Lithium Carbonate

Lithium has been used since the 1800s as a treatment for gout and Seizure Disorder and as of 1900s for mania

Lithium may increase CNS Serotonin levels
Neuroprotective effect
Decreases intracellular Inositol monophosphate concentrations
1. Mood stabilization effect
Inhibits Glycogen Synthase Kinase 3 (GSK3B)
1. Enzyme involved in Neuronal development and Energy Metabolism
2. GSK3B overexpression may be associated with Bipolar Disorder

Lithium Carbonate is a simple salt that is excreted and not metabolized
1. Lithium is an alkali metal (the smallest metal, having atomic number 3)
Steady state reached in 5 days
1. Check Lithium levels 5 days after starting dose or changing dose
2. Steady state will take >5 days to reach in the elderly or reduced Renal Function
Blood levels peak
1. Following immediate release dose: 1-2 hours
2. Following sustained release dose: 4-6 hours
Therapeutic Trough levels
1. Narrow therapeutic window (low threshold for toxicity)
2. Acute mania: 1.0 to 1.2 meq/L
3. Maintenance Bipolar Disorder: 0.8 to 1.0 meq/liter
4. Increasing dose 300 mg/day raises level 0.2 meq/L
Excretion
1. Renal excretion (and 60% reabsorbed at proximal tubules)
2. Drug Clearance is directly proportional to GFR

Lithium Carbonate (immediate release)
1. Capsules or Tablet: 150 mg, 300 mg, 600 mg
2. Oral Solution: 8 mEq/5 ml (8 mEq = 300 mg)
3. Syrup: 300 mg/ 5 ml
Extended Release (Lithobid; Eskalith): 300 mg, 450 mg

Precautions
1. Maintain oral hydration and avoid Salt Restriction
2. Adverse effects are reduced by dividing doses 3-4 times daily and by using extended release forms
Start: 300 mg orally twice daily
1. May adjust dose every 2-3 days as tolerated
Effective dose
1. Target 900 to 1800 mg per day divided twice daily (or 3-4 times daily)
2. Acute Mania: 1800 mg/day divided 2 to 3 times daily orally
3. Bipolar Maintenance: 900 to 1200 mg/day divided 2 to 3 times daily
Titration based on trough serum Lithium concentration
1. Acute Therapy: 0.8 to 1.2 mEq/L
2. Maintenance: 0.6 to 1 mEq/L

FDA approved for children ages 7 years and older
Precautions
1. Maintain oral hydration and avoid Salt Restriction
Weight 20 to 30 kg
1. Start 300 mg capsules (or 8 mEq of solution) orally twice daily
Weight >30 kg
1. Start 300 mg capsules (or 8 mEq of solution) orally three times daily
Titration based on trough serum Lithium concentration
1. Acute Therapy: 0.8 to 1.2 mEq/L
2. Maintenance: 0.8 to 1 mEq/L

Polyuria
Hypothyroidism
1. Often reversible on stopping Lithium
2. Higher Prevalence in women and with increasing age
Weight gain
Fine Tremor
Withdrawal symptoms on stopping
1. More common than with Valproate or Lamotrigine

Avoid in Lactation
Pregnancy Category D
1. Highly Teratogenic
2. Associated with Ebstein Anomaly when exposure in first trimester

Serum Lithium level
1. Day 5 after starting Lithium
2. Then every 1-2 weeks initially
3. Then every 3-6 months
4. Also check serum levels before and 5 days after dose changes
Other labs
1. Schedule
  1. Baseline
  2. Month 3
  3. Month 6
  4. Every 6 to 12 months thereafter
2. Thyroid Stimulating Hormone (TSH)
3. Renal Function tests
  1. Serum Creatinine
  2. Blood Urea Nitrogen