Noninvasive Vagus Nerve Stimulation Effective for Cluster Headache

Researchers pooled data from 2 randomized, double-blind, placebo-controlled trials and found that noninvasive VNS is effective in aborting attacks in episodic cluster headache.

Noninvasive vagal nerve stimulation (nVNS) is effective in aborting attacks in episodic cluster headache and is well tolerated, according to a study published in Cephalalgia.

Researchers pooled data from 2 randomized, double-blind, placebo-controlled trials, ACT1 and ACT2, which evaluated nVNS as an acute treatment for cluster headache. There were a total of 225 adults studied with episodic (n=112) or chronic (n=113) cluster headache from ACT1 (n=133) and ACT2 (n=92) in the nVNS (n=108) and placebo (n=117) groups. The trials were similar in design but with different primary end points.

For ACT1, the end point was “the proportion of participants whose first treated attack had improved (on a 5-point pain intensity scale) from pain intensity of moderate (2), severe (3), or very severe (4) to mild (1) or nil (0) at 15 minutes after treatment initiation.” For ACT2, the primary outcome was “the proportion of all treated attacks that had improved from pain intensity 2 [to] 4 to 0 at 15 minutes after treatment initiation for that attack.” Efficacy end points and adverse events in the total population, and separately in the episodic and chronic cluster headache subgroups, were analyzed.

An interaction was found between treatment group and cluster headache subtype (P <.05). Compared to the placebo group, nVNS was superior in episodic but not chronic cluster headache (for both end points, P <.01). In the pooled study population, the proportion of participants who were pain-free at 15 minutes in ≥50% of treated attacks was higher for nVNS than for placebo (absolute difference, 18%; P =.01) in participants with episodic cluster headache.

A limitation of this study included the presence of interparoxysmal pain, which was not measured in ACT1 or ACT2.

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Researchers concluded that nVNS is effective and well tolerated in aborting attacks in episodic cluster headache. It does not, however, show the same efficacy in adults with chronic cluster headache. Advantages of nVNS included its ease and flexibility of use and its ability to be used for as many attacks as experienced per day, without restrictions in the daily number of treatments and comedications. Further, cardiovascular disease is not a contraindication for nVNS. The investigators remark that “[a]dditional studies are needed to further elucidate the mechanism of action and possibly related reasons for failure in the acute treatment of chronic cluster headache.”

Multiple authors declared associations with the pharmaceutical industry and electroCore, Inc. Please see original reference for a full list of authors’ disclosures.


de Coo IF, Marin JCA, 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 [published online June 10, 2019]. Cephalalgia. doi: 10.1177/0333102419856607