Debbie Lerman

PHILADELPHIA – Insomnia and poor sleep habits may be the cause of the transformation from episodic to chronic migraine, Dr. Anne H. Calhoun said in a poster session at the annual meeting of the American Headache Society.

This hypothesis turns on its head the former paradigm, which was that pain causes medication overuse, which causes migraines to become chronic, which then leads to insomnia and sleep problems.

But insomnia and poor sleep habits may be the cause and not the result of migraine's transformation to chronic.

Based on this assumption, Dr. Calhoun, a neurologist at the University of North Carolina in Chapel Hill, conducted a study to see whether improving sleep habits might improve headaches in chronic migraine sufferers. “We found that when you improve sleep, headaches improve,” she said.

The study included 147 women with chronic migraine seen in an academic headache clinic. The women were given a comprehensive sleep interview and instructed in sleep habit modification. (See box.) They were given the interview and asked about adherence to each of five instructions on all subsequent visits. They recorded their headaches in standardized diaries, from which a headache index was calculated.

At baseline, the women averaged 23 headache days per 28-day recording period, with a mean headache index of 46.1. Of the 147 women, 72.8% met International Classification of Headache Disorders (ICDH-2) criteria for medication overuse headache, and 85% reported awakening tired. The researchers looked at how improvement on each of the five sleep habits–as well as an aggregate of sleep habit improvements–affected headache frequency and severity.

They found that the more detrimental sleep habits women were able to improve, the less frequent and severe their headaches were. For example: for the 28 women who improved on all five detrimental sleep habits, headache frequency was 23.4 on average pre-sleep improvement vs. 10.4 on average post improvement, for an overall improvement of 58.7%. The headache index in the same group improved by 68.5%.

In contrast, for the nine women who managed to improve on only one or none of the detrimental sleep habits, frequency improved by 23.9%, and headache index improved by 26.3%.

Of the 108 women who completed at least 2 visits, 60 women (56%) reverted to episodic migraine after a mean of 2.8 visits.

Further study is needed to see if sleep problems might be a primary factor in the etiology of chronic migraine, rather than a secondary symptom, Dr. Calhoun said in an interview with this newspaper.

“I'd like to see doctors addressing sleep issues as a primary factor in chronic migraine,” she said. “Questions about sleep should move up to the top of the list when we're treating these patients. Then, if we find that patients have poor sleep habits, we can counsel them on how to improve their sleep which may, in turn, have a big impact on their migraines.”

Sleep-Habit Modification For Patients

▸ Plan consistent and adequate time for nocturnal sleep period (8 hours for adults and 10 hours for adolescents).

▸ Eliminate TV, reading, and music in bed.

▸ Decrease sleep-onset latency. (Use visualization technique, and allow no caffeine within 8 hours of bedtime).

▸ Avoid nocturia. (Allow 4 hours between dinner and bedtime, and minimize fluids before bedtime.)

▸ Eliminate naps.

PHILADELPHIA – Insomnia and poor sleep habits may be the cause of the transformation from episodic to chronic migraine, Dr. Anne H. Calhoun said in a poster session at the annual meeting of the American Headache Society.

This hypothesis turns on its head the former paradigm, which was that pain causes medication overuse, which causes migraines to become chronic, which then leads to insomnia and sleep problems.

But insomnia and poor sleep habits may be the cause and not the result of migraine's transformation to chronic.

Based on this assumption, Dr. Calhoun, a neurologist at the University of North Carolina in Chapel Hill, conducted a study to see whether improving sleep habits might improve headaches in chronic migraine sufferers. “We found that when you improve sleep, headaches improve,” she said.

The study included 147 women with chronic migraine seen in an academic headache clinic. The women were given a comprehensive sleep interview and instructed in sleep habit modification. (See box.) They were given the interview and asked about adherence to each of five instructions on all subsequent visits. They recorded their headaches in standardized diaries, from which a headache index was calculated.

At baseline, the women averaged 23 headache days per 28-day recording period, with a mean headache index of 46.1. Of the 147 women, 72.8% met International Classification of Headache Disorders (ICDH-2) criteria for medication overuse headache, and 85% reported awakening tired. The researchers looked at how improvement on each of the five sleep habits–as well as an aggregate of sleep habit improvements–affected headache frequency and severity.

They found that the more detrimental sleep habits women were able to improve, the less frequent and severe their headaches were. For example: for the 28 women who improved on all five detrimental sleep habits, headache frequency was 23.4 on average pre-sleep improvement vs. 10.4 on average post improvement, for an overall improvement of 58.7%. The headache index in the same group improved by 68.5%.

In contrast, for the nine women who managed to improve on only one or none of the detrimental sleep habits, frequency improved by 23.9%, and headache index improved by 26.3%.

Of the 108 women who completed at least 2 visits, 60 women (56%) reverted to episodic migraine after a mean of 2.8 visits.

Further study is needed to see if sleep problems might be a primary factor in the etiology of chronic migraine, rather than a secondary symptom, Dr. Calhoun said in an interview with this newspaper.

“I'd like to see doctors addressing sleep issues as a primary factor in chronic migraine,” she said. “Questions about sleep should move up to the top of the list when we're treating these patients. Then, if we find that patients have poor sleep habits, we can counsel them on how to improve their sleep which may, in turn, have a big impact on their migraines.”

Sleep-Habit Modification For Patients

▸ Plan consistent and adequate time for nocturnal sleep period (8 hours for adults and 10 hours for adolescents).

▸ Eliminate TV, reading, and music in bed.

▸ Decrease sleep-onset latency. (Use visualization technique, and allow no caffeine within 8 hours of bedtime).

▸ Avoid nocturia. (Allow 4 hours between dinner and bedtime, and minimize fluids before bedtime.)

▸ Eliminate naps.

PHILADELPHIA – Insomnia and poor sleep habits may be the cause of the transformation from episodic to chronic migraine, Dr. Anne H. Calhoun said in a poster session at the annual meeting of the American Headache Society.

This hypothesis turns on its head the former paradigm, which was that pain causes medication overuse, which causes migraines to become chronic, which then leads to insomnia and sleep problems.

But insomnia and poor sleep habits may be the cause and not the result of migraine's transformation to chronic.

Based on this assumption, Dr. Calhoun, a neurologist at the University of North Carolina in Chapel Hill, conducted a study to see whether improving sleep habits might improve headaches in chronic migraine sufferers. “We found that when you improve sleep, headaches improve,” she said.

The study included 147 women with chronic migraine seen in an academic headache clinic. The women were given a comprehensive sleep interview and instructed in sleep habit modification. (See box.) They were given the interview and asked about adherence to each of five instructions on all subsequent visits. They recorded their headaches in standardized diaries, from which a headache index was calculated.

At baseline, the women averaged 23 headache days per 28-day recording period, with a mean headache index of 46.1. Of the 147 women, 72.8% met International Classification of Headache Disorders (ICDH-2) criteria for medication overuse headache, and 85% reported awakening tired. The researchers looked at how improvement on each of the five sleep habits–as well as an aggregate of sleep habit improvements–affected headache frequency and severity.

They found that the more detrimental sleep habits women were able to improve, the less frequent and severe their headaches were. For example: for the 28 women who improved on all five detrimental sleep habits, headache frequency was 23.4 on average pre-sleep improvement vs. 10.4 on average post improvement, for an overall improvement of 58.7%. The headache index in the same group improved by 68.5%.

In contrast, for the nine women who managed to improve on only one or none of the detrimental sleep habits, frequency improved by 23.9%, and headache index improved by 26.3%.

Of the 108 women who completed at least 2 visits, 60 women (56%) reverted to episodic migraine after a mean of 2.8 visits.

