What is the recommended treatment for bipolar disorder in children and adolescents?

Treatment of Bipolar Disorder in Children and Adolescents

Primary Pharmacological Treatment

For acute mania in well-defined DSM-IV-TR Bipolar I Disorder, pharmacotherapy with lithium, valproate, or atypical antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine) is the primary treatment. 1, 2

First-Line Medication Selection

The choice of medication should be based on:

• Lithium is FDA-approved for bipolar disorder in patients age 12 and older for both acute mania and maintenance therapy, with response rates of 38-62% in acute mania 2, 3, 4
• Valproate demonstrates higher response rates (53%) compared to lithium (38%) in children and adolescents with mania and mixed episodes 2, 5
• Atypical antipsychotics (aripiprazole, risperidone, quetiapine, olanzapine) provide rapid symptom control and are FDA-approved for acute mania 2, 3, 4
  • Aripiprazole is licensed in France from age 13 and in the USA from age 10 for acute mania 6
  • Risperidone is effective at 0.5-2.5 mg/day for pediatric mania (ages 10-17), with comparable efficacy to higher doses of 3-6 mg/day 4
  • Quetiapine plus valproate is more effective than valproate alone for adolescent mania, with response rates of 87% versus 53% for valproate monotherapy 2, 5

Medication Selection Algorithm

For first-episode acute mania:

• Start with lithium (target level 0.8-1.2 mEq/L) OR valproate (target level 40-90 mcg/mL) as monotherapy 2, 6
• If metabolic concerns are paramount, lithium is preferred over atypical antipsychotics due to lower metabolic risk 2
• If rapid symptom control is needed, consider atypical antipsychotics which provide faster onset than mood stabilizers 2, 3

For severe presentations or treatment-resistant cases:

• Combination therapy with lithium or valproate PLUS an atypical antipsychotic is recommended 1, 2
• Risperidone combined with lithium or valproate demonstrates superior efficacy to mood stabilizers alone 2, 4

Maintenance Therapy

Continue the regimen that effectively treated the acute episode for at least 12-24 months, with some individuals requiring lifelong treatment. 2, 3

• Lithium shows superior evidence for prevention of both manic and depressive episodes in long-term maintenance 2, 3
• Withdrawal of maintenance lithium therapy increases relapse risk dramatically, especially within 6 months of discontinuation 2
• More than 90% of adolescents who were noncompliant with lithium treatment relapsed, compared to 37.5% of compliant patients 2

Treatment of Bipolar Depression

For bipolar depression, the olanzapine-fluoxetine combination is recommended as first-line treatment. 2, 3

• Lamotrigine is particularly effective for preventing depressive episodes in maintenance therapy 2, 3
• Antidepressant monotherapy is contraindicated due to risk of mood destabilization, mania induction, and rapid cycling 1, 2, 3
• When antidepressants are used, they must ALWAYS be combined with a mood stabilizer 2

Monitoring Requirements

For Lithium:

• Baseline: complete blood count, thyroid function tests, urinalysis, BUN, creatinine, serum calcium, pregnancy test in females 2
• Ongoing: lithium levels, renal and thyroid function, urinalysis every 3-6 months 2, 3

For Valproate:

• Baseline: liver function tests, complete blood count, pregnancy test 2
• Ongoing: serum drug levels, hepatic function, hematological indices every 3-6 months 2
• Special concern: valproate is associated with polycystic ovary disease in females and should not be used in women of childbearing age according to NICE and ANSM 6

For Atypical Antipsychotics:

• Baseline: body mass index, waist circumference, blood pressure, fasting glucose, fasting lipid panel 2
• Follow-up: BMI monthly for 3 months then quarterly; blood pressure, glucose, lipids at 3 months then yearly 2, 3

Special Considerations for Preschool Children

Extreme caution must be taken before applying the bipolar disorder diagnosis in preschool children, as diagnostic validity has not been established in this age group. 1

• Highly volatile and reactive toddlers require assessment and intervention, but whether they have bipolar disorder as defined by adult literature remains unestablished 1
• Environmental, developmental, temperamental, and social factors must be addressed before considering aggressive pharmacotherapy 1
• The short- and long-term safety of mood stabilizers and atypical antipsychotics has not been established in very young children 1

Adjunctive Psychosocial Interventions

Psychoeducation and psychosocial interventions should accompany all pharmacotherapy to improve outcomes. 2

• Provide information to patient and family regarding symptoms, course of illness, treatment options, and critical importance of medication adherence 2
• Cognitive-behavioral therapy has strong evidence for both anxiety and depression components of bipolar disorder 2
• Family-focused therapy helps with medication supervision, early warning sign identification, and reducing access to lethal means 2

Critical Pitfalls to Avoid

• Never use antidepressant monotherapy - this can trigger manic episodes or rapid cycling 1, 2, 3
• Avoid inadequate duration of maintenance therapy - premature discontinuation leads to relapse rates exceeding 90% 2
• Do not overlook metabolic monitoring - atypical antipsychotics require careful monitoring for weight gain, diabetes risk, and dyslipidemia 1, 2, 3
• Avoid unnecessary polypharmacy while recognizing that many patients will require more than one medication for optimal control 1, 2
• Do not miss comorbidities such as ADHD, anxiety disorders, or substance use disorders that complicate treatment 2
• Ensure adequate trial duration - systematic medication trials require 6-8 weeks at adequate doses before concluding ineffectiveness 2

Treatment-Resistant Cases

For severely impaired adolescents with manic or depressive episodes who do not respond to medications or cannot tolerate them, electroconvulsive therapy (ECT) may be considered. 3