ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Psychopharmacology
This article is part of the Research TopicCOVID and Psychotropics 2024: Lessons Learnt and Future Directions for ResearchView all 6 articles
Reduced Risk of Severe COVID-19 with Lithium Use: A Large-Scale Comparison with Valproate Users and Other COVID-19 Patients
Provisionally accepted
- 1Ramat-Chen Brüll Mental Health Center, Clalit Health Services, Tel Aviv, Israel
- 2Tel Aviv University Faculty of Medical and Health Sciences, Tel Aviv-Yafo, Israel
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Background: Lithium, a commonly used mood stabilizer with immunomodulatory and antiviral properties, has been hypothesized to lessen the severity of COVID-19, but population-level evidence remains limited. Methods: In this retrospective cohort study, we examined electronic health records from over 1.49 million adults with confirmed COVID-19 in Israel between March 2020 and November 2021. Individuals were categorized based on sustained use of lithium (n=857), valproate (n=5,302), or no exposure to either medication. Severe COVID-19 was defined as hospitalization, respiratory support, extracorporeal membrane oxygenation, or death. To account for baseline differences, we applied inverse probability weighting and logistic regression with correction for rare events. Results: Lithium use was associated with significantly lower odds of severe COVID-19, even though users were older and had more medical comorbidities. In contrast, valproate use was linked to increased risk. Conclusion: These findings suggest that lithium may provide a protective effect against severe COVID-19 outcomes, independent of underlying vulnerability, and support further investigation into the broader health implications of psychotropic medications.
Keywords: COVID-19, clinical outcomes, Lithium, valproate, ECMO, Vaccination
Received: 09 Sep 2025; Accepted: 30 Nov 2025.
Copyright: © 2025 Avni, Blasbalg and Toren. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chen Avni
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