Headache & Migraine

Neurology, once considered a “diagnose and adios” specialty, is gaining newfound, scientific respect. Our vastly improved understanding of neurologic pathophysiology has led to many Food and Drug Administration–approved medications that can specifically enhance treatment outcomes. Medications for migraine, multiple sclerosis, epilepsy, and other chronic neurological diseases have been extended and modernized; for millions of patients, these medicines fulfill their long-awaited needs.

What would Dr Osler have said if he witnessed today’s definition of the practice of medicine? As singular as our patients and their disorders are, the delivery of care is anything but. The processes in the delivery of this care have created many unforeseen twists and turns, thanks to the electronic health record (EHR), the resource-based relative value scale (RBRVS), evaluation and management (E&M) coding, and private health insurance (PHI).

From a neurologist’s perspective, I will elaborate upon these changes that have affected our day-to-day neurology practices. I have practiced general neurology and headache medicine both in private and academic practices, evaluating and treating thousands of inpatients and outpatients in urban and rural healthcare facilities since 1986.

The EHR

Despite herculean, lofty, and sustained efforts by the medical business world to promote EHR adoption worldwide, goals remain unmet. Intended to improve the quality of care and patient outcomes, reduce medical errors, and crystalize communications among providers and with patients, it is instead associated with physician burnout (B), lack of usability (U) and interoperability (I), has likability (L) issues, and provides no productive physician direction (D) – there is an enormous need to BUILD it better.

In my own practice, it is inevitable that I will use my EHR laptop with an unknowing patient. If so, I try to make her feel comfortable in its presence as I strive to stay intent on our discussion. Yet I invariably split my concentration between machine and patient. The machine often gets my full attention, with its confusing and unnecessary medical record notes, tech glitches and screen interruptions, let alone its complicated web of tabs, buttons, links, and obscure prompts. As for fulfilling CMS’ meaningful use criteria to reap financial benefits, I long ago abandoned that effort if earning benefits and reaching the desired patient outcome weren’t on the same path.

We are required to read numerous EHR windows, deal with misused, template-based medical records and the usually faulty copy-and-paste function, which results in flagrant errors. A common example is templating or copy-and-pasting normal examination findings such as “pupils equal, round, and reactive to light and accommodation (PERRLA),” without making modifications for a patient who has obvious abnormal pupillary findings.  It is the EHR that often induces these types of documentation errors.

The EHR, as it exists now, intrudes into our time with patients. But for the past 30 years, the RBRVs have defined how we are compensated for our services. This compensation scale was created to provide a standard system of paying physicians’ services based on resource costs associated with patient care. The resource components are physician work, practice expense, and professional liability insurance. These components make our compensation based on effort rather than effect.

Payments are calculated into relative value units (RVUs), which are often structured into physician employment contracts.¹ There are many RVU calculations and formulas that determine physician reimbursement and compensation; these are not entirely straightforward and too often lack transparency. Despite Dr Osler’s plea in Aequanimitas for physicians to maintain imperturbability and equanimity, that plea goes to the wayside when debating the value of the RBRVS. This system dilutes the complexities of the physician visit, especially for patients with comorbidities, polypharmacy, and cognitive and social concerns.²

Another frustrating, time-absorbing business requirement is E&M coding; the codes came about around the same time as RBRVs. Congress established E&M in the mid-1990s to facilitate medical billing by translating physician-patient encounters into 5-digit codes. In a neurology office, this authentication takes considerable effort, detracts from the patient’s visit, and adds to the documentation requirement to receive insured patient payments.

Years ago, I reviewed neurology insurance claims for a global health service company. I remember the considerable discussion over subjective documentation technicalities, attempting to justify the submitted E&M code. The onerous administrative burden E&M has created continues to evolve, with no end in sight.

Private insurance

When was the last time that you did not have to submit a prior authorization (PA) request to a payer in a week’s worth of days?

PA requests impede timely, efficient, and much-needed vital care while usurping a physician’s decision-making process. In 2020, the American Medical Association released the responses of 1000 physicians who were asked about making PA requests.³ Physicians said that the time delays affected their patients’ health and created adverse events, including hospitalizations. PAs are not only requested for new drugs; physicians report that the increase in the volume of PAs includes requests for existing drugs and services.

It takes staff days to make the requests; most medical practices interact with dozens of different health plans, all with different requirements related to PAs. Insurers often follow the lead of Medicare, and Medicare does not cover most self-injectable medications.⁴

I can report the same experiences. Ten years ago, private insurers rejected ~20% of my practice’s PA requests. Today, more than half of my patients need a PA from their insurer—often for 2 or 3 prescriptions each—and at least half of the requests are rejected. And, unlike 10 years ago, most of my requests are still denied after an appeal.

My patients are mostly migraine patients. When appropriate, I discuss with them the new acute and preventive anti–calcitonin gene-related peptides (anti-CGRPs), which, for the chronic migraine patient, can be a small slice of heaven. Reality strikes, however, when we discuss the likely PA process. This shift no longer focuses on getting likely migraine relief, but instead on the insurance company or companies approving the PA.

Sometimes the PA approval process is only accomplished by patients fighting the PA battle for themselves. One patient recently had to convince her PA oversight insurance representative that, if her PA was denied, her suicide would follow.

And what do patients do if the PA has been denied? Sometimes I must treat a patient with something else, which is often less appropriate for that patient. I have had many patients who have given up during the process.

Industry sees PAs in a different light. A survey⁵ of 44 payers conducted in 2019 found that PAs save money, improve evidence-based care, and so on. Physicians asking for the PAs were singled out as the reasons PAs were denied, as these physicians did not follow proper protocols.

Despite government and PHI policies that are supposed to enhance healthcare delivery and stabilize costs, US healthcare costs stand at $3.6 trillion.^6,7 These medical practice transitions have increased administrative burden, accounting for 34% of US total healthcare expenditures vs 17% in Canada.^8,9

In neurology, successful outcomes are predicated on recognizing the singularity of each patient. The current health system’s need for homogenization is making such recognition difficult. I invite you to read my commentary entitled The Practice of Medicine - Hazy or Invisible Lines, which discusses the unintended consequences of these well-intentioned medical practice adjustments. 

Comments from Alan Rapoport, MD

Editor in Chief, Neurology Reviews

Professor Landy’s article excellently details just some of the roadblocks all neurologists face in providing patient-centric care. Prescribing medication or devices alone does not provide such care, but that is what many doctors must do because of limited time with the patient. Dr Osler was correct; we have to treat the patient who has the disease, not the disease the patient has. Taking an adequate history, conducting a full neurologic examination, documenting both, reviewing outside records, discussing the diagnosis and plan with the patient, ordering appropriate testing, and dictating all of the above in 20 or 30 minutes is impossible to do well. Going forward, we can expect computers and some form of artificial intelligence will help us to be more efficient, but we must keep the patient in the center. No wonder patients are not as happy with the healthcare system and their doctors as they used to be.

Alan Rapoport, MD

Clinical Professor of Neurology

The David Geffen School of Medicine at UCLA, Los Angeles, California

Past President

The International Headache Society (IHS)

Neurology, once considered a “diagnose and adios” specialty, is gaining newfound, scientific respect. Our vastly improved understanding of neurologic pathophysiology has led to many Food and Drug Administration–approved medications that can specifically enhance treatment outcomes. Medications for migraine, multiple sclerosis, epilepsy, and other chronic neurological diseases have been extended and modernized; for millions of patients, these medicines fulfill their long-awaited needs.

What would Dr Osler have said if he witnessed today’s definition of the practice of medicine? As singular as our patients and their disorders are, the delivery of care is anything but. The processes in the delivery of this care have created many unforeseen twists and turns, thanks to the electronic health record (EHR), the resource-based relative value scale (RBRVS), evaluation and management (E&M) coding, and private health insurance (PHI).

From a neurologist’s perspective, I will elaborate upon these changes that have affected our day-to-day neurology practices. I have practiced general neurology and headache medicine both in private and academic practices, evaluating and treating thousands of inpatients and outpatients in urban and rural healthcare facilities since 1986.

The EHR

Despite herculean, lofty, and sustained efforts by the medical business world to promote EHR adoption worldwide, goals remain unmet. Intended to improve the quality of care and patient outcomes, reduce medical errors, and crystalize communications among providers and with patients, it is instead associated with physician burnout (B), lack of usability (U) and interoperability (I), has likability (L) issues, and provides no productive physician direction (D) – there is an enormous need to BUILD it better.

In my own practice, it is inevitable that I will use my EHR laptop with an unknowing patient. If so, I try to make her feel comfortable in its presence as I strive to stay intent on our discussion. Yet I invariably split my concentration between machine and patient. The machine often gets my full attention, with its confusing and unnecessary medical record notes, tech glitches and screen interruptions, let alone its complicated web of tabs, buttons, links, and obscure prompts. As for fulfilling CMS’ meaningful use criteria to reap financial benefits, I long ago abandoned that effort if earning benefits and reaching the desired patient outcome weren’t on the same path.

