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Comorbidities in migraine should guide treatment course

PHILADELPHIA – Anxiety and mood disorders, certain cardiovascular conditions, epilepsy, and poor sleep are all comorbidities in migraineurs that must be considered before choosing a patient’s treatment plan, according to Dr. Deborah I. Friedman.

Treating these comorbidities while minimizing risk factors is essential to chronic migraine prevention, Dr. Friedman told an audience at the Emerging Concepts in Headache Therapy session during this year’s annual meeting of the American Academy of Neurology.

Dr. Deborah Friedman

Modifiable risk factors include the frequency of attack, caffeine intake, medication overuse, obesity, and sleep apnea.

Depression, anxiety, and suicide

Screening for anxiety and depression in migraine patients is important, given the close association between these psychiatric diagnoses and migraine, she said.

"Mood and anxiety disorders are anywhere from 2 to 10 times more prevalent in migraineurs," said Dr. Friedman, professor of neurology at the University of Texas Southwestern Medical Center at Dallas. "And 25% of patients with migraine meet [the] criteria for mood and anxiety disorders."

But teasing out which condition begets which comorbidity can be difficult; each might be a risk factor for the other.

"We know that depression, anxiety, and phobias are bidirectionally linked to migraine. If you have one, you’re more likely to have the other, and vice versa," Dr. Friedman said.

One possible mechanism for this is shared etiologic factors such as genetics. However, whether there is a confounder is still unknown. In the case of adverse childhood experiences and stressful life events, for example, "we know there is a large association of an unfortunate occurrence and migraine," Dr. Friedman said. "Is there a link between these things and posttraumatic stress disorder?"

However, patients with episodic migraine have less risk of developing mood and anxiety disorders, compared with chronic daily headache sufferers, Dr. Friedman said. "The comorbidity may relate to disabling and recurrent pain more than to the migraine itself."

In addition, a population-based cohort study of migraine patients, people with nonmigraine severe headache, and controls with no history of severe headache Dr. Friedman cited indicated statistically significant odds of attempted suicide in migraine when there is depression at baseline (odds ratio, 3.18); anxiety (OR, 4.78); depression and anxiety (OR, 12.1); and a previous suicide attempt (OR, 54.94) (Headache 2012;52:723-31).

Although the link between migraine and depression is high, Dr. Friedman said the link with anxiety is "probably much more common," occurring at a rate of five times more than would be expected in the general population.

For patients deemed to have a psychiatric comorbidity, Dr. Friedman said in an interview that cognitive-behavioral therapy is her preferred first-line therapy, particularly for anxiety and panic.

"It’s easy to reach for a pill to treat anxiety, but in the long haul, I am not sure it really benefits the patient that much because they don’t really gain insight into what’s causing their situation," Dr. Friedman said in the interview. It also might not be possible to "get two birds with one stone" by prescribing one pill to treat headache and depression and/or anxiety, Dr. Friedman said.

PFO and Raynaud’s

The odds that patients with migraine also have patent foramen ovale (PFO) or a right-left shunt are nearly eight times greater than in the general public, according to Dr. Friedman. The prevalence of PFO in migraine with aura is more than twice the rate of the general population.

Some nonrandomized studies have shown benefit to migraine from PFO closure, while the 2006 sham-controlled MIST (Migraine Intervention With STARFlex Technology) trial in the United Kingdom failed to achieve either its primary or secondary endpoints.

"Perhaps those endpoints were not realistic, because they were complete resolution of headache days at 3 months," Dr. Friedman said.

Some posit that the relationship between migraine and PFO might explain the increased risk of ischemic stroke and white matter intensities; however, since results from the PREMIUM and PRIMA studies on PFO and migraine are still pending, Dr. Friedman said there are no clinical recommendations for treating PFO in the context of just migraine at this time.

Raynaud’s phenomenon is another "chicken-egg" dilemma, Dr. Friedman said. Raynaud’s is five times more likely in those with migraine than in the general population, and migraine has similar occurrence rates in Raynaud’s.

