How should I initiate lithium therapy in an adult with bipolar disorder, including contraindications, baseline laboratory evaluation, starting dose, target serum lithium levels, and monitoring schedule?

Lithium Initiation in Adult Bipolar Disorder

Start lithium at 300 mg three times daily (900 mg/day total) for adults, targeting serum levels of 0.8–1.2 mEq/L for acute mania, with baseline labs including CBC, thyroid function, renal function, urinalysis, calcium, and pregnancy test, followed by lithium level checks twice weekly until stabilized. 1, 2

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Absolute Contraindications

• Severe renal impairment (creatinine clearance <30 mL/min) is a contraindication due to lithium's renal elimination and narrow therapeutic window 1
• Pregnancy (particularly first trimester) requires extreme caution due to teratogenic risk; obtain pregnancy test in all females of childbearing potential before initiation 1, 2
• Inability to ensure close monitoring (clinical and laboratory) is a contraindication, as lithium requires facilities for frequent assessment 1, 2

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Baseline Laboratory Evaluation (Before First Dose)

Obtain all of the following before initiating lithium: 1, 2

• Complete blood count (CBC)
• Thyroid function tests (TSH and free T4)
• Renal function: blood urea nitrogen (BUN) and serum creatinine
• Urinalysis
• Serum calcium
• Pregnancy test in females of childbearing age
• Consider baseline ECG in patients >50 years or with cardiac risk factors

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Starting Dose and Titration

Acute Mania: 1, 3

• Start 300 mg three times daily (900 mg/day total) in adults
• For elderly patients or those with renal concerns, start 300 mg twice daily (600 mg/day) 2
• Increase by 300 mg every 3–5 days based on serum levels and tolerability 1

Maintenance Therapy: 4

• Once acute episode resolves, target lower maintenance levels (see below)

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Target Serum Lithium Levels

Acute Mania Treatment: 1, 5, 3

• Target: 0.8–1.2 mEq/L (12-hour post-dose trough level)
• Some patients respond at lower concentrations (0.4–0.7 mEq/L), but response rates increase with levels ≥0.8 mEq/L 3
• Levels >1.2 mEq/L increase toxicity risk without additional efficacy 3

Maintenance/Prophylaxis: 4

• Target: 0.6–0.75 mEq/L for most patients
• Minimum efficacious level is 0.4 mEq/L 4
• Levels >0.75 mEq/L may benefit patients with predominantly manic symptoms but do not improve overall morbidity 4
• Elderly patients: target 0.5–0.8 mEq/L due to increased sensitivity to adverse effects 3

Critical Pitfall: Abrupt reduction of serum levels by >0.2 mEq/L dramatically increases relapse risk 4

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Monitoring Schedule

Acute Phase (First 4–8 Weeks): 2

• Check lithium level twice per week until both laboratory values and clinical symptoms stabilize 2
• Draw levels 12 hours post-dose (trough level) for consistency 3
• Once stable, reduce to weekly monitoring

Maintenance Phase (After Stabilization): 1, 2

• Lithium level: every 3–6 months
• Renal function (BUN, creatinine): every 3–6 months
• Thyroid function (TSH): every 3–6 months
• Urinalysis: every 3–6 months
• Serum calcium: every 6–12 months

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Efficacy Evidence

• High-certainty evidence shows lithium is more effective than placebo for inducing response (OR 2.13) and remission (OR 2.16) in acute mania 5
• Lithium is the gold standard for long-term bipolar disorder treatment, with superior evidence for preventing both manic and depressive episodes 1, 6, 7
• Lithium reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect independent of mood stabilization 1

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Common Adverse Effects and Management

High-Certainty Adverse Effects: 5

• Tremor (OR 3.25 vs. placebo): dose-related; consider dose reduction or propranolol 5
• Somnolence (OR 2.28 vs. placebo): often improves with time or dose adjustment 5
• Weight gain: occurs but evidence is moderate-certainty 5

Monitoring for Toxicity: 1

• Educate patients on early signs: fine tremor, nausea, diarrhea
• Seek immediate care if coarse tremor, confusion, or ataxia develop (signs of severe toxicity) 1

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Critical Pitfalls to Avoid

• Never discontinue lithium abruptly: taper over 2–4 weeks minimum to prevent rebound mania (>90% relapse rate with abrupt stop) 1
• Avoid dehydration and NSAIDs: both increase lithium levels and toxicity risk 1
• Do not underdose: response rates increase with levels ≥0.8 mEq/L in acute mania; many treatment "failures" are due to subtherapeutic levels 3
• Secure medication access in suicidal patients: lithium overdose is lethal; prescribe limited quantities with frequent refills 1

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Combination Therapy Considerations

• For severe mania or psychosis, combine lithium with an atypical antipsychotic (aripiprazole, risperidone, olanzapine, quetiapine) for superior efficacy versus monotherapy 1
• Maintenance therapy should continue for at least 12–24 months after stabilization; some patients require lifelong treatment 1, 6
• Withdrawal of lithium increases relapse risk, especially within 6 months of discontinuation 1

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When to Consider Alternatives

• Olanzapine may be slightly more effective than lithium for acute mania (moderate-certainty evidence) 5
• Valproate shows similar efficacy to lithium for maintenance but has different side-effect profile (hepatotoxicity, weight gain, PCOS risk) 1
• Topiramate is less effective than lithium and should not be first-line 5