We are required to read numerous EHR windows, deal with misused, template-based medical records and the usually faulty copy-and-paste function, which results in flagrant errors. A common example is templating or copy-and-pasting normal examination findings such as “pupils equal, round, and reactive to light and accommodation (PERRLA),” without making modifications for a patient who has obvious abnormal pupillary findings.  It is the EHR that often induces these types of documentation errors.

The EHR, as it exists now, intrudes into our time with patients. But for the past 30 years, the RBRVs have defined how we are compensated for our services. This compensation scale was created to provide a standard system of paying physicians’ services based on resource costs associated with patient care. The resource components are physician work, practice expense, and professional liability insurance. These components make our compensation based on effort rather than effect.

Payments are calculated into relative value units (RVUs), which are often structured into physician employment contracts.¹ There are many RVU calculations and formulas that determine physician reimbursement and compensation; these are not entirely straightforward and too often lack transparency. Despite Dr Osler’s plea in Aequanimitas for physicians to maintain imperturbability and equanimity, that plea goes to the wayside when debating the value of the RBRVS. This system dilutes the complexities of the physician visit, especially for patients with comorbidities, polypharmacy, and cognitive and social concerns.²

Another frustrating, time-absorbing business requirement is E&M coding; the codes came about around the same time as RBRVs. Congress established E&M in the mid-1990s to facilitate medical billing by translating physician-patient encounters into 5-digit codes. In a neurology office, this authentication takes considerable effort, detracts from the patient’s visit, and adds to the documentation requirement to receive insured patient payments.

Years ago, I reviewed neurology insurance claims for a global health service company. I remember the considerable discussion over subjective documentation technicalities, attempting to justify the submitted E&M code. The onerous administrative burden E&M has created continues to evolve, with no end in sight.

Private insurance

When was the last time that you did not have to submit a prior authorization (PA) request to a payer in a week’s worth of days?

PA requests impede timely, efficient, and much-needed vital care while usurping a physician’s decision-making process. In 2020, the American Medical Association released the responses of 1000 physicians who were asked about making PA requests.³ Physicians said that the time delays affected their patients’ health and created adverse events, including hospitalizations. PAs are not only requested for new drugs; physicians report that the increase in the volume of PAs includes requests for existing drugs and services.

It takes staff days to make the requests; most medical practices interact with dozens of different health plans, all with different requirements related to PAs. Insurers often follow the lead of Medicare, and Medicare does not cover most self-injectable medications.⁴

I can report the same experiences. Ten years ago, private insurers rejected ~20% of my practice’s PA requests. Today, more than half of my patients need a PA from their insurer—often for 2 or 3 prescriptions each—and at least half of the requests are rejected. And, unlike 10 years ago, most of my requests are still denied after an appeal.

My patients are mostly migraine patients. When appropriate, I discuss with them the new acute and preventive anti–calcitonin gene-related peptides (anti-CGRPs), which, for the chronic migraine patient, can be a small slice of heaven. Reality strikes, however, when we discuss the likely PA process. This shift no longer focuses on getting likely migraine relief, but instead on the insurance company or companies approving the PA.

Sometimes the PA approval process is only accomplished by patients fighting the PA battle for themselves. One patient recently had to convince her PA oversight insurance representative that, if her PA was denied, her suicide would follow.

And what do patients do if the PA has been denied? Sometimes I must treat a patient with something else, which is often less appropriate for that patient. I have had many patients who have given up during the process.

Industry sees PAs in a different light. A survey⁵ of 44 payers conducted in 2019 found that PAs save money, improve evidence-based care, and so on. Physicians asking for the PAs were singled out as the reasons PAs were denied, as these physicians did not follow proper protocols.

Despite government and PHI policies that are supposed to enhance healthcare delivery and stabilize costs, US healthcare costs stand at $3.6 trillion.^6,7 These medical practice transitions have increased administrative burden, accounting for 34% of US total healthcare expenditures vs 17% in Canada.^8,9

In neurology, successful outcomes are predicated on recognizing the singularity of each patient. The current health system’s need for homogenization is making such recognition difficult. I invite you to read my commentary entitled The Practice of Medicine - Hazy or Invisible Lines, which discusses the unintended consequences of these well-intentioned medical practice adjustments. 

Comments from Alan Rapoport, MD

Editor in Chief, Neurology Reviews

Professor Landy’s article excellently details just some of the roadblocks all neurologists face in providing patient-centric care. Prescribing medication or devices alone does not provide such care, but that is what many doctors must do because of limited time with the patient. Dr Osler was correct; we have to treat the patient who has the disease, not the disease the patient has. Taking an adequate history, conducting a full neurologic examination, documenting both, reviewing outside records, discussing the diagnosis and plan with the patient, ordering appropriate testing, and dictating all of the above in 20 or 30 minutes is impossible to do well. Going forward, we can expect computers and some form of artificial intelligence will help us to be more efficient, but we must keep the patient in the center. No wonder patients are not as happy with the healthcare system and their doctors as they used to be.

Alan Rapoport, MD

Clinical Professor of Neurology

The David Geffen School of Medicine at UCLA, Los Angeles, California

Past President

The International Headache Society (IHS)

Neurology, once considered a “diagnose and adios” specialty, is gaining newfound, scientific respect. Our vastly improved understanding of neurologic pathophysiology has led to many Food and Drug Administration–approved medications that can specifically enhance treatment outcomes. Medications for migraine, multiple sclerosis, epilepsy, and other chronic neurological diseases have been extended and modernized; for millions of patients, these medicines fulfill their long-awaited needs.

What would Dr Osler have said if he witnessed today’s definition of the practice of medicine? As singular as our patients and their disorders are, the delivery of care is anything but. The processes in the delivery of this care have created many unforeseen twists and turns, thanks to the electronic health record (EHR), the resource-based relative value scale (RBRVS), evaluation and management (E&M) coding, and private health insurance (PHI).

From a neurologist’s perspective, I will elaborate upon these changes that have affected our day-to-day neurology practices. I have practiced general neurology and headache medicine both in private and academic practices, evaluating and treating thousands of inpatients and outpatients in urban and rural healthcare facilities since 1986.

The EHR

Despite herculean, lofty, and sustained efforts by the medical business world to promote EHR adoption worldwide, goals remain unmet. Intended to improve the quality of care and patient outcomes, reduce medical errors, and crystalize communications among providers and with patients, it is instead associated with physician burnout (B), lack of usability (U) and interoperability (I), has likability (L) issues, and provides no productive physician direction (D) – there is an enormous need to BUILD it better.

In my own practice, it is inevitable that I will use my EHR laptop with an unknowing patient. If so, I try to make her feel comfortable in its presence as I strive to stay intent on our discussion. Yet I invariably split my concentration between machine and patient. The machine often gets my full attention, with its confusing and unnecessary medical record notes, tech glitches and screen interruptions, let alone its complicated web of tabs, buttons, links, and obscure prompts. As for fulfilling CMS’ meaningful use criteria to reap financial benefits, I long ago abandoned that effort if earning benefits and reaching the desired patient outcome weren’t on the same path.

We are required to read numerous EHR windows, deal with misused, template-based medical records and the usually faulty copy-and-paste function, which results in flagrant errors. A common example is templating or copy-and-pasting normal examination findings such as “pupils equal, round, and reactive to light and accommodation (PERRLA),” without making modifications for a patient who has obvious abnormal pupillary findings.  It is the EHR that often induces these types of documentation errors.

The EHR, as it exists now, intrudes into our time with patients. But for the past 30 years, the RBRVs have defined how we are compensated for our services. This compensation scale was created to provide a standard system of paying physicians’ services based on resource costs associated with patient care. The resource components are physician work, practice expense, and professional liability insurance. These components make our compensation based on effort rather than effect.

Payments are calculated into relative value units (RVUs), which are often structured into physician employment contracts.¹ There are many RVU calculations and formulas that determine physician reimbursement and compensation; these are not entirely straightforward and too often lack transparency. Despite Dr Osler’s plea in Aequanimitas for physicians to maintain imperturbability and equanimity, that plea goes to the wayside when debating the value of the RBRVS. This system dilutes the complexities of the physician visit, especially for patients with comorbidities, polypharmacy, and cognitive and social concerns.²

Another frustrating, time-absorbing business requirement is E&M coding; the codes came about around the same time as RBRVs. Congress established E&M in the mid-1990s to facilitate medical billing by translating physician-patient encounters into 5-digit codes. In a neurology office, this authentication takes considerable effort, detracts from the patient’s visit, and adds to the documentation requirement to receive insured patient payments.

Years ago, I reviewed neurology insurance claims for a global health service company. I remember the considerable discussion over subjective documentation technicalities, attempting to justify the submitted E&M code. The onerous administrative burden E&M has created continues to evolve, with no end in sight.

Private insurance

When was the last time that you did not have to submit a prior authorization (PA) request to a payer in a week’s worth of days?

PA requests impede timely, efficient, and much-needed vital care while usurping a physician’s decision-making process. In 2020, the American Medical Association released the responses of 1000 physicians who were asked about making PA requests.³ Physicians said that the time delays affected their patients’ health and created adverse events, including hospitalizations. PAs are not only requested for new drugs; physicians report that the increase in the volume of PAs includes requests for existing drugs and services.