Clinicians should take note that in addition to avoiding triptans and ergot derivatives in migraine patients with Raynaud’s, "beta-blockers can induce Raynaud’s in patients who have actually never experienced it," Dr. Friedman said, "and they can also make Raynaud’s worse."

However, particularly in patients with migraine who also have prominent autonomic symptoms, calcium channel blockers can treat both conditions, Dr. Friedman said.

 

 

Epilepsy and ‘migralepsy’

The incidence of migraine is nearly 2.5 times greater in persons with epilepsy than in those without it, according to Dr. Friedman.

Perhaps because they share a paroxysmal nature, Dr. Friedman said it is interesting to note that the comorbidities for epilepsy mirror those in migraine, including most major psychiatric diagnoses except psychosis, sleep and movement disorders, fibromyalgia, and asthma.

Seizures known as "migralepsy" that are triggered by migraine with aura can occur in patients either during or within 1 hour of a migraine attack, Dr. Friedman said. The mechanism is thought to be the cortical spread of depression.

Comorbid migraine in epilepsy decreases the likelihood of early treatment response, shortens remission periods, and is associated with intractable epilepsy, requiring polytherapy, Dr. Friedman said.

For those reasons, she recommended that patients not decrease their seizure threshold, either by their behaviors or their medications, and that clinicians select medications that can prevent both migraine and seizures. "Most of the medications we use for migraine do not affect the seizure threshold," she said in a follow-up interview. "Bupropion, venlafaxine, tramadol, [and] some of the antipsychotics and various stimulants (such as attention-deficit/hyperactivity disorder drugs) can do it. "The tricyclic antidepressants have long been associated with lowering the seizure threshold, but there is actually no good evidence that this is true."

Sleep disorders

"Sleep is like caffeine [in migraine]; it’s a double-edged sword," Dr. Friedman said. "Sleeping well can trigger a migraine, but it can also get rid of a migraine. Sleep interferes with pain, but pain interferes with sleep."

There are some data linking somnambulism, nightmares, and bruxism to migraine. "I have been surprised in my own practice how many of my patients tell me they used to sleep walk as a child," he said.

Referring to a 2010 study, Dr. Friedman said severe sleep disturbance was associated with a five times greater frequency of headache than in controls, and that insomnia, sleep initiation, and excessive daytime sleepiness were the most common complaints (J. Headache Pain 2010;11:197-206).

Although snoring and sleep apnea are not considered comorbidities of migraine, they do heighten the risk of episodic migraines becoming chronic, which is why Dr. Friedman recommended screening patients for sleep apnea. Asking patients about their sleep hygiene and sleep histories, including in childhood if they are adults, is important, as is reviewing what they ingest, from caffeine in food and drink to medications.

"Incorporating sleep questionnaires into your practice is very helpful," Dr. Friedman said.

She said she had no relevant financial disclosures.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

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PHILADELPHIA – Anxiety and mood disorders, certain cardiovascular conditions, epilepsy, and poor sleep are all comorbidities in migraineurs that must be considered before choosing a patient’s treatment plan, according to Dr. Deborah I. Friedman.

Treating these comorbidities while minimizing risk factors is essential to chronic migraine prevention, Dr. Friedman told an audience at the Emerging Concepts in Headache Therapy session during this year’s annual meeting of the American Academy of Neurology.

Dr. Deborah Friedman

Modifiable risk factors include the frequency of attack, caffeine intake, medication overuse, obesity, and sleep apnea.

Depression, anxiety, and suicide

Screening for anxiety and depression in migraine patients is important, given the close association between these psychiatric diagnoses and migraine, she said.

"Mood and anxiety disorders are anywhere from 2 to 10 times more prevalent in migraineurs," said Dr. Friedman, professor of neurology at the University of Texas Southwestern Medical Center at Dallas. "And 25% of patients with migraine meet [the] criteria for mood and anxiety disorders."

But teasing out which condition begets which comorbidity can be difficult; each might be a risk factor for the other.

"We know that depression, anxiety, and phobias are bidirectionally linked to migraine. If you have one, you’re more likely to have the other, and vice versa," Dr. Friedman said.

