What is the starting dose of lithium and its common side effects?

Lithium Starting Dose and Side Effects

Starting Dose

The recommended initial lithium carbonate dose is 450-900 mg per day (12-24 mmol), adjusted based on age and body weight, with lower starting doses of 300-450 mg/day appropriate for elderly patients or those at higher risk of toxicity. 1

Age-Based Dosing Strategy:

• Patients <40 years: Start 450-900 mg/day, targeting maintenance of 925-1300 mg/day 1
• Patients 40-60 years: Start lower end of range, targeting maintenance of 740-925 mg/day 1
• Patients >60 years: Start 300-450 mg/day, targeting maintenance of 550-740 mg/day 1

Dosing Schedule:

• Once-daily dosing (single evening dose) is preferred for improved tolerability and compliance, particularly reducing urinary frequency compared to divided dosing 2
• Sustained-release formulations allow twice-daily dosing and reduce peak plasma concentrations by 30-50% without changing overall exposure 1
• Target serum levels: 0.6-0.8 mmol/L (some sources suggest 0.8-1.2 mmol/L for acute treatment) 1, 3

Critical Monitoring Requirements:

• Serum lithium levels must be checked twice weekly during initiation until stable 4, 5
• Draw levels 12 hours post-dose for standard formulations, or 24 hours post-dose for once-daily regimens 1
• Baseline labs required: Complete blood count, thyroid function, urinalysis, BUN, creatinine, serum calcium, and electrolytes 5
• Ongoing monitoring every 3-6 months: GFR, electrolytes, lithium levels, and thyroid function once stable 4, 5

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Common Side Effects

Renal Effects (Most Clinically Significant):

• Polyuria and polydipsia are common, with twice-daily dosing causing significantly higher urinary frequency than once-daily 2
• Nephrotoxicity may occur even at therapeutic levels with prolonged use, causing renal tubular dysfunction 4
• Renal impairment is a contraindication to lithium use 1

Neurological Effects:

• Tremor, cognitive slowing, and impaired memory occur commonly, particularly affecting vigilance, alertness, learning, and short-term memory with long-term use 1
• Dysarthria may worsen in patients with pre-existing speech disorders 6, 5
• Elderly patients are particularly prone to neurotoxicity at higher doses 4
• Cerebellar dysfunction can occur at toxic levels >2 mmol/L 7

Endocrine Effects:

• Thyroid dysfunction requires regular monitoring 5

Cardiovascular Effects:

• Bradycardia, T-wave changes, and AV block have been described 8
• QT prolongation effects are divergent in reports 8

Hematologic Effects:

• Granulocytosis and lymphopenia are expected effects 7

Gastrointestinal Effects:

• Nausea and GI upset, though sustained-release or once-daily formulations significantly reduce GI side effects 1, 2

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Critical Safety Warnings

Narrow Therapeutic Index:

• Toxicity occurs at doses close to therapeutic levels (>1.5 mmol/L causes mild reversible toxicity; >2 mmol/L causes neurological symptoms; prolonged levels >2 mmol/L cause permanent brain damage) 4, 7

Drug Interactions:

• Avoid NSAIDs—they decrease lithium clearance and increase toxicity risk 4
• Caution with antiarrhythmics and other medications affecting renal function 8

Special Populations:

• Pregnancy: May cause fetal harm based on animal and limited human studies 4
• Breastfeeding: Lithium passes freely into breast milk 1
• Renal impairment: Contraindication due to decreased clearance 1
• Elderly: Require lower doses and more frequent monitoring due to neurotoxicity risk 4, 1

Patient Education:

• Patients must be educated about early signs of lithium toxicity (tremor, confusion, ataxia, worsening speech) to facilitate prompt intervention 5
• Maintain adequate hydration and consistent sodium intake 1