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Dual treatment may boost efficacy in chronic migraine
, possibly owing to the synergistic mechanism of action of the two agents, a new study suggests.
“People with chronic migraine may be the toughest to treat. They have the greatest disability, and often insurance companies would prefer monotherapy, but in these patients, sometimes using a multifaceted approach and using different drugs that target different pathophysiologies of migraine can probably provide greater benefit in terms of reducing the frequency and severity of the headaches,” study investigator MaryAnn Mays, MD, staff neurologist at the Headache and Facial Pain Clinic in the Neurologic Institute, Cleveland Clinic, Cleveland, Ohio, said in an interview.
The findings were presented at the annual meeting of the American Headache Society.
Fewer Migraine Days
OnabotulinumtodxinA (onabot) has been shown to selectively inhibit unmyelinated C-fibers but not A-delta-meningeal nociceptors. Anti-CGRP mAb therapies have been shown to prevent the activation of A-delta-fibers but not C-fibers, said Dr. Mays.
For the study, the investigators reviewed the electronic medical records of 194 patients who had been concurrently treated with anti-CGRP mAbs and onabot. Most (86.6%) were women; ages ranged from 36 to 65 years, and at baseline, they had been having an average of 28 (+4.6) monthly migraine days (MMDs).
The number of MMDs were assessed at two periods: 3 months after monotherapy with an anti-CGRP mAb or onabot injections, and 3 months after combined therapy.
Monotherapy reduced the average number of MMDs from 28 to 18.6, for a reduction of 9.4 days (P > .0001).
After initiation of combined therapy, the average number of MMDs decreased further, from 18.6 MMDs to 12.1 MMDs (P > .0001).
In all, the combination of onabot and anti-CGRP mAbs resulted in a total MMD reduction of 15.8 (P > .0001).
In addition, most patients (68%) reported a 50% or greater reduction in MMDs, and 46.4% reported a 75% or greater reduction.
Great News for Patients
Commenting for this article, Rashmi B. Halker Singh, MD, associate professor of neurology at Mayo Clinic, Scottsdale, Arizona, said the study findings “support what we see in clinical practice and what we suspected from preclinical data.”
Single-agent treatment is not sufficient for many patients. Data confirming the benefit of dual therapy will provide more evidence to insurance companies of the need for coverage.
“We have lots of individuals for whom single treatment is not sufficient and who need this combination of treatment, and it is often denied by insurance. There are preclinical data suggesting synergy, but insurance says it is experimental, so the claims get denied. This leaves patients having to choose which drug they want to continue with, and that’s really heartbreaking,” Dr. Halker Singh said.
The importance of this study is that it adds more data to support evidence-based therapies for migraine and to help patients get the treatment they need, she added.
Dr. Mays reports financial relationships with AbbVie, Amgen, and Teva. Dr. Halker Singh reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
, possibly owing to the synergistic mechanism of action of the two agents, a new study suggests.
“People with chronic migraine may be the toughest to treat. They have the greatest disability, and often insurance companies would prefer monotherapy, but in these patients, sometimes using a multifaceted approach and using different drugs that target different pathophysiologies of migraine can probably provide greater benefit in terms of reducing the frequency and severity of the headaches,” study investigator MaryAnn Mays, MD, staff neurologist at the Headache and Facial Pain Clinic in the Neurologic Institute, Cleveland Clinic, Cleveland, Ohio, said in an interview.
The findings were presented at the annual meeting of the American Headache Society.
Fewer Migraine Days
OnabotulinumtodxinA (onabot) has been shown to selectively inhibit unmyelinated C-fibers but not A-delta-meningeal nociceptors. Anti-CGRP mAb therapies have been shown to prevent the activation of A-delta-fibers but not C-fibers, said Dr. Mays.
For the study, the investigators reviewed the electronic medical records of 194 patients who had been concurrently treated with anti-CGRP mAbs and onabot. Most (86.6%) were women; ages ranged from 36 to 65 years, and at baseline, they had been having an average of 28 (+4.6) monthly migraine days (MMDs).
The number of MMDs were assessed at two periods: 3 months after monotherapy with an anti-CGRP mAb or onabot injections, and 3 months after combined therapy.
Monotherapy reduced the average number of MMDs from 28 to 18.6, for a reduction of 9.4 days (P > .0001).
After initiation of combined therapy, the average number of MMDs decreased further, from 18.6 MMDs to 12.1 MMDs (P > .0001).
In all, the combination of onabot and anti-CGRP mAbs resulted in a total MMD reduction of 15.8 (P > .0001).
In addition, most patients (68%) reported a 50% or greater reduction in MMDs, and 46.4% reported a 75% or greater reduction.
Great News for Patients
Commenting for this article, Rashmi B. Halker Singh, MD, associate professor of neurology at Mayo Clinic, Scottsdale, Arizona, said the study findings “support what we see in clinical practice and what we suspected from preclinical data.”
Single-agent treatment is not sufficient for many patients. Data confirming the benefit of dual therapy will provide more evidence to insurance companies of the need for coverage.
“We have lots of individuals for whom single treatment is not sufficient and who need this combination of treatment, and it is often denied by insurance. There are preclinical data suggesting synergy, but insurance says it is experimental, so the claims get denied. This leaves patients having to choose which drug they want to continue with, and that’s really heartbreaking,” Dr. Halker Singh said.
The importance of this study is that it adds more data to support evidence-based therapies for migraine and to help patients get the treatment they need, she added.
Dr. Mays reports financial relationships with AbbVie, Amgen, and Teva. Dr. Halker Singh reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
, possibly owing to the synergistic mechanism of action of the two agents, a new study suggests.
“People with chronic migraine may be the toughest to treat. They have the greatest disability, and often insurance companies would prefer monotherapy, but in these patients, sometimes using a multifaceted approach and using different drugs that target different pathophysiologies of migraine can probably provide greater benefit in terms of reducing the frequency and severity of the headaches,” study investigator MaryAnn Mays, MD, staff neurologist at the Headache and Facial Pain Clinic in the Neurologic Institute, Cleveland Clinic, Cleveland, Ohio, said in an interview.
The findings were presented at the annual meeting of the American Headache Society.
Fewer Migraine Days
OnabotulinumtodxinA (onabot) has been shown to selectively inhibit unmyelinated C-fibers but not A-delta-meningeal nociceptors. Anti-CGRP mAb therapies have been shown to prevent the activation of A-delta-fibers but not C-fibers, said Dr. Mays.
For the study, the investigators reviewed the electronic medical records of 194 patients who had been concurrently treated with anti-CGRP mAbs and onabot. Most (86.6%) were women; ages ranged from 36 to 65 years, and at baseline, they had been having an average of 28 (+4.6) monthly migraine days (MMDs).
The number of MMDs were assessed at two periods: 3 months after monotherapy with an anti-CGRP mAb or onabot injections, and 3 months after combined therapy.
Monotherapy reduced the average number of MMDs from 28 to 18.6, for a reduction of 9.4 days (P > .0001).
After initiation of combined therapy, the average number of MMDs decreased further, from 18.6 MMDs to 12.1 MMDs (P > .0001).
In all, the combination of onabot and anti-CGRP mAbs resulted in a total MMD reduction of 15.8 (P > .0001).
In addition, most patients (68%) reported a 50% or greater reduction in MMDs, and 46.4% reported a 75% or greater reduction.
Great News for Patients
Commenting for this article, Rashmi B. Halker Singh, MD, associate professor of neurology at Mayo Clinic, Scottsdale, Arizona, said the study findings “support what we see in clinical practice and what we suspected from preclinical data.”
Single-agent treatment is not sufficient for many patients. Data confirming the benefit of dual therapy will provide more evidence to insurance companies of the need for coverage.
“We have lots of individuals for whom single treatment is not sufficient and who need this combination of treatment, and it is often denied by insurance. There are preclinical data suggesting synergy, but insurance says it is experimental, so the claims get denied. This leaves patients having to choose which drug they want to continue with, and that’s really heartbreaking,” Dr. Halker Singh said.
The importance of this study is that it adds more data to support evidence-based therapies for migraine and to help patients get the treatment they need, she added.
Dr. Mays reports financial relationships with AbbVie, Amgen, and Teva. Dr. Halker Singh reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM AHS 2023
PFO closure may reduce migraine days and prevent stroke
, according to a discussion at the 2023 Scottsdale Headache Symposium.
In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.
Other right-to-left shunt defects have also been associated with both migraine and stroke, leading Dr. Charles to suggest these defects are more a common denominator.
“Stroke during a migraine is, in fact, very uncommon,” Dr. Charles said. “This raises the possibility that it is not the migraine causing the stroke but rather there is a shared risk factor for stroke and migraine,” said Dr. Charles, referring to PFO as well as other right-to-left shunt defects, such as hereditary hemorrhaging telangiectasia in the lungs.
One Intervention, Two Potential Benefits
Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.
Use of oral contraceptives, which produce a hypercoagulable state, is an example.
“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.
The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
Primary Endpoint Missed in Clinical Trials
The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.
In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).
A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.
There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.
Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.
“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
Migraine Days Might Be a Better Endpoint
For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.
“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.
He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.
One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.
Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.
Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.
“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.
Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”
In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).
The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”
As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.
“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.
Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.
, according to a discussion at the 2023 Scottsdale Headache Symposium.
In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.
Other right-to-left shunt defects have also been associated with both migraine and stroke, leading Dr. Charles to suggest these defects are more a common denominator.
“Stroke during a migraine is, in fact, very uncommon,” Dr. Charles said. “This raises the possibility that it is not the migraine causing the stroke but rather there is a shared risk factor for stroke and migraine,” said Dr. Charles, referring to PFO as well as other right-to-left shunt defects, such as hereditary hemorrhaging telangiectasia in the lungs.
One Intervention, Two Potential Benefits
Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.
Use of oral contraceptives, which produce a hypercoagulable state, is an example.
“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.
The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
Primary Endpoint Missed in Clinical Trials
The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.
In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).
A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.
There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.
Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.
“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
Migraine Days Might Be a Better Endpoint
For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.
“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.
He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.
One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.
Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.
Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.
“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.
Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”
In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).
The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”
As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.
“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.
Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.
, according to a discussion at the 2023 Scottsdale Headache Symposium.
In two clinical trials evaluating whether PFO closure reduces migraine risk, the primary endpoints were not met, but a signal of benefit on secondary endpoints and the association between PFO, migraine, and stroke are among the reasons that PFO closure should be reevaluated, according to Andrew Charles MD, Director of the Goldberg Migraine Program, University of California, Los Angeles.
Other right-to-left shunt defects have also been associated with both migraine and stroke, leading Dr. Charles to suggest these defects are more a common denominator.
“Stroke during a migraine is, in fact, very uncommon,” Dr. Charles said. “This raises the possibility that it is not the migraine causing the stroke but rather there is a shared risk factor for stroke and migraine,” said Dr. Charles, referring to PFO as well as other right-to-left shunt defects, such as hereditary hemorrhaging telangiectasia in the lungs.
One Intervention, Two Potential Benefits
Fixing these defects is therefore at least theoretically attractive for preventing both migraine and stroke, but Dr. Charles said the opportunity for preventing both migraine and stroke is most attractive in migraine patients who have additional stroke risk factors.
Use of oral contraceptives, which produce a hypercoagulable state, is an example.
“Are these the people we should really be thinking about if they have PFO and migraine, particularly migraine with aura?” Dr. Charles asked.
The association between right-to-left shunts and migraine is strong. Although PFO is common, presenting in 20%-25% of the adult population, it has been found in up to 50% of individuals who have migraine with aura. In patients with migraine but no aura, the prevalence of PFO has been estimated to be approximately 35% or still somewhat elevated relative to the general population.
Primary Endpoint Missed in Clinical Trials
The question of whether risk of migraine can be reduced with repair of PFO or other right-to-left shunts remains unresolved. In two high-quality randomized trials undertaken in PFO repair, neither met its primary endpoint. In one of these, called PRIMA, which was terminated early for slow enrollment, the reduction in mean headache attacks was not significant relative to medical therapy.
In the second, called PREMIUM, device closure of PFO also failed to significantly reduce migraine attacks over sham procedure although it was associated with complete migraine remission (10% vs 1%).
A pooled analysis of these two studies that was conducted subsequently concluded that PFO closure reduces mean monthly migraine days (-3.1 vs. -1.9 days; P = -.02) and increases the likelihood of complete migraine cessation (9% vs. 0.7%; P < .001), but Dr. Charles pointed out the primary endpoint was migraine attacks not migraine days, so other analyses can only be considered hypothesis-generating.
There are several reasons to relook at the relationship between migraine and PFO but the potential to prevent both migraine and stroke with PFO closure could be one of the most important.
Several years ago, Dr. Charles and his coinvestigators from UCLA evaluated more than 700 ischemic strokes. Of these, 127 strokes were characterized as cryptogenic because of lack of another identifiable etiology. While 59% of these patients had PFO, which is several times higher than the general population, the prevalence of PFO in patients with a cryptogenic stroke and a history of migraine was 79% in this published study.
“So, in this group of patients who did not have any other clear cause for a stroke, a diagnosis of PFO was very much overrepresented,” Dr. Charles said.
Migraine Days Might Be a Better Endpoint
For patients with migraine who have risk factors for stroke, this makes PFO closure an attractive intervention, but a positive randomized trial is needed. Several are underway. Importantly, the trials now enrolling are using migraine days, which was significantly reduced in both PREMIUM and PRIMA, rather than migraine attacks as the primary endpoint.
“Migraine days is now accepted by the Food and Drug Administration as a criterion of benefit,” reported Jonathan Tobis, MD, Research Director, Interventional Cardiology, UCLA David Geffen School of Medicine, Los Angeles.
He explained that the FDA insisted on migraine attacks as the endpoint for the PREMIUM trial, but this was a far more challenging endpoint on which to show a statistical benefit. He emphasized that a new set of trials will now test efficacy on the basis of migraine days.
One of these trials, called RELIEF, which is randomizing patients to device closure of PFO or a sham procedure. Both groups are receiving clopidogrel or prasugrel based on a previous observation that patients who respond to these drugs are also more likely to respond to PFO closure.
Another trial, called COMPETE-2, is comparing PFO closure with a device to aspirin plus a sham closure. This trial is ongoing in China.
Stroke is not being evaluated as an endpoint in either trial, but Dr. Charles suggested that this does warrant attention.
“I would also just put it out there that, apart from simply migraine, this is a therapeutic approach that we might actually think about in terms of helping to prevent stroke in our migraine patients,” he said.
Senior author of a recent meta-analysis of trials evaluating PFO closure and control of migraine, Ling Liu, MD, Department of Neurology, University of Sichuan, Chengdu, China, agreed that PFO closure for the treatment of migraine deserves “a reevaluation.”
In his meta-analysis of three randomized trials, one pooled study, and eight retrospective case series with 1,165 patients, PFO closure was associated with a nearly 75% reduction (odds ratio [OR], 0.259; P = .0048) reduction in migraine days and 50% increase in resolution of migraine in patients with a history of migraine with aura (OR, 1.586; P = .227).
The incidence of stroke was not evaluated in this meta-analysis, but Dr. Liu believes that the evidence of reducing the burden of migraine with PFO closure is compelling. Given the evidence from this meta-analysis that PFO closure is safe, Dr. Liu maintained that a definitive trial is needed “especially for migraine with frequent aura.”
As an interventional cardiologist, Dr. Tobis said that when PFO closures is performed for prevention of stroke in patients with migraine, it often leads to reduced migraine activity and, in some cases, elimination of migraine. Like others, he believes new analyses should be conducted.
“Everyone involved in this field believes there is something there,” Dr. Tobis said. The missing link is a clinical trial to confirm it.
Dr. Charles and Dr. Liu report no potential conflicts of interest. Dr. Tobis reports a financial relationship with Holistick Medical.
FROM THE 2023 SCOTTSDALE HEADACHE SYMPOSIUM
Drugs to prevent versus those to treat migraine might not share targets
, according to experts attempting to put these puzzle pieces together at the 2023 Scottsdale Headache Symposium.
As the details of the complex chain of molecular events become better understood, there is reason to believe that the targets for aborting events early in the process are not necessarily therapeutic at later stages or vice versa, according to Peter Goadsby, MBBS, MD, PhD, director of the National Institute for Health Research and professor of neurology, King’s College, London.
“I think this explains some of the frustration at trigger modulation. I think we are often trying to modulate a process that has already got started,” he said. The analogy might be closing the barn door after the animals have escaped.
Migraine phases might explain pathology
Given the progress in understanding each step that leads from one phase to the next in migraine onset, this premise is not surprising. Increased blood flow, trigeminal activation, and release of calcitonin gene–related peptide (CGRP) are early events in this process, according to Dr. Goadsby, but there is still uncertainty about the triggers of brainstem stimulation and cranial blood flow that precedes these events.
In his talk about the advances that led to the development of CGRP-targeted therapy, Dr. Goadsby explained how and why CGRP inhibition, along with triptans, pituitary adenylate cyclase–activating polypeptide (PACAP) inhibitors, and ditans, have been developed as treatment targets in migraine, while other once-promising targets, such as substance P inhibition and inducible nitric oxide synthase (INOS) inhibition, have not.
Much of this progress has been by trial and error through clinical studies in which efficacy has or has not been seen. Despite the progress in mapping the release of CGRP and its activity, Dr. Goadsby acknowledged that there is still much about its participation in migraine pathophysiology that remains poorly defined.
“Anyone who tells you that they know how CGRP works I think is blowing smoke, frankly,” Dr. Goadsby said. “Clearly these things are complex.”
CGRP is active in the CSF
This includes the site of action. Dr. Goadsby said that it is widely believed that CGRP inhibitors are active in the dura and not in the cerebrospinal fluid (CSF). However, Dr. Goadsby said that a study undertaken with monoclonal antibodies targeting CGRP have produced compelling evidence that CGRP is reduced in the CSF.
