapies.
Given that CGRP responsiveness may have a genetic component, it is possible that one of the contributors to the link between migraine and Parkinson's disease could lie in patients' genetic predisposition to CGRP activity. Yet, the association between these two common conditions is not thoroughly established, and the role of CGRP in the pathogenesis of Parkinson's disease is not fully validated. Nevertheless, the new developments in treatments that modify CGRP activity could have implications beyond migraine.
Additional References
1. Alexoudi A, Deftereos S. CGRP antagonists: side effects and potential Parkinson's disease development. Headache. 2020;60:789-790. doi: 10.1111/head.13770 Source
2. Blumenfeld A, Durham PL, Feoktistov A, et al. Hypervigilance, allostatic load, and migraine prevention: Antibodies to CGRP or receptor. Neurol Ther. 2021;10:469-497. doi:10.1007/s40120-021-00250-7 Source
The authors of a study published in the December 2023 issue of the Scandinavian Journal of Gastroenterology analyzed data to examine the potential link between gut microbiota and migraine. According to the statistical analysis, the researchers found that "a greater abundance of genus Lactobacillus was associated with a higher risk of migraine and a higher abundance of family Prevotellaceae was related to a decreased risk of migraine." Furthermore, they noted that these gut microbial patterns could be due to a genetic predisposition. The authors suggested that stool sampling could potentially be helpful in the diagnosis of migraine, and that measures to modify gut microbiota in the context of migraine therapy could be identified with future research.
While it is not clear whether migraine is a cause or effect of these alterations, or whether there is another confounding variable, the idea of using diet as a means of reducing migraine risk would be appealing for many patients. This offers hope, but it also leaves a window open for exaggeration and excessive reliance on certain foods or supplements before reliable links are established.
Further examining the genetic factors that might play a role in migraine, a large Korean data analysis published in the December 2023 issue of Epidemiology and Health described a link between migraine and Parkinson's disease. The researchers included 214,193 patients with migraine and 5,879,711 individuals without migraine. According to the statistical analysis, the patients who had migraine with aura showed a 1.35-fold higher risk for Parkinson's disease than individuals without migraine. However, the researchers did not note a statistically significant difference between the risk for Parkinson's disease among patients who had migraine without aura and individuals without migraine.
They also examined other factors, and noted that among individuals with migraine, those who had preexisting dyslipidemia had a higher risk for Parkinson's disease than those who did not have dyslipidemia. Other factors that were not correlated with an association between migraine and Parkinson's disease included cardiovascular risk factors, hypertension, diabetes, smoking status, and high body mass index.
The study authors noted that factors associated with the activity of calcitonin gene-related peptide (CGRP), which is known to play a significant role in the pathophysiology of migraine, could play a role in the link between migraine and Parkinson's disease. They pointed to previous studies that found evidence of elevated CGRP levels in the cerebrospinal fluid of patients with Parkinson's disease as possible evidence of a pathophysiologic link.
An earlier commentary, published in the April 2020 issue of Headache, suggested an implication of CGRP antagonists in the development of neurodegenerative disorders such as Parkinson's disease. The commentary authors noted that previous research correlated midlife migraine to late-life parkinsonism, suggesting a conceivable common pathology, which could include a genetic or environmental predisposition.[1] They also noted that studies suggest a possible link between CGRP and multiple system atrophy, a parkinsonian disorder.[1] They considered the possibility that one of the ways that CGRP could contribute to these disorders is through its role in the recruitment of inflammatory mediators, which can alter the function of nicotinic receptors in the dopaminergic system in Parkinson's disease pathogenesis.[2]
Recent research published in the December 2023 issue of Headache suggests that CGRP responsiveness in migraine therapy could be mediated by genetics. The study included 198 patients who had been typed for genes involved in CGRP signaling or pharmacologic response and were given genetic and polygenic risk scores. Responders were defined as patients who experienced ≥ 50% reduction in migraine days per month at 5.7-month follow-up.
