Lithium Dosing and Monitoring Protocol
Initial Dosing
For acute mania, start with lithium carbonate 600 mg three times daily (1800 mg/day total) to achieve therapeutic serum levels of 1.0-1.5 mEq/L, with elderly patients requiring substantially lower starting doses of 150 mg/day. 1, 2
Standard Adult Dosing
- Acute mania: 600 mg three times daily is the FDA-approved starting regimen for most adults 1
- Initial dose range: 450-900 mg per day (12-24 mmol) depending on age and body weight 3
- Once-daily dosing: A single evening dose using sustained-release formulations is increasingly recommended and improves tolerability with fewer renal side effects compared to divided dosing 3, 4
Special Population Adjustments
- Elderly patients (>60 years): Start at 150 mg/day due to increased sensitivity and reduced clearance; maintenance doses typically 550-740 mg daily 2, 3
- Renal impairment (GFR <60 mL/min/1.73 m²): Use lower doses with more frequent monitoring 2
- Severe renal impairment (GFR <30 mL/min/1.73 m²): Reduce dose by 50% 2
- Patients 40-60 years: Maintenance doses typically 740-925 mg daily 3
- Patients <40 years: Maintenance doses typically 925-1300 mg daily 3
Target Serum Levels
Acute Treatment Phase
- Target range: 1.0-1.5 mEq/L for acute mania 1
- Toxicity threshold: Risk begins at 1.5 mEq/L; serious toxicity occurs at >2.0 mEq/L 2
Maintenance Phase
- Target range: 0.6-1.2 mEq/L for long-term control 1
- Optimal range: 0.6-0.8 mmol/L is now generally accepted, though some favor 0.8-1.2 mmol/L 3
- Augmentation therapy: Lower levels of 0.2-0.6 mEq/L may be adequate when lithium augments antidepressants 2
- Sustained-release preparations: Keep levels in upper range (0.8-1.0 mmol/L) due to later peak concentrations 3
Monitoring Protocol
Baseline Laboratory Assessment
Before initiating lithium, obtain:
- Complete blood count 2
- Thyroid function tests (TSH, free T4) 2
- Renal function (BUN, creatinine, GFR) 2
- Serum electrolytes including calcium 2
- Urinalysis 2
Acute Phase Monitoring
- Frequency: Check serum lithium levels twice per week until levels and clinical condition stabilize 2, 1
- Timing: Draw blood samples 8-12 hours after the previous dose (immediately before next dose) when concentrations are relatively stable 1
- For once-daily dosing: Use the 24-hour trough level as the control value 3
Maintenance Phase Monitoring
- Frequency: Monitor serum lithium levels at least every two months in uncomplicated cases during remission 1
- Clinical assessment: Total reliance must not be placed on serum levels alone; accurate evaluation requires both clinical and laboratory analysis 1
Critical Contraindications and Precautions
Absolute Contraindications
Important Drug Interactions
- NSAIDs: Avoid concomitant use as they increase lithium levels and toxicity risk 2
- Concurrent medication changes: Should be avoided during lithium therapy adjustments 5
Essential Patient Counseling
- Hydration: Maintaining adequate hydration is crucial, especially during intercurrent illness 2
- Pregnancy: Lithium increases perinatal death rate and cardiovascular malformations (especially tricuspid valve abnormalities); women attempting pregnancy must notify their physician and undergo careful monitoring every three days 6
Formulation Considerations
Pharmacokinetic Differences
- Standard-release: Peak plasma concentration at 1.0-2.0 hours; bioavailability 80-100% 3
- Sustained-release: Peak at 4-5 hours; produces 30-50% reduction in peak concentrations without major changes in total exposure 3
- Brain concentrations: Approximately 50% of serum levels, occasionally reaching 75-80% 3
- Elimination half-life: 18-36 hours 3
Clinical Pitfall
Patients on twice-daily dosing require significantly higher total daily doses and experience more urinary frequency compared to once-daily dosing, despite achieving lower serum lithium levels 4. This dose-related renal adverse effect can be mitigated by switching to once-daily evening dosing with sustained-release formulations.