Lithium (medication)

Certain lithium compounds, also known as lithium salts, are used as psychiatric medication, primarily for bipolar disorder and for major depressive disorder. Lithium is taken orally (by mouth).

Common side effects include increased urination, shakiness of the hands, and increased thirst. Serious side effects include hypothyroidism, diabetes insipidus, and lithium toxicity. Blood level monitoring is recommended to decrease the risk of potential toxicity. If levels become too high, diarrhea, vomiting, poor coordination, sleepiness, and ringing in the ears may occur. Lithium is teratogenic and can cause birth defects at high doses, especially during the first trimester of pregnancy. The use of lithium while breastfeeding is controversial; however, many international health authorities advise against it, and the long-term outcomes of perinatal lithium exposure have not been studied. The American Academy of Pediatrics lists lithium as contraindicated for pregnancy and lactation. The United States Food and Drug Administration categorizes lithium as having positive evidence of risk for pregnancy and possible hazardous risk for lactation.

Lithium salts are classified as mood stabilizers. Lithium's mechanism of action is not known.

In the nineteenth century, lithium was used in people who had gout, epilepsy, and cancer. Its use in the treatment of mental disorders began with Carl Lange in Denmark and William Alexander Hammond in New York City, who used lithium to treat mania from the 1870s onwards, based on now-discredited theories involving its effect on uric acid. Use of lithium for mental disorders was re-established (on a different theoretical basis) in 1948 by John Cade in Australia.

Lithium carbonate is on the World Health Organization's List of Essential Medicines, and is available as a generic medication. In 2023, it was the 187th most commonly prescribed medication in the United States, with more than 2 million prescriptions. It appears to be underused in older people, and in certain countries, for reasons including patients' negative beliefs about lithium.

In 1970, lithium was approved by the United States Food and Drug Administration (FDA) for the treatment of bipolar disorder, which remains its primary use in the United States. It is sometimes used when other treatments are not effective in a number of other conditions, including major depression, schizophrenia, disorders of impulse control, and some psychiatric disorders in children. Because the FDA has not approved lithium for the treatment of other disorders, such use is off-label.

The mechanisms of biological action of lithium are only partially understood. For instance, studies of lithium-treated patients with bipolar disorder show that, among many other effects, lithium partially reverses telomere shortening in these patients and also increases mitochondrial function, although how lithium produces these pharmacological effects is not understood. Even the exact mechanisms involved in lithium toxicity are not fully understood.

Lithium is primarily used as a maintenance drug in the treatment of bipolar disorder to stabilize mood and prevent manic episodes, but it may also be helpful in the acute treatment of manic episodes. Although recommended by treatment guidelines for the treatment of depression in bipolar disorder, the evidence that lithium is superior to placebo for acute depression is low-quality; atypical antipsychotics are considered more effective for treating acute depressive episodes. Lithium carbonate treatment was previously considered to be unsuitable for children; however, more recent studies show its effectiveness for treatment of early-onset bipolar disorder in children as young as eight. The required dosage is slightly less than the toxic level (representing a low therapeutic index), requiring close monitoring of blood levels of lithium carbonate during treatment. Within the therapeutic range there is a dose-response relationship. A limited amount of evidence suggests lithium carbonate may contribute to the treatment of substance use disorders for some people with bipolar disorder. Although it is believed that lithium prevents suicide in people with bipolar disorder, a 2022 systematic review found that "Evidence from randomised trials is inconclusive and does not support the idea that lithium prevents suicide or suicidal behaviour."