The analysis revealed an association between nonresponder status and rs12615320-G in RAMP1, a gene that encodes a component of high-affinity CGRP receptors, which increased the risk for nonresponder status. The researchers also identified an association between nonresponder status and rs4680-A in COMT, a gene that has been associated with lower COMT enzymatic activity, chronic pain/fibromyalgia, and a "worrier" phenotype. Nonresponders also had a lower mean genetic risk score than responders. These genetic associations could help identify which patients would be most likely to benefit from anti-CGRP therapies.
Given that CGRP responsiveness may have a genetic component, it is possible that one of the contributors to the link between migraine and Parkinson's disease could lie in patients' genetic predisposition to CGRP activity. Yet, the association between these two common conditions is not thoroughly established, and the role of CGRP in the pathogenesis of Parkinson's disease is not fully validated. Nevertheless, the new developments in treatments that modify CGRP activity could have implications beyond migraine.
Additional References
1. Alexoudi A, Deftereos S. CGRP antagonists: side effects and potential Parkinson's disease development. Headache. 2020;60:789-790. doi: 10.1111/head.13770 Source
2. Blumenfeld A, Durham PL, Feoktistov A, et al. Hypervigilance, allostatic load, and migraine prevention: Antibodies to CGRP or receptor. Neurol Ther. 2021;10:469-497. doi:10.1007/s40120-021-00250-7 Source
Commentary: Examining CGRP Antagonists for Migraine Relief, January 2024
The recent 3-month double-blind study by Schwedt and colleagues included 580 participants and compared the effects of galcanezumab (Emgality) with those of rimegepant (Nurtec ODT). These medications are administered by different methods when used for migraine prevention; galcanezumab is given subcutaneously (SC) every month, whereas rimegepant is taken by mouth every other day. To blind the study, participants were randomly assigned to receive either 120 mg galcanezumab SC per month (after a 240 mg loading dose) and a placebo oral disintegrating tablet every other day or every-other-day 75 mg rimegepant as oral disintegrating tablets and a monthly SC placebo. According to the study authors, 62% of the patients receiving galcanezumab vs 61% of those receiving rimegepant achieved ≥ 50% reduction in monthly migraine headache days after 3 months, with no statistically significant difference between the groups. Comparisons between CGRP receptor antagonists are scarce. The studies tend to be of a short duration and to include small sample sizes — and most are retrospective. To date, physicians who treat patients with these drugs do not have information about the distinguishing characteristics between these treatments that could be used to guide drug selection for subtypes of migraine or different patient populations. As further research emerges, we may see distinctions between these therapies, or we might continue to see that their effects are similar in terms of benefits, duration of action, and patient characteristics.
Many patients who are prescribed these new medications have already been treated with a variety of other previously available migraine therapies, with varying degrees of improvement. Physicians who prescribe treatments for migraine patients often move on to new therapeutic options when patients only experience partial relief, but recent research suggests that even these incomplete responses could be beneficial for patients.
Researchers at the Headache Centre — Neurology Clinic at the Spedali Civili di Brescia in Brescia, Italy, conducted a retrospective study to examine whether previous treatment with onabotulinumtoxinA affected patent response to anti-CGRP mAb (Ceccardi et al). These treatments have differing mechanisms. OnabotulinumtoxinA is an exotoxin produced by Clostridium botulinum that blocks the acetylcholine release from nerve endings temporarily disabling postsynaptic action. Anti-CGRP mAb work by inhibiting the inflammatory receptor, thereby inhibiting the pain sensation.2
Several studies have examined the effects of combining onabotulinumtoxinA (Botox) with anti-CGRP mAb, with varying results. For example, researchers of a study designed to compare the two treatments concluded, "In patients with chronic migraine who have only had a partial response to Botox, adjunctive preventative therapy with a CGRP-mAb drug is safe and effective."2 A review examining several small studies that evaluated the response of dual therapy included a few studies that found no significant differences between an anti-CGRP mAb monotherapy and dual therapy with onabotulinumtoxinA, as well as some studies that noted improvement with dual therapy over either therapy alone. The review authors concluded that a real-life application is not yet determined and that "Further sufficiently powered, placebo-controlled studies are warranted to shed light on potential additive or synergistic effects of combining onabotulinumtoxin A with a CGRP antagonist."3
The Brescia study was designed to examine the effect of previous onabotulinumtoxinA treatment on subsequent anti-CGRP mAb response. The researchers enrolled 128 patients, of whom 51 (39.9%) had previously been treated with onabotulinumtoxinA, with the last dose 3 months before preventive treatment with an anti-CGRP mAb was started. The study was conducted between November 2018 and May 2023. The outcomes noted included monthly headache days, monthly migraine days, mean analgesic consumption, and clinical disability according to the Migraine Disability Assessment test (MIDAS). Participants received 3 months of treatment with an anti-CGRP mAb.
