European Headache and Migraine Trust International Congress (EHMTIC)

LONDON – The recent discovery of the first four genetic susceptibility loci for migraine without aura has zero clinical relevance today for migraine patients or their physicians, according to experts on migraine genetics.

"Whenever there is a new genetic study, you can easily become almost convinced that now we have the gene and we can treat migraine better. No! Currently there is no indication to test migraine patients for specific genes. It wouldn’t help you at all in terms of treatment or prognosis," Dr. Tobias Kurth emphasized at the European Headache and Migraine Trust International Congress.

"Make no mistake: We have achieved a lot over the last years, and many groups continue to do extraordinary work. However, we all have to realize that we still don’t know the precise mechanisms involved in genetic markers of migraine. We haven’t really shown that having these genes is a predictive tool that can tell patients that they will get migraine, or if they have it what their disease course will be," added Dr. Kurth, director of research at the French National Institute of Health and Medical Research, Bordeaux.

Dr. Arn M.J.M. van den Maagdenberg, a coauthor of the recently published genomewide association study that identified the first four susceptibility loci for migraine without aura (Nat. Gen. 2012;44:777-82), presented highlights of the ambitious study, which was carried out by the International Headache Genetics Consortium. The study involved testing 2,326 headache clinic patients with migraine without aura and 4,580 matched controls for roughly 500,000 genetic variants. The investigators then confirmed their results in a separate replication cohort composed of 2,508 patients with migraine without aura and 2,652 controls.

Dr. van den Maagdenberg was quick to agree that the results aren’t clinically relevant, in part because the four genes explain only a small portion of the genetic variance in migraine. However, the findings do implicate specific pathways of importance in the disease process, he noted.

"You can plot these four genes in three different pathways: neuronal, vascular, and pain. You may think you already knew that these pathways are important in migraine, but now we have molecular proof that migraine patients do indeed have genes that predispose them to migraine based on these pathways. Of course, we’ll need to do a lot of further studies of different kinds in order to identify the mechanisms involved," said Dr. van den Maagdenberg of Leiden (the Netherlands) University.

Of the four novel migraine genes, three – MEF2D, ASTN2, and PHACTR1 – are involved in the neuronal pathway. PHACTR1 also figures in the vascular pathway of migraine. And TGFBR2 plays roles in both the vascular and pain pathways, according to the neurologist.

Dr. Kurth has personal experience in fielding overreaction to genetic study findings, both by the public and by health professionals. He was a coinvestigator in a much-publicized report from the Women’s Genome Health Study that identified five single nucleotide polymorphisms (SNPs), or susceptibility loci, that may be associated with increased risk of cardiovascular events in women with migraine.

This was a genomewide association study of 5,122 women with migraine who were followed for 12 years as part of the National Institutes of Health–sponsored Women’s Health Study. One susceptibility locus was associated with a statistically significant and sky-high 12.3-fold risk of cardiovascular death during follow-up. Two others were linked to impressive-sounding 5- and 6.4-fold increased risks of ischemic stroke in women with migraine with aura (PLoS One 2011;6:e22106). But neither Dr. Kurth nor his coworkers really believe those numbers.

"Those odds ratios look quite high, but the number of outcome events is extraordinarily small here: 164 cardiovascular events in 12 years. So despite the statistical significance, these odds ratios are completely meaningless. We have to be extremely careful not to say that these genes are actually the cause of women with migraine getting cardiovascular disease. This is a hypothesis-generating study," Dr. Kurth explained.

Dr. Kurth and Dr. van den Maagdenberg reported having no financial conflicts.

LONDON – The recent discovery of the first four genetic susceptibility loci for migraine without aura has zero clinical relevance today for migraine patients or their physicians, according to experts on migraine genetics.

"Whenever there is a new genetic study, you can easily become almost convinced that now we have the gene and we can treat migraine better. No! Currently there is no indication to test migraine patients for specific genes. It wouldn’t help you at all in terms of treatment or prognosis," Dr. Tobias Kurth emphasized at the European Headache and Migraine Trust International Congress.

"Make no mistake: We have achieved a lot over the last years, and many groups continue to do extraordinary work. However, we all have to realize that we still don’t know the precise mechanisms involved in genetic markers of migraine. We haven’t really shown that having these genes is a predictive tool that can tell patients that they will get migraine, or if they have it what their disease course will be," added Dr. Kurth, director of research at the French National Institute of Health and Medical Research, Bordeaux.

Dr. Arn M.J.M. van den Maagdenberg, a coauthor of the recently published genomewide association study that identified the first four susceptibility loci for migraine without aura (Nat. Gen. 2012;44:777-82), presented highlights of the ambitious study, which was carried out by the International Headache Genetics Consortium. The study involved testing 2,326 headache clinic patients with migraine without aura and 4,580 matched controls for roughly 500,000 genetic variants. The investigators then confirmed their results in a separate replication cohort composed of 2,508 patients with migraine without aura and 2,652 controls.

Dr. van den Maagdenberg was quick to agree that the results aren’t clinically relevant, in part because the four genes explain only a small portion of the genetic variance in migraine. However, the findings do implicate specific pathways of importance in the disease process, he noted.

"You can plot these four genes in three different pathways: neuronal, vascular, and pain. You may think you already knew that these pathways are important in migraine, but now we have molecular proof that migraine patients do indeed have genes that predispose them to migraine based on these pathways. Of course, we’ll need to do a lot of further studies of different kinds in order to identify the mechanisms involved," said Dr. van den Maagdenberg of Leiden (the Netherlands) University.

Of the four novel migraine genes, three – MEF2D, ASTN2, and PHACTR1 – are involved in the neuronal pathway. PHACTR1 also figures in the vascular pathway of migraine. And TGFBR2 plays roles in both the vascular and pain pathways, according to the neurologist.

Dr. Kurth has personal experience in fielding overreaction to genetic study findings, both by the public and by health professionals. He was a coinvestigator in a much-publicized report from the Women’s Genome Health Study that identified five single nucleotide polymorphisms (SNPs), or susceptibility loci, that may be associated with increased risk of cardiovascular events in women with migraine.

This was a genomewide association study of 5,122 women with migraine who were followed for 12 years as part of the National Institutes of Health–sponsored Women’s Health Study. One susceptibility locus was associated with a statistically significant and sky-high 12.3-fold risk of cardiovascular death during follow-up. Two others were linked to impressive-sounding 5- and 6.4-fold increased risks of ischemic stroke in women with migraine with aura (PLoS One 2011;6:e22106). But neither Dr. Kurth nor his coworkers really believe those numbers.

"Those odds ratios look quite high, but the number of outcome events is extraordinarily small here: 164 cardiovascular events in 12 years. So despite the statistical significance, these odds ratios are completely meaningless. We have to be extremely careful not to say that these genes are actually the cause of women with migraine getting cardiovascular disease. This is a hypothesis-generating study," Dr. Kurth explained.

Dr. Kurth and Dr. van den Maagdenberg reported having no financial conflicts.

LONDON – The recent discovery of the first four genetic susceptibility loci for migraine without aura has zero clinical relevance today for migraine patients or their physicians, according to experts on migraine genetics.

"Whenever there is a new genetic study, you can easily become almost convinced that now we have the gene and we can treat migraine better. No! Currently there is no indication to test migraine patients for specific genes. It wouldn’t help you at all in terms of treatment or prognosis," Dr. Tobias Kurth emphasized at the European Headache and Migraine Trust International Congress.

"Make no mistake: We have achieved a lot over the last years, and many groups continue to do extraordinary work. However, we all have to realize that we still don’t know the precise mechanisms involved in genetic markers of migraine. We haven’t really shown that having these genes is a predictive tool that can tell patients that they will get migraine, or if they have it what their disease course will be," added Dr. Kurth, director of research at the French National Institute of Health and Medical Research, Bordeaux.

Dr. Arn M.J.M. van den Maagdenberg, a coauthor of the recently published genomewide association study that identified the first four susceptibility loci for migraine without aura (Nat. Gen. 2012;44:777-82), presented highlights of the ambitious study, which was carried out by the International Headache Genetics Consortium. The study involved testing 2,326 headache clinic patients with migraine without aura and 4,580 matched controls for roughly 500,000 genetic variants. The investigators then confirmed their results in a separate replication cohort composed of 2,508 patients with migraine without aura and 2,652 controls.

Dr. van den Maagdenberg was quick to agree that the results aren’t clinically relevant, in part because the four genes explain only a small portion of the genetic variance in migraine. However, the findings do implicate specific pathways of importance in the disease process, he noted.

"You can plot these four genes in three different pathways: neuronal, vascular, and pain. You may think you already knew that these pathways are important in migraine, but now we have molecular proof that migraine patients do indeed have genes that predispose them to migraine based on these pathways. Of course, we’ll need to do a lot of further studies of different kinds in order to identify the mechanisms involved," said Dr. van den Maagdenberg of Leiden (the Netherlands) University.

Of the four novel migraine genes, three – MEF2D, ASTN2, and PHACTR1 – are involved in the neuronal pathway. PHACTR1 also figures in the vascular pathway of migraine. And TGFBR2 plays roles in both the vascular and pain pathways, according to the neurologist.

Dr. Kurth has personal experience in fielding overreaction to genetic study findings, both by the public and by health professionals. He was a coinvestigator in a much-publicized report from the Women’s Genome Health Study that identified five single nucleotide polymorphisms (SNPs), or susceptibility loci, that may be associated with increased risk of cardiovascular events in women with migraine.

This was a genomewide association study of 5,122 women with migraine who were followed for 12 years as part of the National Institutes of Health–sponsored Women’s Health Study. One susceptibility locus was associated with a statistically significant and sky-high 12.3-fold risk of cardiovascular death during follow-up. Two others were linked to impressive-sounding 5- and 6.4-fold increased risks of ischemic stroke in women with migraine with aura (PLoS One 2011;6:e22106). But neither Dr. Kurth nor his coworkers really believe those numbers.

"Those odds ratios look quite high, but the number of outcome events is extraordinarily small here: 164 cardiovascular events in 12 years. So despite the statistical significance, these odds ratios are completely meaningless. We have to be extremely careful not to say that these genes are actually the cause of women with migraine getting cardiovascular disease. This is a hypothesis-generating study," Dr. Kurth explained.

Dr. Kurth and Dr. van den Maagdenberg reported having no financial conflicts.

LONDON – Funding for headache research and therapy gets the short end of the stick in European neurology.

Two ambitious recent studies tell the tale. One, carried out by the European Brain Council, estimated the annual costs for 19 categories of brain disorders, both neurologic and psychiatric, in 30 European countries. The other study focused specifically on the direct and indirect monetary costs of the major headache disorders, including migraine, tension-type headache, and medication-overuse headache.

Dr. Rigmor Højland Jensen referenced both studies in her address as incoming president of the European Headache Federation at the European Headache and Migraine Trust International Congress.

"Headache is competing with other diseases for funding. These are very important studies we have to include in our arguments all the time," said Dr. Jensen, professor of neurology at the University of Copenhagen.

The European Brain Council study (Eur. J. Neurol. 2012;19:155-62) employed sophisticated modeling techniques to estimate the total cost of brain disorders in Europe in 2010 at 798 billion euros. That’s an average of 1,550 euros per inhabitant.

The average cost per European with a headache disorder in 2010 was 285 euros, a figure that pales in comparison to the 30,000 euros per patient with a neuromuscular disorder. Because headache disorders are so common, though, the total annual cost for headache disorders was calculated at a hefty 43.5 billion euros.

In contrast, the annual total cost for neuromuscular disorders was 7.7 billion euros; for epilepsy, 13.8 billion euros; multiple sclerosis, 14.6 billion euros; Parkinson’s disease, 13.9 billion euros; and traumatic brain injury, 33 billion euros.

"Headaches cost more than epilepsy, multiple sclerosis, and Parkinson’s disease together. And yet how much more research in your department and how many more resources are dedicated to treating these three disorders, compared with headache?" Dr. Jensen asked.

For 2010, the costliest brain disorders in Europe included dementia at 105.2 billion euros, stroke at 64.1 billion euros, and several psychiatric disorders: psychotic disorders came in at 93.9 billion euros, mood disorders at 113.4 billion euros, anxiety disorders at 74.4 billion euros, and addiction disorders at 65.7 billion euros. In addition, the cost of personality disorders was estimated at 27.3 billion euros and somatoform disorders at 21.2 billion euros.

The headache cost study, known as the Eurolight Project, involved extrapolation from a detailed cross-sectional survey conducted in 8,412 individuals in eight countries representing 55% of the adult European Union population.

The investigators calculated the annual cost of headache among 18- to 65-year-olds in the European Union at 173 billion euros. That’s considerably more than the 43.5 billion euros figure cited in the European Brain Council study because, in figuring the estimated indirect costs associated with headache, the Eurolight Project investigators included not only work absenteeism but also reduced productivity while at work.

Sixty-four percent of the estimated annual cost of headache among European adults was apportioned to migraine, 21% to medication-overuse headache, 12% to tension-type headache, and the remainder to other headaches (Eur. J. Neurol. 2012;19:703-11).

Dr. Jensen reported financial relationships with ATI, Medotech, Merck, Neurocore, NorPharma, and Pfizer.

B.Jancin@elsevier.com

LONDON – Funding for headache research and therapy gets the short end of the stick in European neurology.

Two ambitious recent studies tell the tale. One, carried out by the European Brain Council, estimated the annual costs for 19 categories of brain disorders, both neurologic and psychiatric, in 30 European countries. The other study focused specifically on the direct and indirect monetary costs of the major headache disorders, including migraine, tension-type headache, and medication-overuse headache.

Dr. Rigmor Højland Jensen referenced both studies in her address as incoming president of the European Headache Federation at the European Headache and Migraine Trust International Congress.

"Headache is competing with other diseases for funding. These are very important studies we have to include in our arguments all the time," said Dr. Jensen, professor of neurology at the University of Copenhagen.

The European Brain Council study (Eur. J. Neurol. 2012;19:155-62) employed sophisticated modeling techniques to estimate the total cost of brain disorders in Europe in 2010 at 798 billion euros. That’s an average of 1,550 euros per inhabitant.

The average cost per European with a headache disorder in 2010 was 285 euros, a figure that pales in comparison to the 30,000 euros per patient with a neuromuscular disorder. Because headache disorders are so common, though, the total annual cost for headache disorders was calculated at a hefty 43.5 billion euros.

In contrast, the annual total cost for neuromuscular disorders was 7.7 billion euros; for epilepsy, 13.8 billion euros; multiple sclerosis, 14.6 billion euros; Parkinson’s disease, 13.9 billion euros; and traumatic brain injury, 33 billion euros.

"Headaches cost more than epilepsy, multiple sclerosis, and Parkinson’s disease together. And yet how much more research in your department and how many more resources are dedicated to treating these three disorders, compared with headache?" Dr. Jensen asked.

For 2010, the costliest brain disorders in Europe included dementia at 105.2 billion euros, stroke at 64.1 billion euros, and several psychiatric disorders: psychotic disorders came in at 93.9 billion euros, mood disorders at 113.4 billion euros, anxiety disorders at 74.4 billion euros, and addiction disorders at 65.7 billion euros. In addition, the cost of personality disorders was estimated at 27.3 billion euros and somatoform disorders at 21.2 billion euros.

The headache cost study, known as the Eurolight Project, involved extrapolation from a detailed cross-sectional survey conducted in 8,412 individuals in eight countries representing 55% of the adult European Union population.

The investigators calculated the annual cost of headache among 18- to 65-year-olds in the European Union at 173 billion euros. That’s considerably more than the 43.5 billion euros figure cited in the European Brain Council study because, in figuring the estimated indirect costs associated with headache, the Eurolight Project investigators included not only work absenteeism but also reduced productivity while at work.

Sixty-four percent of the estimated annual cost of headache among European adults was apportioned to migraine, 21% to medication-overuse headache, 12% to tension-type headache, and the remainder to other headaches (Eur. J. Neurol. 2012;19:703-11).

Dr. Jensen reported financial relationships with ATI, Medotech, Merck, Neurocore, NorPharma, and Pfizer.

B.Jancin@elsevier.com

LONDON – Funding for headache research and therapy gets the short end of the stick in European neurology.