It takes staff days to make the requests; most medical practices interact with dozens of different health plans, all with different requirements related to PAs. Insurers often follow the lead of Medicare, and Medicare does not cover most self-injectable medications.⁴

I can report the same experiences. Ten years ago, private insurers rejected ~20% of my practice’s PA requests. Today, more than half of my patients need a PA from their insurer—often for 2 or 3 prescriptions each—and at least half of the requests are rejected. And, unlike 10 years ago, most of my requests are still denied after an appeal.

My patients are mostly migraine patients. When appropriate, I discuss with them the new acute and preventive anti–calcitonin gene-related peptides (anti-CGRPs), which, for the chronic migraine patient, can be a small slice of heaven. Reality strikes, however, when we discuss the likely PA process. This shift no longer focuses on getting likely migraine relief, but instead on the insurance company or companies approving the PA.

Sometimes the PA approval process is only accomplished by patients fighting the PA battle for themselves. One patient recently had to convince her PA oversight insurance representative that, if her PA was denied, her suicide would follow.

And what do patients do if the PA has been denied? Sometimes I must treat a patient with something else, which is often less appropriate for that patient. I have had many patients who have given up during the process.

Industry sees PAs in a different light. A survey⁵ of 44 payers conducted in 2019 found that PAs save money, improve evidence-based care, and so on. Physicians asking for the PAs were singled out as the reasons PAs were denied, as these physicians did not follow proper protocols.

Despite government and PHI policies that are supposed to enhance healthcare delivery and stabilize costs, US healthcare costs stand at $3.6 trillion.^6,7 These medical practice transitions have increased administrative burden, accounting for 34% of US total healthcare expenditures vs 17% in Canada.^8,9

In neurology, successful outcomes are predicated on recognizing the singularity of each patient. The current health system’s need for homogenization is making such recognition difficult. I invite you to read my commentary entitled The Practice of Medicine - Hazy or Invisible Lines, which discusses the unintended consequences of these well-intentioned medical practice adjustments. 

Comments from Alan Rapoport, MD

Editor in Chief, Neurology Reviews

Professor Landy’s article excellently details just some of the roadblocks all neurologists face in providing patient-centric care. Prescribing medication or devices alone does not provide such care, but that is what many doctors must do because of limited time with the patient. Dr Osler was correct; we have to treat the patient who has the disease, not the disease the patient has. Taking an adequate history, conducting a full neurologic examination, documenting both, reviewing outside records, discussing the diagnosis and plan with the patient, ordering appropriate testing, and dictating all of the above in 20 or 30 minutes is impossible to do well. Going forward, we can expect computers and some form of artificial intelligence will help us to be more efficient, but we must keep the patient in the center. No wonder patients are not as happy with the healthcare system and their doctors as they used to be.

Alan Rapoport, MD

Clinical Professor of Neurology

The David Geffen School of Medicine at UCLA, Los Angeles, California

Past President

The International Headache Society (IHS)

The theme of the articles this month is migraine and blood vessels. Migraine is a known risk factor for vascular events, it is a known vasodilatory phenomenon, and it is commonly treated with vasoconstrictive medications. Genetic studies are further elucidating the connection between migraine and vascular risk factors. The following studies take this vascular connection to clinical relevance in different ways.

Previous studies have investigated the combination of simvastatin and vitamin D for migraine prevention. Statins have anti-inflammatory properties and migraine can partially be understood as an inflammatory vascular phenomenon. Vitamin D and simvastatin were previously shown to be effective in a randomized trial; this study¹ investigated the combination of atorvastatin with nortriptyline for migraine prevention. Patients were excluded if they had a vitamin D deficiency.

This was a triple-blinded study with one control group, one placebo plus notriptyline group, and one atorvastatin plus nortiptyline group. The nortiptyline dosage was 25mg nightly, and the interventions were given for 24 weeks. The primary outcome was decrease in headache day frequency; secondary outcomes were severity and quality of life as measured by the Migraine-Specific Quality of Life Questionnaire (MSQ).

Migraine frequency was seen to be significantly improved after 24 weeks in the statin group; however severity was not significantly affected. Adverse effects were mild and overall no subjects discontinued due to the intervention. Quality of life was also seen to be better in the combination statin/nortriptyline group.

The results of this study are compelling enough to consider the addition of a tricyclic antidepressant (TCA) for a patient already on a statin or to start a statin (in the appropriate clinical setting) on a patient already on a TCA. The main limiting factor may be the hesitation to use a TCA medication in an older patient, where the anticholinergic effects may be less predictable.

Caffeine has a controversial place in the headache world. Many patients either use caffeine as a way to treat their migraine attacks, or avoid it completely as they are told it is a migraine trigger. Most headache specialists recommend the avoidance of excessive caffeine use (typically considered >150 mg daily) and tell their patients to be consistent about when they consume caffeine. The effect of caffeine on migraine likely is due to its vasoactive property, specifically that it is vasoconstrictive in nature. These vasoactive properties may also be why many studies investigating cerebrovascular reactivity have been inconclusive in the past.

The authors in this study² recruited patients with episodic migraine and divided them based on caffeine use. All subjects underwent transcranial Doppler testing at baseline and after 3 months, caffeine users were instructed to discontinue caffeine in the interim. Doppler testing looked for differences in BHI (breath holding index) of the bilateral posterior cerebral arteries (PCA), which is a standard at their institution. Subjects were only investigated if they were headache-free and had not used a migraine abortive medication in the previous 48 hours. Preventive medications were not controlled for.

Although the investigators recommended discontinuation of caffeine for the caffeine users, only 28% of that subgroup did discontinue. They then subdivided the group of caffeine users into those whose caffeine intake increased, decreased, or stayed the same. Transcranial Doppler testing was performed in all subgroups.

The investigators found a lower BHI-PCA, or decrease in vasodilatory function, in the subgroups that remained on caffeine. Those who stopped caffeine had improvement in this metric, showing the possible reversibility that discontinuation of caffeine can have. It remains unclear precisely how caffeine is vasoactive, and the effects may be via adenosine receptors, endothelial function, neurotransmitter production, or regulation of the autonomic nervous system. The long-term vascular effects of caffeine are unknown, but they do appear to be reversible after a 3 month period.

Migraine, and especially migraine with aura, is well known as a vascular risk factor. The presence of migraine increases the odds ratio of stroke, myocardial ischemia, deep vein thrombosis and other vascular events significantly. The American College of Obstetrics and Gynecology recommends avoiding the use of any estrogen containing medication in the presence of migraine, due to estrogen itself being a pro-thrombotic hormone.  The precise mechanism that leads to this increased risk is unknown.

This study investigated the connection between migraine and large artery atherosclerosis (LAA). This group observed 415 consecutive patients aged 18-54 who presented for a first time ischemic stroke (other neurovascular events, such as cerebral venous sinus thrombosis, subarachnoid hemorrhage with secondary ischemia and transient ischemic attacks, were excluded). Data regarding these patient’s risks factors was collected and analyzed including elevated body mass index (BMI), hypertension, diabetes, tobacco use, and hyperlipidemia.

All patients underwent magnetic resonance imaging (MRI), as well as either magnetic resonance angiography (MRA) or computed tomography angiography (CTA), and duplex ultrasound confirmed the images. Atherosclerosis was classified using a standardized system (ASCOD: atherosclerosis, small-vessel disease, cardiac pathology, other causes, and dissection) that grades atheroslerotic lesions on a 0-3 scale.

The results may be considered counterintuitive. The presence of migraine was negatively associated with the presence of LAA: a history of migraine did not increase the risk of atherosclerosis. This was even the case when controlling for the traditional vascular risk factors. The authors theorize that likely the association between migraine and stroke and other vascular events is not related to atherosclerosis and may be due to other causes.

A genome-wide association study recently identified a specific polymorphism that was shared by migraine and coronary artery disease. But just like this study, the people with migraine had a negative association with coronary artery disease. If people with migraine do develop stroke or other vascular phenomena they typically present younger and healthier, and this may be why this negative correlation exists.

References

1. Sherafat M et al. The preventive effect of the combination of atorvastatin and nortriptyline in migraine-type headache: a randomized, triple-blind, placebo-controlled trial. Neurol Res. 2022 (Jan 17).
2. Gil Y-E et al. Effect of caffeine and caffeine cessation on cerebrovascular reactivity in patients with migraine. Headache. 2022;62(2):169-75 (Feb 3).
3. Gollion C et al. Migraine and large artery atherosclerosis in young adults with ischemic stroke. Headache. 2022;62(2):191-7 (Feb 5).

The theme of the articles this month is migraine and blood vessels. Migraine is a known risk factor for vascular events, it is a known vasodilatory phenomenon, and it is commonly treated with vasoconstrictive medications. Genetic studies are further elucidating the connection between migraine and vascular risk factors. The following studies take this vascular connection to clinical relevance in different ways.

Previous studies have investigated the combination of simvastatin and vitamin D for migraine prevention. Statins have anti-inflammatory properties and migraine can partially be understood as an inflammatory vascular phenomenon. Vitamin D and simvastatin were previously shown to be effective in a randomized trial; this study¹ investigated the combination of atorvastatin with nortriptyline for migraine prevention. Patients were excluded if they had a vitamin D deficiency.

