Lithium has long been a cornerstone treatment for bipolar disorder, particularly for acute mania, yet its broader clinical and neurobiological benefits remain underrecognized. Despite strong evidence for efficacy, lithium is increasingly underutilized in clinical practice, often replaced by antidepressants, antipsychotics, and anticonvulsants. Emerging data suggest that lithium may have a wider range of therapeutic effects, including mood stabilization, neuroprotection, and potential roles in preventing cognitive decline. This commentary argues for a reassessment of lithium’s role in psychiatry, emphasizing its expanded clinical significance.

This article is a narrative commentary synthesizing existing clinical, epidemiological, and preclinical evidence rather than a formal empirical study. The author reviews observational data, randomized controlled trials, and emerging translational findings to present three key perspectives: lithium’s broad therapeutic profile, its role as a disease-modifying agent, and new evidence linking lithium deficiency to cognitive disorders such as mild cognitive impairment (MCI) and Alzheimer’s disease.

The evidence reviewed highlights lithium’s extensive clinical benefits beyond its antimanic effects. Lithium has demonstrated efficacy in preventing both manic and depressive episodes, reducing suicidality, enhancing the effects of other mood stabilizers, and improving long-term outcomes such as relapse rates and rehospitalization. It is associated with neuroprotective effects, including preservation or reversal of gray and white matter abnormalities and normalization of circadian rhythms. Lithium may also improve cognitive outcomes and reduce the risk of dementia, as supported by clinical and epidemiologic studies.

Emerging research suggests lithium may function as a disease-modifying agent in bipolar disorder, particularly when initiated early in the illness course. Early use is associated with a more benign disease trajectory, reduced disability, and improved long-term prognosis. Additionally, recent findings indicate that reduced brain lithium levels may be linked to MCI and Alzheimer’s disease, with lithium supplementation reversing pathological changes and cognitive deficits in preclinical models. Human studies suggest that low-dose lithium may slow cognitive decline and reduce dementia risk.

Despite these benefits, lithium remains underused. Data indicate declining prescription rates over time, with clinicians often overemphasizing potential adverse effects such as renal or thyroid dysfunction, which may be overstated or manageable with monitoring.

The contemporary evidence suggests that lithium has a far broader therapeutic role than traditionally appreciated, including potential disease-modifying and neuroprotective effects. Early and sustained use may improve long-term outcomes in bipolar disorder and possibly mitigate cognitive decline. Given its underutilization, the article advocates for a paradigm shift in clinical practice toward earlier and more widespread use of lithium, along with improved clinician and patient education regarding its benefits and manageable risks.

Reference:
Post RM. Am J Psychiatry 2026;Epub ahead of print:appiajp20250958. Abstract