Table 2.
Reference | Indication studied | n | Stimulation schedule; location | Efficacy | Safety/tolerability |
---|---|---|---|---|---|
Schwartz et al. 27 | Severe congestive heart failure | 8 | 2–10 s on, 6–30 s off for 6 months; right cervical vagus nerve | Significant improvements in NYHA class (P < 0.01), QOL on Minnesota Living With Heart Failure questionnaire (P = 0.001), and left ventricular end systolic volume (P = 0.03) |
Implantation‐related AE: voice alteration (hoarseness) Stimulation‐related AEs: cough; pain at stimulation site, mandible and ear; voice alteration |
De Ferrari et al. 47 | Chronic heart failure | 32 (8 from feasibility phase 27 and 24 from multicenter international phase 47) | Duty cyclea ≤25% (e.g. maximum 10 s on, 30 s off) for 6 months; right cervical vagus nerve |
At 3 and 6 months: 56% and 59% of patients improved by ≥1 NYHA class (P ≤ 0.001) At 6 months: significant improvements in 6‐min walk test (P = 0.0014), QOL on Minnesota Living with Heart Failure questionnaire (P = 0.0001), LVEF (P ≤ 0.0003) and LVESVI (P = 0.02) |
Implantation‐related SAEs: acute pulmonary edema (1 event), surgical revision (1 event) Other possibly related SAEs: dehydration‐related syncope (2 events); syncope resulting from new‐onset atrial fibrillation and hypotension; atrial fibrillation (2 events; 1 was a return to atrial fibrillation after cardioversion) AEs: pain at site of stimulation (n = 6), cough (n = 5), dysphonia (n = 4), mandibular pain (n = 3) and ECG stimulus artifact (n = 1) |
Ben‐Menachem et al. 57 | Refractory focal epilepsy | 5 | 12–15 months after implantation: amplitude was 1.5–2.0 mA, frequency was 20 Hz, duty cyclea was 30 s on, 1.8–3 min off (14.3%–20.3%) with a pulse width of 0.3 ms and a quasi‐trapezoidal pulse shape; left cervical vagus nerve | Seizure frequency reduction of 50% in 2 patients and 25% in 2 patients; rate unchanged in 1 patient | Cough and/or hoarseness not noted until stimulation of 2 mA reached |
Stefan et al. 49 | Pharmacoresistant epilepsy | 10 | 3 times daily (1 h each) for 9 months; left auricular branch of vagus nerve |
50% reduction threshold not reached; seizure frequency was reduced by 45% and 48% in 2 patients and increased in 2 patients |
3 patients discontinued; AEs included hoarseness, headache and constipation |
Busch et al. 50 | Healthy volunteers | 48 | Stable stimulation duration of ~1 h; left auricular branch of vagus nerve | tVNS increased pain threshold and lowered pain sensitivity and pain ratings | No discontinuations or SAEs; AEs included stimulation site sensations of slight pain, pressure, prickling, itching or tickling in 39 patients with active stimulation |
Hein et al. 58 | Major depression | 37 | 15 min once or twice daily, 5 day/week for 2 weeks; bilateral transauricular vagus nerve | Significant reduction (P < 0.0001) in Beck Depression Inventory (self‐report) but not in clinician‐rated Hamilton Depression Rating Scale between active and sham treatments | No vital sign changes; no unpleasant sensations or irritations |
Nesbitt et al. 52, 53 | Intractable CH | 21 | Acute stimulation of 2–4 cycles (90 s each) to abort CH attacks and twice daily as preventive; cervical vagus nerve, ipsilateral to pain |
Overall improvement: estimated subjective improvement of 51% in 18 patients; no change in 3 patients Abortive treatment: 47% of acute attacks were terminated and 27% substantially improved in 15 min Preventive treatment: reduction in 24‐h attack frequency (4.68 ± 2.36 to 2.54 ± 2.12; P < 0.0005) |
AEs included worsening of pain in 1 patient; skin irritation, local skin reaction to conductive gel |
Goadsby et al. 4 | Episodic migraine | 30 | Two 90‐s stimulations 15 min apart; right cervical vagus nerve | Pain relief noted at 2 h for 46 of 79 migraines (58%) treated by 26 patients; 2‐h pain free rate was 28% | AEs included transient muscle or local skin irritation and 2 reports of light‐headedness |
Moscato and Moscato 55 | Chronic migraine | 19 | Two 90‐s stimulations 15 min apart; location not reported | Reduction (P < 0.05) in mean pain scores in overall group at 2 h; 9 patients were pain free, 6 had reduced pain and 4 were unchanged at 2 h | 2 brief episodes of paresthesia |
AE, adverse event; CH, cluster headache; ECG, electrocardiogram; LVEF, left ventricular ejection fraction; LVESVI, left ventricular end systolic volume index; NYHA, New York Heart Association; QOL, quality of life; SAE, serious adverse event; tVNS, transcutaneous VNS; VNS, vagus nerve stimulation.
Duty cycle is the percentage of time that stimulation is on.