BOSTON – The efficacy of occipital nerve stimulation in the first clinical trial of its use in the treatment of refractory migraines suggests that the technique may be a promising option for individuals who have not responded to medication or other established therapies, according to Dr. Joel Saper.

The neurostimulation technique was associated with a significant reduction in both the number of headache days per month and the intensity of pain in nearly 40% of patients with chronic migraine who were randomized to its use in a multicenter feasibility trial, reported Dr. Saper, founder and director of a head pain treatment and research center in Ann Arbor, Mich.

Occipital nerve stimulation (ONS) is achieved by the delivery of asymmetric biphasic electrical pulses via subcutaneous wires attached to the tissue surrounding the occipital nerve, located between the back of the neck and the skull. This form of peripheral nerve stimulation is thought to modulate the path of the migraine circuit and, by so doing, to interrupt the pain signals, said Dr. Saper.

Although previous studies have assessed ONS for the treatment of migraine and other headaches, as well as for occipital neuralgia, these have mostly been retrospective analyses, case series, or uncontrolled trials, he noted.

In the current investigation, called the ONSTIM (Occipital Nerve Stimulation for the Treatment of Intractable Migraine) study, Dr. Saper and colleagues randomized, in a 2:1:1 design, 110 patients from nine centers to one of three conditions: adjustable stimulation, in which patients received the neurostimulator and were able to control the level of stimulation; preset stimulation, or the device-control group, in which the level of stimulation was not adjustable; and standard medical management.

All of the patients included in the study experienced 15 headache days per month, as per ICHD-II (International Classification of Headache Disorders, second edition) criteria for chronic migraine, and none were responsive to available medical therapies. Prior to randomization, all of the patients received diagnostic occipital nerve block (ONB). The first eight patients who failed ONB formed an ancillary group and were offered ONS.

Of the 110 patients, 66 completed the electronic diary data for the 3-month follow-up period, including 28 in the adjustable-stimulation group; 16 in the present-stimulation group; 17 in the medical-management group; and 5 in the ancillary group.

In the final analysis, the investigators used nonparametric methods to compare the ONS intervention group with the two control-condition groups for reduction in headache days per month, decrease in overall pain intensity on a 0–10 scale, and responder rate (defined as a 50% drop in headache days per month and a minimum 3-point drop in overall pain intensity from baseline), Dr. Saper explained.

With respect to headache days per month, the mean reduction from baseline in the device-intervention group was 27%, compared with 9% and 4% for the device- and medication-control groups, respectively. The mean drop in overall pain intensity was 1.5 points for patients in the intervention group, compared with 0.5 and 0.6 in the device and medication controls, he said.

In terms of treatment response, 39% of the patients in the intervention group experienced at least a 50% decrease in headache days per month and a minimum 3-point drop in pain intensity at 3 months, Dr. Saper said. In contrast, only 6% of the device-control group and none of the medically managed patients responded to therapy, he said at the annual meeting of the American Headache Society.

Of interest, he noted, “two of the patients in the ancillary group–all of whom failed ONB–responded to ONS, indicating that ONB may not be predictive of response to ONS.”

No adverse events and no “unanticipated” adverse device events occurred, said Dr. Saper.

“The most common adverse device event was lead migration, which occurred in 12 of the 51 implanted subjects.” Other adverse device events, particularly battery failure, “were consistent with the literature,” he said.

Although additional randomized controlled trials are needed, the findings are important, “particularly to the population of chronic migraine sufferers who do not respond to aggressive medical therapy,” Dr. David Dodick, one of the ONSTIM investigators, said in a symposium on neurostimulation for refractory primary headache disorders at the annual meeting.

If further studies demonstrate the safety and efficacy of ONS, leading to approval and commercialization of the technology, he said, “there may be some relief in sight for these patients.”

The ONSTIM study was sponsored by Medtronic Inc., the developer of the neurostimulation device, and was conducted under an investigational device exemption according to the Food and Drug Administration's device-approval procedures.

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Two patients who failed occipital nerve block responded to the stimulation technique. DR. SAPER

Nerve Stimulation Shows Efficacy for Migraine : Technique associated with fewer headache days, less intense pain in patients with refractory headache.