Two ambitious recent studies tell the tale. One, carried out by the European Brain Council, estimated the annual costs for 19 categories of brain disorders, both neurologic and psychiatric, in 30 European countries. The other study focused specifically on the direct and indirect monetary costs of the major headache disorders, including migraine, tension-type headache, and medication-overuse headache.

Dr. Rigmor Højland Jensen referenced both studies in her address as incoming president of the European Headache Federation at the European Headache and Migraine Trust International Congress.

"Headache is competing with other diseases for funding. These are very important studies we have to include in our arguments all the time," said Dr. Jensen, professor of neurology at the University of Copenhagen.

The European Brain Council study (Eur. J. Neurol. 2012;19:155-62) employed sophisticated modeling techniques to estimate the total cost of brain disorders in Europe in 2010 at 798 billion euros. That’s an average of 1,550 euros per inhabitant.

The average cost per European with a headache disorder in 2010 was 285 euros, a figure that pales in comparison to the 30,000 euros per patient with a neuromuscular disorder. Because headache disorders are so common, though, the total annual cost for headache disorders was calculated at a hefty 43.5 billion euros.

In contrast, the annual total cost for neuromuscular disorders was 7.7 billion euros; for epilepsy, 13.8 billion euros; multiple sclerosis, 14.6 billion euros; Parkinson’s disease, 13.9 billion euros; and traumatic brain injury, 33 billion euros.

"Headaches cost more than epilepsy, multiple sclerosis, and Parkinson’s disease together. And yet how much more research in your department and how many more resources are dedicated to treating these three disorders, compared with headache?" Dr. Jensen asked.

For 2010, the costliest brain disorders in Europe included dementia at 105.2 billion euros, stroke at 64.1 billion euros, and several psychiatric disorders: psychotic disorders came in at 93.9 billion euros, mood disorders at 113.4 billion euros, anxiety disorders at 74.4 billion euros, and addiction disorders at 65.7 billion euros. In addition, the cost of personality disorders was estimated at 27.3 billion euros and somatoform disorders at 21.2 billion euros.

The headache cost study, known as the Eurolight Project, involved extrapolation from a detailed cross-sectional survey conducted in 8,412 individuals in eight countries representing 55% of the adult European Union population.

The investigators calculated the annual cost of headache among 18- to 65-year-olds in the European Union at 173 billion euros. That’s considerably more than the 43.5 billion euros figure cited in the European Brain Council study because, in figuring the estimated indirect costs associated with headache, the Eurolight Project investigators included not only work absenteeism but also reduced productivity while at work.

Sixty-four percent of the estimated annual cost of headache among European adults was apportioned to migraine, 21% to medication-overuse headache, 12% to tension-type headache, and the remainder to other headaches (Eur. J. Neurol. 2012;19:703-11).

Dr. Jensen reported financial relationships with ATI, Medotech, Merck, Neurocore, NorPharma, and Pfizer.

B.Jancin@elsevier.com

LONDON – Enthusiasm is mounting among headache specialists for noninvasive device therapy for acute migraine.

"Normally I’m quite a cynical person, but I think within 10 years time half of my people in the headache clinic won’t be using any medications for their headaches. They’ll have an electronic device of some kind. You get your migraine sorted out, you put your device back in your pants pocket, and you carry on," Dr. Fayyaz Ahmed said at the European Headache and Migraine Trust International Congress.

"I think in about 10 years time you’ll have SIM cards for these neurostimulatory devices, you’ll put the card in an ATM-like machine – perhaps in a supermarket – and you’ll top it up and recharge it," predicted Dr. Ahmed, a consultant neurologist in Hull, England, and chair of the British Association for the Study of Headache.

The noninvasive neurostimulatory therapy most discussed at the congress was the Spring TMS single-pulse transcranial magnetic stimulation device, which since 2011 has been approved in Europe for the acute treatment of migraine. The Spring TMS device is manufactured by U.S.-based eNeura Therapeutics, which is seeking marketing approval from the Food and Drug Administration.

The international congress also saw the presentation of the first multicenter, randomized, sham-controlled study of the noninvasive Cefaly device for prevention of migraine via supraorbital transcutaneous neurostimulation.

"It’s not a revolutionary therapy. The effect size is moderate and inferior to that of the most effective preventive drugs. Its great advantage is that it’s devoid of side effects. I think the Cefaly device is another tool we can use for preventing migraine," Dr. Jean Schoenen concluded in presenting the study data.

Dr. Ahmed said physician and patient interest in noninvasive device therapy is being driven by the sizable proportion of migraine patients who don’t respond adequately to drug therapy, can’t tolerate it, or have contraindications to its use. Plus, some patients would just rather be drug free.

Neurostimulatory therapy for headache has followed an evolutionary process, progressing from highly invasive to minimally invasive and now to noninvasive devices, the neurologist observed.

First came deep brain stimulation of the subthalamic nucleus via implanted electrodes, which proved useful in treating Parkinson’s disease.

In the field of headache, there are 14 published studies of deep brain stimulation of the ventroposterior hypothalamus for treatment of intractable chronic cluster headache in a collective total of 64 patients. Two-thirds responded with at least a 50% decrease in pain. But this highly invasive form of therapy is not effective as acute therapy, only for prevention, and it entails a 3% rate of intracranial bleeding.

Next came minimally invasive systems for occipital nerve stimulation. Response rates have been variable in 10 published studies totaling roughly 500 patients treated for chronic migraine. In addition, the devices are quite expensive and are susceptible to lead migration or breakage and battery depletion.

"Only a couple of centers in the U.K. are doing occipital nerve stimulation now," according to Dr. Ahmed.

Yet there is still commercial interest in developing minimally invasive neurostimulatory therapy for headache. During the London headache congress, St. Jude Medical announced that its Eon family of neurostimulators had just received European regulatory approval for treatment of intractable chronic migraine. Among the newly approved devices is the Eon Mini, which weighs about an ounce and has a 10-mm profile.

The recently published 12-week, double-blind, multicenter pivotal study sponsored by St. Jude Medical involved 157 patients with chronic migraine randomized 2:1 to peripheral nerve stimulation or sham control. Of patients on active therapy, 35% achieved at least a 30% reduction in pain, a rate more than twice that in controls. The active treatment group also had a mean 6.1-day reduction in headache days per month from a baseline of 22 days, compared with a 3-day reduction in controls (Cephalalgia 2012 Oct. 3 [doi: 10.1177/0333102412462642]).

A company spokesperson said St. Jude Medical definitely plans to seek U.S. marketing approval for its Eon neurostimulators.

The best-studied noninvasive neurostimulatory device therapy for migraine is the single-pulse transcranial magnetic stimulation Spring TMS device. It delivers a complete treatment in less than a minute at the first sign of migraine pain and has a side effect profile similar to that of sham therapy in clinical trials, according to Dr. Kevin G. Shields, a neurologist at the National Hospital for Neurology and Neurosurgery in London.

Single-pulse transcranial magnetic stimulation has been in clinical use for 30 years, first diagnostically, then as therapy. The mechanism of benefit has been mapped out. The treatment’s safety is very well established; indeed, the FDA has classified it as a nonsignificant risk technology, he noted.

The major technical advance that’s occurred in single-pulse transcranial magnetic stimulation has been a radical reduction in capacitor size. The equipment has shrunk from refrigerator-size in the therapy’s early development, which took place in London, to the highly portable Spring TMS device that patients can stick in a briefcase and utilize unobtrusively at work, Dr. Shields observed.

The contraindications to use of the device are a history of epilepsy; the presence of metal objects in the head, neck, or upper body; and pacemakers or other cardiac devices.

The evidence base supporting the safety and efficacy of the Spring TMS device includes a published randomized, double-blind, sham-controlled clinical trial conducted in patients with migraine with aura (Lancet Neurol. 2010;9:373-80).

In addition, at the international congress Dr. Mark W. Weatherall of the University of Edinburgh, Scotland, presented the first results of an ongoing multicenter U.K. postmarketing study of the single-pulse transcranial magnetic stimulation device as used in clinical practice. The study population consisted of 13 patients with migraine without aura and 24 having migraine with aura who had been using the device for at least 3 months and collectively had treated 777 attacks.

Efficacy reports were:

• 73% of patients said the device showed good to excellent efficacy, reducing or even alleviating migraine pain. Sixty-three percent pronounced the therapy effective in diminishing other migraine symptoms.

• 55% reported a reduction in the number of headache days per month.

The mean attack duration was 2.46 days before transcranial magnetic stimulation therapy and 0.77 days after subjects started using the device. The benefits were reproducible over the 3-month study period and beyond, and no adverse events were reported, he said.

Dr. Jean Schoenen presented the first randomized trial data on the Cefaly device. The supraorbital transcutaneous neurostimulation device has been available in Europe for 5 years, but until now it had no supporting data from controlled trials.

The device consists of a thin silver band that looks like something out of Star Trek. It is hooked over the ears and worn across the forehead like futuristic sunglasses. Patients don it once daily for 20 minutes. The investigators set the programmable device to deliver a square pulse at 60 Hz, 300 microseconds, and a maximum of 14.99 mA.

The 3-month, multicenter, double-blind, sham-controlled Belgian study involved 67 patients with episodic migraine. The mean number of headache-days per month dropped significantly, from 6.9 at baseline to 4.9 at 3 months in the Cefaly group but was unchanged in controls. Thirty-eight percent of patients using the active device experienced at least a 50% reduction in their number of headache-days per month, compared with 12% of controls. Monthly consumption of triptans for acute therapy was reduced by 36% in the Cefaly-treated patients as a whole and by 75% in the Cefaly responders, reported Dr. Schoenen of the University of Liege, Belgium.

To get a crude idea of how supraorbital transcutaneous neurostimulation stacks up against standard prophylactic drug therapy, Dr. Schoenen turned to the extensive published randomized trial literature on topiramate. While the 50% or greater responder rate in the Cefaly trial was 38%, in the pooled topiramate data it’s 45%. Moreover, topiramate was associated with an impressive average 48% reduction in the number of migraine attacks per month, compared with a 19% decrease with the Cefaly device.

On the other hand, one in four patients assigned to topiramate in the randomized trials dropped out due to side effects. No one experienced any adverse effects from the device therapy, he noted.

This was an investigator-initiated study carried out by the Belgian Headache Society and sponsored by STX-Med, which markets the Cefaly device in Europe. Dr. Schoenen is on the advisory boards of St. Jude Medical, Allergan, and ATI. Dr. Ahmed, Dr. Shields, and Dr. Weatherall are on the speakers bureau for eNeura Therapeutics.

LONDON – Enthusiasm is mounting among headache specialists for noninvasive device therapy for acute migraine.

"Normally I’m quite a cynical person, but I think within 10 years time half of my people in the headache clinic won’t be using any medications for their headaches. They’ll have an electronic device of some kind. You get your migraine sorted out, you put your device back in your pants pocket, and you carry on," Dr. Fayyaz Ahmed said at the European Headache and Migraine Trust International Congress.

"I think in about 10 years time you’ll have SIM cards for these neurostimulatory devices, you’ll put the card in an ATM-like machine – perhaps in a supermarket – and you’ll top it up and recharge it," predicted Dr. Ahmed, a consultant neurologist in Hull, England, and chair of the British Association for the Study of Headache.

The noninvasive neurostimulatory therapy most discussed at the congress was the Spring TMS single-pulse transcranial magnetic stimulation device, which since 2011 has been approved in Europe for the acute treatment of migraine. The Spring TMS device is manufactured by U.S.-based eNeura Therapeutics, which is seeking marketing approval from the Food and Drug Administration.

The international congress also saw the presentation of the first multicenter, randomized, sham-controlled study of the noninvasive Cefaly device for prevention of migraine via supraorbital transcutaneous neurostimulation.

"It’s not a revolutionary therapy. The effect size is moderate and inferior to that of the most effective preventive drugs. Its great advantage is that it’s devoid of side effects. I think the Cefaly device is another tool we can use for preventing migraine," Dr. Jean Schoenen concluded in presenting the study data.

Dr. Ahmed said physician and patient interest in noninvasive device therapy is being driven by the sizable proportion of migraine patients who don’t respond adequately to drug therapy, can’t tolerate it, or have contraindications to its use. Plus, some patients would just rather be drug free.

Neurostimulatory therapy for headache has followed an evolutionary process, progressing from highly invasive to minimally invasive and now to noninvasive devices, the neurologist observed.

First came deep brain stimulation of the subthalamic nucleus via implanted electrodes, which proved useful in treating Parkinson’s disease.

In the field of headache, there are 14 published studies of deep brain stimulation of the ventroposterior hypothalamus for treatment of intractable chronic cluster headache in a collective total of 64 patients. Two-thirds responded with at least a 50% decrease in pain. But this highly invasive form of therapy is not effective as acute therapy, only for prevention, and it entails a 3% rate of intracranial bleeding.

Next came minimally invasive systems for occipital nerve stimulation. Response rates have been variable in 10 published studies totaling roughly 500 patients treated for chronic migraine. In addition, the devices are quite expensive and are susceptible to lead migration or breakage and battery depletion.

"Only a couple of centers in the U.K. are doing occipital nerve stimulation now," according to Dr. Ahmed.

Yet there is still commercial interest in developing minimally invasive neurostimulatory therapy for headache. During the London headache congress, St. Jude Medical announced that its Eon family of neurostimulators had just received European regulatory approval for treatment of intractable chronic migraine. Among the newly approved devices is the Eon Mini, which weighs about an ounce and has a 10-mm profile.

The recently published 12-week, double-blind, multicenter pivotal study sponsored by St. Jude Medical involved 157 patients with chronic migraine randomized 2:1 to peripheral nerve stimulation or sham control. Of patients on active therapy, 35% achieved at least a 30% reduction in pain, a rate more than twice that in controls. The active treatment group also had a mean 6.1-day reduction in headache days per month from a baseline of 22 days, compared with a 3-day reduction in controls (Cephalalgia 2012 Oct. 3 [doi: 10.1177/0333102412462642]).

A company spokesperson said St. Jude Medical definitely plans to seek U.S. marketing approval for its Eon neurostimulators.

The best-studied noninvasive neurostimulatory device therapy for migraine is the single-pulse transcranial magnetic stimulation Spring TMS device. It delivers a complete treatment in less than a minute at the first sign of migraine pain and has a side effect profile similar to that of sham therapy in clinical trials, according to Dr. Kevin G. Shields, a neurologist at the National Hospital for Neurology and Neurosurgery in London.

Single-pulse transcranial magnetic stimulation has been in clinical use for 30 years, first diagnostically, then as therapy. The mechanism of benefit has been mapped out. The treatment’s safety is very well established; indeed, the FDA has classified it as a nonsignificant risk technology, he noted.

The major technical advance that’s occurred in single-pulse transcranial magnetic stimulation has been a radical reduction in capacitor size. The equipment has shrunk from refrigerator-size in the therapy’s early development, which took place in London, to the highly portable Spring TMS device that patients can stick in a briefcase and utilize unobtrusively at work, Dr. Shields observed.

The contraindications to use of the device are a history of epilepsy; the presence of metal objects in the head, neck, or upper body; and pacemakers or other cardiac devices.

The evidence base supporting the safety and efficacy of the Spring TMS device includes a published randomized, double-blind, sham-controlled clinical trial conducted in patients with migraine with aura (Lancet Neurol. 2010;9:373-80).

In addition, at the international congress Dr. Mark W. Weatherall of the University of Edinburgh, Scotland, presented the first results of an ongoing multicenter U.K. postmarketing study of the single-pulse transcranial magnetic stimulation device as used in clinical practice. The study population consisted of 13 patients with migraine without aura and 24 having migraine with aura who had been using the device for at least 3 months and collectively had treated 777 attacks.

Efficacy reports were:

• 73% of patients said the device showed good to excellent efficacy, reducing or even alleviating migraine pain. Sixty-three percent pronounced the therapy effective in diminishing other migraine symptoms.

• 55% reported a reduction in the number of headache days per month.

The mean attack duration was 2.46 days before transcranial magnetic stimulation therapy and 0.77 days after subjects started using the device. The benefits were reproducible over the 3-month study period and beyond, and no adverse events were reported, he said.