One possible mechanism for this is shared etiologic factors such as genetics. However, whether there is a confounder is still unknown. In the case of adverse childhood experiences and stressful life events, for example, "we know there is a large association of an unfortunate occurrence and migraine," Dr. Friedman said. "Is there a link between these things and posttraumatic stress disorder?"

However, patients with episodic migraine have less risk of developing mood and anxiety disorders, compared with chronic daily headache sufferers, Dr. Friedman said. "The comorbidity may relate to disabling and recurrent pain more than to the migraine itself."

In addition, a population-based cohort study of migraine patients, people with nonmigraine severe headache, and controls with no history of severe headache Dr. Friedman cited indicated statistically significant odds of attempted suicide in migraine when there is depression at baseline (odds ratio, 3.18); anxiety (OR, 4.78); depression and anxiety (OR, 12.1); and a previous suicide attempt (OR, 54.94) (Headache 2012;52:723-31).

Although the link between migraine and depression is high, Dr. Friedman said the link with anxiety is "probably much more common," occurring at a rate of five times more than would be expected in the general population.

For patients deemed to have a psychiatric comorbidity, Dr. Friedman said in an interview that cognitive-behavioral therapy is her preferred first-line therapy, particularly for anxiety and panic.

"It’s easy to reach for a pill to treat anxiety, but in the long haul, I am not sure it really benefits the patient that much because they don’t really gain insight into what’s causing their situation," Dr. Friedman said in the interview. It also might not be possible to "get two birds with one stone" by prescribing one pill to treat headache and depression and/or anxiety, Dr. Friedman said.

PFO and Raynaud’s

The odds that patients with migraine also have patent foramen ovale (PFO) or a right-left shunt are nearly eight times greater than in the general public, according to Dr. Friedman. The prevalence of PFO in migraine with aura is more than twice the rate of the general population.

Some nonrandomized studies have shown benefit to migraine from PFO closure, while the 2006 sham-controlled MIST (Migraine Intervention With STARFlex Technology) trial in the United Kingdom failed to achieve either its primary or secondary endpoints.

"Perhaps those endpoints were not realistic, because they were complete resolution of headache days at 3 months," Dr. Friedman said.

Some posit that the relationship between migraine and PFO might explain the increased risk of ischemic stroke and white matter intensities; however, since results from the PREMIUM and PRIMA studies on PFO and migraine are still pending, Dr. Friedman said there are no clinical recommendations for treating PFO in the context of just migraine at this time.

Raynaud’s phenomenon is another "chicken-egg" dilemma, Dr. Friedman said. Raynaud’s is five times more likely in those with migraine than in the general population, and migraine has similar occurrence rates in Raynaud’s.

Clinicians should take note that in addition to avoiding triptans and ergot derivatives in migraine patients with Raynaud’s, "beta-blockers can induce Raynaud’s in patients who have actually never experienced it," Dr. Friedman said, "and they can also make Raynaud’s worse."

However, particularly in patients with migraine who also have prominent autonomic symptoms, calcium channel blockers can treat both conditions, Dr. Friedman said.

 

 

Epilepsy and ‘migralepsy’

The incidence of migraine is nearly 2.5 times greater in persons with epilepsy than in those without it, according to Dr. Friedman.

Perhaps because they share a paroxysmal nature, Dr. Friedman said it is interesting to note that the comorbidities for epilepsy mirror those in migraine, including most major psychiatric diagnoses except psychosis, sleep and movement disorders, fibromyalgia, and asthma.

Seizures known as "migralepsy" that are triggered by migraine with aura can occur in patients either during or within 1 hour of a migraine attack, Dr. Friedman said. The mechanism is thought to be the cortical spread of depression.

Comorbid migraine in epilepsy decreases the likelihood of early treatment response, shortens remission periods, and is associated with intractable epilepsy, requiring polytherapy, Dr. Friedman said.

For those reasons, she recommended that patients not decrease their seizure threshold, either by their behaviors or their medications, and that clinicians select medications that can prevent both migraine and seizures. "Most of the medications we use for migraine do not affect the seizure threshold," she said in a follow-up interview. "Bupropion, venlafaxine, tramadol, [and] some of the antipsychotics and various stimulants (such as attention-deficit/hyperactivity disorder drugs) can do it. "The tricyclic antidepressants have long been associated with lowering the seizure threshold, but there is actually no good evidence that this is true."

