Headache & Migraine

Key clinical point: Compared with nortriptyline alone, its combination with atorvastatin significantly reduces the frequency of headache and improves the quality of life (QOL) in patients with migraine; however, the effect on migraine intensity is nonsignificant.

Major finding: Atorvastatin plus nortriptyline vs. nortriptyline alone led to a significantly lower headache frequency (P = .004) at week 24 in addition to a significant improvement in the QOL at weeks 14 and 24 (both P = .001); however, no significant difference was observed in the headache intensity over 24 weeks.

Study details: This prospective, triple-blind, randomized controlled trial included 68 adult patients with migraine who were randomly assigned to receive atorvastatin plus nortriptyline (n = 34) or placebo plus nortriptyline (n = 34) for 24 weeks.

Disclosures: The study was supported by a grant from the Research and Technology Department of Shahid Sadoughi University of Medical Sciences, Yazd, Iran. The authors reported having no conflicts of interest.

Source: Sherafat M et al. Neurol Res. 2022 (Jan 17). Doi: 10.1080/01616412.2021

Key clinical point: Compared with nortriptyline alone, its combination with atorvastatin significantly reduces the frequency of headache and improves the quality of life (QOL) in patients with migraine; however, the effect on migraine intensity is nonsignificant.

Major finding: Atorvastatin plus nortriptyline vs. nortriptyline alone led to a significantly lower headache frequency (P = .004) at week 24 in addition to a significant improvement in the QOL at weeks 14 and 24 (both P = .001); however, no significant difference was observed in the headache intensity over 24 weeks.

Study details: This prospective, triple-blind, randomized controlled trial included 68 adult patients with migraine who were randomly assigned to receive atorvastatin plus nortriptyline (n = 34) or placebo plus nortriptyline (n = 34) for 24 weeks.

Disclosures: The study was supported by a grant from the Research and Technology Department of Shahid Sadoughi University of Medical Sciences, Yazd, Iran. The authors reported having no conflicts of interest.

Source: Sherafat M et al. Neurol Res. 2022 (Jan 17). Doi: 10.1080/01616412.2021

Key clinical point: Compared with nortriptyline alone, its combination with atorvastatin significantly reduces the frequency of headache and improves the quality of life (QOL) in patients with migraine; however, the effect on migraine intensity is nonsignificant.

Major finding: Atorvastatin plus nortriptyline vs. nortriptyline alone led to a significantly lower headache frequency (P = .004) at week 24 in addition to a significant improvement in the QOL at weeks 14 and 24 (both P = .001); however, no significant difference was observed in the headache intensity over 24 weeks.

Study details: This prospective, triple-blind, randomized controlled trial included 68 adult patients with migraine who were randomly assigned to receive atorvastatin plus nortriptyline (n = 34) or placebo plus nortriptyline (n = 34) for 24 weeks.

Disclosures: The study was supported by a grant from the Research and Technology Department of Shahid Sadoughi University of Medical Sciences, Yazd, Iran. The authors reported having no conflicts of interest.

Source: Sherafat M et al. Neurol Res. 2022 (Jan 17). Doi: 10.1080/01616412.2021

Key clinical point: Rimegepant on a patient treated as needed (PRN) basis reduces monthly migraine days (MMD) without increasing the monthly tablet use and improves health-related quality of life (HRQoL) in patients with acute migraine.

Major finding: Rimegepant reduced the mean MMD from 10.9 days at baseline to 8.9 days by week 52 and led to an increase of 0.08 quality-adjusted life years. The mean monthly tablet use decreased from 7.9 tablets to 7.3 tablets between weeks 4-8 and 48-52.

Study details: This was a post hoc analysis of the phase 2/3 safety BHV3000-201 study including 1,044 patients with a ≥1-year history of migraine and ≥6 MMD who received 75 mg rimegepant up to once daily PRN for up to 52 weeks.

Disclosures: The study was sponsored by Biohaven Pharmaceuticals. CP Schreiber reported being a speaker for various organizations, including Biohaven. The rest of the authors are employees and stock/stock option owners of Biohaven or Broadstreet HEOR (funded by the former).

Source: Johnston K et al. J Headache Pain. 2022;23:10 (Jan 17). Doi: 10.1186/s10194-021-01378-5

Key clinical point: Rimegepant on a patient treated as needed (PRN) basis reduces monthly migraine days (MMD) without increasing the monthly tablet use and improves health-related quality of life (HRQoL) in patients with acute migraine.

Major finding: Rimegepant reduced the mean MMD from 10.9 days at baseline to 8.9 days by week 52 and led to an increase of 0.08 quality-adjusted life years. The mean monthly tablet use decreased from 7.9 tablets to 7.3 tablets between weeks 4-8 and 48-52.

Study details: This was a post hoc analysis of the phase 2/3 safety BHV3000-201 study including 1,044 patients with a ≥1-year history of migraine and ≥6 MMD who received 75 mg rimegepant up to once daily PRN for up to 52 weeks.

Disclosures: The study was sponsored by Biohaven Pharmaceuticals. CP Schreiber reported being a speaker for various organizations, including Biohaven. The rest of the authors are employees and stock/stock option owners of Biohaven or Broadstreet HEOR (funded by the former).

Source: Johnston K et al. J Headache Pain. 2022;23:10 (Jan 17). Doi: 10.1186/s10194-021-01378-5

Key clinical point: Rimegepant on a patient treated as needed (PRN) basis reduces monthly migraine days (MMD) without increasing the monthly tablet use and improves health-related quality of life (HRQoL) in patients with acute migraine.

Major finding: Rimegepant reduced the mean MMD from 10.9 days at baseline to 8.9 days by week 52 and led to an increase of 0.08 quality-adjusted life years. The mean monthly tablet use decreased from 7.9 tablets to 7.3 tablets between weeks 4-8 and 48-52.

Study details: This was a post hoc analysis of the phase 2/3 safety BHV3000-201 study including 1,044 patients with a ≥1-year history of migraine and ≥6 MMD who received 75 mg rimegepant up to once daily PRN for up to 52 weeks.

Disclosures: The study was sponsored by Biohaven Pharmaceuticals. CP Schreiber reported being a speaker for various organizations, including Biohaven. The rest of the authors are employees and stock/stock option owners of Biohaven or Broadstreet HEOR (funded by the former).

Source: Johnston K et al. J Headache Pain. 2022;23:10 (Jan 17). Doi: 10.1186/s10194-021-01378-5

Key clinical point: Galcanezumab improves functioning and decreases disability in patients with treatment-resistant migraine.

Main finding: At month 3, galcanezumab vs. placebo caused a greater improvement in the Migraine-Specific Quality of Life Questionnaire (version 2.1 Role Function-Restrictive) (least-squares mean [LSM] change 23.19 vs. 10.66; P ≤ .0001] and European Quality of Life-5 Dimensions-5 Level Visual Analog Scale (LSM change 3.38 vs. −0.086; P = .0277) scores and a greater reduction in Migraine Disability Assessment total scores (LSM chang, −21.10 vs. −3.30; P ≤ .0001).

Study details: Findings are from the phase 3b CONQUER trial including 462 adult patients with episodic or chronic migraine and no response to previous 2-4 migraine preventive treatment categories who were randomly assigned to double-blind treatment with galcanezumab (n = 232) or placebo (n = 230) for 3 months followed by 3-month open-label treatment with galcanezumab.

Disclosures: Eli Lilly and Company sponsored the study. SJ Tepper and J Ailani declared receiving research grants, speaker's/advisory board member's honoraria, or institutional research funding for clinical trials from various sources, including Eli Lilly. The rest of the authors are employees and stockholders of Eli Lilly.

Source: Tepper SJ et al. Clin Drug Investig. 2022 (Jan 18). Doi: 10.1007/s40261-021-01115-5

Key clinical point: Galcanezumab improves functioning and decreases disability in patients with treatment-resistant migraine.

Main finding: At month 3, galcanezumab vs. placebo caused a greater improvement in the Migraine-Specific Quality of Life Questionnaire (version 2.1 Role Function-Restrictive) (least-squares mean [LSM] change 23.19 vs. 10.66; P ≤ .0001] and European Quality of Life-5 Dimensions-5 Level Visual Analog Scale (LSM change 3.38 vs. −0.086; P = .0277) scores and a greater reduction in Migraine Disability Assessment total scores (LSM chang, −21.10 vs. −3.30; P ≤ .0001).

