What is the safety profile of Wellbutrin (bupropion) in children?

Wellbutrin (Bupropion) Safety Profile in Children

Bupropion is not FDA-approved for use in children under 18 years, and safety data in pediatric populations remain limited, though emerging evidence suggests it may be reasonably well-tolerated when used off-label for depression and ADHD in this age group. 1

FDA Status and Black Box Warnings

• Bupropion carries a black box warning for increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults under 24 years when used as an antidepressant, particularly within the first few months of treatment. 1
• The FDA has not approved bupropion for pediatric use (under 18 years), meaning all use in children is off-label. 1
• A second black box warning exists regarding neuropsychiatric symptoms including changes in behavior, aggression, hostility, agitation, depression, and suicidal ideation, originally identified in smoking cessation contexts but applicable to all bupropion use. 1

Seizure Risk - The Primary Safety Concern

• Seizures represent the most serious dose-dependent adverse effect of bupropion in all age groups, with risk increasing at higher doses and in certain vulnerable populations. 2, 1
• Bupropion is absolutely contraindicated in patients with seizure disorders, eating disorders (anorexia/bulimia), or brain metastases due to substantially elevated seizure risk. 2, 3
• In breastfed infants, two case reports have documented seizures potentially related to bupropion exposure through breast milk, though causality remains uncertain. 4

Pediatric-Specific Safety Data

Real-World Usage Patterns

• A 2024 analysis of 39,833 children (ages 6-17) newly starting bupropion found depression (57%) and ADHD (25%) were the most common indications, with concerning baseline characteristics including suicidal ideation (16.3%), poisoning history (5.9%), and eating disorders (2.2%). 5
• The most commonly prescribed formulation was bupropion extended-release 24-hour 150 mg (62% of initiations). 5

Adverse Events in Clinical Studies

• A 2019 retrospective study of 127 youth (mean age 15.3 years) with depressive disorders found bupropion generally well-tolerated, with irritability being the most common adverse event (9.4%), which resolved spontaneously in most cases or after discontinuation. 6
• In this same study, 36.2% discontinued bupropion before 12 weeks, with 19 patients (15%) stopping due to adverse events and 15 (11.8%) due to poor effectiveness. 6
• A 2017 systematic review of bupropion for pediatric ADHD found that in head-to-head trials, headache occurred more frequently with methylphenidate than bupropion, while other side effects showed no significant differences. 7

Common Side Effects

• Nervousness and insomnia are the most frequently reported side effects across age groups. 8
• Irritability appears particularly common in pediatric populations (9.4% in one study). 6
• Nausea occurs less commonly than with SSRIs, and sexual dysfunction is minimal compared to other antidepressants. 8

Overdose Toxicity - Critical Consideration

• A 2023 analysis specifically warns that bupropion displays more serious neurologic and cardiac toxicities in overdose than tricyclic antidepressants or SSRIs, with steadily increasing poisoning incidence and resultant morbidity/mortality in the 6-19 year age group since 2012. 9
• This toxicity profile is particularly concerning given the high rates of suicidal ideation (16.3%) and poisoning history (5.9%) in children prescribed bupropion. 5, 9

Pregnancy and Lactation Considerations

• Bupropion does not appear associated with major congenital malformations overall, though small absolute increases in left ventricular outflow tract obstruction and ventricular septal defects have been reported with first-trimester exposure, with confounding by indication not ruled out. 4
• Bupropion is present in breast milk at low levels (average 2% of maternal weight-adjusted dose), with generally no adverse events reported except two case reports of seizures in breastfed infants. 4
• The American Journal of Obstetrics and Gynecology guidelines advise "caution" for bupropion use during breastfeeding given very limited data (21 cases). 4

Monitoring Requirements

• Close monitoring for emergence of suicidal thoughts, worsening depression, unusual behavior changes, agitation, or irritability is mandatory, especially during the first few months of treatment or with dose changes. 1
• Patients and families must be educated to immediately report new or worsening mood symptoms, aggressive behavior, panic attacks, insomnia, or impulsivity. 1
• Screen carefully for contraindications including seizure history, eating disorders, and concurrent medications that lower seizure threshold before initiating treatment. 2, 3

Clinical Context and Alternatives

• Despite safety concerns, bupropion demonstrated comparable efficacy to methylphenidate for ADHD in head-to-head trials, though effect sizes were smaller in one large multicenter study. 7
• For depression in youth, a 2019 study showed 45.7% response rate at 12 weeks with significant improvement in Clinical Global Impressions scores. 6
• Given the serious overdose toxicity profile, some experts recommend considering antidepressants less toxic in overdose for the vulnerable 6-19 year age group. 9