Sleep disorders

"Sleep is like caffeine [in migraine]; it’s a double-edged sword," Dr. Friedman said. "Sleeping well can trigger a migraine, but it can also get rid of a migraine. Sleep interferes with pain, but pain interferes with sleep."

There are some data linking somnambulism, nightmares, and bruxism to migraine. "I have been surprised in my own practice how many of my patients tell me they used to sleep walk as a child," he said.

Referring to a 2010 study, Dr. Friedman said severe sleep disturbance was associated with a five times greater frequency of headache than in controls, and that insomnia, sleep initiation, and excessive daytime sleepiness were the most common complaints (J. Headache Pain 2010;11:197-206).

Although snoring and sleep apnea are not considered comorbidities of migraine, they do heighten the risk of episodic migraines becoming chronic, which is why Dr. Friedman recommended screening patients for sleep apnea. Asking patients about their sleep hygiene and sleep histories, including in childhood if they are adults, is important, as is reviewing what they ingest, from caffeine in food and drink to medications.

"Incorporating sleep questionnaires into your practice is very helpful," Dr. Friedman said.

She said she had no relevant financial disclosures.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

PHILADELPHIA – Anxiety and mood disorders, certain cardiovascular conditions, epilepsy, and poor sleep are all comorbidities in migraineurs that must be considered before choosing a patient’s treatment plan, according to Dr. Deborah I. Friedman.

Treating these comorbidities while minimizing risk factors is essential to chronic migraine prevention, Dr. Friedman told an audience at the Emerging Concepts in Headache Therapy session during this year’s annual meeting of the American Academy of Neurology.

Dr. Deborah Friedman

Modifiable risk factors include the frequency of attack, caffeine intake, medication overuse, obesity, and sleep apnea.

Depression, anxiety, and suicide

Screening for anxiety and depression in migraine patients is important, given the close association between these psychiatric diagnoses and migraine, she said.

"Mood and anxiety disorders are anywhere from 2 to 10 times more prevalent in migraineurs," said Dr. Friedman, professor of neurology at the University of Texas Southwestern Medical Center at Dallas. "And 25% of patients with migraine meet [the] criteria for mood and anxiety disorders."

But teasing out which condition begets which comorbidity can be difficult; each might be a risk factor for the other.

"We know that depression, anxiety, and phobias are bidirectionally linked to migraine. If you have one, you’re more likely to have the other, and vice versa," Dr. Friedman said.

One possible mechanism for this is shared etiologic factors such as genetics. However, whether there is a confounder is still unknown. In the case of adverse childhood experiences and stressful life events, for example, "we know there is a large association of an unfortunate occurrence and migraine," Dr. Friedman said. "Is there a link between these things and posttraumatic stress disorder?"

However, patients with episodic migraine have less risk of developing mood and anxiety disorders, compared with chronic daily headache sufferers, Dr. Friedman said. "The comorbidity may relate to disabling and recurrent pain more than to the migraine itself."

In addition, a population-based cohort study of migraine patients, people with nonmigraine severe headache, and controls with no history of severe headache Dr. Friedman cited indicated statistically significant odds of attempted suicide in migraine when there is depression at baseline (odds ratio, 3.18); anxiety (OR, 4.78); depression and anxiety (OR, 12.1); and a previous suicide attempt (OR, 54.94) (Headache 2012;52:723-31).

Although the link between migraine and depression is high, Dr. Friedman said the link with anxiety is "probably much more common," occurring at a rate of five times more than would be expected in the general population.

For patients deemed to have a psychiatric comorbidity, Dr. Friedman said in an interview that cognitive-behavioral therapy is her preferred first-line therapy, particularly for anxiety and panic.

"It’s easy to reach for a pill to treat anxiety, but in the long haul, I am not sure it really benefits the patient that much because they don’t really gain insight into what’s causing their situation," Dr. Friedman said in the interview. It also might not be possible to "get two birds with one stone" by prescribing one pill to treat headache and depression and/or anxiety, Dr. Friedman said.

