How should I initiate lithium therapy in an adult with bipolar I disorder, including dosing, baseline laboratory evaluation, monitoring schedule, and contraindications?

Initiating Lithium Therapy in Adults with Bipolar I Disorder

Baseline Laboratory Evaluation

Before starting lithium, obtain a comprehensive metabolic panel including complete blood count, thyroid function tests (TSH and free T4), urinalysis, blood urea nitrogen, serum creatinine, serum calcium, and a pregnancy test in females of childbearing potential. 1, 2

These baseline studies establish reference values and screen for contraindications, particularly renal or thyroid dysfunction that would complicate lithium therapy 1.

Initial Dosing Strategy

Start lithium at 300 mg twice or three times daily (600-900 mg/day total) in adults, with the goal of achieving therapeutic serum levels of 0.8-1.2 mEq/L for acute mania treatment. 1, 3

• Individual patients may respond at lower concentrations (0.4-0.7 mEq/L), but the probability of response increases significantly at levels above 0.8 mEq/L 3
• For maintenance therapy after stabilization, target levels of 0.6-1.0 mEq/L are appropriate, though some patients require higher concentrations to prevent relapse 1, 3
• Elderly patients or those with renal impairment should start at lower doses (150-300 mg/day) targeting levels of 0.5-0.8 mEq/L due to increased sensitivity to adverse effects 1, 3

Monitoring Schedule

Acute Phase (First 4-8 Weeks)

Check serum lithium levels twice weekly during the acute phase until both laboratory values and clinical symptoms stabilize. 1

• Draw lithium levels 12 hours post-dose at steady state (typically after 5 days at a stable dose) 1, 3
• Adjust doses based on clinical response and serum levels, increasing by 300 mg increments weekly as needed 1
• Monitor for early signs of toxicity: fine tremor, nausea, diarrhea 1

Maintenance Phase (After Stabilization)

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

• More frequent monitoring is warranted if the patient develops intercurrent illness, changes in fluid/salt intake, or addition of interacting medications 1
• Annual comprehensive metabolic reassessment is prudent for long-term therapy 1

Absolute Contraindications

Lithium should not be initiated in patients with severe renal impairment, acute dehydration, significant cardiovascular disease, or conditions causing sodium depletion. 1

• Pregnancy, particularly first trimester, represents a relative contraindication due to teratogenic risk (cardiac malformations) 1
• Breastfeeding is contraindicated as lithium is excreted in breast milk at therapeutic concentrations 1

Critical Safety Considerations

Lithium has a narrow therapeutic index—the difference between therapeutic and toxic levels is small, requiring meticulous monitoring and patient education. 1, 2

• Educate patients to maintain consistent hydration and salt intake, as dehydration or sodium depletion rapidly increases lithium levels 1
• Warn about medications that increase lithium levels: NSAIDs, ACE inhibitors, thiazide diuretics, and loop diuretics 1
• Instruct patients to seek immediate care if coarse tremor, confusion, ataxia, or severe gastrointestinal symptoms develop—these indicate lithium toxicity 1

Duration of Treatment

Continue lithium for at least 12-24 months after achieving mood stabilization; many patients require indefinite treatment. 1, 4

• Lithium withdrawal is associated with dramatically increased relapse risk, especially within 6 months of discontinuation, with over 90% of noncompliant patients relapsing versus 37.5% of compliant patients 1, 4
• If discontinuation is necessary, taper gradually over 2-4 weeks minimum (never abruptly) to minimize rebound mania risk 1

Combination Therapy Considerations

For severe mania or treatment-resistant cases, combine lithium with an atypical antipsychotic (aripiprazole, risperidone, quetiapine, or olanzapine) rather than using lithium monotherapy. 1

• Combination therapy provides superior acute symptom control and relapse prevention compared to monotherapy 1
• The combination that successfully treats the acute episode should be continued for maintenance 1

Unique Advantages of Lithium

Lithium reduces suicide attempts 8.6-fold and completed suicides 9-fold—an effect independent of its mood-stabilizing properties—making it the preferred choice for patients with suicidal ideation or history. 1, 5, 6, 7

• This anti-suicide effect is unique among mood stabilizers and represents a critical consideration in treatment selection 5, 6, 7
• Lithium demonstrates superior long-term efficacy for preventing both manic and depressive episodes compared to other mood stabilizers in non-enriched trials 1, 5, 8

Common Pitfalls to Avoid

• Never initiate lithium without establishing close clinical and laboratory monitoring capabilities—the narrow therapeutic window demands this infrastructure 1, 2
• Do not underdose—many treatment "failures" result from subtherapeutic levels; verify 12-hour trough levels are ≥0.8 mEq/L before concluding inefficacy 3
• Avoid abrupt discontinuation—rapid lithium withdrawal precipitates rebound mania in the majority of patients 1, 4
• Do not overlook medication interactions—NSAIDs and diuretics are commonly prescribed and can precipitate toxicity 1