Acute effects of immediate-release methylphenidate on QbTest performance in adults with untreated ADHD and longstanding polysubstance use: a randomized double-blind placebo-controlled crossover study

Background Although methylphenidate (MPH) is a first-line treatment for adult attention-deficit/hyperactivity disorder (ADHD) in Europe, evidence in individuals with co-occurring ADHD and substance use disorder (SUD) remains limited, particularly in those with longstanding polysubstance use. This study examined the acute effects of immediate-release methylphenidate (IR-MPH) versus placebo on cognitive performance in this population. Methods In this randomized, double-blind, placebo-controlled crossover study, 39 adults with untreated ADHD and longstanding polysubstance use completed the QbTest before and 80 min after a single 20-mg dose of IR-MPH and placebo on separate study days. Objective outcomes were the cardinal QbTest parameters QbActivity, QbInattention, and QbImpulsivity. Subjective outcomes included self-rated expected performance, perceived performance, perceived mental effort, perceived benefit from the study medication, and task comprehension. Repeated-measures analyses of variance (ANOVA) and paired-samples t-tests were used to compare outcomes across conditions. Results Compared with baseline, IR-MPH significantly improved QbInattention [mean difference 1.00, 95% CI (0.55–1.45), p < 0.001], QbActivity [mean difference 0.83, 95% CI (0.37–1.28), p < 0.001], and QbImpulsivity [mean difference 0.83, 95% CI (0.12–1.55), p < 0.001]. These effects remained significant after adjustment for placebo effects. Placebo was associated with significant improvement only in reaction time [mean difference 35.15, 95% CI (2.37–67.84), p < 0.029]. Expected performance and perceived performance improved after IR-MPH but not after placebo, whereas mental effort decreased after both conditions. Participants reported greater perceived benefit from IR-MPH than from placebo. No QbTest order effects were observed. Conclusions IR-MPH was associated with short-term improvements in objective QbTest performance in adults with untreated ADHD and longstanding polysubstance use, whereas placebo effects were limited on objective outcomes and were more evident in subjective experience. These findings support the inclusion of objective assessments alongside self-report when evaluating early treatment response in clinically complex adults with ADHD and co-occurring SUD. Trial registration NCT02477280 in ClinicalTrial.gov, registered on June 22, 2015.