Last updated: September 8, 2023

Summarytoggle arrow icon

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.

Pharmacodynamicstoggle arrow icon

  • Mechanism of action: While the mechanism of action has not been definitively established, inhibition of the phosphoinositol cascade is thought to result in mood stabilization.
  • Steady state: usually reached 4–5 days after initiation or a change in dosage

Pharmacokineticstoggle arrow icon

Indicationstoggle arrow icon

Adverse effectstoggle arrow icon

Overview [2]

Adverse effects occur at therapeutic levels (0.4–1.0 mEq/L) but tend to be more severe at peak serum concentration of the drug.



  • Fine tremor
    • Nonprogessive, symmetric, fine postural tremor in the distal ends of upper extremities
    • Typically occurs when lithium therapy is started or the dose is increased but can occur at any time during the course of treatment
    • Often decreases spontaneously over time
  • Muscle weakness


Cardiac [3]



LITHIUM: “Lithium can cause Irregular Thyroxine levels (hypothyroidism or hyperthyroidism), Heart (Ebstein anomaly), nephrogenic diabetes Insipidus, and Uncontrolled Muscle movements (tremor).”

Treatment of adverse effects [4][5]

  • General measures
    • Reassurance, avoidance of exacerbating factors (e.g., caffeine, stress), and follow-up
    • Dosage adjustment
      • Use of short-acting lithium preparations, divided doses, or a different lithium salt (e.g., citrate instead of carbonate)
      • Reducing the total daily dose of lithium if serum lithium concentration is close to the upper limit of the therapeutic range
  • Tremor: beta blockers (e.g., propranolol) if persistent or severe tremor
  • Nephrogenic diabetes insipidus: amiloride [6]

Lithium poisoning

  • Toxic effects occur at serum levels > 1.5 mEq/L. [7]
  • For details and management, see “Lithium poisoning.”

Monitoring serum levels of lithium is important because of its narrow therapeutic window.

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

Contraindicationstoggle arrow icon

Alternative maintenance treatment options for bipolar disorder include lamotrigine, valproate, and carbamazepine. Valproate and antipsychotics (e.g., olanzepine, quetiapine) 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.

Referencestoggle arrow icon

  1. Willem A Nolen. What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium. Bipolar Disorders. 2019.
  2. Mehta N, Vannozzi R. Lithium-induced electrocardiographic changes: A complete review. Clin Cardiol. 2017; 40 (12): p.1363-1367.doi: 10.1002/clc.22822 . | Open in Read by QxMD
  3. Decker BS, Goldfarb DS, Dargan PI, et al. Extracorporeal treatment for lithium poisoning: rystematic review and recommendations from the EXTRIP workgroup. CJASN. 2015; 10 (5): p.875-887.doi: 10.2215/​CJN.10021014 . | Open in Read by QxMD
  4. Gitlin M. Lithium side effects and toxicity: prevalence and management strategies. Int J Bipolar Disord. 2016; 4 (1).doi: 10.1186/s40345-016-0068-y . | Open in Read by QxMD
  5. Kosten TR, Forrest JN. Treatment of severe lithium-induced polyuria with amiloride.. Am J Psychiatry. 1986; 143 (12): p.1563-1568.doi: 10.1176/ajp.143.12.1563 . | Open in Read by QxMD
  6. Grandjean EM, Aubry JM. Lithium: Updated Human Knowledge Using an Evidence-Based Approach. CNS Drugs. 2009; 23 (4): p.331-349.doi: 10.2165/00023210-200923040-00005 . | Open in Read by QxMD
  7. Lithane. Updated: June 1, 2006. Accessed: May 22, 2017.
  8. Lithium.​​​​​​​. Updated: February 20, 2019. Accessed: May 10, 2019.
  9. Poels EMP, Kamperman AM, Vreeker A, et al. Lithium Use during Pregnancy and the Risk of Miscarriage. Journal of Clinical Medicine. 2020; 9 (6): p.1819.doi: 10.3390/jcm9061819 . | Open in Read by QxMD
  10. Poels EMP, Bijma HH, Galbally M, Bergink V. Lithium during pregnancy and after delivery: a review. International Journal of Bipolar Disorders. 2018; 6 (1).doi: 10.1186/s40345-018-0135-7 . | Open in Read by QxMD
  11. Kennedy MLH. Medication management of bipolar disorder during the reproductive years. Mental Health Clinician. 2017; 7 (6): p.255-261.doi: 10.9740/mhc.2017.11.255 . | Open in Read by QxMD
  12. Shireen A. Hedya; Akshay Avula; Henry D. Swoboda.. Lithium Toxicity. StatPearls. 2020.

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