What are the guidelines for prescribing lithium to an adult with bipolar disorder?

Lithium Prescribing Guidelines for Adults with Bipolar Disorder

Initial Patient Assessment and Baseline Testing

Before prescribing lithium, obtain baseline complete blood count, thyroid function tests (TSH, free T4), urinalysis, blood urea nitrogen, creatinine, serum calcium, and pregnancy test in females of childbearing age 1, 2. These tests identify contraindications and establish baseline organ function for comparison during long-term monitoring.

• Assess renal function carefully, as lithium is renally excreted and can cause progressive nephrotoxicity 2, 3.
• Document baseline thyroid function, since lithium causes hypothyroidism in approximately 6-fold higher rates than untreated populations 3.
• Verify pregnancy status, as lithium carries teratogenic risks 1.

Therapeutic Indications and Evidence Base

Lithium remains the gold standard first-line treatment for bipolar disorder, with superior evidence for both acute mania and long-term maintenance therapy 1, 4, 5.

• Lithium demonstrates antimanic efficacy with response rates of 38-62% in acute mania 1.
• For maintenance therapy, lithium prevents both manic and depressive episodes, with prophylactic response in more than two-thirds of patients 4, 6.
• Lithium uniquely reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect independent of its mood-stabilizing properties 1.
• Lithium shows superior efficacy compared to aripiprazole, valproic acid, and quetiapine for improving manic symptoms 5.

Dosing Strategy

For acute mania, target serum lithium levels of 0.8-1.2 mEq/L; for maintenance therapy, target 0.6-1.0 mEq/L 1.

• Start lithium 300 mg three times daily (900 mg/day) 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 are achieved or response criteria are met 1.
• Some patients respond at lower concentrations, but therapeutic drug monitoring guides optimization 1.
• For elderly patients or those with Alzheimer's disease and mood symptoms, lower lithium levels of 0.2-0.6 mEq/L (achieved with 150-300 mg daily) are generally adequate 7, 1.

Ongoing Monitoring Requirements

Check serum lithium levels twice weekly during acute stabilization, then every 3-6 months once stable 1, 2.

• Monitor renal function (BUN, creatinine, urinalysis) every 3-6 months 1, 2.
• Monitor thyroid function (TSH) every 3-6 months 1, 2.
• Assess for polyuria and polydipsia at each visit, as 10-40% of patients develop nephrogenic diabetes insipidus 3.
• Monitor serum calcium and parathyroid hormone levels periodically, as lithium increases both 3.

Patient Education on Toxicity Recognition

Educate patients on early signs of lithium toxicity: fine tremor, nausea, diarrhea, and instruct them to seek immediate medical attention if coarse tremor, confusion, or ataxia develop 1, 2.

• Lithium toxicity occurs at only twice the therapeutic dose, requiring vigilant monitoring 6.
• Dehydration, sodium depletion, and drug interactions (NSAIDs, ACE inhibitors, thiazide diuretics) increase toxicity risk 1.
• Instruct patients to maintain consistent sodium and fluid intake 1.

Combination Therapy Considerations

For severe mania, psychotic features, or inadequate response to lithium monotherapy after 6-8 weeks at therapeutic levels, add an atypical antipsychotic (aripiprazole, risperidone, quetiapine, or olanzapine) 1.

• Combination therapy with lithium plus an atypical antipsychotic provides superior efficacy compared to monotherapy for acute mania and relapse prevention 1.
• For bipolar depression, combine lithium with an SSRI (preferably fluoxetine, sertraline, or escitalopram) or bupropion, never use antidepressant monotherapy 1.
• Valproate plus lithium is effective for treatment-resistant mania or rapid cycling 1.

Maintenance Therapy Duration

Continue maintenance therapy for at least 12-24 months after mood stabilization; many patients require lifelong treatment 1, 6.

• Withdrawal of lithium dramatically increases relapse risk, especially within 6 months of discontinuation 1.
• More than 90% of noncompliant patients relapse versus 37.5% of compliant patients 1.
• When discontinuing lithium, taper gradually over 2-4 weeks minimum (10-20% reduction every 1-2 weeks) to minimize rebound mania risk 1.

Special Populations and Contraindications

Lithium has limited utility as monotherapy for acute severe mania due to insufficient response in highly agitated patients and delayed onset of action 4.

• For acute agitation, combine lithium with an atypical antipsychotic or add lorazepam 1-2 mg every 4-6 hours as needed 1.
• Lithium is less effective for mixed states and rapid cycling compared to classical bipolar features 6.
• Avoid lithium in patients with significant renal impairment, as absolute risk of renal failure is 0.5% with long-term use 3.

Common Pitfalls to Avoid

• Never discontinue lithium abruptly, as this precipitates rebound mania in >90% of cases 1.
• Do not underdose—ensure therapeutic levels are achieved before concluding treatment failure 1.
• Avoid premature discontinuation of maintenance therapy, as relapse rates exceed 90% in noncompliant patients 1.
• Do not prescribe lithium without establishing a monitoring plan for levels, renal function, and thyroid function 1, 2.
• Implement third-party medication supervision in patients with suicide history, as lithium overdoses are lethal 1.

Adjunctive Psychosocial Interventions

Combine lithium with psychoeducation about symptoms, course of illness, treatment options, and critical importance of medication adherence 1.

• Add cognitive-behavioral therapy for comorbid depression or anxiety 1.
• Implement family-focused therapy to improve medication supervision, early warning sign identification, and treatment adherence 1.