Further study is needed to see if sleep problems might be a primary factor in the etiology of chronic migraine, rather than a secondary symptom, Dr. Calhoun said in an interview with this newspaper.

“I'd like to see doctors addressing sleep issues as a primary factor in chronic migraine,” she said. “Questions about sleep should move up to the top of the list when we're treating these patients. Then, if we find that patients have poor sleep habits, we can counsel them on how to improve their sleep which may, in turn, have a big impact on their migraines.”

Sleep-Habit Modification For Patients

▸ Plan consistent and adequate time for nocturnal sleep period (8 hours for adults and 10 hours for adolescents).

▸ Eliminate TV, reading, and music in bed.

▸ Decrease sleep-onset latency. (Use visualization technique, and allow no caffeine within 8 hours of bedtime).

▸ Avoid nocturia. (Allow 4 hours between dinner and bedtime, and minimize fluids before bedtime.)

▸ Eliminate naps.

PHILADELPHIA – Botulinum toxin type A was found to be an effective, well-tolerated prophylactic treatment for patients with transformed migraine, according to studies that were reported at the annual meeting of the American Headache Society.

The phase II botulinum toxin type A (Botox) trials were intended to identify a responsive patient population and the most appropriate dosing as well as to determine efficacy end points to guide phase III studies. Transformed migraine was defined as 16 or more headache days per month, 50% or more of which were migraines.

Dr. Benjamin Frishberg and Dr. David Dodick, who presented these studies at the meeting, said they found significant improvement with Botox compared with placebo in terms of number of headaches, number of headache days, and use of acute medications. The improvements were most notable in patients who were not on any other type of prophylactic treatment.

Dr. Frishberg is a neurologist in La Jolla, Calif., and Dr. Dodick is a neurologist at the Mayo Clinic in Scottsdale, Ariz. Their studies of Botox were supported by Allergan Inc., which is the drug's manufacturer.

Dr. Frishberg and Dr. Dodick reported on a randomized, double-blind, placebo-controlled study in which 1,200 patients were screened based on 30 days of self-reported headaches entered in an electronic diary.

Of these, 702 patients who reported chronic daily headache (CDH, defined as 16 or more headaches a month) were enrolled in a 30-day, single-blind placebo run-in period.

After this period, patients were classified as either placebo responders, or placebo nonresponders.

The mean age of patients was 43.4 years and 82.9% (582) of them were female. All of the patients had at least one migraine or probable migraine during the 30-day baseline period.

Of the 702 patients, 52% were receiving one or more prophylactic headache treatments, in addition to the treatment given in the trial.

The researchers then conducted a subanalysis that looked at 355 patients in the placebo nonresponse group, of whom 228 (64%) were not using prophylactic headache medications. This subset of 228 patients was aged 19–65 years (mean age of 42.4 years), and 86% female. All of these patients had CDH with 50% or more migraine days per month, which the researchers defined as transformed migraine.

The patients in the subset were randomized to receive injections of Botox (117) or placebo (111). Those in the Botox group received between 105 U and 260 U (average 190 U) over six to seven head and neck muscle areas using a modified follow-the-pain injection paradigm. the investigators said.

No significant differences were found between Botox and placebo in the predetermined primary efficacy end point, which was defined as mean change from baseline in the frequency of headache-free days at day 180 in placebo nonresponders, Dr. Frishberg and Dr. Dodick reported.

Several secondary end points were successfully met. The following statistically significant reductions from baseline were observed:

▸ Headache frequency in placebo nonresponders with 225 U and 150 U of Botox vs. placebo at day 240 (reductions in headache frequency of −8.4, −8.6 and −6.4, days respectively).

▸ Headache days in placebo nonresponders who received Botox vs. placebo at day 180 (40% vs. 20% reduction in headache days).

▸ Number of days of use of acute headache pain medications at day 90 in Botox users, compared with placebo (reduction from baseline of −5.7 vs. −3.3 days), as well as at day 180 (−7.8 vs. −4.1), day 210 (−8.5 vs. −4.0), and day 240 (−9.3 vs. −4.7).

Only 27 of the 702 placebo nonresponders (3.8%) discontinued the study due to adverse events. The most commonly reported adverse events in patients treated with Botox vs. placebo were muscular weakness (22% vs. 0%) and neck pain (13.3% vs. 0.5%).

Based on these results, Botox would seem to show the most promise in treating transformed migraine in patients who are not using other prophylactic medications, Dr. Frishberg said in an interview with this newspaper. Phase III trials were scheduled to begin late last year at 100 sites, he said.

PHILADELPHIA – Botulinum toxin type A was found to be an effective, well-tolerated prophylactic treatment for patients with transformed migraine, according to studies that were reported at the annual meeting of the American Headache Society.

The phase II botulinum toxin type A (Botox) trials were intended to identify a responsive patient population and the most appropriate dosing as well as to determine efficacy end points to guide phase III studies. Transformed migraine was defined as 16 or more headache days per month, 50% or more of which were migraines.

Dr. Benjamin Frishberg and Dr. David Dodick, who presented these studies at the meeting, said they found significant improvement with Botox compared with placebo in terms of number of headaches, number of headache days, and use of acute medications. The improvements were most notable in patients who were not on any other type of prophylactic treatment.

Dr. Frishberg is a neurologist in La Jolla, Calif., and Dr. Dodick is a neurologist at the Mayo Clinic in Scottsdale, Ariz. Their studies of Botox were supported by Allergan Inc., which is the drug's manufacturer.

Dr. Frishberg and Dr. Dodick reported on a randomized, double-blind, placebo-controlled study in which 1,200 patients were screened based on 30 days of self-reported headaches entered in an electronic diary.

Of these, 702 patients who reported chronic daily headache (CDH, defined as 16 or more headaches a month) were enrolled in a 30-day, single-blind placebo run-in period.

After this period, patients were classified as either placebo responders, or placebo nonresponders.

The mean age of patients was 43.4 years and 82.9% (582) of them were female. All of the patients had at least one migraine or probable migraine during the 30-day baseline period.

Of the 702 patients, 52% were receiving one or more prophylactic headache treatments, in addition to the treatment given in the trial.

The researchers then conducted a subanalysis that looked at 355 patients in the placebo nonresponse group, of whom 228 (64%) were not using prophylactic headache medications. This subset of 228 patients was aged 19–65 years (mean age of 42.4 years), and 86% female. All of these patients had CDH with 50% or more migraine days per month, which the researchers defined as transformed migraine.

The patients in the subset were randomized to receive injections of Botox (117) or placebo (111). Those in the Botox group received between 105 U and 260 U (average 190 U) over six to seven head and neck muscle areas using a modified follow-the-pain injection paradigm. the investigators said.

No significant differences were found between Botox and placebo in the predetermined primary efficacy end point, which was defined as mean change from baseline in the frequency of headache-free days at day 180 in placebo nonresponders, Dr. Frishberg and Dr. Dodick reported.

Several secondary end points were successfully met. The following statistically significant reductions from baseline were observed:

▸ Headache frequency in placebo nonresponders with 225 U and 150 U of Botox vs. placebo at day 240 (reductions in headache frequency of −8.4, −8.6 and −6.4, days respectively).

▸ Headache days in placebo nonresponders who received Botox vs. placebo at day 180 (40% vs. 20% reduction in headache days).

▸ Number of days of use of acute headache pain medications at day 90 in Botox users, compared with placebo (reduction from baseline of −5.7 vs. −3.3 days), as well as at day 180 (−7.8 vs. −4.1), day 210 (−8.5 vs. −4.0), and day 240 (−9.3 vs. −4.7).