In addition to comparing patients who had previously received onabotulinumtoxinA with those who did not, the researchers also "aimed to evaluate whether the clinical response to anti-CGRP mAb was affected by the number of previous Onabotulinumtoxin-A administrations.
The documented baseline prior to treatment with an anti-CGRP mAb was as follows: mean monthly headache days 23.7 (SD 5.7), monthly migraine days 13.9 (SD 8.0); mean MIDAS score 108.9 (SD 76.1); and mean analgesic consumption 24.8 (SD 18.8). After 3 months of treatment with an anti-CGRP mAb, both groups experienced significant improvement in all these parameters. Furthermore, after 3 months of treatment with an anti-CGRP mAb, the patients who received at least three onabotulinumtoxinA administrations prior to the study experienced lower MMD compared with those who had received fewer cycles.
For physicians and patients, this outcome provides validation that patients can potentially gain long-term benefits from migraine treatment, even if such interventions do not provide sufficient migraine relief. The conclusion cannot be generalized to other migraine treatment sequences, and the authors did not suggest deliberately postponing any treatment or using any treatment as "priming" for another treatment. Yet physicians may be able to give patients some reassurance that an incomplete response in migraine therapy is not futile.
Migraine treatment can be very effective, but sometimes it is not clear whether patients should take their medication before or during a migraine episode, or whether the signal to take medication should be based on specific symptoms. Many patients wait to take their migraine treatment until they are sure that they will have a migraine, especially if they frequently have prodromal symptoms that do not consistently lead to a migraine. Additionally, some of the new CGRP receptor antagonists are expensive, and many payers only approve a limited amount per month. Patients might not want to waste their CGRP receptor antagonist supply in case they run out before their next refill authorization.
AbbVie, the makers of ubrogepant (Ubrelvy), a CGRP receptor antagonist approved for acute treatment of migraine, conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled, crossover trial of ubrogepant at 75 research centers and headache clinics in the US (Dodick et al). According to the manufacturer, the aim of the trial was to evaluate the efficacy, safety, and tolerability of 100 mg ubrogepant for the acute treatment of migraine when administered during the prodrome of a migraine attack. The study included 518 participants age 18-75 years who had at least a 1-year history of migraine and had had two to eight migraine attacks per month that included symptoms of a moderate to severe headache in each of the 3 months before the study. Because this was a crossover trial, the participants were randomly assigned to either receive placebo for treatment of the first qualifying prodrome event and 100 mg ubrogepant for treatment of the second qualifying prodrome event or to receive 100 mg ubrogepant to treat the first qualifying prodrome event and placebo to treat the second qualifying prodrome event.
According to AbbVie's news release following publication of the study, "Absence of moderate or severe intensity headache within 24 hours was achieved following 46% of qualifying prodrome events when treated with UBRELVY vs 29% of placebo-treated events" and "absence of moderate or severe intensity headache within 48 hours was achieved following 41% of qualifying prodrome events when treated with UBRELVY vs 25% of placebo-treated events" (both P < .0001).4 Safety and tolerability of treatment during the prodromal period were also established.
In clinical practice, these results hold promise because patients can gain some assurance in knowing that taking their migraine treatment during their early prodromal symptoms is safe and could potentially improve the outcome of the event, preventing migraine symptoms for 48 hours. Even for patients who do not have an ample supply of ubrogepant or another CGRP antagonist, taking a treatment that is approved by their doctor at the onset of prodromal symptoms can provide relief compared with waiting until symptoms worsen.