This was a triple-blinded study with one control group, one placebo plus notriptyline group, and one atorvastatin plus nortiptyline group. The nortiptyline dosage was 25mg nightly, and the interventions were given for 24 weeks. The primary outcome was decrease in headache day frequency; secondary outcomes were severity and quality of life as measured by the Migraine-Specific Quality of Life Questionnaire (MSQ).

Migraine frequency was seen to be significantly improved after 24 weeks in the statin group; however severity was not significantly affected. Adverse effects were mild and overall no subjects discontinued due to the intervention. Quality of life was also seen to be better in the combination statin/nortriptyline group.

The results of this study are compelling enough to consider the addition of a tricyclic antidepressant (TCA) for a patient already on a statin or to start a statin (in the appropriate clinical setting) on a patient already on a TCA. The main limiting factor may be the hesitation to use a TCA medication in an older patient, where the anticholinergic effects may be less predictable.

Caffeine has a controversial place in the headache world. Many patients either use caffeine as a way to treat their migraine attacks, or avoid it completely as they are told it is a migraine trigger. Most headache specialists recommend the avoidance of excessive caffeine use (typically considered >150 mg daily) and tell their patients to be consistent about when they consume caffeine. The effect of caffeine on migraine likely is due to its vasoactive property, specifically that it is vasoconstrictive in nature. These vasoactive properties may also be why many studies investigating cerebrovascular reactivity have been inconclusive in the past.

The authors in this study² recruited patients with episodic migraine and divided them based on caffeine use. All subjects underwent transcranial Doppler testing at baseline and after 3 months, caffeine users were instructed to discontinue caffeine in the interim. Doppler testing looked for differences in BHI (breath holding index) of the bilateral posterior cerebral arteries (PCA), which is a standard at their institution. Subjects were only investigated if they were headache-free and had not used a migraine abortive medication in the previous 48 hours. Preventive medications were not controlled for.

Although the investigators recommended discontinuation of caffeine for the caffeine users, only 28% of that subgroup did discontinue. They then subdivided the group of caffeine users into those whose caffeine intake increased, decreased, or stayed the same. Transcranial Doppler testing was performed in all subgroups.

The investigators found a lower BHI-PCA, or decrease in vasodilatory function, in the subgroups that remained on caffeine. Those who stopped caffeine had improvement in this metric, showing the possible reversibility that discontinuation of caffeine can have. It remains unclear precisely how caffeine is vasoactive, and the effects may be via adenosine receptors, endothelial function, neurotransmitter production, or regulation of the autonomic nervous system. The long-term vascular effects of caffeine are unknown, but they do appear to be reversible after a 3 month period.

Migraine, and especially migraine with aura, is well known as a vascular risk factor. The presence of migraine increases the odds ratio of stroke, myocardial ischemia, deep vein thrombosis and other vascular events significantly. The American College of Obstetrics and Gynecology recommends avoiding the use of any estrogen containing medication in the presence of migraine, due to estrogen itself being a pro-thrombotic hormone.  The precise mechanism that leads to this increased risk is unknown.

This study investigated the connection between migraine and large artery atherosclerosis (LAA). This group observed 415 consecutive patients aged 18-54 who presented for a first time ischemic stroke (other neurovascular events, such as cerebral venous sinus thrombosis, subarachnoid hemorrhage with secondary ischemia and transient ischemic attacks, were excluded). Data regarding these patient’s risks factors was collected and analyzed including elevated body mass index (BMI), hypertension, diabetes, tobacco use, and hyperlipidemia.

All patients underwent magnetic resonance imaging (MRI), as well as either magnetic resonance angiography (MRA) or computed tomography angiography (CTA), and duplex ultrasound confirmed the images. Atherosclerosis was classified using a standardized system (ASCOD: atherosclerosis, small-vessel disease, cardiac pathology, other causes, and dissection) that grades atheroslerotic lesions on a 0-3 scale.

The results may be considered counterintuitive. The presence of migraine was negatively associated with the presence of LAA: a history of migraine did not increase the risk of atherosclerosis. This was even the case when controlling for the traditional vascular risk factors. The authors theorize that likely the association between migraine and stroke and other vascular events is not related to atherosclerosis and may be due to other causes.

A genome-wide association study recently identified a specific polymorphism that was shared by migraine and coronary artery disease. But just like this study, the people with migraine had a negative association with coronary artery disease. If people with migraine do develop stroke or other vascular phenomena they typically present younger and healthier, and this may be why this negative correlation exists.

References

1. Sherafat M et al. The preventive effect of the combination of atorvastatin and nortriptyline in migraine-type headache: a randomized, triple-blind, placebo-controlled trial. Neurol Res. 2022 (Jan 17).
2. Gil Y-E et al. Effect of caffeine and caffeine cessation on cerebrovascular reactivity in patients with migraine. Headache. 2022;62(2):169-75 (Feb 3).
3. Gollion C et al. Migraine and large artery atherosclerosis in young adults with ischemic stroke. Headache. 2022;62(2):191-7 (Feb 5).

The theme of the articles this month is migraine and blood vessels. Migraine is a known risk factor for vascular events, it is a known vasodilatory phenomenon, and it is commonly treated with vasoconstrictive medications. Genetic studies are further elucidating the connection between migraine and vascular risk factors. The following studies take this vascular connection to clinical relevance in different ways.

Previous studies have investigated the combination of simvastatin and vitamin D for migraine prevention. Statins have anti-inflammatory properties and migraine can partially be understood as an inflammatory vascular phenomenon. Vitamin D and simvastatin were previously shown to be effective in a randomized trial; this study¹ investigated the combination of atorvastatin with nortriptyline for migraine prevention. Patients were excluded if they had a vitamin D deficiency.

This was a triple-blinded study with one control group, one placebo plus notriptyline group, and one atorvastatin plus nortiptyline group. The nortiptyline dosage was 25mg nightly, and the interventions were given for 24 weeks. The primary outcome was decrease in headache day frequency; secondary outcomes were severity and quality of life as measured by the Migraine-Specific Quality of Life Questionnaire (MSQ).

Migraine frequency was seen to be significantly improved after 24 weeks in the statin group; however severity was not significantly affected. Adverse effects were mild and overall no subjects discontinued due to the intervention. Quality of life was also seen to be better in the combination statin/nortriptyline group.

The results of this study are compelling enough to consider the addition of a tricyclic antidepressant (TCA) for a patient already on a statin or to start a statin (in the appropriate clinical setting) on a patient already on a TCA. The main limiting factor may be the hesitation to use a TCA medication in an older patient, where the anticholinergic effects may be less predictable.

Caffeine has a controversial place in the headache world. Many patients either use caffeine as a way to treat their migraine attacks, or avoid it completely as they are told it is a migraine trigger. Most headache specialists recommend the avoidance of excessive caffeine use (typically considered >150 mg daily) and tell their patients to be consistent about when they consume caffeine. The effect of caffeine on migraine likely is due to its vasoactive property, specifically that it is vasoconstrictive in nature. These vasoactive properties may also be why many studies investigating cerebrovascular reactivity have been inconclusive in the past.

The authors in this study² recruited patients with episodic migraine and divided them based on caffeine use. All subjects underwent transcranial Doppler testing at baseline and after 3 months, caffeine users were instructed to discontinue caffeine in the interim. Doppler testing looked for differences in BHI (breath holding index) of the bilateral posterior cerebral arteries (PCA), which is a standard at their institution. Subjects were only investigated if they were headache-free and had not used a migraine abortive medication in the previous 48 hours. Preventive medications were not controlled for.

Although the investigators recommended discontinuation of caffeine for the caffeine users, only 28% of that subgroup did discontinue. They then subdivided the group of caffeine users into those whose caffeine intake increased, decreased, or stayed the same. Transcranial Doppler testing was performed in all subgroups.

The investigators found a lower BHI-PCA, or decrease in vasodilatory function, in the subgroups that remained on caffeine. Those who stopped caffeine had improvement in this metric, showing the possible reversibility that discontinuation of caffeine can have. It remains unclear precisely how caffeine is vasoactive, and the effects may be via adenosine receptors, endothelial function, neurotransmitter production, or regulation of the autonomic nervous system. The long-term vascular effects of caffeine are unknown, but they do appear to be reversible after a 3 month period.

Migraine, and especially migraine with aura, is well known as a vascular risk factor. The presence of migraine increases the odds ratio of stroke, myocardial ischemia, deep vein thrombosis and other vascular events significantly. The American College of Obstetrics and Gynecology recommends avoiding the use of any estrogen containing medication in the presence of migraine, due to estrogen itself being a pro-thrombotic hormone.  The precise mechanism that leads to this increased risk is unknown.

This study investigated the connection between migraine and large artery atherosclerosis (LAA). This group observed 415 consecutive patients aged 18-54 who presented for a first time ischemic stroke (other neurovascular events, such as cerebral venous sinus thrombosis, subarachnoid hemorrhage with secondary ischemia and transient ischemic attacks, were excluded). Data regarding these patient’s risks factors was collected and analyzed including elevated body mass index (BMI), hypertension, diabetes, tobacco use, and hyperlipidemia.