Only 27 of the 702 placebo nonresponders (3.8%) discontinued the study due to adverse events. The most commonly reported adverse events in patients treated with Botox vs. placebo were muscular weakness (22% vs. 0%) and neck pain (13.3% vs. 0.5%).

Based on these results, Botox would seem to show the most promise in treating transformed migraine in patients who are not using other prophylactic medications, Dr. Frishberg said in an interview with this newspaper. Phase III trials were scheduled to begin late last year at 100 sites, he said.

PHILADELPHIA – Botulinum toxin type A was found to be an effective, well-tolerated prophylactic treatment for patients with transformed migraine, according to studies that were reported at the annual meeting of the American Headache Society.

The phase II botulinum toxin type A (Botox) trials were intended to identify a responsive patient population and the most appropriate dosing as well as to determine efficacy end points to guide phase III studies. Transformed migraine was defined as 16 or more headache days per month, 50% or more of which were migraines.

Dr. Benjamin Frishberg and Dr. David Dodick, who presented these studies at the meeting, said they found significant improvement with Botox compared with placebo in terms of number of headaches, number of headache days, and use of acute medications. The improvements were most notable in patients who were not on any other type of prophylactic treatment.

Dr. Frishberg is a neurologist in La Jolla, Calif., and Dr. Dodick is a neurologist at the Mayo Clinic in Scottsdale, Ariz. Their studies of Botox were supported by Allergan Inc., which is the drug's manufacturer.

Dr. Frishberg and Dr. Dodick reported on a randomized, double-blind, placebo-controlled study in which 1,200 patients were screened based on 30 days of self-reported headaches entered in an electronic diary.

Of these, 702 patients who reported chronic daily headache (CDH, defined as 16 or more headaches a month) were enrolled in a 30-day, single-blind placebo run-in period.

After this period, patients were classified as either placebo responders, or placebo nonresponders.

The mean age of patients was 43.4 years and 82.9% (582) of them were female. All of the patients had at least one migraine or probable migraine during the 30-day baseline period.

Of the 702 patients, 52% were receiving one or more prophylactic headache treatments, in addition to the treatment given in the trial.

The researchers then conducted a subanalysis that looked at 355 patients in the placebo nonresponse group, of whom 228 (64%) were not using prophylactic headache medications. This subset of 228 patients was aged 19–65 years (mean age of 42.4 years), and 86% female. All of these patients had CDH with 50% or more migraine days per month, which the researchers defined as transformed migraine.

The patients in the subset were randomized to receive injections of Botox (117) or placebo (111). Those in the Botox group received between 105 U and 260 U (average 190 U) over six to seven head and neck muscle areas using a modified follow-the-pain injection paradigm. the investigators said.

No significant differences were found between Botox and placebo in the predetermined primary efficacy end point, which was defined as mean change from baseline in the frequency of headache-free days at day 180 in placebo nonresponders, Dr. Frishberg and Dr. Dodick reported.

Several secondary end points were successfully met. The following statistically significant reductions from baseline were observed:

▸ Headache frequency in placebo nonresponders with 225 U and 150 U of Botox vs. placebo at day 240 (reductions in headache frequency of −8.4, −8.6 and −6.4, days respectively).

▸ Headache days in placebo nonresponders who received Botox vs. placebo at day 180 (40% vs. 20% reduction in headache days).

▸ Number of days of use of acute headache pain medications at day 90 in Botox users, compared with placebo (reduction from baseline of −5.7 vs. −3.3 days), as well as at day 180 (−7.8 vs. −4.1), day 210 (−8.5 vs. −4.0), and day 240 (−9.3 vs. −4.7).

Only 27 of the 702 placebo nonresponders (3.8%) discontinued the study due to adverse events. The most commonly reported adverse events in patients treated with Botox vs. placebo were muscular weakness (22% vs. 0%) and neck pain (13.3% vs. 0.5%).

Based on these results, Botox would seem to show the most promise in treating transformed migraine in patients who are not using other prophylactic medications, Dr. Frishberg said in an interview with this newspaper. Phase III trials were scheduled to begin late last year at 100 sites, he said.

PHILADELPHIA – Analgesic and triptan use should be restricted to no more than 10–12 doses a month to prevent patients with episodic migraine or tension type headaches from developing a chronic condition, Volker Limmroth, M.D., Ph.D., reported at the annual meeting of the American Headache Society.

The prevalence of medication-overuse headache (MOH) is approximately 1% in the general global population, said Dr. Limmroth of the department of neurology at the University Hospital in Essen, Germany. He based his estimate on a wide range of epidemiologic studies from around the world.

Before 2003, when the International Classification of Headache Disorders was updated, the definition of MOH (formerly called drug-induced headache), did not cover all available agents, especially not modern antimigraine drugs such as triptans, Dr. Limmroth said.

Now, according to the International Classification of Headache Disorders, second edition, MOH is defined as a headache on 15 or more days a month, with drug intake of ergots, triptansm, or opioids for 10 or more days per month for a minimum of 3 months, or with use of analgesics for 15 or more days per month for a minimum of 3 months. In addition, the chronic headache would disappear or revert to its previous pattern by 2 months after withdrawal.

Based on the new classification, the German Society for Neurology has already issued guidelines limiting the intake of triptans and analgesics to 10 doses per month, Dr. Limmroth said in an interview with this newspaper.

To treat MOH patients who are overusing triptans or analgesics, Dr. Limmroth strongly recommended inpatient withdrawal. “It's important for doctors to realize that the length of time it takes for successful withdrawal is different, depending on the primary headache [whether migraine or tension-type headache] and the medication used,” Dr. Limmroth said. Following withdrawal therapy, patients go back to the number of episodic headaches they had before medication overuse, he said.

Withdrawal symptoms vary according to the drug that has been overused. After withdrawal from triptans, withdrawal symptoms last about 4 days on average. With ergots, they can last up to 7 days. Withdrawal from analgesics can take longer, and even after 2 weeks, 70%–80% of headaches can persist, he said. It is very important to be aware of these variations and to follow patients for a long enough time to ensure successful withdrawal.

“If withdrawal is done correctly, about 60% of the patients with chronic conditions get better and stay better for years,” Dr. Limmroth said.

Nevertheless, relapse is a problem with medication overuse. Overall, including all types of headache medications (triptans, ergots, and analgesics), studies found that about 28% of patients went back to overuse 6 months after withdrawal; 35%, after 1 year; and 42%, after 4 years, Dr. Limmroth said. Relapse is more common with tension-type headaches than with migraines, he added.

“Doctors who treat patients with chronic migraine and MOH need to look very closely within the first year after withdrawal to see whether the frequency of headaches requires preventive treatment,” he said. “Patients should be put on an individualized medication regimen, which they can comply with and tolerate, to prevent the headaches and also to prevent a relapse of overuse,” he said.

PHILADELPHIA – Analgesic and triptan use should be restricted to no more than 10–12 doses a month to prevent patients with episodic migraine or tension type headaches from developing a chronic condition, Volker Limmroth, M.D., Ph.D., reported at the annual meeting of the American Headache Society.

The prevalence of medication-overuse headache (MOH) is approximately 1% in the general global population, said Dr. Limmroth of the department of neurology at the University Hospital in Essen, Germany. He based his estimate on a wide range of epidemiologic studies from around the world.

Before 2003, when the International Classification of Headache Disorders was updated, the definition of MOH (formerly called drug-induced headache), did not cover all available agents, especially not modern antimigraine drugs such as triptans, Dr. Limmroth said.