Study details: Findings are from the phase 3b CONQUER trial including 462 adult patients with episodic or chronic migraine and no response to previous 2-4 migraine preventive treatment categories who were randomly assigned to double-blind treatment with galcanezumab (n = 232) or placebo (n = 230) for 3 months followed by 3-month open-label treatment with galcanezumab.

Disclosures: Eli Lilly and Company sponsored the study. SJ Tepper and J Ailani declared receiving research grants, speaker's/advisory board member's honoraria, or institutional research funding for clinical trials from various sources, including Eli Lilly. The rest of the authors are employees and stockholders of Eli Lilly.

Source: Tepper SJ et al. Clin Drug Investig. 2022 (Jan 18). Doi: 10.1007/s40261-021-01115-5

Key clinical point: Galcanezumab improves functioning and decreases disability in patients with treatment-resistant migraine.

Main finding: At month 3, galcanezumab vs. placebo caused a greater improvement in the Migraine-Specific Quality of Life Questionnaire (version 2.1 Role Function-Restrictive) (least-squares mean [LSM] change 23.19 vs. 10.66; P ≤ .0001] and European Quality of Life-5 Dimensions-5 Level Visual Analog Scale (LSM change 3.38 vs. −0.086; P = .0277) scores and a greater reduction in Migraine Disability Assessment total scores (LSM chang, −21.10 vs. −3.30; P ≤ .0001).

Study details: Findings are from the phase 3b CONQUER trial including 462 adult patients with episodic or chronic migraine and no response to previous 2-4 migraine preventive treatment categories who were randomly assigned to double-blind treatment with galcanezumab (n = 232) or placebo (n = 230) for 3 months followed by 3-month open-label treatment with galcanezumab.

Disclosures: Eli Lilly and Company sponsored the study. SJ Tepper and J Ailani declared receiving research grants, speaker's/advisory board member's honoraria, or institutional research funding for clinical trials from various sources, including Eli Lilly. The rest of the authors are employees and stockholders of Eli Lilly.

Source: Tepper SJ et al. Clin Drug Investig. 2022 (Jan 18). Doi: 10.1007/s40261-021-01115-5

Edoardo Caronna, MD and Patricia Pozo-Rosich, MD, PhD,  Neurology Department, Hospital Universitari Vall d’Hebron, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; and Headache and Neurological Pain Research Group, Vall d’Hebron Research Institute, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. Dr. Pozo-Rosich also serves on the boards of the International Headache Society and Council of the European Headache Federation and is an editor for various peer-reviewed journals, including Cephalalgia and Headache.

Headache is a symptom of the coronavirus disease 2019 (Covid-19), caused by the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the pandemic began, researchers have tried to describe, understand, and help clinicians manage headache in the setting of Covid-19.

The reason is simple: Headache is common, often debilitating, and difficult to treat.¹

Moreover, headache could manifest both in the acute phase of the infection and, once the infection has resolved, in the post-acute phase.¹ Therefore, it is critical for clinicians to know more about headache, as headache can be a common reason that patients seek help, both in the specialized and non-specialized medical care setting.

Definitions and manifestations

While the first step in such a communication would be to define headache attributed to Covid-19, no specific definition exists, as this is a new disease. Therefore, headache attributed to Covid-19 should be defined under the diagnostic criteria, as contained in the International Classification of Headache Disorders-3, as headache attributed to a systemic viral infection.² As this is a secondary headache appearing with an infection, the treating physician needs to rule out possible underlying meningitis and/or encephalitis in the diagnosis. Moreover, other secondary headaches (eg, cerebral venous thrombosis) may appear, so clinicians need to carefully evaluate patients with headache during Covid-19 to detect signs or symptoms that point to other etiologies.

It is also advisable to know the clinical manifestations of headache attributed to Covid-19. Studies published so far have observed two main phenotypes of headache in the acute phase of the infection: one resembles migraine, the other, a tension-type headache.^1,3 Although patients with history of migraine who contract Covid-19 report headache that is more similar to primary headache disorder,⁴ two relevant aspects should be considered. Namely, migraine-like features can be observed in patients without personal migraine history; and Covid-19 patients with such history may perceive that headache they experience in the infection’s acute phase differs from their usual experience, especially regarding increased severity or duration.^5,6 Of note, headache can be a prodromal symptom of the SARS-CoV-2 infection.¹

Evolution of a headache

 Because headache appearing after the acute phase of the infection can persist, often manifesting migraine-like features, it is inordinately helpful for clinicians to know its evolution.¹ This persistent headache, sometimes referred to as post-covid headache, is not aptly named because the post-covid headache is not just one type of headache, but instead can manifest as different headache types.

 A recently published case series in Headache discussed three Covid patients who all experienced persistent headache during the infection’s post-acute phase.⁷ These patients experienced a migraine-like phenotype as have others with mild Covid-19, but their personal history of migraine, as well as their experience with Covid-19 related headache, were substantially different. Some patients had personal migraine history while others did not; some patients experienced no headache in the acute phase but did so in the post-acute phase; and the concomitant symptoms of the post-acute phase, such as insomnia, memory loss, dizziness, fatigue, and brain fog, were differentially expressed by patients.⁷ 

 This case series introduces the concept that patients with no prior history of migraine or any other primary headache disorder can develop a de novo headache because of their SARS-CoV-2 infection. Moreover, it could manifest as a new daily persistent headache. And patients with personal history of migraine may experience sudden chronification in their headache’s characteristics, rather than develop a new type of headache.⁷

 In another study, soon to be published in Cephalalgia, researchers observed that the median duration of headache in the acute phase is 2 weeks. This multicenter Spanish study, in which data on headache duration were available for 874 patients, found that 16% of these particular patients had persistent headache after 9 months. According to this study, headache that does not resolve within the first 3 months is less likely to do so later on.

Treatment

For clinicians, the significance of these findings is straightforward: Patients with headache experienced in the infection’s acute phase that does not seem to resolve post-infection requires continued medical attention. Patients should be monitored, carefully managed, and treated to avoid the onset of a persisting headache. This applies to patients with or without personal migraine history.

But which treatments should be prescribed? As there are no specific therapies for headache attributed to Covid-19, either in the acute or post-acute phase of the infection, clinicians must turn to existing therapies.

As with patients with migraine, patients with persistent headache post-Covid infection need a headache prevention strategy.

The strategy should be based on the following principles:

• treat headache
• treat comorbidities including mood disorders,  insomnia, and so on
• avoid complications such as medication overuse, which may be very common in these patients.

Acute medications

Despite the lack of specific literature on this matter, migraine-like phenotypes may respond to triptans and probably, where available, lasmiditan and gepants. These medications probably represent a therapeutic option for Covid patients with headache, but before prescribing them clinicians should carefully evaluate their use.

Before deciding on the prescription, clinicians should consider not only the medications’ most common contraindications, but also those that are related to Covid-19: the phase of the infection (acute/post-acute); the infection’s severity; and the presence of other Covid-related health problems. The concerns over the use of nonsteroidal anti-inflammatory medications (NSAIDs) and corticosteroids, raised when the pandemic first struck, have greatly dissipated.^8,9 Some patients with prolonged headache may benefit from a brief cycle of corticosteroids, similar to the treatment given to those patients with status migrainosus. Nerve blocks could also be considered.

Preventive medications

Drugs can be prescribed according to the headache phenotype too, but there are no published studies that specifically evaluate headache prevention treatments in patients with persistent headache post-infection. The case series mentioned earlier in this article recorded that patients whose headaches were treated with amitriptyline and onabotulinumtoxinA had reported variable treatment responses to this regimen, according to the patients’ characteristics.⁷

However, one important question regarding the safety of Covid patients with migraine – specifically patients on preventive treatments during the infection’s acute phase – has been somewhat resolved.

Medications such as renin-angiotensin system (RAS) blockers, suspected of possible involvement in the SARs-CoV-2 pathogenicity, seem to be safe.^8,10 And, in another multicenter Spanish study, researchers found that the use of anti-CGRP monoclonal antibodies did not seem to be associated with worse Covid-19 outcomes despite the possible implication of CGRP in modulating inflammatory responses during a viral infection.¹¹

The study of anti-CGRP monoclonal antibodies could be important in the future for another reason: To see whether these medications could be effective as a preventive treatment in patients with persistent headache after Covid-19, regardless of whether these patients have personal migraine history.