Dr. Jean Schoenen presented the first randomized trial data on the Cefaly device. The supraorbital transcutaneous neurostimulation device has been available in Europe for 5 years, but until now it had no supporting data from controlled trials.

The device consists of a thin silver band that looks like something out of Star Trek. It is hooked over the ears and worn across the forehead like futuristic sunglasses. Patients don it once daily for 20 minutes. The investigators set the programmable device to deliver a square pulse at 60 Hz, 300 microseconds, and a maximum of 14.99 mA.

The 3-month, multicenter, double-blind, sham-controlled Belgian study involved 67 patients with episodic migraine. The mean number of headache-days per month dropped significantly, from 6.9 at baseline to 4.9 at 3 months in the Cefaly group but was unchanged in controls. Thirty-eight percent of patients using the active device experienced at least a 50% reduction in their number of headache-days per month, compared with 12% of controls. Monthly consumption of triptans for acute therapy was reduced by 36% in the Cefaly-treated patients as a whole and by 75% in the Cefaly responders, reported Dr. Schoenen of the University of Liege, Belgium.

To get a crude idea of how supraorbital transcutaneous neurostimulation stacks up against standard prophylactic drug therapy, Dr. Schoenen turned to the extensive published randomized trial literature on topiramate. While the 50% or greater responder rate in the Cefaly trial was 38%, in the pooled topiramate data it’s 45%. Moreover, topiramate was associated with an impressive average 48% reduction in the number of migraine attacks per month, compared with a 19% decrease with the Cefaly device.

On the other hand, one in four patients assigned to topiramate in the randomized trials dropped out due to side effects. No one experienced any adverse effects from the device therapy, he noted.

This was an investigator-initiated study carried out by the Belgian Headache Society and sponsored by STX-Med, which markets the Cefaly device in Europe. Dr. Schoenen is on the advisory boards of St. Jude Medical, Allergan, and ATI. Dr. Ahmed, Dr. Shields, and Dr. Weatherall are on the speakers bureau for eNeura Therapeutics.

LONDON – Enthusiasm is mounting among headache specialists for noninvasive device therapy for acute migraine.

"Normally I’m quite a cynical person, but I think within 10 years time half of my people in the headache clinic won’t be using any medications for their headaches. They’ll have an electronic device of some kind. You get your migraine sorted out, you put your device back in your pants pocket, and you carry on," Dr. Fayyaz Ahmed said at the European Headache and Migraine Trust International Congress.

"I think in about 10 years time you’ll have SIM cards for these neurostimulatory devices, you’ll put the card in an ATM-like machine – perhaps in a supermarket – and you’ll top it up and recharge it," predicted Dr. Ahmed, a consultant neurologist in Hull, England, and chair of the British Association for the Study of Headache.

The noninvasive neurostimulatory therapy most discussed at the congress was the Spring TMS single-pulse transcranial magnetic stimulation device, which since 2011 has been approved in Europe for the acute treatment of migraine. The Spring TMS device is manufactured by U.S.-based eNeura Therapeutics, which is seeking marketing approval from the Food and Drug Administration.

The international congress also saw the presentation of the first multicenter, randomized, sham-controlled study of the noninvasive Cefaly device for prevention of migraine via supraorbital transcutaneous neurostimulation.

"It’s not a revolutionary therapy. The effect size is moderate and inferior to that of the most effective preventive drugs. Its great advantage is that it’s devoid of side effects. I think the Cefaly device is another tool we can use for preventing migraine," Dr. Jean Schoenen concluded in presenting the study data.

Dr. Ahmed said physician and patient interest in noninvasive device therapy is being driven by the sizable proportion of migraine patients who don’t respond adequately to drug therapy, can’t tolerate it, or have contraindications to its use. Plus, some patients would just rather be drug free.

Neurostimulatory therapy for headache has followed an evolutionary process, progressing from highly invasive to minimally invasive and now to noninvasive devices, the neurologist observed.

First came deep brain stimulation of the subthalamic nucleus via implanted electrodes, which proved useful in treating Parkinson’s disease.

In the field of headache, there are 14 published studies of deep brain stimulation of the ventroposterior hypothalamus for treatment of intractable chronic cluster headache in a collective total of 64 patients. Two-thirds responded with at least a 50% decrease in pain. But this highly invasive form of therapy is not effective as acute therapy, only for prevention, and it entails a 3% rate of intracranial bleeding.

Next came minimally invasive systems for occipital nerve stimulation. Response rates have been variable in 10 published studies totaling roughly 500 patients treated for chronic migraine. In addition, the devices are quite expensive and are susceptible to lead migration or breakage and battery depletion.

"Only a couple of centers in the U.K. are doing occipital nerve stimulation now," according to Dr. Ahmed.

Yet there is still commercial interest in developing minimally invasive neurostimulatory therapy for headache. During the London headache congress, St. Jude Medical announced that its Eon family of neurostimulators had just received European regulatory approval for treatment of intractable chronic migraine. Among the newly approved devices is the Eon Mini, which weighs about an ounce and has a 10-mm profile.

The recently published 12-week, double-blind, multicenter pivotal study sponsored by St. Jude Medical involved 157 patients with chronic migraine randomized 2:1 to peripheral nerve stimulation or sham control. Of patients on active therapy, 35% achieved at least a 30% reduction in pain, a rate more than twice that in controls. The active treatment group also had a mean 6.1-day reduction in headache days per month from a baseline of 22 days, compared with a 3-day reduction in controls (Cephalalgia 2012 Oct. 3 [doi: 10.1177/0333102412462642]).

A company spokesperson said St. Jude Medical definitely plans to seek U.S. marketing approval for its Eon neurostimulators.

The best-studied noninvasive neurostimulatory device therapy for migraine is the single-pulse transcranial magnetic stimulation Spring TMS device. It delivers a complete treatment in less than a minute at the first sign of migraine pain and has a side effect profile similar to that of sham therapy in clinical trials, according to Dr. Kevin G. Shields, a neurologist at the National Hospital for Neurology and Neurosurgery in London.

Single-pulse transcranial magnetic stimulation has been in clinical use for 30 years, first diagnostically, then as therapy. The mechanism of benefit has been mapped out. The treatment’s safety is very well established; indeed, the FDA has classified it as a nonsignificant risk technology, he noted.

The major technical advance that’s occurred in single-pulse transcranial magnetic stimulation has been a radical reduction in capacitor size. The equipment has shrunk from refrigerator-size in the therapy’s early development, which took place in London, to the highly portable Spring TMS device that patients can stick in a briefcase and utilize unobtrusively at work, Dr. Shields observed.

The contraindications to use of the device are a history of epilepsy; the presence of metal objects in the head, neck, or upper body; and pacemakers or other cardiac devices.

The evidence base supporting the safety and efficacy of the Spring TMS device includes a published randomized, double-blind, sham-controlled clinical trial conducted in patients with migraine with aura (Lancet Neurol. 2010;9:373-80).

In addition, at the international congress Dr. Mark W. Weatherall of the University of Edinburgh, Scotland, presented the first results of an ongoing multicenter U.K. postmarketing study of the single-pulse transcranial magnetic stimulation device as used in clinical practice. The study population consisted of 13 patients with migraine without aura and 24 having migraine with aura who had been using the device for at least 3 months and collectively had treated 777 attacks.

Efficacy reports were:

• 73% of patients said the device showed good to excellent efficacy, reducing or even alleviating migraine pain. Sixty-three percent pronounced the therapy effective in diminishing other migraine symptoms.

• 55% reported a reduction in the number of headache days per month.

The mean attack duration was 2.46 days before transcranial magnetic stimulation therapy and 0.77 days after subjects started using the device. The benefits were reproducible over the 3-month study period and beyond, and no adverse events were reported, he said.

Dr. Jean Schoenen presented the first randomized trial data on the Cefaly device. The supraorbital transcutaneous neurostimulation device has been available in Europe for 5 years, but until now it had no supporting data from controlled trials.

The device consists of a thin silver band that looks like something out of Star Trek. It is hooked over the ears and worn across the forehead like futuristic sunglasses. Patients don it once daily for 20 minutes. The investigators set the programmable device to deliver a square pulse at 60 Hz, 300 microseconds, and a maximum of 14.99 mA.

The 3-month, multicenter, double-blind, sham-controlled Belgian study involved 67 patients with episodic migraine. The mean number of headache-days per month dropped significantly, from 6.9 at baseline to 4.9 at 3 months in the Cefaly group but was unchanged in controls. Thirty-eight percent of patients using the active device experienced at least a 50% reduction in their number of headache-days per month, compared with 12% of controls. Monthly consumption of triptans for acute therapy was reduced by 36% in the Cefaly-treated patients as a whole and by 75% in the Cefaly responders, reported Dr. Schoenen of the University of Liege, Belgium.

To get a crude idea of how supraorbital transcutaneous neurostimulation stacks up against standard prophylactic drug therapy, Dr. Schoenen turned to the extensive published randomized trial literature on topiramate. While the 50% or greater responder rate in the Cefaly trial was 38%, in the pooled topiramate data it’s 45%. Moreover, topiramate was associated with an impressive average 48% reduction in the number of migraine attacks per month, compared with a 19% decrease with the Cefaly device.

On the other hand, one in four patients assigned to topiramate in the randomized trials dropped out due to side effects. No one experienced any adverse effects from the device therapy, he noted.

This was an investigator-initiated study carried out by the Belgian Headache Society and sponsored by STX-Med, which markets the Cefaly device in Europe. Dr. Schoenen is on the advisory boards of St. Jude Medical, Allergan, and ATI. Dr. Ahmed, Dr. Shields, and Dr. Weatherall are on the speakers bureau for eNeura Therapeutics.

LONDON – More than two-thirds of patients with medically refractory chronic cluster headache responded to on-demand, self-administered sphenopalatine ganglion stimulation with acute pain relief, less frequent attacks, or both.

The prophylactic effect – a reduction in cluster attack frequency, but in most cases without acute pain relief – came as a surprise to investigators in the prospective, controlled, multinational Pathway CH-1 study, Dr. Jean Schoenen admitted at the European Headache and Migraine Trust International Congress.

"This was the largest, most rigorous study to date of an implantable medical device for headache treatment. The study was not designed to look at attack frequency; it was designed to look at acute response. Yet, we have this preventive effect that I think now has to be confirmed in another well-designed trial," said Dr. Schoenen, coordinator of the headache research unit at the University of Liege (Belgium).

For more than 100 years, the sphenopalatine ganglion (SPG) has been thought to be a key mediator of the cranial autonomic symptoms and unilateral periorbital pain that define cluster headaches. In the Pathway CH-1 study, Dr. Schoenen and coinvestigators evaluated the efficacy and safety of a miniature electrical neurostimulator implanted in the pterygopalatine fossa near the SPG. The neurostimulator is activated by a hand-held remote controller the patients hold up to their face for on-demand therapy.

A neurosurgeon implants the SPG neurostimulator via a minimally invasive procedure using a transoral, gingival buccal technique that leaves no externally visible scars.

Dr. Schoenen reported on 28 chronic cluster headache patients who were dissatisfied with their current treatment and opted to participate in the trial. They underwent neurostimulator implantation, followed by a minimum 3-week postsurgical stabilization period during which the device remained switched off. During the subsequent controlled experimental phase, they each self-treated a minimum of 30 attacks over a 3- to 8-week period. Once the device was fired up, it couldn’t be employed again for 90 minutes. The remote controller was programmed to randomly deliver full stimulation, subthreshold stimulation, or sham treatment.

Overall, 7of the 28 patients, or 25%, were categorized as acute responders, meaning that full stimulation achieved marked pain relief within 15 minutes with no acute medication in more than half of treated attacks. Another 10 patients (36%) were "frequency responders" who experienced at least a 50% reduction in cluster attack frequency, compared with baseline with no change in preventive medications and with nonacute pain relief. Two patients (7%) were both acute and frequency responders. A total of 32% were nonresponders.

Frequency responders didn’t start experiencing fewer cluster attacks until after the weeks of postsurgical stabilization ended and neurostimulation began. This makes it highly unlikely that the prophylactic effect was somehow due to the surgery itself, according to the neurologist.

Significant pain relief was documented 15 minutes after full stimulation in 67% of treated attacks, half of which involved pain freedom. In contrast, significant pain relief occurred in only 7% of attacks that were addressed with subthreshold stimulation or sham treatment.

Sixty-four percent of subjects showed clinically meaningful and statistically significant reductions in headache disability as indicated by improved scores on the Headache Impact Test-6. Quality of life improved in 75%, as reflected by their scores on the Short Form-36 physical and/or mental component summary scores, Dr. Schoenen continued.

Acute medications were used within 90 minutes of 31% of cluster attacks treated with full stimulation, compared with 78% of those addressed using subthreshold stimulation and 77% that got sham therapy.

Far and away, the most common adverse event involved mild-to-moderate sensory disturbances in the maxillary division of the trigeminal nerve, experienced by 81% of subjects. These symptoms resolved within 3 months. Two patients experienced infections. Two others required device explantation due to lead migration.

The ongoing Pathway CH-1 study will continue on an open-label basis for 1 year post-implantation.

The device, known as the ATI Neurostimulation System, is MRI compatible. It has been approved for marketing by the European regulatory authorities. The manufacturer, Autonomic Technologies of Redwood City, Calif., will also seek Food and Drug Administration approval.

In addition, the company has launched the multicenter, controlled European Pathway M-1 trial in which SPG neurostimulation is being evaluated for the treatment of disabling migraine.

Dr. Rigmor H. Jensen, president of the European Headache Federation, commented that an invasive device such as this will likely be reserved for those few cluster headache patients who are completely refractory to all medications. That’s probably 1%-3% of the cluster headache population, estimated Dr. Jensen, research professor of neurology at the University of Copenhagen.

Dr. Schoenen is a consultant to Autonomic Technologies, which is funding the Pathway CH-1 study.

LONDON – More than two-thirds of patients with medically refractory chronic cluster headache responded to on-demand, self-administered sphenopalatine ganglion stimulation with acute pain relief, less frequent attacks, or both.

The prophylactic effect – a reduction in cluster attack frequency, but in most cases without acute pain relief – came as a surprise to investigators in the prospective, controlled, multinational Pathway CH-1 study, Dr. Jean Schoenen admitted at the European Headache and Migraine Trust International Congress.

"This was the largest, most rigorous study to date of an implantable medical device for headache treatment. The study was not designed to look at attack frequency; it was designed to look at acute response. Yet, we have this preventive effect that I think now has to be confirmed in another well-designed trial," said Dr. Schoenen, coordinator of the headache research unit at the University of Liege (Belgium).

For more than 100 years, the sphenopalatine ganglion (SPG) has been thought to be a key mediator of the cranial autonomic symptoms and unilateral periorbital pain that define cluster headaches. In the Pathway CH-1 study, Dr. Schoenen and coinvestigators evaluated the efficacy and safety of a miniature electrical neurostimulator implanted in the pterygopalatine fossa near the SPG. The neurostimulator is activated by a hand-held remote controller the patients hold up to their face for on-demand therapy.

A neurosurgeon implants the SPG neurostimulator via a minimally invasive procedure using a transoral, gingival buccal technique that leaves no externally visible scars.

Dr. Schoenen reported on 28 chronic cluster headache patients who were dissatisfied with their current treatment and opted to participate in the trial. They underwent neurostimulator implantation, followed by a minimum 3-week postsurgical stabilization period during which the device remained switched off. During the subsequent controlled experimental phase, they each self-treated a minimum of 30 attacks over a 3- to 8-week period. Once the device was fired up, it couldn’t be employed again for 90 minutes. The remote controller was programmed to randomly deliver full stimulation, subthreshold stimulation, or sham treatment.

Overall, 7of the 28 patients, or 25%, were categorized as acute responders, meaning that full stimulation achieved marked pain relief within 15 minutes with no acute medication in more than half of treated attacks. Another 10 patients (36%) were "frequency responders" who experienced at least a 50% reduction in cluster attack frequency, compared with baseline with no change in preventive medications and with nonacute pain relief. Two patients (7%) were both acute and frequency responders. A total of 32% were nonresponders.