Now, according to the International Classification of Headache Disorders, second edition, MOH is defined as a headache on 15 or more days a month, with drug intake of ergots, triptansm, or opioids for 10 or more days per month for a minimum of 3 months, or with use of analgesics for 15 or more days per month for a minimum of 3 months. In addition, the chronic headache would disappear or revert to its previous pattern by 2 months after withdrawal.

Based on the new classification, the German Society for Neurology has already issued guidelines limiting the intake of triptans and analgesics to 10 doses per month, Dr. Limmroth said in an interview with this newspaper.

To treat MOH patients who are overusing triptans or analgesics, Dr. Limmroth strongly recommended inpatient withdrawal. “It's important for doctors to realize that the length of time it takes for successful withdrawal is different, depending on the primary headache [whether migraine or tension-type headache] and the medication used,” Dr. Limmroth said. Following withdrawal therapy, patients go back to the number of episodic headaches they had before medication overuse, he said.

Withdrawal symptoms vary according to the drug that has been overused. After withdrawal from triptans, withdrawal symptoms last about 4 days on average. With ergots, they can last up to 7 days. Withdrawal from analgesics can take longer, and even after 2 weeks, 70%–80% of headaches can persist, he said. It is very important to be aware of these variations and to follow patients for a long enough time to ensure successful withdrawal.

“If withdrawal is done correctly, about 60% of the patients with chronic conditions get better and stay better for years,” Dr. Limmroth said.

Nevertheless, relapse is a problem with medication overuse. Overall, including all types of headache medications (triptans, ergots, and analgesics), studies found that about 28% of patients went back to overuse 6 months after withdrawal; 35%, after 1 year; and 42%, after 4 years, Dr. Limmroth said. Relapse is more common with tension-type headaches than with migraines, he added.

“Doctors who treat patients with chronic migraine and MOH need to look very closely within the first year after withdrawal to see whether the frequency of headaches requires preventive treatment,” he said. “Patients should be put on an individualized medication regimen, which they can comply with and tolerate, to prevent the headaches and also to prevent a relapse of overuse,” he said.

PHILADELPHIA – Analgesic and triptan use should be restricted to no more than 10–12 doses a month to prevent patients with episodic migraine or tension type headaches from developing a chronic condition, Volker Limmroth, M.D., Ph.D., reported at the annual meeting of the American Headache Society.

The prevalence of medication-overuse headache (MOH) is approximately 1% in the general global population, said Dr. Limmroth of the department of neurology at the University Hospital in Essen, Germany. He based his estimate on a wide range of epidemiologic studies from around the world.

Before 2003, when the International Classification of Headache Disorders was updated, the definition of MOH (formerly called drug-induced headache), did not cover all available agents, especially not modern antimigraine drugs such as triptans, Dr. Limmroth said.

Now, according to the International Classification of Headache Disorders, second edition, MOH is defined as a headache on 15 or more days a month, with drug intake of ergots, triptansm, or opioids for 10 or more days per month for a minimum of 3 months, or with use of analgesics for 15 or more days per month for a minimum of 3 months. In addition, the chronic headache would disappear or revert to its previous pattern by 2 months after withdrawal.

Based on the new classification, the German Society for Neurology has already issued guidelines limiting the intake of triptans and analgesics to 10 doses per month, Dr. Limmroth said in an interview with this newspaper.

To treat MOH patients who are overusing triptans or analgesics, Dr. Limmroth strongly recommended inpatient withdrawal. “It's important for doctors to realize that the length of time it takes for successful withdrawal is different, depending on the primary headache [whether migraine or tension-type headache] and the medication used,” Dr. Limmroth said. Following withdrawal therapy, patients go back to the number of episodic headaches they had before medication overuse, he said.

Withdrawal symptoms vary according to the drug that has been overused. After withdrawal from triptans, withdrawal symptoms last about 4 days on average. With ergots, they can last up to 7 days. Withdrawal from analgesics can take longer, and even after 2 weeks, 70%–80% of headaches can persist, he said. It is very important to be aware of these variations and to follow patients for a long enough time to ensure successful withdrawal.

“If withdrawal is done correctly, about 60% of the patients with chronic conditions get better and stay better for years,” Dr. Limmroth said.

Nevertheless, relapse is a problem with medication overuse. Overall, including all types of headache medications (triptans, ergots, and analgesics), studies found that about 28% of patients went back to overuse 6 months after withdrawal; 35%, after 1 year; and 42%, after 4 years, Dr. Limmroth said. Relapse is more common with tension-type headaches than with migraines, he added.

“Doctors who treat patients with chronic migraine and MOH need to look very closely within the first year after withdrawal to see whether the frequency of headaches requires preventive treatment,” he said. “Patients should be put on an individualized medication regimen, which they can comply with and tolerate, to prevent the headaches and also to prevent a relapse of overuse,” he said.

PHILADELPHIA – Children and adolescents who were overweight or obese were not found to have an increased risk for chronic daily headache in a study on CDH risk factors in a pediatric population. CDH was defined in the study as headaches occurring on 15 or more days per month for more than 3 months.

Female gender, psychiatric comorbidity, caffeine use, and analgesic overuse were the only factors found in the study to increase CDH risk. These surprising results were reported by Elza Vasconcellos, M.D., at the annual meeting of the American Headache Society.

“Based on what we know about CDH in grown-ups, we expected a high correlation between high body mass index (BMI) and CDH risk in the pediatric population,” Dr. Vasconcellos, who is director of the Miami Children's Hospital headache center, said in her presentation. But the results of the study did not bear out this hypothesis.

To identify risk factors associated with the development of CDH, the researchers examined the medical records of 226 patients, aged 6–18 years, with a diagnosis of headaches or migraines. After factoring out the patients with nonchronic headaches, the investigators compared 53 patients with CDH and 146 control patients with nondaily headaches (110 with migraines, 18 with tension-type headaches, and 18 with other or mixed-types).

They also compared the BMI and percentage of overweight patients (defined as BMI less than or equal to the 95th percentile of the sex-specific BMI-for-age growth chart) in both headache groups with a control group of 100 healthy pediatric patients who were seen for well-child visits at a pediatric clinic.

The researchers found that 35% of the children with CDH were overusing analgesics more than 15 days per month, compared with none of the patients with nondaily headaches. Of the children with CDH, 34% had a comorbid psychiatric condition, compared with 19% of non-CDH patients. There were significantly more females in the CDH group than the non-CDH group (66% vs. 46%), and more children in the CDH group said they consumed caffeine (in an answer to a yes/no question) than did children in the non-CDH group (95% vs. 80%).

The two groups (CDH vs. non-CDH) were not significantly different in terms of age, sleep hours, handedness, stress, parental marital status, learning difficulties, head trauma, or abnormal neuroimaging.

The researchers found no significant differences between the CDH and non-CDH groups in terms of obesity or overweight. They also found no significant differences in obesity or overweight between all the children with headaches and the control group of healthy patients.

Despite the lack of a significant link between obesity and CDH in this study, Vasconcellos still believes overweight might play an important role in headaches in children and adolescents. “Overall, a significant proportion of the children who visit headache clinics are overweight,” she said in an interview.

PHILADELPHIA – Children and adolescents who were overweight or obese were not found to have an increased risk for chronic daily headache in a study on CDH risk factors in a pediatric population. CDH was defined in the study as headaches occurring on 15 or more days per month for more than 3 months.

Female gender, psychiatric comorbidity, caffeine use, and analgesic overuse were the only factors found in the study to increase CDH risk. These surprising results were reported by Elza Vasconcellos, M.D., at the annual meeting of the American Headache Society.

“Based on what we know about CDH in grown-ups, we expected a high correlation between high body mass index (BMI) and CDH risk in the pediatric population,” Dr. Vasconcellos, who is director of the Miami Children's Hospital headache center, said in her presentation. But the results of the study did not bear out this hypothesis.

