What Food and Drug Administration (FDA)-approved medications and typical starting doses are recommended for treating bipolar disorder in adolescents (10‑17 years)?

FDA-Approved Medications for Adolescent Bipolar Disorder

For adolescents aged 10-17 with bipolar disorder, FDA-approved first-line options include lithium (age 12+), aripiprazole (age 10+), risperidone (age 10+), quetiapine (age 10+), and olanzapine (age 13+), with specific starting doses and titration schedules varying by agent and indication. 1, 2, 3, 4

FDA-Approved Medications by Age and Indication

Lithium (Age 12+)

• Lithium is the only mood stabilizer with FDA approval for adolescents with bipolar disorder, indicated for both acute mania and maintenance therapy starting at age 12. 1, 5
• Start 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. 1
• Target serum level: 0.8-1.2 mEq/L for acute treatment, measured 12 hours after the last dose. 1, 5

Aripiprazole (Age 10+)

• FDA-approved from age 10 for acute mania and maintenance treatment of bipolar I disorder. 1, 5
• Starting dose: 2 mg/day, titrate to target of 10 mg/day (range 5-15 mg/day for adolescents). 1
• Aripiprazole has a favorable metabolic profile compared to other atypical antipsychotics, making it a preferred first-line option when metabolic concerns exist. 1

Risperidone (Age 10+)

• FDA-approved from age 10 for acute mania in bipolar I disorder. 1, 4, 5
• Starting dose: 0.5 mg/day, titrate to target of 2-3 mg/day (range 0.5-6 mg/day). 4
• Monitor closely for metabolic effects including weight gain, glucose elevation, and hyperprolactinemia, which occur more frequently in adolescents than adults. 4, 6

Quetiapine (Age 10+)

• FDA-approved from age 10 for acute mania in bipolar I disorder. 1, 3, 5
• Day 1: 25 mg twice daily; Day 2: 100 mg total daily; Day 3: 200 mg total daily; Day 4: 300 mg total daily; Day 5: 400 mg total daily. 3
• Target dose: 400-600 mg/day (maximum 600 mg/day in adolescents). 3
• Can be administered three times daily based on response and tolerability. 3

Olanzapine (Age 13+)

• FDA-approved from age 13 for acute mania in bipolar I disorder. 1, 2, 5
• Starting dose: 2.5-5 mg once daily, titrate to target of 10 mg/day. 1, 2
• Therapeutic range: 5-20 mg/day, with effects typically evident within 1-2 weeks. 2
• Olanzapine carries the highest risk of weight gain and metabolic syndrome among approved agents, which may lead clinicians to consider other drugs first in adolescents. 2, 6

Non-FDA-Approved but Guideline-Recommended Options

Valproate (Divalproex)

• The American Academy of Child and Adolescent Psychiatry recommends valproate as first-line treatment for acute mania despite lack of FDA approval in adolescents. 1, 5
• Starting dose: 125 mg twice daily, titrate to therapeutic blood level of 40-90 μg/mL (or 50-100 μg/mL for acute treatment). 1
• Valproate is contraindicated in females of childbearing potential due to teratogenicity and risk of polycystic ovary syndrome. 1, 5, 6
• Requires baseline and periodic monitoring of liver function tests and complete blood count every 3-6 months. 1

Critical Baseline Monitoring Requirements

Before Starting Lithium

• Complete blood count, thyroid function tests (TSH, free T4), urinalysis, blood urea nitrogen, serum creatinine, serum calcium, and pregnancy test in females. 1
• During maintenance: lithium levels, renal and thyroid function, and urinalysis every 3-6 months. 1

Before Starting Atypical Antipsychotics

• Body mass index, waist circumference, blood pressure, fasting glucose, and fasting lipid panel. 1, 4
• Follow-up monitoring: BMI monthly for 3 months then quarterly; blood pressure, fasting glucose, and lipids at 3 months then annually. 1, 4

Before Starting Valproate

• Liver function tests (AST, ALT, bilirubin), complete blood count with platelets, and pregnancy test in females. 1

Maintenance Therapy Duration

Continue the effective medication regimen for at least 12-24 months after achieving mood stabilization; some adolescents will require lifelong treatment. 1, 7

• Withdrawal of maintenance therapy, especially lithium, dramatically increases relapse risk within 6 months, with >90% of noncompliant adolescents relapsing versus 37.5% of compliant patients. 1

Common Pitfalls to Avoid

• Never use antidepressant monotherapy in adolescent bipolar disorder—this can trigger manic episodes in up to 58% of youth and cause rapid cycling. 1
• Inadequate trial duration before declaring treatment failure: systematic trials require 6-8 weeks at therapeutic doses before concluding an agent is ineffective. 1
• Failure to monitor metabolic parameters with atypical antipsychotics: weight gain occurs in approximately 16% of pediatric patients and requires proactive dietary counseling from treatment initiation. 1, 6
• Premature discontinuation when symptoms improve: this increases relapse risk dramatically and should be avoided. 1

Adjunctive Psychosocial Interventions

Psychoeducation and psychosocial interventions must accompany all pharmacotherapy to improve outcomes. 1

• Cognitive-behavioral therapy has strong evidence for addressing emotional dysregulation, anxiety, and depression components of bipolar disorder. 1
• Family-focused therapy improves medication adherence, helps with early warning sign identification, and enhances problem-solving and communication skills. 1

Special Considerations for Atypical Antipsychotics

The increased potential for weight gain and dyslipidemia in adolescents compared with adults may lead clinicians to consider prescribing lithium or other drugs first, particularly aripiprazole or ziprasidone which have more favorable metabolic profiles. 1, 2, 6

• Olanzapine and risperidone carry the highest metabolic risk, while aripiprazole, ziprasidone, and lurasidone show minimal metabolic adverse effects. 6
• Hyperprolactinemia, sedation, and weight gain occur more frequently in adolescents than adults with atypical antipsychotic use. 5, 6