Additional References
1. Waliszewska-Prosół M, Vuralli D, Martelletti P. What to do with non-responders to CGRP(r) monoclonal antibodies: Switch to another or move to gepants? J Headache Pain. 2023;24:163. doi: 10.1186/s10194-023-01698-8
2. Pallapothu MR, Quintana Mariñez MG, Chakkera M, et al. Long-term management of migraine with OnabotulinumtoxinA (Botox) vs calcitonin gene-related peptide antibodies (Anti-CGRP). Cureus. 2023;15:e46696. doi: 10.7759/cureus.46696
3. Pellesi L. Combining onabotulinumtoxin A with a CGRP antagonist for chronic migraine prophylaxis: Where do we stand? Front Pain Res (Lausanne). 2023;4:1292994. doi: 10.3389/fpain.2023.1292994
4. AbbVie. Results published in The Lancet show UBRELVY® (ubrogepant) reduces the headache phase of a migraine attack when dosed during the prodrome of migraine. November 16, 2023. Source
The recent 3-month double-blind study by Schwedt and colleagues included 580 participants and compared the effects of galcanezumab (Emgality) with those of rimegepant (Nurtec ODT). These medications are administered by different methods when used for migraine prevention; galcanezumab is given subcutaneously (SC) every month, whereas rimegepant is taken by mouth every other day. To blind the study, participants were randomly assigned to receive either 120 mg galcanezumab SC per month (after a 240 mg loading dose) and a placebo oral disintegrating tablet every other day or every-other-day 75 mg rimegepant as oral disintegrating tablets and a monthly SC placebo. According to the study authors, 62% of the patients receiving galcanezumab vs 61% of those receiving rimegepant achieved ≥ 50% reduction in monthly migraine headache days after 3 months, with no statistically significant difference between the groups. Comparisons between CGRP receptor antagonists are scarce. The studies tend to be of a short duration and to include small sample sizes — and most are retrospective. To date, physicians who treat patients with these drugs do not have information about the distinguishing characteristics between these treatments that could be used to guide drug selection for subtypes of migraine or different patient populations. As further research emerges, we may see distinctions between these therapies, or we might continue to see that their effects are similar in terms of benefits, duration of action, and patient characteristics.
Many patients who are prescribed these new medications have already been treated with a variety of other previously available migraine therapies, with varying degrees of improvement. Physicians who prescribe treatments for migraine patients often move on to new therapeutic options when patients only experience partial relief, but recent research suggests that even these incomplete responses could be beneficial for patients.
Researchers at the Headache Centre — Neurology Clinic at the Spedali Civili di Brescia in Brescia, Italy, conducted a retrospective study to examine whether previous treatment with onabotulinumtoxinA affected patent response to anti-CGRP mAb (Ceccardi et al). These treatments have differing mechanisms. OnabotulinumtoxinA is an exotoxin produced by Clostridium botulinum that blocks the acetylcholine release from nerve endings temporarily disabling postsynaptic action. Anti-CGRP mAb work by inhibiting the inflammatory receptor, thereby inhibiting the pain sensation.2
Several studies have examined the effects of combining onabotulinumtoxinA (Botox) with anti-CGRP mAb, with varying results. For example, researchers of a study designed to compare the two treatments concluded, "In patients with chronic migraine who have only had a partial response to Botox, adjunctive preventative therapy with a CGRP-mAb drug is safe and effective."2 A review examining several small studies that evaluated the response of dual therapy included a few studies that found no significant differences between an anti-CGRP mAb monotherapy and dual therapy with onabotulinumtoxinA, as well as some studies that noted improvement with dual therapy over either therapy alone. The review authors concluded that a real-life application is not yet determined and that "Further sufficiently powered, placebo-controlled studies are warranted to shed light on potential additive or synergistic effects of combining onabotulinumtoxin A with a CGRP antagonist."3
The Brescia study was designed to examine the effect of previous onabotulinumtoxinA treatment on subsequent anti-CGRP mAb response. The researchers enrolled 128 patients, of whom 51 (39.9%) had previously been treated with onabotulinumtoxinA, with the last dose 3 months before preventive treatment with an anti-CGRP mAb was started. The study was conducted between November 2018 and May 2023. The outcomes noted included monthly headache days, monthly migraine days, mean analgesic consumption, and clinical disability according to the Migraine Disability Assessment test (MIDAS). Participants received 3 months of treatment with an anti-CGRP mAb.
