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

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.