The Editor’s choice March 2025

“Lithium and the risk of severe COVID-19 infection“

This quarter’s Editor’s Choice looks at an intriguing study that bridges psychiatry and infectious diseases, offering insights into how medications for mental disorders might interact with physical health risks. Lithium has been used clinically for 70 years, mainly to treat mood disorders and suicide. Competing treatments and exaggerated impressions about complexity and risks of its use have led to a decline in some countries. Lithium is still the standard and most extensively evaluated treatment for bipolar disorder, especially for long-term prophylaxis(1), for unipolar depression(2) and for suicide prevention(3). Lithium has also been linked to a lower occurrence of conditions such as dementia(4), osteoporosis(5), heart attacks(6), and certain types of cancer(7). Some studies have also indicated that lithium might possess antiviral qualities, with potential effectiveness against COVID-19(8).

The authors of the study, titled Lithium and the risk of severe COVID-19 infection: A retrospective population-based register study(9) investigated whether lithium and psychotropic medications such as antipsychotics influence the likelihood of death, hospitalization, and ICU admission due to COVID-19 in patients with bipolar disorder. This retrospective population-based study, approved by Swedish Ethical Review Authority (DNR 2020-02759), used data from Swedish patient registers and encompassed 39,063 adults with bipolar disorder who were under lithium or mood stabilizers (i.e., valproate, lamotrigine, carbamazepine) / typical or atypical antipsychotics used in the long-term. Benzodiazepine use was also analyzed. The outcome measures included COVID-19-related death, hospitalization, and ICU admission during the period from March 2020 to March 2021. Two multivariate regression models were used; one adjusted for age and sex and a second adjusted for drug covariates, age, sex, and somatic comorbidities.

Lithium was prescribed to 44.2 % of patients, either as mono- or combination therapy; other mood stabilizers were prescribed to 55.8 %. There were no significant associations between lithium and COVID-19-associated death, hospitalization, or ICU admission. Atypical antipsychotics were associated with increased odds ratios for COVID-19-associated death (OR 1.58 [95 % CI 1.01-2.47]), hospitalization (OR 1.80 [95 % CI 1.49-2.18]), and ICU admission (OR 2.25 [95 % CI 1.33-3.80]). Benzodiazepines were associated with a significant increase in COVID-19-associated death (OR 1.54 [95 % CI 1.01-2.35]) and hospitalization OR 1.26 [95 % CI 1.03-1.53]).

Once again, lithium continues to be a fundamental pharmacological tool to be worthily included in MD armamentarium. The results highlight the need for further research to explore the complexity of the relationship between psychotropic medications and their interactions with infectious diseases.

References

1. Tondo L, Alda M, Bauer M, Bergink V, Grof P, Hajek T, et al. Clinical use of lithium salts: guide for users and prescribers. International journal of bipolar disorders. 2019;7(1):16.
2. Vázquez GH, Bahji A, Undurraga J, Tondo L, Baldessarini RJ. Efficacy and Tolerability of Combination Treatments for Major Depression: Antidepressants plus Second-Generation Antipsychotics vs. Esketamine vs. Lithium. Journal of psychopharmacology (Oxford, England). 2021;35(8):890-900.
3. Cipriani A, Hawton K, Stockton S, Geddes JR. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ (Clinical research ed). 2013;346:f3646.
4. Kessing LV, Forman JL, Andersen PK. Does lithium protect against dementia? Bipolar disorders. 2010;12(1):87-94.
5. Köhler-Forsberg O, Rohde C, Nierenberg AA, Østergaard SD. Association of Lithium Treatment With the Risk of Osteoporosis in Patients With Bipolar Disorder. JAMA psychiatry. 2022;79(5):454-63.
6. Prosser JM, Fieve RR. Patients receiving lithium therapy have a reduced prevalence of neurological and cardiovascular disorders. Progress in neuro-psychopharmacology & biological psychiatry. 2016;71:39-44.
7. Huang RY, Hsieh KP, Huang WW, Yang YH. Use of lithium and cancer risk in patients with bipolar disorder: population-based cohort study. The British journal of psychiatry : the journal of mental science. 2016;209(5):393-9.
8. Soriano-Torres O, Noa Romero E, González Sosa NL, Enríquez Puertas JM, Fragas Quintero A, García Montero M, et al. Lithium salts as a treatment for COVID-19: Pre-clinical outcomes. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;149:112872.
9. Nilsson NH, Bendix M, Öhlund L, Gibbs A, Widerström M, Werneke U, et al. Lithium and the risk of severe COVID-19 infection: A retrospective population-based register study. Journal of psychosomatic research. 2025;190:112053.