Lithium in a Time of Coronavirus

Table. Steps to prevent lithium toxicity

For the accompanying podcast to this piece, see The Antiviral Side of Lithium.

Psychiatric medications have been fighting infections for decades. The MAOIs were originally used to treat tuberculosis. Thioridazine has been rediscovered as a treatment for antibiotic-resistant infections,¹ and lithium doubles as an antiviral agent.² In an accompanying podcast, I speak with Janusz Rybakowski, MD, PhD, a pioneer in lithium research who helped discover its antiviral properties.

The first inklings of lithium’s antiviral effects came from observations that patients were less likely to catch the common cold, or rhinovirus, while on the medicine. Lithium improves immune function, increasing neutrophil count as well as lymphocytes, leukocytes, and natural killer cells. But lithium’s antiviral properties extend beyond that. It directly impedes viral replication in animal and in vitro studies.²

This was first discovered in the 1980s with the herpes family of viruses. Lithium treated and prevented labile herpes, whether taken orally or as a topical ointment. Since then, lithium has demonstrated antiviral activity against over a dozen viruses, both DNA and RNA types. These include HIV, cytomegalovirus, Epstein-Barr virus, pseudorabies virus, vaccinia, adenovirus, gastroenteritis virus, measles, coxsackievirus, multiple herpetic viruses, and four strands in the coronavirus family.^2-4

Lithium has never been tested against the current coronavirus, officially known as severe acute respiratory syndrome coronavirus 2. Janusz Rybakowski, MD, PhD, who conducted some of the early studies of lithium’s antiherpetic viral effects, sees potential in lithium and plans to organize an international study comparing COVID-19 outcomes in lithium-treated vs. non-lithium treated patients with mood disorders.

Lithium shares a common mechanism with chloroquine, the antimalarial drug that is being explored as a treatment for COVID-19. Both inhibit glycogen synthase kinase 3 (GSK3), a mechanism that is implicated in other antiviral therapies.⁵ There is an important difference between chloroquine and lithium, however. Chloroquine is associated with numerous adverse psychiatric effects, particularly psychosis, mania, and emotional lability.⁶

We are a long way from knowing whether lithium treats the novel coronavirus and whether its risks will outweigh its benefits there. In the meantime, it is reassuring for patients who are taking lithium to know that lithium has pro-immune and antiviral properties. We warn patients about the medical risks of lithium─hypothyroidism, renal insufficiency, cardiac arrhythmia, and drug toxicity─but we need to inform them of its medical benefits as well. Besides its antiviral effects, lithium lowers the risks of stroke, heart disease, cancer, and neurologic illnesses, particularly dementia. In mood disorders, lithium lowers the all-cause mortality rate as well as the rate of psychiatric and medical hospitalizations.^7,8

Viral illnesses also put patients at risk for lithium toxicity, and they should be advised of these preventative steps (see Table):

• Avoid NSAIDs like naproxen and ibuprofen, as these can raise lithium levels. Instead, use acetaminophen for fever control.

• Stay hydrated to prevent toxicity.

• If severe vomiting or diarrhea ensues, physicians should hold lithium until the problem resolves.

Disclosures:

Dr Aiken is the Mood Disorders Section Editor for Psychiatric Times, the Editor in Chief of The Carlat Psychiatry Report, and the Director of the Mood Treatment Center. His written several books on mood disorders, most recently The Depression and Bipolar Workbook. He can be heard in the weekly Carlat Psychiatry Podcast with his co-host Kellie Newsome, PMH-NP. The author does not accept honoraria from pharmaceutical companies but receives royalties from PESI for The Depression and Bipolar Workbook and from W.W. Norton & Co. for Bipolar, Not So Much.

References:

1. Lagadinou M, Onisor MO, Rigas A, et al. Antimicrobial properties on non-antibiotic drugs in the era of increased bacterial resistance. Antibiotics (Basel). 2020;9(3):E107. Published 2020 Mar 2.

2. Rybakowski JK. Antiviral and immunomodulatory effect of lithium. Pharmacopsychiatry. 2000;33(5):159–164.

3. Puertas MC, Salgado M, Morón-López S, et al. Effect of lithium on HIV-1 expression and proviral reservoir size in the CD4+ T cells of antiretroviral therapy suppressed patients. AIDS. 2014;28(14):2157–2159.

4. Nowalk JK and Walkowiak J. Lithium and coronaviral infections. A scoping review. [version 2; peer review: 1 approved, 1 approved with reservations]. F1000Research 2020, 9:93 (https://doi.org/10.12688/f1000research.22299.2)

5. Post RM. The new news about lithium: an underutilized treatment in the united states. Neuropsychopharmacology. 2018;43(5):1174–1179.  

6. Chen PH, Chao TF, Kao YH, Chen YJ. Lithium interacts with cardiac remodeling: the fundamental value in the pharmacotherapy of bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2019;88:208–214.