In addition to comparing patients who had previously received onabotulinumtoxinA with those who did not, the researchers also "aimed to evaluate whether the clinical response to anti-CGRP mAb was affected by the number of previous Onabotulinumtoxin-A administrations.
The documented baseline prior to treatment with an anti-CGRP mAb was as follows: mean monthly headache days 23.7 (SD 5.7), monthly migraine days 13.9 (SD 8.0); mean MIDAS score 108.9 (SD 76.1); and mean analgesic consumption 24.8 (SD 18.8). After 3 months of treatment with an anti-CGRP mAb, both groups experienced significant improvement in all these parameters. Furthermore, after 3 months of treatment with an anti-CGRP mAb, the patients who received at least three onabotulinumtoxinA administrations prior to the study experienced lower MMD compared with those who had received fewer cycles.
For physicians and patients, this outcome provides validation that patients can potentially gain long-term benefits from migraine treatment, even if such interventions do not provide sufficient migraine relief. The conclusion cannot be generalized to other migraine treatment sequences, and the authors did not suggest deliberately postponing any treatment or using any treatment as "priming" for another treatment. Yet physicians may be able to give patients some reassurance that an incomplete response in migraine therapy is not futile.
Migraine treatment can be very effective, but sometimes it is not clear whether patients should take their medication before or during a migraine episode, or whether the signal to take medication should be based on specific symptoms. Many patients wait to take their migraine treatment until they are sure that they will have a migraine, especially if they frequently have prodromal symptoms that do not consistently lead to a migraine. Additionally, some of the new CGRP receptor antagonists are expensive, and many payers only approve a limited amount per month. Patients might not want to waste their CGRP receptor antagonist supply in case they run out before their next refill authorization.
AbbVie, the makers of ubrogepant (Ubrelvy), a CGRP receptor antagonist approved for acute treatment of migraine, conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled, crossover trial of ubrogepant at 75 research centers and headache clinics in the US (Dodick et al). According to the manufacturer, the aim of the trial was to evaluate the efficacy, safety, and tolerability of 100 mg ubrogepant for the acute treatment of migraine when administered during the prodrome of a migraine attack. The study included 518 participants age 18-75 years who had at least a 1-year history of migraine and had had two to eight migraine attacks per month that included symptoms of a moderate to severe headache in each of the 3 months before the study. Because this was a crossover trial, the participants were randomly assigned to either receive placebo for treatment of the first qualifying prodrome event and 100 mg ubrogepant for treatment of the second qualifying prodrome event or to receive 100 mg ubrogepant to treat the first qualifying prodrome event and placebo to treat the second qualifying prodrome event.
According to AbbVie's news release following publication of the study, "Absence of moderate or severe intensity headache within 24 hours was achieved following 46% of qualifying prodrome events when treated with UBRELVY vs 29% of placebo-treated events" and "absence of moderate or severe intensity headache within 48 hours was achieved following 41% of qualifying prodrome events when treated with UBRELVY vs 25% of placebo-treated events" (both P < .0001).4 Safety and tolerability of treatment during the prodromal period were also established.
In clinical practice, these results hold promise because patients can gain some assurance in knowing that taking their migraine treatment during their early prodromal symptoms is safe and could potentially improve the outcome of the event, preventing migraine symptoms for 48 hours. Even for patients who do not have an ample supply of ubrogepant or another CGRP antagonist, taking a treatment that is approved by their doctor at the onset of prodromal symptoms can provide relief compared with waiting until symptoms worsen.