An interesting and important message to close this article. Although headache experienced in the infection’s acute phase could be extremely disabling for patients, the evidence points to the presence of headache as a marker of a better Covid-19 prognosis, in terms of a shorter infection period and a lower risk of mortality among hospitalized patients.^1,3,12  

This brief communication contains current information to help clinicians treat and inform their patients with Covid-sourced headache. Yet, we must keep in mind that the majority of the data reported here and published in the literature refer to studies conducted during the first wave of the pandemic. The emergence of new SARS-CoV-2 variants and vaccines have enormously changed the disease’s clinical presentation and course, so future studies are warranted to re-assess the validity of these findings under new conditions.

Edoardo Caronna, MD and Patricia Pozo-Rosich, MD, PhD,  Neurology Department, Hospital Universitari Vall d’Hebron, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; and Headache and Neurological Pain Research Group, Vall d’Hebron Research Institute, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. Dr. Pozo-Rosich also serves on the boards of the International Headache Society and Council of the European Headache Federation and is an editor for various peer-reviewed journals, including Cephalalgia and Headache.

Headache is a symptom of the coronavirus disease 2019 (Covid-19), caused by the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the pandemic began, researchers have tried to describe, understand, and help clinicians manage headache in the setting of Covid-19.

The reason is simple: Headache is common, often debilitating, and difficult to treat.¹

Moreover, headache could manifest both in the acute phase of the infection and, once the infection has resolved, in the post-acute phase.¹ Therefore, it is critical for clinicians to know more about headache, as headache can be a common reason that patients seek help, both in the specialized and non-specialized medical care setting.

Definitions and manifestations

While the first step in such a communication would be to define headache attributed to Covid-19, no specific definition exists, as this is a new disease. Therefore, headache attributed to Covid-19 should be defined under the diagnostic criteria, as contained in the International Classification of Headache Disorders-3, as headache attributed to a systemic viral infection.² As this is a secondary headache appearing with an infection, the treating physician needs to rule out possible underlying meningitis and/or encephalitis in the diagnosis. Moreover, other secondary headaches (eg, cerebral venous thrombosis) may appear, so clinicians need to carefully evaluate patients with headache during Covid-19 to detect signs or symptoms that point to other etiologies.

It is also advisable to know the clinical manifestations of headache attributed to Covid-19. Studies published so far have observed two main phenotypes of headache in the acute phase of the infection: one resembles migraine, the other, a tension-type headache.^1,3 Although patients with history of migraine who contract Covid-19 report headache that is more similar to primary headache disorder,⁴ two relevant aspects should be considered. Namely, migraine-like features can be observed in patients without personal migraine history; and Covid-19 patients with such history may perceive that headache they experience in the infection’s acute phase differs from their usual experience, especially regarding increased severity or duration.^5,6 Of note, headache can be a prodromal symptom of the SARS-CoV-2 infection.¹

Evolution of a headache

 Because headache appearing after the acute phase of the infection can persist, often manifesting migraine-like features, it is inordinately helpful for clinicians to know its evolution.¹ This persistent headache, sometimes referred to as post-covid headache, is not aptly named because the post-covid headache is not just one type of headache, but instead can manifest as different headache types.

 A recently published case series in Headache discussed three Covid patients who all experienced persistent headache during the infection’s post-acute phase.⁷ These patients experienced a migraine-like phenotype as have others with mild Covid-19, but their personal history of migraine, as well as their experience with Covid-19 related headache, were substantially different. Some patients had personal migraine history while others did not; some patients experienced no headache in the acute phase but did so in the post-acute phase; and the concomitant symptoms of the post-acute phase, such as insomnia, memory loss, dizziness, fatigue, and brain fog, were differentially expressed by patients.⁷ 

 This case series introduces the concept that patients with no prior history of migraine or any other primary headache disorder can develop a de novo headache because of their SARS-CoV-2 infection. Moreover, it could manifest as a new daily persistent headache. And patients with personal history of migraine may experience sudden chronification in their headache’s characteristics, rather than develop a new type of headache.⁷

 In another study, soon to be published in Cephalalgia, researchers observed that the median duration of headache in the acute phase is 2 weeks. This multicenter Spanish study, in which data on headache duration were available for 874 patients, found that 16% of these particular patients had persistent headache after 9 months. According to this study, headache that does not resolve within the first 3 months is less likely to do so later on.

Treatment

For clinicians, the significance of these findings is straightforward: Patients with headache experienced in the infection’s acute phase that does not seem to resolve post-infection requires continued medical attention. Patients should be monitored, carefully managed, and treated to avoid the onset of a persisting headache. This applies to patients with or without personal migraine history.

But which treatments should be prescribed? As there are no specific therapies for headache attributed to Covid-19, either in the acute or post-acute phase of the infection, clinicians must turn to existing therapies.

As with patients with migraine, patients with persistent headache post-Covid infection need a headache prevention strategy.

The strategy should be based on the following principles:

• treat headache
• treat comorbidities including mood disorders,  insomnia, and so on
• avoid complications such as medication overuse, which may be very common in these patients.

Acute medications

Despite the lack of specific literature on this matter, migraine-like phenotypes may respond to triptans and probably, where available, lasmiditan and gepants. These medications probably represent a therapeutic option for Covid patients with headache, but before prescribing them clinicians should carefully evaluate their use.

Before deciding on the prescription, clinicians should consider not only the medications’ most common contraindications, but also those that are related to Covid-19: the phase of the infection (acute/post-acute); the infection’s severity; and the presence of other Covid-related health problems. The concerns over the use of nonsteroidal anti-inflammatory medications (NSAIDs) and corticosteroids, raised when the pandemic first struck, have greatly dissipated.^8,9 Some patients with prolonged headache may benefit from a brief cycle of corticosteroids, similar to the treatment given to those patients with status migrainosus. Nerve blocks could also be considered.

Preventive medications

Drugs can be prescribed according to the headache phenotype too, but there are no published studies that specifically evaluate headache prevention treatments in patients with persistent headache post-infection. The case series mentioned earlier in this article recorded that patients whose headaches were treated with amitriptyline and onabotulinumtoxinA had reported variable treatment responses to this regimen, according to the patients’ characteristics.⁷

However, one important question regarding the safety of Covid patients with migraine – specifically patients on preventive treatments during the infection’s acute phase – has been somewhat resolved.

Medications such as renin-angiotensin system (RAS) blockers, suspected of possible involvement in the SARs-CoV-2 pathogenicity, seem to be safe.^8,10 And, in another multicenter Spanish study, researchers found that the use of anti-CGRP monoclonal antibodies did not seem to be associated with worse Covid-19 outcomes despite the possible implication of CGRP in modulating inflammatory responses during a viral infection.¹¹

The study of anti-CGRP monoclonal antibodies could be important in the future for another reason: To see whether these medications could be effective as a preventive treatment in patients with persistent headache after Covid-19, regardless of whether these patients have personal migraine history.

An interesting and important message to close this article. Although headache experienced in the infection’s acute phase could be extremely disabling for patients, the evidence points to the presence of headache as a marker of a better Covid-19 prognosis, in terms of a shorter infection period and a lower risk of mortality among hospitalized patients.^1,3,12  

This brief communication contains current information to help clinicians treat and inform their patients with Covid-sourced headache. Yet, we must keep in mind that the majority of the data reported here and published in the literature refer to studies conducted during the first wave of the pandemic. The emergence of new SARS-CoV-2 variants and vaccines have enormously changed the disease’s clinical presentation and course, so future studies are warranted to re-assess the validity of these findings under new conditions.

Edoardo Caronna, MD and Patricia Pozo-Rosich, MD, PhD,  Neurology Department, Hospital Universitari Vall d’Hebron, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; and Headache and Neurological Pain Research Group, Vall d’Hebron Research Institute, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. Dr. Pozo-Rosich also serves on the boards of the International Headache Society and Council of the European Headache Federation and is an editor for various peer-reviewed journals, including Cephalalgia and Headache.

Headache is a symptom of the coronavirus disease 2019 (Covid-19), caused by the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the pandemic began, researchers have tried to describe, understand, and help clinicians manage headache in the setting of Covid-19.

The reason is simple: Headache is common, often debilitating, and difficult to treat.¹

Moreover, headache could manifest both in the acute phase of the infection and, once the infection has resolved, in the post-acute phase.¹ Therefore, it is critical for clinicians to know more about headache, as headache can be a common reason that patients seek help, both in the specialized and non-specialized medical care setting.

Definitions and manifestations

While the first step in such a communication would be to define headache attributed to Covid-19, no specific definition exists, as this is a new disease. Therefore, headache attributed to Covid-19 should be defined under the diagnostic criteria, as contained in the International Classification of Headache Disorders-3, as headache attributed to a systemic viral infection.² As this is a secondary headache appearing with an infection, the treating physician needs to rule out possible underlying meningitis and/or encephalitis in the diagnosis. Moreover, other secondary headaches (eg, cerebral venous thrombosis) may appear, so clinicians need to carefully evaluate patients with headache during Covid-19 to detect signs or symptoms that point to other etiologies.