PFO and Raynaud’s

The odds that patients with migraine also have patent foramen ovale (PFO) or a right-left shunt are nearly eight times greater than in the general public, according to Dr. Friedman. The prevalence of PFO in migraine with aura is more than twice the rate of the general population.

Some nonrandomized studies have shown benefit to migraine from PFO closure, while the 2006 sham-controlled MIST (Migraine Intervention With STARFlex Technology) trial in the United Kingdom failed to achieve either its primary or secondary endpoints.

"Perhaps those endpoints were not realistic, because they were complete resolution of headache days at 3 months," Dr. Friedman said.

Some posit that the relationship between migraine and PFO might explain the increased risk of ischemic stroke and white matter intensities; however, since results from the PREMIUM and PRIMA studies on PFO and migraine are still pending, Dr. Friedman said there are no clinical recommendations for treating PFO in the context of just migraine at this time.

Raynaud’s phenomenon is another "chicken-egg" dilemma, Dr. Friedman said. Raynaud’s is five times more likely in those with migraine than in the general population, and migraine has similar occurrence rates in Raynaud’s.

Clinicians should take note that in addition to avoiding triptans and ergot derivatives in migraine patients with Raynaud’s, "beta-blockers can induce Raynaud’s in patients who have actually never experienced it," Dr. Friedman said, "and they can also make Raynaud’s worse."

However, particularly in patients with migraine who also have prominent autonomic symptoms, calcium channel blockers can treat both conditions, Dr. Friedman said.

 

 

Epilepsy and ‘migralepsy’

The incidence of migraine is nearly 2.5 times greater in persons with epilepsy than in those without it, according to Dr. Friedman.

Perhaps because they share a paroxysmal nature, Dr. Friedman said it is interesting to note that the comorbidities for epilepsy mirror those in migraine, including most major psychiatric diagnoses except psychosis, sleep and movement disorders, fibromyalgia, and asthma.

Seizures known as "migralepsy" that are triggered by migraine with aura can occur in patients either during or within 1 hour of a migraine attack, Dr. Friedman said. The mechanism is thought to be the cortical spread of depression.

Comorbid migraine in epilepsy decreases the likelihood of early treatment response, shortens remission periods, and is associated with intractable epilepsy, requiring polytherapy, Dr. Friedman said.

For those reasons, she recommended that patients not decrease their seizure threshold, either by their behaviors or their medications, and that clinicians select medications that can prevent both migraine and seizures. "Most of the medications we use for migraine do not affect the seizure threshold," she said in a follow-up interview. "Bupropion, venlafaxine, tramadol, [and] some of the antipsychotics and various stimulants (such as attention-deficit/hyperactivity disorder drugs) can do it. "The tricyclic antidepressants have long been associated with lowering the seizure threshold, but there is actually no good evidence that this is true."

Sleep disorders

"Sleep is like caffeine [in migraine]; it’s a double-edged sword," Dr. Friedman said. "Sleeping well can trigger a migraine, but it can also get rid of a migraine. Sleep interferes with pain, but pain interferes with sleep."

There are some data linking somnambulism, nightmares, and bruxism to migraine. "I have been surprised in my own practice how many of my patients tell me they used to sleep walk as a child," he said.

Referring to a 2010 study, Dr. Friedman said severe sleep disturbance was associated with a five times greater frequency of headache than in controls, and that insomnia, sleep initiation, and excessive daytime sleepiness were the most common complaints (J. Headache Pain 2010;11:197-206).

Although snoring and sleep apnea are not considered comorbidities of migraine, they do heighten the risk of episodic migraines becoming chronic, which is why Dr. Friedman recommended screening patients for sleep apnea. Asking patients about their sleep hygiene and sleep histories, including in childhood if they are adults, is important, as is reviewing what they ingest, from caffeine in food and drink to medications.

"Incorporating sleep questionnaires into your practice is very helpful," Dr. Friedman said.

She said she had no relevant financial disclosures.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

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