• Clinical science

Lithium

Summary

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.

Pharmacodynamics

  • 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

Pharmacokinetics

95% of lithium is excreted by the kidneys; . It is freely filtered at the glomerulus and mostly reabsorbed in the proximal convoluted tubule via sodium channels. [1]

Indications

  • First-line therapy for bipolar disorder [2][3]
    • Mood stabilization in patients with acute mania
    • Maintenance therapy
  • Augmentation in treatment-resistant depression

Adverse effects

General adverse effects [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. [4]

Lithium toxicity [8]

Toxicity occurs at serum levels > 1.5 mEq/L.

To remember the most common side effects of LITHIUM, think: “Lithium can cause Irregular Thyroxine levels (hypothyroidism or hyperthyroidism), Heart (Ebstein anomaly), nephrogenic diabetes Insipidus, and Uncontrolled Muslce movements (tremor).”

Treatment [9]

  • 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 [10]
  • Nephrogenic diabetes insipidus: amiloride [11]
  • Lithium toxicity
    • Discontinuation of lithium
    • Hydration with isotonic fluid (0.9% NaCl solution) and electrolyte correction to promote lithium clearance
    • Hemodialysis: first-line treatment for severe lithium toxicity
      • Indications [9]
        • 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
      • Hemodialysis should be continued until serum lithium concentration is < 1.0 mEq/L or for a minimum of 6 hours (if the serum lithium concentration cannot be measured).
    • 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.

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

Contraindications

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.

  • 1. Shireen A. Hedya; Akshay Avula; Henry D. Swoboda. Lithium Toxicity. StatPearls. 2020. url: https://www.ncbi.nlm.nih.gov/books/NBK499992/.
  • 2. Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-Hill Education; 2014.
  • 3. Drugs.com. Lithane. https://www.drugs.com/pro/lithane.html. Updated June 1, 2006. Accessed May 22, 2017.
  • 4. 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. url: https://onlinelibrary.wiley.com/doi/full/10.1111/bdi.12805.
  • 5. Mehta N, Vannozzi R. Lithium-induced electrocardiographic changes: A complete review. Clin Cardiol. 2017; 40(12): pp. 1363–1367. doi: 10.1002/clc.22822.
  • 6. Michael Gitlin. Lithium side effects and toxicity: prevalence and management strategies. International Journal of Bipolar Disorders. 2016. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5164879.
  • 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. 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): pp. 875–887. doi: 10.2215/​CJN.10021014.
  • 10. 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.
  • 11. Kosten TR, Forrest JN. Treatment of severe lithium-induced polyuria with amiloride. Am J Psychiatry. 1986; 143(12): pp. 1563–1568. doi: 10.1176/ajp.143.12.1563.
  • 12. Lithium. https://www.drugs.com/ppa/lithium.html​​​​​​​. Updated February 20, 2019. Accessed May 10, 2019.
last updated 09/11/2020
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