What is the recommended first‑line maintenance treatment, including drug choice, dosing, and monitoring, for an adult with Bipolar I disorder who has no contraindications to lithium?

First-Line Maintenance Treatment for Bipolar I Disorder

Lithium is the recommended first-line maintenance treatment for adults with Bipolar I disorder who have no contraindications, with a target serum level of 0.6–1.0 mEq/L for maintenance therapy. 1, 2, 3

Evidence Supporting Lithium as First-Line

Lithium demonstrates superior evidence for long-term efficacy in maintenance therapy compared to other mood stabilizers, particularly for preventing manic and hypomanic episodes. 1 Recent placebo-controlled trials confirm lithium's definite efficacy in bipolar disorder, and it remains recommended as first-line in all current guidelines despite decreased use over recent years. 2 Lithium is more effective in preventing episodes of the manic/hypomanic type, including mixed episodes, than preventing depressive episodes. 2

Lithium uniquely reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect independent of its mood-stabilizing properties. 1 This anti-suicidal benefit is unmatched by other mood stabilizers and represents a critical advantage for long-term treatment. 2

Dosing Protocol

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. 1
• Increase weekly by 300 mg increments until therapeutic levels of 0.8–1.2 mEq/L are achieved for acute treatment. 1

Maintenance Dosing

• Target serum lithium concentration of 0.6–1.0 mEq/L for maintenance therapy. 1, 3
• Some patients respond at lower concentrations, but therapeutic monitoring guides optimization. 1

Baseline Laboratory Assessment

Before initiating lithium, obtain: 1

• Complete blood count
• Thyroid function tests (TSH and free T4)
• Urinalysis
• Blood urea nitrogen and serum creatinine
• Serum calcium
• Pregnancy test in females of childbearing age

Monitoring Schedule

Acute Phase

• Check serum lithium concentration twice per week until both laboratory level and clinical symptoms stabilize. 1
• Obtain lithium level after 5 days at steady-state dosing. 1

Maintenance Phase

• Monitor lithium levels, renal function (BUN, creatinine), thyroid function (TSH), and urinalysis every 3–6 months. 1
• Assess for early signs of lithium toxicity: fine tremor, nausea, diarrhea. 1
• Seek immediate medical attention if coarse tremor, confusion, or ataxia develop. 1

Duration of Maintenance Therapy

Continue lithium for at least 12–24 months after achieving mood stabilization. 1, 3 Some patients require lifelong treatment, particularly those with multiple severe episodes or rapid cycling. 1 Withdrawal of maintenance lithium therapy dramatically increases relapse risk, especially within 6 months following discontinuation, with over 90% of noncompliant patients relapsing versus 37.5% of compliant patients. 1

Alternative First-Line Options

If lithium is contraindicated or not tolerated, alternative first-line maintenance options include: 3

• Quetiapine monotherapy
• Divalproex (valproate) monotherapy
• Lamotrigine monotherapy (particularly effective for preventing depressive episodes) 1, 3
• Asenapine monotherapy
• Aripiprazole monotherapy

Valproate demonstrates response rates of 53% in acute mania and is particularly effective for mixed or dysphoric mania, though it has less robust controlled maintenance data than lithium. 4, 5 Lamotrigine offers a complementary spectrum to lithium by stabilizing mood "from below baseline" and preventing depressive episodes. 5

Combination Therapy Considerations

Combination therapy with lithium plus an atypical antipsychotic provides superior efficacy compared to monotherapy for severe presentations and relapse prevention. 1 If inadequate response occurs after 6–8 weeks at therapeutic lithium levels, consider adding an atypical antipsychotic (aripiprazole, risperidone, or quetiapine). 1

Critical Safety Measures

• Educate patients and families on lithium toxicity signs and the importance of maintaining adequate hydration and salt intake. 1
• Prescribe limited quantities with frequent refills to minimize stockpiling risk in patients with suicide history. 1
• Store lithium securely, as overdoses can be lethal. 1
• Never discontinue lithium abruptly—taper gradually over 2–4 weeks minimum to minimize rebound mania risk. 1

Common Pitfalls to Avoid

• Inadequate trial duration: Conduct systematic 6–8 week trials at therapeutic doses before concluding lithium is ineffective. 1
• Premature discontinuation: Maintenance therapy must continue for 12–24 months minimum, as >90% of noncompliant patients relapse. 1
• Insufficient monitoring: Regular assessment of lithium levels, renal function, and thyroid function every 3–6 months is essential. 1
• Rapid tapering: Never taper faster than 10–20% reductions every 1–2 weeks when discontinuing lithium. 1