Assessing theEffects of Metabolic Disruption, Body Mass Index and Inflammation on Depressive Symptoms in Post-COVID-19 Condition: A Randomized Controlled Trialon Vortioxetine.

Abstract

To date, there areno therapeutics thathave gained regulatory approval by the United States Food and Drug Administration (FDA)for the treatment ofpost-COVID-19 condition (PCC), a debilitating conditioncharacterized by cognitive impairment and mood symptoms. Additionally, persistent inflammation, metabolic dysfunction, and risks associated with an elevated body mass index (BMI) have been observed. Herein, we aimed to assess the efficacy of vortioxetine in improving depressive symptoms among individuals with PCC, as modulated byinflammation, metabolic dysfunction, and BMI. In this post-hoc analysis, we present preliminary data obtained froman 8-week randomized, double-blind, placebo-controlled trial. Participants included adults aged 18years and older residing in Canada who were experiencing symptoms of World Health Organization (WHO)-defined PCC. Recruitment began November 2021 and ended January 2023. Of the 200 participants enrolled, 147 were randomized (1:1) to receive vortioxetine (5-20mg, n = 73) or placebo (n = 74) for daily treatment under double-blind conditions. The primary outcome measure was the change from baseline to endpoint in the 16-Item Quick Inventory of Depressive Symptomatology Self-Report Questionnaire (QIDS-SR-16). Our findings revealed significant effects for time (χ2 = 9.601, p = 0.002), treatment (χ2 = 9.135, p = 0.003), and the treatment × time × CRP × TG-HDL × BMI interaction (χ2 = 26.092, p < 0.001) onPCC-related depressive symptoms in the adjusted model. Moreover, the between-group analysis showed a significant improvement with vortioxetine at endpoint as compared to placebo(mean difference = - 5.41, SEM = 1.335, p < 0.001). Overall, vortioxetine significantly improved depressive symptomsamong participantswith PCC in the adjusted model. Notably, individuals with baseline markers of increasedinflammation, metabolic disruption, and elevated BMI exhibited a more pronounced antidepressant effect at endpoint. NCT05047952 (ClinicalTrials.gov).