Frequency responders didn’t start experiencing fewer cluster attacks until after the weeks of postsurgical stabilization ended and neurostimulation began. This makes it highly unlikely that the prophylactic effect was somehow due to the surgery itself, according to the neurologist.

Significant pain relief was documented 15 minutes after full stimulation in 67% of treated attacks, half of which involved pain freedom. In contrast, significant pain relief occurred in only 7% of attacks that were addressed with subthreshold stimulation or sham treatment.

Sixty-four percent of subjects showed clinically meaningful and statistically significant reductions in headache disability as indicated by improved scores on the Headache Impact Test-6. Quality of life improved in 75%, as reflected by their scores on the Short Form-36 physical and/or mental component summary scores, Dr. Schoenen continued.

Acute medications were used within 90 minutes of 31% of cluster attacks treated with full stimulation, compared with 78% of those addressed using subthreshold stimulation and 77% that got sham therapy.

Far and away, the most common adverse event involved mild-to-moderate sensory disturbances in the maxillary division of the trigeminal nerve, experienced by 81% of subjects. These symptoms resolved within 3 months. Two patients experienced infections. Two others required device explantation due to lead migration.

The ongoing Pathway CH-1 study will continue on an open-label basis for 1 year post-implantation.

The device, known as the ATI Neurostimulation System, is MRI compatible. It has been approved for marketing by the European regulatory authorities. The manufacturer, Autonomic Technologies of Redwood City, Calif., will also seek Food and Drug Administration approval.

In addition, the company has launched the multicenter, controlled European Pathway M-1 trial in which SPG neurostimulation is being evaluated for the treatment of disabling migraine.

Dr. Rigmor H. Jensen, president of the European Headache Federation, commented that an invasive device such as this will likely be reserved for those few cluster headache patients who are completely refractory to all medications. That’s probably 1%-3% of the cluster headache population, estimated Dr. Jensen, research professor of neurology at the University of Copenhagen.

Dr. Schoenen is a consultant to Autonomic Technologies, which is funding the Pathway CH-1 study.

LONDON – More than two-thirds of patients with medically refractory chronic cluster headache responded to on-demand, self-administered sphenopalatine ganglion stimulation with acute pain relief, less frequent attacks, or both.

The prophylactic effect – a reduction in cluster attack frequency, but in most cases without acute pain relief – came as a surprise to investigators in the prospective, controlled, multinational Pathway CH-1 study, Dr. Jean Schoenen admitted at the European Headache and Migraine Trust International Congress.

"This was the largest, most rigorous study to date of an implantable medical device for headache treatment. The study was not designed to look at attack frequency; it was designed to look at acute response. Yet, we have this preventive effect that I think now has to be confirmed in another well-designed trial," said Dr. Schoenen, coordinator of the headache research unit at the University of Liege (Belgium).

For more than 100 years, the sphenopalatine ganglion (SPG) has been thought to be a key mediator of the cranial autonomic symptoms and unilateral periorbital pain that define cluster headaches. In the Pathway CH-1 study, Dr. Schoenen and coinvestigators evaluated the efficacy and safety of a miniature electrical neurostimulator implanted in the pterygopalatine fossa near the SPG. The neurostimulator is activated by a hand-held remote controller the patients hold up to their face for on-demand therapy.

A neurosurgeon implants the SPG neurostimulator via a minimally invasive procedure using a transoral, gingival buccal technique that leaves no externally visible scars.

Dr. Schoenen reported on 28 chronic cluster headache patients who were dissatisfied with their current treatment and opted to participate in the trial. They underwent neurostimulator implantation, followed by a minimum 3-week postsurgical stabilization period during which the device remained switched off. During the subsequent controlled experimental phase, they each self-treated a minimum of 30 attacks over a 3- to 8-week period. Once the device was fired up, it couldn’t be employed again for 90 minutes. The remote controller was programmed to randomly deliver full stimulation, subthreshold stimulation, or sham treatment.

Overall, 7of the 28 patients, or 25%, were categorized as acute responders, meaning that full stimulation achieved marked pain relief within 15 minutes with no acute medication in more than half of treated attacks. Another 10 patients (36%) were "frequency responders" who experienced at least a 50% reduction in cluster attack frequency, compared with baseline with no change in preventive medications and with nonacute pain relief. Two patients (7%) were both acute and frequency responders. A total of 32% were nonresponders.

Frequency responders didn’t start experiencing fewer cluster attacks until after the weeks of postsurgical stabilization ended and neurostimulation began. This makes it highly unlikely that the prophylactic effect was somehow due to the surgery itself, according to the neurologist.

Significant pain relief was documented 15 minutes after full stimulation in 67% of treated attacks, half of which involved pain freedom. In contrast, significant pain relief occurred in only 7% of attacks that were addressed with subthreshold stimulation or sham treatment.

Sixty-four percent of subjects showed clinically meaningful and statistically significant reductions in headache disability as indicated by improved scores on the Headache Impact Test-6. Quality of life improved in 75%, as reflected by their scores on the Short Form-36 physical and/or mental component summary scores, Dr. Schoenen continued.

Acute medications were used within 90 minutes of 31% of cluster attacks treated with full stimulation, compared with 78% of those addressed using subthreshold stimulation and 77% that got sham therapy.

Far and away, the most common adverse event involved mild-to-moderate sensory disturbances in the maxillary division of the trigeminal nerve, experienced by 81% of subjects. These symptoms resolved within 3 months. Two patients experienced infections. Two others required device explantation due to lead migration.

The ongoing Pathway CH-1 study will continue on an open-label basis for 1 year post-implantation.

The device, known as the ATI Neurostimulation System, is MRI compatible. It has been approved for marketing by the European regulatory authorities. The manufacturer, Autonomic Technologies of Redwood City, Calif., will also seek Food and Drug Administration approval.

In addition, the company has launched the multicenter, controlled European Pathway M-1 trial in which SPG neurostimulation is being evaluated for the treatment of disabling migraine.

Dr. Rigmor H. Jensen, president of the European Headache Federation, commented that an invasive device such as this will likely be reserved for those few cluster headache patients who are completely refractory to all medications. That’s probably 1%-3% of the cluster headache population, estimated Dr. Jensen, research professor of neurology at the University of Copenhagen.

Dr. Schoenen is a consultant to Autonomic Technologies, which is funding the Pathway CH-1 study.

LONDON – Frovatriptan may be the triptan of choice for the acute treatment of menstrual migraine attacks, according to reanalyses of data from double-blind, randomized crossover trials involving the drug.

Frovatriptan’s lengthy half-life – the longest of all the triptans – and prolonged duration of clinical effect make it a particularly attractive option for the treatment of menstrual migraine attacks, which are typically longer in duration and more susceptible to relapse than migraine not related to menstruation, said Dr. Lidia Savi, a neurologist at the University of Turin (Italy).

At the European Headache and Migraine Trust International Congress, she presented a secondary analysis of data from a published, double-blind, randomized, multicenter crossover trial of frovatriptan (Frova) versus almotriptan (Axert) for the acute treatment of migraine (J. Headache Pain 2011;12:361-8). Both men and women were included in the parent study. The newer secondary analysis was restricted to the 67 participants with regular menstrual cycles.

In 155 menstrual migraine attacks treated in double-blind fashion, the two triptans displayed similar short-term efficacy, as reflected in pain relief and pain-free episodes 2 and 4 hours post treatment. However, the recurrence rate within 48 hours after treatment was just 9% in frovatriptan-treated episodes, significantly less than the 24% rate for almotriptan (J. Headache Pain 2012;13:401-6).

In a separate presentation, Dr. Anne MacGregor emphasized that menstrually related migraine is a distinct clinical entity. Affected women find it considerably more problematic than migraine occurring at other times of the menstrual cycle.

She cited a study by other investigators who prospectively studied headache episodes in 107 women with frequent and disabling migraine attacks, both menstrually related and otherwise. The menstrually related attacks were significantly less likely to be pain free at 2 hours post treatment, were more likely to last longer than 72 hours, were more severe, had more associated symptoms, were more susceptible to relapse, and inflicted greater disability (Cephalalgia 2010;30:1187-94).

When not managed effectively, menstrual migraine attacks often cause women to develop a greater fear of migraine, with resultant added psychological and functional disability between episodes, said Dr. MacGregor of the Barts Sexual Health Centre at St. Bartholomew’s Hospital and the London School of Medicine and Dentistry.

"Frovatriptan is something that can give these patients that little extra bit of control. This is something quite positive that we can take home as a message to our patients: Frovatriptan is an option worth trying for menstrual attacks of migraine," she added.

Dr. Gianni Allais presented a pooled analysis of Dr. Savi’s study plus two other published Italian randomized, double-blind crossover clinical trials of frovatriptan versus rizatriptan (Maxalt) (J. Headache Pain 2011;12:609-15) and zolmitriptan (Zomig) (Neurol. Sci. 2011;32[suppl. 1]:S99-104). The pooled subgroup analysis covered the 187 women with at least one episode of menstrual migraine treated with frovatriptan and one episode treated with one of the other triptans.

Rates of being pain free and having pain relief 2 and 4 hours post treatment were similar across the board. However, recurrence rates were significantly lower for frovatriptan-treated episodes than for those treated with any of the other agents. At 24 hours of follow-up, the recurrence rate was 11% following frovatriptan versus 24% collectively for the comparator triptans. The 48-hour recurrence rate was 15% with frovatriptan, compared with 26% for the other triptans in this recently published pooled analysis (Neurol. Sci. 2012;33[suppl. 1]:S65-9), reported Dr. Allais of the women’s headache center at the University of Turin.

The frovastatin studies were funded by the Menarini Group, which markets the triptan in Italy. Dr. Savi, Dr. MacGregor, and Dr. Allais serve as consultants to the company.

LONDON – Frovatriptan may be the triptan of choice for the acute treatment of menstrual migraine attacks, according to reanalyses of data from double-blind, randomized crossover trials involving the drug.

Frovatriptan’s lengthy half-life – the longest of all the triptans – and prolonged duration of clinical effect make it a particularly attractive option for the treatment of menstrual migraine attacks, which are typically longer in duration and more susceptible to relapse than migraine not related to menstruation, said Dr. Lidia Savi, a neurologist at the University of Turin (Italy).

At the European Headache and Migraine Trust International Congress, she presented a secondary analysis of data from a published, double-blind, randomized, multicenter crossover trial of frovatriptan (Frova) versus almotriptan (Axert) for the acute treatment of migraine (J. Headache Pain 2011;12:361-8). Both men and women were included in the parent study. The newer secondary analysis was restricted to the 67 participants with regular menstrual cycles.

In 155 menstrual migraine attacks treated in double-blind fashion, the two triptans displayed similar short-term efficacy, as reflected in pain relief and pain-free episodes 2 and 4 hours post treatment. However, the recurrence rate within 48 hours after treatment was just 9% in frovatriptan-treated episodes, significantly less than the 24% rate for almotriptan (J. Headache Pain 2012;13:401-6).

In a separate presentation, Dr. Anne MacGregor emphasized that menstrually related migraine is a distinct clinical entity. Affected women find it considerably more problematic than migraine occurring at other times of the menstrual cycle.

She cited a study by other investigators who prospectively studied headache episodes in 107 women with frequent and disabling migraine attacks, both menstrually related and otherwise. The menstrually related attacks were significantly less likely to be pain free at 2 hours post treatment, were more likely to last longer than 72 hours, were more severe, had more associated symptoms, were more susceptible to relapse, and inflicted greater disability (Cephalalgia 2010;30:1187-94).

When not managed effectively, menstrual migraine attacks often cause women to develop a greater fear of migraine, with resultant added psychological and functional disability between episodes, said Dr. MacGregor of the Barts Sexual Health Centre at St. Bartholomew’s Hospital and the London School of Medicine and Dentistry.

"Frovatriptan is something that can give these patients that little extra bit of control. This is something quite positive that we can take home as a message to our patients: Frovatriptan is an option worth trying for menstrual attacks of migraine," she added.

Dr. Gianni Allais presented a pooled analysis of Dr. Savi’s study plus two other published Italian randomized, double-blind crossover clinical trials of frovatriptan versus rizatriptan (Maxalt) (J. Headache Pain 2011;12:609-15) and zolmitriptan (Zomig) (Neurol. Sci. 2011;32[suppl. 1]:S99-104). The pooled subgroup analysis covered the 187 women with at least one episode of menstrual migraine treated with frovatriptan and one episode treated with one of the other triptans.

Rates of being pain free and having pain relief 2 and 4 hours post treatment were similar across the board. However, recurrence rates were significantly lower for frovatriptan-treated episodes than for those treated with any of the other agents. At 24 hours of follow-up, the recurrence rate was 11% following frovatriptan versus 24% collectively for the comparator triptans. The 48-hour recurrence rate was 15% with frovatriptan, compared with 26% for the other triptans in this recently published pooled analysis (Neurol. Sci. 2012;33[suppl. 1]:S65-9), reported Dr. Allais of the women’s headache center at the University of Turin.

The frovastatin studies were funded by the Menarini Group, which markets the triptan in Italy. Dr. Savi, Dr. MacGregor, and Dr. Allais serve as consultants to the company.

LONDON – Frovatriptan may be the triptan of choice for the acute treatment of menstrual migraine attacks, according to reanalyses of data from double-blind, randomized crossover trials involving the drug.

Frovatriptan’s lengthy half-life – the longest of all the triptans – and prolonged duration of clinical effect make it a particularly attractive option for the treatment of menstrual migraine attacks, which are typically longer in duration and more susceptible to relapse than migraine not related to menstruation, said Dr. Lidia Savi, a neurologist at the University of Turin (Italy).

At the European Headache and Migraine Trust International Congress, she presented a secondary analysis of data from a published, double-blind, randomized, multicenter crossover trial of frovatriptan (Frova) versus almotriptan (Axert) for the acute treatment of migraine (J. Headache Pain 2011;12:361-8). Both men and women were included in the parent study. The newer secondary analysis was restricted to the 67 participants with regular menstrual cycles.

In 155 menstrual migraine attacks treated in double-blind fashion, the two triptans displayed similar short-term efficacy, as reflected in pain relief and pain-free episodes 2 and 4 hours post treatment. However, the recurrence rate within 48 hours after treatment was just 9% in frovatriptan-treated episodes, significantly less than the 24% rate for almotriptan (J. Headache Pain 2012;13:401-6).

In a separate presentation, Dr. Anne MacGregor emphasized that menstrually related migraine is a distinct clinical entity. Affected women find it considerably more problematic than migraine occurring at other times of the menstrual cycle.

She cited a study by other investigators who prospectively studied headache episodes in 107 women with frequent and disabling migraine attacks, both menstrually related and otherwise. The menstrually related attacks were significantly less likely to be pain free at 2 hours post treatment, were more likely to last longer than 72 hours, were more severe, had more associated symptoms, were more susceptible to relapse, and inflicted greater disability (Cephalalgia 2010;30:1187-94).

When not managed effectively, menstrual migraine attacks often cause women to develop a greater fear of migraine, with resultant added psychological and functional disability between episodes, said Dr. MacGregor of the Barts Sexual Health Centre at St. Bartholomew’s Hospital and the London School of Medicine and Dentistry.

"Frovatriptan is something that can give these patients that little extra bit of control. This is something quite positive that we can take home as a message to our patients: Frovatriptan is an option worth trying for menstrual attacks of migraine," she added.

Dr. Gianni Allais presented a pooled analysis of Dr. Savi’s study plus two other published Italian randomized, double-blind crossover clinical trials of frovatriptan versus rizatriptan (Maxalt) (J. Headache Pain 2011;12:609-15) and zolmitriptan (Zomig) (Neurol. Sci. 2011;32[suppl. 1]:S99-104). The pooled subgroup analysis covered the 187 women with at least one episode of menstrual migraine treated with frovatriptan and one episode treated with one of the other triptans.

Rates of being pain free and having pain relief 2 and 4 hours post treatment were similar across the board. However, recurrence rates were significantly lower for frovatriptan-treated episodes than for those treated with any of the other agents. At 24 hours of follow-up, the recurrence rate was 11% following frovatriptan versus 24% collectively for the comparator triptans. The 48-hour recurrence rate was 15% with frovatriptan, compared with 26% for the other triptans in this recently published pooled analysis (Neurol. Sci. 2012;33[suppl. 1]:S65-9), reported Dr. Allais of the women’s headache center at the University of Turin.

