How do I initiate lithium therapy in an adult with bipolar disorder, including baseline renal, thyroid, electrolyte, calcium, CBC labs, ECG criteria, dosing schedule, target serum lithium levels, and follow‑up monitoring?

How to Initiate and Monitor Lithium Therapy in Adults with Bipolar Disorder

Start lithium at 300 mg three times daily (900 mg/day total) for acute mania, targeting serum levels of 1.0–1.5 mEq/L during the acute phase, then reduce to 0.6–1.2 mEq/L for maintenance therapy. 1

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Baseline Laboratory Assessment (Before First Dose)

Obtain the following labs before initiating lithium:

• Complete blood count (CBC) 2, 3
• Thyroid function tests: TSH and free T4 2, 3, 4
• Renal function: serum creatinine, blood urea nitrogen (BUN), urinalysis 2, 3, 1
• Serum calcium 2, 3
• Serum electrolytes 2
• Pregnancy test in females of childbearing potential 2, 3

Baseline ECG is not routinely required unless the patient has cardiac risk factors, pre-existing cardiac disease, or is elderly. 4

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Dosing Schedule

Acute Mania Phase

• Start with 600 mg three times daily (1800 mg/day total) to rapidly achieve therapeutic levels of 1.0–1.5 mEq/L. 1
• Alternative conservative approach: Begin at 300 mg three times daily (900 mg/day) and titrate upward based on serum levels and clinical response. 1
• Elderly patients require lower doses (often 150–300 mg/day) and may exhibit toxicity at levels ordinarily tolerated by younger adults. 1

Maintenance Phase

• Target dose is typically 300 mg three or four times daily (900–1200 mg/day) to maintain serum levels of 0.6–1.2 mEq/L. 1, 4
• Some patients respond at lower concentrations (0.6–0.8 mEq/L), which may reduce side effects while maintaining efficacy. 4

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Target Serum Lithium Levels

Acute Treatment

• 1.0–1.5 mEq/L for acute mania. 1
• Draw levels 8–12 hours after the previous dose (trough level) to ensure accurate measurement. 1

Maintenance Treatment

• 0.6–1.2 mEq/L for long-term prophylaxis, with most guidelines favoring 0.6–0.8 mEq/L to balance efficacy and tolerability. 1, 4
• Levels below 0.6 mEq/L are subtherapeutic and associated with higher relapse rates. 5
• Levels above 1.5 mEq/L indicate toxicity risk, even in patients without overt symptoms. 1

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Monitoring Schedule for Serum Lithium Levels

Acute Phase (First 4–6 Weeks)

• Check lithium levels twice per week until both the serum level and clinical symptoms stabilize. 1, 6
• Adjust dose based on levels and clinical response; do not rely solely on serum levels—clinical assessment is essential. 1

Maintenance Phase

• Check lithium levels every 2 months in stable, uncomplicated patients. 1
• Check every 3–6 months if the patient has been stable for an extended period. 2, 3, 4
• More frequent monitoring (monthly or sooner) is required if there are dose changes, new medications, renal function changes, or signs of toxicity. 4

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Monitoring Renal and Thyroid Function

Baseline (Before Starting Lithium)

• Serum creatinine, BUN, urinalysis (including specific gravity or osmolality after water deprivation to assess tubular function). 2, 3, 1
• TSH and free T4. 2, 3, 4

Maintenance Monitoring

• Renal function (creatinine, BUN, urinalysis): every 3–6 months. 2, 3, 4
• Thyroid function (TSH, free T4): every 3–6 months. 2, 3, 4
• Serum calcium: every 6–12 months to screen for lithium-induced hyperparathyroidism. 7

Progressive or sudden changes in renal function—even within the normal range—indicate the need for treatment reevaluation. 1

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Monitoring for Adverse Effects

Common Side Effects to Assess at Every Visit

• Fine tremor, nausea, diarrhea, polyuria, polydipsia (early signs of toxicity or nephrogenic diabetes insipidus). 1, 7
• Weight gain, cognitive dulling, sedation. 4

Serious Adverse Effects Requiring Immediate Attention

• Coarse tremor, confusion, ataxia, slurred speech (signs of lithium toxicity). 1
• Severe polyuria (>3 liters/day) or polydipsia (nephrogenic diabetes insipidus). 1, 7
• Goiter or symptoms of hypothyroidism (fatigue, cold intolerance, weight gain). 7, 8

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ECG Criteria and Cardiac Monitoring

Baseline ECG is not routinely required for lithium initiation unless the patient has:

• Pre-existing cardiac disease (arrhythmias, conduction abnormalities). 4
• Risk factors for QTc prolongation (family history of sudden cardiac death, concurrent QTc-prolonging medications). 4
• Age >65 years. 4

Lithium itself does not significantly prolong QTc, but it can cause sinus node dysfunction and T-wave flattening at therapeutic levels. 4

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Special Populations

Elderly Patients

• Start at lower doses (150–300 mg/day) and target lower serum levels (0.4–0.8 mEq/L). 1, 4
• Monitor renal function more frequently (every 3 months) due to age-related decline in glomerular filtration rate. 4

Pregnancy and Breastfeeding

• Lithium is teratogenic, particularly in the first trimester (increased risk of Ebstein's anomaly). 1
• If lithium must be continued during pregnancy, maintain the lowest effective dose and monitor levels weekly in the third trimester. 4
• Lithium is excreted in breast milk; breastfeeding is generally discouraged. 4

Patients with Renal Impairment

• Avoid lithium if creatinine clearance is <30 mL/min. 4
• Use lower doses and monitor levels more frequently (every 2–4 weeks) if creatinine clearance is 30–60 mL/min. 4

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Duration of Maintenance Therapy

• Continue lithium for at least 12–24 months after achieving mood stabilization. 2, 9
• Some patients require lifelong therapy, particularly those with multiple severe episodes, rapid cycling, or poor response to alternative agents. 2, 9
• Withdrawal of lithium increases relapse risk, especially within the first 6 months after discontinuation (>90% relapse rate in noncompliant patients vs. 37.5% in compliant patients). 2, 9

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Common Pitfalls to Avoid

• Underdosing during acute mania: Levels below 1.0 mEq/L are often insufficient for acute symptom control. 1
• Inadequate monitoring frequency: Twice-weekly levels during acute phase are essential to prevent toxicity and ensure therapeutic dosing. 1, 6
• Ignoring subtherapeutic levels: 42.4% of lithium levels in clinical practice fall below the therapeutic range, contributing to relapse. 5
• Abrupt discontinuation: Always taper lithium over 2–4 weeks minimum to reduce rebound mania risk. 2, 4
• Failure to monitor renal and thyroid function: Chronic lithium therapy can cause nephrogenic diabetes insipidus, hypothyroidism, and hyperparathyroidism. 1, 7, 8
• Dehydration and sodium depletion: Educate patients to maintain adequate hydration and avoid low-sodium diets, as these increase lithium retention and toxicity risk. 1, 4

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Patient Education

Instruct patients to:

• Maintain consistent fluid and salt intake to avoid fluctuations in lithium levels. 4
• Avoid NSAIDs (ibuprofen, naproxen), which reduce lithium clearance and increase toxicity risk. 4
• Report early signs of toxicity immediately: coarse tremor, confusion, severe nausea, vomiting, or diarrhea. 1
• Secure lithium and remove access to lethal quantities, especially in patients with suicidal ideation, as lithium overdoses can be fatal. 2