Lithium Toxicity

Updated: Jun 02, 2017
  • Author: David C Lee, MD; Chief Editor: Michael A Miller, MD  more...
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Practice Essentials

Lithium is commonly used as maintenance treatment of bipolar disorder. Lithium poisoning occurs frequently, since it is used in a population at high risk for overdose. Furthermore, lithium has a relatively narrow therapeutic index that predisposes patients on lithium maintenance treatment to poisoning with relatively minor changes in medications or health status. [1]

Clinically, the three main categories of lithium poisoning are as follows (see Presentation):

  • Acute – Manifestations are predominantly gastrointestinal (GI), but progression to neuromuscular signs may occur
  • Acute-on-chronic – Both GI and neurologic manifestations may be present
  • Chronic – Manifestations are primarily neurologic

Lithium levels should be measured in symptomatic patients. However, levels may not correlate with clinical symptoms due to the kinetic profile of lithium. Multiple measurements may be indicated to evaluate the effects of treatment and in patients who have taken sustained-release tablets (see Workup).

Supportive therapy is the mainstay of treatment of lithium toxicity. Airway protection is crucial due to emesis and risk of aspiration. Seizures can be controlled with benzodiazepines, phenobarbital, or propofol. See Treatment.





Lithium has been used in medicine since the 1870s. Lithium was initially used to treat depression, gout, and neutropenia, and for cluster headache prophylaxis, but it fell out of favor because of its side effects. The US Food and Drug Administration (FDA) banned the use of lithium in the 1940s because of fatalities but lifted the ban in 1970.




The central nervous system (CNS) is the major organ system affected, although the renal, gastrointestinal (GI), endocrine, and cardiovascular (CV) systems also may be involved.

Lithium is available only for oral administration. It is almost completely absorbed from the GI tract. Peak levels occur 2-4 hours postingestion, although absorption can be much slower in massive overdose or with ingestion of sustained-release preparations.

Lithium dosing

Lithium is minimally protein bound (< 10%) and has an apparent volume of distribution of 0.6-1 L/kg. The therapeutic dose is 300-2700 mg/d with desired serum levels of 0.6-1.2 mEq/L.

Lithium clearance is predominantly through the kidneys. Because it is minimally protein bound, lithium is freely filtered at a rate that depends on the glomerular filtration rate (GFR). Consequently, dosing must be adjusted on the basis of renal function. Individuals with chronic renal insufficiency must be closely monitored if placed on lithium therapy.

Most filtered lithium is reabsorbed in the proximal tubule; thus, drugs known to inhibit proximal tubular reabsorption, such as carbonic anhydrase inhibitors and aminophylline, may increase excretion. Diuretics acting distally to the proximal tubule, such as thiazides and spironolactone, do not directly affect the fractional excretion of lithium (although they may affect serum lithium levels indirectly through their effects on volume status). Reabsorption of lithium is increased and toxicity is more likely in patients who are hyponatremic or volume depleted, both of which are possible consequences of diuretic therapy.

Lithium half-life

The plasma elimination half-life of a single dose of lithium is from 12-27 hours (varies with age). The half-life increases to approximately 36 hours in elderly persons (secondary to decreased GFR). Additionally, half-life may be considerably longer with chronic lithium use.




United States

In 2015, the American Association of Poison Control Centers’ National Poison Data System reported 7143 case mentions and 3825 single exposures to lithium. [2] The figures are similar to those reported in the preceding 5 years. [3]


In the 3825 single exposures to lithium reported to the American Association of Poison Control Centers’ National Poison Data System in 2015, outcomes were moderate in 1372 cases and major in 164 cases, with one death. [2] Lethal outcomes in lithium toxicity are generally secondary to severe CNS effects with subsequent cardiovascular collapse. Renal, gastrointestinal, and endocrine morbidity may also occur.


In 2015, of the 3825 single exposures to lithium reported to the American Association of Poison Control Centers’ National Poison Data System, 3017 (79%) were in patients aged 20 years or older; 462 (12%) were in patients 13 to 19 years old, and 129 (4%) were in children younger than 6 years. [2]