“They clearly get into the CSF,” said Dr. Goadsby, noting that the barrier between peripheral blood and the CSF “is different from the blood-brain barrier.”
Widely regarded as playing a pivotal role in the development of CGRP as a therapeutic target in migraine, Dr. Goadsby spent some time speculating about its potential for preventing the earliest steps in the process that leads from the premonitory state to allodynia, prodromal symptoms, migraine, and postdromal recovery.
Of triggers, “light is my favorite example,” he said. He noted that many patients are convinced that light initiates the subsequent steps that end in a migraine. This is fair assumption for those who have seen a sequence of events in which light in the absence of any other symptom always precedes prodromal symptoms and migraine.
“Why would you not think that?” he asked. “Unless you point out that the attack had already started and the reason that you are noticing the light is because of photophobia that started during the premonitory phase.”
It is increasingly clear that CGRP inhibition does have clinical benefit when started at early signs of a coming migraine, according to Dr. Goadsby. He cited a phase 3 study published just days before he spoke at the Scottsdale Headache Symposium. Called PRODROME, the study associated the CGRP receptor antagonist ubrogepant, which is already approved for treatment of migraine, with a significant reduction in the risk of moderate to severe headache relative to placebo when measured 24 hours after randomization (46% vs. 29%; P < .0001).
Brain activity monitoring supports phases
Citing imaging studies in his own laboratory, Todd J. Schwedt, MD, chair of neurology research, Mayo Clinic, Phoenix, substantiated several of the points made by Dr. Goadsby in a separate talk he made on migraine phases. By monitoring brain activity during each phase of migraine, he suggested his data support the role of CGRP in producing an inflammatory response as well as sensitizing the trigeminal cervical system in steps that appear to be important to the pain process.
Dr. Schwedt showed several pieces of evidence suggesting that CGRP is an early mediator even if it is not necessarily the first step in a process for every patient. However, like Dr. Goadsby, Dr. Schwedt also acknowledged that the interplay between events is complex and might differ between patients.
Yet, he says that brain activity on imaging is not the only evidence of the role of CGRP activation early in the process leading toward migraine.
“I am a little biased towards imaging, but it’s not just about imaging,” Dr. Schwedt said.
“If we look at preictal salivary CGRP levels and then follow them into the headache phase, we see the levels increase, but they go back to normal a couple of hours into the attack and then stay normal, presumably, until the patient gets closer to the next attack,” Dr. Schwedt said.
Despite progress there is more to be done to determine why CGRP is released and whether it can be inhibited early to abort migraine before the headache phase, but both Dr. Goadsby and Dr. Schwedt pointed to this as a very early event. This is not to say that others, such as cortical spreading depression, do not have an equally important role in the evolution of migraine, but each expert considers migraine phases to be useful divisions for tracing the sequence of pathogenic events.
The phase of a migraine attack and their corresponding symptoms “can be mapped to altered brain function and release of neuropeptides and neurotransmitters,” Dr. Schwedt said. The implication is that better targets for blocking migraine before it reaches the headache phase might be discovered in these early phases.
Dr. Goadsby and Dr. Schwedt listed more than 10 pharmaceutical companies to which they have financial relationships, but both claimed that none of these relationships posed a potential conflict of interest.
, according to experts attempting to put these puzzle pieces together at the 2023 Scottsdale Headache Symposium.
As the details of the complex chain of molecular events become better understood, there is reason to believe that the targets for aborting events early in the process are not necessarily therapeutic at later stages or vice versa, according to Peter Goadsby, MBBS, MD, PhD, director of the National Institute for Health Research and professor of neurology, King’s College, London.
“I think this explains some of the frustration at trigger modulation. I think we are often trying to modulate a process that has already got started,” he said. The analogy might be closing the barn door after the animals have escaped.
Migraine phases might explain pathology
Given the progress in understanding each step that leads from one phase to the next in migraine onset, this premise is not surprising. Increased blood flow, trigeminal activation, and release of calcitonin gene–related peptide (CGRP) are early events in this process, according to Dr. Goadsby, but there is still uncertainty about the triggers of brainstem stimulation and cranial blood flow that precedes these events.
In his talk about the advances that led to the development of CGRP-targeted therapy, Dr. Goadsby explained how and why CGRP inhibition, along with triptans, pituitary adenylate cyclase–activating polypeptide (PACAP) inhibitors, and ditans, have been developed as treatment targets in migraine, while other once-promising targets, such as substance P inhibition and inducible nitric oxide synthase (INOS) inhibition, have not.
Much of this progress has been by trial and error through clinical studies in which efficacy has or has not been seen. Despite the progress in mapping the release of CGRP and its activity, Dr. Goadsby acknowledged that there is still much about its participation in migraine pathophysiology that remains poorly defined.
“Anyone who tells you that they know how CGRP works I think is blowing smoke, frankly,” Dr. Goadsby said. “Clearly these things are complex.”
CGRP is active in the CSF
This includes the site of action. Dr. Goadsby said that it is widely believed that CGRP inhibitors are active in the dura and not in the cerebrospinal fluid (CSF). However, Dr. Goadsby said that a study undertaken with monoclonal antibodies targeting CGRP have produced compelling evidence that CGRP is reduced in the CSF.
“They clearly get into the CSF,” said Dr. Goadsby, noting that the barrier between peripheral blood and the CSF “is different from the blood-brain barrier.”
Widely regarded as playing a pivotal role in the development of CGRP as a therapeutic target in migraine, Dr. Goadsby spent some time speculating about its potential for preventing the earliest steps in the process that leads from the premonitory state to allodynia, prodromal symptoms, migraine, and postdromal recovery.
Of triggers, “light is my favorite example,” he said. He noted that many patients are convinced that light initiates the subsequent steps that end in a migraine. This is fair assumption for those who have seen a sequence of events in which light in the absence of any other symptom always precedes prodromal symptoms and migraine.
“Why would you not think that?” he asked. “Unless you point out that the attack had already started and the reason that you are noticing the light is because of photophobia that started during the premonitory phase.”
It is increasingly clear that CGRP inhibition does have clinical benefit when started at early signs of a coming migraine, according to Dr. Goadsby. He cited a phase 3 study published just days before he spoke at the Scottsdale Headache Symposium. Called PRODROME, the study associated the CGRP receptor antagonist ubrogepant, which is already approved for treatment of migraine, with a significant reduction in the risk of moderate to severe headache relative to placebo when measured 24 hours after randomization (46% vs. 29%; P < .0001).
Brain activity monitoring supports phases
Citing imaging studies in his own laboratory, Todd J. Schwedt, MD, chair of neurology research, Mayo Clinic, Phoenix, substantiated several of the points made by Dr. Goadsby in a separate talk he made on migraine phases. By monitoring brain activity during each phase of migraine, he suggested his data support the role of CGRP in producing an inflammatory response as well as sensitizing the trigeminal cervical system in steps that appear to be important to the pain process.
Dr. Schwedt showed several pieces of evidence suggesting that CGRP is an early mediator even if it is not necessarily the first step in a process for every patient. However, like Dr. Goadsby, Dr. Schwedt also acknowledged that the interplay between events is complex and might differ between patients.
Yet, he says that brain activity on imaging is not the only evidence of the role of CGRP activation early in the process leading toward migraine.
“I am a little biased towards imaging, but it’s not just about imaging,” Dr. Schwedt said.
“If we look at preictal salivary CGRP levels and then follow them into the headache phase, we see the levels increase, but they go back to normal a couple of hours into the attack and then stay normal, presumably, until the patient gets closer to the next attack,” Dr. Schwedt said.
Despite progress there is more to be done to determine why CGRP is released and whether it can be inhibited early to abort migraine before the headache phase, but both Dr. Goadsby and Dr. Schwedt pointed to this as a very early event. This is not to say that others, such as cortical spreading depression, do not have an equally important role in the evolution of migraine, but each expert considers migraine phases to be useful divisions for tracing the sequence of pathogenic events.
The phase of a migraine attack and their corresponding symptoms “can be mapped to altered brain function and release of neuropeptides and neurotransmitters,” Dr. Schwedt said. The implication is that better targets for blocking migraine before it reaches the headache phase might be discovered in these early phases.
Dr. Goadsby and Dr. Schwedt listed more than 10 pharmaceutical companies to which they have financial relationships, but both claimed that none of these relationships posed a potential conflict of interest.
, according to experts attempting to put these puzzle pieces together at the 2023 Scottsdale Headache Symposium.
As the details of the complex chain of molecular events become better understood, there is reason to believe that the targets for aborting events early in the process are not necessarily therapeutic at later stages or vice versa, according to Peter Goadsby, MBBS, MD, PhD, director of the National Institute for Health Research and professor of neurology, King’s College, London.
“I think this explains some of the frustration at trigger modulation. I think we are often trying to modulate a process that has already got started,” he said. The analogy might be closing the barn door after the animals have escaped.
Migraine phases might explain pathology
Given the progress in understanding each step that leads from one phase to the next in migraine onset, this premise is not surprising. Increased blood flow, trigeminal activation, and release of calcitonin gene–related peptide (CGRP) are early events in this process, according to Dr. Goadsby, but there is still uncertainty about the triggers of brainstem stimulation and cranial blood flow that precedes these events.
In his talk about the advances that led to the development of CGRP-targeted therapy, Dr. Goadsby explained how and why CGRP inhibition, along with triptans, pituitary adenylate cyclase–activating polypeptide (PACAP) inhibitors, and ditans, have been developed as treatment targets in migraine, while other once-promising targets, such as substance P inhibition and inducible nitric oxide synthase (INOS) inhibition, have not.
Much of this progress has been by trial and error through clinical studies in which efficacy has or has not been seen. Despite the progress in mapping the release of CGRP and its activity, Dr. Goadsby acknowledged that there is still much about its participation in migraine pathophysiology that remains poorly defined.
“Anyone who tells you that they know how CGRP works I think is blowing smoke, frankly,” Dr. Goadsby said. “Clearly these things are complex.”
CGRP is active in the CSF
This includes the site of action. Dr. Goadsby said that it is widely believed that CGRP inhibitors are active in the dura and not in the cerebrospinal fluid (CSF). However, Dr. Goadsby said that a study undertaken with monoclonal antibodies targeting CGRP have produced compelling evidence that CGRP is reduced in the CSF.
“They clearly get into the CSF,” said Dr. Goadsby, noting that the barrier between peripheral blood and the CSF “is different from the blood-brain barrier.”
Widely regarded as playing a pivotal role in the development of CGRP as a therapeutic target in migraine, Dr. Goadsby spent some time speculating about its potential for preventing the earliest steps in the process that leads from the premonitory state to allodynia, prodromal symptoms, migraine, and postdromal recovery.
Of triggers, “light is my favorite example,” he said. He noted that many patients are convinced that light initiates the subsequent steps that end in a migraine. This is fair assumption for those who have seen a sequence of events in which light in the absence of any other symptom always precedes prodromal symptoms and migraine.
“Why would you not think that?” he asked. “Unless you point out that the attack had already started and the reason that you are noticing the light is because of photophobia that started during the premonitory phase.”
It is increasingly clear that CGRP inhibition does have clinical benefit when started at early signs of a coming migraine, according to Dr. Goadsby. He cited a phase 3 study published just days before he spoke at the Scottsdale Headache Symposium. Called PRODROME, the study associated the CGRP receptor antagonist ubrogepant, which is already approved for treatment of migraine, with a significant reduction in the risk of moderate to severe headache relative to placebo when measured 24 hours after randomization (46% vs. 29%; P < .0001).
Brain activity monitoring supports phases
Citing imaging studies in his own laboratory, Todd J. Schwedt, MD, chair of neurology research, Mayo Clinic, Phoenix, substantiated several of the points made by Dr. Goadsby in a separate talk he made on migraine phases. By monitoring brain activity during each phase of migraine, he suggested his data support the role of CGRP in producing an inflammatory response as well as sensitizing the trigeminal cervical system in steps that appear to be important to the pain process.
Dr. Schwedt showed several pieces of evidence suggesting that CGRP is an early mediator even if it is not necessarily the first step in a process for every patient. However, like Dr. Goadsby, Dr. Schwedt also acknowledged that the interplay between events is complex and might differ between patients.
Yet, he says that brain activity on imaging is not the only evidence of the role of CGRP activation early in the process leading toward migraine.
“I am a little biased towards imaging, but it’s not just about imaging,” Dr. Schwedt said.
“If we look at preictal salivary CGRP levels and then follow them into the headache phase, we see the levels increase, but they go back to normal a couple of hours into the attack and then stay normal, presumably, until the patient gets closer to the next attack,” Dr. Schwedt said.
Despite progress there is more to be done to determine why CGRP is released and whether it can be inhibited early to abort migraine before the headache phase, but both Dr. Goadsby and Dr. Schwedt pointed to this as a very early event. This is not to say that others, such as cortical spreading depression, do not have an equally important role in the evolution of migraine, but each expert considers migraine phases to be useful divisions for tracing the sequence of pathogenic events.
The phase of a migraine attack and their corresponding symptoms “can be mapped to altered brain function and release of neuropeptides and neurotransmitters,” Dr. Schwedt said. The implication is that better targets for blocking migraine before it reaches the headache phase might be discovered in these early phases.
Dr. Goadsby and Dr. Schwedt listed more than 10 pharmaceutical companies to which they have financial relationships, but both claimed that none of these relationships posed a potential conflict of interest.
FROM THE 2023 SCOTTSDALE HEADACHE SYMPOSIUM
Adolescents with migraine need smooth handoff to adult care
, according to a headache specialist who treats adults and children and spoke at the 2023 Scottsdale Headache Symposium.
“I would start at about the age of 15 or 16,” said Hope L. O’Brien, MD, Headache Center of Hope, University of Cincinnati.
Describing the steps that she thinks should be included in an effective transition, Dr. O’Brien maintained, “you will have a greater chance of successful transition and lessen the likelihood of the chronicity and the poor outcomes that we see in adults.”
Dr. O’Brien, who developed a headache clinic that serves individuals between the ages of 15 and 27, has substantial experience with headache patients in this age range. She acknowledged that there are no guideline recommendations for how best to guide the transition from pediatric to adult care, but she has developed some strategies at her own institution, including a tool for determining when the transition should be considered.
“Transition readiness is something that you need to think about,” she said. “You don’t just do it [automatically] at the age of 18.”
TRAQ questionnaire is helpful
The Transition Readiness Assessment Questionnaire (TRAQ) is one tool that can be helpful, according to Dr. O’Brien, This tool, which can be used to evaluate whether young patients feel prepared to describe their own health status and needs and advocate on their own behalf, is not specific to headache, but the principle is particularly important in headache because of the importance of the patient’s history. Dr. O’Brien said that a fellow in her program, Allyson Bazarsky, MD, who is now affiliated with the University of Vermont Medical Center, Burlington, validated TRAQ for headache about 6 years ago.
“TRAQ is available online. It’s free. You can download it as a PDF,” Dr. O’Brien said. In fact, several age-specific versions can now be found readily on a web search for TRAQ questionnaire.
Ultimately, TRAQ helps the clinician to gauge what patients know about their disease, the medications they are taking, and the relevance of any comorbidities, such as mood disorders. It also provides insight about the ability to understand their health issues and to communicate well with caregivers.
Dr. O’Brien sees this as a process over time, rather than something to be implemented a few months before the transition.
“It is important to start making the shift during childhood and talking directly to the child,” Dr. O’Brien said. If education about the disease and its triggers are started relatively early in adolescence, the transition will not only be easier, but patients might have a chance to understand and control their disease at an earlier age.
With this kind of approach, most children are at least in the preparation stage by age 18 years. However, the age at which patients are suitable for transition varies substantially. Many patients 18 years of age or older are in the “action phase,” meaning it is time to take steps to transition.
Again, based on the interrelationship between headache and comorbidities, particularly mood disorders, such as depression and anxiety, the goal should not be limited to headache. Young adults should be educated about taking responsibility for their overall health.
In addition to educating the patient, Dr. O’Brien recommended preparing a transfer packet, such as the one described in an article published in Headache. Geared for communicating with the clinician who will take over care, the contents should include a detailed medical history along with the current treatment plan and list of medications that have been effective and those that have failed, according to Dr. O’Brien.
“An emergency plan in the form of an emergency department letter in case the patient needs to seek emergent care at an outside facility” is also appropriate, Dr. O’Brien said.
The patient should be aware of what is in the transfer pack in order to participate in an informed discussion of health care with the adult neurologist.
Poor transition linked to poor outcomes
A substantial proportion of adolescents with migraine continue to experience episodes as an adult, particularly those with a delayed diagnosis of migraine, those with a first degree relative who has migraine, and those with poor health habits, but this is not inevitable. Dr. O’Brien noted that “unsuccessful transition of care” into adulthood is a factor associated with poorer outcomes, making it an appropriate target for optimizing outcomes.
“Have that discussion on transfer of care with an action plan and do that early, especially in those with chronic or persistent disability headaches,” Dr. O’Brien emphasized.
This is pertinent advice, according to Amy A. Gelfand, MD, director of the child and adolescent headache program at Benioff Children’s Hospitals, University of California, San Francisco. Senior author of a comprehensive review article on pediatric migraine in Neurologic Clinics, Dr. Gelfand said the practical value of young adults learning what medications they are taking, and why, can place them in a better position to monitor their disease and to understand when a clinical visit is appropriate.
“I agree that it is important to help young adults (i.e., 18- or 19-year-olds) to prepare for the transition from the pediatric health care environment to the adult one,” said Dr. Gelfand, who has written frequently on this and related topics, such as the impact of comorbidities on outcome.
Dr. O’Brien reports financial relationships with AbbVie, Eli Lilly, Guidepoint, Pfizer, and Vector Psychometric Group. Dr. Gelfand reports financial relationships with Allergan, Eli Lilly, EMKinetics, eNeura, Teva and Zosano.