It is also advisable to know the clinical manifestations of headache attributed to Covid-19. Studies published so far have observed two main phenotypes of headache in the acute phase of the infection: one resembles migraine, the other, a tension-type headache.^1,3 Although patients with history of migraine who contract Covid-19 report headache that is more similar to primary headache disorder,⁴ two relevant aspects should be considered. Namely, migraine-like features can be observed in patients without personal migraine history; and Covid-19 patients with such history may perceive that headache they experience in the infection’s acute phase differs from their usual experience, especially regarding increased severity or duration.^5,6 Of note, headache can be a prodromal symptom of the SARS-CoV-2 infection.¹

Evolution of a headache

 Because headache appearing after the acute phase of the infection can persist, often manifesting migraine-like features, it is inordinately helpful for clinicians to know its evolution.¹ This persistent headache, sometimes referred to as post-covid headache, is not aptly named because the post-covid headache is not just one type of headache, but instead can manifest as different headache types.

 A recently published case series in Headache discussed three Covid patients who all experienced persistent headache during the infection’s post-acute phase.⁷ These patients experienced a migraine-like phenotype as have others with mild Covid-19, but their personal history of migraine, as well as their experience with Covid-19 related headache, were substantially different. Some patients had personal migraine history while others did not; some patients experienced no headache in the acute phase but did so in the post-acute phase; and the concomitant symptoms of the post-acute phase, such as insomnia, memory loss, dizziness, fatigue, and brain fog, were differentially expressed by patients.⁷ 

 This case series introduces the concept that patients with no prior history of migraine or any other primary headache disorder can develop a de novo headache because of their SARS-CoV-2 infection. Moreover, it could manifest as a new daily persistent headache. And patients with personal history of migraine may experience sudden chronification in their headache’s characteristics, rather than develop a new type of headache.⁷

 In another study, soon to be published in Cephalalgia, researchers observed that the median duration of headache in the acute phase is 2 weeks. This multicenter Spanish study, in which data on headache duration were available for 874 patients, found that 16% of these particular patients had persistent headache after 9 months. According to this study, headache that does not resolve within the first 3 months is less likely to do so later on.

Treatment

For clinicians, the significance of these findings is straightforward: Patients with headache experienced in the infection’s acute phase that does not seem to resolve post-infection requires continued medical attention. Patients should be monitored, carefully managed, and treated to avoid the onset of a persisting headache. This applies to patients with or without personal migraine history.

But which treatments should be prescribed? As there are no specific therapies for headache attributed to Covid-19, either in the acute or post-acute phase of the infection, clinicians must turn to existing therapies.

As with patients with migraine, patients with persistent headache post-Covid infection need a headache prevention strategy.

The strategy should be based on the following principles:

• treat headache
• treat comorbidities including mood disorders,  insomnia, and so on
• avoid complications such as medication overuse, which may be very common in these patients.

Acute medications

Despite the lack of specific literature on this matter, migraine-like phenotypes may respond to triptans and probably, where available, lasmiditan and gepants. These medications probably represent a therapeutic option for Covid patients with headache, but before prescribing them clinicians should carefully evaluate their use.

Before deciding on the prescription, clinicians should consider not only the medications’ most common contraindications, but also those that are related to Covid-19: the phase of the infection (acute/post-acute); the infection’s severity; and the presence of other Covid-related health problems. The concerns over the use of nonsteroidal anti-inflammatory medications (NSAIDs) and corticosteroids, raised when the pandemic first struck, have greatly dissipated.^8,9 Some patients with prolonged headache may benefit from a brief cycle of corticosteroids, similar to the treatment given to those patients with status migrainosus. Nerve blocks could also be considered.

Preventive medications

Drugs can be prescribed according to the headache phenotype too, but there are no published studies that specifically evaluate headache prevention treatments in patients with persistent headache post-infection. The case series mentioned earlier in this article recorded that patients whose headaches were treated with amitriptyline and onabotulinumtoxinA had reported variable treatment responses to this regimen, according to the patients’ characteristics.⁷

However, one important question regarding the safety of Covid patients with migraine – specifically patients on preventive treatments during the infection’s acute phase – has been somewhat resolved.

Medications such as renin-angiotensin system (RAS) blockers, suspected of possible involvement in the SARs-CoV-2 pathogenicity, seem to be safe.^8,10 And, in another multicenter Spanish study, researchers found that the use of anti-CGRP monoclonal antibodies did not seem to be associated with worse Covid-19 outcomes despite the possible implication of CGRP in modulating inflammatory responses during a viral infection.¹¹

The study of anti-CGRP monoclonal antibodies could be important in the future for another reason: To see whether these medications could be effective as a preventive treatment in patients with persistent headache after Covid-19, regardless of whether these patients have personal migraine history.

An interesting and important message to close this article. Although headache experienced in the infection’s acute phase could be extremely disabling for patients, the evidence points to the presence of headache as a marker of a better Covid-19 prognosis, in terms of a shorter infection period and a lower risk of mortality among hospitalized patients.^1,3,12  

This brief communication contains current information to help clinicians treat and inform their patients with Covid-sourced headache. Yet, we must keep in mind that the majority of the data reported here and published in the literature refer to studies conducted during the first wave of the pandemic. The emergence of new SARS-CoV-2 variants and vaccines have enormously changed the disease’s clinical presentation and course, so future studies are warranted to re-assess the validity of these findings under new conditions.

Any other docs out there have patients on what I call the migraine-go-round?

I first discovered this ride when I started in practice, though back then it was with triptans. You know the game, you’d start someone on one drug because you had samples, or a coupon, or both. A few months later the coupon had run out, and their insurance wouldn’t cover it, so you’d move them to another drug. Maxalt to Imitrex to Zomig to Relpax to Axert to Maxalt.

The ride continued until the majority had gone generic, and I’d almost forgotten about it. You can’t do it with seizure patients or Parkinson’s disease.

But with the advent of the CGRP era, it seems to have started again. Coverage coupons have a limited number of refills, or the deal changes, or a pharmacy stops taking them, or an insurance company changes their mind, or whatever. So we go from Aimovig to Emgality to Qulipta to Ajovy to Nurtec to Aimovig (not necessarily in that order).

It’s annoying (not just for the patients, but for me and my staff as we try to keep up with it), and obviously it doesn’t work for everyone because each patient responds differently. But, if it works, it at least gets some degree of coverage until an insurance company finally approves a given drug for that person. And even then a patient’s own financial circumstances or changing job situation can keep things spinning.

When you finally step off the ride you have to pore back through the chart to figure out which, if any, worked best, or had side effects, or whatever.

A good part of modern medicine is adapting to these sorts of things. Patient care isn’t always as simple as “take this and call me in the morning.” Sometimes we have to play the game to get things done.

The trick is learning the rules on the fly – for all involved.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Any other docs out there have patients on what I call the migraine-go-round?

I first discovered this ride when I started in practice, though back then it was with triptans. You know the game, you’d start someone on one drug because you had samples, or a coupon, or both. A few months later the coupon had run out, and their insurance wouldn’t cover it, so you’d move them to another drug. Maxalt to Imitrex to Zomig to Relpax to Axert to Maxalt.

The ride continued until the majority had gone generic, and I’d almost forgotten about it. You can’t do it with seizure patients or Parkinson’s disease.

But with the advent of the CGRP era, it seems to have started again. Coverage coupons have a limited number of refills, or the deal changes, or a pharmacy stops taking them, or an insurance company changes their mind, or whatever. So we go from Aimovig to Emgality to Qulipta to Ajovy to Nurtec to Aimovig (not necessarily in that order).

It’s annoying (not just for the patients, but for me and my staff as we try to keep up with it), and obviously it doesn’t work for everyone because each patient responds differently. But, if it works, it at least gets some degree of coverage until an insurance company finally approves a given drug for that person. And even then a patient’s own financial circumstances or changing job situation can keep things spinning.

When you finally step off the ride you have to pore back through the chart to figure out which, if any, worked best, or had side effects, or whatever.

A good part of modern medicine is adapting to these sorts of things. Patient care isn’t always as simple as “take this and call me in the morning.” Sometimes we have to play the game to get things done.

The trick is learning the rules on the fly – for all involved.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Any other docs out there have patients on what I call the migraine-go-round?

