10 research outputs found
Effects of methylphenidate on executive functioning in attention-deficit/hyperactivity disorder across the lifespan:A meta-regression analysis
Attention-deficit/hyperactivity disorder (ADHD) in childhood and adulthood is often treated with the psychostimulant methylphenidate (MPH). However, it is unknown whether cognitive effects of MPH depend on age in individuals with ADHD, while animal studies have suggested age-related effects. In this meta-analysis, we first determined the effects of MPH on response inhibition, working memory and sustained attention, but our main goal was to examine whether these effects are moderated by age. A systematic literature search using PubMed, PsycINFO, Web of Science and MEDLINE for double-blind, placebo-controlled studies with MPH resulted in 25 studies on response inhibition (n = 775), 13 studies on working memory (n = 559) and 29 studies on sustained attention (n = 956) (mean age range 4.8–50.1 years). The effects of MPH on response inhibition [effect size (ES) = 0.40, p < 0.0001, 95% confidence interval (CI) 0.22–0.58], working memory (ES = 0.24, p = 0.053, 95% CI 0.00–0.48) and sustained attention (ES = 0.42, p < 0.0001, 95% CI 26–0.59) were small to moderate. No linear or quadratic age-dependencies were observed, indicating that effects of MPH on executive functions are independent of age in children and adults with ADHD. However, adolescent studies are lacking and needed to conclude a lack of an age-dependency across the lifespan
Is er een typisch neuropsychologisch profiel bij volwassenen met ADHD?: Een ontwikkelingsperspectief
Er is in de afgelopen decennia uitgebreid onderzoek gedaan naar cognitieve problemen bij kinderen, maar ook naar cognitieve problemen bij volwassenen met de gedragsdiagnose ADHD. Het idee is dat de geobserveerde symptomen te relateren zijn aan executieve functieproblemen, delay-aversion, tijdverwerking en arousal. Dit betekent niet dat er een typisch neuropsychologisch profiel is voor volwassenen met ADHD. We zien dat de cognitieve problemen vaak nog aanwezig blijven als de gedragsproblemen afnemen, maar hierbij is de vraag in welke mate de cognitieve problemen gerelateerd zijn aan ADHD of juist het gevolg zijn van langdurig medicatiegebruik. Daarnaast is sprake van veel heterogeniteit in het type cognitieve problemen dat volwassenen met een ADHD-diagnose nog hebben. Er kan naar onze mening dus niet gesproken worden van een typisch neuropsychologisch ADHD-profiel. In dit kwalitatieve overzichtsartikel zal dit geĂŻllustreerd worden op basis van een serie recente bevindingen
The age-dependent effects of a single-dose methylphenidate challenge on cerebral perfusion in patients with attention-deficit/hyperactivity disorder
Methylphenidate (MPH) is a stimulant drug and an effective treatment for attention-deficit/hyperactivity disorder (ADHD) in both children and adults. Pre-clinical studies suggest that the response to stimulants is dependent on age, which may reflect the ontogeny of the dopamine (DA) system, which continues to develop throughout childhood and adolescence. Therefore, the aim of this study was to investigate the modulating effect of age on the cerebral blood flow (CBF) response to MPH in stimulant treatment-naive children and adults with ADHD. Ninety-eight stimulant treatment-naive male pediatric (10-12 years) and adult (23-40 years) patients with ADHD were included in this study. The CBF response to an acute challenge with MPH (0.5 mg/kg) was measured using arterial spin labeling (ASL) pharmacological magnetic resonance imaging, as a proxy for DA function. Region-of-interest (ROI) analyses were carried out for the striatum, thalamus and medial prefrontal cortex and in addition voxel-wise analyses were conducted. An acute challenge with MPH decreased CBF in both children and adults in cortical areas, although to a greater extent in adults. In contrast, ROI analyses showed that MPH decreased thalamic CBF only in children, but not adults. Our findings highlight the importance of taking the developmental perspective into account when studying the effects of stimulants in ADHD patients
Effects of 16 Weeks of Methylphenidate Treatment on Actigraph-Assessed Sleep Measures in Medication-Naive Children With ADHD
Methylphenidate (MPH) improves behavioral symptoms of attention-deficit/hyperactivity disorder (ADHD). Its effects on sleep, however, are insufficiently known, as trials with MPH in medication-naive children were so far restricted to relatively short trial durations. Here, we assessed effects of prolonged MPH treatment on sleep in medication-naive boys in a 16-weeks double-blind, placebo controlled, multicenter clinical trial with immediate-release MPH (ePOD-MPH trial, NTR3103). Seventy-five medication-naive boys, aged 10–12 years, were screened for eligibility using ADHD DSM-IV criteria. Sleep was assessed using actigraphy, diaries and questionnaires prior to randomization, in week 8, and 1 week after trial end. Fifty boys (mean age 11.4y, SD 0.9) were randomized to MPH or placebo. Linear mixed model analysis demonstrated a significant time-by-treatment interaction effect (p = 0.007) on sleep efficiency. Post-hoc analyses demonstrated that the two groups did not differ from each other (p = 0.94) during treatment (week 8), but that sleep efficiency was significantly improved in the MPH (p = 0.005), but