, according to a headache specialist who treats adults and children and spoke at the 2023 Scottsdale Headache Symposium.
“I would start at about the age of 15 or 16,” said Hope L. O’Brien, MD, Headache Center of Hope, University of Cincinnati.
Describing the steps that she thinks should be included in an effective transition, Dr. O’Brien maintained, “you will have a greater chance of successful transition and lessen the likelihood of the chronicity and the poor outcomes that we see in adults.”
Dr. O’Brien, who developed a headache clinic that serves individuals between the ages of 15 and 27, has substantial experience with headache patients in this age range. She acknowledged that there are no guideline recommendations for how best to guide the transition from pediatric to adult care, but she has developed some strategies at her own institution, including a tool for determining when the transition should be considered.
“Transition readiness is something that you need to think about,” she said. “You don’t just do it [automatically] at the age of 18.”
TRAQ questionnaire is helpful
The Transition Readiness Assessment Questionnaire (TRAQ) is one tool that can be helpful, according to Dr. O’Brien, This tool, which can be used to evaluate whether young patients feel prepared to describe their own health status and needs and advocate on their own behalf, is not specific to headache, but the principle is particularly important in headache because of the importance of the patient’s history. Dr. O’Brien said that a fellow in her program, Allyson Bazarsky, MD, who is now affiliated with the University of Vermont Medical Center, Burlington, validated TRAQ for headache about 6 years ago.
“TRAQ is available online. It’s free. You can download it as a PDF,” Dr. O’Brien said. In fact, several age-specific versions can now be found readily on a web search for TRAQ questionnaire.
Ultimately, TRAQ helps the clinician to gauge what patients know about their disease, the medications they are taking, and the relevance of any comorbidities, such as mood disorders. It also provides insight about the ability to understand their health issues and to communicate well with caregivers.
Dr. O’Brien sees this as a process over time, rather than something to be implemented a few months before the transition.
“It is important to start making the shift during childhood and talking directly to the child,” Dr. O’Brien said. If education about the disease and its triggers are started relatively early in adolescence, the transition will not only be easier, but patients might have a chance to understand and control their disease at an earlier age.
With this kind of approach, most children are at least in the preparation stage by age 18 years. However, the age at which patients are suitable for transition varies substantially. Many patients 18 years of age or older are in the “action phase,” meaning it is time to take steps to transition.
Again, based on the interrelationship between headache and comorbidities, particularly mood disorders, such as depression and anxiety, the goal should not be limited to headache. Young adults should be educated about taking responsibility for their overall health.
In addition to educating the patient, Dr. O’Brien recommended preparing a transfer packet, such as the one described in an article published in Headache. Geared for communicating with the clinician who will take over care, the contents should include a detailed medical history along with the current treatment plan and list of medications that have been effective and those that have failed, according to Dr. O’Brien.
“An emergency plan in the form of an emergency department letter in case the patient needs to seek emergent care at an outside facility” is also appropriate, Dr. O’Brien said.
The patient should be aware of what is in the transfer pack in order to participate in an informed discussion of health care with the adult neurologist.
Poor transition linked to poor outcomes
A substantial proportion of adolescents with migraine continue to experience episodes as an adult, particularly those with a delayed diagnosis of migraine, those with a first degree relative who has migraine, and those with poor health habits, but this is not inevitable. Dr. O’Brien noted that “unsuccessful transition of care” into adulthood is a factor associated with poorer outcomes, making it an appropriate target for optimizing outcomes.
“Have that discussion on transfer of care with an action plan and do that early, especially in those with chronic or persistent disability headaches,” Dr. O’Brien emphasized.
This is pertinent advice, according to Amy A. Gelfand, MD, director of the child and adolescent headache program at Benioff Children’s Hospitals, University of California, San Francisco. Senior author of a comprehensive review article on pediatric migraine in Neurologic Clinics, Dr. Gelfand said the practical value of young adults learning what medications they are taking, and why, can place them in a better position to monitor their disease and to understand when a clinical visit is appropriate.
“I agree that it is important to help young adults (i.e., 18- or 19-year-olds) to prepare for the transition from the pediatric health care environment to the adult one,” said Dr. Gelfand, who has written frequently on this and related topics, such as the impact of comorbidities on outcome.
Dr. O’Brien reports financial relationships with AbbVie, Eli Lilly, Guidepoint, Pfizer, and Vector Psychometric Group. Dr. Gelfand reports financial relationships with Allergan, Eli Lilly, EMKinetics, eNeura, Teva and Zosano.
, according to a headache specialist who treats adults and children and spoke at the 2023 Scottsdale Headache Symposium.
“I would start at about the age of 15 or 16,” said Hope L. O’Brien, MD, Headache Center of Hope, University of Cincinnati.
Describing the steps that she thinks should be included in an effective transition, Dr. O’Brien maintained, “you will have a greater chance of successful transition and lessen the likelihood of the chronicity and the poor outcomes that we see in adults.”
Dr. O’Brien, who developed a headache clinic that serves individuals between the ages of 15 and 27, has substantial experience with headache patients in this age range. She acknowledged that there are no guideline recommendations for how best to guide the transition from pediatric to adult care, but she has developed some strategies at her own institution, including a tool for determining when the transition should be considered.
“Transition readiness is something that you need to think about,” she said. “You don’t just do it [automatically] at the age of 18.”
TRAQ questionnaire is helpful
The Transition Readiness Assessment Questionnaire (TRAQ) is one tool that can be helpful, according to Dr. O’Brien, This tool, which can be used to evaluate whether young patients feel prepared to describe their own health status and needs and advocate on their own behalf, is not specific to headache, but the principle is particularly important in headache because of the importance of the patient’s history. Dr. O’Brien said that a fellow in her program, Allyson Bazarsky, MD, who is now affiliated with the University of Vermont Medical Center, Burlington, validated TRAQ for headache about 6 years ago.
“TRAQ is available online. It’s free. You can download it as a PDF,” Dr. O’Brien said. In fact, several age-specific versions can now be found readily on a web search for TRAQ questionnaire.
Ultimately, TRAQ helps the clinician to gauge what patients know about their disease, the medications they are taking, and the relevance of any comorbidities, such as mood disorders. It also provides insight about the ability to understand their health issues and to communicate well with caregivers.
Dr. O’Brien sees this as a process over time, rather than something to be implemented a few months before the transition.
“It is important to start making the shift during childhood and talking directly to the child,” Dr. O’Brien said. If education about the disease and its triggers are started relatively early in adolescence, the transition will not only be easier, but patients might have a chance to understand and control their disease at an earlier age.
With this kind of approach, most children are at least in the preparation stage by age 18 years. However, the age at which patients are suitable for transition varies substantially. Many patients 18 years of age or older are in the “action phase,” meaning it is time to take steps to transition.
Again, based on the interrelationship between headache and comorbidities, particularly mood disorders, such as depression and anxiety, the goal should not be limited to headache. Young adults should be educated about taking responsibility for their overall health.
In addition to educating the patient, Dr. O’Brien recommended preparing a transfer packet, such as the one described in an article published in Headache. Geared for communicating with the clinician who will take over care, the contents should include a detailed medical history along with the current treatment plan and list of medications that have been effective and those that have failed, according to Dr. O’Brien.
“An emergency plan in the form of an emergency department letter in case the patient needs to seek emergent care at an outside facility” is also appropriate, Dr. O’Brien said.
The patient should be aware of what is in the transfer pack in order to participate in an informed discussion of health care with the adult neurologist.
Poor transition linked to poor outcomes
A substantial proportion of adolescents with migraine continue to experience episodes as an adult, particularly those with a delayed diagnosis of migraine, those with a first degree relative who has migraine, and those with poor health habits, but this is not inevitable. Dr. O’Brien noted that “unsuccessful transition of care” into adulthood is a factor associated with poorer outcomes, making it an appropriate target for optimizing outcomes.
“Have that discussion on transfer of care with an action plan and do that early, especially in those with chronic or persistent disability headaches,” Dr. O’Brien emphasized.
This is pertinent advice, according to Amy A. Gelfand, MD, director of the child and adolescent headache program at Benioff Children’s Hospitals, University of California, San Francisco. Senior author of a comprehensive review article on pediatric migraine in Neurologic Clinics, Dr. Gelfand said the practical value of young adults learning what medications they are taking, and why, can place them in a better position to monitor their disease and to understand when a clinical visit is appropriate.
“I agree that it is important to help young adults (i.e., 18- or 19-year-olds) to prepare for the transition from the pediatric health care environment to the adult one,” said Dr. Gelfand, who has written frequently on this and related topics, such as the impact of comorbidities on outcome.
Dr. O’Brien reports financial relationships with AbbVie, Eli Lilly, Guidepoint, Pfizer, and Vector Psychometric Group. Dr. Gelfand reports financial relationships with Allergan, Eli Lilly, EMKinetics, eNeura, Teva and Zosano.
FROM THE 2023 SCOTTSDALE HEADACHE SYMPOSIUM
Avoid adding to minority stress when treating headache in LGBTQIA+ patients
It is “important not to assume that just because someone is a member of the LGBTQ+ community they will need psychiatric or behavioral health support,” said Maya A. Marzouk, PhD, division of behavioral medicine and clinical psychology, Cincinnati Children’s Hospital Medical Center.
Instead, it is useful not to make any assumptions. There is a potential association between minority status and headache susceptibility, but it is more reasonable initially to address the diagnosis and treatment of headache in LGBTQIA+ patients the same way it is addressed in any other patient, Dr. Marzouk said at the 2023 Scottsdale Headache Symposium.
The acronym to describe individuals with gender identities different from male and female and sexual orientations not limited to heterosexuality has been in almost constant evolution over several decades. An addition sign that accompanies LGBTQIA refers to those who do not identify with any letters in the acronym (lesbian, gay, bisexual, transsexual, queer/questioning, intersex, and asexual).
Take steps to normalize the interaction
Although many clinicians have been acclimated to these diverse identifies, not all have risen above preconceptions that become obstacles to effective care, according to Dr. Marzouk. In the context of headache management, Dr. Marzouk emphasized the need to be respectful of the range of gender identities and sexual orientations and to take steps to normalize the interaction.
For example, Dr. Marzouk advised using gender-neutral language at the start of each patient encounter and ask open-ended questions about gender, sexual identify, and pronouns to avoid patient discomfort from misidentification. In turn, the clinicians can establish their own gender identification and preferred pronouns to reinforce the idea that doing so is normal behavior.
This change in approach should be made “for all patients. Do not try to guess who needs them,” she said.
Intake forms and office atmosphere, such as signs and images, should also be welcoming to all patients, she added. Rather than trying to make adjustments for a LGBTQIA+ visit, Dr. Marzouk said a uniform approach helps normalize the experience of LGBTQIA+ patients without singling them out.
Despite the effort to provide an open and welcoming environment, Dr. Marzouk acknowledged that mistakes are difficult to avoid for those with limited experience serving the LGBTQIA+ community. When mistakes are made, she advised clinicians to immediately acknowledge the mistake and ask for guidance from the patient.
The potential offense is making the patient feel “other” or abnormal.
A higher rate of migraine
The interactions that LBGTQIA+ patients have with others outside their community is a possible explanation for the substantial rate of headache as well as headache with comorbid psychiatric disorders in this population.
In a survey published in 2020, the rate of migraine was 19.7% in heterosexual women, 26.7% in lesbians, and 36.8% in bisexual women. Among men, it rose from 9.8% in heterosexuals to 14.8% in gays and then to 22.8% in bisexuals.
Migraine relative to headache is also associated with more mood disorders among LGBTQIA+ individuals. In a study published in 2022, LGBTQIA+ patients with migraine relative to those with headache were more likely to have depression (46.4% vs. 22.3%; P < .001), anxiety (72.1% vs. 51.6%; P < .001), and posttraumatic stress disorder (37.5% vs. 21.4%; P < .001).
A vicious cycle of underdiagnosis and undertreatment
These associations are consistent with minority stress theory, according to Dr. Marzouk. This theory postulates that the associated stress of discrimination, rejection, and microaggressions, such as explicit efforts to make LGBTQIA+ individuals to feel “other,” produces epigenetic changes and dysregulation of the hypothalamic-pituitary-adrenal axis. In turn, this plays a role in the pathogenesis of migraine.
The inconsistency with which minority stress affects LGBTQIA+ patients might be due to relative differences in social support, coping skills, an innate resilience to these effects, Dr. Marzouk explained.
Dr. Marzouk characterized the LGBTQIA+ community as “underserved” for treatment of headache. She suggested that medical mistrust and self-blame among LGBTQIA+ individuals might be factors contributing to a vicious cycle of underdiagnosis and undertreatment. Efforts by the medical community to reach out to the LGBTQIA+ community are appropriate to address an unmet need.
“Individuals with psychiatric comorbidities may experience even more benefit from migraine care,” she said.
Clinical studies should be more inclusive
While agreeing in principle with these remarks, Eric A. Kaiser, MD, PhD, department of neurology, University of Pennsylvania, Philadelphia, said that this area would be better advanced if studies routinely included patients with diverse-gender identities and sexual orientations. Speaking about how to organize these studies, Dr. Kaiser suggested that enrollment criteria should explicitly seek these individuals and that these differences should be captured in the baseline characteristics.
“For example, gender options could include man, woman, non-binary, gender diverse, gender nonconforming, or gender nonspecified,” he said.
To close “the significant knowledge gap that exists in managing headache disorders in sexually- and gender- diverse people,” Dr. Kaiser said that clinical research studies, like patient treatment of diverse populations, “should be conducted with welcoming and affirming practices.”
Dr. Marzouk reported no potential conflicts of interest. Dr. Kaiser reported financial relationships with Amgen and Lundbeck.
It is “important not to assume that just because someone is a member of the LGBTQ+ community they will need psychiatric or behavioral health support,” said Maya A. Marzouk, PhD, division of behavioral medicine and clinical psychology, Cincinnati Children’s Hospital Medical Center.
Instead, it is useful not to make any assumptions. There is a potential association between minority status and headache susceptibility, but it is more reasonable initially to address the diagnosis and treatment of headache in LGBTQIA+ patients the same way it is addressed in any other patient, Dr. Marzouk said at the 2023 Scottsdale Headache Symposium.
The acronym to describe individuals with gender identities different from male and female and sexual orientations not limited to heterosexuality has been in almost constant evolution over several decades. An addition sign that accompanies LGBTQIA refers to those who do not identify with any letters in the acronym (lesbian, gay, bisexual, transsexual, queer/questioning, intersex, and asexual).
Take steps to normalize the interaction
Although many clinicians have been acclimated to these diverse identifies, not all have risen above preconceptions that become obstacles to effective care, according to Dr. Marzouk. In the context of headache management, Dr. Marzouk emphasized the need to be respectful of the range of gender identities and sexual orientations and to take steps to normalize the interaction.
For example, Dr. Marzouk advised using gender-neutral language at the start of each patient encounter and ask open-ended questions about gender, sexual identify, and pronouns to avoid patient discomfort from misidentification. In turn, the clinicians can establish their own gender identification and preferred pronouns to reinforce the idea that doing so is normal behavior.
This change in approach should be made “for all patients. Do not try to guess who needs them,” she said.
Intake forms and office atmosphere, such as signs and images, should also be welcoming to all patients, she added. Rather than trying to make adjustments for a LGBTQIA+ visit, Dr. Marzouk said a uniform approach helps normalize the experience of LGBTQIA+ patients without singling them out.
Despite the effort to provide an open and welcoming environment, Dr. Marzouk acknowledged that mistakes are difficult to avoid for those with limited experience serving the LGBTQIA+ community. When mistakes are made, she advised clinicians to immediately acknowledge the mistake and ask for guidance from the patient.
The potential offense is making the patient feel “other” or abnormal.
A higher rate of migraine
The interactions that LBGTQIA+ patients have with others outside their community is a possible explanation for the substantial rate of headache as well as headache with comorbid psychiatric disorders in this population.
In a survey published in 2020, the rate of migraine was 19.7% in heterosexual women, 26.7% in lesbians, and 36.8% in bisexual women. Among men, it rose from 9.8% in heterosexuals to 14.8% in gays and then to 22.8% in bisexuals.
Migraine relative to headache is also associated with more mood disorders among LGBTQIA+ individuals. In a study published in 2022, LGBTQIA+ patients with migraine relative to those with headache were more likely to have depression (46.4% vs. 22.3%; P < .001), anxiety (72.1% vs. 51.6%; P < .001), and posttraumatic stress disorder (37.5% vs. 21.4%; P < .001).
A vicious cycle of underdiagnosis and undertreatment
These associations are consistent with minority stress theory, according to Dr. Marzouk. This theory postulates that the associated stress of discrimination, rejection, and microaggressions, such as explicit efforts to make LGBTQIA+ individuals to feel “other,” produces epigenetic changes and dysregulation of the hypothalamic-pituitary-adrenal axis. In turn, this plays a role in the pathogenesis of migraine.
The inconsistency with which minority stress affects LGBTQIA+ patients might be due to relative differences in social support, coping skills, an innate resilience to these effects, Dr. Marzouk explained.
Dr. Marzouk characterized the LGBTQIA+ community as “underserved” for treatment of headache. She suggested that medical mistrust and self-blame among LGBTQIA+ individuals might be factors contributing to a vicious cycle of underdiagnosis and undertreatment. Efforts by the medical community to reach out to the LGBTQIA+ community are appropriate to address an unmet need.
“Individuals with psychiatric comorbidities may experience even more benefit from migraine care,” she said.
Clinical studies should be more inclusive
While agreeing in principle with these remarks, Eric A. Kaiser, MD, PhD, department of neurology, University of Pennsylvania, Philadelphia, said that this area would be better advanced if studies routinely included patients with diverse-gender identities and sexual orientations. Speaking about how to organize these studies, Dr. Kaiser suggested that enrollment criteria should explicitly seek these individuals and that these differences should be captured in the baseline characteristics.
