Comparative Incidence of Oppositional Defiant and Conduct Disorders in ADHD: Bupropion vs. Stimulant Treatments

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is often complicated by comorbid Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD), which worsen outcomes. Stimulants, the standard ADHD treatment, may exacerbate aggression and oppositional behaviors, while bupropion, an atypical antidepressant, has emerged as a potential alternative with fewer behavioral risks. Objective: This study evaluates whether ADHD patients treated with bupropion have lower incidences of ODD and CD compared to those treated with stimulants. Methods: A retrospective cohort study was conducted using the TriNetX Global Collaborative Network. ADHD patients treated with stimulants (n=372,330) or bupropion (n=132,457) were analyzed. Patients with prior ODD, CD, or tobacco use were excluded. Incidence rates of ODD and CD were compared using measures of association and Kaplan-Meier survival analysis. Results: The incidence of ODD was significantly higher in the stimulant cohort (1.3%) compared to the bupropion cohort (0.5%) with a risk difference of 0.8% (95% CI: 0.007-0.009) and a risk ratio of 2.7 (95% CI: 2.484-2.934). Similarly, CD incidence was higher in the stimulant cohort (1.9%) versus the bupropion cohort (1.0%), with a risk difference of 0.9% (95% CI: 0.008-0.010) and a risk ratio of 1.864 (95% CI: 1.756-1.978). Kaplan-Meier analysis confirmed higher risks of ODD and CD in stimulant-treated patients. Conclusion: Bupropion is associated with a lower risk of ODD and CD in ADHD patients compared to stimulants. These findings suggest that bupropion may be a safer alternative for ADHD patients at risk for these comorbid disorders, though further research is needed to confirm these results and explore underlying mechanisms. While this study provides valuable insights, the retrospective design introduces potential limitations, including biases from unmeasured confounders and the risk of incomplete or inaccurate data in the database.