June 27, 2012 — Results of a new analysis, a subgroup analysis of a previous trial, show significant between-group improvements in the number and severity of headaches in patients with intractable chronic migraine using occipital nerve stimulation.
Although the primary endpoint of the study as established by the US Food and Drug Administration—a 50% or greater reduction in pain measured using a visual analogue scale (VAS)—was not met in the overall trial of patients with chronic migraine or probable migraine, a significant difference was seen at the 40% reduction level and in many secondary endpoints, the authors note. The new subanalysis looked at those patients meeting criteria for intractable chronic migraine.
"The results provide the best evidence yet that stimulating the occipital nerve reduces the number and severity of headaches and improves quality of life in difficult to treat patients," said lead author, Stephen B. Silberstein, MD, professor of neurology, and director of Jefferson Headache Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
These findings were presented during the American Headache Society's 54th Annual Scientific Meeting, held in Los Angeles, California. The work was supported by St. Jude Medical Neuromodulation Division, Plano, Texas.
Stimulating the occipital nerve is believed to inhibit sensory trigeminal pathways that are involved in migraine pain. "You're not stimulating the nerve because it's a source of migraine pain; you're stimulating the nerve because it acts as a major modulator to turn off pain from the head and neck," said Dr. Silberstein. "When the stimulator is on, patients may feel a 'low level buzz' in their head," he noted.
"Unlike with deep brain stimulation for the treatment of Parkinson's disease and other disorders, this procedure involves stimulating a peripheral nerve, so it doesn't carry the same risks," he explained.
The study included 125 patients with intractable chronic migraine. They had to have suffered a headache of at least moderate severity that lasted 4 or more hours on 15 or more days a month, and to have failed treatment with at least 3 preventative drugs.
In the original study, the 157 patients with chronic or probable migraine who were included had to have had 15 or more days of headache, to have tried at least 2 migraine-specific acute medications and at least 2 different classes of prophylactic medications, and to have been refractory.
All patients had been implanted with a neurostimulation device for the original trial, and then were randomly assigned to active stimulation (n = 88) or to a control group that received no stimulation (n = 37). Most patients (n = 122) completed the study.
In terms of headache pain relief, the study found significant between-group differences in percentages of patients achieving 10% (P = .001), 20% ( P = .006), and 30% (P = .011) reduction, using mean daily average VAS measurements.
Dr. Silberstein pointed out that this represents a major benefit for patients who were very disabled, having failed to respond to several earlier treatments. "Essentially, if you have pain all the time that's severe and incapacitating, and you are a 7 on a pain scale from 0 to 10, and you can reduce that to 3 or 4, that's a dramatic improvement."
Significantly more patients receiving active treatment categorized their headache pain relief as good or better (P = .001). "Half of the patients who received active stimulation said the relief was 'excellent' or 'good,' and another 20% said it was 'fair,' so about 70% of patients were extremely or moderately satisfied," commented Dr. Silberstein.
As for the number of headache days, participants in the active group reported a 28.3% reduction compared with 11.4% in the control group—a significant between-group difference (95% confidence interval [CI], -7.0 to -1.7; P = .002). Statistically significant group differences were also noted for the percentages of patients achieving 10%, 20%, 30%, and 40% reduction in headache days.
In addition, significant group differences were reported in MIDAS (Migraine Disability Assessment) scores (total scores improved by 72.9 in the active group vs 27.2 in the control group) and in Zung pain and distress scores (reduction of 14.6 points in the active group vs 5.5 points in the control group).
The most common hardware-related adverse event was lead migration, which accounted for 15.3% of all events. The most common biological event was site-related persistent pain and/or numbness (22.2% of all events), and the most common stimulation-related adverse event was unintended stimulation effects (6.9% of all events). Non–device-related or procedure-related events accounted for 12.5% of all events.
About 2% of the world's population has chronic migraine, and if only 1 out of 10 of them were intractable, "you're talking about a lot of people who might benefit [from this treatment approach]," said Dr. Silberstein.
The approach is not cheap, at an estimated $30,000 to $40,000, "which would basically be 4 years' worth of Botox [or botulinum toxin]," said Dr. Silberstein.
Dr. Silberstein explained that it is possible that stimulating other nerves might also bring headache relief, for example, other researchers are investigating the role of the supraorbital nerve in headache.
"The next step for the research team is to determine what studies the FDA will require to move ahead with the device approval process," commented Dr. Silberstein.
Invited to comment, Peter Goadsby, MD, PhD, professor of neurology, from the University of California at San Francisco (UCSF), and director of the UCSF Headache Center, observed that a major limitation of the study is that it is not strictly blinded in that those in the control group would not get the tingling "pins and needles" sensation at the back of the head that those in the active treatment group would have felt.
Adverse effects related to lead migration were another concern for Dr. Goadsby, but perhaps a bigger issue for him was that the primary endpoint in the original study was negative.
"It's not that I'm suggesting the study is entirely unblinded or entirely negative, but that we have to take what we see with a grain of salt and know that we're on a journey, and this is part of it," he told Medscape Medical News. "The study is instructive, but the point I want to make is that it's not a slam dunk."
Dr. Goadsby pointed out that it is not clear how this subgroup differed from participants in the first study other than that instead of failing at least 3 medications, participants in the original analysis had to have tried and failed at least 2 migraine-specific acute medications, and to have tried and failed at least 2 different classes of prophylactic medications.
"One should always be very careful about subgroup analyses," he said. "It's possible that this is an interesting observation; it's also possible that it's as much happenstance as anything else."
Dr. Silberstein and coauthors Joel Saper, MD, Billy Hub, MD, PhD, and Nagy Mekhail, MD, PhD, are paid consultants for St. Jude Medical Neuromodulation Division. Dr. Goadsby has disclosed no relevant financial relationships.
American Headache Society 54th Annual Scientific Meeting. Abstract 010. Presented June 22, 2012.
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Cite this: Occipital Nerve Stimulation Promising in Intractable Migraine - Medscape - Jun 27, 2012.