Vortioxetine for the treatment of post-COVID-19 condition: a randomized controlled trial

Abstract

Hitherto no therapeutic has received regulatory approval for the treatment of Post-COVID-19 Condition (PCC). Cognitive deficits, mood symptoms, and significant reduction in health-related quality of life (HRQoL) are highly replicated and debilitating aspects of PCC. We sought to determine the impact of vortioxetine on the foregoing symptoms and HRQoL in persons living with PCC. An 8-week randomized, double-blind, placebo-controlled study of adults ≥ 18 years of age residing in Canada and who are experiencing symptoms of World Health Organization (WHO)-defined PCC, with a history of confirmed SARS-CoV-2 infection, was conducted. Recruitment began November 2021 and ended January 2023. Of the 200 participants enrolled (487 invited: 121 ineligible and 59 eligible but declined participation; 307 cleared pre-screening stage), a total of 149 participants were randomized (1:1) to receive either vortioxetine (5-20 mg, n = 75) or placebo (n = 74) daily for 8 weeks of double-blind treatment (i.e., endpoint). The primary outcome was the change from baseline-to-endpoint in the Digit Symbol Substitution Test (DSST). Secondary outcomes included the effect on depressive symptoms and HRQoL, as measured by changes from baseline-to-endpoint on the Quick Inventory of Depressive Symptomatology-16-item (QIDS-SR16) and World Health Organization Wellbeing Scale-5-item (WHO-5), respectively. A total of 68 (90.7%) participants randomized to vortioxetine and 73 (98.6%) participants randomized to placebo completed all 8 weeks. Between-group analysis did not show a significant difference in the overall change in cognitive function (p = 0.361, 95% CI [-0.179, 0.492]). However, in the fully adjusted model, a significant treatment-by-time interaction was observed in favor of vortioxetine treatment with baseline c-reactive protein (CRP) as a moderator (p = 0.012). In addition, a significant improvement in DSST scores were observed in vortioxetine- versus placebo-treated participants in those whose baseline CRP was above the mean (p = 0.045). Moreover, significant improvement was obtained in measures of depressive symptoms (p < 0.001, 95% CI [-4.378, -2.323]) and HRQoL (p < 0.001, 95% CI [2.297, 4.647]) in vortioxetine-treated participants and between the treatment groups (depressive symptoms: p = 0.026, 95% CI [-2.847, -0.185]; HRQoL: p = 0.004, 95% CI [0.774, 3.938]). Although vortioxetine did not improve cognitive function in the unadjusted model, when adjusting for CRP, a significant pro-cognitive effect was observed; antidepressant effects and improvement in HRQoL in this debilitating disorder were also noted.

Impact of Baseline Anxiety on Well-being in People with Post-COVID-19 Condition: A Secondary Analysis

“…The study protocol was approved by Advarra, a local research ethics board that operates in compliance with Health Canada Regulations (IRB#00000971), and it was conducted in accordance with Good Clinical Practice principles and the Declaration of Helsinki. The manuscript reporting the primary outcomes of this trial is reported elsewhere 21 …”

“…19 Although a direct correlation between anxiety and well-being in PCC remains to be established, anxiety disorders have wellcharacterized negative effects on well-being outside the context of PCC. 20,21 The primary objective of this study is to evaluate the association between anxiety and measures of well-being in individuals with PCC. The findings of this research will ascertain whether anxiety serves as a predictor of diminished well-being in PCC and determine whether the WHO-5 can be a screening tool for anxiety in PCC.…”

“…Although a direct correlation between anxiety and well-being in PCC remains to be established, anxiety disorders have well-characterized negative effects on well-being outside the context of PCC 20 , 21 . The primary objective of this study is to evaluate the association between anxiety and measures of well-being in individuals with PCC.…”

The Impact of Cognitive Function on Health-Related Quality of Life in Persons with Post-COVID-19 Condition: A Randomized Controlled Trial on Vortioxetine

“…This is a post-hoc evaluation of a randomized, double-blind, flexible-dosed, placebo controlled clinical trial examining the effectiveness of vortioxetine in treating PCC patient’s cognitive impairments. The methodology, and data for this study, are sourced from a primary study that is now published (ClinicalTrials.gov number, NCT05047952) (McIntyre et al, 2023).…”

Subjective and Objective Measures of Cognitive Function are Correlated in Persons with Post-COVID-19 Condition: A Secondary Analysis of a Randomized Controlled Trial

“…A comprehensive list of all secondary outcomes in the primary trial are reported elsewhere. 22 In the post-hoc analysis herein, we evaluated the association between subjective measures of cognition, as measured by the PDQ-20, and objective measures of cognition, as measured by the DSST and TMT-A/B in adults with PCC at baseline.…”