Lithium is a simple alkali metal, the salt of which acts as a mood stabilizing agent which has been extensively used for the treatment of mania for more than 50 years. Lithium has been associated with rare instances of mild serum aminotransferase elevations, but has not been convincingly linked to clinically apparent acute liver injury.


Lithium (lith' ee um) is the lightest elemental metal and is normally found in low concentrations in human tissue. Lithium salts are highly water soluble and have been used medically for many years. While lithium has no psychotropic effects in normal individuals, it has potent mood stabilizing properties in patients with bipolar disorders, mania and recurrent depression. The mechanism of action of lithium is unknown, but is thought to be mediated by its replacement of sodium ions and disruption of membrane potentials in the central nervous system. It may also act by differential effects on neurotransmitter induced depolarization of membranes or interference with phosphatidylinositol pathways. Lithium was approved for use in bipolar illness in the United States in 1970 and it is still widely used for this indication. Lithium has also been used off-label in therapy of schizophrenia, alcohol dependence, attention deficit disorder and migraine headaches. Lithium is available as capsules or tablets of 150, 300, 450 and 600 mg in generic forms as well in several brand names including Carbolith, Duralith and Eskalith. A typical maintenance dose regimen is 600 to 900 mg daily. Lithium levels are generally monitored because of the narrow therapeutic window between toxicity and effectiveness aiming for levels between 0.6 and 1.2 mEq/L in chronic situations (higher in acute). Common side effects include metallic taste, nausea, tremor, polyuria, polydipsia and weight gain. Uncommon side effects include hypothyroidism. The major serious adverse event is severe lithium toxicity with can include polyuria, hyponatremia, renal disease and encephalopathy. Because of its narrow therapeutic window, lithium requires careful monitoring of drug levels.


Liver test abnormalities have been reported to occur in a small proportion of patients on long term therapy with lithium. These abnormalities are usually asymptomatic and transient, reversing even with continuation of medication. Instances of more marked elevations in serum aminotransferases have been reported in patients taking overdoses of lithium, but the other metabolic and systemic effects of lithium overdose generally overshadow hepatic adverse effects. Lithium has not been associated with instances of clinically apparent acute liver injury with jaundice.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism by which lithium causes serum aminotransferase elevations is not known. Some instances of serum aminotransferase elevations occurring on lithium therapy may be due to nonalcoholic fatty liver disease caused by weight gain that occurs in at least one-quarter of treated patients and ranges from 4.5 to 12 kg, generally during the first 1 to 2 years of therapy.

Outcome and Management

The serum aminotransferase elevations that occur on lithium therapy are usually self-limited and do not require dose modification or discontinuation of therapy. No instances of acute liver failure or chronic liver disease have been attributed to lithium.

Drug Class: Antipsychotic Agents, Drugs for Bipolar Disorders, Trace Elements and Metals



Lithium – Generic, Carbolith®, Duralith®, Eskalith®


Antipsychotic Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 04 June 2019

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    (Expert review of hepatotoxicity of psychiatric medications published in 1999; lithium is not discussed).
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    (Textbook of pharmacology and therapeutics).
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    (4 cases of use of lithium in patients with other significant conditions; one patient with heart failure developed jaundice and hepatomegaly attributed to passive congestion rather than lithium).
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    (17 year old man developed bilirubin elevations after taking lithium for 12 days [rising from 1.4 at baseline to 3.3 mg/dL], while all other tests were normal; authors suspected Gilbert syndrome exacerbated by lithium).
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    (26 year old man developed mild increases in ALT levels [peak 105 U/L] after 2 months of lithium treatment which decreased on stopping and increased again on restarting on two occasions [from 11 to 56 U/L and 19 to 56 U/L]; no symptoms and no mention of bilirubin elevations or weight gain).
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