key: cord-0971266-8l54pz1c
authors: Rojas‐Velasquez, Danilo; Lifland, Brooke; Caro, Mario Andres
title: Supratherapeutic lithium levels in COVID‐19 infection
date: 2022-02-17
journal: Bipolar Disord
DOI: 10.1111/bdi.13183
sha: 646e4039a2c193f35820ed6b807694f93dc462a6
doc_id: 971266
cord_uid: 8l54pz1c

Lithium levels are often checked in the inpatient setting when a patient has clear indications of acute kidney injury. Lithium levels can become supratherapeutic in COVID‐19 infection even after normalization of creatinine. Lithium levels should be checked routinely in patients with COVID‐19 infection in order to avoid supratherapeutic levels.

at her psychiatric baseline. She is usually fully oriented, conversant, and able to maintain employment by working in a store. Her outpatient psychiatrist noted that the patient decompensates psychiatrically when lithium levels drop below 0.9-1.0 mmol/L, with resultant aggression and self-injurious behavior.

Additional workup revealed hyperammonemia of 64 umol/L and a normal valproic acid level. Due to hyperammonemia, valproic acid and topiramate were held, and levocarnitine supplementation was started, resulting in normalization of ammonia levels after 8 days.

By HD 3, Ms. A's inattention and disorientation resolved, and she returned to her psychiatric baseline.

Initially, the patient's presentation was thought to be due to delirium secondary to AKI, decreased renal clearance of lithium, hyperammonemia, and COVID-19. Her lithium dose was reduced to 300 mg daily with a plan to titrate her dose, as her AKI had resolved by HD 2. Ms. A did not receive diuretics, nonsteroidal antiinflammatories, angiotensin-converting enzyme (ACE) inhibitors, or other medications that can cause lithium toxicity.

By HD 16, a steady-state trough lithium level was supratherapeutic at 1.25 mmol/L, despite the patient being on 450 mg BID, which was 75% of her home dose (see Table 1 ). Her lithium dose was decreased to 300 mg daily and 450 mg nightly, with a repeat lithium trough level of 0.97 mmol/L on HD 19.

Ms. B, a 24-year-old woman, presented to the emergency department with 2 weeks of fever, cough, and fatigue. She had a history of asthma, obstructive sleep apnea, selective mutism, ADHD, schizoaffective disorder, and borderline personality disorder. Her psychiatric medications consisted of chlorpromazine 50 mg daily as needed for agitation, clozapine 100 mg in the morning and 200 mg at night, lithium 450 mg in the morning and 750 mg at night, and lisdexamfetamine 40 mg daily. She had been on a stable lithium dose for at least a year. A lithium level 3 months prior was 0.73 mEq/L.

In the emergency department, her oxygen saturation was 98% on room air. SARS CoV-2 PCR was positive. Laboratory results were notable for C-reactive protein 34.7 mg/L, ferritin 384 ng/ml, and fibrinogen 509 mg/dl. Creatinine was 0.9 mg/dl (baseline 0.7 mg/dl).

She was not tested for proteinuria. Urine toxicology was positive for amphetamines due to her lisdexamfetamine prescription. Sodium, potassium, glucose, white blood cell count, D-dimer, PT, INR, and liver function tests were unremarkable. Chest X-ray showed a left lower lobe airspace consolidation. She was admitted for COVID-19 pneumonia.

Psychiatric examination revealed a woman who was fully oriented and oddly related with a concrete thought process. She endorsed depressive symptoms and chronic suicidal ideation without intent or plan. She denied other psychiatric symptoms. Staff at her group home confirmed that this was her psychiatric baseline.

Ms. B received four doses of hydroxychloroquine, after which the hydroxychloroquine was discontinued due to QTc prolongation TA B L E 1 Lithium dose, lithium level, and creatinine over time Lithium toxicity can result from medications that alter renal excretion, such as ACE inhibitors, NSAIDs, and diuretics, but neither of our patients were on these medications. In our two cases we do not suspect that clozapine, chlorpromazine, clozapine, lisdexamfetamine, montelukast, or pantoprazole resulted in supratherapeutic lithium levels, as these do not affect renal excretion of lithium. In

Ms. As case, she was taking topiramate of 50 mg at bedtime prior to admission. There is one case report suggesting that topiramate can result in lithium toxicity, but this case report does describe the dose topiramate or lithium the patient was receiving, and it appears that toxicity was precipitated by addition of topiramate. 2 Our patient was receiving both lithium and low-dose topiramate for long-term psychiatric management and did not experience lithium toxicity. Furthermore, topiramate was discontinued due to hyperammonemia, and repeat lithium levels continued to be elevated despite decreasing its dose, suggesting that the main cause for this abnormality was COVID-19. In both patients, the benefits of continuing lithium treatment outweighed potential risks, as both patients had a history of severe self-injurious behaviors, mood instability, and suicidal ideation that were minimized with lithium.

There are only two prior publications describing lithium toxicity in the setting of AKI and COVID-19 infection. 3 

Lithium titration can be challenging in patients with COVID-19, even in patients with mild or no AKI. Psychiatrists should be aware of the need to monitor lithium levels longitudinally in COVID-19 patients to avoid lithium toxicity. Future studies are warranted to elucidate potential mechanisms of renal damage from COVID-19, its effects on lithium pharmacophysiology, and long-term effects.

The authors obtained surrogate consent from each patient's legal guardian for publication of this anonymized case report.

The authors have no conflicts of interest to disclose.

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Lithium's antiviral effects: a potential drug for CoViD-19 disease?

Topiramate-induced lithium toxicity

Lithium toxicity in two coronavirus disease 2019 (COVID-19) patients

Lithium intoxication in COVID-19: a case report

Renal injury by SARS-CoV-2 infection: a systematic review