When starting lithium in a patient, which baseline laboratory tests and monitoring (renal function, electrolytes, thyroid function, complete blood count, pregnancy test, ECG if cardiac risk) are required before and during therapy, and what is the recommended initial dose?

Lithium Initiation and Monitoring Protocol

Baseline Laboratory Testing Required Before Starting Lithium

Before prescribing the first dose of lithium, you must obtain a comprehensive baseline laboratory panel including complete blood count, serum electrolytes, blood urea nitrogen, serum creatinine with estimated glomerular filtration rate (eGFR), thyroid function tests (TSH and free T4), fasting glucose or glycated hemoglobin, serum calcium, urinalysis, and a pregnancy test in all individuals of childbearing potential. 1

Critical Baseline Tests:

• Renal function: BUN, creatinine, eGFR, urinalysis 1, 2
• Thyroid function: TSH, free T4 1, 2
• Electrolytes: Sodium, potassium (correct hypokalemia before starting) 1
• Serum calcium: To establish baseline for parathyroid monitoring 1
• Complete blood count: Particularly if history of blood disorders 2
• Pregnancy test: Mandatory in women of childbearing potential 1
• ECG: Required if age >40 years, cardiac risk factors present, or combining with QT-prolonging drugs 1

Additional Baseline Assessments:

• Metabolic parameters: Fasting glucose or HbA1c, lipid panel 1
• Body mass index and blood pressure 1

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Initial Lithium Dosing Strategy

For adults with normal renal function, start lithium carbonate at 300 mg three times daily (900 mg/day total) if weight ≥30 kg, or 300 mg twice daily (600 mg/day) if weight <30 kg, with the goal of reaching therapeutic levels of 0.8-1.2 mEq/L for acute mania treatment. 3, 1

Standard Adult Dosing:

• Age <40 years: Initial dose 450-900 mg/day, maintenance typically 925-1300 mg/day 4
• Age 40-60 years: Initial dose 450-900 mg/day, maintenance typically 740-925 mg/day 4
• Age >60 years: Initial dose 300-600 mg/day, maintenance typically 550-740 mg/day 4

Special Populations:

• Elderly or renally impaired: Start with 125-250 mg once daily, extend dosing intervals rather than increasing individual doses 1
• Moderate renal impairment (eGFR 30-60): Start at 50% of usual dose, use once-daily dosing 1
• Severe renal impairment (eGFR <30): Lithium is generally contraindicated; if used, requires at least monthly monitoring 1

Dosing Schedule Options:

• Twice daily: Standard approach with immediate-release formulations 4
• Once daily (evening): Acceptable with sustained-release formulations, may improve compliance 4, 1
• Three times daily: Traditional but midday compliance is questionable 4

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Monitoring Schedule During Treatment

Acute Phase (First 4-8 Weeks):

Check serum lithium levels twice per week until both the laboratory level and clinical symptoms stabilize, then reduce monitoring frequency. 1, 2

• First lithium level: Draw 5-7 days after starting or any dose change (after reaching steady state) 1, 4
• Timing of blood draw: Exactly 12 hours after last dose for twice-daily dosing, or 24 hours after dose for once-daily regimens 4, 1
• Target range for acute mania: 0.8-1.2 mEq/L (some patients respond at 0.6-0.8 mEq/L) 4, 5, 1
• Renal function check: Repeat creatinine 2-4 weeks after initiation to capture early changes 1

Dose Adjustments:

• Increase by 300 mg/day weekly until therapeutic levels achieved or response criteria met 3, 1
• Monitor more frequently (every 1-2 weeks) after dose adjustments, addition of interacting medications, changes in renal function, or significant weight changes 1

Maintenance Phase (After Stabilization):

Once stable, monitor serum lithium levels, renal function (BUN, creatinine), thyroid function (TSH), and urinalysis every 3-6 months. 1, 2

• Lithium levels: Every 3-6 months 1
• Renal function: Creatinine, eGFR every 3-6 months 1
• Thyroid function: TSH annually (more frequently in women <60 years who are at higher risk) 1, 6
• Serum calcium: Every 6 months (hypercalcemia occurs in ~25% of long-term users) 1
• Weight and blood pressure: Annually 1
• Target maintenance level: 0.6-1.0 mEq/L 4, 1

High-Risk Situations Requiring Intensified Monitoring:

• Patients taking NSAIDs, ACE inhibitors, ARBs, or thiazide diuretics: Increase monitoring frequency due to elevated toxicity risk 1
• eGFR <60 mL/min/1.73 m²: More frequent than standard 3-6 month intervals 1
• eGFR <30 mL/min/1.73 m²: Monitor at least monthly 1
• Intercurrent illness: Check levels more frequently, maintain hydration 1

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Critical Thresholds and Actions

Renal Function Changes:

• Creatinine increase ≤30% from baseline: Acceptable, continue monitoring 1
• Creatinine increase >50% or >266 μmol/L: Review nephrotoxic medications, consider dose reduction 1
• Creatinine increase >100% or >310 μmol/L: Discontinue lithium 1

Electrolyte Abnormalities:

• Potassium >5.5 mmol/L: Review lithium dose, consider temporary discontinuation 1
• Hypokalemia or hypomagnesemia: Must be corrected before lithium initiation 1

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Common Pitfalls to Avoid

• Never wait beyond 7-8 days to check initial levels – steady state is achieved by then and delays necessary dose adjustments 1
• Avoid checking levels too early – lithium requires 5-7 half-lives (7-10 days) to reach steady state 1
• Do not use extremely low starting doses (150 mg twice daily) unless elderly or augmentation strategy – this produces subtherapeutic levels of 0.2-0.6 mEq/L inadequate for acute bipolar disorder 1
• Never discontinue lithium abruptly – taper over minimum 2-4 weeks to prevent rebound mania (>90% relapse rate with abrupt stop) 2
• Avoid concomitant NSAIDs – dramatically increases nephrotoxicity risk 1
• Do not delay treatment waiting for baseline labs in acute mania – can start antipsychotic immediately while ordering labs 2
• Ensure adequate hydration and salt intake – dehydration and sodium depletion increase lithium levels 1

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Drug Interactions Requiring Increased Monitoring

• NSAIDs: Decrease lithium clearance, increase toxicity risk 1
• ACE inhibitors/ARBs: Increase lithium levels 1
• Thiazide diuretics: Significantly increase lithium retention 1
• Loop diuretics: Less interaction than thiazides but still require monitoring 1

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Patient Education Essentials

• Signs of lithium toxicity: Fine tremor, nausea, diarrhea (early); coarse tremor, confusion, ataxia (seek immediate care) 2
• Maintain consistent fluid and salt intake – avoid dehydration 1
• Secure medication storage – lithium overdoses can be lethal, especially critical in suicidal patients 2
• Medication adherence is critical – >90% of noncompliant patients relapse vs. 37.5% of compliant patients 2