What is the appropriate initial lithium dose and titration plan for adults (including elderly or patients with reduced renal function) and for children, and what baseline and follow‑up laboratory monitoring is required?

Lithium Starting Dose and Titration

Initial Dosing for Adults

For adults with normal renal function, start lithium carbonate at 450-900 mg per day (12-24 mmol), typically divided into two doses, with the initial dose determined by age and body weight. 1

Age-Based Starting Doses

• Adults <40 years: Start 450-900 mg daily, targeting maintenance of 925-1300 mg daily (25-35 mmol) 1
• Adults 40-60 years: Start 450-750 mg daily, targeting maintenance of 740-925 mg daily (20-25 mmol) 1
• Adults >60 years: Start 300-450 mg daily, targeting maintenance of 550-740 mg daily (15-20 mmol) 1

Dosing Schedule

• Standard-release formulations: Administer twice daily (morning and evening), avoiding three-times-daily schedules due to poor compliance with midday doses 1
• Sustained-release formulations: Can be given once daily in the evening or twice daily 1

Initial Dosing for Elderly and Reduced Renal Function

For elderly patients or those with renal impairment, start with 0.125 mg (125 mcg) to 0.25 mg once daily, with dose adjustments based on renal function. 2

• Severe renal impairment (eGFR <30 mL/min/1.73 m²): Lithium is relatively contraindicated; if used, start at the lowest possible dose and monitor at least monthly 3
• Moderate renal impairment (eGFR 30-60 mL/min/1.73 m²): Reduce starting dose by 50% and extend dosing intervals rather than increasing individual doses 2
• Octogenarians: Mean therapeutic levels of 0.42 mmol/L are effective and well-tolerated, requiring lower doses than younger adults 4

Initial Dosing for Children

For pediatric patients, the American Academy of Child and Adolescent Psychiatry recommends starting at a low dose and titrating by 150-300 mg increments to achieve therapeutic levels of 0.6-0.8 mmol/L. 5

• Pediatric patients may require relatively higher doses per kilogram of body weight compared to adults 5
• Dose adjustments should be made every 5-7 days based on serum levels and clinical response 5

Titration Plan

Monitoring During Acute Phase

• Check serum lithium levels twice weekly until both the serum level and clinical condition stabilize 3
• Draw levels 12 hours after the last dose for standard-release formulations, or 24 hours after the last dose for once-daily administration 1
• Steady-state is reached after 7-8 days (approximately 5-7 half-lives), at which point dose adjustments can be made 3

Target Therapeutic Ranges

• Standard-release formulations: 0.6-0.8 mmol/L for maintenance; 1.0-1.5 mmol/L for acute mania 3, 1
• Sustained-release formulations: 0.8-1.0 mmol/L (upper range) due to later peak concentrations 1
• Elderly or augmentation strategies: 0.2-0.6 mmol/L may be appropriate 3

Dose Adjustment Strategy

• Increase doses by 150-300 mg increments based on serum levels and clinical response 5
• Recheck levels 5-7 days after each dose adjustment 5
• In renal impairment, extend dosing intervals (e.g., once daily or every other day) rather than increasing individual doses to avoid toxic peak concentrations 2

Baseline Laboratory Monitoring

Before initiating lithium, obtain the following baseline tests: 3

• Complete blood count with differential 3
• Comprehensive metabolic panel including serum electrolytes, blood urea nitrogen, and serum creatinine with estimated glomerular filtration rate (eGFR) 3
• Thyroid function tests (TSH, free T4) 3
• Urinalysis 3
• Serum calcium levels 3
• Fasting glucose or glycated hemoglobin 3
• Pregnancy test in all women of childbearing potential 3

Follow-Up Laboratory Monitoring

During Acute Treatment Phase

• Serum lithium levels: Twice weekly until stable 3
• Renal function and electrolytes: 2-4 weeks after initiation to capture early changes 3
• Recheck 1-2 weeks after any dose adjustment 3

During Maintenance Phase (Stable Patients)

• Serum lithium levels: Every 3 months 3
• Renal function (eGFR, creatinine), electrolytes, thyroid function (TSH), and calcium: Every 6 months 3
• Weight and blood pressure: Annually 3

Intensified Monitoring Situations

Increase monitoring frequency to 1-2 weeks after: 3

• Dose adjustments
• Addition of interacting medications (NSAIDs, ACE inhibitors, ARBs, thiazide diuretics)
• Changes in renal function
• Significant weight changes
• Development of acute illness

Patients with Reduced Renal Function

• eGFR 30-60 mL/min/1.73 m²: Monitor more frequently than standard 3-6 month intervals 3
• eGFR <30 mL/min/1.73 m²: Monitor at least monthly 3

Critical Thresholds Requiring Action

Creatinine Changes

• Increase ≤30% from baseline: Acceptable, continue monitoring 3
• Increase >50% or >266 μmol/L: Review other nephrotoxic medications and consider dose reduction 3
• Increase >100% or >310 μmol/L: Discontinue lithium 3

Electrolyte Abnormalities

• Potassium >5.5 mmol/L: Review lithium dose and consider temporary discontinuation 3

Thyroid Dysfunction

• Women under 60 years are at higher risk for thyroid dysfunction (20-30% develop hypothyroidism on long-term therapy) and may warrant more frequent monitoring 3

Hypercalcemia

• Occurs in approximately 25% of long-term lithium patients; check parathyroid hormone if calcium is elevated 3

Common Pitfalls and How to Avoid Them

Drug Interactions

Avoid concomitant NSAIDs due to significant nephrotoxicity risk and reduced lithium clearance 3

• NSAIDs, ACE inhibitors, ARBs, and thiazide diuretics all increase lithium toxicity risk and require increased monitoring frequency 3

Hydration and Acute Illness

• Maintain adequate hydration during intercurrent illness 3
• Temporarily discontinue lithium if the patient develops serious intercurrent illness that increases acute kidney injury risk (especially if eGFR <60 mL/min/1.73 m²) 3
• Check levels more frequently during illness 3

Restarting After Interruption

• After a one-week interruption, restart at 50-75% of the previous maintenance dose and retitrate gradually based on clinical response and serum levels 6
• Patients with normal renal function who are not taking interacting medications may restart at the full previous dose, but those on NSAIDs, thiazide diuretics, or with acute illness should avoid restarting due to increased toxicity risk 3

Pregnancy Considerations

• Lithium is teratogenic in the first trimester 7
• Lithium clearance increases by 30-50% during the last months of pregnancy due to increased glomerular filtration rate, requiring dose adjustments 1
• Lithium passes freely into breast milk 1