“For example, gender options could include man, woman, non-binary, gender diverse, gender nonconforming, or gender nonspecified,” he said.
To close “the significant knowledge gap that exists in managing headache disorders in sexually- and gender- diverse people,” Dr. Kaiser said that clinical research studies, like patient treatment of diverse populations, “should be conducted with welcoming and affirming practices.”
Dr. Marzouk reported no potential conflicts of interest. Dr. Kaiser reported financial relationships with Amgen and Lundbeck.
It is “important not to assume that just because someone is a member of the LGBTQ+ community they will need psychiatric or behavioral health support,” said Maya A. Marzouk, PhD, division of behavioral medicine and clinical psychology, Cincinnati Children’s Hospital Medical Center.
Instead, it is useful not to make any assumptions. There is a potential association between minority status and headache susceptibility, but it is more reasonable initially to address the diagnosis and treatment of headache in LGBTQIA+ patients the same way it is addressed in any other patient, Dr. Marzouk said at the 2023 Scottsdale Headache Symposium.
The acronym to describe individuals with gender identities different from male and female and sexual orientations not limited to heterosexuality has been in almost constant evolution over several decades. An addition sign that accompanies LGBTQIA refers to those who do not identify with any letters in the acronym (lesbian, gay, bisexual, transsexual, queer/questioning, intersex, and asexual).
Take steps to normalize the interaction
Although many clinicians have been acclimated to these diverse identifies, not all have risen above preconceptions that become obstacles to effective care, according to Dr. Marzouk. In the context of headache management, Dr. Marzouk emphasized the need to be respectful of the range of gender identities and sexual orientations and to take steps to normalize the interaction.
For example, Dr. Marzouk advised using gender-neutral language at the start of each patient encounter and ask open-ended questions about gender, sexual identify, and pronouns to avoid patient discomfort from misidentification. In turn, the clinicians can establish their own gender identification and preferred pronouns to reinforce the idea that doing so is normal behavior.
This change in approach should be made “for all patients. Do not try to guess who needs them,” she said.
Intake forms and office atmosphere, such as signs and images, should also be welcoming to all patients, she added. Rather than trying to make adjustments for a LGBTQIA+ visit, Dr. Marzouk said a uniform approach helps normalize the experience of LGBTQIA+ patients without singling them out.
Despite the effort to provide an open and welcoming environment, Dr. Marzouk acknowledged that mistakes are difficult to avoid for those with limited experience serving the LGBTQIA+ community. When mistakes are made, she advised clinicians to immediately acknowledge the mistake and ask for guidance from the patient.
The potential offense is making the patient feel “other” or abnormal.
A higher rate of migraine
The interactions that LBGTQIA+ patients have with others outside their community is a possible explanation for the substantial rate of headache as well as headache with comorbid psychiatric disorders in this population.
In a survey published in 2020, the rate of migraine was 19.7% in heterosexual women, 26.7% in lesbians, and 36.8% in bisexual women. Among men, it rose from 9.8% in heterosexuals to 14.8% in gays and then to 22.8% in bisexuals.
Migraine relative to headache is also associated with more mood disorders among LGBTQIA+ individuals. In a study published in 2022, LGBTQIA+ patients with migraine relative to those with headache were more likely to have depression (46.4% vs. 22.3%; P < .001), anxiety (72.1% vs. 51.6%; P < .001), and posttraumatic stress disorder (37.5% vs. 21.4%; P < .001).
A vicious cycle of underdiagnosis and undertreatment
These associations are consistent with minority stress theory, according to Dr. Marzouk. This theory postulates that the associated stress of discrimination, rejection, and microaggressions, such as explicit efforts to make LGBTQIA+ individuals to feel “other,” produces epigenetic changes and dysregulation of the hypothalamic-pituitary-adrenal axis. In turn, this plays a role in the pathogenesis of migraine.
The inconsistency with which minority stress affects LGBTQIA+ patients might be due to relative differences in social support, coping skills, an innate resilience to these effects, Dr. Marzouk explained.
Dr. Marzouk characterized the LGBTQIA+ community as “underserved” for treatment of headache. She suggested that medical mistrust and self-blame among LGBTQIA+ individuals might be factors contributing to a vicious cycle of underdiagnosis and undertreatment. Efforts by the medical community to reach out to the LGBTQIA+ community are appropriate to address an unmet need.
“Individuals with psychiatric comorbidities may experience even more benefit from migraine care,” she said.
Clinical studies should be more inclusive
While agreeing in principle with these remarks, Eric A. Kaiser, MD, PhD, department of neurology, University of Pennsylvania, Philadelphia, said that this area would be better advanced if studies routinely included patients with diverse-gender identities and sexual orientations. Speaking about how to organize these studies, Dr. Kaiser suggested that enrollment criteria should explicitly seek these individuals and that these differences should be captured in the baseline characteristics.
“For example, gender options could include man, woman, non-binary, gender diverse, gender nonconforming, or gender nonspecified,” he said.
To close “the significant knowledge gap that exists in managing headache disorders in sexually- and gender- diverse people,” Dr. Kaiser said that clinical research studies, like patient treatment of diverse populations, “should be conducted with welcoming and affirming practices.”
Dr. Marzouk reported no potential conflicts of interest. Dr. Kaiser reported financial relationships with Amgen and Lundbeck.
FROM THE 2023 SCOTTSDALE HEADACHE SYMPOSIUM
What is the proper treatment for posttraumatic headache? Expert debate
AUSTIN, TEX – There are no guidelines available, nor is there much quality evidence to support one decision or another, according to two experts who debated the question at the annual meeting of the American Headache Society.
Early treatment
Frank Conidi, DO, spoke first, and pointed out the need to define both early treatment and the condition being treated. Is it early-treatment abortive, is it preventative, and if the patient has a concussion, is it a mild traumatic brain injury (TBI), or severe TBI?
The majority of patients with posttraumatic headache will meet criteria for migraine or probable migraine. “It can be anywhere from 58% to upwards of 90%. And if you see these patients, it makes sense, because posttraumatic headache patients are disabled by their headaches,” said Dr. Conidi, director of the Florida Center for Headache and Sports Neurology.
He argued for early treatment to reduce chronification. “We know that if headaches are left untreated, they’re going to start to spiral up and become daily. This leads to the development of peripheral and central sensitization and lowers the threshold for further migraine attacks,” said Dr. Conidi.
He noted that patients with posttraumatic headache often have comorbidities such as sleep issues, neck pain, or posttraumatic stress disorder, all of which are risk factors for chronification. Treatment does not necessarily mean medication, however. “The mainstay of posttraumatic headache treatment is actually physical and cognitive activity to tolerance. And what I call the 20/5 rule: 20 minutes of physical activity with 5-minute chill breaks. In addition, we use light sub-aerobic exercise 3 to 5 days out in concussion, [which] has been shown to improve concussion recovery time,” he said.
Dr. Conidi suggested treatment of triggers, such as neck issues and whiplash symptoms. “Probably the best treatment I’ve ever seen, and I published on this, are pericranial nerve blocks. Pericranial nerve blocks work wonderfully. If you’re going to block the pericranial nerves, block them all, not just the occipital. Block the trigeminal branches. I’ve actually been able to locate a little two-and-a-half-inch plastic Luer-lock catheter that I can hook on a 1-cc syringe with viscous lidocaine, and I can do sphenopalatine ganglion blocks on all my patients now for under 25 cents. So we’ve been combining the nerve blocks, and we’ve been using them early. Oftentimes the patients won’t have any further headaches, especially if it’s [after] a concussion,” he said.
With respect to concussion-related posttraumatic headache, he summed up: “We’re aggressive early. We’re using intervention. We’re layering our treatment. We’re using medications: prednisone, NSAIDS, and now we have gepants. We’ve been having good success with using gepants,” he said.
Treatment of TBI patients is broadly similar, with the main difference being that neurologists typically won’t see such patients early on as they may be in rehab facilities or hospitals for extended periods. “You may not be getting [to see] them for 1 or 2 months. In that case, you want to educate your neurosurgery and your [physical medicine and rehabilitation] colleagues on the treatment.
Finally, he described work that his group has done in using stimulants for posttraumatic headache. “Stimulants not only treat the cognitive symptoms, but they give the patient cognitive reserve and we find that it gets the patient through the day so they actually have less headaches. It’s a form of prevention. I know there are shortages nationally of both Adderall and Ritalin, but we have had excellent results in our posttraumatic patients using these types of medications,” said Dr. Conidi.
Delayed treatment
Amaal J. Starling, MD, offered a counterargument, but she narrowed the question down to whether preventive treatment should be used within one and a half months of the injury, which she defined as early treatment. Her argument against early preventive treatment centered around the core value of beneficence – to act for the benefit of the patient, and avoid harm.
She discussed the natural history of posttraumatic headache, which is largely self-limited. For example, an NCAA study that found 88% of concussions had symptom resolution within 1 week, and 86% of posttraumatic headache resolved within 1 week. “If individuals routinely are having a self-limited course, there is no need for early treatment with a preventive treatment option because the majority of posttraumatic headache is resolving within that one-and-a-half-month postinjury threshold. The better recommendation, as provided in evidence from Dr. Conidi’s presentation, is to provide supportive care, including acute medications or acute treatment options like nerve blocks for acute pain relief and symptom relief,” said Dr. Starling, associate professor of neurology at Mayo Clinic in Scottsdale, Ariz.
Dr. Starling expressed concern that preventive medications could lead to worsening of comorbidities. For example, posttraumatic headache is often associated with autonomic dysfunction and visual vestibular dysfunction. The former commonly occurs with concussion and is similar to postural orthostatic tachycardia syndrome (POTS), and the second most common symptom of POTS is headache, according to Dr. Starling. Posttraumatic POTS is treated similarly to idiopathic POTS, with a nonpharmacologic approach. One element of POTS management is to withdraw exacerbating medications such as beta-blockers, tricyclic antidepressants, and SNRIs. “These look strikingly similar to some of the headache preventive medications that we might consider for somebody, and so the concern is early preventive treatment with these medications to treat the posttraumatic headache may actually worsen some of these comorbidities that are present in our posttraumatic headache patients. We have to be careful about potentially exacerbating comorbidities with early preventive treatment,” she said.
Prevention medications for headache can also worsen visual vestibular dysfunction, such as dizziness. There are some data suggesting that vestibular rehabilitation and vision therapy can improve dizziness, but also headache. “We all know that many of our preventive medications for headache could potentially exacerbate visual vestibular symptoms, so we have to be careful about that. So again, first do no harm. Posttraumatic POTS is common and causes headache. Posttraumatic vestibular dysfunction is common and causes headache. Instead of initiating a headache preventive medication early, we recommend to identify these comorbidities and provide targeted treatment. Treatment of these comorbidities may, in and of itself, improve the headache. We also we have to be careful because some preventive medications may worsen the comorbidities,” said Dr. Starling.
Areas of agreement
Dr. Conidi agreed that preventative treatment is less likely to be needed for concussion patients, but said that TBI patients are more likely to require it to prevent chronification. Dr. Starling agreed that chronification is an important concern, but she noted that many posttraumatic headache patients are athletes, and preventative medications can also lead to issues that might interfere with return to play, such as decreased sweating, or weight gain or loss. This is complicated by the fact that titration and weaning periods can be long. “We have to be very careful about these medications’ side effects, especially when we don’t have the evidence to demonstrate that it is worth the potential risk of being put on these medications,” she said.
The debate led Catherin Chong, PhD, to ask about the state of the field. “There’s a posttraumatic headache special interest section here [at AHS 2023], and the question that really is coming up at every meeting is, is there some coherence in the field? Is it too early or is it time for a position statement?” asked Dr. Chong, a career scientist at Mayo Clinic (Phoenix). Dr. Chong comoderated the debate and ensuing discussion.
Dr. Starling felt it’s too early for a position statement, but a scoping review could identify research questions that could lead to a position statement. “I’m really excited about the work that’s being done to identify the cohort of individuals with acute posttraumatic headache that may chronify to persistent posttraumatic headache so that we can minimize the risk of exposing the large cohort that’s going to be likely self-limited to a treatment option. Then we can identify those individuals where that risk is worth it because they’re the ones that could lead to chronification. Figuring out if that’s looking at levels of allodynia or other factors that can [help identify those at most risk] would be important,” she said.
Dr. Conidi agreed with the need for more information on the parameters to be studied, but he expressed the belief that any position statement would be a consensus statement. “It’s not going to have any hard evidence behind it, but I do think we need [a position statement]. Even in the general neurology world, there’s a huge lack of understanding of how to treat these patients,” he said.
Dr. Conidi did not make any disclosures. Dr. Starling has consulted for AbbVie, Allergan, Amgen, Axsome Therapeutics, Everyday Health, Lundbeck, Med-IQ, Medscape, Neurolief, Satsuma, and WebMD. Dr. Chong has no relevant financial disclosures.
AUSTIN, TEX – There are no guidelines available, nor is there much quality evidence to support one decision or another, according to two experts who debated the question at the annual meeting of the American Headache Society.
Early treatment
Frank Conidi, DO, spoke first, and pointed out the need to define both early treatment and the condition being treated. Is it early-treatment abortive, is it preventative, and if the patient has a concussion, is it a mild traumatic brain injury (TBI), or severe TBI?
The majority of patients with posttraumatic headache will meet criteria for migraine or probable migraine. “It can be anywhere from 58% to upwards of 90%. And if you see these patients, it makes sense, because posttraumatic headache patients are disabled by their headaches,” said Dr. Conidi, director of the Florida Center for Headache and Sports Neurology.
He argued for early treatment to reduce chronification. “We know that if headaches are left untreated, they’re going to start to spiral up and become daily. This leads to the development of peripheral and central sensitization and lowers the threshold for further migraine attacks,” said Dr. Conidi.
He noted that patients with posttraumatic headache often have comorbidities such as sleep issues, neck pain, or posttraumatic stress disorder, all of which are risk factors for chronification. Treatment does not necessarily mean medication, however. “The mainstay of posttraumatic headache treatment is actually physical and cognitive activity to tolerance. And what I call the 20/5 rule: 20 minutes of physical activity with 5-minute chill breaks. In addition, we use light sub-aerobic exercise 3 to 5 days out in concussion, [which] has been shown to improve concussion recovery time,” he said.
Dr. Conidi suggested treatment of triggers, such as neck issues and whiplash symptoms. “Probably the best treatment I’ve ever seen, and I published on this, are pericranial nerve blocks. Pericranial nerve blocks work wonderfully. If you’re going to block the pericranial nerves, block them all, not just the occipital. Block the trigeminal branches. I’ve actually been able to locate a little two-and-a-half-inch plastic Luer-lock catheter that I can hook on a 1-cc syringe with viscous lidocaine, and I can do sphenopalatine ganglion blocks on all my patients now for under 25 cents. So we’ve been combining the nerve blocks, and we’ve been using them early. Oftentimes the patients won’t have any further headaches, especially if it’s [after] a concussion,” he said.
With respect to concussion-related posttraumatic headache, he summed up: “We’re aggressive early. We’re using intervention. We’re layering our treatment. We’re using medications: prednisone, NSAIDS, and now we have gepants. We’ve been having good success with using gepants,” he said.
Treatment of TBI patients is broadly similar, with the main difference being that neurologists typically won’t see such patients early on as they may be in rehab facilities or hospitals for extended periods. “You may not be getting [to see] them for 1 or 2 months. In that case, you want to educate your neurosurgery and your [physical medicine and rehabilitation] colleagues on the treatment.
Finally, he described work that his group has done in using stimulants for posttraumatic headache. “Stimulants not only treat the cognitive symptoms, but they give the patient cognitive reserve and we find that it gets the patient through the day so they actually have less headaches. It’s a form of prevention. I know there are shortages nationally of both Adderall and Ritalin, but we have had excellent results in our posttraumatic patients using these types of medications,” said Dr. Conidi.
Delayed treatment
Amaal J. Starling, MD, offered a counterargument, but she narrowed the question down to whether preventive treatment should be used within one and a half months of the injury, which she defined as early treatment. Her argument against early preventive treatment centered around the core value of beneficence – to act for the benefit of the patient, and avoid harm.
She discussed the natural history of posttraumatic headache, which is largely self-limited. For example, an NCAA study that found 88% of concussions had symptom resolution within 1 week, and 86% of posttraumatic headache resolved within 1 week. “If individuals routinely are having a self-limited course, there is no need for early treatment with a preventive treatment option because the majority of posttraumatic headache is resolving within that one-and-a-half-month postinjury threshold. The better recommendation, as provided in evidence from Dr. Conidi’s presentation, is to provide supportive care, including acute medications or acute treatment options like nerve blocks for acute pain relief and symptom relief,” said Dr. Starling, associate professor of neurology at Mayo Clinic in Scottsdale, Ariz.
Dr. Starling expressed concern that preventive medications could lead to worsening of comorbidities. For example, posttraumatic headache is often associated with autonomic dysfunction and visual vestibular dysfunction. The former commonly occurs with concussion and is similar to postural orthostatic tachycardia syndrome (POTS), and the second most common symptom of POTS is headache, according to Dr. Starling. Posttraumatic POTS is treated similarly to idiopathic POTS, with a nonpharmacologic approach. One element of POTS management is to withdraw exacerbating medications such as beta-blockers, tricyclic antidepressants, and SNRIs. “These look strikingly similar to some of the headache preventive medications that we might consider for somebody, and so the concern is early preventive treatment with these medications to treat the posttraumatic headache may actually worsen some of these comorbidities that are present in our posttraumatic headache patients. We have to be careful about potentially exacerbating comorbidities with early preventive treatment,” she said.
