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Lithium poisoning

Jeanmarie Perrone, MD, FACMT
Pia Chatterjee, MD
Section Editor
Stephen J Traub, MD
Deputy Editor
Jonathan Grayzel, MD, FAAEM


"Lithia" water was first used in the late 1800s to treat mania and gout. Over time, and likely due to low lithium content, "Lithia" water was ultimately replaced by lithium tablets. With the higher concentrations in the tablets, lithium's association with tremors and weakness became apparent and in 1898 the first descriptions of lithium toxicity appeared [1]. About a half century later, the calming effects of lithium in 10 patients with mania were described [2]; the drug's more toxic effects were recognized when lithium chloride was used as a salt substitute in patients with heart failure in 1949 [3].

Lithium's toxic effects limited its clinical use until appropriate serum monitoring became more readily available. In the 1970s, Lithium carbonate was approved in the United States for the treatment of acute mania and bipolar disorder and it has been in use ever since. In 2014, there were 6850 cases of lithium intoxication reported to the American Association of Poison Control Centers [4-6].

This topic will review the diagnosis and management of acute and chronic lithium poisoning. The therapeutic use of lithium, major side effects of lithium therapy, and other aspects of the management of patients with acute poisoning are discussed separately. A summary table to facilitate emergent management of lithium poisoning is provided (table 1). (See "Bipolar disorder in adults: Pharmacotherapy for acute mania and hypomania" and "Bipolar disorder in adults: Choosing maintenance treatment" and "Renal toxicity of lithium" and "Lithium and the thyroid" and "General approach to drug poisoning in adults".)


Lithium's exact mechanism of action is not clearly understood. It affects two intracellular signaling pathways, inositol monophosphate and glycogen synthase kinase-3 [7]. Lithium decreases intracellular inositol, which may be a mechanism for mood stabilization. Lithium also inhibits glycogen synthase kinase-3, a component of diverse signaling pathways involved in energy metabolism, neuroprotection, and neuroplasticity.

Lithium has a narrow therapeutic index; a large proportion of patients on chronic lithium therapy experience at least one episode of toxicity during treatment [8]. The highest intracellular lithium levels are found in the brain and the kidneys.


