- Lithium has been used since the 1800s as a treatment for gout and Seizure Disorder and as of 1900s for mania
- Pregnancy
- Associated with Ebstein Anomaly when exposure in first trimester
- Lithium may increase CNS Serotonin levels
- Neuroprotective effect
- Decreases intracellular Inositol monophosphate concentrations
- Mood stabilization effect
- Inhibits Glycogen Synthase Kinase 3 (GSK3B)
- Enzyme involved in Neuronal development and Energy Metabolism
- GSK3B overexpression may be associated with Bipolar Disorder
- Lithium Carbonate is a simple salt that is excreted and not metabolized
- Lithium is an alkali metal (the smallest metal, having atomic number 3)
- Steady state reached in 5 days
- Check Lithium levels 5 days after starting dose or changing dose
- Steady state will take >5 days to reach in the elderly or reduced Renal Function
- Blood levels peak
- Following immediate release dose: 1-2 hours
- Following sustained release dose: 4-6 hours
- Therapeutic Trough levels
- Narrow therapeutic window (low threshold for toxicity)
- Acute mania: 1.0 to 1.2 meq/L
- Maintenance Bipolar Disorder: 0.8 to 1.0 meq/liter
- Increasing dose 300 mg/day raises level 0.2 meq/L
- Excretion
- Renal excretion (and 60% reabsorbed at proximal tubules)
- Drug Clearance is directly proportional to GFR
- Lithium Carbonate (immediate release)
- Capsules or Tablet: 150 mg, 300 mg, 600 mg
- Oral Solution: 8 mEq/5 ml (8 mEq = 300 mg)
- Syrup: 300 mg/ 5 ml
- Extended Release (Lithobid; Eskalith): 300 mg, 450 mg
- Adults
- Precautions
- Maintain oral hydration and avoid Salt Restriction
- Adverse effects are reduced by dividing doses 3-4 times daily and by using extended release forms
- Start: 300 mg orally twice daily
- May adjust dose every 2-3 days as tolerated
- Effective dose
- Target 900 to 1800 mg per day divided twice daily (or 3-4 times daily)
- Acute Mania: 1800 mg/day divided 2 to 3 times daily orally
- Bipolar Maintenance: 900 to 1200 mg/day divided 2 to 3 times daily
- Titration based on trough serum Lithium concentration
- Acute Therapy: 0.8 to 1.2 mEq/L
- Maintenance: 0.6 to 1 mEq/L
- Children
- FDA approved for children ages 7 years and older
- Precautions
- Maintain oral hydration and avoid Salt Restriction
- Weight 20 to 30 kg
- Start 300 mg capsules (or 8 mEq of solution) orally twice daily
- Weight >30 kg
- Start 300 mg capsules (or 8 mEq of solution) orally three times daily
- Titration based on trough serum Lithium concentration
- Acute Therapy: 0.8 to 1.2 mEq/L
- Maintenance: 0.8 to 1 mEq/L
- General
- Polyuria
-
Hypothyroidism
- Often reversible on stopping Lithium
- Higher Prevalence in women and with increasing age
- Weight gain
- Fine Tremor
- Withdrawal symptoms on stopping
- More common than with Valproate or Lamotrigine
- Toxicity
- Avoid in Lactation
- Pregnancy Category D
- Highly Teratogenic
- Associated with Ebstein Anomaly when exposure in first trimester
- Drugs that increase Lithium levels
- Serum Lithium level
- Day 5 after starting Lithium
- Then every 1-2 weeks initially
- Then every 3-6 months
- Also check serum levels before and 5 days after dose changes
- Other labs
- Schedule
- Baseline
- Month 3
- Month 6
- Every 6 to 12 months thereafter
- Thyroid Stimulating Hormone (TSH)
- Renal Function tests
- Schedule
- Lithium Immediate Release
- Lithium Extended Release
- Perrone and Chatterjee (2018) UpToDate, accessed 8/20/2018