Medscape is available in 5 Language Editions – Choose your Edition here.


Lithium Toxicity Clinical Presentation

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


As with all toxic ingestions, it is important to determine the amount, time, co-ingestants, and reason for ingestion. Toxicity does not often correlate with the measured lithium level since clinical toxicity is affected by the type of the poisoning.

Clinical features

Three main categories of lithium poisoning are as follows: acute, acute-on-chronic, and chronic.

Acute poisoning

These patients usually do not have a tissue body burden and symptoms are predominately gastrointestinal (GI), including nausea, vomiting, cramping, and sometimes diarrhea. Progression of acute toxicity can involve neuromuscular signs such as tremulousness, dystonia, hyperreflexia, and ataxia. Cardiac dysrhythmias have been reported but rarely occur. The most common electrocardiographic finding is T-wave flattening.

Acute-on-chronic poisoning

These patients take lithium regularly and have taken a larger dose recently. These patients may display both GI and neurologic symptoms, and serum levels can be difficult to interpret. Patients should be treated according to their clinical manifestations.

Chronic poisoning

These patients typically have a large body burden of lithium and may be difficult to treat. Chronic lithium toxicity is usually precipitated with introduction of new medication that may impair renal function/excretion or cause a hypovolemic state. Symptoms are primarily neurologic. Mental status is often altered and can progress to coma and seizures if the diagnosis is unrecognized. Many severely poisoned patients can develop a syndrome of irreversible lithium-effectuated neurotoxicity (SILENT) such as cognitive impairment, sensorimotor peripheral neuropathy, and cerebellar dysfunction.

Drug interactions

Three major drug classes have been identified as potential precipitants of lithium toxicity, as follows:

  • Diuretics that promote renal sodium wasting
  • Angiotensin-converting enzyme (ACE) inhibitors that reduce glomerular filtration rate (GFR) and enhance the tubular reabsorption of lithium
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) that reduce the glomerular filtration rate (GFR) and interrupt of renal prostaglandin synthesis

Systemic effects

Renal toxicity is common with chronic lithium therapy, with nephrogenic diabetes insipidus being the most severe manifestation. Lithium inhibits the action of antidiuretic hormone (ADH) on the distal renal tubule, impairing sodium and water reabsorption. Other manifestations of lithium toxicity on the kidney include renal tubular acidosis, chronic tubulointerstitial nephritis, and nephrotic syndrome.

The most common endocrine disorder secondary to chronic toxicity is hypothyroidism. Lithium is taken up avidly by thyroid cells and blocks thyroid hormone release from thyroglobulin, which inhibits adenylate cyclase and prevents thyroid-stimulating hormone (TSH) from activating thyroid cells via the TSH receptor. It may also affect thyroid hormone synthesis. Myxedema coma has been reported as a complication of toxicity.

Acute exposure to lithium can cause leukocytosis, whereas chronic exposure can produce aplastic anemia.

Patients who are on long-term lithium therapy can develop localized edema, dermatitis, and skin ulcers.



Neurologic effects of lithium toxicity include the following:

  • Tremors
  • Lethargy
  • Confusion
  • Seizures
  • Coma

Gastrointestinal effects of lithium toxicity include the following:

  • Nausea
  • Vomiting
  • Crampy abdominal pain
  • Diarrhea

Mild-to-moderate lithium toxicity is characterized by tremor, weakness, and mild confusion. Moderate-to-severe lithium toxicity is characterized by the following:

  • Altered mental status
  • Muscle fasciculations
  • Stupor
  • Seizures
  • Coma
  • Hyperreflexia
  • Cardiovascular collapse
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].

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.