Occipital nerve stimulation safely reduces frequency of chronic cluster headache

Occipital nerve stimulation significantly reduced attack frequency and was safe and well-tolerated in patients with medically intractable chronic cluster headaches, according to a study published in Lancet Neurology.

“[We] compared the effects of 100% versus 30% of the individually accepted electrical dose of [occipital nerve stimulation (ONS)] in a randomized, double-blind study,” Leopoldine A Wilbrink, MD, of the department of neurology at Leiden University Medical Centre in the Netherlands, and colleagues wrote. “Both intensities were hypothesized to cause similar paresthesia, mitigating the risk of unmasking, while also showing differential efficacy, as has been described for a range of neurostimulation modalities. Our study aimed to expand the preventive treatment options for patients with [medically intractable chronic cluster headache (MICCH)], further understanding of the mode of action of ONS and how it can be investigated in clinical trials, and further understanding of neurostimulation in general.”

Wilbrink and colleagues enrolled patients with MICCH in an investigator-initiated, international, multicenter, double-blind, phase 3, electrical dose-controlled clinical trial at four hospitals in the Netherlands, Belgium, Germany and Hungary. They observed patients for 12 weeks. Those who had experienced at least four attacks per week and had a history of being nonresponsive to at least three standard preventive drugs were randomly assigned to 24 weeks of OSN at either 100% intensity (n = 65) or 30% intensity (n = 66).

“Because ONS causes paresthesia, preventing masked comparison versus placebo, we compared high-intensity versus low-intensity ONS, which are hypothesized to cause similar paresthesia, but with different efficacy,” Wilbrink and colleagues wrote.

At 25 to 48 weeks, patients received individually optimized open-label ONS, according to the study. The primary outcome was weekly mean attack frequency at weeks 21 to 24 compared with baseline. In addition, investigators wanted to determine if a decrease demonstrated a group-wise difference.

At weeks 21 to 24, the median weekly mean attack frequencies in the entire population decreased to 7.38 from baseline (2.5-18.5; P < .0001). Wilbrink and colleagues noted this was a median change of –5.21 attacks per week (–11.18 to –0.19; P <·.0001).

In the 100% ONS stimulation group, the mean attack frequency decreased from 17.58 (9.83-29.33) at baseline to 9.5 (3-21.25) at 21 to 24 weeks (median change from baseline, –4.08, –11.92 to –0.25). For the 30% ONS stimulation group, the mean attack frequency decreased from 15 (9.25-22.33) to 6.75 (1.5-16.5; –6.5, –10.83 to –0.08). Wilbrink and colleagues wrote.

Study data showed that at the end of the masked phase at weeks 21 to 24, the difference in median weekly mean attack frequency between the groups was –2.42 (95% CI, –5.17 to 3.33).

According to the researchers, ONS was “safe and well-tolerated.” During the masked study phase, 129 adverse events occurred in the 100% ONS group and 95 in the 30% ONS group. Investigators considered 17 of the adverse events in the 100% ONS group and eight in the 30% ONS group as serious because those events required hospital admission due to minor hardware-related issues. The most commonly reported adverse events included local pain, impaired wound healing, neck stiffness and hardware damage.

In a related editorial, Denys Fontaine, MD, PhD, of the department of neurosurgery, and Michel Lanteri-Minet, MD, of the department of pain — both at the Côte d'Azur University in France — said Wilbrink and colleagues’ study did offer enough strong evidence of high-intensity ONS in MICCH. They noted there were no significant differences seen between the two electric doses used in the study.

“However, considering the significant difference between baseline and the end of the randomized stimulation phase in both groups (about half of the patients showed a 50% decrease in attack frequency), the findings of this study support the favorable results of previous real-world studies, and indicate that a substantial proportion of patients with intractable chronic cluster headache, although not all, could have their condition substantially improved by ONS,” Fontaine and Lanteri-Minet wrote. “We hope that these data will help health authorities to recognize the efficacy of ONS and consider its approval for use in patients with intractable chronic cluster headache.”