Additional References
1. Waliszewska-Prosół M, Vuralli D, Martelletti P. What to do with non-responders to CGRP(r) monoclonal antibodies: Switch to another or move to gepants? J Headache Pain. 2023;24:163. doi: 10.1186/s10194-023-01698-8
2. Pallapothu MR, Quintana Mariñez MG, Chakkera M, et al. Long-term management of migraine with OnabotulinumtoxinA (Botox) vs calcitonin gene-related peptide antibodies (Anti-CGRP). Cureus. 2023;15:e46696. doi: 10.7759/cureus.46696
3. Pellesi L. Combining onabotulinumtoxin A with a CGRP antagonist for chronic migraine prophylaxis: Where do we stand? Front Pain Res (Lausanne). 2023;4:1292994. doi: 10.3389/fpain.2023.1292994
4. AbbVie. Results published in The Lancet show UBRELVY® (ubrogepant) reduces the headache phase of a migraine attack when dosed during the prodrome of migraine. November 16, 2023. Source
The recent 3-month double-blind study by Schwedt and colleagues included 580 participants and compared the effects of galcanezumab (Emgality) with those of rimegepant (Nurtec ODT). These medications are administered by different methods when used for migraine prevention; galcanezumab is given subcutaneously (SC) every month, whereas rimegepant is taken by mouth every other day. To blind the study, participants were randomly assigned to receive either 120 mg galcanezumab SC per month (after a 240 mg loading dose) and a placebo oral disintegrating tablet every other day or every-other-day 75 mg rimegepant as oral disintegrating tablets and a monthly SC placebo. According to the study authors, 62% of the patients receiving galcanezumab vs 61% of those receiving rimegepant achieved ≥ 50% reduction in monthly migraine headache days after 3 months, with no statistically significant difference between the groups. Comparisons between CGRP receptor antagonists are scarce. The studies tend to be of a short duration and to include small sample sizes — and most are retrospective. To date, physicians who treat patients with these drugs do not have information about the distinguishing characteristics between these treatments that could be used to guide drug selection for subtypes of migraine or different patient populations. As further research emerges, we may see distinctions between these therapies, or we might continue to see that their effects are similar in terms of benefits, duration of action, and patient characteristics.
Many patients who are prescribed these new medications have already been treated with a variety of other previously available migraine therapies, with varying degrees of improvement. Physicians who prescribe treatments for migraine patients often move on to new therapeutic options when patients only experience partial relief, but recent research suggests that even these incomplete responses could be beneficial for patients.
Researchers at the Headache Centre — Neurology Clinic at the Spedali Civili di Brescia in Brescia, Italy, conducted a retrospective study to examine whether previous treatment with onabotulinumtoxinA affected patent response to anti-CGRP mAb (Ceccardi et al). These treatments have differing mechanisms. OnabotulinumtoxinA is an exotoxin produced by Clostridium botulinum that blocks the acetylcholine release from nerve endings temporarily disabling postsynaptic action. Anti-CGRP mAb work by inhibiting the inflammatory receptor, thereby inhibiting the pain sensation.2
Several studies have examined the effects of combining onabotulinumtoxinA (Botox) with anti-CGRP mAb, with varying results. For example, researchers of a study designed to compare the two treatments concluded, "In patients with chronic migraine who have only had a partial response to Botox, adjunctive preventative therapy with a CGRP-mAb drug is safe and effective."2 A review examining several small studies that evaluated the response of dual therapy included a few studies that found no significant differences between an anti-CGRP mAb monotherapy and dual therapy with onabotulinumtoxinA, as well as some studies that noted improvement with dual therapy over either therapy alone. The review authors concluded that a real-life application is not yet determined and that "Further sufficiently powered, placebo-controlled studies are warranted to shed light on potential additive or synergistic effects of combining onabotulinumtoxin A with a CGRP antagonist."3
The Brescia study was designed to examine the effect of previous onabotulinumtoxinA treatment on subsequent anti-CGRP mAb response. The researchers enrolled 128 patients, of whom 51 (39.9%) had previously been treated with onabotulinumtoxinA, with the last dose 3 months before preventive treatment with an anti-CGRP mAb was started. The study was conducted between November 2018 and May 2023. The outcomes noted included monthly headache days, monthly migraine days, mean analgesic consumption, and clinical disability according to the Migraine Disability Assessment test (MIDAS). Participants received 3 months of treatment with an anti-CGRP mAb.
In addition to comparing patients who had previously received onabotulinumtoxinA with those who did not, the researchers also "aimed to evaluate whether the clinical response to anti-CGRP mAb was affected by the number of previous Onabotulinumtoxin-A administrations.