All patients underwent magnetic resonance imaging (MRI), as well as either magnetic resonance angiography (MRA) or computed tomography angiography (CTA), and duplex ultrasound confirmed the images. Atherosclerosis was classified using a standardized system (ASCOD: atherosclerosis, small-vessel disease, cardiac pathology, other causes, and dissection) that grades atheroslerotic lesions on a 0-3 scale.

The results may be considered counterintuitive. The presence of migraine was negatively associated with the presence of LAA: a history of migraine did not increase the risk of atherosclerosis. This was even the case when controlling for the traditional vascular risk factors. The authors theorize that likely the association between migraine and stroke and other vascular events is not related to atherosclerosis and may be due to other causes.

A genome-wide association study recently identified a specific polymorphism that was shared by migraine and coronary artery disease. But just like this study, the people with migraine had a negative association with coronary artery disease. If people with migraine do develop stroke or other vascular phenomena they typically present younger and healthier, and this may be why this negative correlation exists.

References

1. Sherafat M et al. The preventive effect of the combination of atorvastatin and nortriptyline in migraine-type headache: a randomized, triple-blind, placebo-controlled trial. Neurol Res. 2022 (Jan 17).
2. Gil Y-E et al. Effect of caffeine and caffeine cessation on cerebrovascular reactivity in patients with migraine. Headache. 2022;62(2):169-75 (Feb 3).
3. Gollion C et al. Migraine and large artery atherosclerosis in young adults with ischemic stroke. Headache. 2022;62(2):191-7 (Feb 5).

Anti–calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies are effective for patients with chronic migraine and medication overuse headache regardless of detoxification strategy, according to investigators.

Abruptly discontinuing overused analgesics with health care provider oversight – a frequently resource-intensive and challenging process – is no more effective for controlling medication overuse headache than simply advising patients to stop, reported lead author Umberto Pensato, MD, of the University of Bologna, Italy, and colleagues.

“[C]urrently, the abrupt discontinuation of the overused painkiller(s), accompanied by the start of a pharmacological preventive therapy, is the most recommended strategy [for medication overuse headache],” the investigators wrote in Cephalalgia. “While painkiller(s) withdrawal could be accomplished on an outpatient basis in most cases, an in-hospital setting may be required to achieve successful discontinuation in a subgroup of patients with medication overuse headache, further weighing on individual and hospital costs. Additionally hampering this approach, the abrupt discontinuation of the overused painkiller(s) invariably results in disabling withdrawal symptoms for up to 2 weeks, including a transitory worsening of headache, the so-called ‘rebound headache.’ ”
 

Inpatient or outpatient: Does it matter?

According to Dr. Pensato and colleagues, early evidence suggests that previous painkiller withdrawal does not impact the efficacy of anti-CGRPs for medication overuse headache, yet relevant data remain scarce. To address this knowledge gap, they conducted a prospective, real-world study exploring the relationship between detoxification and outcomes after starting anti-CGRP therapy.

Out of 401 patients enrolled based on initiation of erenumab or galcanezumab, 111 satisfied inclusion criteria, including diagnosis of chronic migraine and medication overuse headache, at least 28 days of analgesic usage and headache days per month in the preceding 3 months, and other factors. Of these 111 patients, 83 underwent in-hospital detox, while the remaining 28 patients, who declined detox based on personal reasons or COVID-19–related bed shortage, were advised to discontinue overused medication on an outpatient basis (without oversight).

The primary endpoint was medication overuse headache responder rate after 3 months, as defined by ICHD-3 diagnostic criteria. Secondary endpoints included 6-item headache impact test (HIT-6), monthly headache days (MHD), migraine disability assessment score (MIDAS), mean pain intensity (MPI), monthly pain medication intake (MPMI), baseline predictors of response/refractoriness, and safety.

Three months after starting anti-CGRP therapy, 59% of patients had resolution of medication overuse headache, including 57% in the inpatient detox group and 64% in the outpatient group, a difference that was not statistically significant (P = .4788). Approximately half of the patients (51%) had at least 50% reduction in monthly headache days; although the rate was numerically lower in the inpatient group compared with the outpatient group, the difference was again not significant (51% vs. 54%; P = .8393).

“Our results support the emerging evidence that anti-CGRP drugs may be effective in these patients irrespective of the detoxification program,” the investigators concluded. “Further studies are needed to definitively confirm these results, potentially leading to a paradigm shift in the management of medication overuse headache.”
 

Abrupt or gradual detox?

According to Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, the study was hampered by two major design limitations.

“The biggest problem I see is that the two groups were treated very differently for their detoxification,” Dr. Rapoport said. “One group was detoxified abruptly in the hospital, so the authors were sure that the patients were off acute-care medication before they started their preventives. The other group was advised to stop their medication on an outpatient basis. The issue is that we have no follow-up as to whether the outpatients did or did not abruptly detoxify. A bigger issue was that the two groups were not randomized so there are many other variables that may have come into consideration.”

Still, Dr. Rapoport, a past president of the International Headache Society (IHS), noted that the findings strengthen a growing body of evidence supporting the efficacy of monoclonal antibodies for medication overuse headache regardless of detoxification strategy. He cited a 2020 study by Carlsen and colleagues conducted at the Danish Headache Center in Copenhagen, which reported similar medication overuse headache outcomes across three randomized cohorts whether they received preventive therapy with detoxification, preventive therapy without detoxification, or detoxification followed 2 months later by preventive therapy.

“What I have noticed since we have had monoclonal antibodies in our armamentarium is that these drugs work very well even when the patient has not fully detoxified,” Dr. Rapoport said. “What I do with my patients is not teach them how to detoxify now, but simply educate them to take fewer acute care medications as their headaches get better from the monoclonal antibodies; they should try to take fewer acute care medications for milder, shorter headaches, and just let them go away on their own. Previous research suggests that even when a patient is not educated at all about medication overuse headache and the reason for detoxification, monoclonal antibodies still work in the presence of medication overuse headache, and improve it.”

The investigators disclosed relationships with Allergan, Novartis, Teva, and others. Dr. Rapoport is on the speakers bureau for AbbVie.

Anti–calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies are effective for patients with chronic migraine and medication overuse headache regardless of detoxification strategy, according to investigators.

Abruptly discontinuing overused analgesics with health care provider oversight – a frequently resource-intensive and challenging process – is no more effective for controlling medication overuse headache than simply advising patients to stop, reported lead author Umberto Pensato, MD, of the University of Bologna, Italy, and colleagues.

“[C]urrently, the abrupt discontinuation of the overused painkiller(s), accompanied by the start of a pharmacological preventive therapy, is the most recommended strategy [for medication overuse headache],” the investigators wrote in Cephalalgia. “While painkiller(s) withdrawal could be accomplished on an outpatient basis in most cases, an in-hospital setting may be required to achieve successful discontinuation in a subgroup of patients with medication overuse headache, further weighing on individual and hospital costs. Additionally hampering this approach, the abrupt discontinuation of the overused painkiller(s) invariably results in disabling withdrawal symptoms for up to 2 weeks, including a transitory worsening of headache, the so-called ‘rebound headache.’ ”
 

Inpatient or outpatient: Does it matter?

According to Dr. Pensato and colleagues, early evidence suggests that previous painkiller withdrawal does not impact the efficacy of anti-CGRPs for medication overuse headache, yet relevant data remain scarce. To address this knowledge gap, they conducted a prospective, real-world study exploring the relationship between detoxification and outcomes after starting anti-CGRP therapy.

Out of 401 patients enrolled based on initiation of erenumab or galcanezumab, 111 satisfied inclusion criteria, including diagnosis of chronic migraine and medication overuse headache, at least 28 days of analgesic usage and headache days per month in the preceding 3 months, and other factors. Of these 111 patients, 83 underwent in-hospital detox, while the remaining 28 patients, who declined detox based on personal reasons or COVID-19–related bed shortage, were advised to discontinue overused medication on an outpatient basis (without oversight).

The primary endpoint was medication overuse headache responder rate after 3 months, as defined by ICHD-3 diagnostic criteria. Secondary endpoints included 6-item headache impact test (HIT-6), monthly headache days (MHD), migraine disability assessment score (MIDAS), mean pain intensity (MPI), monthly pain medication intake (MPMI), baseline predictors of response/refractoriness, and safety.

Three months after starting anti-CGRP therapy, 59% of patients had resolution of medication overuse headache, including 57% in the inpatient detox group and 64% in the outpatient group, a difference that was not statistically significant (P = .4788). Approximately half of the patients (51%) had at least 50% reduction in monthly headache days; although the rate was numerically lower in the inpatient group compared with the outpatient group, the difference was again not significant (51% vs. 54%; P = .8393).

“Our results support the emerging evidence that anti-CGRP drugs may be effective in these patients irrespective of the detoxification program,” the investigators concluded. “Further studies are needed to definitively confirm these results, potentially leading to a paradigm shift in the management of medication overuse headache.”
 

Abrupt or gradual detox?

According to Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, the study was hampered by two major design limitations.

