Stimulant Persistence in Adult ADHD : A Retrospective Analysis of a Large Clinical Cohort

ABSTRACT Introduction Network meta‐analyses suggest dexamphetamines (dAMP) may yield more favourable short‐term outcomes than methylphenidate (MPH) in adults with ADHD, yet evidence on long‐term comparative persistence remains scarce. This study compared 12‐month treatment persistence between MPH and dAMP in a large multicentre cohort and explored associations with ADHD clinical presentations and objectively measured core symptoms. Methods Stimulant persistence was defined by the primary outcome, ‘time‐to‐transition’, the interval from initiation to switching stimulant classes, transitioning to non‐stimulants or complete discontinuation. Patients were censored at 12 months or at last clinical contact. A multivariable mixed‐effects Cox proportional hazard model with a random intercept for clinicians was used to estimate hazard ratios (HR) and assess the relative impact of stimulant class on persistence, including its interactions with DSM‐based clinical presentations and objective indices. Results Among 12,995 participants (49% female), 62% initiated dAMP and 38% MPH. Median time‐to‐transition was 33.1 weeks for dAMP versus 15.0 weeks for MPH. MPH was associated with a 45% increased hazard for non‐persistence compared to dAMP (HR = 1.45, 95% CI [1.36–1.55]). Regarding clinical and objective factors, hyperactive/impulsive presentation (HR = 1.14, p = 0.025) and objective impulsivity (HR = 1.05, p = 0.002) were independently associated with non‐persistence. A significant interaction was observed between stimulant class and objective hyperactivity ( p = 0.003), indicating that dAMP's persistence advantage became more pronounced with increasing motor activity (HR = 1.09). Nevertheless, these associations were secondary to the overarching effect of the stimulant class itself. Conclusion Treatment with dAMP demonstrates significantly superior 12‐month persistence compared to MPH in adults with ADHD. While clinical and objective measures of impulsivity and hyperactivity identify patients at higher risk for treatment non‐persistence, dAMP's advantage remains consistent across all presentations. These findings suggest that prioritizing dAMP may enhance long‐term treatment persistence in adult ADHD clinical practice.