What is the proper protocol for prescribing and managing lithium (lithium carbonate) therapy?

Lithium Prescribing and Management Protocol

Initial Assessment and Baseline Testing

Before initiating lithium, obtain comprehensive baseline laboratory work including complete blood count, thyroid function tests (TSH, free T4), renal function (BUN, creatinine, GFR), serum electrolytes including calcium, and urinalysis. 1

Contraindications to Screen For:

• Significant renal impairment (GFR < 60 ml/min/1.73 m² requires special consideration) 1, 2
• Cardiovascular disease 1, 2
• Severe dehydration or sodium depletion 1, 2
• Current diuretic use (lithium toxicity risk is very high) 2

If the psychiatric indication is life-threatening and the patient has these contraindications, lithium may only be used with daily serum level monitoring, hospitalization, and extremely low doses. 2

Starting Doses

Standard Adult Dosing:

• For acute mania, start with 600 mg three times daily (1800 mg/day total) to achieve therapeutic serum levels of 1.0-1.5 mEq/L. 2
• For patients under 40 years: 925-1300 mg daily (25-35 mmol) 3
• For patients 40-60 years: 740-925 mg daily (20-25 mmol) 3

Special Populations:

• Elderly patients: Start with 150 mg/day due to increased sensitivity and reduced clearance. 1
• Patients over 60 years: 550-740 mg daily (15-20 mmol) 3
• GFR 30-60 ml/min/1.73 m²: Use lower doses with more frequent monitoring 1, 4
• GFR < 30 ml/min/1.73 m²: Reduce dose by 50% 1, 4

Augmentation Strategy:

• When augmenting antidepressants, lower blood levels (0.2-0.6 mEq/L) may be adequate, achieved with 300-450 mg/day. 1, 5

Therapeutic Monitoring Schedule

Acute Phase:

Check serum lithium levels twice per week until levels and clinical condition stabilize. 1, 2

Maintenance Phase:

Monitor serum lithium levels at least every two months in uncomplicated cases during remission. 2

Timing of Blood Draws:

Draw blood samples 8-12 hours after the previous dose (trough level) when lithium concentrations are relatively stable. 2 For once-daily dosing, draw at 24 hours post-dose. 3

Target Therapeutic Ranges

Acute Mania:

• Target: 1.0-1.5 mEq/L 2

Long-term Maintenance:

• Target: 0.6-1.2 mEq/L 2
• Some evidence supports 0.6-0.8 mEq/L as adequate for most patients 3

Antidepressant Augmentation:

• Target: 0.2-0.6 mEq/L (lower levels may be effective) 1, 5

Toxicity Recognition and Prevention

Critical Toxicity Thresholds:

Toxicity risk begins at 1.5 mEq/L, with serious toxicity occurring at >2.0 mEq/L. 1, 4 This narrow therapeutic window means toxicity can occur at doses close to therapeutic levels. 1

Patients Abnormally Sensitive to Lithium:

Some patients exhibit toxic signs at serum levels of 1.0-1.5 mEq/L, particularly elderly patients who often require reduced dosages. 2

Key Safety Measures:

• Avoid concomitant NSAIDs as they increase lithium levels and toxicity risk 1
• Maintain adequate hydration, especially during intercurrent illness 1
• Ensure stable sodium intake (sodium depletion increases lithium retention) 2
• Do not rely solely on serum levels—accurate evaluation requires both clinical and laboratory analysis 2

Ongoing Monitoring Beyond Lithium Levels

Renal Function:

• Monitor creatinine and GFR regularly, as lithium clearance decreases with aging 3
• Renal concentrating capacity may be reduced over time 6

Thyroid Function:

• Periodic TSH and free T4 monitoring (lithium affects thyroid function) 1

Calcium and PTH:

• Monitor serum calcium, as lithium lowers urinary calcium excretion and increases serum calcium concentrations 6

Special Clinical Situations

Pregnancy:

Lithium use in early pregnancy is associated with increased cardiovascular anomalies in newborns, particularly tricuspid valve abnormalities. 6 Women on lithium who plan pregnancy must notify their physician immediately. 6 Lithium clearance increases by 30-50% during the last months of pregnancy due to increased GFR. 3

Breastfeeding:

Lithium passes freely into breast milk. 3

Dosing Schedule Considerations

Administer lithium two to three times daily for standard formulations, or once daily in the evening for sustained-release preparations. 3 Sustained-release formulations reduce peak plasma concentrations by 30-50% and should target the upper therapeutic range (0.8-1.0 mEq/L rather than 0.6-0.8 mEq/L). 3

Response Timeline

Most patients who respond to lithium augmentation do so rapidly (within 7 days), though some may require 3-6 weeks of combined treatment. 7, 5 In augmentation studies, 76% of responders showed improvement within one week. 5