Effects of one single-dose methylphenidate compared to one single-dose placebo on QbTest performance in adults with untreated ADHD: a randomized controlled trial.

BACKGROUND: Treatment of adults with attention-deficit/hyperactivity disorder (ADHD) primary involves methylphenidate (MPH). Earlier studies have identified placebo responders to increase toward the end of the treatment periods. However, little is known about the immediate effects of placebo on the core symptoms of ADHD in adults. The present study aimed to examine the effects of one single-dose MPH compared to one single-dose placebo during clinical assessments with continuous performance tests (CPT). METHODS: In a randomized study with cross-over design, 40 adults between 19 and 64 years (72.5% women) with untreated ADHD were consecutively enrolled. The study comprised two trial days with four days in between. The QbTest was performed twice on the same day, before and 80 min after intake of one single-dose 20 mg immediate release methylphenidate (IR-MPH) and with one single-dose placebo, in randomized order. RESULTS: Performance improved in QbInattention, F (3, 117) = 38.25, p < 0.001, after given IR-MPH (mean diff = 1.14) and after placebo (mean diff = 0.60) with the effect sizes 1.17 and 0.63 respectively. IR-MPH improved performance in QbActivity (mean diff = 0.81, p < 0.001) and QbImpulsivity (mean diff = 0.46, p < 0.04). The proportion of improvements (a decrease by ≥ 0.5 Qb-score) in the parameters QbInattention, QbActivity and QbImpulsivity were 90%, 60% and 52.5%, respectively. After given placebo, corresponding proportions were 60%, 30% and 35%, respectively. CONCLUSIONS: There seems to be an immediate placebo response in the core symptom inattention. The effect of placebo cannot be ruled out and must be taken in consideration during drug trials with continuous performance tests (CPTs). TRIAL REGISTRATION: ClinicalTrials.gov; Identifier: NCT02473185.

Contrasting expectancy effects with objective measures in adults with untreated ADHD during QbTest.

Expectancy has been associated with neuropsychological assessments and cognitive performance. However, little is known about the effects of expectations in clinical assessments during drug trials with continuous performance tests (CPTs). In a randomized, double-blind study with cross-over design, we examined if the participants' self-reported expectations changed after one-single dose immediate release methylphenidate (MPH) and after one-single dose placebo during the QbTest. Forty adults between 19 and 64 years (72.5% women) with un treated ADHD were consecutively enrolled in the study and their assessments of expected performance, mental effort, perceived performance and help from the pill were analyzed. The study comprised two trial days with four days in between. The QbTest was performed twice on the same day, before and 80 minutes after a pill. Our study demonstrates that there were expectancy effects during CPTs. Participants reported lower mental effort and improved their performance in the coronary parameter QbInattention both after MPH and after placebo. No significant differences in expected performance were reported. The participants seemed to show some uncertainty when assessing their expected performance, however, they could evaluate their performance afterwards. In clinical practice, the focus should be on reinforcing patients' expectations in order to increase treatment effects.