The frovastatin studies were funded by the Menarini Group, which markets the triptan in Italy. Dr. Savi, Dr. MacGregor, and Dr. Allais serve as consultants to the company.

LONDON – Plain old aspirin proved far and away the most effective of the various agents used for prophylaxis of migraine with aura in an Italian study, with 86% of aspirin-treated patients reporting at least a 50% reduction in frequency of attacks.

"We found the probability of treatment success with acetylsalicylic acid at 300 mg once daily was about six times greater than with other prophylactic agents," Dr. Lidia T. Savi reported at the European Headache and Migraine Trust International Congress.

©jimdeli/Fotolia.com

Dr. Savi, a neurologist at the University of Turin (Italy), presented a retrospective analysis of 194 consecutive patients at the university’s headache center who were placed on prophylactic therapy for migraine with aura. Ninety were on aspirin at 300 mg/day. The rest were on various widely used prophylactic medications, with propranolol and topiramate topping the list.

The primary end point was treatment success as defined at week 32 by at least a 50% reduction in the frequency of attacks of migraine with aura, compared with baseline. Eighty-six percent of patients on aspirin for prophylaxis met this end point; indeed, 41% of the aspirin-treated group also met the more rigorous standard of ‘extremely improved’ as defined by a 75% reduction in attack frequency. Fourteen percent of patients were rated unimproved.

In contrast, 46% of patients on prophylactic agents other than aspirin were unimproved. Only 17% were judged extremely improved and 37% were improved.

Aspirin prophylaxis at the 300 mg dose was, as expected, very well tolerated, with nobody switching to another agent within 32 weeks due to side effects. Moreover, treatment success rates in the aspirin group were the same at 16 weeks as at 32 weeks, so patients and their physicians can expect to see evidence of response to prophylactic aspirin in a relatively short time, Dr. Savi continued.

In a multivariate analysis adjusted for age, gender, disease duration, and other variables, only prophylactic aspirin was independently associated with a positive treatment response. Patients on prophylactic aspirin were an adjusted 6.3-fold more likely than were those on other drugs to have at least a 50% reduction in migraine with aura frequency.

The prevalence of migraine with aura in the general population is estimated at 1%-5%. Most affected patients find the aura more disturbing and disruptive than the subsequent head pain.

Prior studies comparing prophylactic agents for migraine with aura have typically reported aspirin to be only mildly effective. However, these studies often contained only small numbers of patients and muddied the waters by mixing together subjects who had migraine with aura and those who had migraine without aura, according to Dr. Savi.

A double-blind, placebo-controlled study with a larger patient sample will be needed to confirm the Italian findings, she added.

Prophylactic aspirin’s mechanism of benefit in migraine with aura isn’t known. But the disorder has been linked to platelet dysfunction, and Dr. Savi’s hypothesis is that daily aspirin prevents migraine with aura attacks by curbing formation of microemboli.

Audience member Dr. Jean Schoenen of the University of Liege (Belgium) asked how many patients in the Italian series were on lamotrigine, which he considers the best agent for prevention of attacks of migraine with aura. Dr. Savi replied that none were. She said she and her colleagues seldom prescribe lamotrigine (Lamictal) anymore because they’ve found the discontinuation rate is so high.

Dr. Savi reported having no financial conflicts.

LONDON – Plain old aspirin proved far and away the most effective of the various agents used for prophylaxis of migraine with aura in an Italian study, with 86% of aspirin-treated patients reporting at least a 50% reduction in frequency of attacks.

"We found the probability of treatment success with acetylsalicylic acid at 300 mg once daily was about six times greater than with other prophylactic agents," Dr. Lidia T. Savi reported at the European Headache and Migraine Trust International Congress.

©jimdeli/Fotolia.com

Dr. Savi, a neurologist at the University of Turin (Italy), presented a retrospective analysis of 194 consecutive patients at the university’s headache center who were placed on prophylactic therapy for migraine with aura. Ninety were on aspirin at 300 mg/day. The rest were on various widely used prophylactic medications, with propranolol and topiramate topping the list.

The primary end point was treatment success as defined at week 32 by at least a 50% reduction in the frequency of attacks of migraine with aura, compared with baseline. Eighty-six percent of patients on aspirin for prophylaxis met this end point; indeed, 41% of the aspirin-treated group also met the more rigorous standard of ‘extremely improved’ as defined by a 75% reduction in attack frequency. Fourteen percent of patients were rated unimproved.

In contrast, 46% of patients on prophylactic agents other than aspirin were unimproved. Only 17% were judged extremely improved and 37% were improved.

Aspirin prophylaxis at the 300 mg dose was, as expected, very well tolerated, with nobody switching to another agent within 32 weeks due to side effects. Moreover, treatment success rates in the aspirin group were the same at 16 weeks as at 32 weeks, so patients and their physicians can expect to see evidence of response to prophylactic aspirin in a relatively short time, Dr. Savi continued.

In a multivariate analysis adjusted for age, gender, disease duration, and other variables, only prophylactic aspirin was independently associated with a positive treatment response. Patients on prophylactic aspirin were an adjusted 6.3-fold more likely than were those on other drugs to have at least a 50% reduction in migraine with aura frequency.

The prevalence of migraine with aura in the general population is estimated at 1%-5%. Most affected patients find the aura more disturbing and disruptive than the subsequent head pain.

Prior studies comparing prophylactic agents for migraine with aura have typically reported aspirin to be only mildly effective. However, these studies often contained only small numbers of patients and muddied the waters by mixing together subjects who had migraine with aura and those who had migraine without aura, according to Dr. Savi.

A double-blind, placebo-controlled study with a larger patient sample will be needed to confirm the Italian findings, she added.

Prophylactic aspirin’s mechanism of benefit in migraine with aura isn’t known. But the disorder has been linked to platelet dysfunction, and Dr. Savi’s hypothesis is that daily aspirin prevents migraine with aura attacks by curbing formation of microemboli.

Audience member Dr. Jean Schoenen of the University of Liege (Belgium) asked how many patients in the Italian series were on lamotrigine, which he considers the best agent for prevention of attacks of migraine with aura. Dr. Savi replied that none were. She said she and her colleagues seldom prescribe lamotrigine (Lamictal) anymore because they’ve found the discontinuation rate is so high.

Dr. Savi reported having no financial conflicts.

LONDON – Plain old aspirin proved far and away the most effective of the various agents used for prophylaxis of migraine with aura in an Italian study, with 86% of aspirin-treated patients reporting at least a 50% reduction in frequency of attacks.

"We found the probability of treatment success with acetylsalicylic acid at 300 mg once daily was about six times greater than with other prophylactic agents," Dr. Lidia T. Savi reported at the European Headache and Migraine Trust International Congress.

©jimdeli/Fotolia.com

Dr. Savi, a neurologist at the University of Turin (Italy), presented a retrospective analysis of 194 consecutive patients at the university’s headache center who were placed on prophylactic therapy for migraine with aura. Ninety were on aspirin at 300 mg/day. The rest were on various widely used prophylactic medications, with propranolol and topiramate topping the list.

The primary end point was treatment success as defined at week 32 by at least a 50% reduction in the frequency of attacks of migraine with aura, compared with baseline. Eighty-six percent of patients on aspirin for prophylaxis met this end point; indeed, 41% of the aspirin-treated group also met the more rigorous standard of ‘extremely improved’ as defined by a 75% reduction in attack frequency. Fourteen percent of patients were rated unimproved.

In contrast, 46% of patients on prophylactic agents other than aspirin were unimproved. Only 17% were judged extremely improved and 37% were improved.

Aspirin prophylaxis at the 300 mg dose was, as expected, very well tolerated, with nobody switching to another agent within 32 weeks due to side effects. Moreover, treatment success rates in the aspirin group were the same at 16 weeks as at 32 weeks, so patients and their physicians can expect to see evidence of response to prophylactic aspirin in a relatively short time, Dr. Savi continued.

In a multivariate analysis adjusted for age, gender, disease duration, and other variables, only prophylactic aspirin was independently associated with a positive treatment response. Patients on prophylactic aspirin were an adjusted 6.3-fold more likely than were those on other drugs to have at least a 50% reduction in migraine with aura frequency.

The prevalence of migraine with aura in the general population is estimated at 1%-5%. Most affected patients find the aura more disturbing and disruptive than the subsequent head pain.

Prior studies comparing prophylactic agents for migraine with aura have typically reported aspirin to be only mildly effective. However, these studies often contained only small numbers of patients and muddied the waters by mixing together subjects who had migraine with aura and those who had migraine without aura, according to Dr. Savi.

A double-blind, placebo-controlled study with a larger patient sample will be needed to confirm the Italian findings, she added.

Prophylactic aspirin’s mechanism of benefit in migraine with aura isn’t known. But the disorder has been linked to platelet dysfunction, and Dr. Savi’s hypothesis is that daily aspirin prevents migraine with aura attacks by curbing formation of microemboli.

Audience member Dr. Jean Schoenen of the University of Liege (Belgium) asked how many patients in the Italian series were on lamotrigine, which he considers the best agent for prevention of attacks of migraine with aura. Dr. Savi replied that none were. She said she and her colleagues seldom prescribe lamotrigine (Lamictal) anymore because they’ve found the discontinuation rate is so high.

Dr. Savi reported having no financial conflicts.

LONDON – Occipital nerve blocks are an effective, safe, and well-tolerated therapy in patients with exacerbation of chronic or episodic cluster headache, according to two observational studies presented at the European Headache and Migraine Trust International Congress.

"It’s a treatment that can suppress attacks temporarily or reduce pain intensity in a high percentage of patients. From the clinical point of view, we gain 1 or 2 or 3 weeks of time to titrate up the standard medications so they can take effect. The patients are attack-free for some days, and they like that very much," observed Dr. Charly Gaul of University Hospital in Essen, Germany.

At the congress, he presented a prospective study of occipital nerve blocks in 101 patients with intractable, disabling cluster headaches insufficiently controlled by the established preventive and acute medications. Sixty-one patients had episodic cluster headache; the other 40 had the less commonly encountered chronic cluster headache, characterized by multiple daily excruciating attacks with no or only brief remission periods.

All subjects received a single occipital nerve block (ONB) of the greater and lesser occipital nerve using 10 mg of triamcinolone along with bupivacaine 0.5% for local anesthesia. The patients completed a headache questionnaire prior to and again 3 and 10 days after receiving the ONB and then once more upon recurrence of their headache attacks.

A total of 83% of patients demonstrated a complete or partial response to their ONB. Efficacy was greater in the episodic cluster headache cohort: 41 of the 61 such patients became completely or temporarily attack free for a mean of 34 days, as did 20 of 40 patients with chronic cluster headache, for a notably briefer mean of 14 days.

Headache frequency in the episodic cluster headache group fell from a mean of 2.9 attacks/day at baseline to 0.7 attacks/day during the first 3 days following ONB and 1.1/day on days 7-10 post treatment. Self-reported pain intensity of attacks on a 0-10 scale improved from 8.4 at baseline to 2.3 in the first several days post-treatment and 3.3 on days 7-10 following the injection.

The average number of headaches per day in the chronic cluster headache cohort dropped from 3.3 at baseline to 1.1 during days 1-3 and 1.9 on days 7-10 post treatment. Pain intensity scores fell from a baseline of 7.9 to 3.9 shortly after ONB and 5.9 on days 7-10 post treatment, Dr. Gaul continued.

Adverse events (all minor) occurred in 11% of patients, the most common of which was a non–cluster headache, occurring in 3% of participants. Injection site pain and occipital muscle tension were among the other adverse events. No severe adverse events occurred.

Questions about ONB therapy that still remain to be answered in future controlled studies include the most efficient dose, the optimal number of injections, whether they should be administered uni- or bilaterally, and the type of steroids that work best. It seems that at present everyone working in this field is using a different injection concoction, the neurologist noted.

In a separate presentation at the congress, Dr. Norazah Abu Bakar of the National Hospital for Neurology and Neurosurgery, London, reported on 83 patients with chronic cluster headache treated with up to three unilateral ONB injections given at 3-month intervals at that institution.

The impetus for this retrospective study focusing on patients with refractory chronic cluster headache, she explained, was that while a recent noteworthy French randomized, double-blind, placebo-controlled clinical trial has shown ONB to be an effective therapy in patients with episodic cluster headache (Lancet Neurol. 2011;10:891-7), that study included only 15 patients with chronic cluster headache. Thus, few data are available on ONB in the 10% or so of cluster headache patients saddled with the extremely burdensome chronic cluster headache.

The ONB used in her study entailed a unilateral injection of a mixture of 80 mg of methylprednisolone and 2 mL of lidocaine 2%. Thirty of the 83 patients (36%) responded to a first injection with a complete pain-free interval lasting for a median of 14 days. Another 29 had partial pain relief, defined as greater than 50% improvement, lasting an average of 18 days. There were 19 nonresponders, and 5 patients experienced deterioration lasting for a median of 14 days.

Mean headache frequency in the overall group improved from 4.2 attacks/day at baseline to 1.7/day post treatment. Self-rated pain intensity went from a mean of 9.5 to 3.9 on a 10-point scale. And there was a further benefit: mean attack duration dropped from 108 minutes to 52 minutes.

The median latency period for a favorable response or headache worsening was 1 day after the injection. Patients reported no serious adverse events following treatment. One-third of subjects reported mild adverse events, mostly self-limited tenderness at the injection site, neck stiffness, and dizziness. No cutaneous atrophy or alopecia occurred after the injection.

Responders to the first injection were offered a second after 3 months, an interval chosen to minimize the risk of side effects due to overexposure to steroids. Among 45 patients treated a second time, 19 had a complete response and 16 a partial response with greater than 50% improvement. The median response duration was 18 days.

Three months later, 28 patients had a third ONB. Eleven showed a complete response and nine were partial responders, with a median response duration of 25 days.

Fourteen patients received a fourth injection, resulting in complete response in seven and partial response in three. The response duration averaged 23 days.

"Given the good tolerability profile when this simple procedure is performed every 3 months, occipital nerve blocks can play a useful role in the management of chronic cluster headache, allowing for periods of relief from an otherwise highly disabling disorder," she concluded.

Cluster headache is a rare disorder characterized by attacks of unilateral pain, typically orbital, supraorbital, and/or temporal. The attacks generally last from 15 minutes to 3 hours. They occur with a frequency ranging from once every day or 2 up to eight per day. Episodic cluster headache occurs in skeins running for weeks to months, followed by remission periods that can last for months.

Dr. Gaul and Dr. Abu Bakar reported having no financial conflicts.

LONDON – Occipital nerve blocks are an effective, safe, and well-tolerated therapy in patients with exacerbation of chronic or episodic cluster headache, according to two observational studies presented at the European Headache and Migraine Trust International Congress.

"It’s a treatment that can suppress attacks temporarily or reduce pain intensity in a high percentage of patients. From the clinical point of view, we gain 1 or 2 or 3 weeks of time to titrate up the standard medications so they can take effect. The patients are attack-free for some days, and they like that very much," observed Dr. Charly Gaul of University Hospital in Essen, Germany.

At the congress, he presented a prospective study of occipital nerve blocks in 101 patients with intractable, disabling cluster headaches insufficiently controlled by the established preventive and acute medications. Sixty-one patients had episodic cluster headache; the other 40 had the less commonly encountered chronic cluster headache, characterized by multiple daily excruciating attacks with no or only brief remission periods.

All subjects received a single occipital nerve block (ONB) of the greater and lesser occipital nerve using 10 mg of triamcinolone along with bupivacaine 0.5% for local anesthesia. The patients completed a headache questionnaire prior to and again 3 and 10 days after receiving the ONB and then once more upon recurrence of their headache attacks.

A total of 83% of patients demonstrated a complete or partial response to their ONB. Efficacy was greater in the episodic cluster headache cohort: 41 of the 61 such patients became completely or temporarily attack free for a mean of 34 days, as did 20 of 40 patients with chronic cluster headache, for a notably briefer mean of 14 days.