Prevention medications for headache can also worsen visual vestibular dysfunction, such as dizziness. There are some data suggesting that vestibular rehabilitation and vision therapy can improve dizziness, but also headache. “We all know that many of our preventive medications for headache could potentially exacerbate visual vestibular symptoms, so we have to be careful about that. So again, first do no harm. Posttraumatic POTS is common and causes headache. Posttraumatic vestibular dysfunction is common and causes headache. Instead of initiating a headache preventive medication early, we recommend to identify these comorbidities and provide targeted treatment. Treatment of these comorbidities may, in and of itself, improve the headache. We also we have to be careful because some preventive medications may worsen the comorbidities,” said Dr. Starling.
Areas of agreement
Dr. Conidi agreed that preventative treatment is less likely to be needed for concussion patients, but said that TBI patients are more likely to require it to prevent chronification. Dr. Starling agreed that chronification is an important concern, but she noted that many posttraumatic headache patients are athletes, and preventative medications can also lead to issues that might interfere with return to play, such as decreased sweating, or weight gain or loss. This is complicated by the fact that titration and weaning periods can be long. “We have to be very careful about these medications’ side effects, especially when we don’t have the evidence to demonstrate that it is worth the potential risk of being put on these medications,” she said.
The debate led Catherin Chong, PhD, to ask about the state of the field. “There’s a posttraumatic headache special interest section here [at AHS 2023], and the question that really is coming up at every meeting is, is there some coherence in the field? Is it too early or is it time for a position statement?” asked Dr. Chong, a career scientist at Mayo Clinic (Phoenix). Dr. Chong comoderated the debate and ensuing discussion.
Dr. Starling felt it’s too early for a position statement, but a scoping review could identify research questions that could lead to a position statement. “I’m really excited about the work that’s being done to identify the cohort of individuals with acute posttraumatic headache that may chronify to persistent posttraumatic headache so that we can minimize the risk of exposing the large cohort that’s going to be likely self-limited to a treatment option. Then we can identify those individuals where that risk is worth it because they’re the ones that could lead to chronification. Figuring out if that’s looking at levels of allodynia or other factors that can [help identify those at most risk] would be important,” she said.
Dr. Conidi agreed with the need for more information on the parameters to be studied, but he expressed the belief that any position statement would be a consensus statement. “It’s not going to have any hard evidence behind it, but I do think we need [a position statement]. Even in the general neurology world, there’s a huge lack of understanding of how to treat these patients,” he said.
Dr. Conidi did not make any disclosures. Dr. Starling has consulted for AbbVie, Allergan, Amgen, Axsome Therapeutics, Everyday Health, Lundbeck, Med-IQ, Medscape, Neurolief, Satsuma, and WebMD. Dr. Chong has no relevant financial disclosures.
AUSTIN, TEX – There are no guidelines available, nor is there much quality evidence to support one decision or another, according to two experts who debated the question at the annual meeting of the American Headache Society.
Early treatment
Frank Conidi, DO, spoke first, and pointed out the need to define both early treatment and the condition being treated. Is it early-treatment abortive, is it preventative, and if the patient has a concussion, is it a mild traumatic brain injury (TBI), or severe TBI?
The majority of patients with posttraumatic headache will meet criteria for migraine or probable migraine. “It can be anywhere from 58% to upwards of 90%. And if you see these patients, it makes sense, because posttraumatic headache patients are disabled by their headaches,” said Dr. Conidi, director of the Florida Center for Headache and Sports Neurology.
He argued for early treatment to reduce chronification. “We know that if headaches are left untreated, they’re going to start to spiral up and become daily. This leads to the development of peripheral and central sensitization and lowers the threshold for further migraine attacks,” said Dr. Conidi.
He noted that patients with posttraumatic headache often have comorbidities such as sleep issues, neck pain, or posttraumatic stress disorder, all of which are risk factors for chronification. Treatment does not necessarily mean medication, however. “The mainstay of posttraumatic headache treatment is actually physical and cognitive activity to tolerance. And what I call the 20/5 rule: 20 minutes of physical activity with 5-minute chill breaks. In addition, we use light sub-aerobic exercise 3 to 5 days out in concussion, [which] has been shown to improve concussion recovery time,” he said.
Dr. Conidi suggested treatment of triggers, such as neck issues and whiplash symptoms. “Probably the best treatment I’ve ever seen, and I published on this, are pericranial nerve blocks. Pericranial nerve blocks work wonderfully. If you’re going to block the pericranial nerves, block them all, not just the occipital. Block the trigeminal branches. I’ve actually been able to locate a little two-and-a-half-inch plastic Luer-lock catheter that I can hook on a 1-cc syringe with viscous lidocaine, and I can do sphenopalatine ganglion blocks on all my patients now for under 25 cents. So we’ve been combining the nerve blocks, and we’ve been using them early. Oftentimes the patients won’t have any further headaches, especially if it’s [after] a concussion,” he said.
With respect to concussion-related posttraumatic headache, he summed up: “We’re aggressive early. We’re using intervention. We’re layering our treatment. We’re using medications: prednisone, NSAIDS, and now we have gepants. We’ve been having good success with using gepants,” he said.
Treatment of TBI patients is broadly similar, with the main difference being that neurologists typically won’t see such patients early on as they may be in rehab facilities or hospitals for extended periods. “You may not be getting [to see] them for 1 or 2 months. In that case, you want to educate your neurosurgery and your [physical medicine and rehabilitation] colleagues on the treatment.
Finally, he described work that his group has done in using stimulants for posttraumatic headache. “Stimulants not only treat the cognitive symptoms, but they give the patient cognitive reserve and we find that it gets the patient through the day so they actually have less headaches. It’s a form of prevention. I know there are shortages nationally of both Adderall and Ritalin, but we have had excellent results in our posttraumatic patients using these types of medications,” said Dr. Conidi.
Delayed treatment
Amaal J. Starling, MD, offered a counterargument, but she narrowed the question down to whether preventive treatment should be used within one and a half months of the injury, which she defined as early treatment. Her argument against early preventive treatment centered around the core value of beneficence – to act for the benefit of the patient, and avoid harm.
She discussed the natural history of posttraumatic headache, which is largely self-limited. For example, an NCAA study that found 88% of concussions had symptom resolution within 1 week, and 86% of posttraumatic headache resolved within 1 week. “If individuals routinely are having a self-limited course, there is no need for early treatment with a preventive treatment option because the majority of posttraumatic headache is resolving within that one-and-a-half-month postinjury threshold. The better recommendation, as provided in evidence from Dr. Conidi’s presentation, is to provide supportive care, including acute medications or acute treatment options like nerve blocks for acute pain relief and symptom relief,” said Dr. Starling, associate professor of neurology at Mayo Clinic in Scottsdale, Ariz.
Dr. Starling expressed concern that preventive medications could lead to worsening of comorbidities. For example, posttraumatic headache is often associated with autonomic dysfunction and visual vestibular dysfunction. The former commonly occurs with concussion and is similar to postural orthostatic tachycardia syndrome (POTS), and the second most common symptom of POTS is headache, according to Dr. Starling. Posttraumatic POTS is treated similarly to idiopathic POTS, with a nonpharmacologic approach. One element of POTS management is to withdraw exacerbating medications such as beta-blockers, tricyclic antidepressants, and SNRIs. “These look strikingly similar to some of the headache preventive medications that we might consider for somebody, and so the concern is early preventive treatment with these medications to treat the posttraumatic headache may actually worsen some of these comorbidities that are present in our posttraumatic headache patients. We have to be careful about potentially exacerbating comorbidities with early preventive treatment,” she said.
Prevention medications for headache can also worsen visual vestibular dysfunction, such as dizziness. There are some data suggesting that vestibular rehabilitation and vision therapy can improve dizziness, but also headache. “We all know that many of our preventive medications for headache could potentially exacerbate visual vestibular symptoms, so we have to be careful about that. So again, first do no harm. Posttraumatic POTS is common and causes headache. Posttraumatic vestibular dysfunction is common and causes headache. Instead of initiating a headache preventive medication early, we recommend to identify these comorbidities and provide targeted treatment. Treatment of these comorbidities may, in and of itself, improve the headache. We also we have to be careful because some preventive medications may worsen the comorbidities,” said Dr. Starling.
Areas of agreement
Dr. Conidi agreed that preventative treatment is less likely to be needed for concussion patients, but said that TBI patients are more likely to require it to prevent chronification. Dr. Starling agreed that chronification is an important concern, but she noted that many posttraumatic headache patients are athletes, and preventative medications can also lead to issues that might interfere with return to play, such as decreased sweating, or weight gain or loss. This is complicated by the fact that titration and weaning periods can be long. “We have to be very careful about these medications’ side effects, especially when we don’t have the evidence to demonstrate that it is worth the potential risk of being put on these medications,” she said.
The debate led Catherin Chong, PhD, to ask about the state of the field. “There’s a posttraumatic headache special interest section here [at AHS 2023], and the question that really is coming up at every meeting is, is there some coherence in the field? Is it too early or is it time for a position statement?” asked Dr. Chong, a career scientist at Mayo Clinic (Phoenix). Dr. Chong comoderated the debate and ensuing discussion.
Dr. Starling felt it’s too early for a position statement, but a scoping review could identify research questions that could lead to a position statement. “I’m really excited about the work that’s being done to identify the cohort of individuals with acute posttraumatic headache that may chronify to persistent posttraumatic headache so that we can minimize the risk of exposing the large cohort that’s going to be likely self-limited to a treatment option. Then we can identify those individuals where that risk is worth it because they’re the ones that could lead to chronification. Figuring out if that’s looking at levels of allodynia or other factors that can [help identify those at most risk] would be important,” she said.
Dr. Conidi agreed with the need for more information on the parameters to be studied, but he expressed the belief that any position statement would be a consensus statement. “It’s not going to have any hard evidence behind it, but I do think we need [a position statement]. Even in the general neurology world, there’s a huge lack of understanding of how to treat these patients,” he said.
Dr. Conidi did not make any disclosures. Dr. Starling has consulted for AbbVie, Allergan, Amgen, Axsome Therapeutics, Everyday Health, Lundbeck, Med-IQ, Medscape, Neurolief, Satsuma, and WebMD. Dr. Chong has no relevant financial disclosures.
AT AHS 2023
Prodrome treatment with ubrogepant prevents migraines
AUSTIN, TEX – , according to results from a new randomized, crossover study. Researchers took pains to identify migraineurs who could predict an ensuing headache 75% of the time based on prodromal symptoms. Those who could make such predictions were allowed into the randomized study.
Patients are quite good at predicting ensuing headaches when encouraged to do so, according to Peter J. Goadsby, MBBS, MD, PhD, who presented the study findings at the annual meeting of the American Headache Society.
“I find it quite useful to ask patients about these [symptoms]: Have you got cognitive clouding? Do you pass more urine? Have you got mood change? Do you feel fatigue? Associated with the attack, is how I phrase it. Get them first into the idea of thinking about the symptoms, and then get them to think about when they’re occurring. Certainly with things like brain fog, many patients will tell you that it happens. If you ask them whether they’re 100% [certain] when that’s happening, they will tell you [they’re] not. This is part of taking a history and building a relationship with the patient,” Dr. Goadsby, professor of neurology at the University of California, Los Angeles, said during the Q&A after his presentation.
‘Significant’ finding
“This is a significant finding because what patients really want is not to develop their headache and no medication has been shown to prevent a headache during the prodrome,” said Alan M. Rapoport, MD, a board certified neurologist and headache expert, as well as clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews. Successful treatment during the prodrome treatment could eliminate the need for use of preventive medication, which might decrease the patient’s adverse effects, he said.
Session comoderator Jason J. Sico, MD, took note of the patient experience during the prodrome period. “One of many noteworthy things is the large percentage of people that reported disability during prodrome before the headache. I just find that staggering, though not surprising to many of us,” he said during the session. Dr. Sico is associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rapoport and Dr. Sico were not involved in the study.
Probing the prodrome
The study included a 60-day screening period, which had to include between 3 and 16 recorded prodrome events. Headaches had to occur within 1-6 hours in at least 75% of prodrome events. Study subjects were then randomized to 100 mg ubrogepant or placebo for up to 60 days. After their first prodrome event, they entered a 7-day washout period, and then crossed over to the other group until they experienced a second prodrome event.
During the screening period, 81.5% of prodromal events identified by patients were followed by a headache within 1-6 hours of onset. Nearly 10% of the time headache occurred in 1 hour or less, 81.5% between 1 and 6 hours, and 4.5% between 6 and 24 hours after prodrome. Commonly reported prodromal symptoms included sensitivity to light (57.2%), fatigue (50.1%), neck pain (41.9%), sensitivity to sound (33.9%), and dizziness (27.8%).
The study included 247 patients in the first sequence, and 233 in the second sequence. Patient characteristics were similar in both. Ubrogepant treatment led to a greater absence of moderate- or severe-intensity headache within 24 hours of the dose (45.5% vs. 28.6% headache-free; odds ratio [OR], 2.09; P < .0001). They were also more likely to report normal functioning over 24 hours (OR, 1.66; P < .0001) and to have absence of headache within 24 hours (23.7% vs. 13.9%; OR, 1.93; P < .0001).
Between 73% and 75% of participants reported at least mild functional disability before taking medication. Two hours after a dose, ubrogepant led to a higher rate of normal functioning (37.0% vs. 26.1%; P < .001). Ubrogepant had a similar positive effect on sensitivity to light, fatigue, neck pain, sensitivity to sound, and dizziness. Adverse events were higher during ubrogepant treatment (13.2% vs. 9.1%), and included nausea, dizziness, fatigue, and somnolence, all of which were mild. “One is really scraping the barrel [to identify adverse events]. There were no serious adverse events,” said Dr. Goadsby.
A unique result?
One questioner asked if other medications used during the prodrome might yield similar results. Dr. Goadsby expressed doubt. “I think the evidence for other treatments is not terribly good. The triptan evidence is really poor. There is no randomized, placebo-controlled trial of a triptan explicitly in promontory symptomatology. There are randomized placebo controlled trials of triptans during the aura phase. The best one was the injected sumatriptan study, and it failed. So, as far as I can see from the randomized-controlled data, triptans don’t do this, and we don’t have good data for nonsteroidals and other therapies,” said Dr. Goadsby.
The researchers showed that you could treat a patient in advance of the headache to actually prevent the headache a significant number of times; it also reduced the prodromal events and it got patients back to normal functioning to a greater extent.
Dr. Goadsby was asked how many patients are typically able to identify prodrome periods on their own. He estimated that about one in three can do it initially. “I think if you teach people how to do this, it becomes very common. I would say four out of five people in my practice are able to talk about this, but you have to introduce the topic. They’ve had [prodrome symptoms], but they haven’t thought about it for a while. This is one of the things where headache doctors can offer real benefit in helping educate patients,” said Dr. Goadsby.
Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. He is editor-in-chief of Neurology Reviews and on the Editorial Board of CNS Drugs. Dr. Goadsby has financial ties to Amgen, Eli Lilly, Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Dr. Reddy’s Laboratories, Electrocore, eNeura, Massachusetts Medical Society, MedicoLegal work, Novartis, Oxford University Press, Teva Pharmaceuticals, Trigemina, Up-to-Date, and Wolters Kluwer. He has a patent for headache assigned to eNeura without fee.
AUSTIN, TEX – , according to results from a new randomized, crossover study. Researchers took pains to identify migraineurs who could predict an ensuing headache 75% of the time based on prodromal symptoms. Those who could make such predictions were allowed into the randomized study.
Patients are quite good at predicting ensuing headaches when encouraged to do so, according to Peter J. Goadsby, MBBS, MD, PhD, who presented the study findings at the annual meeting of the American Headache Society.
“I find it quite useful to ask patients about these [symptoms]: Have you got cognitive clouding? Do you pass more urine? Have you got mood change? Do you feel fatigue? Associated with the attack, is how I phrase it. Get them first into the idea of thinking about the symptoms, and then get them to think about when they’re occurring. Certainly with things like brain fog, many patients will tell you that it happens. If you ask them whether they’re 100% [certain] when that’s happening, they will tell you [they’re] not. This is part of taking a history and building a relationship with the patient,” Dr. Goadsby, professor of neurology at the University of California, Los Angeles, said during the Q&A after his presentation.
‘Significant’ finding
“This is a significant finding because what patients really want is not to develop their headache and no medication has been shown to prevent a headache during the prodrome,” said Alan M. Rapoport, MD, a board certified neurologist and headache expert, as well as clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews. Successful treatment during the prodrome treatment could eliminate the need for use of preventive medication, which might decrease the patient’s adverse effects, he said.
Session comoderator Jason J. Sico, MD, took note of the patient experience during the prodrome period. “One of many noteworthy things is the large percentage of people that reported disability during prodrome before the headache. I just find that staggering, though not surprising to many of us,” he said during the session. Dr. Sico is associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rapoport and Dr. Sico were not involved in the study.
Probing the prodrome
The study included a 60-day screening period, which had to include between 3 and 16 recorded prodrome events. Headaches had to occur within 1-6 hours in at least 75% of prodrome events. Study subjects were then randomized to 100 mg ubrogepant or placebo for up to 60 days. After their first prodrome event, they entered a 7-day washout period, and then crossed over to the other group until they experienced a second prodrome event.
During the screening period, 81.5% of prodromal events identified by patients were followed by a headache within 1-6 hours of onset. Nearly 10% of the time headache occurred in 1 hour or less, 81.5% between 1 and 6 hours, and 4.5% between 6 and 24 hours after prodrome. Commonly reported prodromal symptoms included sensitivity to light (57.2%), fatigue (50.1%), neck pain (41.9%), sensitivity to sound (33.9%), and dizziness (27.8%).
