• Clinical science

Lithium

Abstract

Lithium is a psychiatric medication used primarily as first-line therapy for bipolar affective disorders. It is also indicated in treatment-resistant depression (TRD) and reduces the risk of suicide in depressive patients. The specific mechanism by which lithium acts to stabilize mood is still not definitively known. It is thought to be due to the inhibition of the phosphoinositide cascade causing a decrease in cyclic adenosine monophosphate (cAMP) levels. Short-term side effects of lithium are predominantly gastrointestinal, while long-term side effects involve neurological symptoms. Lithium therapy has a very narrow therapeutic index; frequent monitoring is therefore required to prevent toxicity.

Side effects

Gastrointestinal
CNS and peripheral nervous system
  • Fine tremors → can be treated with propranolol (β-blocker)
  • Hyperreflexia
  • Decreases the seizure threshold (esp. if predisposing lesions exist)
  • Weight gain
Thyroid
Renal
Cardiovascular
Skin

Lithium intoxication

  • Etiology: serum lithium levels > 1.5 mEq/L / 1.5–2.0 mmol/L
    • Overdosage due to frequent intake
    • Renal impairment
    • Low sodium diet or increased perspiration
    • Diuretic therapy (e.g., loop or thiazide diuretics)
  • Pathophysiology: : impaired concentration of urine (due to lithium nephropathy) + uncompensated fluid losses (due to confusion or disabling comorbidities) → severe dehydrationlithium toxicity
  • Clinical features
    • Lithium intoxication can be explained under three categories, as follows
      • Acute toxicity: : seen in patients with a low tissue level of lithium (not on regular therapy), who have acutely taken a large dose
      • Acute on chronic toxicity: : seen in patients who are on chronic lithium therapy with a low tissue level, but have taken a larger dose acutely
      • Chronic toxicity: : seen in patients with a high tissue level of the drug; (long term treatment) with recent high doses; , or the introduction of new therapy that exacerbates lithium effects
    • System-specific description of features
      • Neurological (earliest and predominant feature): dysarthria, vertigo, ataxia, nystagmus; (especially downbeat nystagmus), dysdiadochokinesia, tremor, somnolence, delirium.
      • Neuromuscular: fine tremors, muscle twitches (fasciculations)
      • Gastrointestinal: vomiting, diarrhea, abdominal pain
      • Psychiatric: apathy, psychomotor impairment
      • Others : dysrhythmias, renal failure with oliguria, myxedema coma
  • Treatment
    • Symptomatic therapy
      • Correct fluid and electrolyte balance
      • Ventilatory support, if required
      • Treat seizures and/or dysrhythmias
    • In severe intoxication
      • IV fluid therapy: 0.9% NaCl solution (possibly in combination with forced diuresis)
      • Hemodialysis
        • Indications
          • Serum lithium concentration > 4.0 mEq/L
          • 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 mininum of 6 hours (if serum lithium concentration cannot be measured)

Lithium has a narrow therapeutic window!

References:[1][2][3][4][5][6][7]

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

Indications

References:[1][2][3]

Contraindications

If prophylaxis of a bipolar disorder is needed in a case with an absolute contraindication against lithium, anticonvulsants (e.g., lamotrigine) can be used as an alternative drug!

References:[3][8]

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

Guidelines & therapy recommendations

  • Monitoring serum levels of lithium is important because of its narrow therapeutic window.
  • Consistent serum levels are usually expected after 5–7 days.
  • Due to its slow onset of action, effects are expected 1–2 weeks after initiation of treatment.
  • Optimal range of lithium serum level: 0.5–0.8 mmol/L for long-term treatment and 1.0–1.2 mmol/L for short-term treatment
  • How to implement lithium monitoring
    • Lithium serum level: every 6–8 weeks (weekly controls when initiating lithium treatment)
    • Half-time: 12–24 hours → Blood sample for serum level monitoring should be taken just before pill intake. If that is not possible, a blood sample should be taken 12 hours after pill intake!
  • Suggested dosage: lithium 2–3 time daily

Special patient groups

Before prescribing lithium in young women, evaluate thyroid function, renal function, and human chorionic gonadotropin levels to rule out pregnancy!

References:[3]

  • 1. Le T, Bhushan V. First Aid for the USMLE Step 1 2015. McGraw-Hill Education; 2014.
  • 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. 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.
  • 5. 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.
  • 6. 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.
  • 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. 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 11/30/2018
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