“The biggest problem I see is that the two groups were treated very differently for their detoxification,” Dr. Rapoport said. “One group was detoxified abruptly in the hospital, so the authors were sure that the patients were off acute-care medication before they started their preventives. The other group was advised to stop their medication on an outpatient basis. The issue is that we have no follow-up as to whether the outpatients did or did not abruptly detoxify. A bigger issue was that the two groups were not randomized so there are many other variables that may have come into consideration.”

Still, Dr. Rapoport, a past president of the International Headache Society (IHS), noted that the findings strengthen a growing body of evidence supporting the efficacy of monoclonal antibodies for medication overuse headache regardless of detoxification strategy. He cited a 2020 study by Carlsen and colleagues conducted at the Danish Headache Center in Copenhagen, which reported similar medication overuse headache outcomes across three randomized cohorts whether they received preventive therapy with detoxification, preventive therapy without detoxification, or detoxification followed 2 months later by preventive therapy.

“What I have noticed since we have had monoclonal antibodies in our armamentarium is that these drugs work very well even when the patient has not fully detoxified,” Dr. Rapoport said. “What I do with my patients is not teach them how to detoxify now, but simply educate them to take fewer acute care medications as their headaches get better from the monoclonal antibodies; they should try to take fewer acute care medications for milder, shorter headaches, and just let them go away on their own. Previous research suggests that even when a patient is not educated at all about medication overuse headache and the reason for detoxification, monoclonal antibodies still work in the presence of medication overuse headache, and improve it.”

The investigators disclosed relationships with Allergan, Novartis, Teva, and others. Dr. Rapoport is on the speakers bureau for AbbVie.

Anti–calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies are effective for patients with chronic migraine and medication overuse headache regardless of detoxification strategy, according to investigators.

Abruptly discontinuing overused analgesics with health care provider oversight – a frequently resource-intensive and challenging process – is no more effective for controlling medication overuse headache than simply advising patients to stop, reported lead author Umberto Pensato, MD, of the University of Bologna, Italy, and colleagues.

“[C]urrently, the abrupt discontinuation of the overused painkiller(s), accompanied by the start of a pharmacological preventive therapy, is the most recommended strategy [for medication overuse headache],” the investigators wrote in Cephalalgia. “While painkiller(s) withdrawal could be accomplished on an outpatient basis in most cases, an in-hospital setting may be required to achieve successful discontinuation in a subgroup of patients with medication overuse headache, further weighing on individual and hospital costs. Additionally hampering this approach, the abrupt discontinuation of the overused painkiller(s) invariably results in disabling withdrawal symptoms for up to 2 weeks, including a transitory worsening of headache, the so-called ‘rebound headache.’ ”
 

Inpatient or outpatient: Does it matter?

According to Dr. Pensato and colleagues, early evidence suggests that previous painkiller withdrawal does not impact the efficacy of anti-CGRPs for medication overuse headache, yet relevant data remain scarce. To address this knowledge gap, they conducted a prospective, real-world study exploring the relationship between detoxification and outcomes after starting anti-CGRP therapy.

Out of 401 patients enrolled based on initiation of erenumab or galcanezumab, 111 satisfied inclusion criteria, including diagnosis of chronic migraine and medication overuse headache, at least 28 days of analgesic usage and headache days per month in the preceding 3 months, and other factors. Of these 111 patients, 83 underwent in-hospital detox, while the remaining 28 patients, who declined detox based on personal reasons or COVID-19–related bed shortage, were advised to discontinue overused medication on an outpatient basis (without oversight).

The primary endpoint was medication overuse headache responder rate after 3 months, as defined by ICHD-3 diagnostic criteria. Secondary endpoints included 6-item headache impact test (HIT-6), monthly headache days (MHD), migraine disability assessment score (MIDAS), mean pain intensity (MPI), monthly pain medication intake (MPMI), baseline predictors of response/refractoriness, and safety.

Three months after starting anti-CGRP therapy, 59% of patients had resolution of medication overuse headache, including 57% in the inpatient detox group and 64% in the outpatient group, a difference that was not statistically significant (P = .4788). Approximately half of the patients (51%) had at least 50% reduction in monthly headache days; although the rate was numerically lower in the inpatient group compared with the outpatient group, the difference was again not significant (51% vs. 54%; P = .8393).

“Our results support the emerging evidence that anti-CGRP drugs may be effective in these patients irrespective of the detoxification program,” the investigators concluded. “Further studies are needed to definitively confirm these results, potentially leading to a paradigm shift in the management of medication overuse headache.”
 

Abrupt or gradual detox?

According to Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, the study was hampered by two major design limitations.

“The biggest problem I see is that the two groups were treated very differently for their detoxification,” Dr. Rapoport said. “One group was detoxified abruptly in the hospital, so the authors were sure that the patients were off acute-care medication before they started their preventives. The other group was advised to stop their medication on an outpatient basis. The issue is that we have no follow-up as to whether the outpatients did or did not abruptly detoxify. A bigger issue was that the two groups were not randomized so there are many other variables that may have come into consideration.”

Still, Dr. Rapoport, a past president of the International Headache Society (IHS), noted that the findings strengthen a growing body of evidence supporting the efficacy of monoclonal antibodies for medication overuse headache regardless of detoxification strategy. He cited a 2020 study by Carlsen and colleagues conducted at the Danish Headache Center in Copenhagen, which reported similar medication overuse headache outcomes across three randomized cohorts whether they received preventive therapy with detoxification, preventive therapy without detoxification, or detoxification followed 2 months later by preventive therapy.

“What I have noticed since we have had monoclonal antibodies in our armamentarium is that these drugs work very well even when the patient has not fully detoxified,” Dr. Rapoport said. “What I do with my patients is not teach them how to detoxify now, but simply educate them to take fewer acute care medications as their headaches get better from the monoclonal antibodies; they should try to take fewer acute care medications for milder, shorter headaches, and just let them go away on their own. Previous research suggests that even when a patient is not educated at all about medication overuse headache and the reason for detoxification, monoclonal antibodies still work in the presence of medication overuse headache, and improve it.”

The investigators disclosed relationships with Allergan, Novartis, Teva, and others. Dr. Rapoport is on the speakers bureau for AbbVie.

Key clinical point: Atogepant shows a favorable safety and efficacy profile in the prophylactic treatment of episodic migraine.

Major finding: Atogepant (10 mg, 30 mg, and 60 mg) vs. placebo caused a significant reduction in mean monthly migraine (P < .00001, P < .00001, and P = .007; respectively), headache (P < .00001, P < .00001, and P = .001; respectively), and medication use (all P < .00001) days; an increase in the ≥50% responder rate (P = .0008, P = .02, and P = .04; respectively); and a nonsignificant difference in the outcomes of adverse events (P = .57, P = .64, and P = .68; respectively).

Study details: Findings are from a meta-analysis of 3 randomized controlled trials including 2,466 adult patients with episodic migraine who received atogepant (10 mg, 30 mg, or 60 mg once daily) or placebo.

Disclosures: The study was supported by the Suzhou Health Talents Training Project. None of the authors declared any conflicts of interest.

Source: Tao X et al. J Headache Pain. 2022;23:19 (Jan 29). Doi: 10.1186/s10194-022-01391-2

Key clinical point: Atogepant shows a favorable safety and efficacy profile in the prophylactic treatment of episodic migraine.

Major finding: Atogepant (10 mg, 30 mg, and 60 mg) vs. placebo caused a significant reduction in mean monthly migraine (P < .00001, P < .00001, and P = .007; respectively), headache (P < .00001, P < .00001, and P = .001; respectively), and medication use (all P < .00001) days; an increase in the ≥50% responder rate (P = .0008, P = .02, and P = .04; respectively); and a nonsignificant difference in the outcomes of adverse events (P = .57, P = .64, and P = .68; respectively).

Study details: Findings are from a meta-analysis of 3 randomized controlled trials including 2,466 adult patients with episodic migraine who received atogepant (10 mg, 30 mg, or 60 mg once daily) or placebo.

Disclosures: The study was supported by the Suzhou Health Talents Training Project. None of the authors declared any conflicts of interest.

Source: Tao X et al. J Headache Pain. 2022;23:19 (Jan 29). Doi: 10.1186/s10194-022-01391-2

Key clinical point: Atogepant shows a favorable safety and efficacy profile in the prophylactic treatment of episodic migraine.

Major finding: Atogepant (10 mg, 30 mg, and 60 mg) vs. placebo caused a significant reduction in mean monthly migraine (P < .00001, P < .00001, and P = .007; respectively), headache (P < .00001, P < .00001, and P = .001; respectively), and medication use (all P < .00001) days; an increase in the ≥50% responder rate (P = .0008, P = .02, and P = .04; respectively); and a nonsignificant difference in the outcomes of adverse events (P = .57, P = .64, and P = .68; respectively).

Study details: Findings are from a meta-analysis of 3 randomized controlled trials including 2,466 adult patients with episodic migraine who received atogepant (10 mg, 30 mg, or 60 mg once daily) or placebo.

Disclosures: The study was supported by the Suzhou Health Talents Training Project. None of the authors declared any conflicts of interest.

Source: Tao X et al. J Headache Pain. 2022;23:19 (Jan 29). Doi: 10.1186/s10194-022-01391-2

Key clinical point: Discontinuation of anticalcitonin gene-related protein (CGRP) monoclonal antibodies (mAb) leads to a progressive increase in monthly migraine days (MMD) and analgesic use from the first month, which, on reinitiation, revert to values comparable with those in the last month of treatment.