I first discovered this ride when I started in practice, though back then it was with triptans. You know the game, you’d start someone on one drug because you had samples, or a coupon, or both. A few months later the coupon had run out, and their insurance wouldn’t cover it, so you’d move them to another drug. Maxalt to Imitrex to Zomig to Relpax to Axert to Maxalt.

The ride continued until the majority had gone generic, and I’d almost forgotten about it. You can’t do it with seizure patients or Parkinson’s disease.

But with the advent of the CGRP era, it seems to have started again. Coverage coupons have a limited number of refills, or the deal changes, or a pharmacy stops taking them, or an insurance company changes their mind, or whatever. So we go from Aimovig to Emgality to Qulipta to Ajovy to Nurtec to Aimovig (not necessarily in that order).

It’s annoying (not just for the patients, but for me and my staff as we try to keep up with it), and obviously it doesn’t work for everyone because each patient responds differently. But, if it works, it at least gets some degree of coverage until an insurance company finally approves a given drug for that person. And even then a patient’s own financial circumstances or changing job situation can keep things spinning.

When you finally step off the ride you have to pore back through the chart to figure out which, if any, worked best, or had side effects, or whatever.

A good part of modern medicine is adapting to these sorts of things. Patient care isn’t always as simple as “take this and call me in the morning.” Sometimes we have to play the game to get things done.

The trick is learning the rules on the fly – for all involved.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Cluster headache attacks induced by either pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) or vasoactive intestinal polypeptide (VIP) do not lead to changes in plasma levels of calcitonin gene-related peptide (CGRP) or markers of mast cell activation such as tryptase and histamine, a new study has found.

“Whether cluster headache attacks provoked by CGRP and PACAP38/VIP are mediated by distinct signaling pathways will be worth investigating in forthcoming studies,” wrote Lanfranco Pellesi, MD, of the Danish Headache Center at the University of Copenhagen, and his coauthors. The study was published in Cephalalgia.

To assess how these biochemical variables might contribute to cluster headache attacks, the researchers launched a randomized, double-blind trial of data from 44 Danish participants with cluster headache. The average age of the patients was 38 years; 14 had active episodic cluster headache, 15 had episodic cluster headache in remission, and 15 had chronic cluster headache.

All patients received a continuous infusion of either PACAP38 (10 pmol/kg per minute) or VIP (8 pmol/kg per minute) over a 20-minute period, using a time- and volume-controlled infusion pump. Blood was collected for analysis at fixed time points, including at baseline, at the end of the infusion, 10 minutes after the infusion, and 70 minutes after the infusion. Technical problems led to missing values in 285 out of 1,144 planned plasma samples.

PACAP38 infusion resulted in a cluster headache attack in 13 of the 44 participants and VIP induced an attack in 12 of the 44. No differences in plasma CGRP (P = .7074), tryptase (P = .6673), and histamine (P = .4792) levels were found between patients who developed attacks and those who did not, and the plasma concentrations did not differ among the various blood-drawing time points.

There was also no difference in plasma CGRP levels between patients with active episodic cluster headache, those with episodic cluster headache in remission, and those with chronic cluster headache. After post hoc analysis, plasma tryptase and plasma histamine levels were similar among the three cluster headache patient groups.

The final link to the cluster headache puzzle has not yet been found

“We know a lot about cluster headache: how it presents, how we can stop it acutely, and how we can stop it preventively. But we don’t know everything about all the neurotransmitters involved, the triggers that start an attack, or the causes of pain,” Alan Rapoport, MD, professor of neurology at the University of California, Los Angeles (UCLA), and past president of the International Headache Society, said in an interview. “This study was performed to find the answer to a small piece of the puzzle. Is CGRP the missing link for patients who begin a cluster attack, or should we be looking elsewhere?

“I would be cautious and say it appears that it doesn’t seem to be related, but further studies may show something different,” he added. “The reason for my qualification: There is a monoclonal antibody [galcanezumab], which grabs CGRP and prevents it from docking on its receptor, that has been approved for preventive treatment of episodic cluster headache. When you have episodic cluster, go into a cluster period, and take galcanezumab, it could and should decrease the number of attacks that you would ordinarily have had. That means it is related somewhat. But it certainly doesn’t work for everyone, so more investigations like this are needed.”

“What’s important about this study is that it opens up the possibility that there is another way into the cluster attack that could be operationalized for therapeutic purposes,” Peter Goadsby, MD, PhD, professor of neurology at UCLA and president of the American Headache Society, said in an interview.

When asked about the authors’ stated interest in investigating “if monoclonal antibodies targeting the CGRP pathway prevent PACAP38- or VIP-induced cluster headache attacks” as a follow-up, Dr. Goadsby strongly backed the idea. “If I sound excited about actually exploring whether that was a useful treatment or not, it’s because cluster headache is a dreadful condition. And the sooner you could work out whether it was useful or put the money into something else, well, that’s where I’d go.

“I think the principle here of doing experimental medicine, getting into human work with targets like this at the earliest possible time, is something that is not done as often as would be appropriate,” he added. “There is not enough investment, in my view, in early phase experimental work, which really just gets to that next step. Broadly speaking, the encouragement and support of experimental medicine is crucial to developing new therapies.”

The authors recognized their study’s potential limitations, including it’s being an exploratory study with results that should be interpreted cautiously. They acknowledged discrepancies with previous studies of plasma CGRP during cluster headache attacks, offering “different methodologies, including intra-assay differences and the location of blood sampling” as a possible reason. They also explained that some of the data are missing “completely at random” due to their policy of discarding all observations with incomplete laboratory measurements, adding that the impact on their sample size was “only modest.”

“In spite of these limitations,” Dr. Rapoport said, “this is an excellent study that shows us that PACAP38- and VIP-induced cluster headache attacks are not associated with alterations in plasma CGRP or in histamine and tryptase.”

Regarding potential conflicts of interest, one author reported being employed at the testing lab where the histamine measurements were conducted, as did another author who serves as the lab’s scientific adviser. A third author reported receiving personal fees from various pharmaceutical companies.

Cluster headache attacks induced by either pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) or vasoactive intestinal polypeptide (VIP) do not lead to changes in plasma levels of calcitonin gene-related peptide (CGRP) or markers of mast cell activation such as tryptase and histamine, a new study has found.

“Whether cluster headache attacks provoked by CGRP and PACAP38/VIP are mediated by distinct signaling pathways will be worth investigating in forthcoming studies,” wrote Lanfranco Pellesi, MD, of the Danish Headache Center at the University of Copenhagen, and his coauthors. The study was published in Cephalalgia.

To assess how these biochemical variables might contribute to cluster headache attacks, the researchers launched a randomized, double-blind trial of data from 44 Danish participants with cluster headache. The average age of the patients was 38 years; 14 had active episodic cluster headache, 15 had episodic cluster headache in remission, and 15 had chronic cluster headache.

All patients received a continuous infusion of either PACAP38 (10 pmol/kg per minute) or VIP (8 pmol/kg per minute) over a 20-minute period, using a time- and volume-controlled infusion pump. Blood was collected for analysis at fixed time points, including at baseline, at the end of the infusion, 10 minutes after the infusion, and 70 minutes after the infusion. Technical problems led to missing values in 285 out of 1,144 planned plasma samples.

PACAP38 infusion resulted in a cluster headache attack in 13 of the 44 participants and VIP induced an attack in 12 of the 44. No differences in plasma CGRP (P = .7074), tryptase (P = .6673), and histamine (P = .4792) levels were found between patients who developed attacks and those who did not, and the plasma concentrations did not differ among the various blood-drawing time points.

There was also no difference in plasma CGRP levels between patients with active episodic cluster headache, those with episodic cluster headache in remission, and those with chronic cluster headache. After post hoc analysis, plasma tryptase and plasma histamine levels were similar among the three cluster headache patient groups.

The final link to the cluster headache puzzle has not yet been found

“We know a lot about cluster headache: how it presents, how we can stop it acutely, and how we can stop it preventively. But we don’t know everything about all the neurotransmitters involved, the triggers that start an attack, or the causes of pain,” Alan Rapoport, MD, professor of neurology at the University of California, Los Angeles (UCLA), and past president of the International Headache Society, said in an interview. “This study was performed to find the answer to a small piece of the puzzle. Is CGRP the missing link for patients who begin a cluster attack, or should we be looking elsewhere?

