Which two antidepressants are FDA‑approved for the acute treatment of major depressive disorder in children and adolescents?

FDA-Approved Antidepressants for Pediatric Major Depressive Disorder

Fluoxetine and escitalopram are the only two antidepressants approved by the FDA for the treatment of major depressive disorder in children and adolescents. 1, 2, 3, 4

Specific FDA Approvals

Fluoxetine

• Approved for children ≥8 years of age with major depressive disorder 2, 4
• The only antidepressant with demonstrated efficacy in two placebo-controlled, randomized clinical trials of pediatric depression 5
• Fluoxetine 20 mg daily achieved a 41% remission rate versus 20% with placebo in controlled trials 2
• The FDA label explicitly states approval for "treatment of major depressive disorder" in pediatric patients 4

Escitalopram

• Approved only for adolescents aged 12–17 years, not for younger children 1, 2, 3
• The FDA indication specifies "acute and maintenance treatment of major depressive disorder in adults and in adolescents 12 to 17 years of age" 3
• Escitalopram is not approved for children under age 12 2

Comparative Efficacy Evidence

• In network meta-analysis of 34 trials including 5,260 participants, only fluoxetine was statistically significantly more effective than placebo (standardized mean difference -0.51,95% CrI -0.99 to -0.03) 6
• The number needed to treat (NNT) for major depressive disorder is 10, while the number needed to harm (NNH) for suicidality is 112, yielding a risk-benefit ratio of 1 to 11.2 times favorable 7
• Fluoxetine demonstrated superior tolerability compared to duloxetine and imipramine in pediatric populations 6

Other Antidepressants Without FDA Approval

• Sertraline has positive efficacy data from pooled studies but is not FDA-approved for pediatric depression 1, 7
• Citalopram, paroxetine, venlafaxine, and other antidepressants lack FDA approval for pediatric major depressive disorder 1
• Imipramine, venlafaxine, and duloxetine had significantly more discontinuations due to adverse events than placebo 6

Clinical Algorithm for Selection

• Start with fluoxetine as the first-line agent for children ≥8 years with major depressive disorder 1, 2
• Use escitalopram as an alternative for adolescents ≥12 years if fluoxetine is contraindicated or not tolerated 1, 2
• Initial fluoxetine dosing: 10 mg daily for one week, then increase to 20 mg daily (the standard therapeutic dose) 1, 2
• Maximum fluoxetine dose: 60 mg daily 1
• Initial escitalopram dosing: 10 mg daily, with maximum dose of 20 mg daily 1

Critical Safety Monitoring

• In-person visit within 1 week of starting treatment, followed by weekly contact during the first month 2
• The absolute risk of suicidal thoughts or behaviors is approximately 1% with antidepressants versus 0.2% with placebo (NNH = 143) 2
• Higher initial doses are associated with increased risk of intentional self-harm—always start at recommended starting doses 1
• All SSRIs must be tapered gradually rather than stopped abruptly to avoid withdrawal phenomena 1

Combination Therapy

• Fluoxetine plus cognitive-behavioral therapy achieved a 71% response rate versus 35% for placebo, significantly superior to either treatment alone 2
• Combined therapy produces significant improvements in overall functional outcomes beyond symptom reduction 2

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