P.7.d.012 Effects of methylphenidate on cognition in ADHD across the lifespan: preliminary results of a meta-regression analysis

Abstract

Purpose: Stimulants like methylphenidate (MPH) are the first choice of pharmacological interventions for children and adults with attention-deficit hyperactivity disorder [1]. However, the human brain is in development until the early 20’s [2], and different behavioral responses to MPH have been shown for younger compared to older children [3]. This raises the question whether cognitive effects of MPH are related to the developmental stage of individuals with ADHD, and whether MPH effect might be associated with medication history of participants. Thus, the aims of the present meta-analysis were to determine whether the effect of MPH on cognitive functions is age-related, and whether medication naivety is associated with MPH effect. Methods: Double-blind, placebo controlled trials, reporting data on the effects of MPH on response inhibition, working memory and sustained attention, were included in a meta-regression analysis. Only samples with an ADHD diagnosis were included. In order to ensure comparability of effect sizes across study designs, an estimated correlation between measurements of 0.5 was taken into account when calculating effect sizes of crossover designs. Age and medication naivety were included in the analysis as moderators. Preliminary results: Forty-five studies (n = 1534) with 61 data points were included in the analyses, resulting in mean effect sizes of 0.41 for response inhibition (95%CI [0.22–0.61]), 0.27 for working memory (95%CI [−0.01–0.55]), and 0.45 for sustained attention (95%CI [0.26–0.63]). Effects of MPH on response inhibition and sustained attention were significant (both p< 0.0001). The mean effect size for working memory was not significant (p= 0.021). Overall, age did not significantly moderate the effect of MPH (QM = 0.02, df = 1, p= 0.90), but an age– response relationship was found for working memory (QM = 4.42, df = 1, p= 0.04). The influence of medication naivety was assessed with single dose trials in which the population was either described as 100% naive (5 studies), or as 0% naive (8 studies). Medication naivety of samples was not a significant moderator of MPH effect (QM = 0.34, df = 1, p= 0.56). Discussion: The present analysis shows moderate positive effects of MPH on response inhibition and sustained attention. The mean effect size for working memory studies was not significant. Interestingly, an age–response relationship was only found for working memory studies, with adult studies demonstrating larger effects. It is uncertain whether this reflects a heightened sensitivity to MPH of adult working memory, as this analysis only comprised two studies with adults and no studies with adolescents. This stresses the need for additional MPH trials with adolescents and adults. In addition, no relationship between naivety to stimulants and MPH effect was found, indicating that acute effects of MPH might be independent of treatment history.