Headache frequency in the episodic cluster headache group fell from a mean of 2.9 attacks/day at baseline to 0.7 attacks/day during the first 3 days following ONB and 1.1/day on days 7-10 post treatment. Self-reported pain intensity of attacks on a 0-10 scale improved from 8.4 at baseline to 2.3 in the first several days post-treatment and 3.3 on days 7-10 following the injection.

The average number of headaches per day in the chronic cluster headache cohort dropped from 3.3 at baseline to 1.1 during days 1-3 and 1.9 on days 7-10 post treatment. Pain intensity scores fell from a baseline of 7.9 to 3.9 shortly after ONB and 5.9 on days 7-10 post treatment, Dr. Gaul continued.

Adverse events (all minor) occurred in 11% of patients, the most common of which was a non–cluster headache, occurring in 3% of participants. Injection site pain and occipital muscle tension were among the other adverse events. No severe adverse events occurred.

Questions about ONB therapy that still remain to be answered in future controlled studies include the most efficient dose, the optimal number of injections, whether they should be administered uni- or bilaterally, and the type of steroids that work best. It seems that at present everyone working in this field is using a different injection concoction, the neurologist noted.

In a separate presentation at the congress, Dr. Norazah Abu Bakar of the National Hospital for Neurology and Neurosurgery, London, reported on 83 patients with chronic cluster headache treated with up to three unilateral ONB injections given at 3-month intervals at that institution.

The impetus for this retrospective study focusing on patients with refractory chronic cluster headache, she explained, was that while a recent noteworthy French randomized, double-blind, placebo-controlled clinical trial has shown ONB to be an effective therapy in patients with episodic cluster headache (Lancet Neurol. 2011;10:891-7), that study included only 15 patients with chronic cluster headache. Thus, few data are available on ONB in the 10% or so of cluster headache patients saddled with the extremely burdensome chronic cluster headache.

The ONB used in her study entailed a unilateral injection of a mixture of 80 mg of methylprednisolone and 2 mL of lidocaine 2%. Thirty of the 83 patients (36%) responded to a first injection with a complete pain-free interval lasting for a median of 14 days. Another 29 had partial pain relief, defined as greater than 50% improvement, lasting an average of 18 days. There were 19 nonresponders, and 5 patients experienced deterioration lasting for a median of 14 days.

Mean headache frequency in the overall group improved from 4.2 attacks/day at baseline to 1.7/day post treatment. Self-rated pain intensity went from a mean of 9.5 to 3.9 on a 10-point scale. And there was a further benefit: mean attack duration dropped from 108 minutes to 52 minutes.

The median latency period for a favorable response or headache worsening was 1 day after the injection. Patients reported no serious adverse events following treatment. One-third of subjects reported mild adverse events, mostly self-limited tenderness at the injection site, neck stiffness, and dizziness. No cutaneous atrophy or alopecia occurred after the injection.

Responders to the first injection were offered a second after 3 months, an interval chosen to minimize the risk of side effects due to overexposure to steroids. Among 45 patients treated a second time, 19 had a complete response and 16 a partial response with greater than 50% improvement. The median response duration was 18 days.

Three months later, 28 patients had a third ONB. Eleven showed a complete response and nine were partial responders, with a median response duration of 25 days.

Fourteen patients received a fourth injection, resulting in complete response in seven and partial response in three. The response duration averaged 23 days.

"Given the good tolerability profile when this simple procedure is performed every 3 months, occipital nerve blocks can play a useful role in the management of chronic cluster headache, allowing for periods of relief from an otherwise highly disabling disorder," she concluded.

Cluster headache is a rare disorder characterized by attacks of unilateral pain, typically orbital, supraorbital, and/or temporal. The attacks generally last from 15 minutes to 3 hours. They occur with a frequency ranging from once every day or 2 up to eight per day. Episodic cluster headache occurs in skeins running for weeks to months, followed by remission periods that can last for months.

Dr. Gaul and Dr. Abu Bakar reported having no financial conflicts.

LONDON – Occipital nerve blocks are an effective, safe, and well-tolerated therapy in patients with exacerbation of chronic or episodic cluster headache, according to two observational studies presented at the European Headache and Migraine Trust International Congress.

"It’s a treatment that can suppress attacks temporarily or reduce pain intensity in a high percentage of patients. From the clinical point of view, we gain 1 or 2 or 3 weeks of time to titrate up the standard medications so they can take effect. The patients are attack-free for some days, and they like that very much," observed Dr. Charly Gaul of University Hospital in Essen, Germany.

At the congress, he presented a prospective study of occipital nerve blocks in 101 patients with intractable, disabling cluster headaches insufficiently controlled by the established preventive and acute medications. Sixty-one patients had episodic cluster headache; the other 40 had the less commonly encountered chronic cluster headache, characterized by multiple daily excruciating attacks with no or only brief remission periods.

All subjects received a single occipital nerve block (ONB) of the greater and lesser occipital nerve using 10 mg of triamcinolone along with bupivacaine 0.5% for local anesthesia. The patients completed a headache questionnaire prior to and again 3 and 10 days after receiving the ONB and then once more upon recurrence of their headache attacks.

A total of 83% of patients demonstrated a complete or partial response to their ONB. Efficacy was greater in the episodic cluster headache cohort: 41 of the 61 such patients became completely or temporarily attack free for a mean of 34 days, as did 20 of 40 patients with chronic cluster headache, for a notably briefer mean of 14 days.

Headache frequency in the episodic cluster headache group fell from a mean of 2.9 attacks/day at baseline to 0.7 attacks/day during the first 3 days following ONB and 1.1/day on days 7-10 post treatment. Self-reported pain intensity of attacks on a 0-10 scale improved from 8.4 at baseline to 2.3 in the first several days post-treatment and 3.3 on days 7-10 following the injection.

The average number of headaches per day in the chronic cluster headache cohort dropped from 3.3 at baseline to 1.1 during days 1-3 and 1.9 on days 7-10 post treatment. Pain intensity scores fell from a baseline of 7.9 to 3.9 shortly after ONB and 5.9 on days 7-10 post treatment, Dr. Gaul continued.

Adverse events (all minor) occurred in 11% of patients, the most common of which was a non–cluster headache, occurring in 3% of participants. Injection site pain and occipital muscle tension were among the other adverse events. No severe adverse events occurred.

Questions about ONB therapy that still remain to be answered in future controlled studies include the most efficient dose, the optimal number of injections, whether they should be administered uni- or bilaterally, and the type of steroids that work best. It seems that at present everyone working in this field is using a different injection concoction, the neurologist noted.

In a separate presentation at the congress, Dr. Norazah Abu Bakar of the National Hospital for Neurology and Neurosurgery, London, reported on 83 patients with chronic cluster headache treated with up to three unilateral ONB injections given at 3-month intervals at that institution.

The impetus for this retrospective study focusing on patients with refractory chronic cluster headache, she explained, was that while a recent noteworthy French randomized, double-blind, placebo-controlled clinical trial has shown ONB to be an effective therapy in patients with episodic cluster headache (Lancet Neurol. 2011;10:891-7), that study included only 15 patients with chronic cluster headache. Thus, few data are available on ONB in the 10% or so of cluster headache patients saddled with the extremely burdensome chronic cluster headache.

The ONB used in her study entailed a unilateral injection of a mixture of 80 mg of methylprednisolone and 2 mL of lidocaine 2%. Thirty of the 83 patients (36%) responded to a first injection with a complete pain-free interval lasting for a median of 14 days. Another 29 had partial pain relief, defined as greater than 50% improvement, lasting an average of 18 days. There were 19 nonresponders, and 5 patients experienced deterioration lasting for a median of 14 days.

Mean headache frequency in the overall group improved from 4.2 attacks/day at baseline to 1.7/day post treatment. Self-rated pain intensity went from a mean of 9.5 to 3.9 on a 10-point scale. And there was a further benefit: mean attack duration dropped from 108 minutes to 52 minutes.

The median latency period for a favorable response or headache worsening was 1 day after the injection. Patients reported no serious adverse events following treatment. One-third of subjects reported mild adverse events, mostly self-limited tenderness at the injection site, neck stiffness, and dizziness. No cutaneous atrophy or alopecia occurred after the injection.

Responders to the first injection were offered a second after 3 months, an interval chosen to minimize the risk of side effects due to overexposure to steroids. Among 45 patients treated a second time, 19 had a complete response and 16 a partial response with greater than 50% improvement. The median response duration was 18 days.

Three months later, 28 patients had a third ONB. Eleven showed a complete response and nine were partial responders, with a median response duration of 25 days.

Fourteen patients received a fourth injection, resulting in complete response in seven and partial response in three. The response duration averaged 23 days.

"Given the good tolerability profile when this simple procedure is performed every 3 months, occipital nerve blocks can play a useful role in the management of chronic cluster headache, allowing for periods of relief from an otherwise highly disabling disorder," she concluded.

Cluster headache is a rare disorder characterized by attacks of unilateral pain, typically orbital, supraorbital, and/or temporal. The attacks generally last from 15 minutes to 3 hours. They occur with a frequency ranging from once every day or 2 up to eight per day. Episodic cluster headache occurs in skeins running for weeks to months, followed by remission periods that can last for months.

Dr. Gaul and Dr. Abu Bakar reported having no financial conflicts.

LONDON  – Roughly 40% of the cost of 6 months of onabotulinumtoxinA for the treatment of chronic migraine is offset by resultant decreased use of emergency departments, urgent care facilities, and migraine-related hospitalizations, according to a prospective, real-world, cost-benefit study conducted in clinical practice.

"The associated savings offset a reasonable proportion of the cost of treatment for the entire group – nonresponders as well as responders – and there were a fair number of nonresponders because this was a severely affected group," Dr. John F. Rothrock said at the European Headache and Migraine Trust International Congress.

Moreover, the 40% figure undoubtedly underestimates the total savings by a considerable margin because it includes only migraine-related direct medical costs for emergency department and urgent care visits and hospitalizations. Additional savings would be expected as a result of reduced need for abortive medications and prophylactic therapies, as well as decreased work absenteeism, which is a "gigantic" indirect cost associated with chronic migraine, noted Dr. Rothrock, professor and chief of neurosciences at the University of Nevada, Reno.

Chronic migraine, defined as migraine headaches an average of at least 15 days per month, affects 1%-2% of U.S. adults. The costs, both economic and in terms of diminished quality of life, are enormous. Botox is the only Food and Drug Administration (FDA)-approved therapy for this common disorder.

But onabotulinumtoxinA (Botox) is also an expensive therapy, and that’s what prompted Dr. Rothrock to systematically study the treatment’s real-world economic impact.

He reported on 230 consecutive chronic migraine patients treated with Botox using the same protocol as in the two pivotal PREEMPT (Phase III Research Evaluating Migraine Prophylaxis Therapy) studies (Cephalalgia 2010;30:793-803 and 804-14) that led to FDA approval of an indication for Botox in treating chronic migraine: namely, injections at baseline, 3 months, and 6 months.

Nearly three-quarters of participants in Dr. Rothrock’s study were rated as having "very severe disability" using the MIDAS (Migraine Disability Assessment Score) system. The majority of patients had a median 36-month history of daily or near-daily headache. Subjects had tried a median of three appropriately dosed prophylactic agents before they received Botox. Thirty-seven percent of participants had symptomatic headache medication overuse.

Forty-eight percent of patients had a positive treatment response to Botox as defined by at least a 50% reduction in the number of headache days per month during month 6, compared with the month prior to starting treatment. In other words, they were successfully converted from chronic to episodic migraine.

The cost of a Botox treatment session, including the drug and reimbursement for the procedure, was estimated at $1,300. Costs for emergency department visits and other end points were based upon national averages.

The reduction in direct medical costs in the overall group during the 6 months after starting Botox was a mean $1,025, compared with the 6 months prior to beginning therapy. This was driven mainly by a mean 0.92 fewer emergency department visits and 0.39 fewer urgent care visits.

Asked when he typically resorts to Botox in patients with migraine, Dr. Rothrock replied that while many physicians reserve it for end-of-the-line therapy, as an advocate of evidence-based medicine, he disagrees with that approach.

"There’s clear evidence that Botox works. It’s the only FDA-approved treatment in the United States for chronic migraine, period," said Dr. Rothrock, who is the editor-in-chief of the journal Headache.

"But I think if you look at the literature concerning topiramate you’ll find that topiramate owns a pretty good evidence base," the neurologist continued. "My approach to the chronic migraine patient who’s topiramate naïve, which is a rare thing, is to try topiramate first. And if they tolerate it well, which is often a problem, and they respond well, then that’s great. I do that for cost reasons. It’s a lot cheaper than beginning Botox. But if they don’t respond to topiramate or they can’t tolerate it and they can’t then try zonisamide, a molecularly similar drug that has a middling-weak evidence base, then I’ll go straight to Botox. It’s my second-line therapy."

Aside from topiramate, the myriad other drugs used off-label for prophylaxis of chronic migraine have virtually no supporting evidence for that application, Dr. Rothrock observed.

"And I would maintain that the longer the patient remains in chronic migraine, the tougher will be your job to get them out of chronic migraine. So we can fiddle around with verapamil, et cetera, for chronic migraine, but I really would urge you to consider putting Botox very close to the top of your treatment armamentarium," he concluded.

The study was supported by a grant from Allergan. Dr. Rothrock reported serving as a consultant to the company

LONDON  – Roughly 40% of the cost of 6 months of onabotulinumtoxinA for the treatment of chronic migraine is offset by resultant decreased use of emergency departments, urgent care facilities, and migraine-related hospitalizations, according to a prospective, real-world, cost-benefit study conducted in clinical practice.

"The associated savings offset a reasonable proportion of the cost of treatment for the entire group – nonresponders as well as responders – and there were a fair number of nonresponders because this was a severely affected group," Dr. John F. Rothrock said at the European Headache and Migraine Trust International Congress.

Moreover, the 40% figure undoubtedly underestimates the total savings by a considerable margin because it includes only migraine-related direct medical costs for emergency department and urgent care visits and hospitalizations. Additional savings would be expected as a result of reduced need for abortive medications and prophylactic therapies, as well as decreased work absenteeism, which is a "gigantic" indirect cost associated with chronic migraine, noted Dr. Rothrock, professor and chief of neurosciences at the University of Nevada, Reno.

Chronic migraine, defined as migraine headaches an average of at least 15 days per month, affects 1%-2% of U.S. adults. The costs, both economic and in terms of diminished quality of life, are enormous. Botox is the only Food and Drug Administration (FDA)-approved therapy for this common disorder.

But onabotulinumtoxinA (Botox) is also an expensive therapy, and that’s what prompted Dr. Rothrock to systematically study the treatment’s real-world economic impact.

He reported on 230 consecutive chronic migraine patients treated with Botox using the same protocol as in the two pivotal PREEMPT (Phase III Research Evaluating Migraine Prophylaxis Therapy) studies (Cephalalgia 2010;30:793-803 and 804-14) that led to FDA approval of an indication for Botox in treating chronic migraine: namely, injections at baseline, 3 months, and 6 months.

Nearly three-quarters of participants in Dr. Rothrock’s study were rated as having "very severe disability" using the MIDAS (Migraine Disability Assessment Score) system. The majority of patients had a median 36-month history of daily or near-daily headache. Subjects had tried a median of three appropriately dosed prophylactic agents before they received Botox. Thirty-seven percent of participants had symptomatic headache medication overuse.

Forty-eight percent of patients had a positive treatment response to Botox as defined by at least a 50% reduction in the number of headache days per month during month 6, compared with the month prior to starting treatment. In other words, they were successfully converted from chronic to episodic migraine.

The cost of a Botox treatment session, including the drug and reimbursement for the procedure, was estimated at $1,300. Costs for emergency department visits and other end points were based upon national averages.

The reduction in direct medical costs in the overall group during the 6 months after starting Botox was a mean $1,025, compared with the 6 months prior to beginning therapy. This was driven mainly by a mean 0.92 fewer emergency department visits and 0.39 fewer urgent care visits.

Asked when he typically resorts to Botox in patients with migraine, Dr. Rothrock replied that while many physicians reserve it for end-of-the-line therapy, as an advocate of evidence-based medicine, he disagrees with that approach.