not placebo group (p = 0.87) 1 week after trial end. The lack of MPH's negative effects on sleep during treatment differ from most previous studies and could be explained by the relatively long trial duration in our study and the medication-naive status of our sample; suggesting that evaluating sleep problems only shortly after treatment onset presents an incomplete picture, because it might not be representative for sleep quality after longer treatment periods. Our findings of improved sleep after trial end could be due to rebound effects or longer-term effects of MPH treatment and therefore require replication. Clinical Trial Registration: Central Committee on Research Involving Human Subjects (an independent registry, identifier NL34509.000.10) before enrollment of the first subject and The Netherlands National Trial Register, identifier NTR3103
Effects of prolonged methylphenidate treatment on amygdala reactivity and connectivity: a randomized controlled trial in stimulant treatment-naive, male participants with ADHD
Background Problems with emotional processing are widely reported in individuals with attention-deficit/hyperactivity disorder (ADHD). Although methylphenidate (MPH) effectively alleviates inattention and hyperactivity symptoms in ADHD, its effects on emotional processing and internalizing symptoms have remained elusive. While we previously found that acute MPH administration modulated neural mechanisms underlying emotional processing in an age-dependent manner, the effects of prolonged administration remained unknown. Objectives Therefore, we investigated: (i) whether prolonged MPH treatment influences neural substrates (amygdala reactivity and connectivity) of emotional processing, and (ii) whether these effects are modulated by age. Methods The “effects of Psychotropic drugs On Developing brain-MPH” (“ePOD-MPH”) randomized controlled trial was a 16-week double-blind, placebo-controlled, multi-center trial with MPH in 50 boys (10–12 years of age) and 49 men (23–40 years of age), all stimulant treatment-naive and diagnosed with ADHD. Participants performed an emotional face-matching task during functional magnetic resonance imaging. We assessed their symptoms of ADHD and internalizing symptoms at baseline, during the trial (8 weeks), and 1 week after the trial end (17 weeks). Results and Conclusions We did not find effects of prolonged MPH treatment on emotional processing, as measured by amygdala reactivity and connectivity and internalizing symptoms in this trial with stimulant treatment-naive participants. This differs from our findings on emotional processing following acute MPH administration and the effects of prolonged MPH treatment on the dopamine system, which were both modulated by age. Interestingly, prolonged MPH treatment did improve ADHD symptoms, although depressive and anxiety symptoms showed a medication-independent decrease. Furthermore, our data indicate that baseline internalizing symptoms may be used to predict MPH treatment effects on ADHD symptoms, particularly in (male) adults with ADHD
Age-dependent effects of methylphenidate on the human dopaminergic system in young vs adult patients with attention-deficit/hyperactivity disorder: A randomized clinical trial
textabstractIMPORTANCE Although numerous children receivemethylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly lasting effects of methylphenidate on the human dopaminergic system. OBJECTIVES To determine whether the effects of methylphenidate on the dopaminergic system are modified by age and to test the hypothesis that methylphenidate treatment of young but not adult patients with ADHD induces lasting effects on the cerebral blood flow response to dopamine challenge, a noninvasive probe for dopamine function. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled trial (Effects of Psychotropic Drugs on Developing Brain-Methylphenidate) among ADHD referral centers in the greater Amsterdam area in the Netherlands between June 1, 2011, and June 15, 2015. Additional inclusion criteria were male sex, age 10 to 12 years or 23 to 40 years, and stimulant treatment-naive status. INTERVENTIONS Treatment with either methylphenidate or a matched placebo for 16 weeks. MAIN OUTCOMES AND MEASURES Change in the cerebral blood flowresponse to an acute challenge with methylphenidate, noninvasively assessed using pharmacological magnetic resonance imaging, between baseline and 1 week after treatment. Data were analyzed using intent-to-treat analyses. RESULTS Among 131 individuals screened for eligibility, 99 patients met DSM-IV criteria for ADHD, and 50 participants were randomized to receivemethylphenidate and 49 to placebo. Sixteen weeks of methylphenidate treatment increased the cerebral blood flow response to methylphenidate within the thalamus (mean difference, 6.5; 95%CI, 0.4-12.6; P = .04) of children aged 10 to 12 years old but not in adults or in the placebo group. In the striatum, the methylphenidate condition differed significantly from placebo in children but not in adults (mean difference, 7.7; 95%CI, 0.7-14.8; P = .03). CONCLUSIONS AND RELEVANCE We confirm preclinical data and demonstrate age-dependent effects of methylphenidate treatment on human extracellular dopamine striatal-thalamic circuitry. Given its societal relevance, these data warrant replication in larger groups with longer follow-up