What is the appropriate initial dose, titration schedule, target therapeutic serum lithium concentration, monitoring labs, contraindications, and common adverse effects for lithium in an adult with bipolar disorder?

Lithium for Bipolar Disorder: Clinical Management Guide

Initial Dosing

Start lithium at 300 mg three times daily (900 mg/day total) for patients weighing ≥30 kg, or 300 mg twice daily (600 mg/day) for patients <30 kg, with weekly dose increases of 300 mg until therapeutic levels are achieved. 1

• For acute mania, target serum concentrations of 0.8–1.2 mEq/L 1, 2
• For maintenance therapy, target 0.6–1.0 mEq/L 1, 2
• Some patients respond at lower concentrations (0.4–0.7 mEq/L), but therapeutic monitoring guides optimization 1, 3
• In elderly patients (≥75 years), consider lower target ranges of 0.5–0.8 mEq/L initially due to increased sensitivity to adverse effects 2
• For patients with Alzheimer's disease and mood symptoms, a range of 0.2–0.6 mEq/L is generally adequate, usually achieved with 150–300 mg per day 1

Titration Schedule and Monitoring

During acute treatment, measure serum lithium concentrations twice per week until both laboratory values and clinical symptoms stabilize. 1, 4

• Check lithium level after 5 days at steady-state dosing 1
• Therapeutic effects typically become apparent after 1–2 weeks 1
• An adequate trial requires 4–6 weeks at therapeutic doses before concluding ineffectiveness 1
• Response rates for acute mania range from 38–62% 1
• Once stable, monitor lithium levels every 3–6 months 1, 5

Baseline Laboratory Assessment

Before initiating lithium, obtain complete blood count, thyroid function tests (TSH and free T4), urinalysis, blood urea nitrogen, serum creatinine, serum calcium, and pregnancy test in females of childbearing potential. 1, 5

This comprehensive baseline establishes reference values for detecting future toxicity or organ dysfunction 1.

Ongoing Monitoring Requirements

Monitor lithium levels, renal function (BUN and creatinine), thyroid function (TSH), and urinalysis every 3–6 months during maintenance therapy. 1, 5

• Assess mood symptoms weekly during the first month, then monthly once stabilized 1
• Evaluate suicidality at every visit, given the high suicide risk in bipolar patients 1
• Screen for adverse effects including tremor, nausea, diarrhea, and polyuria at each appointment 1
• Monitor for signs of lithium toxicity: fine tremor, nausea, diarrhea initially; coarse tremor, confusion, or ataxia indicate severe toxicity requiring immediate medical attention 1

Contraindications and Special Populations

Lithium is contraindicated in patients with severe renal impairment, as the drug is entirely dependent on stable kidney function for safe use. 4

• Exercise extreme caution in patients with cardiovascular disease, as lithium has a narrow therapeutic index 4
• In pregnancy, weigh risks carefully; lithium crosses the placenta and requires specialized monitoring 2
• For elderly patients, start with lower doses and target lower serum concentrations (0.5–0.8 mEq/L) due to increased sensitivity to neurotoxicity 2, 3
• Patients must maintain adequate hydration and stable salt intake, as dehydration and sodium depletion increase lithium levels and toxicity risk 1

Common Adverse Effects

The most common adverse effects include fine tremor, nausea, diarrhea, polyuria, polydipsia, and weight gain. 1, 5

• Renal effects: Polyuria and polydipsia occur commonly; long-term use may impair renal concentrating ability 1
• Thyroid effects: Hypothyroidism develops in a significant proportion of patients; monitor TSH every 3–6 months 1, 5
• Neurological effects: Fine tremor is common and dose-related; coarse tremor indicates toxicity 1
• Gastrointestinal effects: Nausea and diarrhea are frequent, especially during initiation 1
• Metabolic effects: Weight gain occurs but is NOT associated with significant sedation, distinguishing lithium from valproate 1
• Cognitive effects: Some patients report subjective cognitive dulling at therapeutic doses 6

Unique Anti-Suicidal Properties

Lithium reduces suicide attempts by 8.6-fold and completed suicides by 9-fold—an effect independent of its mood-stabilizing properties. 1, 5

• This anti-suicidal benefit stems from central serotonin-enhancing properties, reduction of aggression/impulsivity, and modulation of stress responses 1
• No other mood stabilizer (valproate, lamotrigine, carbamazepine) has demonstrated comparable suicide-prevention efficacy 1
• For suicidal patients, implement third-party medication supervision and prescribe limited quantities (7–14 day supplies) to minimize stockpiling risk, as lithium overdoses can be lethal 1

Maintenance Therapy Duration

Continue lithium for at least 12–24 months after achieving mood stabilization; some patients require lifelong treatment. 1

• Withdrawal of maintenance lithium dramatically increases relapse risk, especially within 6 months following discontinuation 1
• More than 90% of adolescents who were noncompliant with lithium relapsed, compared to 37.5% of compliant patients 1, 5
• When discontinuation is necessary, taper gradually over 2–4 weeks minimum (never abruptly) to minimize rebound mania risk 1
• Slower tapers extending 4–8 weeks may be prudent for patients with history of rapid relapse or severe episodes 1

Critical Safety Measures

Lithium has a narrow therapeutic window (0.5–1.2 mM) with 1.5 mM representing the lower limit of risk for intoxication. 4

• Educate patients and families on early signs of toxicity: fine tremor, nausea, diarrhea 1
• Instruct patients to seek immediate medical attention if coarse tremor, confusion, or ataxia develop 1
• Parents must secure lithium and remove access to lethal quantities, particularly in suicidal adolescents 1
• Lithium overdoses can be fatal and require emergency intervention 1
• Ensure patients maintain consistent hydration and avoid NSAIDs, which can increase lithium levels 2

Combination Therapy Considerations

For severe mania with psychotic features or treatment-resistant cases, combine lithium with an atypical antipsychotic (aripiprazole, risperidone, quetiapine, or olanzapine). 1, 5

• Combination therapy provides superior efficacy compared to monotherapy for both acute symptom control and relapse prevention 1
• The combination of lithium plus an atypical antipsychotic is first-line treatment for severe presentations 1, 5
• Continue combination therapy for at least 12–24 months once stability is achieved 1
• For bipolar depression, lithium may be combined with an SSRI (preferably fluoxetine, sertraline, or escitalopram) or bupropion, but never use antidepressants as monotherapy due to risk of mood destabilization and manic induction 1

FDA Approval Status

Lithium is FDA-approved for bipolar disorder in patients age 12 and older, making it the only mood stabilizer with this approval in adolescents. 1, 5, 7