Transcutaneous stimulation of the cervical branch of the vagus nerve for cluster headache and migraine

5 Safety

This section describes safety outcomes from the published literature that the committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.

5.1 In a randomised controlled trial of 97 patients with cluster headache, transcutaneous vagus nerve stimulation (tVNS) was judged to cause cluster headache in 2% (1/48) of patients in the standard care plus tVNS group and 10% (5/49) of patients initially in the standard care alone group but who then received adjunctive tVNS in a 4‑week extension phase. In the same study, headaches that were not cluster headaches were reported in 8% (4/48) of patients in the standard care plus tVNS group and 2% (1/49) of patients initially in the standard care alone group.

5.2 Dizziness was reported in 6% (3/48) of patients in the standard care plus tVNS group and 6% (3/49) of patients in the standard care alone group in the randomised controlled trial of 97 patients with chronic cluster headache (no further details on timing in relation to tVNS provided).

5.3 Oropharyngeal pain was reported in 6% (3/48) of patients in the standard care plus tVNS group and 2% (1/49) of patients in the standard care alone group in the randomised controlled trial of 97 patients with chronic cluster headache.

5.4 Moderate shoulder pain or spasm was reported in 7% (2/28) of patients in a case series of 30 patients with migraine (no further details on timing in relation to tVNS provided).

5.5 Mild lip or facial drooping was reported in 7% (2/28) of patients in the case series of 30 patients with migraine (no further details on timing in relation to tVNS provided).

5.6 Neck stiffness was reported in 18% (5/28) of patients in the case series of 30 patients with migraine (no further details on timing in relation to tVNS provided).

5.7 Reddening of the skin around the treatment site was reported in 7% (2/28) of patients in the case series of 30 patients with migraine.

5.8 In the randomised controlled trial of 97 patients with chronic cluster headache treated by standard care plus tVNS or standard care alone, 1 or more of the following device‑related adverse events were reported in 27% (13/48) of patients in the standard care plus tVNS group: depressed mood, malaise, oropharyngeal pain, induced cluster headache, muscle twitching, muscle spasms, hot flushes, acne, pain, throat tightness, dizziness, hyperhidrosis, toothache, decreased appetite and skin irritation. One or more of the following device‑related adverse events were reported in 14% (7/49) of patients initially in the standard care alone group: erythema, facial oedema, induced cluster headache, chest pain, fatigue, depressed mood, pruritus, musculoskeletal stiffness and parosmia. All adverse events occurred during the extension phase of the study when these patients received adjunctive tVNS.

5.9 A single occurrence of the following adverse events was reported in the case series of 30 patients with migraine: mild confusion that lasted for 2 hours after neurostimulation, joint pain, mild twitching of neck muscles, mild swelling of the neck, tinnitus in 1 ear, fever (39ºC), a raspy voice, fatigue, coughing and sneezing.

5.10 Palpitations were reported in 1 patient in a case series (conference abstract) of 18 patients with various primary headache disorders. In the same study, tonic muscle contraction was reported in 17% (3/18) of patients and cervical muscle spasm was reported in 1 patient.

5.11 In addition to safety outcomes reported in the literature, specialist advisers are asked about anecdotal adverse events (events which they have heard about) and about theoretical adverse events (events which they think might possibly occur, even if they have never done so). For this procedure, specialist advisers listed the following anecdotal adverse events: shortness of breath and changes in blood pressure. They considered that cardiac arrhythmia and interaction with pacemaker devices were theoretical adverse events.