What are the treatment options for bipolar disorder?

Treatment Options for Bipolar Disorder

First-line treatment for bipolar disorder includes lithium, valproate, or atypical antipsychotics, with specific medication selection based on the phase of illness and patient characteristics. 1, 2

Treatment by Phase of Illness

Acute Mania/Mixed Episodes

• Start with lithium, valproate, or an atypical antipsychotic (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) 1, 2
• For severe presentations, consider combination therapy with lithium or valproate plus an atypical antipsychotic 1
• Lithium is FDA-approved for bipolar disorder in patients 12 years and older 2
• Atypical antipsychotics may provide more rapid symptom control than mood stabilizers alone 1
• Ziprasidone for acute manic/mixed episodes: Start at 40 mg twice daily with food, increase to 60-80 mg twice daily on day 2 3
• Olanzapine is FDA-approved for acute treatment of manic or mixed episodes as monotherapy and as adjunct to lithium or valproate 4

Bipolar Depression

• Olanzapine-fluoxetine combination is FDA-approved for bipolar depression in adults 2
• Lamotrigine is effective for bipolar depression, particularly for prevention of depressive episodes 2
• Antidepressant monotherapy is not recommended due to risk of mood destabilization 1, 2
• When adding antidepressants for bipolar depression, always use them in combination with a mood stabilizer to prevent mood destabilization 2

Maintenance Therapy

• Continue the regimen that effectively treated the acute episode for at least 12-24 months 5, 1, 2
• Most patients with Bipolar I disorder will require ongoing medication therapy to prevent relapse; some individuals will need lifelong treatment 5
• Lithium shows superior evidence for prevention of both manic and depressive episodes 1, 2
• Lithium significantly reduces suicide risk (8.6-fold reduction in suicide attempt recurrence) 2
• Lamotrigine is approved for maintenance therapy in adults and is particularly effective for preventing depressive episodes 2
• Ziprasidone can be used for maintenance treatment of bipolar I disorder as an adjunct to lithium or valproate at the same dose on which the patient was initially stabilized (40-80 mg twice daily) 3

Medication Selection Algorithm

1. First Episode of Mania/Mixed Episode:

   • Start with lithium (if no contraindications) or valproate 1, 2
   • Alternative: atypical antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) 2

2. For Bipolar Depression:

   • Olanzapine-fluoxetine combination as first-line 1, 2
   • Alternative: mood stabilizer with careful addition of an antidepressant 1

3. For Maintenance Therapy:

   • Continue the effective acute treatment regimen 1, 2
   • Lithium or valproate are preferred options 1
   • Consider lamotrigine particularly for preventing depressive episodes 2

Monitoring Requirements

• Regular monitoring of medication levels, metabolic parameters, and organ function is essential 1, 2
• For lithium: baseline laboratory assessment should include complete blood cell counts, thyroid function tests, urinalysis, blood urea nitrogen, creatinine, and serum calcium levels 5
• Once a stable lithium dose is obtained, lithium levels, renal and thyroid function, and urinalyses should be monitored every 3-6 months 5
• For valproate: baseline liver function tests, complete blood count, and pregnancy test 5, 2
• Serum drug levels, hepatic and hematological indices should be monitored periodically (every 3-6 months) for valproate 5
• Regular monitoring for metabolic side effects of medications, particularly atypical antipsychotics 1

Important Clinical Considerations

• Avoid unnecessary polypharmacy while recognizing that many patients will require more than one medication for optimal control 1, 2
• Medication trials should be systematic, with a 6-8 week trial of a mood-stabilizing agent using adequate doses before adding or substituting other mood stabilizers 5
• Antidepressant monotherapy can trigger manic episodes or rapid cycling 1, 2
• Over 50% of patients with bipolar disorder are not adherent to treatment, contributing to poorer outcomes 6
• Bipolar disorder reduces life expectancy by approximately 12-14 years, with increased cardiovascular mortality 6
• Psychoeducation and psychosocial interventions should accompany pharmacotherapy to improve outcomes 1

Special Populations

• For adolescents (ages 13-17): Start with lower doses and carefully monitor for side effects 2
• The increased potential for weight gain and dyslipidemia with atypical antipsychotics in adolescents may lead clinicians to consider prescribing other drugs first 4
• Lithium is the only FDA-approved agent for bipolar disorder in youths age 12 and older 1
• When treating comorbid ADHD, stabilize mood symptoms first before adding stimulants 5, 1

Common Pitfalls to Avoid

• Inadequate duration of maintenance therapy leads to high relapse rates - >90% of adolescents who were noncompliant with lithium treatment relapsed 5, 1
• Failure to monitor for metabolic side effects of medications, particularly atypical antipsychotics 1
• Overlooking comorbidities such as substance use disorders, anxiety disorders, or ADHD that may complicate treatment 1
• Withdrawal of maintenance lithium therapy has been associated with increased risk of relapse, especially within 6 months following discontinuation 5
• Prescription patterns have changed over time with decreased lithium use and increased use of lamotrigine and quetiapine, though lithium remains the most effective drug overall 7, 8