Pharm 101: Lithium

Class

Mood stabiliser

Pharmacodynamics

• Mechanism of action uncertain
• Suppresses inositol signalling and inhibits glycogen synthase kinase-3 (GSK-3), a multifunctional protein kinase
• No significant antagonistic actions on CNS or autonomic nervous system receptors

Pharmacokinetics

• Bioavailability 100%
• Complete absorption within 6-8 hours, peak plasma levels 30-120 minutes
• Volume of distribution initially 0.5L/kg, rising to 0.7-0.9L/kg (distributes in total body water)
• No protein binding
• No metabolism
• Half life 20 hours
• Renal excretion
  • Clearance is 20% of creatinine
  • Lithium excretion is reduced by proximal tubular reabsorption
  • Drugs such as thiazide diuretics increase activity of this resorptive mechanism and can precipitate lithium toxicity
  • NSAIDs and ACE-inhibitors also increase plasma levels

Clinical uses

• Bipolar Affective Disorder
• Recurrent depression with a cyclic pattern
• Can be used in combination with other therapies to treat acute major depression and schizoaffective disorder
• Requires serum monitoring:
  • Therapeutic concentration 0.6-1.4 mmol/L
  • Initial levels or levels following dosage adjustments should be taken 5 days after initiation of treatment
  • Levels should be measured 10-12 hours after last dose
  • Treatment of toxicity is supportive and haemodialysis

Adverse effects

• Neurological:
  • Tremor
  • Ataxia
  • Psychiatric disturbances at toxic concentrations
• Endocrine:
  • Hypothyroidism
  • Diabetes insipidus
• Renal dysfunction
• Edema
• Cardiac adverse events:
  • Sick sinus syndrome is a contraindication to use because Lithium further depresses the sinus node
  • T-wave flattening is often seen on ECG with Lithium use but is of uncertain signicance
• Pregnancy:
  • Ebstein’s anomaly (further research required to establish certainty regarding this)
  • Increased clearance during pregnancy
  • Passage in breast milk can predispose newborns to Lithium toxicity

Further Reading

• Long N. Lithium Toxicity. LITFL
• Rotella J. Lithium, Vomiting and Diarrhoea. LITFL