To identify risk factors associated with the development of CDH, the researchers examined the medical records of 226 patients, aged 6–18 years, with a diagnosis of headaches or migraines. After factoring out the patients with nonchronic headaches, the investigators compared 53 patients with CDH and 146 control patients with nondaily headaches (110 with migraines, 18 with tension-type headaches, and 18 with other or mixed-types).

They also compared the BMI and percentage of overweight patients (defined as BMI less than or equal to the 95th percentile of the sex-specific BMI-for-age growth chart) in both headache groups with a control group of 100 healthy pediatric patients who were seen for well-child visits at a pediatric clinic.

The researchers found that 35% of the children with CDH were overusing analgesics more than 15 days per month, compared with none of the patients with nondaily headaches. Of the children with CDH, 34% had a comorbid psychiatric condition, compared with 19% of non-CDH patients. There were significantly more females in the CDH group than the non-CDH group (66% vs. 46%), and more children in the CDH group said they consumed caffeine (in an answer to a yes/no question) than did children in the non-CDH group (95% vs. 80%).

The two groups (CDH vs. non-CDH) were not significantly different in terms of age, sleep hours, handedness, stress, parental marital status, learning difficulties, head trauma, or abnormal neuroimaging.

The researchers found no significant differences between the CDH and non-CDH groups in terms of obesity or overweight. They also found no significant differences in obesity or overweight between all the children with headaches and the control group of healthy patients.

Despite the lack of a significant link between obesity and CDH in this study, Vasconcellos still believes overweight might play an important role in headaches in children and adolescents. “Overall, a significant proportion of the children who visit headache clinics are overweight,” she said in an interview.

PHILADELPHIA – Children and adolescents who were overweight or obese were not found to have an increased risk for chronic daily headache in a study on CDH risk factors in a pediatric population. CDH was defined in the study as headaches occurring on 15 or more days per month for more than 3 months.

Female gender, psychiatric comorbidity, caffeine use, and analgesic overuse were the only factors found in the study to increase CDH risk. These surprising results were reported by Elza Vasconcellos, M.D., at the annual meeting of the American Headache Society.

“Based on what we know about CDH in grown-ups, we expected a high correlation between high body mass index (BMI) and CDH risk in the pediatric population,” Dr. Vasconcellos, who is director of the Miami Children's Hospital headache center, said in her presentation. But the results of the study did not bear out this hypothesis.

To identify risk factors associated with the development of CDH, the researchers examined the medical records of 226 patients, aged 6–18 years, with a diagnosis of headaches or migraines. After factoring out the patients with nonchronic headaches, the investigators compared 53 patients with CDH and 146 control patients with nondaily headaches (110 with migraines, 18 with tension-type headaches, and 18 with other or mixed-types).

They also compared the BMI and percentage of overweight patients (defined as BMI less than or equal to the 95th percentile of the sex-specific BMI-for-age growth chart) in both headache groups with a control group of 100 healthy pediatric patients who were seen for well-child visits at a pediatric clinic.

The researchers found that 35% of the children with CDH were overusing analgesics more than 15 days per month, compared with none of the patients with nondaily headaches. Of the children with CDH, 34% had a comorbid psychiatric condition, compared with 19% of non-CDH patients. There were significantly more females in the CDH group than the non-CDH group (66% vs. 46%), and more children in the CDH group said they consumed caffeine (in an answer to a yes/no question) than did children in the non-CDH group (95% vs. 80%).

The two groups (CDH vs. non-CDH) were not significantly different in terms of age, sleep hours, handedness, stress, parental marital status, learning difficulties, head trauma, or abnormal neuroimaging.

The researchers found no significant differences between the CDH and non-CDH groups in terms of obesity or overweight. They also found no significant differences in obesity or overweight between all the children with headaches and the control group of healthy patients.

Despite the lack of a significant link between obesity and CDH in this study, Vasconcellos still believes overweight might play an important role in headaches in children and adolescents. “Overall, a significant proportion of the children who visit headache clinics are overweight,” she said in an interview.

PHILADELPHIA – Millions of U.S. patients who could benefit from migraine prophylaxis are not being offered this treatment by their doctors, Stephen Silberstein, M.D., said at the annual meeting of the American Headache Society.

Based on the results of the American Migraine Prevalence and Prevention (AMPP) study, Dr. Silberstein estimated that 7.7 million U.S. patients (3% of the population) should be offered preventive treatment for migraines and another 3.8 million (1.5% of population) should consider preventive treatment.

The study found, however, that of those candidates, only about 1 in 10 was actually receiving migraine prophylaxis.

The AMPP study was based on a survey mailed to 120,000 households selected to be representative of the U.S. population with respect to gender, age, and census region.

Surveys were returned from 77,879 households (a 65% response rate), yielding data for 162,576 household members aged 12 years or older. The study was funded by an educational grant from Ortho-McNeil Neurologics.

Using the ICHD-2 (International Classification of Headache Disorders updated in 2003) criteria, the researchers determined the overall prevalence of migraine in the United States to be around 12%, with a prevalence of 5%–6% in men and 17%–18% in women.

These numbers confirmed the findings of early surveys conducted in 1989 and 1999, said Dr. Silberstein, who is director of the headache center at Thomas Jefferson University Hospital in Philadelphia.

None of the earlier surveys, however, looked at candidates for prophylaxis.

To do this, Dr. Silberstein and his colleagues used data from the AMPP study to determine the severity and frequency of survey responders' migraine attacks.

Based on expert consensus, they then identified two groups for whom they said prophylaxis should be considered:

▸ Those who reported 6+ migraine days per month; or 4+ migraine days with at least some impairment; or 3+ migraine days with severe impairment or requiring bed rest.

▸ Those who reported 4–5 migraine days per month with normal functioning; 3 migraine days with some impairment; or 2 migraine days with some or greater impairment.

They found that of all the migraine sufferers identified through the survey, 26% fell into the first group and 13% fell into the second. They then extrapolated the data to the general population.

“These results clearly show that not only is migraine underdiagnosed, but when it's diagnosed, it's undertreated,” Dr. Silberstein told this newspaper.

“Doctors need to be aware that migraine is more than an individual attack,” he said. “When it becomes more frequent and disabling, it needs to be prevented,” he said.

He also stressed the need for more dialogue between doctors and patients regarding preventive treatment, and the importance of exploring the wide range of preventive strategies available.

Depending on the possible causes of the migraines, they might be prevented using medications, biofeedback, discontinuation of medications, or other strategies. “Preventive treatment includes everything we do,” he said.

PHILADELPHIA – Millions of U.S. patients who could benefit from migraine prophylaxis are not being offered this treatment by their doctors, Stephen Silberstein, M.D., said at the annual meeting of the American Headache Society.

Based on the results of the American Migraine Prevalence and Prevention (AMPP) study, Dr. Silberstein estimated that 7.7 million U.S. patients (3% of the population) should be offered preventive treatment for migraines and another 3.8 million (1.5% of population) should consider preventive treatment.

The study found, however, that of those candidates, only about 1 in 10 was actually receiving migraine prophylaxis.

The AMPP study was based on a survey mailed to 120,000 households selected to be representative of the U.S. population with respect to gender, age, and census region.

Surveys were returned from 77,879 households (a 65% response rate), yielding data for 162,576 household members aged 12 years or older. The study was funded by an educational grant from Ortho-McNeil Neurologics.

Using the ICHD-2 (International Classification of Headache Disorders updated in 2003) criteria, the researchers determined the overall prevalence of migraine in the United States to be around 12%, with a prevalence of 5%–6% in men and 17%–18% in women.

