CNSPulse
T31

DECREASE IN NEGATIVE MOOD AND INCREASE IN POSITIVE MOOD DURING 12 MONTHS OF VAGAL NERVE STIMULATION

Koen Demyttenaere — Bernhard T. Baune2, James Blackwell3, Maxine Dibué3, Christoph Kraus4, Fritz-Georg Lehnhardt5, Shannon Majewski3, Christine Reif-Leonhard6, Norbert Scherbaum7, Maria Strauß8, Allan Young9, R. Hamish McAllister-Williams10, Koen Demyttenaere1 1University Psychiatric Center KuLeuven, Campus Leuven, 2University of Muenster, 3LivaNova LLC, 4Medical University of Vienna, 5University Hospital of Cologne, 6University Hospital Frankfurt-Goethe University Frankfurt, 7LVR-University Hospital Essen, Medical Faculty of the University of Duisburg-Essen, 8, University of Leipzig Medical Center, 9Imperial College London, 10Newcastle University

2026 ASCP Annual Meeting

In the Diagnostic and Statistical Manual of Mental Disorders, excessive negative mood and anhedonia, defined as loss of interest and pleasure, are considered core depressive symptoms. However, reduced positive mood is not mentioned as a “depressive symptom” despite it being a stronger predictor of excess mortality in those with depression, when compared with increased negative mood. Further, in their expectations from treatment, patients rank increase in positive mood, hedonic tone, and “meaningfulness of life” as more important than decrease in negative mood (1). Implanted vagus nerve stimulation (VNS) is approved by the US Food and Drug Administration for treatment-resistant depression. Recently, it has been shown that adjunctive VNS treatment in patients with difficult-to-treat depression (DTD) results in clinically meaningful benefits in depressive symptoms, function, and quality of life. Here we present data from RESTORE-LIFE on the impact of 12 months of adjunctive VNS treatment on dimensions of negative and positive mental health. RESTORE-LIFE is a prospective, observational, multi-site, European, post-market naturalistic study intended to assess short-, mid-, and long-term effectiveness and efficiency outcomes among patients with DTD treated with concurrent VNS therapy (2). Participants were aged 18 years or older and had a chronic ( > 2 years) or recurrent (≥2 prior episodes) major depressive episode that had not sufficiently responded to antidepressant treatments. Analyses were conducted to assess dimensions of negative (depression severity, suicidality, anxiety, negative affect) and positive (life satisfaction and enjoyment, positive affect, hedonic tone, overall functioning, cognitive functioning, meaningfulness of life, and happiness) mental health, correlations between these changes, and the predictors of 12-month outcomes (using regression analyses) on depression scales, suicidality, life satisfaction and enjoyment, and meaningfulness of life. This interim analysis included the first 100 patients who reached 12 months. Statistically significant improvements over 12 months were found on all variables assessing depressed mood, negative affect, suicidality, life satisfaction, positive affect, hedonic tone, cognitive functioning, overall functioning, meaningfulness of life, and happiness. Larger effect sizes (ES) were observed for the clinician-rated Montgomery-Åsberg Depression Rating Scale (ES: −0.77), the patient-rated Quick Inventory of Depressive Symptomatology–Self-Report (ES: −0.54), and suicidality (ES: 0.57) scores. More moderate improvements were observed for the Quality of Life Enjoyment and Satisfaction Questionnaire–Short Form score (ES: 0.38) and the Leuven Affect and Pleasure Scale score (ES for negative affect: −0.38; ES for positive affect, hedonic tone, cognitive functioning, overall functioning, meaningfulness of life, and happiness was between 0.26 and 0.40). At 12 months, only changes from baseline in negative mood predicted negative mood, changes from baseline in negative mood and changes in positive mood predicted suicidality, and only changes from baseline in positive mood predicted positive mood. In conclusion, among patients with DTD in a real-world setting, 12 months of concurrent VNS therapy was associated with a significant decrease in negative mental health and an increase in positive mental health, both of which seem to be independent dimensions.