Vortioxetine for the Treatment of Post-COVID-19 Condition: A Randomized Controlled Trial
Angela Kwan1, Lee Phan2, Rodrigo Mansur2, Joshua Rosenblat2, Ziji Guo2, Gia Han Le2, Kayla Teopiz2, Felicia Ceban3, Julia Bailey2, Ranuk Ramachandra2, Joshua Di Vincenzo2, Sebastian Badulescu2, Pawel Drzadzewski2, Roger McIntyre2
1Faculty of Medicine, University of Ottawa, 2Brain and Cognition Discovery Foundation, 3Michael G. DeGroote School of Medicine, McMaster University
Objective:
We sought to determine the impact of vortioxetine on cognitive deficits, mood symptoms and health-related quality of life (HRQoL) in persons living with Post-COVID-19 Condition (PCC).
Background:
Hitherto no therapeutic has received regulatory approval for the treatment of PCC. Cognitive deficits, mood symptoms and significant reduction in HRQoL are highly replicated and debilitating aspects of PCC.
Design/Methods:
An 8-week randomized, double-blind, placebo-controlled study of adults ≥ 18 years old residing in Canada with World Health Organization (WHO)-defined PCC symptoms and a history of confirmed SARS-CoV-2 infection was conducted. Recruitment began November 2021 and ended January 2023. Of the 200 participants enrolled, 149 participants were randomized (1:1) to receive vortioxetine (5-20 mg, n = 75) or placebo (n = 74) daily for 8 weeks of double-blind treatment. The primary outcome was the change from baseline-to-endpoint in the Digit Symbol Substitution Test (DSST). Secondary outcomes included changes from baseline-to-endpoint in the Quick Inventory of Depressive Symptomatology-16-item (QIDS-SR16) and World Health Organization Wellbeing Scale-5-item (WHO-5).
Results:
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 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). Moreover, significant improvement was obtained in measures of depressive symptoms (p < 0.001) and HRQoL (p < 0.001) in vortioxetine-treated participants and between the treatment groups (depressive symptoms: p = 0.026; HRQoL: p = 0.004).
Conclusions:
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.