Lithium Dose Titration Strategy
Increase lithium carbonate by 300 mg increments (typically from 300 mg three times daily to 600 mg three times daily), checking serum levels twice weekly during acute treatment until therapeutic levels of 1.0-1.5 mEq/L are achieved for acute mania, or 0.6-1.2 mEq/L for maintenance therapy. 1
Initial Dosing and Titration Protocol
Standard Adult Dosing
- Start with 300 mg three times daily (900 mg/day total) for most adults under 40 years old 1, 2
- For patients 40-60 years: start with 600-750 mg/day in divided doses 2
- For patients over 60 years: start with 450-600 mg/day in divided doses 2
- Increase by 300 mg increments (adding one 300 mg dose) every 3-7 days based on serum levels and clinical response 1
Target Therapeutic Levels
- Acute mania: 1.0-1.5 mEq/L (typically requires 600 mg three times daily = 1800 mg/day) 1
- Maintenance therapy: 0.6-1.2 mEq/L (typically requires 300 mg three or four times daily = 900-1200 mg/day) 1
- Augmentation of antidepressants: 0.2-0.6 mEq/L (lower doses of 150 mg twice daily may suffice) 3
Monitoring During Dose Adjustments
Acute Phase Monitoring
- Check serum lithium levels twice per week until both serum level and clinical condition stabilize 1, 3
- Draw blood samples 8-12 hours after the previous dose (trough level) 1
- Increase monitoring to 1-2 weeks after each dose adjustment 3
Critical Safety Thresholds
- Toxicity begins at 1.5 mEq/L 4
- Serious toxicity occurs at >2.0 mEq/L 4, 5
- Serum levels of 1.5-2.0 mEq/L may cause mild, reversible toxic effects on kidney, liver, heart, and glands 5
- Levels >2 mEq/L may cause neurological symptoms including cerebellar dysfunction 5
Special Population Adjustments
Elderly Patients
- Use lower starting doses (150-300 mg twice daily) as elderly patients often exhibit toxicity at levels ordinarily tolerated by younger patients 1
- Target maintenance levels of 0.5-0.8 mEq/L rather than standard 0.6-1.2 mEq/L 3
- Increase by smaller increments (150 mg) every 5-7 days 2
Renal Impairment
- GFR 30-60 mL/min/1.73 m²: Reduce dose by 25-50%, monitor monthly, and extend dosing intervals rather than reducing individual doses 3, 4
- GFR <30 mL/min/1.73 m²: Reduce dose by 50%, consider risk-benefit of continuing lithium, monitor at least monthly 3
- Extend dosing intervals (e.g., from twice daily to once daily, or once daily to every other day) rather than reducing individual dose amounts to avoid subtherapeutic troughs 3
Dosing Schedule Considerations
Once-Daily vs. Multiple Daily Doses
- Once-daily evening dosing with sustained-release formulation improves compliance and may reduce side effects, particularly urinary frequency 2, 6
- Once-daily dosing reduces urinary frequency compared to twice-daily dosing 6
- With sustained-release preparations, target the upper range of therapeutic levels (0.8-1.0 mEq/L) rather than 0.6-0.8 mEq/L for standard formulations 2
- For once-daily dosing, draw serum levels at 24 hours post-dose rather than 12 hours 2
Common Pitfalls to Avoid
Drug Interactions Requiring Dose Adjustment
- NSAIDs decrease lithium clearance by 25-40% and should be avoided; if unavoidable, reduce lithium dose and monitor weekly 7, 3, 8
- Thiazide diuretics increase lithium levels by 25-40%; reduce lithium dose by 25-50% when starting thiazides 8
- ACE inhibitors and ARBs may impair lithium elimination; increase monitoring frequency to weekly when initiating these medications 3, 8
Situations Requiring Temporary Discontinuation
- Serious intercurrent illness that increases acute kidney injury risk (especially if GFR <60 mL/min/1.73 m²) 7, 3
- Maintain hydration during illness and check levels more frequently 3