Main finding: At months 2 and 3 after discontinuation, a significant increase in MMD (P = .003 and P < .001, respectively) and analgesic use (both P < .001) was observed compared with month 12 of treatment. In the reinitiation month, the MMD (P = .40), days with ≥1 analgesic used (P = .83), and number of analgesics used (P = .74) were similar to the treatment month 12 values.

Study details: Findings are from a single-center, prospective, observational study involving 44 patients >18 years of age with treatment-resistant chronic migraine who received erenumab or galcanezumab for 12 months before a 3-month treatment discontinuation phase and 1 month of reinitiation.

Disclosures: The study received no specific funding. Some authors reported receiving personal fees or grants from various sources.

Source: Iannone LF et al. Eur J Neurol. 2022 (Jan 31). Doi: 10.1111/ene.15260

Key clinical point: Discontinuation of anticalcitonin gene-related protein (CGRP) monoclonal antibodies (mAb) leads to a progressive increase in monthly migraine days (MMD) and analgesic use from the first month, which, on reinitiation, revert to values comparable with those in the last month of treatment.

Main finding: At months 2 and 3 after discontinuation, a significant increase in MMD (P = .003 and P < .001, respectively) and analgesic use (both P < .001) was observed compared with month 12 of treatment. In the reinitiation month, the MMD (P = .40), days with ≥1 analgesic used (P = .83), and number of analgesics used (P = .74) were similar to the treatment month 12 values.

Study details: Findings are from a single-center, prospective, observational study involving 44 patients >18 years of age with treatment-resistant chronic migraine who received erenumab or galcanezumab for 12 months before a 3-month treatment discontinuation phase and 1 month of reinitiation.

Disclosures: The study received no specific funding. Some authors reported receiving personal fees or grants from various sources.

Source: Iannone LF et al. Eur J Neurol. 2022 (Jan 31). Doi: 10.1111/ene.15260

Key clinical point: Discontinuation of anticalcitonin gene-related protein (CGRP) monoclonal antibodies (mAb) leads to a progressive increase in monthly migraine days (MMD) and analgesic use from the first month, which, on reinitiation, revert to values comparable with those in the last month of treatment.

Main finding: At months 2 and 3 after discontinuation, a significant increase in MMD (P = .003 and P < .001, respectively) and analgesic use (both P < .001) was observed compared with month 12 of treatment. In the reinitiation month, the MMD (P = .40), days with ≥1 analgesic used (P = .83), and number of analgesics used (P = .74) were similar to the treatment month 12 values.

Study details: Findings are from a single-center, prospective, observational study involving 44 patients >18 years of age with treatment-resistant chronic migraine who received erenumab or galcanezumab for 12 months before a 3-month treatment discontinuation phase and 1 month of reinitiation.

Disclosures: The study received no specific funding. Some authors reported receiving personal fees or grants from various sources.

Source: Iannone LF et al. Eur J Neurol. 2022 (Jan 31). Doi: 10.1111/ene.15260

Key clinical point: The efficacy and safety of eptinezumab in preventing migraine realized in the PROMISE-1 and PROMISE-2 trials remain unperturbed by the intrinsic baseline characteristics of the study participants, including sex, age, and body mass index (BMI).

Main finding: The ≥50% migraine responder rate (MRR) was ≥10% higher with eptinezumab relative to placebo for most demographic factors, except in the case of obesity; although patients with a BMI of 30-35 kg/m² receiving eptinezumab vs. placebo showed improved ≥50% MRR, the separation was <10%. Eptinezumab was generally safe, and no new treatment-emergent adverse events were identified.

Study details: This was a post hoc subgroup analysis of adult patients with episodic or chronic migraine from the phase 3 PROMISE-1 and PROMISE-2 trials, respectively, which included a total of 1,960 patients in the safety analysis and 1,737 patients (99.8%) in the efficacy analysis.

Disclosures: The study received financial support from H. Lundbeck A/S. The authors disclosed having no conflicts of interest.

Source: Martin V et al. Clin Ther. 2022 (Feb 9). Doi: 10.1016/j.clinthera.2022.01.006

Key clinical point: The efficacy and safety of eptinezumab in preventing migraine realized in the PROMISE-1 and PROMISE-2 trials remain unperturbed by the intrinsic baseline characteristics of the study participants, including sex, age, and body mass index (BMI).

Main finding: The ≥50% migraine responder rate (MRR) was ≥10% higher with eptinezumab relative to placebo for most demographic factors, except in the case of obesity; although patients with a BMI of 30-35 kg/m² receiving eptinezumab vs. placebo showed improved ≥50% MRR, the separation was <10%. Eptinezumab was generally safe, and no new treatment-emergent adverse events were identified.

Study details: This was a post hoc subgroup analysis of adult patients with episodic or chronic migraine from the phase 3 PROMISE-1 and PROMISE-2 trials, respectively, which included a total of 1,960 patients in the safety analysis and 1,737 patients (99.8%) in the efficacy analysis.

Disclosures: The study received financial support from H. Lundbeck A/S. The authors disclosed having no conflicts of interest.

Source: Martin V et al. Clin Ther. 2022 (Feb 9). Doi: 10.1016/j.clinthera.2022.01.006

Key clinical point: The efficacy and safety of eptinezumab in preventing migraine realized in the PROMISE-1 and PROMISE-2 trials remain unperturbed by the intrinsic baseline characteristics of the study participants, including sex, age, and body mass index (BMI).

Main finding: The ≥50% migraine responder rate (MRR) was ≥10% higher with eptinezumab relative to placebo for most demographic factors, except in the case of obesity; although patients with a BMI of 30-35 kg/m² receiving eptinezumab vs. placebo showed improved ≥50% MRR, the separation was <10%. Eptinezumab was generally safe, and no new treatment-emergent adverse events were identified.

Study details: This was a post hoc subgroup analysis of adult patients with episodic or chronic migraine from the phase 3 PROMISE-1 and PROMISE-2 trials, respectively, which included a total of 1,960 patients in the safety analysis and 1,737 patients (99.8%) in the efficacy analysis.

Disclosures: The study received financial support from H. Lundbeck A/S. The authors disclosed having no conflicts of interest.

Source: Martin V et al. Clin Ther. 2022 (Feb 9). Doi: 10.1016/j.clinthera.2022.01.006

Key clinical point: Patients with migraine present with a 20% higher risk of developing neovascular age-related macular degeneration (AMD) compared with individuals without migraine.

Main finding: A significantly higher proportion of patients with neovascular AMD vs. control individuals had migraine before the index date (6.1% vs. 4.9%; P < .001), with an adjusted (for age, sex, monthly income, geographic location, urbanization, hyperlipidemia, diabetes, coronary heart disease, hypertension, and cataract surgery) odds ratio of 1.201 (P < .001).

Study details: This nationwide, population-based study included 20,333 patients aged 40 years or older diagnosed with neovascular AMD in at least 2 claims, with the first diagnosis date defined as the index date. They were propensity score-matched (1:4) with 81,332 nonneovascular AMD control individuals.

Disclosures: No source of funding was declared. None of the authors identified any conflicts of interest.

Source: Kuang TM et al. Sci Rep. 2022;12:1792 (Feb 2). Doi: 10.1038/s41598-022-05638-5

Key clinical point: Patients with migraine present with a 20% higher risk of developing neovascular age-related macular degeneration (AMD) compared with individuals without migraine.

Main finding: A significantly higher proportion of patients with neovascular AMD vs. control individuals had migraine before the index date (6.1% vs. 4.9%; P < .001), with an adjusted (for age, sex, monthly income, geographic location, urbanization, hyperlipidemia, diabetes, coronary heart disease, hypertension, and cataract surgery) odds ratio of 1.201 (P < .001).

Study details: This nationwide, population-based study included 20,333 patients aged 40 years or older diagnosed with neovascular AMD in at least 2 claims, with the first diagnosis date defined as the index date. They were propensity score-matched (1:4) with 81,332 nonneovascular AMD control individuals.

Disclosures: No source of funding was declared. None of the authors identified any conflicts of interest.

Source: Kuang TM et al. Sci Rep. 2022;12:1792 (Feb 2). Doi: 10.1038/s41598-022-05638-5

Key clinical point: Patients with migraine present with a 20% higher risk of developing neovascular age-related macular degeneration (AMD) compared with individuals without migraine.

Main finding: A significantly higher proportion of patients with neovascular AMD vs. control individuals had migraine before the index date (6.1% vs. 4.9%; P < .001), with an adjusted (for age, sex, monthly income, geographic location, urbanization, hyperlipidemia, diabetes, coronary heart disease, hypertension, and cataract surgery) odds ratio of 1.201 (P < .001).

Study details: This nationwide, population-based study included 20,333 patients aged 40 years or older diagnosed with neovascular AMD in at least 2 claims, with the first diagnosis date defined as the index date. They were propensity score-matched (1:4) with 81,332 nonneovascular AMD control individuals.

Disclosures: No source of funding was declared. None of the authors identified any conflicts of interest.

