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BENEFITS OF ADJUNCTIVE VAGUS NERVE STIMULATION IN DIFFICULT-TO-TREAT DEPRESSION: OUTCOMES OF A NATURALISTIC EUROPEAN COHORT (RESTORE-LIFE) COMPARED TO THE USA RECOVER RANDOMIZED CONTROLLED TRIAL

R. Hamish McAllister-Williams — Tiago da Silva Costa1, Bernhard T. Baune2, James Blackwell3, Maxine Dibué3, Christoph Kraus4, Ying Chieh (Lisa) Lee3, Fritz-Georg Lehnhardt5, Shannon Majewski3, Christine Reif-Leonhard6, Norbert Scherbaum7, Maria Strauß8, Allan Young9, Koen Demyttenaere10, Koen Demyttenaere10 1Newcastle University, 2University of Muenster, 3LivaNova LLC, 4Clinical Division of General Psychiatry, Medical University of Vienna, 5 University Hospital of Cologne, 6Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt-Goethe University Frankfurt, 7LVRUniversity Hospital Essen, Medical Faculty of the University of Duisburg-Essen, 8University of Leipzig Medical Center, 9Imperial College London, 10University Psychiatric Center KuLeuven, Campus Leuven

2026 ASCP Annual Meeting

Major depressive disorder (MDD) which proves difficult-to-treat (difficult-to-treat depression: DTD) is associated with chronic and/or recurrent depressive symptoms and severe impairments in quality of life (QoL) and functioning. Vagus nerve stimulation (VNS) is an approved, long-term adjunctive treatment for patients with DTD. Its effectiveness in improving QoL and functioning has recently been supported by the US-based RECOVER, randomized, triple-blind, sham-controlled trial. This enrolled adults with moderate-to-severe MDD depressive episodes, randomized 1:1 to receive adjunctive active or sham VNS for 12 months. RESTORELIFE is a European prospective, observational, multicenter, post-marketing study assessing the efficacy and effectiveness of VNS therapy in adults with DTD, reflecting the naturalistic clinical practice of VNS in these patients. Inclusion criteria were minimal: a documented diagnosis of chronic ( > 2 years) or recurrent (two or more prior episodes) major depressive episode with unsatisfactory response to antidepressant treatments. Here we present the 12-month effectiveness data of VNS therapy in RESTORE-LIFE and compare the findings to those published for RECOVER (NCT03887715) (1,2). In the interim RESTORE-LIFE dataset (n=147), 25.9% of participants had bipolar disorder: RECOVER (n=493) included exclusively patients with MDD (a bipolar RECOVER study is ongoing). At baseline severity of depression (mean [SD] Montgomery-Åsberg Depression Rating Scale [MADRS] score) was slightly higher in RECOVER (34.2 [4.9]) versus RESTORE-LIFE (30.2 [8.4]). Participants had similar QoL; the mean (SD) Mini Quality of Life Enjoyment and Satisfaction Questionnaire (Mini-Q-LES-Q) scores were 15.4 (5.2) in RESTORE-LIFE and 15.0 (4.1) in RECOVER. Both studies included participants with severe DTD, with the mean (SD) number of lifetime failed antidepressant treatments (medications, ECT, TMS and psychotherapies) being 13.3 (8.4) in RECOVER and 15.6 (10.7) in RESTORE-LIFE. Participants in RESTORE-LIFE had a greater mean number of lifetime psychiatric hospitalizations (8.6 vs 2.2) and a greater proportion had received prior electroconvulsive therapy (85.2% vs 45.3%) compared to those in RECOVER (possibly reflecting differences in health care provision). The effectiveness of VNS therapy was similar across both studies. The mean percent time in partial response, response, and remission over 12 months on the clinician-rated MADRS was 41.1%, 24.5%, and 14.7% in RESTORE-LIFE and 32.9%, 18.9%, and 9.5% in RECOVER. Similar results were observed on the patient-rated Quick Inventory of Depressive Symptomatology–Self-Report, with slightly greater proportions in RECOVER versus RESTORE-LIFE for partial response (40.5% vs 29.3%), response (25.2% vs 18.4%), and remission (12.4% vs 14.3%). Mean percent time in clinically meaningful benefit in the Mini-Q-LES-Q (≥11.89% increase from baseline) was 32.0% in RESTORE-LIFE and 45.4% in RECOVER. Safety of VNS was also evaluated in RESTORE-LIFE and compared to that in RECOVER. These data support the conclusion that the benefits in symptoms and QoL with VNS in participants with marked DTD seen in a randomized clinical trial in the United States are generalizable to patients treated naturalistically in a different, European, health care setting.