These numbers confirmed the findings of early surveys conducted in 1989 and 1999, said Dr. Silberstein, who is director of the headache center at Thomas Jefferson University Hospital in Philadelphia.

None of the earlier surveys, however, looked at candidates for prophylaxis.

To do this, Dr. Silberstein and his colleagues used data from the AMPP study to determine the severity and frequency of survey responders' migraine attacks.

Based on expert consensus, they then identified two groups for whom they said prophylaxis should be considered:

▸ Those who reported 6+ migraine days per month; or 4+ migraine days with at least some impairment; or 3+ migraine days with severe impairment or requiring bed rest.

▸ Those who reported 4–5 migraine days per month with normal functioning; 3 migraine days with some impairment; or 2 migraine days with some or greater impairment.

They found that of all the migraine sufferers identified through the survey, 26% fell into the first group and 13% fell into the second. They then extrapolated the data to the general population.

“These results clearly show that not only is migraine underdiagnosed, but when it's diagnosed, it's undertreated,” Dr. Silberstein told this newspaper.

“Doctors need to be aware that migraine is more than an individual attack,” he said. “When it becomes more frequent and disabling, it needs to be prevented,” he said.

He also stressed the need for more dialogue between doctors and patients regarding preventive treatment, and the importance of exploring the wide range of preventive strategies available.

Depending on the possible causes of the migraines, they might be prevented using medications, biofeedback, discontinuation of medications, or other strategies. “Preventive treatment includes everything we do,” he said.

PHILADELPHIA – Millions of U.S. patients who could benefit from migraine prophylaxis are not being offered this treatment by their doctors, Stephen Silberstein, M.D., said at the annual meeting of the American Headache Society.

Based on the results of the American Migraine Prevalence and Prevention (AMPP) study, Dr. Silberstein estimated that 7.7 million U.S. patients (3% of the population) should be offered preventive treatment for migraines and another 3.8 million (1.5% of population) should consider preventive treatment.

The study found, however, that of those candidates, only about 1 in 10 was actually receiving migraine prophylaxis.

The AMPP study was based on a survey mailed to 120,000 households selected to be representative of the U.S. population with respect to gender, age, and census region.

Surveys were returned from 77,879 households (a 65% response rate), yielding data for 162,576 household members aged 12 years or older. The study was funded by an educational grant from Ortho-McNeil Neurologics.

Using the ICHD-2 (International Classification of Headache Disorders updated in 2003) criteria, the researchers determined the overall prevalence of migraine in the United States to be around 12%, with a prevalence of 5%–6% in men and 17%–18% in women.

These numbers confirmed the findings of early surveys conducted in 1989 and 1999, said Dr. Silberstein, who is director of the headache center at Thomas Jefferson University Hospital in Philadelphia.

None of the earlier surveys, however, looked at candidates for prophylaxis.

To do this, Dr. Silberstein and his colleagues used data from the AMPP study to determine the severity and frequency of survey responders' migraine attacks.

Based on expert consensus, they then identified two groups for whom they said prophylaxis should be considered:

▸ Those who reported 6+ migraine days per month; or 4+ migraine days with at least some impairment; or 3+ migraine days with severe impairment or requiring bed rest.

▸ Those who reported 4–5 migraine days per month with normal functioning; 3 migraine days with some impairment; or 2 migraine days with some or greater impairment.

They found that of all the migraine sufferers identified through the survey, 26% fell into the first group and 13% fell into the second. They then extrapolated the data to the general population.

“These results clearly show that not only is migraine underdiagnosed, but when it's diagnosed, it's undertreated,” Dr. Silberstein told this newspaper.

“Doctors need to be aware that migraine is more than an individual attack,” he said. “When it becomes more frequent and disabling, it needs to be prevented,” he said.

He also stressed the need for more dialogue between doctors and patients regarding preventive treatment, and the importance of exploring the wide range of preventive strategies available.

Depending on the possible causes of the migraines, they might be prevented using medications, biofeedback, discontinuation of medications, or other strategies. “Preventive treatment includes everything we do,” he said.

PHILADELPHIA – Migraine patients have an increased risk for subclinical brain lesions that sometimes resemble lesions found in patients with multiple sclerosis or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, according to a population-based MRI study conducted in the Netherlands.

The presence of these lesions in migraine patients also raises controversial issues regarding the development of chronic migraine and potential prophylactic treatment, said Michel Ferrari, M.D., who discussed these issues in a presentation at the annual meeting of the American Headache Society.

In the CAMERA study, Dr. Ferrari, a neurologist at Leiden University Medical Center (LUMC) in the Netherlands, and his colleagues there and at the National Institutes of Health used MRI to identify brain infarcts and white matter lesions in 435 Dutch adults aged 34–63. The investigators compared the MRI images in three groups: 161 patients who had migraine with aura, 134 patients who had migraine without aura, and 140 controls without migraine.

They found a significant increase in subclinical deep white matter lesions in patients with migraine, compared with controls–most significantly, in women who had migraine with aura.

Questions raised by this study, according to Dr. Ferrari, include: Do the lesions cause any functional changes in migraineurs' brains? Are the lesions related to severity or chronification of migraines? How might this affect migraine treatment (if it is assumed there are progressive changes in the brain)? Can earlier, more aggressive migraine treatment lower the risk for lesions, thus lowering risk of the migraines becoming chronic?

As for the causes of the lesions, Dr. Ferrari mentioned multiple possibilities, including ischemia, cortical spreading depression, genetic factors, apoptosis, and, although unlikely, patent foramen ovale. Any of these could be contributing factors in causing lesions, he said, and they could also be comorbid conditions with migraines.

There is not enough evidence yet to indicate whether the migraines are causally related to the lesions or not.

Dr. Ferrari emphasized that a great deal of additional research is needed to address these issues and that no clinical recommendations can be made based on the results of the CAMERA MRI study. These need confirmation first.

“We worried that publishing this study would lead physicians to make a shortcut from lesions to treatment,” Dr. Ferrari said in an interview with this newspaper. “We should not treat a picture; we should treat a patient,” he cautioned.

Still, he said, clinicians should be aware of the issues and especially of the frequent confusion, on the part of physicians who are viewing MRIs, between migraine and other conditions–mainly multiple sclerosis.

If lesions are found, clinicians need to take a very careful history to figure out the cause of the lesions before making a diagnosis, he said.

In a related study, no difference in white matter lesions and infarcts was found between stroke patients with a history of migraines and those without migraine. (See sidebar.)

MRIs show (left to right) coexisting MS and migraine; migraine alone; and coexisting cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and migraine. Photos courtesy Dr. Michel Ferrari

Migraines: No Link to Lesions, Infarcts

There was no difference in the number and volume of white matter lesions or the number, location, and size of cerebral infarcts in stroke patients with a history of migraine compared to stroke patients without migraine, in an MRI study of 83 patients.

These results were reported by Hans Katzberg, M.D., of the University of Toronto, at the AHS meeting.

“We wanted to look at whether brain lesions in patients with migraine and stroke might be different, indicating a possible link between brain changes associated with migraine and an increased risk for stroke,” Dr. Katzberg said in an interview.

The results of the study did not indicate a general association. Still, he said, “our cohort did include a subgroup of migraine patients with stroke with no other obvious etiology, and these patients will be important to study further.”

PHILADELPHIA – Migraine patients have an increased risk for subclinical brain lesions that sometimes resemble lesions found in patients with multiple sclerosis or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, according to a population-based MRI study conducted in the Netherlands.

