What is the recommended protocol for initiating lithium therapy, including indications, contraindications, baseline investigations, starting dose, titration schedule, and monitoring?

How to Start Lithium

Lithium should be initiated with baseline laboratory assessment (CBC, TSH, free T4, BUN, creatinine, urinalysis, calcium, pregnancy test), starting at 300 mg twice daily (or 150 mg/day in elderly), with serum levels checked twice weekly until stable, targeting 0.8-1.2 mEq/L for acute mania or 0.6-1.0 mEq/L for maintenance. 1, 2

Indications for Lithium Therapy

• Lithium is FDA-approved and first-line treatment for bipolar disorder in patients age 12 and older, effective for acute mania, maintenance therapy, and prevention of both manic and depressive episodes. 1
• Lithium demonstrates superior long-term efficacy compared to other mood stabilizers, with response rates of 38-62% in acute mania. 1, 3
• Lithium uniquely reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect independent of its mood-stabilizing properties. 1
• Consider lithium as first-line for patients with classical bipolar I disorder, family history of lithium response, or high suicide risk. 1, 4

Contraindications and Precautions

• Absolute contraindications include significant renal impairment (GFR <30 ml/min/1.73 m²), severe dehydration, sodium depletion, and concomitant MAO inhibitor use. 2
• Relative contraindications include cardiovascular disease, pregnancy (especially first trimester), and inability to maintain adequate hydration. 2
• Avoid NSAIDs as they increase lithium levels and toxicity risk; use acetaminophen for pain management instead. 2
• Patients must have access to facilities for close clinical monitoring and routine laboratory testing. 2

Baseline Investigations Required

Before initiating lithium, obtain: 1, 2

• Complete blood count (CBC)
• Thyroid function tests: TSH and free T4
• Renal function: BUN, creatinine, calculated GFR
• Urinalysis
• Serum calcium
• Serum electrolytes
• Pregnancy test in females of childbearing potential
• Baseline weight, blood pressure, and pulse

Starting Dose Protocol

Standard Adult Dosing

• Start with 300 mg twice daily (600 mg/day total) for adults weighing ≥30 kg. 1
• For patients <30 kg, start with 300 mg twice daily (600 mg/day). 1

Elderly or Renally-Impaired Dosing

• For elderly patients or those with GFR 30-60 ml/min/1.73 m², start at 150 mg/day due to increased sensitivity and reduced clearance. 2
• For GFR <30 ml/min/1.73 m², reduce dose by 50% and increase monitoring frequency. 2

Pediatric Dosing (Age 12+)

• Start with 300 mg three times daily (900 mg/day) for adolescents ≥30 kg. 1
• For adolescents <30 kg, start with 300 mg twice daily (600 mg/day). 1

Titration Schedule

• Increase dose by 300 mg weekly based on clinical response and serum levels. 1
• Check serum lithium levels twice per week during acute phase until levels and clinical condition stabilize. 2
• Draw lithium levels 12 hours post-dose (trough level) for accurate interpretation. 2
• Target serum level of 0.8-1.2 mEq/L for acute mania treatment. 1, 2
• Target serum level of 0.6-1.0 mEq/L for maintenance therapy. 2
• Some patients respond at lower concentrations (0.2-0.6 mEq/L), particularly when lithium is used to augment antidepressants. 2

Monitoring Protocol

Acute Phase (First 4-8 Weeks)

• Check serum lithium levels twice weekly until stable. 2
• Monitor for early signs of toxicity: fine tremor, nausea, diarrhea. 1
• Assess clinical response weekly using standardized measures. 1
• Monitor weight, as lithium commonly causes weight gain. 5

Maintenance Phase (After Stabilization)

• Check lithium levels, renal function (BUN, creatinine), thyroid function (TSH), and urinalysis every 3-6 months. 1, 2, 5
• Monitor for signs of toxicity: coarse tremor, confusion, ataxia require immediate medical attention. 1
• Assess for hypothyroidism symptoms, as lithium-induced hypothyroidism can present with anxiety-like symptoms. 5
• Continue monitoring weight and provide lifestyle interventions as needed. 5

Patient Education and Safety Measures

• Educate patients on maintaining adequate hydration (8-10 glasses of water daily) and consistent salt intake. 2
• Instruct patients to report immediately: coarse tremor, confusion, ataxia, severe nausea/vomiting, or diarrhea. 1
• Warn that toxicity can occur at doses close to therapeutic levels, with serious toxicity at >2.0 mEq/L. 2
• Advise patients to avoid dehydration during illness, exercise, or hot weather. 2
• For patients with suicide risk, implement third-party medication supervision and prescribe limited quantities with frequent refills, as lithium overdoses can be lethal. 1

Combination Therapy Considerations

• For severe mania or psychotic features, combine lithium with an atypical antipsychotic (aripiprazole, risperidone, quetiapine, or olanzapine) from the start. 1
• Combination therapy provides superior acute control and relapse prevention compared to monotherapy. 1
• For acute agitation, add lorazepam 1-2 mg every 4-6 hours as needed while lithium reaches therapeutic levels. 1
• Benzodiazepines should be time-limited (days to weeks) to avoid tolerance. 1

Duration of Treatment

• Continue lithium for at least 12-24 months after achieving mood stabilization. 1, 5
• Some patients require lifelong treatment, particularly those with multiple severe episodes, rapid cycling, or high suicide risk. 1
• Withdrawal of lithium dramatically increases relapse risk, with >90% of noncompliant patients relapsing versus 37.5% of compliant patients. 1
• If discontinuation is necessary, taper gradually over 2-4 weeks minimum—never discontinue abruptly—to minimize rebound mania risk. 1

Common Pitfalls to Avoid

• Never start lithium without baseline renal and thyroid function tests, as undetected dysfunction increases toxicity risk. 2
• Do not underdose—inadequate serum levels (e.g., 0.4 mEq/L) will not provide therapeutic benefit. 1
• Avoid combining lithium with NSAIDs; this combination significantly increases lithium levels and toxicity risk. 2
• Do not delay treatment waiting for lab results in acute mania—start an atypical antipsychotic immediately while ordering baseline labs. 1
• Never rapid-load lithium, as this increases neurotoxicity risk; gradual titration is mandatory. 1
• Do not discontinue lithium prematurely—maintenance therapy requires at least 12-24 months to prevent relapse. 1, 5