“I would be cautious and say it appears that it doesn’t seem to be related, but further studies may show something different,” he added. “The reason for my qualification: There is a monoclonal antibody [galcanezumab], which grabs CGRP and prevents it from docking on its receptor, that has been approved for preventive treatment of episodic cluster headache. When you have episodic cluster, go into a cluster period, and take galcanezumab, it could and should decrease the number of attacks that you would ordinarily have had. That means it is related somewhat. But it certainly doesn’t work for everyone, so more investigations like this are needed.”

“What’s important about this study is that it opens up the possibility that there is another way into the cluster attack that could be operationalized for therapeutic purposes,” Peter Goadsby, MD, PhD, professor of neurology at UCLA and president of the American Headache Society, said in an interview.

When asked about the authors’ stated interest in investigating “if monoclonal antibodies targeting the CGRP pathway prevent PACAP38- or VIP-induced cluster headache attacks” as a follow-up, Dr. Goadsby strongly backed the idea. “If I sound excited about actually exploring whether that was a useful treatment or not, it’s because cluster headache is a dreadful condition. And the sooner you could work out whether it was useful or put the money into something else, well, that’s where I’d go.

“I think the principle here of doing experimental medicine, getting into human work with targets like this at the earliest possible time, is something that is not done as often as would be appropriate,” he added. “There is not enough investment, in my view, in early phase experimental work, which really just gets to that next step. Broadly speaking, the encouragement and support of experimental medicine is crucial to developing new therapies.”

The authors recognized their study’s potential limitations, including it’s being an exploratory study with results that should be interpreted cautiously. They acknowledged discrepancies with previous studies of plasma CGRP during cluster headache attacks, offering “different methodologies, including intra-assay differences and the location of blood sampling” as a possible reason. They also explained that some of the data are missing “completely at random” due to their policy of discarding all observations with incomplete laboratory measurements, adding that the impact on their sample size was “only modest.”

“In spite of these limitations,” Dr. Rapoport said, “this is an excellent study that shows us that PACAP38- and VIP-induced cluster headache attacks are not associated with alterations in plasma CGRP or in histamine and tryptase.”

Regarding potential conflicts of interest, one author reported being employed at the testing lab where the histamine measurements were conducted, as did another author who serves as the lab’s scientific adviser. A third author reported receiving personal fees from various pharmaceutical companies.

Cluster headache attacks induced by either pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) or vasoactive intestinal polypeptide (VIP) do not lead to changes in plasma levels of calcitonin gene-related peptide (CGRP) or markers of mast cell activation such as tryptase and histamine, a new study has found.

“Whether cluster headache attacks provoked by CGRP and PACAP38/VIP are mediated by distinct signaling pathways will be worth investigating in forthcoming studies,” wrote Lanfranco Pellesi, MD, of the Danish Headache Center at the University of Copenhagen, and his coauthors. The study was published in Cephalalgia.

To assess how these biochemical variables might contribute to cluster headache attacks, the researchers launched a randomized, double-blind trial of data from 44 Danish participants with cluster headache. The average age of the patients was 38 years; 14 had active episodic cluster headache, 15 had episodic cluster headache in remission, and 15 had chronic cluster headache.

All patients received a continuous infusion of either PACAP38 (10 pmol/kg per minute) or VIP (8 pmol/kg per minute) over a 20-minute period, using a time- and volume-controlled infusion pump. Blood was collected for analysis at fixed time points, including at baseline, at the end of the infusion, 10 minutes after the infusion, and 70 minutes after the infusion. Technical problems led to missing values in 285 out of 1,144 planned plasma samples.

PACAP38 infusion resulted in a cluster headache attack in 13 of the 44 participants and VIP induced an attack in 12 of the 44. No differences in plasma CGRP (P = .7074), tryptase (P = .6673), and histamine (P = .4792) levels were found between patients who developed attacks and those who did not, and the plasma concentrations did not differ among the various blood-drawing time points.

There was also no difference in plasma CGRP levels between patients with active episodic cluster headache, those with episodic cluster headache in remission, and those with chronic cluster headache. After post hoc analysis, plasma tryptase and plasma histamine levels were similar among the three cluster headache patient groups.

The final link to the cluster headache puzzle has not yet been found

“We know a lot about cluster headache: how it presents, how we can stop it acutely, and how we can stop it preventively. But we don’t know everything about all the neurotransmitters involved, the triggers that start an attack, or the causes of pain,” Alan Rapoport, MD, professor of neurology at the University of California, Los Angeles (UCLA), and past president of the International Headache Society, said in an interview. “This study was performed to find the answer to a small piece of the puzzle. Is CGRP the missing link for patients who begin a cluster attack, or should we be looking elsewhere?

“I would be cautious and say it appears that it doesn’t seem to be related, but further studies may show something different,” he added. “The reason for my qualification: There is a monoclonal antibody [galcanezumab], which grabs CGRP and prevents it from docking on its receptor, that has been approved for preventive treatment of episodic cluster headache. When you have episodic cluster, go into a cluster period, and take galcanezumab, it could and should decrease the number of attacks that you would ordinarily have had. That means it is related somewhat. But it certainly doesn’t work for everyone, so more investigations like this are needed.”

“What’s important about this study is that it opens up the possibility that there is another way into the cluster attack that could be operationalized for therapeutic purposes,” Peter Goadsby, MD, PhD, professor of neurology at UCLA and president of the American Headache Society, said in an interview.

When asked about the authors’ stated interest in investigating “if monoclonal antibodies targeting the CGRP pathway prevent PACAP38- or VIP-induced cluster headache attacks” as a follow-up, Dr. Goadsby strongly backed the idea. “If I sound excited about actually exploring whether that was a useful treatment or not, it’s because cluster headache is a dreadful condition. And the sooner you could work out whether it was useful or put the money into something else, well, that’s where I’d go.

“I think the principle here of doing experimental medicine, getting into human work with targets like this at the earliest possible time, is something that is not done as often as would be appropriate,” he added. “There is not enough investment, in my view, in early phase experimental work, which really just gets to that next step. Broadly speaking, the encouragement and support of experimental medicine is crucial to developing new therapies.”

The authors recognized their study’s potential limitations, including it’s being an exploratory study with results that should be interpreted cautiously. They acknowledged discrepancies with previous studies of plasma CGRP during cluster headache attacks, offering “different methodologies, including intra-assay differences and the location of blood sampling” as a possible reason. They also explained that some of the data are missing “completely at random” due to their policy of discarding all observations with incomplete laboratory measurements, adding that the impact on their sample size was “only modest.”

“In spite of these limitations,” Dr. Rapoport said, “this is an excellent study that shows us that PACAP38- and VIP-induced cluster headache attacks are not associated with alterations in plasma CGRP or in histamine and tryptase.”

Regarding potential conflicts of interest, one author reported being employed at the testing lab where the histamine measurements were conducted, as did another author who serves as the lab’s scientific adviser. A third author reported receiving personal fees from various pharmaceutical companies.

Most people avoid smartphones when they have a migraine headache, but a noninvasive treatment for episodic migraines may change that.

A smartphone-enabled device, cleared by the Food and Drug Administration in early 2021, uses technology to trick the brain into releasing the neurotransmitters serotonin and noradrenaline that can help ease migraine pain.

Tina Montgomery, 58, has suffered from migraines since childhood and spent years looking for something to help manage them. Doctors consider her a “chronic” sufferer in that she has more than 14 migraines a month (fewer than 14 is considered “episodic”). Prescription antidepressants, anticonvulsants, and botulinum toxin shots as preventive treatments helped a little but not enough.

A few years ago, she found some relief using a new preventive injectable medication that targets a peptide known as CGRP, combined with an oral CGRP rescue medication, ubrogepant (Ubrelvy). However, by early 2021, Ms. Montgomery’s chronic migraines were back as she faced stress from the pandemic and her role as a caregiver for her aging parents.

“I was going through so much medication. I just didn’t feel good taking so much,” she said.

Looking for relief, she read about Nerivio, a wearable migraine treatment device that uses remote electrical neuromodulation (REN). She mentioned the device to her neurologist, and he agreed she might benefit from trying it out. Today, she uses the device whenever she feels a migraine may be imminent, she said.

“It really helps me stave off migraines I feel coming on and the milder ones where I would normally hesitate to use prescription medication because [insurance] limits the number of pills they give you in a month,” she said. “I follow through with the Nerivio treatment and usually find that my migraine doesn’t fully develop or is completely gone, and I don’t get a migraine at all.”
 

Taking it on the arm

The device works by stimulating nerves at the back of the arm right around the triceps. “Those nerve fibers relay information to the brain stem [so it can] work its magic and use the brain’s own natural mechanisms for reducing pain,” said Brian M. Grosberg, MD, director of the Hartford Healthcare Ayer Neuroscience Institute Headache Center, West Hartford, Conn.  