The presence of these lesions in migraine patients also raises controversial issues regarding the development of chronic migraine and potential prophylactic treatment, said Michel Ferrari, M.D., who discussed these issues in a presentation at the annual meeting of the American Headache Society.

In the CAMERA study, Dr. Ferrari, a neurologist at Leiden University Medical Center (LUMC) in the Netherlands, and his colleagues there and at the National Institutes of Health used MRI to identify brain infarcts and white matter lesions in 435 Dutch adults aged 34–63. The investigators compared the MRI images in three groups: 161 patients who had migraine with aura, 134 patients who had migraine without aura, and 140 controls without migraine.

They found a significant increase in subclinical deep white matter lesions in patients with migraine, compared with controls–most significantly, in women who had migraine with aura.

Questions raised by this study, according to Dr. Ferrari, include: Do the lesions cause any functional changes in migraineurs' brains? Are the lesions related to severity or chronification of migraines? How might this affect migraine treatment (if it is assumed there are progressive changes in the brain)? Can earlier, more aggressive migraine treatment lower the risk for lesions, thus lowering risk of the migraines becoming chronic?

As for the causes of the lesions, Dr. Ferrari mentioned multiple possibilities, including ischemia, cortical spreading depression, genetic factors, apoptosis, and, although unlikely, patent foramen ovale. Any of these could be contributing factors in causing lesions, he said, and they could also be comorbid conditions with migraines.

There is not enough evidence yet to indicate whether the migraines are causally related to the lesions or not.

Dr. Ferrari emphasized that a great deal of additional research is needed to address these issues and that no clinical recommendations can be made based on the results of the CAMERA MRI study. These need confirmation first.

“We worried that publishing this study would lead physicians to make a shortcut from lesions to treatment,” Dr. Ferrari said in an interview with this newspaper. “We should not treat a picture; we should treat a patient,” he cautioned.

Still, he said, clinicians should be aware of the issues and especially of the frequent confusion, on the part of physicians who are viewing MRIs, between migraine and other conditions–mainly multiple sclerosis.

If lesions are found, clinicians need to take a very careful history to figure out the cause of the lesions before making a diagnosis, he said.

In a related study, no difference in white matter lesions and infarcts was found between stroke patients with a history of migraines and those without migraine. (See sidebar.)

MRIs show (left to right) coexisting MS and migraine; migraine alone; and coexisting cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and migraine. Photos courtesy Dr. Michel Ferrari

Migraines: No Link to Lesions, Infarcts

There was no difference in the number and volume of white matter lesions or the number, location, and size of cerebral infarcts in stroke patients with a history of migraine compared to stroke patients without migraine, in an MRI study of 83 patients.

These results were reported by Hans Katzberg, M.D., of the University of Toronto, at the AHS meeting.

“We wanted to look at whether brain lesions in patients with migraine and stroke might be different, indicating a possible link between brain changes associated with migraine and an increased risk for stroke,” Dr. Katzberg said in an interview.

The results of the study did not indicate a general association. Still, he said, “our cohort did include a subgroup of migraine patients with stroke with no other obvious etiology, and these patients will be important to study further.”

PHILADELPHIA – Migraine patients have an increased risk for subclinical brain lesions that sometimes resemble lesions found in patients with multiple sclerosis or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, according to a population-based MRI study conducted in the Netherlands.

The presence of these lesions in migraine patients also raises controversial issues regarding the development of chronic migraine and potential prophylactic treatment, said Michel Ferrari, M.D., who discussed these issues in a presentation at the annual meeting of the American Headache Society.

In the CAMERA study, Dr. Ferrari, a neurologist at Leiden University Medical Center (LUMC) in the Netherlands, and his colleagues there and at the National Institutes of Health used MRI to identify brain infarcts and white matter lesions in 435 Dutch adults aged 34–63. The investigators compared the MRI images in three groups: 161 patients who had migraine with aura, 134 patients who had migraine without aura, and 140 controls without migraine.

They found a significant increase in subclinical deep white matter lesions in patients with migraine, compared with controls–most significantly, in women who had migraine with aura.

Questions raised by this study, according to Dr. Ferrari, include: Do the lesions cause any functional changes in migraineurs' brains? Are the lesions related to severity or chronification of migraines? How might this affect migraine treatment (if it is assumed there are progressive changes in the brain)? Can earlier, more aggressive migraine treatment lower the risk for lesions, thus lowering risk of the migraines becoming chronic?

As for the causes of the lesions, Dr. Ferrari mentioned multiple possibilities, including ischemia, cortical spreading depression, genetic factors, apoptosis, and, although unlikely, patent foramen ovale. Any of these could be contributing factors in causing lesions, he said, and they could also be comorbid conditions with migraines.

There is not enough evidence yet to indicate whether the migraines are causally related to the lesions or not.

Dr. Ferrari emphasized that a great deal of additional research is needed to address these issues and that no clinical recommendations can be made based on the results of the CAMERA MRI study. These need confirmation first.

“We worried that publishing this study would lead physicians to make a shortcut from lesions to treatment,” Dr. Ferrari said in an interview with this newspaper. “We should not treat a picture; we should treat a patient,” he cautioned.

Still, he said, clinicians should be aware of the issues and especially of the frequent confusion, on the part of physicians who are viewing MRIs, between migraine and other conditions–mainly multiple sclerosis.

If lesions are found, clinicians need to take a very careful history to figure out the cause of the lesions before making a diagnosis, he said.

In a related study, no difference in white matter lesions and infarcts was found between stroke patients with a history of migraines and those without migraine. (See sidebar.)

MRIs show (left to right) coexisting MS and migraine; migraine alone; and coexisting cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and migraine. Photos courtesy Dr. Michel Ferrari

Migraines: No Link to Lesions, Infarcts

There was no difference in the number and volume of white matter lesions or the number, location, and size of cerebral infarcts in stroke patients with a history of migraine compared to stroke patients without migraine, in an MRI study of 83 patients.

These results were reported by Hans Katzberg, M.D., of the University of Toronto, at the AHS meeting.

“We wanted to look at whether brain lesions in patients with migraine and stroke might be different, indicating a possible link between brain changes associated with migraine and an increased risk for stroke,” Dr. Katzberg said in an interview.

The results of the study did not indicate a general association. Still, he said, “our cohort did include a subgroup of migraine patients with stroke with no other obvious etiology, and these patients will be important to study further.”

PHILADELPHIA – For the first time, the triptan, zolmitriptan nasal spray has been found to be effective in the short-term treatment of migraines in adolescents, Paul Winner, D.O., reported at the annual meeting of the American Headache Society.

Seven triptans are currently approved for adult migraine treatment, but none of them are approved for use in adolescents, noted Dr. Winner, director of the Palm Beach (Fla.) Headache Center.

He reported on a multicenter, randomized, double-blind, placebo-controlled trial that used a novel design in which 248 adolescents were initially enrolled, and then 171 were selected for the intent-to-treat group based on lack of response to zolmitriptan in a single-blind placebo challenge (see box).

The study was supported by AstraZeneca, the maker of zolmitriptan nasal spray (Zomig). Dr. Winner has served as a researcher, speaker, and consultant to the company.

In the 171 adolescents (mean age 14.1 years), who were treated for a total of 275 migraine attacks, zolmitriptan nasal spray produced significantly higher headache response rates than placebo at 1 hour post dose (58% vs. 43%), with an onset of action as early as 15 minutes.

At 1 hour after treatment, 28% of the adolescents in the zolmitriptan group were pain free, compared with 10% of those in the placebo group.

Also, 51% of those in the zolmitriptan group were able to resume normal activities vs. 38% of those in the placebo group. At 2 hours after treatment, 54% of those in the zolmitriptan group were pain free, vs. 36% of those in the placebo group.

