• 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.

Effects

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

Cause Symptoms
Acute toxicity
  • Acute increase in lithium dosage in patients with a low baseline lithium serum level (i.e., not on regular therapy)
  • Primarily gastrointestinal symptoms: nausea, vomiting, and diarrhea
  • Neuromuscular symptoms may develop (tremor, ataxia, hyperreflexia).
  • ECG may show T-wave flattening.
Acute on chronic toxicity
  • Acute increase in lithium dosage in patients with a therapeutic baseline lithium serum level (i.e., long-term therapy)
  • Gastrointestinal symptoms and neurological symptoms dominate.
Chronic 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
        • Expected time required to reduce serum lithium concentration to < 1.0 mEq/L is > 36 hours
      • 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 (0.8–1.2 mEq/L).

References:[2][3][4][5][6][1][7][8][9][10]

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

Indications

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

References:[2][3][4]

Contraindications

  • Absolute contraindications
  • Relative contraindications
    • Concurrent diuretic use
    • Dehydration, sodium depletion
    • First trimester of pregnancy: if lithium is needed during pregnancy, aim for the minimum effective dose and monitor serum levels regularly.

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.

References:[4][11][12]

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

Pharmacokinetics

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]

Guidelines & therapy recommendations

  • Monitoring serum levels of lithium is important because of its narrow therapeutic window.
  • Steady state serum levels are usually reached 4–5 days after initiation or a change in dosage.
  • Due to its slow onset of action, effects are expected 1–2 weeks after initiation of treatment.
  • Optimal range of lithium serum level: 0.8 mmol/L–1.2 mmol/L for acute management and long-term maintenance
  • How to implement lithium monitoring
    • Lithium serum level: 5–7 days after initiating treatment or a dose change, or every 6–12 months for patients on steady doses
    • Half-life : 12–24 hours → A blood sample for serum level monitoring should be taken 12 hours after the last dose.
  • Suggested dosage: lithium 2–3 times daily
  • 1. 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.
  • 2. Le T, Bhushan V. First Aid for the USMLE Step 1 2015. McGraw-Hill Education; 2014.
  • 3. Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-Hill Education; 2014.
  • 4. Drugs.com. Lithane. https://www.drugs.com/pro/lithane.html. Updated June 1, 2006. Accessed May 22, 2017.
  • 5. Lee DC, Miller MA. Lithium Toxicity. In: Lithium Toxicity. New York, NY: WebMD. http://emedicine.medscape.com/article/815523. Updated February 1, 2015. Accessed May 22, 2017.
  • 6. 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.
  • 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 05/13/2019
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