ArticleJournal of affective disorders2026
Treatment patterns and comparative clinical outcomes of ADHD medications in adolescents and young adults with comorbid major depressive disorder.
Article in Journal of affective disorders, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveThis study examined how comorbid major depressive disorder (MDD) influences ADHD treatment patterns and compared the associations between specific ADHD medication classes and clinical outcomes in adolescents and young adults aged 10-24 years.
methodsThis retrospective comparative cohort study analyzed electronic health records from the TriNetX US Collaborative Network (2010-2025). Among 1,026,253 patients with ADHD, 223,665 (21.8%) had comorbid MDD. Propensity score matching yielded balanced cohorts (ADHD-only and ADHD + MDD; 159,259 per cohort). ADHD treatment patterns were assessed prospectively over 12 months. Within the ADHD + MDD cohort, Cox proportional hazards regression examined whether CNS stimulants versus non-stimulants (including bupropion) differed in their associations with suicidality, antipsychotic initiation, mood stabilizer initiation, and intensive healthcare utilization.
resultsCompared with ADHD-only, ADHD + MDD was associated with higher overall ADHD medication prescribing, driven primarily by non-stimulants, particularly bupropion (RR 3.75, 95% CI 3.58-3.92), while racial and ethnic minority patients received fewer ADHD medications. New CNS stimulant prescriptions declined following MDD diagnosis (RR 0.92, 95% CI 0.91-0.93), especially in non-psychiatric settings. Among ADHD + MDD, CNS stimulants were associated with more favorable clinical outcomes compared with non-stimulants (aHRs 0.49-0.68). Bupropion demonstrated outcomes broadly comparable to CNS stimulants for suicidality and mood stabilizer initiation.
conclusionsComorbid MDD is associated with substantial shifts in ADHD medication prescribing toward non-stimulants, yet CNS stimulants were associated with the most favorable clinical outcomes, with bupropion emerging as a clinically meaningful alternative when a non-stimulant is considered. These findings should be validated in future longitudinal prospective studies and randomized clinical trials.
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