There were no serious adverse events, and no one withdrew from the study because of adverse events.

“We found that the treatment was effective, fast, and well tolerated,” Dr. Winner told this newspaper.

“Hopefully, this will begin the process of getting some of these medications [triptans] approved for adolescents, a group that can clearly benefit from them,” he noted.

Triptans should not be used in all adolescents with migraine, he added, but there is a definite need for such treatment in those who do not respond to over-the-counter medications and have migraine-related disability that prevents them from normal functioning.

Study Excluded Placebo Responders

In previous studies on triptans in adolescents, placebo response rates that were significantly higher than those in adult patients with migraine prevented primary end points from reaching statistical significance, Dr. Winner said.

So he and his associates used a novel design that excluded patients who responded to placebo.

The study initially enrolled 248 adolescents and treated all of their migraine attacks with placebo nasal spray. In this single-blind phase of the study, patients who responded within 15 minutes were excluded, leaving only 171 placebo nonresponders in the intent-to-treat group.

In the double-blind phase, placebo response rates were similar to those in adult studies, Dr. Winner said.

The use of a placebo challenge to screen out placebo responders “needs to be the standard of design moving forward,” he said. “Old designs just don't work.”

The study design yielded an interesting finding, he added: “Once a placebo nonresponder, not always a placebo nonresponder.”

The Food and Drug Administration, which initially approved the placebo challenge design, requested an analysis that included all 248 patients. This analysis assumed that all patients in the placebo-response group (none of whom actually received subsequent treatment) would have responded to placebo and not responded to treatment, had they been included in the double-blind part of the study. In this worst-case scenario, no significant results were obtained.

PHILADELPHIA – For the first time, the triptan, zolmitriptan nasal spray has been found to be effective in the short-term treatment of migraines in adolescents, Paul Winner, D.O., reported at the annual meeting of the American Headache Society.

Seven triptans are currently approved for adult migraine treatment, but none of them are approved for use in adolescents, noted Dr. Winner, director of the Palm Beach (Fla.) Headache Center.

He reported on a multicenter, randomized, double-blind, placebo-controlled trial that used a novel design in which 248 adolescents were initially enrolled, and then 171 were selected for the intent-to-treat group based on lack of response to zolmitriptan in a single-blind placebo challenge (see box).

The study was supported by AstraZeneca, the maker of zolmitriptan nasal spray (Zomig). Dr. Winner has served as a researcher, speaker, and consultant to the company.

In the 171 adolescents (mean age 14.1 years), who were treated for a total of 275 migraine attacks, zolmitriptan nasal spray produced significantly higher headache response rates than placebo at 1 hour post dose (58% vs. 43%), with an onset of action as early as 15 minutes.

At 1 hour after treatment, 28% of the adolescents in the zolmitriptan group were pain free, compared with 10% of those in the placebo group.

Also, 51% of those in the zolmitriptan group were able to resume normal activities vs. 38% of those in the placebo group. At 2 hours after treatment, 54% of those in the zolmitriptan group were pain free, vs. 36% of those in the placebo group.

There were no serious adverse events, and no one withdrew from the study because of adverse events.

“We found that the treatment was effective, fast, and well tolerated,” Dr. Winner told this newspaper.

“Hopefully, this will begin the process of getting some of these medications [triptans] approved for adolescents, a group that can clearly benefit from them,” he noted.

Triptans should not be used in all adolescents with migraine, he added, but there is a definite need for such treatment in those who do not respond to over-the-counter medications and have migraine-related disability that prevents them from normal functioning.

Study Excluded Placebo Responders

In previous studies on triptans in adolescents, placebo response rates that were significantly higher than those in adult patients with migraine prevented primary end points from reaching statistical significance, Dr. Winner said.

So he and his associates used a novel design that excluded patients who responded to placebo.

The study initially enrolled 248 adolescents and treated all of their migraine attacks with placebo nasal spray. In this single-blind phase of the study, patients who responded within 15 minutes were excluded, leaving only 171 placebo nonresponders in the intent-to-treat group.

In the double-blind phase, placebo response rates were similar to those in adult studies, Dr. Winner said.

The use of a placebo challenge to screen out placebo responders “needs to be the standard of design moving forward,” he said. “Old designs just don't work.”

The study design yielded an interesting finding, he added: “Once a placebo nonresponder, not always a placebo nonresponder.”

The Food and Drug Administration, which initially approved the placebo challenge design, requested an analysis that included all 248 patients. This analysis assumed that all patients in the placebo-response group (none of whom actually received subsequent treatment) would have responded to placebo and not responded to treatment, had they been included in the double-blind part of the study. In this worst-case scenario, no significant results were obtained.

PHILADELPHIA – For the first time, the triptan, zolmitriptan nasal spray has been found to be effective in the short-term treatment of migraines in adolescents, Paul Winner, D.O., reported at the annual meeting of the American Headache Society.

Seven triptans are currently approved for adult migraine treatment, but none of them are approved for use in adolescents, noted Dr. Winner, director of the Palm Beach (Fla.) Headache Center.

He reported on a multicenter, randomized, double-blind, placebo-controlled trial that used a novel design in which 248 adolescents were initially enrolled, and then 171 were selected for the intent-to-treat group based on lack of response to zolmitriptan in a single-blind placebo challenge (see box).

The study was supported by AstraZeneca, the maker of zolmitriptan nasal spray (Zomig). Dr. Winner has served as a researcher, speaker, and consultant to the company.

In the 171 adolescents (mean age 14.1 years), who were treated for a total of 275 migraine attacks, zolmitriptan nasal spray produced significantly higher headache response rates than placebo at 1 hour post dose (58% vs. 43%), with an onset of action as early as 15 minutes.

At 1 hour after treatment, 28% of the adolescents in the zolmitriptan group were pain free, compared with 10% of those in the placebo group.

Also, 51% of those in the zolmitriptan group were able to resume normal activities vs. 38% of those in the placebo group. At 2 hours after treatment, 54% of those in the zolmitriptan group were pain free, vs. 36% of those in the placebo group.

There were no serious adverse events, and no one withdrew from the study because of adverse events.

“We found that the treatment was effective, fast, and well tolerated,” Dr. Winner told this newspaper.

“Hopefully, this will begin the process of getting some of these medications [triptans] approved for adolescents, a group that can clearly benefit from them,” he noted.

Triptans should not be used in all adolescents with migraine, he added, but there is a definite need for such treatment in those who do not respond to over-the-counter medications and have migraine-related disability that prevents them from normal functioning.

Study Excluded Placebo Responders

In previous studies on triptans in adolescents, placebo response rates that were significantly higher than those in adult patients with migraine prevented primary end points from reaching statistical significance, Dr. Winner said.

So he and his associates used a novel design that excluded patients who responded to placebo.

The study initially enrolled 248 adolescents and treated all of their migraine attacks with placebo nasal spray. In this single-blind phase of the study, patients who responded within 15 minutes were excluded, leaving only 171 placebo nonresponders in the intent-to-treat group.

In the double-blind phase, placebo response rates were similar to those in adult studies, Dr. Winner said.

The use of a placebo challenge to screen out placebo responders “needs to be the standard of design moving forward,” he said. “Old designs just don't work.”

The study design yielded an interesting finding, he added: “Once a placebo nonresponder, not always a placebo nonresponder.”

The Food and Drug Administration, which initially approved the placebo challenge design, requested an analysis that included all 248 patients. This analysis assumed that all patients in the placebo-response group (none of whom actually received subsequent treatment) would have responded to placebo and not responded to treatment, had they been included in the double-blind part of the study. In this worst-case scenario, no significant results were obtained.