A meta-analysis of 2 double-blind, sham-controlled trials found that noninvasive vagus nerve stimulation (nVNS) was effective for the acute treatment of episodic, but not chronic, cluster headache (CH). The findings from this analysis were published in Cephalalgia.

Data from a total of 225 patients with episodic (n=112) or chronic (n=113) CH were pooled from the ACT1 and ACT2 sham-controlled trials. Participants in both trials were required to treat headache attacks after onset with 3 consecutive 120-second nVNS applications. The ACT2 trial allowed up to 3 additional applications if pain did not dissipate at 9 minutes after the first treatment. Patients in the ACT1 trial applied nVNS to the right cervical vagus nerve, whereas participants in ACT2 were allowed to treat ipsilateral to the CH pain. Changes in pain intensity and pain-free status were the respective primary outcomes in ACT1 and ACT2.

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Overall, a total of 108 patients used nVNS and 117 patients used the sham control. At 15 minutes after the first treated attack, more patients with episodic CH in ACT1 achieved the primary outcome when they used nVNS vs sham control (ACT1: absolute difference, 24% [P =.01]; pooled: absolute difference, 27% [P <.01]). This finding was not observed in the ACT2 patient population (absolute difference, 35%; P =.07).

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A higher proportion of patients with episodic CH who were treated with nVNS achieved a pain-free status at 15 minutes (ACT1: absolute difference, 9% [P <.05]; ACT2: absolute difference, 41% [P <.05]; pooled: absolute difference, 22% [P <.01]). In addition, a higher proportion of patients with episodic CH who achieved a pain-free status at 15 minutes in ≥50% of treated attacks were treated with nVNS vs control in the pooled cohort (absolute difference, 18%; P =.01). Adverse events leading to discontinuation was observed in only 4 patients.

Limitations of the analysis include the lack of measurements for interparoxysmal pain, as well as the relatively small number of participants and short follow-up periods.

The study researchers concluded that nVNS is effective at terminating attacks in episodic cluster headache, but does not offer the same efficacy for chronic cluster headache. “nVNS offers several advantages over existing treatment options,” the researchers added, “including its ease and flexibility of use and its ability to be used for as many attacks as the patient experiences per day, without restrictions to daily number of treatments and co-medications.”

Disclosures: The study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


de Coo IF, Marin JC, Silberstein SD, et al. Differential efficacy of non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A meta-analysis. Cephalalgia. 2019;39(8):967-977.