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Literature review current through: Sep 2016. | This topic last updated: Sep 29, 2016.
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  1. Strobusch AD, Jefferson JW. The checkered history of lithium in medicine. Pharm Hist 1980; 22:72.
  2. CADE JF. Lithium salts in the treatment of psychotic excitement. Med J Aust 1949; 2:349.
  3. CORCORAN AC, TAYLOR RD, PAGE IH. Lithium poisoning from the use of salt substitutes. J Am Med Assoc 1949; 139:685.
  4. Pauzé DK, Brooks DE. Lithium toxicity from an Internet dietary supplement. J Med Toxicol 2007; 3:61.
  5. Bronstein AC, Spyker DA, Cantilena LR Jr, et al. 2010 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 28th Annual Report. Clin Toxicol (Phila) 2011; 49:910.
  6. Mowry JB, Spyker DA, Brooks DE, et al. 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol (Phila) 2015; 53:962.
  7. Meltzer, H. Antipsychotic Agents & Lithium. In: Basic and Clinical Pharmacology, 11th ed, McGraw Hill, New York 2009. p.487.
  8. Amdisen A. Clinical features and management of lithium poisoning. Med Toxicol Adverse Drug Exp 1988; 3:18.
  9. Ward ME, Musa MN, Bailey L. Clinical pharmacokinetics of lithium. J Clin Pharmacol 1994; 34:280.
  10. Dupuis RE, Cooper AA, Rosamond LJ, Campbell-Bright S. Multiple delayed peak lithium concentrations following acute intoxication with an extended-release product. Ann Pharmacother 1996; 30:356.
  11. Jefferson JW, Kalin NH. Serum lithium levels and long-term diuretic use. JAMA 1979; 241:1134.
  12. Phelan KM, Mosholder AD, Lu S. Lithium interaction with the cyclooxygenase 2 inhibitors rofecoxib and celecoxib and other nonsteroidal anti-inflammatory drugs. J Clin Psychiatry 2003; 64:1328.
  13. Timmer RT, Sands JM. Lithium intoxication. J Am Soc Nephrol 1999; 10:666.
  14. Boton R, Gaviria M, Batlle DC. Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy. Am J Kidney Dis 1987; 10:329.
  15. Demers RG, Heninger GR. Electrocardiographic T-wave changes during lithium carbonate treatment. JAMA 1971; 218:381.
  16. Offerman SR, Alsop JA, Lee J, Holmes JF. Hospitalized lithium overdose cases reported to the California Poison Control System. Clin Toxicol (Phila) 2010; 48:443.
  17. White B, Larry J, Kantharia BK. Protracted presyncope and profound bradycardia due to lithium toxicity. Int J Cardiol 2008; 125:e48.
  18. Farag S, Watson RD, Honeybourne D. Symptomatic junctional bradycardia due to lithium intoxication in patient with previously normal electrocardiogram. Lancet 1994; 343:1371.
  19. Munshi KR, Thampy A. The syndrome of irreversible lithium-effectuated neurotoxicity. Clin Neuropharmacol 2005; 28:38.
  20. Schou M. Long-lasting neurological sequelae after lithium intoxication. Acta Psychiatr Scand 1984; 70:594.
  21. Von Hartitzsch B, Hoenich NA, Leigh RJ, et al. Permanent neurological sequelae despite haemodialysis for lithium intoxication. Br Med J 1972; 4:757.
  22. Singer I, Rotenberg D. Mechanisms of lithium action. N Engl J Med 1973; 289:254.
  23. Oakley PW, Whyte IM, Carter GL. Lithium toxicity: an iatrogenic problem in susceptible individuals. Aust N Z J Psychiatry 2001; 35:833.
  24. Carmen J, Okafor K, Ike E. The effects of lithium therapy on leukocytes: a 1-year follow-up study. J Natl Med Assoc 1993; 85:301.
  25. Wills BK, Mycyk MB, Mazor S, et al. Factitious lithium toxicity secondary to lithium heparin-containing blood tubes. J Med Toxicol 2006; 2:61.
  26. Speirs J, Hirsch SR. Severe lithium toxicity with "normal" serum concentrations. Br Med J 1978; 1:815.
  27. Venkatarathnamma PN, Patil AR, Nanjundaiah N. Fatal lithium toxicity with therapeutic levels--a case report. Int J Clin Pharmacol Ther 2011; 49:336.
  28. Peng J. Case report on lithium intoxication with normal lithium levels. Shanghai Arch Psychiatry 2014; 26:103.
  29. Linakis JG, Lacouture PG, Eisenberg MS, et al. Administration of activated charcoal or sodium polystyrene sulfonate (Kayexalate) as gastric decontamination for lithium intoxication: an animal model. Pharmacol Toxicol 1989; 65:387.
  30. Linakis JG, Eisenberg MS, Lacouture PG, et al. Multiple-dose sodium polystyrene sulfonate in lithium intoxication: an animal model. Pharmacol Toxicol 1992; 70:38.