The study included 247 patients in the first sequence, and 233 in the second sequence. Patient characteristics were similar in both. Ubrogepant treatment led to a greater absence of moderate- or severe-intensity headache within 24 hours of the dose (45.5% vs. 28.6% headache-free; odds ratio [OR], 2.09; P < .0001). They were also more likely to report normal functioning over 24 hours (OR, 1.66; P < .0001) and to have absence of headache within 24 hours (23.7% vs. 13.9%; OR, 1.93; P < .0001).
Between 73% and 75% of participants reported at least mild functional disability before taking medication. Two hours after a dose, ubrogepant led to a higher rate of normal functioning (37.0% vs. 26.1%; P < .001). Ubrogepant had a similar positive effect on sensitivity to light, fatigue, neck pain, sensitivity to sound, and dizziness. Adverse events were higher during ubrogepant treatment (13.2% vs. 9.1%), and included nausea, dizziness, fatigue, and somnolence, all of which were mild. “One is really scraping the barrel [to identify adverse events]. There were no serious adverse events,” said Dr. Goadsby.
A unique result?
One questioner asked if other medications used during the prodrome might yield similar results. Dr. Goadsby expressed doubt. “I think the evidence for other treatments is not terribly good. The triptan evidence is really poor. There is no randomized, placebo-controlled trial of a triptan explicitly in promontory symptomatology. There are randomized placebo controlled trials of triptans during the aura phase. The best one was the injected sumatriptan study, and it failed. So, as far as I can see from the randomized-controlled data, triptans don’t do this, and we don’t have good data for nonsteroidals and other therapies,” said Dr. Goadsby.
The researchers showed that you could treat a patient in advance of the headache to actually prevent the headache a significant number of times; it also reduced the prodromal events and it got patients back to normal functioning to a greater extent.
Dr. Goadsby was asked how many patients are typically able to identify prodrome periods on their own. He estimated that about one in three can do it initially. “I think if you teach people how to do this, it becomes very common. I would say four out of five people in my practice are able to talk about this, but you have to introduce the topic. They’ve had [prodrome symptoms], but they haven’t thought about it for a while. This is one of the things where headache doctors can offer real benefit in helping educate patients,” said Dr. Goadsby.
Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. He is editor-in-chief of Neurology Reviews and on the Editorial Board of CNS Drugs. Dr. Goadsby has financial ties to Amgen, Eli Lilly, Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Dr. Reddy’s Laboratories, Electrocore, eNeura, Massachusetts Medical Society, MedicoLegal work, Novartis, Oxford University Press, Teva Pharmaceuticals, Trigemina, Up-to-Date, and Wolters Kluwer. He has a patent for headache assigned to eNeura without fee.
AUSTIN, TEX – , according to results from a new randomized, crossover study. Researchers took pains to identify migraineurs who could predict an ensuing headache 75% of the time based on prodromal symptoms. Those who could make such predictions were allowed into the randomized study.
Patients are quite good at predicting ensuing headaches when encouraged to do so, according to Peter J. Goadsby, MBBS, MD, PhD, who presented the study findings at the annual meeting of the American Headache Society.
“I find it quite useful to ask patients about these [symptoms]: Have you got cognitive clouding? Do you pass more urine? Have you got mood change? Do you feel fatigue? Associated with the attack, is how I phrase it. Get them first into the idea of thinking about the symptoms, and then get them to think about when they’re occurring. Certainly with things like brain fog, many patients will tell you that it happens. If you ask them whether they’re 100% [certain] when that’s happening, they will tell you [they’re] not. This is part of taking a history and building a relationship with the patient,” Dr. Goadsby, professor of neurology at the University of California, Los Angeles, said during the Q&A after his presentation.
‘Significant’ finding
“This is a significant finding because what patients really want is not to develop their headache and no medication has been shown to prevent a headache during the prodrome,” said Alan M. Rapoport, MD, a board certified neurologist and headache expert, as well as clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews. Successful treatment during the prodrome treatment could eliminate the need for use of preventive medication, which might decrease the patient’s adverse effects, he said.
Session comoderator Jason J. Sico, MD, took note of the patient experience during the prodrome period. “One of many noteworthy things is the large percentage of people that reported disability during prodrome before the headache. I just find that staggering, though not surprising to many of us,” he said during the session. Dr. Sico is associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rapoport and Dr. Sico were not involved in the study.
Probing the prodrome
The study included a 60-day screening period, which had to include between 3 and 16 recorded prodrome events. Headaches had to occur within 1-6 hours in at least 75% of prodrome events. Study subjects were then randomized to 100 mg ubrogepant or placebo for up to 60 days. After their first prodrome event, they entered a 7-day washout period, and then crossed over to the other group until they experienced a second prodrome event.
During the screening period, 81.5% of prodromal events identified by patients were followed by a headache within 1-6 hours of onset. Nearly 10% of the time headache occurred in 1 hour or less, 81.5% between 1 and 6 hours, and 4.5% between 6 and 24 hours after prodrome. Commonly reported prodromal symptoms included sensitivity to light (57.2%), fatigue (50.1%), neck pain (41.9%), sensitivity to sound (33.9%), and dizziness (27.8%).
The study included 247 patients in the first sequence, and 233 in the second sequence. Patient characteristics were similar in both. Ubrogepant treatment led to a greater absence of moderate- or severe-intensity headache within 24 hours of the dose (45.5% vs. 28.6% headache-free; odds ratio [OR], 2.09; P < .0001). They were also more likely to report normal functioning over 24 hours (OR, 1.66; P < .0001) and to have absence of headache within 24 hours (23.7% vs. 13.9%; OR, 1.93; P < .0001).
Between 73% and 75% of participants reported at least mild functional disability before taking medication. Two hours after a dose, ubrogepant led to a higher rate of normal functioning (37.0% vs. 26.1%; P < .001). Ubrogepant had a similar positive effect on sensitivity to light, fatigue, neck pain, sensitivity to sound, and dizziness. Adverse events were higher during ubrogepant treatment (13.2% vs. 9.1%), and included nausea, dizziness, fatigue, and somnolence, all of which were mild. “One is really scraping the barrel [to identify adverse events]. There were no serious adverse events,” said Dr. Goadsby.
A unique result?
One questioner asked if other medications used during the prodrome might yield similar results. Dr. Goadsby expressed doubt. “I think the evidence for other treatments is not terribly good. The triptan evidence is really poor. There is no randomized, placebo-controlled trial of a triptan explicitly in promontory symptomatology. There are randomized placebo controlled trials of triptans during the aura phase. The best one was the injected sumatriptan study, and it failed. So, as far as I can see from the randomized-controlled data, triptans don’t do this, and we don’t have good data for nonsteroidals and other therapies,” said Dr. Goadsby.
The researchers showed that you could treat a patient in advance of the headache to actually prevent the headache a significant number of times; it also reduced the prodromal events and it got patients back to normal functioning to a greater extent.
Dr. Goadsby was asked how many patients are typically able to identify prodrome periods on their own. He estimated that about one in three can do it initially. “I think if you teach people how to do this, it becomes very common. I would say four out of five people in my practice are able to talk about this, but you have to introduce the topic. They’ve had [prodrome symptoms], but they haven’t thought about it for a while. This is one of the things where headache doctors can offer real benefit in helping educate patients,” said Dr. Goadsby.
Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. He is editor-in-chief of Neurology Reviews and on the Editorial Board of CNS Drugs. Dr. Goadsby has financial ties to Amgen, Eli Lilly, Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Dr. Reddy’s Laboratories, Electrocore, eNeura, Massachusetts Medical Society, MedicoLegal work, Novartis, Oxford University Press, Teva Pharmaceuticals, Trigemina, Up-to-Date, and Wolters Kluwer. He has a patent for headache assigned to eNeura without fee.
FROM AHS 2023
Migraine treatment with rimegepant linked to reduced barbiturate use
AUSTIN – , according to a real-world analysis. Butalbital is the only commonly prescribed short-acting barbiturate in the United States, according to Noah Rosen, MD, who presented the study at the annual meeting of the American Headache Society.
Despite its effectiveness, the drug carries a risk of abuse as well as neurologic side effects, and has also been linked to an increase in medication overuse headache, which in turn can affect quality of life and lead to more disability and health care costs. “Although acute treatment recommendations supported by AHS discourage the use of barbiturates for the acute treatment of migraine, butalbital and associated medications are still widely prescribed, so effective, low-risk novel abortive and preventive therapies that have potential barbiturate-sparing characteristics do have the potential to help people with migraine,” said Dr. Rosen during his presentation. He is the program director of neurology at Hofstra Northwell Health, Hempstead, N.Y.
His group previously showed an association between rimegepant initiation and a reduction in opioid use in another real-world analysis.
The present study retrospectively analyzed data from 34,486 patients drawn from the U.S.-based Longitudinal Access and Adjudication Data (LAAD) produced by IQVIA, which is an anonymized integrated commercial medical and prescription claims database. The period studied was between November 2015 and November 2022. The median age was 47 and 89% were female. Eligibility criteria included the presence of at least 6 months of baseline data before exposure to rimegepant and at least 6 months of follow-up, at least two rimegepant refills, and at least one butalbital prescription during the baseline period.
During the baseline period, the mean number of milligrams of butalbital dispensed was 1,012, and this dropped to 742 during follow-up (–26.7%). The mean number of butalbital prescription fills dropped from 0.47 to 0.32 (–32.0%). About half of patients (49.4%) had no butalbital refills after starting rimegepant. The researchers also examined triptan use and found no difference. “We saw that it actually made no significant difference with the deflection from baseline or discontinuation if they had been given a triptan or not. This seemed to concur with my own experiences with triptan use and not affecting barbiturate dosing,” said Dr. Rosen.
‘Good news’
The results are good news, according to Jason Sico, MD, who comoderated the session. “I remember being a PGY-2 neurology resident and hearing a lecture from Stew Tepper [now professor of medicine at Geisel School of Medicine at Dartmouth, Hanover, N.H.] that fiorinal and fioricet were the F words of headache medicine, so it’s really great to see a modality that could lower barbiturate use,” said Dr. Sico, who is an associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rosen responded: “I don’t mean to malign a single chemical, because fioricet has provided many people treatment over time, but with the introduction of newer options, we would hope to see a trend toward that use.”
A listener on the virtual platform asked whether the decline in barbiturate use could be due to education by the provider on the dangers of barbiturate use when rimegepant was prescribed. “This is one of those big limitations of claims data analysis is we can speculate what the influence or the cause is, because this type of data analysis does not show causation. There are many different things that could influence the discontinuation. Education is a huge one, although you would hope that if somebody is prescribed butalbital on a regular basis, that there’s some physician contact or education that’s part of that as well. But it’s possible it plays a role,” said Dr. Rosen.
Any strategy to reduce butalbital use in migraine is important
Alan Rapoport, MD, who attended the session, was also asked to comment on the study. “Butalbital-containing medications can help headache pain but have not been approved by the FDA for a migraine indication. They can also decrease anxiety in the migraine patient, but if used frequently, they cause dependency. When used too often, butalbital-containing medications are major causes of medication overuse headache. They’re often used with other acute care medications such as triptans and over-the-counter products, and combinations of these drugs can be even more of a problem because one only needs to use any of these medicines in combination for 10 days a month or more, for at least 3 months, for a doctor to diagnose a patient with medication overuse headache. So any attempt and success to reduce the frequency of taking butalbital-containing medication is important. That can be done by counseling the patient to take fewer tablets per month, but this often does not work. This study shows a good success rate in reducing the use of these medications by treating the patient with rimegepant 75 mg ODT given once every other day. This dose has been approved by the FDA for prevention in migraine, but has not previously been shown as a treatment for overuse of butalbital or medication. Previous studies have shown that rimegepant reduced migraine days per month and the use of acute care medications monthly. It this study, rimegepant decreases the number of butalbital-containing medications taken,” said Dr. Rapoport, who is a clinical professor of neurology at the University of California, Los Angeles, and editor in chief of Neurology Reviews.
Dr. Rosen has financial ties to Allergan/Abbvie, Amgen, BioHaven, Eli Lilly, Lundbeck, Novartis, Supernus, and Teva. Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureaus of AbbVie, Dr. Reddy’s, Impel, Pfizer, and Teva Pharmaceutical Industries. He is editor in chief of Neurology Reviews and on the editorial board of CNS Drugs.
AUSTIN – , according to a real-world analysis. Butalbital is the only commonly prescribed short-acting barbiturate in the United States, according to Noah Rosen, MD, who presented the study at the annual meeting of the American Headache Society.
Despite its effectiveness, the drug carries a risk of abuse as well as neurologic side effects, and has also been linked to an increase in medication overuse headache, which in turn can affect quality of life and lead to more disability and health care costs. “Although acute treatment recommendations supported by AHS discourage the use of barbiturates for the acute treatment of migraine, butalbital and associated medications are still widely prescribed, so effective, low-risk novel abortive and preventive therapies that have potential barbiturate-sparing characteristics do have the potential to help people with migraine,” said Dr. Rosen during his presentation. He is the program director of neurology at Hofstra Northwell Health, Hempstead, N.Y.
His group previously showed an association between rimegepant initiation and a reduction in opioid use in another real-world analysis.
The present study retrospectively analyzed data from 34,486 patients drawn from the U.S.-based Longitudinal Access and Adjudication Data (LAAD) produced by IQVIA, which is an anonymized integrated commercial medical and prescription claims database. The period studied was between November 2015 and November 2022. The median age was 47 and 89% were female. Eligibility criteria included the presence of at least 6 months of baseline data before exposure to rimegepant and at least 6 months of follow-up, at least two rimegepant refills, and at least one butalbital prescription during the baseline period.
During the baseline period, the mean number of milligrams of butalbital dispensed was 1,012, and this dropped to 742 during follow-up (–26.7%). The mean number of butalbital prescription fills dropped from 0.47 to 0.32 (–32.0%). About half of patients (49.4%) had no butalbital refills after starting rimegepant. The researchers also examined triptan use and found no difference. “We saw that it actually made no significant difference with the deflection from baseline or discontinuation if they had been given a triptan or not. This seemed to concur with my own experiences with triptan use and not affecting barbiturate dosing,” said Dr. Rosen.
‘Good news’
The results are good news, according to Jason Sico, MD, who comoderated the session. “I remember being a PGY-2 neurology resident and hearing a lecture from Stew Tepper [now professor of medicine at Geisel School of Medicine at Dartmouth, Hanover, N.H.] that fiorinal and fioricet were the F words of headache medicine, so it’s really great to see a modality that could lower barbiturate use,” said Dr. Sico, who is an associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rosen responded: “I don’t mean to malign a single chemical, because fioricet has provided many people treatment over time, but with the introduction of newer options, we would hope to see a trend toward that use.”
A listener on the virtual platform asked whether the decline in barbiturate use could be due to education by the provider on the dangers of barbiturate use when rimegepant was prescribed. “This is one of those big limitations of claims data analysis is we can speculate what the influence or the cause is, because this type of data analysis does not show causation. There are many different things that could influence the discontinuation. Education is a huge one, although you would hope that if somebody is prescribed butalbital on a regular basis, that there’s some physician contact or education that’s part of that as well. But it’s possible it plays a role,” said Dr. Rosen.
Any strategy to reduce butalbital use in migraine is important
Alan Rapoport, MD, who attended the session, was also asked to comment on the study. “Butalbital-containing medications can help headache pain but have not been approved by the FDA for a migraine indication. They can also decrease anxiety in the migraine patient, but if used frequently, they cause dependency. When used too often, butalbital-containing medications are major causes of medication overuse headache. They’re often used with other acute care medications such as triptans and over-the-counter products, and combinations of these drugs can be even more of a problem because one only needs to use any of these medicines in combination for 10 days a month or more, for at least 3 months, for a doctor to diagnose a patient with medication overuse headache. So any attempt and success to reduce the frequency of taking butalbital-containing medication is important. That can be done by counseling the patient to take fewer tablets per month, but this often does not work. This study shows a good success rate in reducing the use of these medications by treating the patient with rimegepant 75 mg ODT given once every other day. This dose has been approved by the FDA for prevention in migraine, but has not previously been shown as a treatment for overuse of butalbital or medication. Previous studies have shown that rimegepant reduced migraine days per month and the use of acute care medications monthly. It this study, rimegepant decreases the number of butalbital-containing medications taken,” said Dr. Rapoport, who is a clinical professor of neurology at the University of California, Los Angeles, and editor in chief of Neurology Reviews.
Dr. Rosen has financial ties to Allergan/Abbvie, Amgen, BioHaven, Eli Lilly, Lundbeck, Novartis, Supernus, and Teva. Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureaus of AbbVie, Dr. Reddy’s, Impel, Pfizer, and Teva Pharmaceutical Industries. He is editor in chief of Neurology Reviews and on the editorial board of CNS Drugs.
AUSTIN – , according to a real-world analysis. Butalbital is the only commonly prescribed short-acting barbiturate in the United States, according to Noah Rosen, MD, who presented the study at the annual meeting of the American Headache Society.
Despite its effectiveness, the drug carries a risk of abuse as well as neurologic side effects, and has also been linked to an increase in medication overuse headache, which in turn can affect quality of life and lead to more disability and health care costs. “Although acute treatment recommendations supported by AHS discourage the use of barbiturates for the acute treatment of migraine, butalbital and associated medications are still widely prescribed, so effective, low-risk novel abortive and preventive therapies that have potential barbiturate-sparing characteristics do have the potential to help people with migraine,” said Dr. Rosen during his presentation. He is the program director of neurology at Hofstra Northwell Health, Hempstead, N.Y.
His group previously showed an association between rimegepant initiation and a reduction in opioid use in another real-world analysis.
The present study retrospectively analyzed data from 34,486 patients drawn from the U.S.-based Longitudinal Access and Adjudication Data (LAAD) produced by IQVIA, which is an anonymized integrated commercial medical and prescription claims database. The period studied was between November 2015 and November 2022. The median age was 47 and 89% were female. Eligibility criteria included the presence of at least 6 months of baseline data before exposure to rimegepant and at least 6 months of follow-up, at least two rimegepant refills, and at least one butalbital prescription during the baseline period.
