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Lithium Toxicity

  • Author: David C Lee, MD; Chief Editor: Asim Tarabar, MD  more...
Updated: Feb 02, 2015


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.

Presently, 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.



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 is dependent upon the glomerular filtration rate (GFR). Consequently, dosing must be adjusted based on 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 2013, the American Association of Poison Control Centers’ National Poison Data System reported 6610 case mentions and 3488 single exposures to lithium.[1] The figures are similar to those reported in the preceding 5 years.[2]


In the 3488 single exposures to lithium reported to the American Association of Poison Control Centers’ National Poison Data System in 2013, outcomes were moderate in 1180 cases and major in 153 cases, with five deaths.[1] Lethal outcomes in lithium toxicity are generally secondary to severe CNS effects with subsequent cardiovascular collapse. Renal, gastrointestinal, and endocrine morbidity may also occur.


No predilection exists.


In 2013, of the 3488 single exposures to lithium reported to the American Association of Poison Control Centers’ National Poison Data System, 2722 (78%) were in patients aged 20 years or older; 391 (11%) were in patients 13 to 19 years old, and 138 (4%) were in children younger than 6 years.[1]

Contributor Information and Disclosures

David C Lee, MD Research Director, Department of Emergency Medicine, Associate Professor, North Shore University Hospital and New York University Medical School

David C Lee, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.


Amit Gupta, MD Department of Emergency Medicine, Staten Island University Hospital

Amit Gupta, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

John G Benitez, MD, MPH Associate Professor, Department of Medicine, Medical Toxicology, Vanderbilt University Medical Center; Managing Director, Tennessee Poison Center

John G Benitez, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Undersea and Hyperbaric Medical Society, Wilderness Medical Society, American College of Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Mark S Slabinski, MD, FACEP, FAAEM Vice President, EMP Medical Group

Mark S Slabinski, MD, FACEP, FAAEM is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Ohio State Medical Association

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, James G Linakis, PhD, MD, to the development and writing of this article.

  1. Mowry JB, Spyker DA, Cantilena LR Jr, McMillan N, Ford M. 2013 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 31st Annual Report. Clin Toxicol (Phila). 2014 Dec. 52(10):1032-283. [Medline]. [Full Text].

  2. National Poison Data System Annual Reports. American Association of Poison Control Centers. Available at Accessed: February 2, 2015.

  3. Linakis JG, Savitt DL, Wu TY, Lockhart GR, Lacouture PG. Use of sodium polystyrene sulfonate for reduction of plasma lithium concentrations after chronic lithium dosing in mice. J Toxicol Clin Toxicol. 1998. 36(4):309-13. [Medline].

  4. Ghannoum M, Lavergne V, Yue CS, Ayoub P, Perreault MM, Roy L. Successful treatment of lithium toxicity with sodium polystyrene sulfonate: a retrospective cohort study. Clin Toxicol (Phila). 2010 Jan. 48(1):34-41. [Medline].

  5. Bretaudeau Deguigne M, Hamel JF, Boels D, Harry P. Lithium poisoning: the value of early digestive tract decontamination. Clin Toxicol (Phila). 2013 May. 51(4):243-8. [Medline].

  6. Decker BS, Goldfarb DS, Dargan PI, Friesen M, Gosselin S, Hoffman RS, et al. Extracorporeal Treatment for Lithium Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup. Clin J Am Soc Nephrol. 2015 Jan 12. [Medline].

  7. Menghini VV, Albright RC Jr. Treatment of lithium intoxication with continuous venovenous hemodiafiltration. Am J Kidney Dis. 2000 Sep. 36(3):E21. [Medline].

  8. van Bommel EF, Kalmeijer MD, Ponssen HH. Treatment of life-threatening lithium toxicity with high-volume continuous venovenous hemofiltration. Am J Nephrol. 2000 Sep-Oct. 20(5):408-11. [Medline].

  9. Alexander MP, Farag YM, Mittal BV, Rennke HG, Singh AK. Lithium toxicity: a double-edged sword. Kidney Int. 2008 Jan. 73(2):233-7. [Medline].

  10. Aral H, Vecchio-Sadus A. Toxicity of lithium to humans and the environment--a literature review. Ecotoxicol Environ Saf. 2008 Jul. 70(3):349-56. [Medline].

  11. Burkhart, K. Lithium. Rosen's Emergency Medicine: Concepts and Clinical Practice. Sixth Edition. Mosby Elsevier; 2006. 2442-2444.

  12. Chen KP, Shen WW, Lu ML. Implication of serum concentration monitoring in patients with lithium intoxication. Psychiatry Clin Neurosci. 2004 Feb. 58(1):25-9. [Medline].

  13. Eyer F, Pfab R, Felgenhauer N, et al. Lithium poisoning: pharmacokinetics and clearance during different therapeutic measures. J Clin Psychopharmacol. 2006 Jun. 26(3):325-30. [Medline].

  14. Freeman MP, Freeman SA. Lithium: clinical considerations in internal medicine. Am J Med. 2006 Jun. 119(6):478-81. [Medline].

  15. Giles JJ, Bannigan JG. Tetatogenic and developmental effects of lithium. Curr Pharm Des. 2006. 12(12):1531-41.

  16. Gitlin M. Lithium and the kidney: an updated review. Drug Saf. 1999 Mar. 20(3):231-43. [Medline].

  17. Greller H. Lithium. Goldfrank's Toxicologic Emergencies. Eighth. McGraw-Hill; 2006. 1052-1058.

  18. Groleau G. Lithium toxicity. Emerg Med Clin North Am. 1994 May. 12(2):511-31. [Medline].

  19. Hsu CH, Liu PY, Chen JH, Yeh TL, Tsai HY, Lin LJ. Electrocardiographic abnormalities as predictors for over-range lithium levels. Cardiology. 2005. 103(2):101-6. [Medline].

  20. Juurlink DN, Mamdani MM, Kopp A, Rochon PA, Shulman KI, Redelmeier DA. Drug-induced lithium toxicity in the elderly: a population-based study. J Am Geriatr Soc. 2004 May. 52(5):794-8. [Medline].

  21. Lee DC, Klachko MN. Falsely elevated lithium levels in plasma samples obtained in lithium containing tubes. J Toxicol Clin Toxicol. 1996. 34(4):467-9. [Medline].

  22. Ng YW, Tiu SC, Choi KL, Chan FK, Choi CH, Kong PS. Use of lithium in the treatment of thyrotoxicosis. Hong Kong Med J. 2006 Aug. 12(4):254-9. [Medline].

  23. Rosenqvist M, Bergfeldt L, Aili H, Mathe AA. Sinus node dysfunction during long-term lithium treatment. Br Heart J. 1993 Oct. 70(4):371-5. [Medline].

  24. Scharman EJ. Methods used to decrease lithium absorption or enhance elimination. J Toxicol Clin Toxicol. 1997. 35(6):601-8. [Medline].

  25. Timmer RT, Sands JM. Lithium intoxication. J Am Soc Nephrol. 1999 Mar. 10(3):666-74. [Medline].

  26. Zimmerman JL. Poisonings and overdoses in the intensive care unit: general and specific management issues. Crit Care Med. 2003 Dec. 31(12):2794-801. [Medline].

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