Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder with peripartum onset: A multicenter, open-label, controlled proof-of-concept clinical trial (DELOS-1)

Postpartum depression has a high prevalence in the United States (~13 %) and often goes undertreated/untreated. We conducted a multicenter, open-label, proof-of-concept trial to assess the Nēsos wearable, non-invasive, transcutaneous auricular vagus nerve stimulation (taVNS) system for the treatment of major depressive disorder with peripartum onset (PPD). Women (n = 25), ages 18 to 45, within 9 months postpartum, and diagnosed with PPD were enrolled at 3 sites. The study included 6 weeks open-label therapy and 2 weeks observation. Efficacy outcomes included change from baseline (CFB) in Hamilton Rating Scale for Depression (HAM D17) total scores, HAM-D17 response and remission , and patient and clinician global impression of change (PGIC, CGIC) scores. Analysis included descriptive statistics and mixed-effects models for repeated measures. The most common AEs (≥5 %) were discomfort (n = 5), headache (n = 3), and dizziness (n = 2); all resolved without intervention. No serious AEs or deaths occurred. Baseline mean HAM-D17 score was 18.4. Week 6 least squares (LS) mean CFB in HAM-D17 score was −9.7; 74 % achieved response and 61 % achieved remission. At week 6, at least some improvement was reported by 21 of 22 (95 %) clinicians on CGIC and 22 of 23 (96 %) participants on PGIC. This was a single-arm, open-label study, and enrollment was limited to participants with mild-to-moderate peripartum depression. Results from this proof-of-concept study suggest that the Nēsos taVNS system is well tolerated and may be an effective non-invasive, non-pharmacological treatment for major depressive disorder with peripartum onset. Further evaluation in larger sham-controlled studies is needed. ClinicalTrials.gov NCT03972995 • Peripartum depression is highly prevalent and often goes undertreated/untreated. • Non-pharmacologic treatment options are needed for women with peripartum depression. • The Nēsos non-invasive vagus nerve stimulation system was well tolerated. • Reductions in depression were observed; a larger, controlled study is warranted.