Can a 16-year-old be prescribed Wellbutrin (bupropion) for major depressive disorder?

Can a 16-Year-Old Take Wellbutrin?

No, bupropion (Wellbutrin) is not FDA-approved for use in adolescents under 18 years of age for major depressive disorder, and fluoxetine remains the only antidepressant with FDA approval for pediatric depression (ages 8 and older). 1, 2 However, bupropion may be prescribed off-label in select cases after careful risk-benefit assessment and with close monitoring for suicidal ideation.

FDA Approval Status and Black Box Warning

• Bupropion lacks FDA approval for pediatric depression, distinguishing it from fluoxetine, which is the sole FDA-approved antidepressant for children and adolescents aged 8 years or older. 1
• All antidepressants, including bupropion, carry a black box warning for increased risk of suicidal thoughts and behaviors in patients younger than 24 years, particularly during the first 1-2 months of treatment. 1, 2
• This warning applies regardless of whether the medication is used on-label or off-label in this age group. 1

Off-Label Use: Evidence and Considerations

While not FDA-approved, emerging evidence suggests bupropion may be effective in adolescents when other options have failed or are contraindicated:

• A retrospective chart review of 127 youth (mean age 15.3 years) with depressive disorders showed significant improvement over 12 weeks, with 45.7% achieving response (CGI-Depression-I score ≤2) at a mean dose of 180 mg/day. 3
• An open trial in 11 adolescents demonstrated a 74% reduction in depression scores (mean SIGH-SAD scores decreased from 31.3 to 8.2), with 72.3% showing improvement at a mean dose of 362 mg/day. 4
• These studies provide preliminary evidence but are limited by small sample sizes, lack of placebo controls, and retrospective design. 3, 4

Critical Safety Screening Before Prescribing

Before considering bupropion in a 16-year-old, verify the absence of absolute contraindications: 5, 2

• Seizure history or conditions predisposing to seizures (epilepsy, brain tumor, stroke, head trauma, eating disorders)
• Current or recent MAOI use (within 14 days)
• Eating disorders (bulimia nervosa or anorexia nervosa—bupropion significantly increases seizure risk in these patients)
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs
• Uncontrolled hypertension
• Moderate to severe hepatic or renal impairment

Dosing Protocol for Adolescents (If Prescribed Off-Label)

Start low and titrate slowly to minimize adverse effects and seizure risk: 5, 3

• Initial dose: 37.5-75 mg once daily in the morning
• Titration: Increase by 37.5-75 mg every 3-7 days as tolerated
• Target dose: 150 mg twice daily (300 mg/day total) for sustained-release formulation
• Maximum dose: Do not exceed 300 mg/day in adolescents to maintain seizure risk at approximately 0.1% 5, 2
• Timing: Administer second dose before 3 PM to minimize insomnia risk 5

Mandatory Monitoring Requirements

Close monitoring is non-negotiable in adolescent patients: 1, 5

• Week 1-2: Assess for suicidal ideation, agitation, irritability, or unusual behavioral changes (risk for suicide attempts is greatest during first 1-2 months) 1
• Weeks 4,8,12: Evaluate therapeutic response using standardized depression scales
• Throughout treatment: Monitor blood pressure and heart rate (bupropion can elevate both parameters) 5, 2
• If no adequate response by 6-8 weeks at therapeutic doses, modify treatment approach 1

Common Adverse Effects in Adolescents

The most frequently reported adverse effects in adolescent studies include: 4, 3

• Insomnia (55% in one study—mitigated by avoiding late-day dosing)
• Irritability (9.4%—often resolves spontaneously or with dose reduction)
• Weight loss (55%)
• Dry mouth, headache, agitation (minority of patients)
• Discontinuation rate: 36.2% discontinued before 12 weeks in one study (19 due to adverse events, 15 due to poor effectiveness) 3

Clinical Advantages in Select Adolescent Populations

Bupropion may be particularly beneficial for adolescents with: 5, 6, 7

• Depression with prominent apathy, low energy, or hypersomnia (due to activating noradrenergic/dopaminergic properties)
• Concerns about sexual dysfunction (significantly lower rates compared to SSRIs)
• Concerns about weight gain (associated with weight loss or minimal weight change, unlike many SSRIs)
• Comorbid smoking cessation needs (addresses both depression and nicotine dependence)

Why Fluoxetine Should Be Considered First

Fluoxetine remains the evidence-based first-line choice for adolescent depression: 1

• It is the only FDA-approved antidepressant for children and adolescents aged 8 years or older
• It has the most robust safety and efficacy data in pediatric populations
• The same black box warning for suicidality applies to fluoxetine, so this risk does not favor bupropion

Clinical Decision Algorithm

1. First-line: Prescribe fluoxetine (FDA-approved for ages 8+) unless contraindicated 1
2. If fluoxetine fails or is not tolerated: Consider other SSRIs (paroxetine, sertraline) with established pediatric data 1
3. If multiple SSRIs fail or specific contraindications exist: Consider off-label bupropion only after:
   • Ruling out all absolute contraindications 5, 2
   • Discussing black box warning and increased monitoring requirements with patient and family 1
   • Establishing a plan for weekly monitoring during the first month 1
4. Never use bupropion as first-line in adolescents given lack of FDA approval and limited pediatric data 1, 3

Common Pitfalls to Avoid

• Do not exceed 300 mg/day in adolescents—higher doses substantially increase seizure risk 5, 2
• Do not prescribe to patients with eating disorders—this is an absolute contraindication due to dramatically elevated seizure risk 5, 2
• Do not skip the 1-2 week monitoring window—this is when suicidal ideation risk peaks 1
• Do not assume bioequivalence between formulations—monitor closely when switching between brand/generic or SR/XL formulations 5