What are the next steps for treating depression and irritability in a 14-year-old who has tried fluoxetine (Prozac) and escitalopram (Lexapro)?

Medication Options for Depression and Irritability in a 14-Year-Old After Fluoxetine and Escitalopram

For a 14-year-old who has tried fluoxetine (Prozac) and escitalopram (Lexapro) for depression and irritability, sertraline (Zoloft) is the recommended next medication option due to its established efficacy and safety profile in adolescents. 1

Evidence-Based Medication Selection Algorithm

First-Line Options Already Tried:

• Fluoxetine and escitalopram have both been tried without adequate response 1
• Both medications have demonstrated efficacy in adolescents with depression, with response rates of 52-61% for fluoxetine and 63-64% for escitalopram 1

Recommended Next Steps:

1. Try sertraline (Zoloft):

   • Demonstrated 63% response rate versus 53% for placebo (p=.05) in adolescents 1
   • Considered a second-choice antidepressant after fluoxetine for juvenile depression 2
   • Has established efficacy in the adolescent population 1

2. If sertraline is ineffective, consider:

   • Citalopram (though evidence shows less robust response rates of 47-51%) 1
   • Combination therapy with cognitive behavioral therapy (CBT) and medication 1

3. Medications to avoid as next steps:

   • Paroxetine - higher rates of sexual dysfunction and intolerable adverse effects in adolescents 1
   • Duloxetine and venlafaxine - found to be most intolerable in depressed youth 1
   • Venlafaxine - associated with higher risk of suicide-related outcomes compared to other antidepressants 3

Important Clinical Considerations

Monitoring Requirements:

• Begin monitoring for treatment response and adverse effects within 1-2 weeks of medication initiation 1
• Pay particular attention to emergence of suicidal thoughts/behaviors, especially during the first 1-2 months 1, 4
• Monitor for:
  • Agitation, irritability, or unusual changes in behavior 4, 5
  • Worsening depression or anxiety 4
  • Physical side effects (headaches, nausea, etc.) 1

Duration of Treatment Trial:

• Allow 6-8 weeks at an adequate dose to determine effectiveness 1
• If no response after adequate trial, reassess diagnosis and treatment plan 1
• Consider whether comorbid disorders or psychosocial factors were inadequately addressed 1

Combination Therapy:

• Consider adding CBT to medication treatment 1
• The Treatment of Adolescent Depression Study showed combination of fluoxetine and CBT was superior to either treatment alone 1
• If switching to sertraline is ineffective, combination therapy may provide additional benefit 1

Common Pitfalls to Avoid

• Inadequate dosing or duration: Ensure adequate trial before concluding medication ineffectiveness 1
• Overlooking psychosocial factors: Depression may be exacerbated by academic/social challenges that require psychosocial interventions 1
• Insufficient monitoring: Close monitoring is essential, especially for suicidal ideation 1, 4
• Polypharmacy without clear rationale: Have a clear rationale before using medication combinations 1
• Ignoring irritability component: Consider that SSRIs like sertraline may help with both depression and irritability symptoms 6

Special Considerations for Adolescents

• Adolescents may require larger doses and more upward dose adjustments than younger children 1
• Screen for bipolar disorder before initiating antidepressants, as they may precipitate manic episodes 4
• Antidepressants carry a boxed warning about increased risk of suicidal thoughts/behaviors in children and adolescents 4, 5
• Despite this risk, evidence suggests 6 times more teenagers benefit from antidepressants than are harmed 1

By following this approach, clinicians can make evidence-based decisions for treating depression and irritability in adolescents who have not responded to initial SSRI trials.