Lithium Aspartate Therapy Ineffective for Post–COVID-19 Condition Fatigue, Brain Fog

For patients with neurologic post–COVID-19 condition (PCC), lithium aspartate therapy was not effective at reducing symptoms of fatigue and cognitive dysfunction, according to a new study published in JAMA Network Open.¹

The study did, however, indicate that a higher dose of lithium aspartate may be effective in reducing cognitive symptoms, but another trial is needed to confirm the results.

For patients with PCC, symptoms of COVID-19 persist at least 4 weeks after recovering from the initial infection. There are currently no approved treatments for neurologic PCC. Due to lithium’s neuroprotective qualities, the researchers hypothesized that it could be a potential treatment for neurologic PCC.

Neurologic symptoms of post–COVID-19 condition did not experience symptom improvement with lithium aspartate therapy. | image credit: freshidea - stock.adobe.com

The researchers performed a randomized, double-blind, placebo-controlled trial with 3 weeks of follow-up; all participants were then enrolled in an open-label lithium dose-finding study with 6 weeks of follow-up. Participants included those who reported fatigue or cognitive dysfunction that persisted more than 4 weeks after testing positive for COVID-19. Other inclusion criteria were a Fatigue Severity Scale-7 (FSS-7) or Brain Fog Severity Scale (BFSS) score of 28 or more, a Beck Depression Inventory-II score of less than 24, and no history of other conditions that could cause fatigue or cognitive dysfunction. Overall, 52 participants were enrolled (30 men, 22 women; mean age, 58.54 years). The primary outcome was the change in sum of FSS-7 and BFSS scores.

In the initial trial, participants were randomly assigned 1:1 to receive lithium aspartate (10 mg to 15 mg per day) or placebo for 3 weeks followed by open-label lithium aspartate (10 mg to 15 mg per day) for 2 weeks. Two participants who had been assigned to lithium therapy were lost to follow-up. Participants took 2 capsules (5 mg each) of lithium for the first 10 days; if their symptoms persisted, they could take 3 capsules each for the last 11 days.

READ MORE: FDA Authorizes IND For Phase 2 Clinical Trial Evaluating Treatment for Post–COVID-19 Condition

The results showed no significant differences in the primary outcome scores between the treatment and placebo groups (-3.6; 95% CI, -16.6 to 9.5). The researchers did not observe any significant differences in the secondary outcomes between the two groups, including Insomnia Severity Scale, Generalized Anxiety Scale-2, Short Form-12 Health Survey (physical and mental), Well-Being Scale, Headache and Body Pain Bother Scale, Digit Symbol Substitution, and Delayed Recall Tests from the Montreal Cognitive Assessment.

In the dose-finding study, the researchers invited 43 participants—excluding those who responded to the placebo—to take open-label lithium aspartate doses of up to 45 mg per day for 6 weeks. Participants initially took 2 5 mg capsules of lithium aspartate twice daily for 7 days before increasing to a maximum dosage of 45 mg a day. Follow-up occurred 3 weeks after each participant achieved the maximum dosage.

Of the 5 participants in the dose-finding study, 3 saw significantly greater reductions in fatigue and cognitive dysfunction compared with the 15 mg per day dose. Even among these participants, the researchers observed a more significant reduction in symptoms among the participants who had serum lithium levels of 0.18 and 0.49 mEq/L compared with 0.10 mEq/L.

The researchers note that the dose-finding study is limited by its size and selection bias. However, future studies that target serum lithium levels of 0.18 to 0.50 mEq/L are warranted to address the dearth of evidence-based treatments for the large number of patients with neurologic PCC.

READ MORE: COVID-19 Resource Center

Reference

1.Guttuso, T Jr, Zhu J, Wilding G. Lithium aspartate for long COVID fatigue and cognitive dysfunction: a randomized clinical trial. JAMA Netw Open. 2024;7(10):e2436874. doi:10.1001/jamanetworkopen.2024.36874