One of the world’s experts on bipolar disorder, Robert Post, wrote an update on lithium in the March 2026 issue of the American Journal of Psychiatry.
Lithium is often thought of primarily as a treatment for mania. In fact, its potential benefits are much broader. This article examines three emerging ways of understanding lithium’s clinical and biological effects and why it may deserve greater consideration in the treatment of bipolar disorder.
First, lithium appears to differ from many other medications used in bipolar disorder because of the breadth of its effects. In addition to treating mania, lithium may help reduce depressive episodes, prevent future mood episodes, lower suicide risk, and improve long-term illness stability.
Second, lithium may be best understood as a disease-modifying treatment. In other areas of medicine, such as multiple sclerosis, pre-diabetes, and rheumatoid arthritis, disease-modifying medications are used early to slow illness progression and reduce future disability. A similar argument can be made for lithium: when clinically appropriate, using it earlier in the course of bipolar disorder may help protect against worsening mood instability, repeated episodes, and functional decline. In other words, lithium doesn’t just treat acute episodes, it changes the course of the disorder.
Third, recent research has raised the possibility that lithium may also play a role in cognitive health. A study published in Nature reported evidence of reduced lithium levels in the brains of people with mild cognitive impairment and Alzheimer’s disease. In animal models, lithium deficiency was associated with cognitive and biological abnormalities, some of which improved when lithium was restored.
The same research suggested that lithium orotate may behave differently from standard lithium formulations in experimental models, including less sequestration within Alzheimer’s-related plaques. These findings are preliminary and do not establish lithium orotate as a proven treatment for cognitive impairment or Alzheimer’s disease. However, they raise important questions about lithium’s biological role and may lead to new directions in research.
Taken together, these findings support a broader view of lithium—not simply as an antimanic medication, but as a treatment with potentially preventive, neuroprotective, and disease-modifying properties.
References
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