The documented baseline prior to treatment with an anti-CGRP mAb was as follows: mean monthly headache days 23.7 (SD 5.7), monthly migraine days 13.9 (SD 8.0); mean MIDAS score 108.9 (SD 76.1); and mean analgesic consumption 24.8 (SD 18.8). After 3 months of treatment with an anti-CGRP mAb, both groups experienced significant improvement in all these parameters. Furthermore, after 3 months of treatment with an anti-CGRP mAb, the patients who received at least three onabotulinumtoxinA administrations prior to the study experienced lower MMD compared with those who had received fewer cycles.
For physicians and patients, this outcome provides validation that patients can potentially gain long-term benefits from migraine treatment, even if such interventions do not provide sufficient migraine relief. The conclusion cannot be generalized to other migraine treatment sequences, and the authors did not suggest deliberately postponing any treatment or using any treatment as "priming" for another treatment. Yet physicians may be able to give patients some reassurance that an incomplete response in migraine therapy is not futile.
Migraine treatment can be very effective, but sometimes it is not clear whether patients should take their medication before or during a migraine episode, or whether the signal to take medication should be based on specific symptoms. Many patients wait to take their migraine treatment until they are sure that they will have a migraine, especially if they frequently have prodromal symptoms that do not consistently lead to a migraine. Additionally, some of the new CGRP receptor antagonists are expensive, and many payers only approve a limited amount per month. Patients might not want to waste their CGRP receptor antagonist supply in case they run out before their next refill authorization.
AbbVie, the makers of ubrogepant (Ubrelvy), a CGRP receptor antagonist approved for acute treatment of migraine, conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled, crossover trial of ubrogepant at 75 research centers and headache clinics in the US (Dodick et al). According to the manufacturer, the aim of the trial was to evaluate the efficacy, safety, and tolerability of 100 mg ubrogepant for the acute treatment of migraine when administered during the prodrome of a migraine attack. The study included 518 participants age 18-75 years who had at least a 1-year history of migraine and had had two to eight migraine attacks per month that included symptoms of a moderate to severe headache in each of the 3 months before the study. Because this was a crossover trial, the participants were randomly assigned to either receive placebo for treatment of the first qualifying prodrome event and 100 mg ubrogepant for treatment of the second qualifying prodrome event or to receive 100 mg ubrogepant to treat the first qualifying prodrome event and placebo to treat the second qualifying prodrome event.
According to AbbVie's news release following publication of the study, "Absence of moderate or severe intensity headache within 24 hours was achieved following 46% of qualifying prodrome events when treated with UBRELVY vs 29% of placebo-treated events" and "absence of moderate or severe intensity headache within 48 hours was achieved following 41% of qualifying prodrome events when treated with UBRELVY vs 25% of placebo-treated events" (both P < .0001).4 Safety and tolerability of treatment during the prodromal period were also established.
In clinical practice, these results hold promise because patients can gain some assurance in knowing that taking their migraine treatment during their early prodromal symptoms is safe and could potentially improve the outcome of the event, preventing migraine symptoms for 48 hours. Even for patients who do not have an ample supply of ubrogepant or another CGRP antagonist, taking a treatment that is approved by their doctor at the onset of prodromal symptoms can provide relief compared with waiting until symptoms worsen.
Additional References
1. Waliszewska-Prosół M, Vuralli D, Martelletti P. What to do with non-responders to CGRP(r) monoclonal antibodies: Switch to another or move to gepants? J Headache Pain. 2023;24:163. doi: 10.1186/s10194-023-01698-8
2. Pallapothu MR, Quintana Mariñez MG, Chakkera M, et al. Long-term management of migraine with OnabotulinumtoxinA (Botox) vs calcitonin gene-related peptide antibodies (Anti-CGRP). Cureus. 2023;15:e46696. doi: 10.7759/cureus.46696
3. Pellesi L. Combining onabotulinumtoxin A with a CGRP antagonist for chronic migraine prophylaxis: Where do we stand? Front Pain Res (Lausanne). 2023;4:1292994. doi: 10.3389/fpain.2023.1292994
4. AbbVie. Results published in The Lancet show UBRELVY® (ubrogepant) reduces the headache phase of a migraine attack when dosed during the prodrome of migraine. November 16, 2023. Source