Lithium Toxicity

5 Jan

Submitted by Christina Brown, M.D.

QUICK PEARLS:lithium-300x225

Use – Mood stabilizing drug for bipolar disorder and depression.

Epidemiology – In 2010, there were 6307 cases of lithium intoxication reported to the American Association of Poison Control Centers [2,3].  A large proportion of patients on chronic lithium therapy experience at least one episode of toxicity during treatment [4].  

Pharmacodynamics – narrow therapeutic index. 

GI absorption: 

Therapeutic –

  • immediate release – Peaks at 1 to 2 hours s/p ingestion.
  • Sustained release – 2 to 4 hours s/p ingestion. 

Up to 12 hours or longer may be required before peak levels are reached in acute overdose [5,6].

Lithium is a small molecule (74 Daltons) with no protein or tissue binding and is therefore amenable to hemodialysis.  Renal excretion. 

Risk factors – GI losses, acute decompensated heart failure, cirrhosis, diuretics, NSAIDs or ACE inhibitors [7-9].   Elderly patients have a lower glomerular filtration rate and a reduced volume of distribution (d/t to reductions in lean body mass and total body water). 


Clinical Presentation

Acute – Nausea, vomiting, and diarrhea; late neurologic sequelae

Chronic  – Neurologic findings; sluggishness, ataxia, confusion, agitation, and/or neuromuscular excitability (tremors, myoclonus)

Severe – Seizures, non-convulsive status epilepticus, or encephalopathy


Diagnostic Evaluation

Normal [Lithium] – 0.8-1.2 mEq/L.  Concentration may not correlate w/ severity.

Labs – BMP, CBC, Acetaminophen, Salicylate





Hemodialysis  – Indications:

Lithium > 4 mEq/L; regardless of clinical status

Lithium > 2.5mEq/L + signs of significant lithium toxicity (eg, seizures, depressed mental status), has renal insufficiency or other conditions that limit lithium excretion, or suffers from an illness that would be exacerbated by aggressive IV fluid hydration (eg, heart failure) [1].


  2. Pauzé DK, Brooks DE. Lithium toxicity from an Internet dietary supplement. J Med Toxicol 2007; 3:61.
  3. 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.
  4. Amdisen A. Clinical features and management of lithium poisoning. Med Toxicol Adverse Drug Exp 1988; 3:18.
  5. Ward ME, Musa MN, Bailey L. Clinical pharmacokinetics of lithium. J Clin Pharmacol 1994; 34:280.
  6. 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.
  7. Jefferson JW, Kalin NH. Serum lithium levels and long-term diuretic use. JAMA 1979; 241:1134.
  8. 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.
  9. Timmer RT, Sands JM. Lithium intoxication. J Am Soc Nephrol 1999; 10:666.
  10. 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.
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