Systematic review and meta-analysis of vagus nerve stimulation in the treatment of depression: variable results based on study designs

PURPOSE: To determine the efficacy of vagus nerve stimulation (VNS) for treatment of depression. METHODS: We conducted a systematic review and meta-analysis of analytical studies. Efficacy was evaluated according to severity of illness and percentage of responders. RESULTS: We identified 687 references. Of these, 14 met the selection criteria and were included in the review. The meta-analysis of efficacy for uncontrolled studies showed a significant reduction in scores at the Hamilton Depression Rating Scale endpoint, and the percentage of responders was 31.8% ([23.2% to 41.8%], P<0.001). However, the randomised control trial which covered a sample of 235 patients with depression, reported no statistically significant differences between the active intervention and placebo groups (OR=1.61 [95%CI 0.72 to 3.62]; P=0.25). To study the cause of this heterogeneity, a meta-regression was performed. The adjusted coefficient of determination (R2(Adj)) was 0.84, which implies that an 84% variation in effect size across the studies was explained by baseline severity of depression (P