During the baseline period, the mean number of milligrams of butalbital dispensed was 1,012, and this dropped to 742 during follow-up (–26.7%). The mean number of butalbital prescription fills dropped from 0.47 to 0.32 (–32.0%). About half of patients (49.4%) had no butalbital refills after starting rimegepant. The researchers also examined triptan use and found no difference. “We saw that it actually made no significant difference with the deflection from baseline or discontinuation if they had been given a triptan or not. This seemed to concur with my own experiences with triptan use and not affecting barbiturate dosing,” said Dr. Rosen.
‘Good news’
The results are good news, according to Jason Sico, MD, who comoderated the session. “I remember being a PGY-2 neurology resident and hearing a lecture from Stew Tepper [now professor of medicine at Geisel School of Medicine at Dartmouth, Hanover, N.H.] that fiorinal and fioricet were the F words of headache medicine, so it’s really great to see a modality that could lower barbiturate use,” said Dr. Sico, who is an associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rosen responded: “I don’t mean to malign a single chemical, because fioricet has provided many people treatment over time, but with the introduction of newer options, we would hope to see a trend toward that use.”
A listener on the virtual platform asked whether the decline in barbiturate use could be due to education by the provider on the dangers of barbiturate use when rimegepant was prescribed. “This is one of those big limitations of claims data analysis is we can speculate what the influence or the cause is, because this type of data analysis does not show causation. There are many different things that could influence the discontinuation. Education is a huge one, although you would hope that if somebody is prescribed butalbital on a regular basis, that there’s some physician contact or education that’s part of that as well. But it’s possible it plays a role,” said Dr. Rosen.
Any strategy to reduce butalbital use in migraine is important
Alan Rapoport, MD, who attended the session, was also asked to comment on the study. “Butalbital-containing medications can help headache pain but have not been approved by the FDA for a migraine indication. They can also decrease anxiety in the migraine patient, but if used frequently, they cause dependency. When used too often, butalbital-containing medications are major causes of medication overuse headache. They’re often used with other acute care medications such as triptans and over-the-counter products, and combinations of these drugs can be even more of a problem because one only needs to use any of these medicines in combination for 10 days a month or more, for at least 3 months, for a doctor to diagnose a patient with medication overuse headache. So any attempt and success to reduce the frequency of taking butalbital-containing medication is important. That can be done by counseling the patient to take fewer tablets per month, but this often does not work. This study shows a good success rate in reducing the use of these medications by treating the patient with rimegepant 75 mg ODT given once every other day. This dose has been approved by the FDA for prevention in migraine, but has not previously been shown as a treatment for overuse of butalbital or medication. Previous studies have shown that rimegepant reduced migraine days per month and the use of acute care medications monthly. It this study, rimegepant decreases the number of butalbital-containing medications taken,” said Dr. Rapoport, who is a clinical professor of neurology at the University of California, Los Angeles, and editor in chief of Neurology Reviews.
Dr. Rosen has financial ties to Allergan/Abbvie, Amgen, BioHaven, Eli Lilly, Lundbeck, Novartis, Supernus, and Teva. Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureaus of AbbVie, Dr. Reddy’s, Impel, Pfizer, and Teva Pharmaceutical Industries. He is editor in chief of Neurology Reviews and on the editorial board of CNS Drugs.
FROM AHS 2023
Anti-CGRP monoclonal antibody offers relief from migraine and comorbid depression
AUSTIN, TEX. – , new research shows.
Patients with both conditions who were randomly assigned to receive fremanezumab showed a statistically significant reduction in both the 17-item Hamilton Depression Rating Scale (HAMD-17) and the nine-criteria Patient Health Questionnaire (PHQ-9) scores, compared with matched controls who received placebo.
The results from the UNITE trial were presented at the annual meeting of the American Headache Society.
Long-standing questions
“It’s been well known for a long time that migraine is comorbid with a number of illnesses, and one of the most common is depression,” said study investigator Richard B. Lipton, a professor of neurology at Albert Einstein College of Medicine and the director of the Montefiore Headache Center, New York.
“Do you treat the depression? Do you treat the migraine? Do you independently treat both? Those have been long-standing questions for clinicians,” Dr. Lipton said.
Investigators randomly assigned 330 adults with migraine who were diagnosed with moderate-to-severe MDD (defined as a PHQ-9 score of 10 or greater) to receive 225 mg subcutaneous monthly fremanezumab (n = 164) or placebo (n = 166) for 12 weeks.
The trial continued as an open-label trial for another 12 weeks.
During the double-blind phase of the study, the mean change from baseline in the HAMD-17 score with placebo was –4.6 at week 8 and –5.4 at week 12, compared with –6.0 with fremanezumab at week 8 (P = .0205) and –6.7 at week 12 (P = .0228).
The change from baseline in PHQ-9 total score at week 8 was –5.8 for placebo and –7.1 for fremanezumab (P = .0283). At week 12, the change was –6.3 for placebo versus –7.8 for fremanezumab (P = .0108). These reductions were maintained throughout the open-label period of the trial.
The beneficial effect on depression and migraine demonstrated in the study is interesting on several levels, Dr. Lipton said.
“One, it tells us that if the patient has migraine and depression and you treat with fremanezumab, both disorders get better to a statistically significant degree. That’s critically important,” he said.
“The other thing, and this is actually what I find most interesting about this study, is that fremanezumab doesn’t get into the brain. There are many antimigraine therapies that do, so you can treat a patient with migraine and depression with a tricyclic antidepressant.”
“It may make the migraine better and the depression better, but you don’t know if the benefit in depression comes from the improvement in migraine, because of course the antidepressant works for both conditions. Maybe there are people who would disagree with this, but my interpretation [of the trial results] is that the depression got better because the migraine got better,” he added.
The link between migraine and depression is well established, Dr. Lipton added. Longitudinal studies have shown that people with depression but without migraine develop migraine at increased rates, compared with people with no depression. Conversely, people with migraine but no depression develop depression at increased rates.
“Both disorders may have a common substrate, but I also think many forms of chronic pain lead to depression, and that’s the part we’re making better,” he said.
If fremanezumab has this dual effect on migraine and depression, it is possible that other anti-CGRP drugs will have a similar effect, Dr. Lipton said.
“Honestly, my hope is that other companies that make effective drugs will do similar studies to see if other monoclonal antibodies that target CGRP have the same effect. My guess is that all of them work but until the studies are done, I’m going to use fremanezumab, the one that has been studied, in my patients.”
He added that depression is an important comorbidity of migraine and represents a huge challenge for clinicians. “A lot of headache patients want to know what to do about comorbid anxiety or comorbid depression. I run a headache center in a specialty practice, and when people come in with migraine, they almost always come in with migraine and depression or anxiety or another pain disorder, or something else, and one of the great challenges in the practice is managing these comorbidities,” he said.
A bidirectional relationship
The overlap between migraine and depression and anxiety has been known for quite a while, agreed Elizabeth W. Loder, MD, MPH, vice chair of academic affairs, department of neurology, Brigham and Women’s Hospital, and professor of neurology at Harvard Medical School, both in Boston.
“I think the relationship is generally viewed as bidirectional and causality is uncertain. I still do not think I would assume that any drug that reduces migraine would reduce depression,” said Dr. Loder.
However, she added, the fremanezumab study data are interesting. “The effects of any drug on depression could be due to improvement of migraine or it could be due to some other effect of the treatment on depression. That is what makes these results so intriguing. If the findings are borne out by other studies, it could mean that these treatments would be preferred to those older ones in patients with depression,” Dr. Loder said.
Also commenting on the findings, Huma Sheikh, MD, CEO of NY Neurology Medicine PC, said the study is important because it confirms the strong association between migraine and depression. “Both conditions have similar underlying neurobiological pathophysiologies, and if you are impacting one area in the brain with the CGRP inhibitors, you might also be targeting some of the receptors or pathways that are involved in depression,” Dr. Sheikh said.
The study was funded by Teva Pharmaceuticals. Dr. Lipton reported financial relationships with Teva and multiple other pharmaceutical companies. Dr. Loder and Dr. Sheikh have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AUSTIN, TEX. – , new research shows.
Patients with both conditions who were randomly assigned to receive fremanezumab showed a statistically significant reduction in both the 17-item Hamilton Depression Rating Scale (HAMD-17) and the nine-criteria Patient Health Questionnaire (PHQ-9) scores, compared with matched controls who received placebo.
The results from the UNITE trial were presented at the annual meeting of the American Headache Society.
Long-standing questions
“It’s been well known for a long time that migraine is comorbid with a number of illnesses, and one of the most common is depression,” said study investigator Richard B. Lipton, a professor of neurology at Albert Einstein College of Medicine and the director of the Montefiore Headache Center, New York.
“Do you treat the depression? Do you treat the migraine? Do you independently treat both? Those have been long-standing questions for clinicians,” Dr. Lipton said.
Investigators randomly assigned 330 adults with migraine who were diagnosed with moderate-to-severe MDD (defined as a PHQ-9 score of 10 or greater) to receive 225 mg subcutaneous monthly fremanezumab (n = 164) or placebo (n = 166) for 12 weeks.
The trial continued as an open-label trial for another 12 weeks.
During the double-blind phase of the study, the mean change from baseline in the HAMD-17 score with placebo was –4.6 at week 8 and –5.4 at week 12, compared with –6.0 with fremanezumab at week 8 (P = .0205) and –6.7 at week 12 (P = .0228).
The change from baseline in PHQ-9 total score at week 8 was –5.8 for placebo and –7.1 for fremanezumab (P = .0283). At week 12, the change was –6.3 for placebo versus –7.8 for fremanezumab (P = .0108). These reductions were maintained throughout the open-label period of the trial.
The beneficial effect on depression and migraine demonstrated in the study is interesting on several levels, Dr. Lipton said.
“One, it tells us that if the patient has migraine and depression and you treat with fremanezumab, both disorders get better to a statistically significant degree. That’s critically important,” he said.
“The other thing, and this is actually what I find most interesting about this study, is that fremanezumab doesn’t get into the brain. There are many antimigraine therapies that do, so you can treat a patient with migraine and depression with a tricyclic antidepressant.”
“It may make the migraine better and the depression better, but you don’t know if the benefit in depression comes from the improvement in migraine, because of course the antidepressant works for both conditions. Maybe there are people who would disagree with this, but my interpretation [of the trial results] is that the depression got better because the migraine got better,” he added.
The link between migraine and depression is well established, Dr. Lipton added. Longitudinal studies have shown that people with depression but without migraine develop migraine at increased rates, compared with people with no depression. Conversely, people with migraine but no depression develop depression at increased rates.
“Both disorders may have a common substrate, but I also think many forms of chronic pain lead to depression, and that’s the part we’re making better,” he said.
If fremanezumab has this dual effect on migraine and depression, it is possible that other anti-CGRP drugs will have a similar effect, Dr. Lipton said.
“Honestly, my hope is that other companies that make effective drugs will do similar studies to see if other monoclonal antibodies that target CGRP have the same effect. My guess is that all of them work but until the studies are done, I’m going to use fremanezumab, the one that has been studied, in my patients.”
He added that depression is an important comorbidity of migraine and represents a huge challenge for clinicians. “A lot of headache patients want to know what to do about comorbid anxiety or comorbid depression. I run a headache center in a specialty practice, and when people come in with migraine, they almost always come in with migraine and depression or anxiety or another pain disorder, or something else, and one of the great challenges in the practice is managing these comorbidities,” he said.
A bidirectional relationship
The overlap between migraine and depression and anxiety has been known for quite a while, agreed Elizabeth W. Loder, MD, MPH, vice chair of academic affairs, department of neurology, Brigham and Women’s Hospital, and professor of neurology at Harvard Medical School, both in Boston.
“I think the relationship is generally viewed as bidirectional and causality is uncertain. I still do not think I would assume that any drug that reduces migraine would reduce depression,” said Dr. Loder.
However, she added, the fremanezumab study data are interesting. “The effects of any drug on depression could be due to improvement of migraine or it could be due to some other effect of the treatment on depression. That is what makes these results so intriguing. If the findings are borne out by other studies, it could mean that these treatments would be preferred to those older ones in patients with depression,” Dr. Loder said.
Also commenting on the findings, Huma Sheikh, MD, CEO of NY Neurology Medicine PC, said the study is important because it confirms the strong association between migraine and depression. “Both conditions have similar underlying neurobiological pathophysiologies, and if you are impacting one area in the brain with the CGRP inhibitors, you might also be targeting some of the receptors or pathways that are involved in depression,” Dr. Sheikh said.
The study was funded by Teva Pharmaceuticals. Dr. Lipton reported financial relationships with Teva and multiple other pharmaceutical companies. Dr. Loder and Dr. Sheikh have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AUSTIN, TEX. – , new research shows.
Patients with both conditions who were randomly assigned to receive fremanezumab showed a statistically significant reduction in both the 17-item Hamilton Depression Rating Scale (HAMD-17) and the nine-criteria Patient Health Questionnaire (PHQ-9) scores, compared with matched controls who received placebo.
The results from the UNITE trial were presented at the annual meeting of the American Headache Society.
Long-standing questions
“It’s been well known for a long time that migraine is comorbid with a number of illnesses, and one of the most common is depression,” said study investigator Richard B. Lipton, a professor of neurology at Albert Einstein College of Medicine and the director of the Montefiore Headache Center, New York.
“Do you treat the depression? Do you treat the migraine? Do you independently treat both? Those have been long-standing questions for clinicians,” Dr. Lipton said.
Investigators randomly assigned 330 adults with migraine who were diagnosed with moderate-to-severe MDD (defined as a PHQ-9 score of 10 or greater) to receive 225 mg subcutaneous monthly fremanezumab (n = 164) or placebo (n = 166) for 12 weeks.
The trial continued as an open-label trial for another 12 weeks.
During the double-blind phase of the study, the mean change from baseline in the HAMD-17 score with placebo was –4.6 at week 8 and –5.4 at week 12, compared with –6.0 with fremanezumab at week 8 (P = .0205) and –6.7 at week 12 (P = .0228).
The change from baseline in PHQ-9 total score at week 8 was –5.8 for placebo and –7.1 for fremanezumab (P = .0283). At week 12, the change was –6.3 for placebo versus –7.8 for fremanezumab (P = .0108). These reductions were maintained throughout the open-label period of the trial.
The beneficial effect on depression and migraine demonstrated in the study is interesting on several levels, Dr. Lipton said.
“One, it tells us that if the patient has migraine and depression and you treat with fremanezumab, both disorders get better to a statistically significant degree. That’s critically important,” he said.
“The other thing, and this is actually what I find most interesting about this study, is that fremanezumab doesn’t get into the brain. There are many antimigraine therapies that do, so you can treat a patient with migraine and depression with a tricyclic antidepressant.”
“It may make the migraine better and the depression better, but you don’t know if the benefit in depression comes from the improvement in migraine, because of course the antidepressant works for both conditions. Maybe there are people who would disagree with this, but my interpretation [of the trial results] is that the depression got better because the migraine got better,” he added.
The link between migraine and depression is well established, Dr. Lipton added. Longitudinal studies have shown that people with depression but without migraine develop migraine at increased rates, compared with people with no depression. Conversely, people with migraine but no depression develop depression at increased rates.
“Both disorders may have a common substrate, but I also think many forms of chronic pain lead to depression, and that’s the part we’re making better,” he said.
If fremanezumab has this dual effect on migraine and depression, it is possible that other anti-CGRP drugs will have a similar effect, Dr. Lipton said.
“Honestly, my hope is that other companies that make effective drugs will do similar studies to see if other monoclonal antibodies that target CGRP have the same effect. My guess is that all of them work but until the studies are done, I’m going to use fremanezumab, the one that has been studied, in my patients.”
He added that depression is an important comorbidity of migraine and represents a huge challenge for clinicians. “A lot of headache patients want to know what to do about comorbid anxiety or comorbid depression. I run a headache center in a specialty practice, and when people come in with migraine, they almost always come in with migraine and depression or anxiety or another pain disorder, or something else, and one of the great challenges in the practice is managing these comorbidities,” he said.
A bidirectional relationship
The overlap between migraine and depression and anxiety has been known for quite a while, agreed Elizabeth W. Loder, MD, MPH, vice chair of academic affairs, department of neurology, Brigham and Women’s Hospital, and professor of neurology at Harvard Medical School, both in Boston.
“I think the relationship is generally viewed as bidirectional and causality is uncertain. I still do not think I would assume that any drug that reduces migraine would reduce depression,” said Dr. Loder.
However, she added, the fremanezumab study data are interesting. “The effects of any drug on depression could be due to improvement of migraine or it could be due to some other effect of the treatment on depression. That is what makes these results so intriguing. If the findings are borne out by other studies, it could mean that these treatments would be preferred to those older ones in patients with depression,” Dr. Loder said.
Also commenting on the findings, Huma Sheikh, MD, CEO of NY Neurology Medicine PC, said the study is important because it confirms the strong association between migraine and depression. “Both conditions have similar underlying neurobiological pathophysiologies, and if you are impacting one area in the brain with the CGRP inhibitors, you might also be targeting some of the receptors or pathways that are involved in depression,” Dr. Sheikh said.
The study was funded by Teva Pharmaceuticals. Dr. Lipton reported financial relationships with Teva and multiple other pharmaceutical companies. Dr. Loder and Dr. Sheikh have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT AHS 2023
Can a puff of cool air up the nose stop acute migraine?
AUSTIN, TEX. – , according to the results of a small study. Most patients reported relief of their symptoms after receiving 15 minutes of transnasal evaporative cooling, without any need for rescue medication.
