How should lithium be initiated and monitored for bipolar disorder, including starting dose, target serum concentrations, contraindications, and adverse effects?

Lithium Initiation and Monitoring in Bipolar Disorder

Starting Dose and Titration

Initiate 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 of 0.8-1.2 mEq/L are achieved for acute treatment. 1

• For older adults (≥70 years), start with lower doses (150-300 mg daily) targeting a reduced therapeutic range of 0.2-0.6 mEq/L initially, as elderly patients have increased vulnerability to toxicity and cognitive changes 1
• Therapeutic effects typically become apparent after 1-2 weeks at adequate serum concentrations 1
• An adequate trial requires 6-8 weeks at therapeutic doses before concluding ineffectiveness 1

Target Serum Concentrations

Maintain serum lithium levels at 0.8-1.2 mEq/L for acute mania treatment, then reduce to 0.6-1.0 mEq/L for maintenance therapy. 1, 2

• Some patients may respond at lower concentrations, but therapeutic monitoring guides optimization 1
• During acute mania, check lithium levels twice per week until both laboratory values and clinical symptoms stabilize 1
• Once stable, monitor lithium levels every 3-6 months during maintenance therapy 1, 2

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

This comprehensive baseline establishes reference values for detecting emerging toxicity or organ dysfunction during treatment 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, 2

• Check lithium level after 5 days at steady-state dosing when adjusting doses 1
• Monitor for early signs of toxicity: fine tremor, nausea, diarrhea 1
• Seek immediate medical attention if coarse tremor, confusion, or ataxia develop 1

Absolute Contraindications

• Severe renal impairment or renal failure 1
• Pregnancy (particularly first trimester, though risk-benefit must be weighed) 1
• Inability to maintain adequate hydration or salt intake 1
• Inability to comply with regular blood monitoring 1

Relative Contraindications and Cautions

• Pre-existing kidney disease requires baseline renal function assessment and more frequent monitoring 1
• Pre-existing thyroid problems necessitate closer thyroid function monitoring 1
• Patients taking NSAIDs, ACE inhibitors, or thiazide diuretics (increase lithium levels) 1
• Dehydration states or conditions causing significant fluid loss 1

Common Adverse Effects

Tremor and somnolence are the most common adverse effects, occurring significantly more frequently than with placebo. 3

• Tremor: Occurs in approximately 3.25 times more patients on lithium versus placebo (high-certainty evidence) 3
• Somnolence: Occurs in approximately 2.28 times more patients on lithium versus placebo (high-certainty evidence) 3
• Weight gain may occur, though evidence is moderate-certainty 3
• Polyuria and polydipsia from nephrogenic diabetes insipidus 4
• Hypothyroidism (monitor TSH every 3-6 months) 1
• Cognitive dulling or "mental fog" 4

Serious Adverse Effects Requiring Immediate Attention

• Lithium toxicity: Coarse tremor, confusion, ataxia, seizures, arrhythmias 1
• Acute renal failure 4
• Serotonin syndrome when combined with serotonergic agents (within 24-48 hours of combination) 1

Critical Safety Measures

Educate patients and families to maintain adequate hydration and consistent salt intake, as dehydration and sodium depletion dramatically increase lithium toxicity risk. 1

• Store lithium securely, especially in patients with suicide history, as lithium overdoses can be lethal 1
• Prescribe limited quantities with frequent refills to minimize stockpiling risk in high-risk patients 1
• Implement third-party medication supervision for patients with overdose history 1

Unique Anti-Suicidal Properties

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

This unique benefit makes lithium particularly valuable for patients with bipolar disorder and suicidality 1, 5

Discontinuation Protocol

Never discontinue lithium abruptly—taper gradually over 2-4 weeks minimum (10-20% reduction every 1-2 weeks) to minimize rebound mania risk, which exceeds 90% with sudden cessation. 1

• Slower tapers extending 4-8 weeks are prudent for patients with history of rapid relapse or severe episodes 1
• Withdrawal of lithium dramatically increases relapse risk, especially within 6 months following discontinuation 1
• More than 90% of noncompliant adolescents relapsed versus 37.5% of compliant patients 1

Maintenance Therapy Duration

Continue lithium maintenance therapy for at least 12-24 months after mood stabilization; some patients require lifelong treatment when benefits outweigh risks. 1, 6

Premature discontinuation leads to high relapse rates and should be avoided 1

Common Pitfalls to Avoid

• Underdosing or inadequate trial duration before concluding treatment failure 1
• Insufficient monitoring of renal and thyroid function 1
• Failure to educate patients about maintaining hydration and recognizing early toxicity signs 1
• Rapid discontinuation without proper tapering 1
• Combining with medications that increase lithium levels without dose adjustment 1