Source: Kuang TM et al. Sci Rep. 2022;12:1792 (Feb 2). Doi: 10.1038/s41598-022-05638-5

Key clinical point: Clinical management of pain intensity and disability in patients with migraine would benefit from closely monitoring their dietary nutrient patterns.

Main finding: After adjusting for all confounders, higher consumption of vitamins B1 (thiamine), B3 (niacin), and B9 (folic acid). and carbohydrate, protein, and total fiber was positively associated with pain intensity as assessed using the Visual Analogue Scale (regression coefficient [β] 0.37; P < .001), whereas that of vitamins A, K, C, B6, B2 (riboflavin), and calcium and magnesium was negatively associated with migraine-related disability measured by Migraine Disability Assessment (β −3.14; P = .01).

Study details: Findings are from a cross-sectional study involving 266 adult women with migraine and no chronic disease.

Disclosures: The study was sponsored by the Tehran University of Medical Sciences, Iran. The authors reported having no conflicts of interest.

Source: Bahrampour N et al. Br J Nutr. 2022 (Jan 17). Doi: 10.1017/S0007114522000046

Key clinical point: Clinical management of pain intensity and disability in patients with migraine would benefit from closely monitoring their dietary nutrient patterns.

Main finding: After adjusting for all confounders, higher consumption of vitamins B1 (thiamine), B3 (niacin), and B9 (folic acid). and carbohydrate, protein, and total fiber was positively associated with pain intensity as assessed using the Visual Analogue Scale (regression coefficient [β] 0.37; P < .001), whereas that of vitamins A, K, C, B6, B2 (riboflavin), and calcium and magnesium was negatively associated with migraine-related disability measured by Migraine Disability Assessment (β −3.14; P = .01).

Study details: Findings are from a cross-sectional study involving 266 adult women with migraine and no chronic disease.

Disclosures: The study was sponsored by the Tehran University of Medical Sciences, Iran. The authors reported having no conflicts of interest.

Source: Bahrampour N et al. Br J Nutr. 2022 (Jan 17). Doi: 10.1017/S0007114522000046

Key clinical point: Clinical management of pain intensity and disability in patients with migraine would benefit from closely monitoring their dietary nutrient patterns.

Main finding: After adjusting for all confounders, higher consumption of vitamins B1 (thiamine), B3 (niacin), and B9 (folic acid). and carbohydrate, protein, and total fiber was positively associated with pain intensity as assessed using the Visual Analogue Scale (regression coefficient [β] 0.37; P < .001), whereas that of vitamins A, K, C, B6, B2 (riboflavin), and calcium and magnesium was negatively associated with migraine-related disability measured by Migraine Disability Assessment (β −3.14; P = .01).

Study details: Findings are from a cross-sectional study involving 266 adult women with migraine and no chronic disease.

Disclosures: The study was sponsored by the Tehran University of Medical Sciences, Iran. The authors reported having no conflicts of interest.

Source: Bahrampour N et al. Br J Nutr. 2022 (Jan 17). Doi: 10.1017/S0007114522000046

Key clinical point: Migraine, migraine with aura (MWA), and migraine without aura (MWoA) are negatively associated with large artery atherosclerosis (LAA) in young patients with ischemic stroke, irrespective of traditional vascular risk factors.

Major finding: LAA of any grade was significantly less frequent in patients with migraine (P < .001), MWA (P < .001), and MWoA (P = .005) vs. those without migraine. Migraine (adjusted odds ratio [aOR] 0.44; P = .005), MWoA (aOR 0.42; P = .020), and MWA (aOR 0.47; P = .037) vs. no migraine showed a negative association with LAA of any grade.

Study details: Findings are from a cross-sectional study including 415 patients aged 18-54 years with first-ever acute ischemic stroke, of which 144 had migraine (MWA, n = 76; MWoA, n = 68).

Disclosures: No funding was received for this study. The authors declared no conflicts of interest.

Source: Gollion C et al. Headache. 2022;62(2):191-7 (Feb 5). Doi: 10.1111/head.14265

Key clinical point: Migraine, migraine with aura (MWA), and migraine without aura (MWoA) are negatively associated with large artery atherosclerosis (LAA) in young patients with ischemic stroke, irrespective of traditional vascular risk factors.

Major finding: LAA of any grade was significantly less frequent in patients with migraine (P < .001), MWA (P < .001), and MWoA (P = .005) vs. those without migraine. Migraine (adjusted odds ratio [aOR] 0.44; P = .005), MWoA (aOR 0.42; P = .020), and MWA (aOR 0.47; P = .037) vs. no migraine showed a negative association with LAA of any grade.

Study details: Findings are from a cross-sectional study including 415 patients aged 18-54 years with first-ever acute ischemic stroke, of which 144 had migraine (MWA, n = 76; MWoA, n = 68).

Disclosures: No funding was received for this study. The authors declared no conflicts of interest.

Source: Gollion C et al. Headache. 2022;62(2):191-7 (Feb 5). Doi: 10.1111/head.14265

Key clinical point: Migraine, migraine with aura (MWA), and migraine without aura (MWoA) are negatively associated with large artery atherosclerosis (LAA) in young patients with ischemic stroke, irrespective of traditional vascular risk factors.

Major finding: LAA of any grade was significantly less frequent in patients with migraine (P < .001), MWA (P < .001), and MWoA (P = .005) vs. those without migraine. Migraine (adjusted odds ratio [aOR] 0.44; P = .005), MWoA (aOR 0.42; P = .020), and MWA (aOR 0.47; P = .037) vs. no migraine showed a negative association with LAA of any grade.

Study details: Findings are from a cross-sectional study including 415 patients aged 18-54 years with first-ever acute ischemic stroke, of which 144 had migraine (MWA, n = 76; MWoA, n = 68).

Disclosures: No funding was received for this study. The authors declared no conflicts of interest.

Source: Gollion C et al. Headache. 2022;62(2):191-7 (Feb 5). Doi: 10.1111/head.14265

Key clinical point: Chronic caffeine use is associated with a reduced cerebrovascular reactivity (CVR) in the posterior circulation of patients with episodic migraine, whereas caffeine cessation is associated with a significantly improved CVR.

Major finding: The breath-holding index (BHI) of the posterior cerebral arteries (PCA) was lower in caffeine users vs. nonusers (median 1.1 vs. 1.3; P = .03), with caffeine cessation being associated with a significant improvement in PCA-BHI (median 1.1 at baseline vs. 1.3 at 3 months of follow-up; P = .03) and independently associated with changes in PCA-BHI (adjusted unstandardized β 0.27; P = .04).

Study details: Findings are from a prospective, longitudinal, observational study of 84 adult patients with episodic migraine and no vascular risk factors, of whom 56 were caffeine users and were instructed to discontinue caffeine use.

Disclosures: The study was supported by the Dong-A ST and National Research Foundation of Korea grant funded by the Korean government. The authors declared no conflicts of interest.

Source: Gil Y-E et al. Headache. 2022;62(2):169-75 (Feb 3). Doi: 10.1111/head.14263

Key clinical point: Chronic caffeine use is associated with a reduced cerebrovascular reactivity (CVR) in the posterior circulation of patients with episodic migraine, whereas caffeine cessation is associated with a significantly improved CVR.

Major finding: The breath-holding index (BHI) of the posterior cerebral arteries (PCA) was lower in caffeine users vs. nonusers (median 1.1 vs. 1.3; P = .03), with caffeine cessation being associated with a significant improvement in PCA-BHI (median 1.1 at baseline vs. 1.3 at 3 months of follow-up; P = .03) and independently associated with changes in PCA-BHI (adjusted unstandardized β 0.27; P = .04).

Study details: Findings are from a prospective, longitudinal, observational study of 84 adult patients with episodic migraine and no vascular risk factors, of whom 56 were caffeine users and were instructed to discontinue caffeine use.

Disclosures: The study was supported by the Dong-A ST and National Research Foundation of Korea grant funded by the Korean government. The authors declared no conflicts of interest.

Source: Gil Y-E et al. Headache. 2022;62(2):169-75 (Feb 3). Doi: 10.1111/head.14263

Key clinical point: Chronic caffeine use is associated with a reduced cerebrovascular reactivity (CVR) in the posterior circulation of patients with episodic migraine, whereas caffeine cessation is associated with a significantly improved CVR.

Major finding: The breath-holding index (BHI) of the posterior cerebral arteries (PCA) was lower in caffeine users vs. nonusers (median 1.1 vs. 1.3; P = .03), with caffeine cessation being associated with a significant improvement in PCA-BHI (median 1.1 at baseline vs. 1.3 at 3 months of follow-up; P = .03) and independently associated with changes in PCA-BHI (adjusted unstandardized β 0.27; P = .04).

Study details: Findings are from a prospective, longitudinal, observational study of 84 adult patients with episodic migraine and no vascular risk factors, of whom 56 were caffeine users and were instructed to discontinue caffeine use.

Disclosures: The study was supported by the Dong-A ST and National Research Foundation of Korea grant funded by the Korean government. The authors declared no conflicts of interest.

Source: Gil Y-E et al. Headache. 2022;62(2):169-75 (Feb 3). Doi: 10.1111/head.14263