The cooling may modulate the sphenopalatine ganglion, a large ganglion implicated in migraine, said lead author Larry Charleston IV, MD, director of the headache and facial pain division, and professor of neurology at Michigan State University, East Lansing.
“The transnasal evaporative cooling device cools by blowing dry, ambient air across the nasal turbinates and may work by neuromodulation via the sphenopalatine ganglion for migraine,” Dr. Charleston said.
The findings were presented at the annual meeting of the American Headache Society.
A ‘cool’ approach to migraine treatment
“Everyone who has migraine disease needs abortive treatment,” Dr. Charleston said. “There is a need for safe and effective acute treatment for migraine. As we understand more about the pathophysiology of migraine, we learn that peripheral input plays a role in migraine disease.
“I was excited to learn of the device and to learn how we might take advantage of our knowledge of the sphenopalatine ganglia in the treatment of migraine, and was very enthusiastic to be involved in researching a nonpharmacological treatment to abort migraine attacks,” he said. “I thought this approach to migraine treatment was really ‘cool.’ ”
Twenty-four patients who met diagnostic criteria for episodic migraine with or without aura were randomized to receive 15 minutes of cooling induced by the CoolStat Transnasal Thermal Regulating Device (CoolTech LLC), or to a sham treatment with a CoolStat sham device.
Participants receiving active treatment were further randomized to receive one of the following flow rates: 24 liters per minute (LPM; n = 6 patients), 18 LPM (n = 9 patients), and 6 LPM (n = 9 patients).
All patients were instructed to get to their headache clinic during a migraine attack to start treatment.
The researchers looked at pain levels and most bothersome symptoms at baseline, and then at 2 and 24 hours after treatment. The primary endpoint was pain relief at 2 hours. Other endpoints included tolerability, relief from most bothersome symptoms, and freedom from pain at 2 hours.
The results showed that 88% (8/9 patients) of the 6-LPM group reported pain relief at 2 hours. Of these, 44% (4/9) reported being pain free at 2 hours, all without need for rescue medication. Similarly, pain relief at 2 hours occurred in 44% (4/9) of patients in the 18-LPM group, and in 50% (3/6) of the patients in the 24-LPM group.
No participants in the 18-LPM or the 24-LPM groups reported pain freedom at 2 hours.
Most bothersome symptoms were reduced. Response was greater with 6-LPM treatment. At 2 hours, 77% (7/9) of patients in the 6-LPM group reported relief of their symptoms, followed by 66% (6/9) of the 18-LPM group and 50% (3/6) of the 24-LPM group.
However, nasal discomfort was a bothersome adverse effect, Dr. Charleston noted. The rate of nasal discomfort occurred in all groups but was lower in the 6-LPM group.
Moderate intranasal discomfort during treatment was reported by 11% of the 6-LPM group, compared with 33% (3/9) in the 18-LPM group and 83% (5/6) in the 24-LPM group.
However, the study was terminated due to insufficient subject accrual rate.
“Originally, 87 participants were recruited and consented. It may have been challenging for some to come in to study clinic sites for the study treatment at the onset of their migraine attacks. The next iteration of the treatment device is a more portable model and study treatment may be used at home. This will likely be more convenient and enhance study participation,” Dr. Charleston said.
The data in the current study will help inform dose ranging analyses in future studies, to optimize efficacy and increase tolerability, he added.
The findings are promising and merit further assessment in a larger study with a sham control group, said Richard B. Lipton, MD, Edwin S. Lowe Professor and vice chair of neurology, and director of the Montefiore Headache Center, Albert Einstein College of Medicine, New York.
“Charleston et al. report that the lowest flow dose (6 liters per minute) was most effective, with a 2-hour pain-relief rate of 88% and a 2-hour pain-free rate of 50%, but, though these rates of pain relief and pain freedom are high, caution in interpretation is required,” Dr. Lipton said.
“The sample size is very modest with only nine patients in the 6-liter-per-minute treatment arm. In addition, the study lacks results from the group that got the sham device, making it difficult to contextualize the findings,” Dr. Lipton said.
He added that it is unusual for higher doses to be less effective but that may be because air flow higher than 6 LPM is irritating to the nasal mucosa during migraine attacks.
Always a need for effective nonpharmaceuticals
Also commenting on this study, Nina Riggins, MD, director of the Headache Center at the University of California, San Diego, said she found the novel device “exciting and really clever.
“I really enjoyed reviewing this abstract because I am a big fan of sphenopalatine ganglion block in the palatine ganglion. When we do those, we basically apply numbing medication to decrease the sensation and discharges coming from this group of neural cells in order to decrease pain,” Dr. Riggins said. “The procedure is very well tolerated and usually sphenopalatine ganglion blocks are used in patients when we do not want any side effects, such as in pregnant and postpartum women.”
The novel technique has the potential to have fewer side effects than those of oral medications, she said. “For example, the triptans are effective drugs but they constrict the blood vessels and we don’t want to use them in people with heart disease or history of stroke. This is where these potentially safer devices can play an important role. We can have more options to offer our patients,” Dr. Riggins said.
“I am super excited and looking forward to see what will come out of future research. I am really grateful that the authors are looking into new neuromodulation devices which can be so useful,” she said.
Migraine is the second leading cause of disability worldwide, Dr. Riggins noted. “It peaks in the years when people are most productive and affects families and communities. Medications are good, of course, but now with these novel devices, these are wonderful areas for research. Also now, we can offer so much more to people with migraine and other headache disorders,” she said.
“When I started in the field, I remember we were very limited in resources, and now, it’s just so wonderful.”
The study was sponsored by CoolTech Corp LLC. Dr. Charleston reports financial relationships with Allergan/AbbVie, Amgen, Amneal, Biohaven, Haleon, Linpharma, Satsuma, and Teva, and that he has received CME honoraria from the American Headache Society and the American Academy of Neurology. Dr. Lipton reports financial relationships with multiple pharmaceutical companies. Dr. Riggins reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AUSTIN, TEX. – , according to the results of a small study. Most patients reported relief of their symptoms after receiving 15 minutes of transnasal evaporative cooling, without any need for rescue medication.
The cooling may modulate the sphenopalatine ganglion, a large ganglion implicated in migraine, said lead author Larry Charleston IV, MD, director of the headache and facial pain division, and professor of neurology at Michigan State University, East Lansing.
“The transnasal evaporative cooling device cools by blowing dry, ambient air across the nasal turbinates and may work by neuromodulation via the sphenopalatine ganglion for migraine,” Dr. Charleston said.
The findings were presented at the annual meeting of the American Headache Society.
A ‘cool’ approach to migraine treatment
“Everyone who has migraine disease needs abortive treatment,” Dr. Charleston said. “There is a need for safe and effective acute treatment for migraine. As we understand more about the pathophysiology of migraine, we learn that peripheral input plays a role in migraine disease.
“I was excited to learn of the device and to learn how we might take advantage of our knowledge of the sphenopalatine ganglia in the treatment of migraine, and was very enthusiastic to be involved in researching a nonpharmacological treatment to abort migraine attacks,” he said. “I thought this approach to migraine treatment was really ‘cool.’ ”
Twenty-four patients who met diagnostic criteria for episodic migraine with or without aura were randomized to receive 15 minutes of cooling induced by the CoolStat Transnasal Thermal Regulating Device (CoolTech LLC), or to a sham treatment with a CoolStat sham device.
Participants receiving active treatment were further randomized to receive one of the following flow rates: 24 liters per minute (LPM; n = 6 patients), 18 LPM (n = 9 patients), and 6 LPM (n = 9 patients).
All patients were instructed to get to their headache clinic during a migraine attack to start treatment.
The researchers looked at pain levels and most bothersome symptoms at baseline, and then at 2 and 24 hours after treatment. The primary endpoint was pain relief at 2 hours. Other endpoints included tolerability, relief from most bothersome symptoms, and freedom from pain at 2 hours.
The results showed that 88% (8/9 patients) of the 6-LPM group reported pain relief at 2 hours. Of these, 44% (4/9) reported being pain free at 2 hours, all without need for rescue medication. Similarly, pain relief at 2 hours occurred in 44% (4/9) of patients in the 18-LPM group, and in 50% (3/6) of the patients in the 24-LPM group.
No participants in the 18-LPM or the 24-LPM groups reported pain freedom at 2 hours.
Most bothersome symptoms were reduced. Response was greater with 6-LPM treatment. At 2 hours, 77% (7/9) of patients in the 6-LPM group reported relief of their symptoms, followed by 66% (6/9) of the 18-LPM group and 50% (3/6) of the 24-LPM group.
However, nasal discomfort was a bothersome adverse effect, Dr. Charleston noted. The rate of nasal discomfort occurred in all groups but was lower in the 6-LPM group.
Moderate intranasal discomfort during treatment was reported by 11% of the 6-LPM group, compared with 33% (3/9) in the 18-LPM group and 83% (5/6) in the 24-LPM group.
However, the study was terminated due to insufficient subject accrual rate.
“Originally, 87 participants were recruited and consented. It may have been challenging for some to come in to study clinic sites for the study treatment at the onset of their migraine attacks. The next iteration of the treatment device is a more portable model and study treatment may be used at home. This will likely be more convenient and enhance study participation,” Dr. Charleston said.
The data in the current study will help inform dose ranging analyses in future studies, to optimize efficacy and increase tolerability, he added.
The findings are promising and merit further assessment in a larger study with a sham control group, said Richard B. Lipton, MD, Edwin S. Lowe Professor and vice chair of neurology, and director of the Montefiore Headache Center, Albert Einstein College of Medicine, New York.
“Charleston et al. report that the lowest flow dose (6 liters per minute) was most effective, with a 2-hour pain-relief rate of 88% and a 2-hour pain-free rate of 50%, but, though these rates of pain relief and pain freedom are high, caution in interpretation is required,” Dr. Lipton said.
“The sample size is very modest with only nine patients in the 6-liter-per-minute treatment arm. In addition, the study lacks results from the group that got the sham device, making it difficult to contextualize the findings,” Dr. Lipton said.
He added that it is unusual for higher doses to be less effective but that may be because air flow higher than 6 LPM is irritating to the nasal mucosa during migraine attacks.
Always a need for effective nonpharmaceuticals
Also commenting on this study, Nina Riggins, MD, director of the Headache Center at the University of California, San Diego, said she found the novel device “exciting and really clever.
“I really enjoyed reviewing this abstract because I am a big fan of sphenopalatine ganglion block in the palatine ganglion. When we do those, we basically apply numbing medication to decrease the sensation and discharges coming from this group of neural cells in order to decrease pain,” Dr. Riggins said. “The procedure is very well tolerated and usually sphenopalatine ganglion blocks are used in patients when we do not want any side effects, such as in pregnant and postpartum women.”
The novel technique has the potential to have fewer side effects than those of oral medications, she said. “For example, the triptans are effective drugs but they constrict the blood vessels and we don’t want to use them in people with heart disease or history of stroke. This is where these potentially safer devices can play an important role. We can have more options to offer our patients,” Dr. Riggins said.
“I am super excited and looking forward to see what will come out of future research. I am really grateful that the authors are looking into new neuromodulation devices which can be so useful,” she said.
Migraine is the second leading cause of disability worldwide, Dr. Riggins noted. “It peaks in the years when people are most productive and affects families and communities. Medications are good, of course, but now with these novel devices, these are wonderful areas for research. Also now, we can offer so much more to people with migraine and other headache disorders,” she said.
“When I started in the field, I remember we were very limited in resources, and now, it’s just so wonderful.”
The study was sponsored by CoolTech Corp LLC. Dr. Charleston reports financial relationships with Allergan/AbbVie, Amgen, Amneal, Biohaven, Haleon, Linpharma, Satsuma, and Teva, and that he has received CME honoraria from the American Headache Society and the American Academy of Neurology. Dr. Lipton reports financial relationships with multiple pharmaceutical companies. Dr. Riggins reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AUSTIN, TEX. – , according to the results of a small study. Most patients reported relief of their symptoms after receiving 15 minutes of transnasal evaporative cooling, without any need for rescue medication.
The cooling may modulate the sphenopalatine ganglion, a large ganglion implicated in migraine, said lead author Larry Charleston IV, MD, director of the headache and facial pain division, and professor of neurology at Michigan State University, East Lansing.
“The transnasal evaporative cooling device cools by blowing dry, ambient air across the nasal turbinates and may work by neuromodulation via the sphenopalatine ganglion for migraine,” Dr. Charleston said.
The findings were presented at the annual meeting of the American Headache Society.
A ‘cool’ approach to migraine treatment
“Everyone who has migraine disease needs abortive treatment,” Dr. Charleston said. “There is a need for safe and effective acute treatment for migraine. As we understand more about the pathophysiology of migraine, we learn that peripheral input plays a role in migraine disease.
“I was excited to learn of the device and to learn how we might take advantage of our knowledge of the sphenopalatine ganglia in the treatment of migraine, and was very enthusiastic to be involved in researching a nonpharmacological treatment to abort migraine attacks,” he said. “I thought this approach to migraine treatment was really ‘cool.’ ”
Twenty-four patients who met diagnostic criteria for episodic migraine with or without aura were randomized to receive 15 minutes of cooling induced by the CoolStat Transnasal Thermal Regulating Device (CoolTech LLC), or to a sham treatment with a CoolStat sham device.
Participants receiving active treatment were further randomized to receive one of the following flow rates: 24 liters per minute (LPM; n = 6 patients), 18 LPM (n = 9 patients), and 6 LPM (n = 9 patients).
All patients were instructed to get to their headache clinic during a migraine attack to start treatment.
The researchers looked at pain levels and most bothersome symptoms at baseline, and then at 2 and 24 hours after treatment. The primary endpoint was pain relief at 2 hours. Other endpoints included tolerability, relief from most bothersome symptoms, and freedom from pain at 2 hours.
The results showed that 88% (8/9 patients) of the 6-LPM group reported pain relief at 2 hours. Of these, 44% (4/9) reported being pain free at 2 hours, all without need for rescue medication. Similarly, pain relief at 2 hours occurred in 44% (4/9) of patients in the 18-LPM group, and in 50% (3/6) of the patients in the 24-LPM group.
No participants in the 18-LPM or the 24-LPM groups reported pain freedom at 2 hours.
Most bothersome symptoms were reduced. Response was greater with 6-LPM treatment. At 2 hours, 77% (7/9) of patients in the 6-LPM group reported relief of their symptoms, followed by 66% (6/9) of the 18-LPM group and 50% (3/6) of the 24-LPM group.
However, nasal discomfort was a bothersome adverse effect, Dr. Charleston noted. The rate of nasal discomfort occurred in all groups but was lower in the 6-LPM group.
Moderate intranasal discomfort during treatment was reported by 11% of the 6-LPM group, compared with 33% (3/9) in the 18-LPM group and 83% (5/6) in the 24-LPM group.
However, the study was terminated due to insufficient subject accrual rate.
“Originally, 87 participants were recruited and consented. It may have been challenging for some to come in to study clinic sites for the study treatment at the onset of their migraine attacks. The next iteration of the treatment device is a more portable model and study treatment may be used at home. This will likely be more convenient and enhance study participation,” Dr. Charleston said.
The data in the current study will help inform dose ranging analyses in future studies, to optimize efficacy and increase tolerability, he added.
The findings are promising and merit further assessment in a larger study with a sham control group, said Richard B. Lipton, MD, Edwin S. Lowe Professor and vice chair of neurology, and director of the Montefiore Headache Center, Albert Einstein College of Medicine, New York.
“Charleston et al. report that the lowest flow dose (6 liters per minute) was most effective, with a 2-hour pain-relief rate of 88% and a 2-hour pain-free rate of 50%, but, though these rates of pain relief and pain freedom are high, caution in interpretation is required,” Dr. Lipton said.
“The sample size is very modest with only nine patients in the 6-liter-per-minute treatment arm. In addition, the study lacks results from the group that got the sham device, making it difficult to contextualize the findings,” Dr. Lipton said.
He added that it is unusual for higher doses to be less effective but that may be because air flow higher than 6 LPM is irritating to the nasal mucosa during migraine attacks.
Always a need for effective nonpharmaceuticals
Also commenting on this study, Nina Riggins, MD, director of the Headache Center at the University of California, San Diego, said she found the novel device “exciting and really clever.
“I really enjoyed reviewing this abstract because I am a big fan of sphenopalatine ganglion block in the palatine ganglion. When we do those, we basically apply numbing medication to decrease the sensation and discharges coming from this group of neural cells in order to decrease pain,” Dr. Riggins said. “The procedure is very well tolerated and usually sphenopalatine ganglion blocks are used in patients when we do not want any side effects, such as in pregnant and postpartum women.”
The novel technique has the potential to have fewer side effects than those of oral medications, she said. “For example, the triptans are effective drugs but they constrict the blood vessels and we don’t want to use them in people with heart disease or history of stroke. This is where these potentially safer devices can play an important role. We can have more options to offer our patients,” Dr. Riggins said.
“I am super excited and looking forward to see what will come out of future research. I am really grateful that the authors are looking into new neuromodulation devices which can be so useful,” she said.
Migraine is the second leading cause of disability worldwide, Dr. Riggins noted. “It peaks in the years when people are most productive and affects families and communities. Medications are good, of course, but now with these novel devices, these are wonderful areas for research. Also now, we can offer so much more to people with migraine and other headache disorders,” she said.
“When I started in the field, I remember we were very limited in resources, and now, it’s just so wonderful.”
The study was sponsored by CoolTech Corp LLC. Dr. Charleston reports financial relationships with Allergan/AbbVie, Amgen, Amneal, Biohaven, Haleon, Linpharma, Satsuma, and Teva, and that he has received CME honoraria from the American Headache Society and the American Academy of Neurology. Dr. Lipton reports financial relationships with multiple pharmaceutical companies. Dr. Riggins reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
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