What is the most appropriate medication for anxiety and depression in a 13‑year‑old with persistent anxiety and depression who failed sertraline, and who also has attention‑deficit/hyperactivity disorder and functional (psychogenic) seizures?

Medication for Anxiety and Depression in a 13-Year-Old After Sertraline Failure with ADHD and Functional Seizures

Switch to fluoxetine as the next SSRI trial, as it is the only antidepressant with guideline-level evidence for adolescents with depression, and address ADHD with methylphenidate only after mood stabilization is achieved.

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Primary Pharmacologic Strategy

First-Line Antidepressant Selection

• Fluoxetine is the only SSRI recommended by WHO guidelines for adolescents (13–18 years) with depressive episodes in non-specialist settings, with explicit guidance that other SSRIs and tricyclic antidepressants should not be used. 1
• The American Academy of Child and Adolescent Psychiatry (AACAP) guidelines state that fluoxetine—but not other SSRIs or TCAs—may be considered for adolescents with depressive episodes, with close monitoring for suicidal ideation and behavior required. 1
• Start fluoxetine at 10 mg daily for 1 week to assess tolerability, then increase to 20 mg daily as the therapeutic target dose. 1
• Adolescents on fluoxetine must be monitored closely for suicide ideas and behavior, as SSRIs carry a black-box warning for increased suicidal thinking through age 24 (absolute risk 1% vs. 0.2% for placebo, NNH=143). 1

Why Not Continue SSRI Trials Beyond Fluoxetine

• WHO guidelines explicitly state that pharmacological interventions should not be considered for children and adolescents with anxiety disorders in non-specialist settings, suggesting that after fluoxetine failure, referral to specialty care is appropriate rather than cycling through additional SSRIs. 1
• The evidence base for SSRIs other than fluoxetine in adolescent depression is insufficient to support their use in primary care settings. 1

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ADHD Management Strategy

Timing of ADHD Treatment Initiation

• Do not initiate ADHD medication until depressive and anxiety symptoms are adequately controlled, as untreated mood disorders can masquerade as ADHD treatment failure and stimulants may worsen anxiety if introduced prematurely. 2
• Approximately 10% of adolescents with recurrent depression/anxiety have comorbid ADHD, and treatment of mood symptoms alone will likely be inadequate to restore optimal functioning when ADHD remains unaddressed. 2

First-Line ADHD Medication After Mood Stabilization

• Methylphenidate is the preferred first-line stimulant for adolescents with ADHD and comorbid anxiety/depression, with the strongest evidence base and 70–80% response rates when properly titrated. 2
• Begin with long-acting methylphenidate formulations (e.g., OROS-methylphenidate 18 mg once daily) to provide all-day coverage and minimize rebound symptoms. 2
• Titrate methylphenidate by 18 mg weekly up to 54–72 mg daily maximum, using systematic dose optimization rather than weight-based calculations. 2
• Stimulants work within days, allowing rapid assessment of ADHD symptom response, unlike the 6–12 weeks required for non-stimulants like atomoxetine. 2

Evidence Supporting Stimulants in Anxious Youth

• The Multimodal Treatment Study of Children with ADHD (MTA) demonstrated that stimulants do not exacerbate anxiety in patients with comorbid anxiety disorders; in fact, response rates to ADHD treatment were higher in the anxious subgroup. 2
• If ADHD symptoms improve on methylphenidate but anxiety persists, add cognitive-behavioral therapy (CBT) rather than increasing medication, as combination CBT plus medication is superior to either alone for anxiety disorders. 1, 3

Non-Stimulant Alternative if Stimulants Are Contraindicated

• Atomoxetine (starting at 40 mg daily, titrating to 60–100 mg daily) is the only FDA-approved non-stimulant for ADHD in adolescents and has specific evidence for efficacy in patients with comorbid anxiety. 2
• Atomoxetine requires 6–12 weeks to achieve full therapeutic effect (versus days for stimulants) and has medium-range effect sizes (≈0.7 vs. ≈1.0 for stimulants). 2
• Atomoxetine carries an FDA black-box warning for increased suicidal ideation in children and adolescents, requiring close monitoring during the first few months and at dose changes. 2

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Special Consideration: Functional Seizures

Medication Safety in Functional Seizures

• Functional (psychogenic) seizures are not true epileptic seizures and do not require antiepileptic drugs; they are a manifestation of psychological distress and respond to psychiatric treatment. 1
• SSRIs (fluoxetine) should be used cautiously in patients with a history of seizure disorder, though functional seizures do not represent a true seizure disorder. 1
• Stimulants (methylphenidate) should be used cautiously in patients with a history of seizure disorder, but functional seizures are not a contraindication to stimulant use. 2
• WHO guidelines warn against overinterpretation of EEG findings and misdiagnosis of epilepsy, which is an important problem; ensure functional seizures are correctly diagnosed before withholding effective psychiatric medications. 1

Psychosocial Intervention for Functional Seizures

• Cognitive-behavioral therapy is the primary evidence-based treatment for functional seizures, addressing the underlying psychological mechanisms. 1
• Psychoeducation about the nature of functional seizures (i.e., that they are not epileptic and do not require antiepileptic drugs) is essential for the patient and family. 1

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Monitoring and Follow-Up

Initial Phase (Weeks 1–8)

• Assess treatment response at 4 weeks and 8 weeks using standardized validated instruments for depression and anxiety symptoms. 1
• Monitor for suicidal ideation at every visit, particularly during the first few months of fluoxetine treatment and at dose changes. 1
• If little improvement occurs after 8 weeks of fluoxetine at 20 mg daily despite good adherence, refer to child and adolescent psychiatry for consideration of combination therapy (fluoxetine plus CBT) or alternative treatments. 1

After ADHD Medication Initiation

• Monitor blood pressure and pulse at baseline and at each visit during methylphenidate titration. 2
• Track height and weight at every visit, as stimulants can suppress growth by 1–2 cm from predicted adult height. 2
• Assess sleep quality and appetite changes, as these are common adverse effects of stimulants. 2

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Common Pitfalls to Avoid

• Do not use antidepressant monotherapy to treat both depression and ADHD; no single antidepressant is proven to effectively treat both conditions, and ADHD requires separate pharmacologic intervention. 2
• Do not initiate stimulants before mood stabilization is achieved, as this can worsen anxiety and complicate assessment of treatment response. 2
• Do not assume functional seizures are a contraindication to psychiatric medications; they are a psychological phenomenon requiring psychiatric treatment, not antiepileptic drugs. 1
• Do not cycle through multiple SSRIs in primary care after fluoxetine failure; WHO guidelines recommend referral to specialty care for adolescents with treatment-resistant depression. 1
• Do not underdose fluoxetine; 20 mg daily is the therapeutic target for adolescents, and inadequate dosing is a common reason for apparent treatment failure. 1

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Referral Indications

• Refer to child and adolescent psychiatry if fluoxetine fails after an adequate 8-week trial at 20 mg daily, as this represents treatment-resistant depression requiring specialty care. 1, 4
• Refer if suicidal ideation emerges or worsens during fluoxetine treatment, as this requires immediate psychiatric evaluation. 1
• Refer if functional seizures persist despite CBT, as this may indicate a more complex conversion disorder requiring specialized intervention. 1