• Clinical science



Lithium is a psychiatric medication used primarily as a first-line therapy for bipolar disorder. It is also used in treatment-resistant depression to augment antidepressants. The specific mechanism by which lithium acts to stabilize mood is not definitively known, but it is thought to be due to inhibition of the phosphoinositol cascade. Common side effects include gastrointestinal distress (nausea, diarrhea), polyuria, polydipsia, and tremor. Lithium therapy has a very narrow therapeutic index; frequent monitoring is therefore required to prevent toxicity.


While the mechanism of action has not been definitively established, inhibition of the phosphoinositol cascade is thought to result in mood stabilization.

Side effects

Side effects occur at therapeutic levels (0.8-1.2 mEq/L) but tend to be more severe at peak serum concentration of the drug.

To remember the most common side effects of lithium, think LiTHIUM: Low Thyroid (hypothyroidism), Heart (Ebstein anomaly), Insipidus (nephrogenic diabetes insipidus), Unwanted Movements (tremor).

Lithium toxicity

  • Management
    • Discontinue lithium
    • Hydration with isotonic fluid and electrolyte correction to promote lithium clearance
    • Hemodialysis
      • First-line treatment for severe lithium toxicity
      • Indications [1]
        • Serum lithium concentration > 5.0 mEq/L
        • Serum lithium concentration > 4.0 mEq/L with kidney dysfunction
        • Altered mental status, seizures, and/or life-threatening arrhythmias
    • Ventilatory support, if required
    • Whole bowel irrigation with polyethylene glycol can also be considered.
    • Activated charcoal does NOT prevent the absorption of lithium.

Monitoring serum levels of lithium is important because of its narrow therapeutic window (0.8–1.2 mEq/L).


We list the most important adverse effects. The selection is not exhaustive.


  • First-line therapy for bipolar disorder
    • Mood stabilization in patients with acute mania
    • Maintenance therapy
  • Augmentation in treatment-resistant depression



Alternative maintenance treatment options for bipolar disorder include valproate, quetiapine, and lamotrigine. Valproate, carbamazepine, and antipsychotics can be used for treatment of acute mania and hypomania.

Before prescribing lithium to women of child-bearing age, evaluate thyroid function, renal function, and human chorionic gonadotropin levels to rule out pregnancy.


We list the most important contraindications. The selection is not exhaustive.


Excreted almost entirely via the kidneys; most of the lithium filtered by the kidneys is reabsorbed at the proximal convoluted tubule via sodium channels. [8]

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  • 7. Sarlis NJ. Lithium-Induced Goiter. In: Griffing GT. Lithium-Induced Goiter. New York, NY: WebMD. https://emedicine.medscape.com/article/120243. Updated February 27, 2015. Accessed May 15, 2018.
  • 8. Timmer RT, Sands JM. Lithium intoxication. J Am Soc Nephrol. 1999; 10(3): pp. 666–74. pmid: 10073618.
  • 9. Gitlin M. Lithium side effects and toxicity: prevalence and management strategies. International Journal of Bipolar Disorders. 2016; 4(1). doi: 10.1186/s40345-016-0068-y.
  • 10. Mehta N, Vannozzi R. Lithium-induced electrocardiographic changes: A complete review. Clin Cardiol. 2017; 40(12): pp. 1363–1367. doi: 10.1002/clc.22822.
  • 11. Stewart PM, Grieve J, Nairn IM, Padfield PL, Edwards CR. Lithium inhibits the action of fludrocortisone on the kidney. Clin Endocrinol (Oxf). 1987; 27(1): pp. 63–8. pmid: 3115635.
  • 12. Lithium. https://www.drugs.com/ppa/lithium.html​​​​​​​. Updated February 20, 2019. Accessed May 10, 2019.
  • Kaplan. USMLE Step 1 Lecture Notes 2016: Pharmacology. New York, NY: Kaplan; 2015.
last updated 04/03/2020
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