• 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 and reduces the risk of suicide in patients with major depressive disorder. The specific mechanism by which lithium acts to stabilize mood is still 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 of lithium use [1][2]

Side effects related to lithium use can occur even at therapeutic levels .

Lithium toxicity [3][1]

  • Because lithium has a very narrow therapeutic window, patients require frequent monitoring.
  • Definition: serum lithium levels > 1.5 mEq/L (1.5–2.0 mmol/L)
    • Acute toxicity: seen in patients with a low baseline level of lithium (not on regular therapy) who have acutely taken a large dose (e.g., suicide attempt)
    • Acute on chronic toxicity: seen in patients receiving long-term lithium treatment who have taken a larger dose acutely
    • Chronic toxicity: seen in patients receiving long-term lithium; treatment; usually occurs due to a recent dose increase, new renal impairment, or newly introduced therapy that exacerbates lithium effects
  • Risk factors [3]
  • Clinical features
    • Acute toxicity and acute on chronic toxicity
      • Gastrointestinal features (nausea, vomiting, diarrhea) predominant
      • Neurological features (lethargy, ataxia, altered mental status, neuromuscular excitability) may appear in late stages.
      • ECG changes (e.g., T-wave flattening) may occur.
    • Chronic toxicity
      • Neurological features (lethargy, ataxia, altered mental status, neuromuscular excitability) manifest first.
      • ECG changes may occur (e.g., T-wave flattening).
    • Neurologic
    • Gastrointestinal
    • Cardiovascular
    • Renal: acute kidney injury
    • Endocrine: myxedema coma
    • Psychiatric: apathy, psychomotor impairment
  • Treatment
    • Discontinue lithium
    • Hydration with isotonic fluid and electrolyte correction; to promote lithium clearance
    • Hemodialysis
      • First-line treatment for severe lithium toxicity
      • Indications [4]
        • 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.

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

References:[5][6][7][8][9][4][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:[5][6][7]

Contraindications

  • Absolute contraindications
  • Relative contraindications

Anticonvulsants (e.g., lamotrigine) are an alternative treatment option for bipolar disorder that can be used when lithium is contraindicated.

References:[7][11]

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. [3]

Guidelines & therapy recommendations

  • Monitoring serum levels of lithium is important because of its narrow therapeutic window.
  • Steady state serum levels are usually expected 4–5 days after initiation or a change in dose.
  • 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

Special patient groups

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

  • 1. 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.
  • 2. Mehta N, Vannozzi R. Lithium-induced electrocardiographic changes: A complete review. Clin Cardiol. 2017; 40(12): pp. 1363–1367. doi: 10.1002/clc.22822.
  • 3. Timmer RT, Sands JM. Lithium intoxication. J Am Soc Nephrol. 1999; 10(3): pp. 666–74. pmid: 10073618.
  • 4. 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.
  • 5. Le T, Bhushan V. First Aid for the USMLE Step 1 2015. McGraw-Hill Education; 2014.
  • 6. Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-Hill Education; 2014.
  • 7. Drugs.com. Lithane. https://www.drugs.com/pro/lithane.html. Updated June 1, 2006. Accessed May 22, 2017.
  • 8. 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.
  • 9. 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.
  • 10. 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.
  • 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.
  • Kaplan. USMLE Step 1 Lecture Notes 2016: Pharmacology. New York, NY: Kaplan; 2015.
last updated 04/01/2019
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