"There’s clear evidence that Botox works. It’s the only FDA-approved treatment in the United States for chronic migraine, period," said Dr. Rothrock, who is the editor-in-chief of the journal Headache.

"But I think if you look at the literature concerning topiramate you’ll find that topiramate owns a pretty good evidence base," the neurologist continued. "My approach to the chronic migraine patient who’s topiramate naïve, which is a rare thing, is to try topiramate first. And if they tolerate it well, which is often a problem, and they respond well, then that’s great. I do that for cost reasons. It’s a lot cheaper than beginning Botox. But if they don’t respond to topiramate or they can’t tolerate it and they can’t then try zonisamide, a molecularly similar drug that has a middling-weak evidence base, then I’ll go straight to Botox. It’s my second-line therapy."

Aside from topiramate, the myriad other drugs used off-label for prophylaxis of chronic migraine have virtually no supporting evidence for that application, Dr. Rothrock observed.

"And I would maintain that the longer the patient remains in chronic migraine, the tougher will be your job to get them out of chronic migraine. So we can fiddle around with verapamil, et cetera, for chronic migraine, but I really would urge you to consider putting Botox very close to the top of your treatment armamentarium," he concluded.

The study was supported by a grant from Allergan. Dr. Rothrock reported serving as a consultant to the company

LONDON  – Roughly 40% of the cost of 6 months of onabotulinumtoxinA for the treatment of chronic migraine is offset by resultant decreased use of emergency departments, urgent care facilities, and migraine-related hospitalizations, according to a prospective, real-world, cost-benefit study conducted in clinical practice.

"The associated savings offset a reasonable proportion of the cost of treatment for the entire group – nonresponders as well as responders – and there were a fair number of nonresponders because this was a severely affected group," Dr. John F. Rothrock said at the European Headache and Migraine Trust International Congress.

Moreover, the 40% figure undoubtedly underestimates the total savings by a considerable margin because it includes only migraine-related direct medical costs for emergency department and urgent care visits and hospitalizations. Additional savings would be expected as a result of reduced need for abortive medications and prophylactic therapies, as well as decreased work absenteeism, which is a "gigantic" indirect cost associated with chronic migraine, noted Dr. Rothrock, professor and chief of neurosciences at the University of Nevada, Reno.

Chronic migraine, defined as migraine headaches an average of at least 15 days per month, affects 1%-2% of U.S. adults. The costs, both economic and in terms of diminished quality of life, are enormous. Botox is the only Food and Drug Administration (FDA)-approved therapy for this common disorder.

But onabotulinumtoxinA (Botox) is also an expensive therapy, and that’s what prompted Dr. Rothrock to systematically study the treatment’s real-world economic impact.

He reported on 230 consecutive chronic migraine patients treated with Botox using the same protocol as in the two pivotal PREEMPT (Phase III Research Evaluating Migraine Prophylaxis Therapy) studies (Cephalalgia 2010;30:793-803 and 804-14) that led to FDA approval of an indication for Botox in treating chronic migraine: namely, injections at baseline, 3 months, and 6 months.

Nearly three-quarters of participants in Dr. Rothrock’s study were rated as having "very severe disability" using the MIDAS (Migraine Disability Assessment Score) system. The majority of patients had a median 36-month history of daily or near-daily headache. Subjects had tried a median of three appropriately dosed prophylactic agents before they received Botox. Thirty-seven percent of participants had symptomatic headache medication overuse.

Forty-eight percent of patients had a positive treatment response to Botox as defined by at least a 50% reduction in the number of headache days per month during month 6, compared with the month prior to starting treatment. In other words, they were successfully converted from chronic to episodic migraine.

The cost of a Botox treatment session, including the drug and reimbursement for the procedure, was estimated at $1,300. Costs for emergency department visits and other end points were based upon national averages.

The reduction in direct medical costs in the overall group during the 6 months after starting Botox was a mean $1,025, compared with the 6 months prior to beginning therapy. This was driven mainly by a mean 0.92 fewer emergency department visits and 0.39 fewer urgent care visits.

Asked when he typically resorts to Botox in patients with migraine, Dr. Rothrock replied that while many physicians reserve it for end-of-the-line therapy, as an advocate of evidence-based medicine, he disagrees with that approach.

"There’s clear evidence that Botox works. It’s the only FDA-approved treatment in the United States for chronic migraine, period," said Dr. Rothrock, who is the editor-in-chief of the journal Headache.

"But I think if you look at the literature concerning topiramate you’ll find that topiramate owns a pretty good evidence base," the neurologist continued. "My approach to the chronic migraine patient who’s topiramate naïve, which is a rare thing, is to try topiramate first. And if they tolerate it well, which is often a problem, and they respond well, then that’s great. I do that for cost reasons. It’s a lot cheaper than beginning Botox. But if they don’t respond to topiramate or they can’t tolerate it and they can’t then try zonisamide, a molecularly similar drug that has a middling-weak evidence base, then I’ll go straight to Botox. It’s my second-line therapy."

Aside from topiramate, the myriad other drugs used off-label for prophylaxis of chronic migraine have virtually no supporting evidence for that application, Dr. Rothrock observed.

"And I would maintain that the longer the patient remains in chronic migraine, the tougher will be your job to get them out of chronic migraine. So we can fiddle around with verapamil, et cetera, for chronic migraine, but I really would urge you to consider putting Botox very close to the top of your treatment armamentarium," he concluded.

The study was supported by a grant from Allergan. Dr. Rothrock reported serving as a consultant to the company

LONDON  – Twenty-five percent of chronic migraine patients experience at least a 75% reduction in headache days per month after 6 months of treatment with onabotulinumtoxinA, according to a new analysis of data from the landmark PREEMPT trials.

"That’s what I tell my patients to expect: If they go on Botox [onabotulinumtoxinA], they have a 1 in 4 chance of a 75% or greater reduction in headache symptoms over 6 months of therapy," Dr. David W. Dodick said at the European Headache and Migraine Trust International Congress.

PREEMPT (Phase III Research Evaluating Migraine Prophylaxis Therapy) consisted of two pivotal trials that resulted in Food and Drug Administration licensure of Botox as the only approved treatment for chronic migraine, an often-disabling disorder that affects 1%-2% of the U.S. adult population.

PREEMPT involved 1,384 adults with chronic migraine as defined by the International Classification of Headache Disorders, 2nd edition, criteria – basically, an average of at least 15 days of headache per month – at 122 U.S. and European sites. Participants were randomized double-blind to Botox or placebo injections at baseline, 12, and 24 weeks. Then the placebo group was crossed over to open-label Botox, which all subjects received at weeks 36 and 48.

The previously reported primary end point was the change in frequency of headache days per month between baseline and 6 months. Botox significantly outperformed placebo, achieving a mean 8.4-day decrease in headache days per month from the pretreatment baseline of 19.9 days, compared with a 6.6-day drop with placebo (Cephalalgia 2010;30:793-803 and 804-14).

Dr. Dodick’s report on the proportion of patients achieving at least a 75% reduction in headache days per month was just one of several secondary end points in PREEMPT presented at the congress for the first time. Some PREEMPT investigators indicated they found these secondary outcome measures more clinically relevant than the primary study end point.

"The primary end point was perhaps one I wouldn’t have chosen myself," said Dr. John F. Rothrock, professor and chief of neurosciences at the University of Nevada, Reno, and editor-in-chief of the journal Headache. "The fact that you lose 1.8 headache days per month if you treat your patient with Botox is not really very exciting to me. It doesn’t lead me to be very enthusiastic about implementing a therapy that costs as much as Botox."

"A far more interesting end point to me – and one that was a secondary assessment in PREEMPT – was in how many patients do you achieve remission from chronic migraine back to episodic migraine with implementation of Botox therapy? Because that’s really what we’re after as clinicians: not just lopping off a couple of headache days per month, but how often can I wipe the slate clean and take that patient who has headache on more days than not – and in some cases, daily – and give them a headache-free or nearly headache-free existence off prophylactic medications and only occasionally using abortive therapy?" he continued.

The good news is that at the study’s end at week 56, roughly 70% of patients had achieved a 50% or greater reduction in headache days per month, compared with baseline. The divergence between active treatment and placebo in this secondary outcome measure was already significant at the first assessment, just 4 weeks after the first treatment session. The divergence grew through the first 6 months, then diminished once the former placebo group went on Botox, Dr. Rothrock noted.

The one potentially treatment-related serious adverse event seen in the study was status migrainosus requiring hospitalization. The incidence was 0.1% in the Botox arm and zero in the placebo group.

"I’ve now treated just short of 1,000 patients with Botox using the PREEMPT protocol, and it’s really unusual to run into a clinically significant side effect. The most common side effect in the PREEMPT trials was neck pain and stiffness. Patients talk about a wobbly neck or bobble head, a weakness in the neck. Other than that, it’s a very clean therapy, especially compared to other things that we use to try to suppress chronic migraine and get it to remit to episodic migraine," the neurologist observed.

Dr. Dodick agreed that the primary end point in PREEMPT doesn’t come close to capturing the whole story regarding Botox therapy.

"My own clinical experience using it for the last 12 years is that some patients have a significant reduction in headache days, while others who’ve had one continuous headache continue to do so with zero days reduction, but the severity is dramatically reduced. Their consumption of acute medications decreases and their response to medications is enhanced. So if you look at just one clinical end point – headache days per month – you may miss a dramatic improvement that occurs with no reduction in days," said Dr. Dodick, professor of neurology at the Mayo Clinic, Phoenix, and a past president of the American Headache Society.

Another newly analyzed secondary end point was the response rate per treatment cycle in PREEMPT. Dr. Dodick reported that 49% of participants responded to the first Botox injection with at 50% or greater reduction in their frequency of headache days per month. An additional 11% achieved this benchmark only after the second treatment cycle, and another 10% did so after the third.

"Just because a patient doesn’t respond to one injection doesn’t mean we shouldn’t try a second. I generally don’t go beyond two nonresponding injections. But don’t stop after one," he urged.

That advice is consistent with the results of an appraisal by the U.K. National Institute for Health and Clinical Excellence (NICE), which deemed Botox for chronic migraine "an appropriate use of NHS [National Health Service] resources," with the proviso that the treatment be stopped if it hasn’t achieved a 30% reduction in the number of headache days per month after two cycles.

THE PREEMPT trials and the new secondary analyses were sponsored by Allergan. Both Dr. Dodick and Dr. Rothrock reported receiving research funds from and consulting for the company.

LONDON  – Twenty-five percent of chronic migraine patients experience at least a 75% reduction in headache days per month after 6 months of treatment with onabotulinumtoxinA, according to a new analysis of data from the landmark PREEMPT trials.

"That’s what I tell my patients to expect: If they go on Botox [onabotulinumtoxinA], they have a 1 in 4 chance of a 75% or greater reduction in headache symptoms over 6 months of therapy," Dr. David W. Dodick said at the European Headache and Migraine Trust International Congress.

PREEMPT (Phase III Research Evaluating Migraine Prophylaxis Therapy) consisted of two pivotal trials that resulted in Food and Drug Administration licensure of Botox as the only approved treatment for chronic migraine, an often-disabling disorder that affects 1%-2% of the U.S. adult population.

PREEMPT involved 1,384 adults with chronic migraine as defined by the International Classification of Headache Disorders, 2nd edition, criteria – basically, an average of at least 15 days of headache per month – at 122 U.S. and European sites. Participants were randomized double-blind to Botox or placebo injections at baseline, 12, and 24 weeks. Then the placebo group was crossed over to open-label Botox, which all subjects received at weeks 36 and 48.

The previously reported primary end point was the change in frequency of headache days per month between baseline and 6 months. Botox significantly outperformed placebo, achieving a mean 8.4-day decrease in headache days per month from the pretreatment baseline of 19.9 days, compared with a 6.6-day drop with placebo (Cephalalgia 2010;30:793-803 and 804-14).

Dr. Dodick’s report on the proportion of patients achieving at least a 75% reduction in headache days per month was just one of several secondary end points in PREEMPT presented at the congress for the first time. Some PREEMPT investigators indicated they found these secondary outcome measures more clinically relevant than the primary study end point.

"The primary end point was perhaps one I wouldn’t have chosen myself," said Dr. John F. Rothrock, professor and chief of neurosciences at the University of Nevada, Reno, and editor-in-chief of the journal Headache. "The fact that you lose 1.8 headache days per month if you treat your patient with Botox is not really very exciting to me. It doesn’t lead me to be very enthusiastic about implementing a therapy that costs as much as Botox."

"A far more interesting end point to me – and one that was a secondary assessment in PREEMPT – was in how many patients do you achieve remission from chronic migraine back to episodic migraine with implementation of Botox therapy? Because that’s really what we’re after as clinicians: not just lopping off a couple of headache days per month, but how often can I wipe the slate clean and take that patient who has headache on more days than not – and in some cases, daily – and give them a headache-free or nearly headache-free existence off prophylactic medications and only occasionally using abortive therapy?" he continued.

The good news is that at the study’s end at week 56, roughly 70% of patients had achieved a 50% or greater reduction in headache days per month, compared with baseline. The divergence between active treatment and placebo in this secondary outcome measure was already significant at the first assessment, just 4 weeks after the first treatment session. The divergence grew through the first 6 months, then diminished once the former placebo group went on Botox, Dr. Rothrock noted.

The one potentially treatment-related serious adverse event seen in the study was status migrainosus requiring hospitalization. The incidence was 0.1% in the Botox arm and zero in the placebo group.

"I’ve now treated just short of 1,000 patients with Botox using the PREEMPT protocol, and it’s really unusual to run into a clinically significant side effect. The most common side effect in the PREEMPT trials was neck pain and stiffness. Patients talk about a wobbly neck or bobble head, a weakness in the neck. Other than that, it’s a very clean therapy, especially compared to other things that we use to try to suppress chronic migraine and get it to remit to episodic migraine," the neurologist observed.

Dr. Dodick agreed that the primary end point in PREEMPT doesn’t come close to capturing the whole story regarding Botox therapy.

"My own clinical experience using it for the last 12 years is that some patients have a significant reduction in headache days, while others who’ve had one continuous headache continue to do so with zero days reduction, but the severity is dramatically reduced. Their consumption of acute medications decreases and their response to medications is enhanced. So if you look at just one clinical end point – headache days per month – you may miss a dramatic improvement that occurs with no reduction in days," said Dr. Dodick, professor of neurology at the Mayo Clinic, Phoenix, and a past president of the American Headache Society.

Another newly analyzed secondary end point was the response rate per treatment cycle in PREEMPT. Dr. Dodick reported that 49% of participants responded to the first Botox injection with at 50% or greater reduction in their frequency of headache days per month. An additional 11% achieved this benchmark only after the second treatment cycle, and another 10% did so after the third.

"Just because a patient doesn’t respond to one injection doesn’t mean we shouldn’t try a second. I generally don’t go beyond two nonresponding injections. But don’t stop after one," he urged.

That advice is consistent with the results of an appraisal by the U.K. National Institute for Health and Clinical Excellence (NICE), which deemed Botox for chronic migraine "an appropriate use of NHS [National Health Service] resources," with the proviso that the treatment be stopped if it hasn’t achieved a 30% reduction in the number of headache days per month after two cycles.

THE PREEMPT trials and the new secondary analyses were sponsored by Allergan. Both Dr. Dodick and Dr. Rothrock reported receiving research funds from and consulting for the company.

LONDON  – Twenty-five percent of chronic migraine patients experience at least a 75% reduction in headache days per month after 6 months of treatment with onabotulinumtoxinA, according to a new analysis of data from the landmark PREEMPT trials.

"That’s what I tell my patients to expect: If they go on Botox [onabotulinumtoxinA], they have a 1 in 4 chance of a 75% or greater reduction in headache symptoms over 6 months of therapy," Dr. David W. Dodick said at the European Headache and Migraine Trust International Congress.

PREEMPT (Phase III Research Evaluating Migraine Prophylaxis Therapy) consisted of two pivotal trials that resulted in Food and Drug Administration licensure of Botox as the only approved treatment for chronic migraine, an often-disabling disorder that affects 1%-2% of the U.S. adult population.

