Impacts of metabolic disruption, body mass index and inflammation on cognitive function in post-COVID-19 condition: a randomized controlled trial on vortioxetine

Angela T H Kwan; Gia Han Le; Ziji Guo; Felicia Ceban; Kayla M Teopiz; Taeho Greg Rhee; Roger Ho; Joshua D Di Vincenzo; Sebastian Badulescu; Shakila Meshkat; Bing Cao; Joshua D Rosenblat; Donovan A Dev; Lee Phan; Mehala Subramaniapillai; Roger S McIntyre

doi:10.1186/s12991-024-00494-1

Impacts of metabolic disruption, body mass index and inflammation on cognitive function in post-COVID-19 condition: a randomized controlled trial on vortioxetine

Ann Gen Psychiatry. 2024 Feb 29;23(1):10. doi: 10.1186/s12991-024-00494-1.

Authors

Angela T H Kwan^{1

2}, Gia Han Le^{1

3}, Ziji Guo^{1

4}, Felicia Ceban^{1

5}, Kayla M Teopiz¹, Taeho Greg Rhee^{6

7}, Roger Ho^{8

9}, Joshua D Di Vincenzo¹, Sebastian Badulescu^{1

3}, Shakila Meshkat¹, Bing Cao¹⁰, Joshua D Rosenblat^{1

11}, Donovan A Dev¹, Lee Phan¹, Mehala Subramaniapillai¹, Roger S McIntyre^{12

13

14}

Affiliations

¹ Brain and Cognition Discovery Foundation, 77 Bloor Street West, Suite 617, Toronto, ON, M5S 1M2, Canada.
² Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
³ Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
⁴ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
⁵ Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
⁶ Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
⁷ Department of Public Health Sciences, University of Connecticut School of Medicine, Storrs, USA.
⁸ Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁹ Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore.
¹⁰ Key Laboratory of Cognition and Personality, Faculty of Psychology, Ministry of Education, Southwest University, Chongqing, 400715, P. R. China.
¹¹ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
¹² Brain and Cognition Discovery Foundation, 77 Bloor Street West, Suite 617, Toronto, ON, M5S 1M2, Canada. roger.mcintyre@bcdf.org.
¹³ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. roger.mcintyre@bcdf.org.
¹⁴ Department of Psychiatry, University of Toronto, Toronto, ON, Canada. roger.mcintyre@bcdf.org.

Abstract

Background: Post-COVID-19 Condition (PCC), as defined by the World Health Organization (WHO), currently lacks any regulatory-approved treatments and is characterized by persistent and debilitating cognitive impairment and mood symptoms. Additionally, metabolic dysfunction, chronic inflammation and the associated risks of elevated body mass index (BMI) have been reported. In this study, we aim to investigate the efficacy of vortioxetine in improving cognitive deficits in individuals with PCC, accounting for the interaction of metabolic dysfunction, elevated inflammation and BMI.

Methods: This is a post-hoc analysis of an 8-week randomized, double-blind, placebo-controlled trial that was conducted among adults aged 18 years and older living in Canada who were experiencing WHO-defined PCC symptoms. The recruitment of participants began in November 2021 and concluded in January 2023. A total of 200 individuals were enrolled, where 147 were randomized in a 1:1 ratio to receive either vortioxetine (5-20 mg, n = 73) or placebo (n = 74) for daily treatment under double-blind conditions. The primary outcome measure was the change in the Digit Symbol Substitution Test (DSST) score from baseline to endpoint.

Results: Our findings showed significant effects for time (χ² = 7.771, p = 0.005), treatment (χ² = 7.583, p = 0.006) and the treatment x time x CRP x TG-HDL x BMI interaction (χ² = 11.967, p = 0.018) on cognitive function. Moreover, the between-group analysis showed a significant improvement with vortioxetine at endpoint (mean difference = 0.621, SEM = 0.313, p = 0.047).

Conclusion: Overall, vortioxetine demonstrated significant improvements in cognitive deficits among individuals with baseline markers of metabolic dysfunction, elevated inflammation and higher BMI at endpoint as compared to placebo.

Trial registration: NCT05047952 (ClinicalTrials.gov; Registration Date: September 17, 2021).

Keywords: Body mass index (BMI); Cognitive function; Digit symbol substitution test (DSST); Inflammation; Long COVID; Metabolic dysfunction; Vortioxetine.

Associated data

ClinicalTrials.gov/NCT05047952