  31. Favin FD, Klein-Schwartz W, Oderda GM, Rose SR. In vitro study of lithium carbonate adsorption by activated charcoal. J Toxicol Clin Toxicol 1988; 26:443.
  32. Smith SW, Ling LJ, Halstenson CE. Whole-bowel irrigation as a treatment for acute lithium overdose. Ann Emerg Med 1991; 20:536.
  33. Bretaudeau Deguigne M, Hamel JF, Boels D, Harry P. Lithium poisoning: the value of early digestive tract decontamination. Clin Toxicol (Phila) 2013; 51:243.
  34. Thanacoody R, Caravati EM, Troutman B, et al. Position paper update: whole bowel irrigation for gastrointestinal decontamination of overdose patients. Clin Toxicol (Phila) 2015; 53:5.
  35. Bélanger DR, Tierney MG, Dickinson G. Effect of sodium polystyrene sulfonate on lithium bioavailability. Ann Emerg Med 1992; 21:1312.
  36. Linakis JG, Hull KM, Lacouture PG, et al. Sodium polystyrene sulfonate treatment for lithium toxicity: effects on serum potassium concentrations. Acad Emerg Med 1996; 3:333.
  37. Linakis JG, Hull KM, Lee CM, et al. Effect of delayed treatment with sodium polystyrene sulfonate on serum lithium concentrations in mice. Acad Emerg Med 1995; 2:681.
  38. Ghannoum M, Lavergne V, Yue CS, et al. Successful treatment of lithium toxicity with sodium polystyrene sulfonate: a retrospective cohort study. Clin Toxicol (Phila) 2010; 48:34.
  39. Scharman EJ. Methods used to decrease lithium absorption or enhance elimination. J Toxicol Clin Toxicol 1997; 35:601.
  40. Garella S. Extracorporeal techniques in the treatment of exogenous intoxications. Kidney Int 1988; 33:735.
  41. Simard M, Gumbiner B, Lee A, et al. Lithium carbonate intoxication. A case report and review of the literature. Arch Intern Med 1989; 149:36.
  42. DePaulo JR Jr. Lithium. Psychiatr Clin North Am 1984; 7:587.
  43. Hauger RL, O'Connor KA, Yudofsky S, Meltzer HL. Lithium toxicity: when is hemodialysis necessary? Acta Psychiatr Scand 1990; 81:515.
  44. Fenves AZ, Emmett M, White MG. Lithium intoxication associated with acute renal failure. South Med J 1984; 77:1472.
  45. Vodovar D, El Balkhi S, Curis E, et al. Lithium poisoning in the intensive care unit: predictive factors of severity and indications for extracorporeal toxin removal to improve outcome. Clin Toxicol (Phila) 2016; 54:615.
  46. Mowry JB, Burdmann EA, Anseeuw K, et al. Extracorporeal treatment for digoxin poisoning: systematic review and recommendations from the EXTRIP Workgroup. Clin Toxicol (Phila) 2016; 54:103.
  47. Lavonas EJ, Buchanan J. Hemodialysis for lithium poisoning. Cochrane Database Syst Rev 2015; :CD007951.
  48. Clendeninn NJ, Pond SM, Kaysen G, et al. Potential pitfalls in the evaluation of the usefulness of hemodialysis for the removal of lithium. J Toxicol Clin Toxicol 1982; 19:341.
  49. Okusa MD, Crystal LJ. Clinical manifestations and management of acute lithium intoxication. Am J Med 1994; 97:383.
  50. Friedberg RC, Spyker DA, Herold DA. Massive overdoses with sustained-release lithium carbonate preparations: pharmacokinetic model based on two case studies. Clin Chem 1991; 37:1205.
  51. Goodman JW, Goldfarb DS. The role of continuous renal replacement therapy in the treatment of poisoning. Semin Dial 2006; 19:402.
  52. Hansen HE, Amdisen A. Lithium intoxication. (Report of 23 cases and review of 100 cases from the literature). Q J Med 1978; 47:123.
  53. Jacobsen D, Aasen G, Frederichsen P, Eisenga B. Lithium intoxication: pharmacokinetics during and after terminated hemodialysis in acute intoxications. J Toxicol Clin Toxicol 1987; 25:81.
  54. Beckmann U, Oakley PW, Dawson AH, Byth PL. Efficacy of continuous venovenous hemodialysis in the treatment of severe lithium toxicity. J Toxicol Clin Toxicol 2001; 39:393.
  55. Bellomo R, Kearly Y, Parkin G, et al. Treatment of life-threatening lithium toxicity with continuous arterio-venous hemodiafiltration. Crit Care Med 1991; 19:836.
  56. Leblanc M, Raymond M, Bonnardeaux A, et al. Lithium poisoning treated by high-performance continuous arteriovenous and venovenous hemodiafiltration. Am J Kidney Dis 1996; 27:365.
  57. Meyer RJ, Flynn JT, Brophy PD, et al. Hemodialysis followed by continuous hemofiltration for treatment of lithium intoxication in children. Am J Kidney Dis 2001; 37:1044.