Vortioxetine Improves Cognition and Quality of Life in Racially and Ethnically Minoritized Individuals With Post-COVID-19 Condition: A Randomized, Double-blind, Placebo-controlled Trial
Angela Kwan1, Moiz Lakhani1, Roger McIntyre2
1University of Ottawa Faculty of Medicine, 2University of Toronto
Objective:
To evaluate whether vortioxetine improves health-related quality of life (HRQoL) in individuals with post-COVID-19 condition (PCC) and examine cognitive and racial moderators of treatment response.
Background:
PCC is a major global health challenge with no approved evidence-based therapies. Cognitive and psychological impairments are among its most disabling and persistent effects, disproportionately affecting racially and ethnically minoritized populations. These inequities contribute to major declines in HRQoL and global productivity, underscoring the urgent need for equity-focused, mechanism-informed interventions to improve recovery, functioning, and well-being.
Design/Methods:
This post hoc secondary analysis of an 8-week, randomised, double-blind, placebo-controlled trial is, to our knowledge, the first worldwide to assess vortioxetine’s effects on HRQoL in PCC, stratified by baseline cognition and race. The trial enrolled 147 adults aged 18-65 years in Canada meeting WHO-defined PCC criteria and randomised (1:1) to vortioxetine (5-20 mg daily) or placebo. HRQoL (WHO-5) and cognition (DSST) were analysed in the intention-to-treat population using generalised estimating equations and general linear models by racial subgroups (Asian, other minoritised groups, White).
Results:
Vortioxetine significantly improved HRQoL compared with placebo (treatment-by-time interaction: χ²=7.39, p=0.007). A four-way interaction among treatment, time, cognition, and race (χ²=25.72, p<0.001) showed benefits varied by cognition and race. Among vortioxetine recipients, cognition-linked disparities across racial groups attenuated from baseline (β=0.085, p=0.002) to week 8 (β=0.111, p=0.059), whereas disparities persisted in the placebo group. The greatest HRQoL improvement was observed in other minoritised participants (mean difference 8.17, SE=1.19, p=0.006), particularly those with higher baseline cognition (F=81.02, p=0.002). Asian participants also improved (mean difference 26.14, SE=0.86, p=0.021). No significant benefit was observed in White participants.
Conclusions:
Vortioxetine improved HRQoL in PCC and reduced racial disparities, providing the first evidence for an equity-focused, mechanism-informed therapeutic strategy, with the greatest benefit observed among cognitively intact participants from racially and ethnically marginalised groups.
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