Clinical response to a single-dose methylphenidate challenge is indicative of treatment response at two months in adults with ADHD.

Stimulants such as methylphenidate (MPH) are the first-line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD). Although stimulants are effective at a group level, individual response varies, which advocates for tailored treatment approaches. Prior studies suggested that neurobiological measures following a single dose of stimulants are indicative of longer-term clinical response. To expand these findings, we tested whether an association between acute and longer-term treatment response can also be identified using measures commonly used in clinic. Sixty adults with ADHD completed clinico-neuropsychological measures, including the Barkley Adult ADHD Rating Scale-IV (BAARS-IV) and the Quantitative behavior (Qb) test, following a single dose of MPH (20 mg) and placebo. These measures were repeated after two-month MPH treatment to ascertain response. We tested associations between single-dose and longer-term response using univariate and multivariable (Lasso) regression approaches. We also ran correlations between predicted and true outcome measures. Univariate regressions showed significant associations between single-dose and two-month improvement in BAARS hyperactivity/impulsivity and Qb scores (all p < 0.001 but Qb activity, p = 0.006). Multivariable models including acute response and baseline clinicodemographic measures yielded significant correlations between predicted and actual values for all BAARS-IV and Qb scores at follow-up, except for BAARS inattention and Qb activity. Most had large/very large effect size (up to r = 0.69). These findings suggest that specific clinico-neuropsychological changes following a single dose of MPH may be indicative of longer-term treatment response, especially when combined with pre-treatment clinico-demographic characteristics. Once validated in larger and more heterogeneous samples, these results may support more informed and individualized treatment approaches for ADHD.