These mechanisms are like a bait-and-switch for the brain, said Britany Klenofsky, MD, assistant professor of neurology, Icahn School of Medicine at Mount Sinai, New York. “You’re trying to stimulate pain somewhere else [on the body] to tell the brain to protect itself and release [the neurotransmitter] serotonin,” she said. “You do this by putting the device on your arm, an area that’s away from the head where the pain is actively occurring, turning the device on, and increasing the stimulation to a nearly painful stimulus.”

This pseudo pain prompts the brain to release serotonin, the feel-good hormone along with norepinephrine and noradrenaline. The device works best when it’s used as soon as a migraine starts, so patients should hook up Nerivio within the first 20-30 minutes of onset of pain, said Dr. Grosberg, who was an investigator on the double-blind treatment study that led to FDA clearance. If patients wait too long, the device may not work.

This is why as soon as Ms. Montgomery feels a migraine aura (there are six types of migraine auras, including visual changes and muscle weakness) that occurs right before a migraine strikes, she puts the device armband on her upper arm and launches its smartphone app. Then she turns on the device for a 45-minute treatment, which begins with what she characterizes as tingling and vibration sensations on her arm. She turns up the intensity of the sensations, which are mild electric currents, until they are well-felt but not painful.

Ms. Montgomery said she can use the device and multitask since there’s no need for her to lie down or sit in a darkened room. And since it is worn on the arm, she can wear it under a shirtsleeve while working or out in public without anyone noticing. She also uses the app’s migraine diary and guided meditation to help reduce the anxiety that often accompanies her migraines.

The device is approved for adolescents and adults and can be used for both episodic and chronic migraines. From an efficacy standpoint, the device provides relief about as well as a commonly used pharmaceutical class of drugs, triptans. About 37% of people with episodic migraine achieved complete freedom from pain 2 hours after their treatment. In addition, about two-thirds of people reported pain relief after 2 hours, which is better success than people find with many prescription and nonprescription drugs.

A separate study looked at acute treatment for chronic migraine sufferers and found nearly 60% of people using the device found relief and 21% said they were pain-free after 2 hours. Almost two-thirds of those who experienced pain relief were pain-free 24 hours after the treatment.
 

Finding the perfect patient

There are other FDA-cleared noninvasive devices to treat migraines. One device, CEFALY, is an external trigeminal nerve stimulation device that sits on the forehead. Another device, SpringTMS, uses transcranial magnetic stimulation on the back of the head. A third option, the gammaCore Sapphire, is placed on the neck to stimulate the vagus nerve. All three have been cleared by the FDA to work as preventive and acute treatments for migraine.

Theranica, the company that developed Nerivio, is trying to boost use of the device by allowing patients to get a prescription via telehealth visits with a physician.

The company, as well as the companies behind the other neuromodulation devices, are marketing their treatments to children ages 12 and up since nonpharmacologic options are often preferable for parents, said Thomas Berk, MD, a clinical associate professor in the division of headache at NYU Langone Health in New York.

Dr. Berk said the devices could be appealing for those people who don’t want or can’t take medication, such as pregnant women or those who don’t respond well to drugs. “[They] could also be used by somebody who needs something in addition to a medication,” he said.

For now, people like Ms. Montgomery say they are happy to have another tool in their migraine arsenal. “Overall, I’m taking less medication because I haven’t had to have my Ubrelvy refilled as often as I used to,” she said. “It’s really helped me manage changes and stresses in my life.”

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

Most people avoid smartphones when they have a migraine headache, but a noninvasive treatment for episodic migraines may change that.

A smartphone-enabled device, cleared by the Food and Drug Administration in early 2021, uses technology to trick the brain into releasing the neurotransmitters serotonin and noradrenaline that can help ease migraine pain.

Tina Montgomery, 58, has suffered from migraines since childhood and spent years looking for something to help manage them. Doctors consider her a “chronic” sufferer in that she has more than 14 migraines a month (fewer than 14 is considered “episodic”). Prescription antidepressants, anticonvulsants, and botulinum toxin shots as preventive treatments helped a little but not enough.

A few years ago, she found some relief using a new preventive injectable medication that targets a peptide known as CGRP, combined with an oral CGRP rescue medication, ubrogepant (Ubrelvy). However, by early 2021, Ms. Montgomery’s chronic migraines were back as she faced stress from the pandemic and her role as a caregiver for her aging parents.

“I was going through so much medication. I just didn’t feel good taking so much,” she said.

Looking for relief, she read about Nerivio, a wearable migraine treatment device that uses remote electrical neuromodulation (REN). She mentioned the device to her neurologist, and he agreed she might benefit from trying it out. Today, she uses the device whenever she feels a migraine may be imminent, she said.

“It really helps me stave off migraines I feel coming on and the milder ones where I would normally hesitate to use prescription medication because [insurance] limits the number of pills they give you in a month,” she said. “I follow through with the Nerivio treatment and usually find that my migraine doesn’t fully develop or is completely gone, and I don’t get a migraine at all.”
 

Taking it on the arm

The device works by stimulating nerves at the back of the arm right around the triceps. “Those nerve fibers relay information to the brain stem [so it can] work its magic and use the brain’s own natural mechanisms for reducing pain,” said Brian M. Grosberg, MD, director of the Hartford Healthcare Ayer Neuroscience Institute Headache Center, West Hartford, Conn.  

These mechanisms are like a bait-and-switch for the brain, said Britany Klenofsky, MD, assistant professor of neurology, Icahn School of Medicine at Mount Sinai, New York. “You’re trying to stimulate pain somewhere else [on the body] to tell the brain to protect itself and release [the neurotransmitter] serotonin,” she said. “You do this by putting the device on your arm, an area that’s away from the head where the pain is actively occurring, turning the device on, and increasing the stimulation to a nearly painful stimulus.”

This pseudo pain prompts the brain to release serotonin, the feel-good hormone along with norepinephrine and noradrenaline. The device works best when it’s used as soon as a migraine starts, so patients should hook up Nerivio within the first 20-30 minutes of onset of pain, said Dr. Grosberg, who was an investigator on the double-blind treatment study that led to FDA clearance. If patients wait too long, the device may not work.

This is why as soon as Ms. Montgomery feels a migraine aura (there are six types of migraine auras, including visual changes and muscle weakness) that occurs right before a migraine strikes, she puts the device armband on her upper arm and launches its smartphone app. Then she turns on the device for a 45-minute treatment, which begins with what she characterizes as tingling and vibration sensations on her arm. She turns up the intensity of the sensations, which are mild electric currents, until they are well-felt but not painful.

Ms. Montgomery said she can use the device and multitask since there’s no need for her to lie down or sit in a darkened room. And since it is worn on the arm, she can wear it under a shirtsleeve while working or out in public without anyone noticing. She also uses the app’s migraine diary and guided meditation to help reduce the anxiety that often accompanies her migraines.

The device is approved for adolescents and adults and can be used for both episodic and chronic migraines. From an efficacy standpoint, the device provides relief about as well as a commonly used pharmaceutical class of drugs, triptans. About 37% of people with episodic migraine achieved complete freedom from pain 2 hours after their treatment. In addition, about two-thirds of people reported pain relief after 2 hours, which is better success than people find with many prescription and nonprescription drugs.

A separate study looked at acute treatment for chronic migraine sufferers and found nearly 60% of people using the device found relief and 21% said they were pain-free after 2 hours. Almost two-thirds of those who experienced pain relief were pain-free 24 hours after the treatment.
 

Finding the perfect patient

There are other FDA-cleared noninvasive devices to treat migraines. One device, CEFALY, is an external trigeminal nerve stimulation device that sits on the forehead. Another device, SpringTMS, uses transcranial magnetic stimulation on the back of the head. A third option, the gammaCore Sapphire, is placed on the neck to stimulate the vagus nerve. All three have been cleared by the FDA to work as preventive and acute treatments for migraine.

Theranica, the company that developed Nerivio, is trying to boost use of the device by allowing patients to get a prescription via telehealth visits with a physician.

The company, as well as the companies behind the other neuromodulation devices, are marketing their treatments to children ages 12 and up since nonpharmacologic options are often preferable for parents, said Thomas Berk, MD, a clinical associate professor in the division of headache at NYU Langone Health in New York.

Dr. Berk said the devices could be appealing for those people who don’t want or can’t take medication, such as pregnant women or those who don’t respond well to drugs. “[They] could also be used by somebody who needs something in addition to a medication,” he said.

