Cervical Noninvasive Vagus Nerve Stimulation for Migraine and Cluster Headache: A Systematic Review and Meta-Analysis

Background Noninvasive vagus nerve stimulation (nVNS) has been proposed as a new neuromodulation therapy to treat primary headache disorders. The purpose of this study was to analyze the effectiveness and safety of peripheral nerve stimulation of the cervical branch of the vagal nerve for primary headache disorders. Methods A systematic review and meta-analysis of the literature was carried out on randomized controlled trials of nVNS for treating headaches. We searched the Medline, Embase, and CENTRAL databases until January 29, 2019. A random-effects model was used to report all outcomes. The primary outcomes were a reduction in headache days or attacks and pain-free status within 30 min. Secondary outcomes were: the pain-relief status within 30 min, the pain-relief status at 60 min, abortive medication use, >= 50% responder rate, pain-free status in >= 50% of treated attacks, adverse events, and satisfaction. Results In total, 983 patients were included from six trials. We found that nVNS was effective in achieving a pain-free status within 30 min (odds ratio [OR], 2.27; 95% confidence interval [CI], 1.16~4.44;p= 0.02), pain-relief status within 30 min (OR, 1.8; 95% CI, 1.17~2.78;p= 0.007), pain-relief status at 60 min (OR, 1.93; 95% CI, 1.2~3.1;p= 0.006), a reduction in abortive medication use (OR, 0.61; 95% CI, 0.41~0.92;p= 0.02), and pain-free status in >= 50% of treated attacks (OR, 2.15; 95% CI, 1.27~3.66;p= 0.005) compared to sham-device treatment. There were no significant differences in decreased headache days (standardized mean difference (SMD), -0.159; 95% CI, -0.357~0.04;p= 0.117), adverse events (OR, 1.084; 95% CI, 0.559~2.104;p= 0.811), or satisfaction (OR, 1.45; 95% CI, 0.97~2.17;p= 0.07) between nVNS and sham-device treatment. The >= 50% responder rate could not be determined (OR, 3.34; 95% CI, 0.83~13.33;p= 0.09;I-2=73%). Conclusions Cervical nVNS is effective for acute pain relief for migraine and cluster headache. Systematic review registration PROSPERO registration number CRD42019126009.