PREEMPT involved 1,384 adults with chronic migraine as defined by the International Classification of Headache Disorders, 2nd edition, criteria – basically, an average of at least 15 days of headache per month – at 122 U.S. and European sites. Participants were randomized double-blind to Botox or placebo injections at baseline, 12, and 24 weeks. Then the placebo group was crossed over to open-label Botox, which all subjects received at weeks 36 and 48.

The previously reported primary end point was the change in frequency of headache days per month between baseline and 6 months. Botox significantly outperformed placebo, achieving a mean 8.4-day decrease in headache days per month from the pretreatment baseline of 19.9 days, compared with a 6.6-day drop with placebo (Cephalalgia 2010;30:793-803 and 804-14).

Dr. Dodick’s report on the proportion of patients achieving at least a 75% reduction in headache days per month was just one of several secondary end points in PREEMPT presented at the congress for the first time. Some PREEMPT investigators indicated they found these secondary outcome measures more clinically relevant than the primary study end point.

"The primary end point was perhaps one I wouldn’t have chosen myself," said Dr. John F. Rothrock, professor and chief of neurosciences at the University of Nevada, Reno, and editor-in-chief of the journal Headache. "The fact that you lose 1.8 headache days per month if you treat your patient with Botox is not really very exciting to me. It doesn’t lead me to be very enthusiastic about implementing a therapy that costs as much as Botox."

"A far more interesting end point to me – and one that was a secondary assessment in PREEMPT – was in how many patients do you achieve remission from chronic migraine back to episodic migraine with implementation of Botox therapy? Because that’s really what we’re after as clinicians: not just lopping off a couple of headache days per month, but how often can I wipe the slate clean and take that patient who has headache on more days than not – and in some cases, daily – and give them a headache-free or nearly headache-free existence off prophylactic medications and only occasionally using abortive therapy?" he continued.

The good news is that at the study’s end at week 56, roughly 70% of patients had achieved a 50% or greater reduction in headache days per month, compared with baseline. The divergence between active treatment and placebo in this secondary outcome measure was already significant at the first assessment, just 4 weeks after the first treatment session. The divergence grew through the first 6 months, then diminished once the former placebo group went on Botox, Dr. Rothrock noted.

The one potentially treatment-related serious adverse event seen in the study was status migrainosus requiring hospitalization. The incidence was 0.1% in the Botox arm and zero in the placebo group.

"I’ve now treated just short of 1,000 patients with Botox using the PREEMPT protocol, and it’s really unusual to run into a clinically significant side effect. The most common side effect in the PREEMPT trials was neck pain and stiffness. Patients talk about a wobbly neck or bobble head, a weakness in the neck. Other than that, it’s a very clean therapy, especially compared to other things that we use to try to suppress chronic migraine and get it to remit to episodic migraine," the neurologist observed.

Dr. Dodick agreed that the primary end point in PREEMPT doesn’t come close to capturing the whole story regarding Botox therapy.

"My own clinical experience using it for the last 12 years is that some patients have a significant reduction in headache days, while others who’ve had one continuous headache continue to do so with zero days reduction, but the severity is dramatically reduced. Their consumption of acute medications decreases and their response to medications is enhanced. So if you look at just one clinical end point – headache days per month – you may miss a dramatic improvement that occurs with no reduction in days," said Dr. Dodick, professor of neurology at the Mayo Clinic, Phoenix, and a past president of the American Headache Society.

Another newly analyzed secondary end point was the response rate per treatment cycle in PREEMPT. Dr. Dodick reported that 49% of participants responded to the first Botox injection with at 50% or greater reduction in their frequency of headache days per month. An additional 11% achieved this benchmark only after the second treatment cycle, and another 10% did so after the third.

"Just because a patient doesn’t respond to one injection doesn’t mean we shouldn’t try a second. I generally don’t go beyond two nonresponding injections. But don’t stop after one," he urged.

That advice is consistent with the results of an appraisal by the U.K. National Institute for Health and Clinical Excellence (NICE), which deemed Botox for chronic migraine "an appropriate use of NHS [National Health Service] resources," with the proviso that the treatment be stopped if it hasn’t achieved a 30% reduction in the number of headache days per month after two cycles.

THE PREEMPT trials and the new secondary analyses were sponsored by Allergan. Both Dr. Dodick and Dr. Rothrock reported receiving research funds from and consulting for the company.

LONDON – Chronic musculoskeletal complaints and chronic daily headache share a bidirectional causal relationship in which patients with either condition are predisposed over time to develop the other one.

This key finding from a large, longitudinal, population-based Norwegian study has importance both for front-line clinicians as well as academic researchers, Dr. Lars J. Stovner observed at the European Headache and Migraine Trust International Congress.

"From a practical point of view, one can say that if one has a patient with one of these common complaints, one should try hard to treat it effectively not only to bring relief to the patient but to prevent the development of the other condition," said Dr. Stovner of the Norwegian University of Science and Technology, Trondheim.

The new observation of a bidirectional relationship between chronic musculoskeletal pain and chronic daily headache – that is, headache on an average of 15 or more days per month – may also have import in terms of understanding the relevant pathophysiology. It suggests the disorders may share a common underlying cause.

"It says that chronic pain in the body is probably very much related to chronic headache. As we’ve heard elsewhere at this conference, they are both basically brain disorders," he continued.

Dr. Stovner presented data from two consecutive surveys conducted 11 years apart as part of the Nord-Trondelag Health Study (HUNT). HUNT 2 included 51,383 adults queried in 1995-1997, of whom 26,197 completed the HUNT 3 questions regarding headache and chronic musculoskeletal pain at follow-up in 2006-2008.

Participants with chronic musculoskeletal complaints at baseline in HUNT 2 proved to have a 1.8-fold increased risk of developing chronic daily headache 11 years later in HUNT 3, compared with subjects without baseline chronic musculoskeletal pain in a multivariate analysis adjusted for the known potential confounders of age, gender, anxiety, depression, and socioeconomic status.

Moreover, subjects with chronic daily headache but not chronic musculoskeletal pain in HUNT 2 had an identical adjusted 1.8-fold increased risk of developing chronic musculoskeletal pain in HUNT 3. The risk climbed even higher, to 2.7-fold, when the analysis was restricted to individuals with widespread chronic musculoskeletal complaints in HUNT 3.

"This is a huge population-based prospective study running for longer than 10 years," commented session cochair Dr. Zaza Katsarava of Evangelist Hospital in Unna, Germany. "The results clearly show there are no separate physiologic baskets for migraine and back pain. They are both part of an entire pain matrix that is impaired."

Another HUNT analysis Dr. Stovner presented separately at the congress focused on the distinction between medication overuse headache and chronic daily headache without medication overuse. The study population consisted of 25,598 adults with no chronic daily headache in 1995-1997 at HUNT 2. Eleven years later, at the HUNT 3 follow-up, 201 subjects had developed medication overuse headache, for an incidence rate of 0.72 cases per 1,000 person-years.

"I think that’s perhaps a bit lower than would be expected from some of the retrospective studies done before in other countries, which suggest an incidence of medication overuse headache of 1%-1.5% per year," he noted.

Another 246 subjects developed chronic daily headache without medication overuse.

The key finding in this analysis was that several of the risk factors for development of medication overuse headache were not risk factors for chronic daily headache without medication overuse, indicating that these two disorders are pathogenetically distinct conditions, according to Dr. Stovner.

Shared risk factors for development of the two forms of chronic headache were female gender, having little education, chronic musculoskeletal complaints, insomnia, and headache at baseline.

In contrast, risk factors unique to the development of medication overuse headache included regular use of tranquilizers at baseline, which was associated with a 5.2-fold increased risk; a combination of gastrointestinal complaints, chronic musculoskeletal complaints, and anxiety and/or depression as defined by a Hospital Anxiety and Depression Scale score in excess of 11, which carried a 5-fold risk; smoking, which doubled the risk of subsequent medication overuse headache; and physical inactivity, which also was linked to a 2-fold elevated risk.

The implication of these findings is that the prevention and treatment of medication overuse headache should focus on the treatment of medical and psychiatric comorbid conditions, the use of tranquilizers, and lifestyle changes directed at smoking cessation and increased physical activity, Dr. Stovner concluded.

HUNT is supported by Norwegian governmental research funds. Dr. Stovner reported having no financial conflicts.

LONDON – Chronic musculoskeletal complaints and chronic daily headache share a bidirectional causal relationship in which patients with either condition are predisposed over time to develop the other one.

This key finding from a large, longitudinal, population-based Norwegian study has importance both for front-line clinicians as well as academic researchers, Dr. Lars J. Stovner observed at the European Headache and Migraine Trust International Congress.

"From a practical point of view, one can say that if one has a patient with one of these common complaints, one should try hard to treat it effectively not only to bring relief to the patient but to prevent the development of the other condition," said Dr. Stovner of the Norwegian University of Science and Technology, Trondheim.

The new observation of a bidirectional relationship between chronic musculoskeletal pain and chronic daily headache – that is, headache on an average of 15 or more days per month – may also have import in terms of understanding the relevant pathophysiology. It suggests the disorders may share a common underlying cause.

"It says that chronic pain in the body is probably very much related to chronic headache. As we’ve heard elsewhere at this conference, they are both basically brain disorders," he continued.

Dr. Stovner presented data from two consecutive surveys conducted 11 years apart as part of the Nord-Trondelag Health Study (HUNT). HUNT 2 included 51,383 adults queried in 1995-1997, of whom 26,197 completed the HUNT 3 questions regarding headache and chronic musculoskeletal pain at follow-up in 2006-2008.

Participants with chronic musculoskeletal complaints at baseline in HUNT 2 proved to have a 1.8-fold increased risk of developing chronic daily headache 11 years later in HUNT 3, compared with subjects without baseline chronic musculoskeletal pain in a multivariate analysis adjusted for the known potential confounders of age, gender, anxiety, depression, and socioeconomic status.

Moreover, subjects with chronic daily headache but not chronic musculoskeletal pain in HUNT 2 had an identical adjusted 1.8-fold increased risk of developing chronic musculoskeletal pain in HUNT 3. The risk climbed even higher, to 2.7-fold, when the analysis was restricted to individuals with widespread chronic musculoskeletal complaints in HUNT 3.

"This is a huge population-based prospective study running for longer than 10 years," commented session cochair Dr. Zaza Katsarava of Evangelist Hospital in Unna, Germany. "The results clearly show there are no separate physiologic baskets for migraine and back pain. They are both part of an entire pain matrix that is impaired."

Another HUNT analysis Dr. Stovner presented separately at the congress focused on the distinction between medication overuse headache and chronic daily headache without medication overuse. The study population consisted of 25,598 adults with no chronic daily headache in 1995-1997 at HUNT 2. Eleven years later, at the HUNT 3 follow-up, 201 subjects had developed medication overuse headache, for an incidence rate of 0.72 cases per 1,000 person-years.

"I think that’s perhaps a bit lower than would be expected from some of the retrospective studies done before in other countries, which suggest an incidence of medication overuse headache of 1%-1.5% per year," he noted.

Another 246 subjects developed chronic daily headache without medication overuse.

The key finding in this analysis was that several of the risk factors for development of medication overuse headache were not risk factors for chronic daily headache without medication overuse, indicating that these two disorders are pathogenetically distinct conditions, according to Dr. Stovner.

Shared risk factors for development of the two forms of chronic headache were female gender, having little education, chronic musculoskeletal complaints, insomnia, and headache at baseline.

In contrast, risk factors unique to the development of medication overuse headache included regular use of tranquilizers at baseline, which was associated with a 5.2-fold increased risk; a combination of gastrointestinal complaints, chronic musculoskeletal complaints, and anxiety and/or depression as defined by a Hospital Anxiety and Depression Scale score in excess of 11, which carried a 5-fold risk; smoking, which doubled the risk of subsequent medication overuse headache; and physical inactivity, which also was linked to a 2-fold elevated risk.

The implication of these findings is that the prevention and treatment of medication overuse headache should focus on the treatment of medical and psychiatric comorbid conditions, the use of tranquilizers, and lifestyle changes directed at smoking cessation and increased physical activity, Dr. Stovner concluded.

HUNT is supported by Norwegian governmental research funds. Dr. Stovner reported having no financial conflicts.

LONDON – Chronic musculoskeletal complaints and chronic daily headache share a bidirectional causal relationship in which patients with either condition are predisposed over time to develop the other one.

This key finding from a large, longitudinal, population-based Norwegian study has importance both for front-line clinicians as well as academic researchers, Dr. Lars J. Stovner observed at the European Headache and Migraine Trust International Congress.

"From a practical point of view, one can say that if one has a patient with one of these common complaints, one should try hard to treat it effectively not only to bring relief to the patient but to prevent the development of the other condition," said Dr. Stovner of the Norwegian University of Science and Technology, Trondheim.

The new observation of a bidirectional relationship between chronic musculoskeletal pain and chronic daily headache – that is, headache on an average of 15 or more days per month – may also have import in terms of understanding the relevant pathophysiology. It suggests the disorders may share a common underlying cause.

"It says that chronic pain in the body is probably very much related to chronic headache. As we’ve heard elsewhere at this conference, they are both basically brain disorders," he continued.

Dr. Stovner presented data from two consecutive surveys conducted 11 years apart as part of the Nord-Trondelag Health Study (HUNT). HUNT 2 included 51,383 adults queried in 1995-1997, of whom 26,197 completed the HUNT 3 questions regarding headache and chronic musculoskeletal pain at follow-up in 2006-2008.

Participants with chronic musculoskeletal complaints at baseline in HUNT 2 proved to have a 1.8-fold increased risk of developing chronic daily headache 11 years later in HUNT 3, compared with subjects without baseline chronic musculoskeletal pain in a multivariate analysis adjusted for the known potential confounders of age, gender, anxiety, depression, and socioeconomic status.

Moreover, subjects with chronic daily headache but not chronic musculoskeletal pain in HUNT 2 had an identical adjusted 1.8-fold increased risk of developing chronic musculoskeletal pain in HUNT 3. The risk climbed even higher, to 2.7-fold, when the analysis was restricted to individuals with widespread chronic musculoskeletal complaints in HUNT 3.

"This is a huge population-based prospective study running for longer than 10 years," commented session cochair Dr. Zaza Katsarava of Evangelist Hospital in Unna, Germany. "The results clearly show there are no separate physiologic baskets for migraine and back pain. They are both part of an entire pain matrix that is impaired."

Another HUNT analysis Dr. Stovner presented separately at the congress focused on the distinction between medication overuse headache and chronic daily headache without medication overuse. The study population consisted of 25,598 adults with no chronic daily headache in 1995-1997 at HUNT 2. Eleven years later, at the HUNT 3 follow-up, 201 subjects had developed medication overuse headache, for an incidence rate of 0.72 cases per 1,000 person-years.

"I think that’s perhaps a bit lower than would be expected from some of the retrospective studies done before in other countries, which suggest an incidence of medication overuse headache of 1%-1.5% per year," he noted.

Another 246 subjects developed chronic daily headache without medication overuse.

The key finding in this analysis was that several of the risk factors for development of medication overuse headache were not risk factors for chronic daily headache without medication overuse, indicating that these two disorders are pathogenetically distinct conditions, according to Dr. Stovner.

Shared risk factors for development of the two forms of chronic headache were female gender, having little education, chronic musculoskeletal complaints, insomnia, and headache at baseline.

In contrast, risk factors unique to the development of medication overuse headache included regular use of tranquilizers at baseline, which was associated with a 5.2-fold increased risk; a combination of gastrointestinal complaints, chronic musculoskeletal complaints, and anxiety and/or depression as defined by a Hospital Anxiety and Depression Scale score in excess of 11, which carried a 5-fold risk; smoking, which doubled the risk of subsequent medication overuse headache; and physical inactivity, which also was linked to a 2-fold elevated risk.

The implication of these findings is that the prevention and treatment of medication overuse headache should focus on the treatment of medical and psychiatric comorbid conditions, the use of tranquilizers, and lifestyle changes directed at smoking cessation and increased physical activity, Dr. Stovner concluded.

HUNT is supported by Norwegian governmental research funds. Dr. Stovner reported having no financial conflicts.