For now, people like Ms. Montgomery say they are happy to have another tool in their migraine arsenal. “Overall, I’m taking less medication because I haven’t had to have my Ubrelvy refilled as often as I used to,” she said. “It’s really helped me manage changes and stresses in my life.”

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

Most people avoid smartphones when they have a migraine headache, but a noninvasive treatment for episodic migraines may change that.

A smartphone-enabled device, cleared by the Food and Drug Administration in early 2021, uses technology to trick the brain into releasing the neurotransmitters serotonin and noradrenaline that can help ease migraine pain.

Tina Montgomery, 58, has suffered from migraines since childhood and spent years looking for something to help manage them. Doctors consider her a “chronic” sufferer in that she has more than 14 migraines a month (fewer than 14 is considered “episodic”). Prescription antidepressants, anticonvulsants, and botulinum toxin shots as preventive treatments helped a little but not enough.

A few years ago, she found some relief using a new preventive injectable medication that targets a peptide known as CGRP, combined with an oral CGRP rescue medication, ubrogepant (Ubrelvy). However, by early 2021, Ms. Montgomery’s chronic migraines were back as she faced stress from the pandemic and her role as a caregiver for her aging parents.

“I was going through so much medication. I just didn’t feel good taking so much,” she said.

Looking for relief, she read about Nerivio, a wearable migraine treatment device that uses remote electrical neuromodulation (REN). She mentioned the device to her neurologist, and he agreed she might benefit from trying it out. Today, she uses the device whenever she feels a migraine may be imminent, she said.

“It really helps me stave off migraines I feel coming on and the milder ones where I would normally hesitate to use prescription medication because [insurance] limits the number of pills they give you in a month,” she said. “I follow through with the Nerivio treatment and usually find that my migraine doesn’t fully develop or is completely gone, and I don’t get a migraine at all.”
 

Taking it on the arm

The device works by stimulating nerves at the back of the arm right around the triceps. “Those nerve fibers relay information to the brain stem [so it can] work its magic and use the brain’s own natural mechanisms for reducing pain,” said Brian M. Grosberg, MD, director of the Hartford Healthcare Ayer Neuroscience Institute Headache Center, West Hartford, Conn.  

These mechanisms are like a bait-and-switch for the brain, said Britany Klenofsky, MD, assistant professor of neurology, Icahn School of Medicine at Mount Sinai, New York. “You’re trying to stimulate pain somewhere else [on the body] to tell the brain to protect itself and release [the neurotransmitter] serotonin,” she said. “You do this by putting the device on your arm, an area that’s away from the head where the pain is actively occurring, turning the device on, and increasing the stimulation to a nearly painful stimulus.”

This pseudo pain prompts the brain to release serotonin, the feel-good hormone along with norepinephrine and noradrenaline. The device works best when it’s used as soon as a migraine starts, so patients should hook up Nerivio within the first 20-30 minutes of onset of pain, said Dr. Grosberg, who was an investigator on the double-blind treatment study that led to FDA clearance. If patients wait too long, the device may not work.

This is why as soon as Ms. Montgomery feels a migraine aura (there are six types of migraine auras, including visual changes and muscle weakness) that occurs right before a migraine strikes, she puts the device armband on her upper arm and launches its smartphone app. Then she turns on the device for a 45-minute treatment, which begins with what she characterizes as tingling and vibration sensations on her arm. She turns up the intensity of the sensations, which are mild electric currents, until they are well-felt but not painful.

Ms. Montgomery said she can use the device and multitask since there’s no need for her to lie down or sit in a darkened room. And since it is worn on the arm, she can wear it under a shirtsleeve while working or out in public without anyone noticing. She also uses the app’s migraine diary and guided meditation to help reduce the anxiety that often accompanies her migraines.

The device is approved for adolescents and adults and can be used for both episodic and chronic migraines. From an efficacy standpoint, the device provides relief about as well as a commonly used pharmaceutical class of drugs, triptans. About 37% of people with episodic migraine achieved complete freedom from pain 2 hours after their treatment. In addition, about two-thirds of people reported pain relief after 2 hours, which is better success than people find with many prescription and nonprescription drugs.

A separate study looked at acute treatment for chronic migraine sufferers and found nearly 60% of people using the device found relief and 21% said they were pain-free after 2 hours. Almost two-thirds of those who experienced pain relief were pain-free 24 hours after the treatment.
 

Finding the perfect patient

There are other FDA-cleared noninvasive devices to treat migraines. One device, CEFALY, is an external trigeminal nerve stimulation device that sits on the forehead. Another device, SpringTMS, uses transcranial magnetic stimulation on the back of the head. A third option, the gammaCore Sapphire, is placed on the neck to stimulate the vagus nerve. All three have been cleared by the FDA to work as preventive and acute treatments for migraine.

Theranica, the company that developed Nerivio, is trying to boost use of the device by allowing patients to get a prescription via telehealth visits with a physician.

The company, as well as the companies behind the other neuromodulation devices, are marketing their treatments to children ages 12 and up since nonpharmacologic options are often preferable for parents, said Thomas Berk, MD, a clinical associate professor in the division of headache at NYU Langone Health in New York.

Dr. Berk said the devices could be appealing for those people who don’t want or can’t take medication, such as pregnant women or those who don’t respond well to drugs. “[They] could also be used by somebody who needs something in addition to a medication,” he said.

For now, people like Ms. Montgomery say they are happy to have another tool in their migraine arsenal. “Overall, I’m taking less medication because I haven’t had to have my Ubrelvy refilled as often as I used to,” she said. “It’s really helped me manage changes and stresses in my life.”

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

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Key clinical point: General anesthesia administered during major surgery poses a similar risk of postoperative migraine as neuraxial anesthesia.

Main finding: General anesthesia was not associated with a significantly higher risk of postoperative migraine compared with neuraxial anesthesia (adjusted odds ratio [aOR] 0.93; P = .357), even across patient subgroups varying in age (≥65 years: aOR 0.94; P = .698; <65 years: aOR 0.93; P = .397) or migraine subtype (with aura: aOR 1.02; P = .929; without aura: aOR 0.73; P = .069).

Study details: The data come from a nationwide population-based cohort study that matched 68,131 patients with no prior history of migraine undergoing major surgery with general anesthesia with an equal number of those undergoing neuraxial anesthesia-supported surgery.

Disclosures: The study was sponsored by Taipei Medical University, Taiwan. The authors declared having no conflicts of interest.

Source: Liao C-Y et al. Int J Environ Res Public Health. 2021;19(1):362 (Dec 30). Doi: 10.3390/ijerph19010362.

Key clinical point: General anesthesia administered during major surgery poses a similar risk of postoperative migraine as neuraxial anesthesia.

Main finding: General anesthesia was not associated with a significantly higher risk of postoperative migraine compared with neuraxial anesthesia (adjusted odds ratio [aOR] 0.93; P = .357), even across patient subgroups varying in age (≥65 years: aOR 0.94; P = .698; <65 years: aOR 0.93; P = .397) or migraine subtype (with aura: aOR 1.02; P = .929; without aura: aOR 0.73; P = .069).

Study details: The data come from a nationwide population-based cohort study that matched 68,131 patients with no prior history of migraine undergoing major surgery with general anesthesia with an equal number of those undergoing neuraxial anesthesia-supported surgery.

Disclosures: The study was sponsored by Taipei Medical University, Taiwan. The authors declared having no conflicts of interest.

Source: Liao C-Y et al. Int J Environ Res Public Health. 2021;19(1):362 (Dec 30). Doi: 10.3390/ijerph19010362.

Key clinical point: General anesthesia administered during major surgery poses a similar risk of postoperative migraine as neuraxial anesthesia.

Main finding: General anesthesia was not associated with a significantly higher risk of postoperative migraine compared with neuraxial anesthesia (adjusted odds ratio [aOR] 0.93; P = .357), even across patient subgroups varying in age (≥65 years: aOR 0.94; P = .698; <65 years: aOR 0.93; P = .397) or migraine subtype (with aura: aOR 1.02; P = .929; without aura: aOR 0.73; P = .069).

Study details: The data come from a nationwide population-based cohort study that matched 68,131 patients with no prior history of migraine undergoing major surgery with general anesthesia with an equal number of those undergoing neuraxial anesthesia-supported surgery.

Disclosures: The study was sponsored by Taipei Medical University, Taiwan. The authors declared having no conflicts of interest.

Source: Liao C-Y et al. Int J Environ Res Public Health. 2021;19(1):362 (Dec 30). Doi: 10.3390/ijerph19010362.