OBJECTIVE: Our study aimed to evaluate the effectiveness and safety of transcutaneous auricular vagus nerve stimulation (taVNS) for treating mild to moderate depression in patients with epilepsy (PWE). METHODS: A single-arm, prospective, multi-center, pre-post controlled study was conducted in Eastern China. After a four-week baseline period, PWE with mild to moderate depression began treatment with taVNS, administered for 30 min, three times daily, over a 12-week period. The primary outcome measure was the change in 24-item Hamilton Depression Rating Scale (HAMD) scores from baseline to week 12. Secondary outcomes included the response and remission rates for depression at week 12, as well as changes in the 14-item Hamilton Anxiety Rating Scale (HAMA), the Pittsburgh Sleep Quality Index (PSQI), and the Quality of Life in Epilepsy Inventory-31 (QOLIE-31) scores, and seizure frequency at weeks 4 and 12 compared to baseline. Adverse events (AEs) were recorded to assess the safety of taVNS. Both modified Intention-To-Treat (mITT) and Per-Protocol (PP) analyses were employed. RESULTS: Sixty-nine participants were enrolled in this study. Of these, 61 (88.4 %) completed the 4-week treatment phase, and 50 (72.5 %) finished the 12-week treatment phase. In the mITT analysis, HAMD scores significantly decreased by 4.54 ± 7.44 (p <
0.001) from baseline to week 12, with clinical response in 16 (26.2 %) and remission in 15 (24.6 %) patients. HAMA scores also decreased significantly by week 4 (3.23 ± 5.18, p <
0.001) and week 12 (4.95 ± 6.78, p <
0.001). PSQI scores and seizure frequency showed non-significant changes at week 4, but seizure frequency decreased significantly by week 12 (0.03 ± 10.47, p = 0.038). In the PP analysis, similar improvements were observed. After 12 weeks of taVNS compared to baseline, HAMD scores decreased significantly by 5.32 ± 8.98 (p <
0.001), with 32 % of patients achieving a clinical response and 24 % achieving clinical remission. And HAMA scores also decreased by 5.66 ± 7.54 (p <
0.001), seizure frequency by 0.14 ± 11.03 (p = 0.018), and PSQI scores by 1.06 ± 4.14 (p = 0.076).There was a significant increase in QOLIE-31 scores by 5.17 ± 14.71 (p = 0.020). Ten (14.5 %) patients experienced non-serious adverse events, the most common of which was ear pain (n = 4)
one patient withdrew due to tinnitus enhancement
all resolved after reducing the stimulation intensity or stopping the treatment. CONCLUSION: Our study suggests that taVNS may effectively improve depressive symptoms in PWE. This may be an efficacious and safe treatment for mild to moderate depression in PWE.