Cognitive Effects Of Methylphenidate Research Articles

Cognitive effects of methylphenidate in Parkinson's disease patients using electrophysiological measures

Cognitive effects of methylphenidate in Parkinson's disease patients using electrophysiological measures

Stratifying drug treatment of cognitive impairments after traumatic brain injury using neuroimaging.

Cognitive impairment is common following traumatic brain injury. Dopaminergic drugs can enhance cognition after traumatic brain injury, but individual responses are highly variable. This may be due to variability in dopaminergic damage between patients. We investigate whether measuring dopamine transporter levels using 123I-ioflupane single-photon emission computed tomography (SPECT) predicts response to methylphenidate, a stimulant with dopaminergic effects. Forty patients with moderate-severe traumatic brain injury and cognitive impairments completed a randomized, double-blind, placebo-controlled, crossover study. 123I-ioflupane SPECT, MRI and neuropsychological testing were performed. Patients received 0.3 mg/kg of methylphenidate or placebo twice a day in 2-week blocks. Subjects received neuropsychological assessment after each block and completed daily home cognitive testing during the trial. The primary outcome measure was change in choice reaction time produced by methylphenidate and its relationship to stratification of patients into groups with normal and low dopamine transporter binding in the caudate. Overall, traumatic brain injury patients showed slow information processing speed. Patients with low caudate dopamine transporter binding showed improvement in response times with methylphenidate compared to placebo [median change = -16 ms; 95% confidence interval (CI): -28 to -3 ms; P = 0.02]. This represents a 27% improvement in the slowing produced by traumatic brain injury. Patients with normal dopamine transporter binding did not improve. Daily home-based choice reaction time results supported this: the low dopamine transporter group improved (median change -19 ms; 95% CI: -23 to -7 ms; P = 0.002) with no change in the normal dopamine transporter group (P = 0.50). The low dopamine transporter group also improved on self-reported and caregiver apathy assessments (P = 0.03 and P = 0.02, respectively). Both groups reported improvements in fatigue (P = 0.03 and P = 0.007). The cognitive effects of methylphenidate after traumatic brain injury were only seen in patients with low caudate dopamine transporter levels. This shows that identifying patients with a hypodopaminergic state after traumatic brain injury can help stratify the choice of cognitive enhancing therapy.

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.

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

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.

Cognitive effects of methylphenidate in healthy volunteers: a review of single dose studies

Methylphenidate (MPH), a stimulant drug with dopamine and noradrenaline reuptake inhibition properties, is mainly prescribed in attention deficit hyperactivity disorder, is increasingly used by the general population, intending to enhance their cognitive function. In this literature review, we aim to answer whether this is effective. We present a novel way to determine the extent to which MPH enhances cognitive performance in a certain domain. Namely, we quantify this by a percentage that reflects the number of studies showing performance enhancing effects of MPH. To evaluate whether the dose-response relationship follows an inverted-U-shaped curve, MPH effects on cognition are also quantified for low, medium and high doses, respectively. The studies reviewed here show that single doses of MPH improve cognitive performance in the healthy population in the domains of working memory (65% of included studies) and speed of processing (48%), and to a lesser extent may also improve verbal learning and memory (31%), attention and vigilance (29%) and reasoning and problem solving (18%), but does not have an effect on visual learning and memory. MPH effects are dose-dependent and the dose-response relationship differs between cognitive domains. MPH use is associated with side effects and other adverse consequences, such as potential abuse. Future studies should focus on MPH specifically to adequately asses its benefits in relation to the risks specific to this drug.

Cognitive effects of methylphenidate and levodopa in healthy volunteers

Our previous study showed enhanced declarative memory consolidation after acute methylphenidate (MPH) administration. The primary aim of the current study was to investigate the duration of this effect. Secondary, the dopaminergic contribution of MPH effects, the electrophysiological correlates of declarative memory, and the specificity of memory enhancing effects of MPH to declarative memory were assessed. Effects of 40mg of MPH on memory performance were compared to 100mg of levodopa (LEV) in a placebo-controlled crossover study with 30 healthy volunteers. Memory performance testing included a word learning test, the Sternberg memory scanning task, a paired associates learning task, and a spatial working memory task. During the word learning test, event-related brain potentials (ERPs) were measured. MPH failed to enhance retention of words at a 30min delay, but it improved 24h delayed memory recall relative to PLA and LEV. Furthermore, during encoding, the P3b and P600 ERP latencies were prolonged and the P600 amplitude was larger after LEV compared to PLA and MPH. MPH speeded response times on the Sternberg Memory Scanning task and improved performance on the Paired Associates Learning task, relative to LEV, but not PLA. Performance on the Spatial working memory task was not affected by the treatments. These findings suggest that MPH and LEV might have opposite effects on memory

Influence of methylphenidate treatment assumptions on cognitive function in healthy young adults in a double-blind, placebo-controlled trial

BackgroundIncreasing numbers of students use stimulants such as methylphenidate (MPH) to improve their study capacity, making them prone to subsequent prolonged drug abuse. This study explored the cognitive effects of MPH in students who either assumed they received MPH or assumed they received a placebo.MethodsIn a double-blind, randomized, placebo-controlled trial with a between-subjects design, 21 students were subjected to partial sleep deprivation, receiving no more than 4 hours sleep the night before they were tested. In the morning, they were given either a placebo or 20 mg of MPH. They then performed free recall verbal tests and Go/No-Go tasks repeatedly, their moods were evaluated using Profile of Mood States and their tiredness was assessed using a visual analog scale, with evaluation of vigilance.ResultsNo significant differences were found between those subjects who received MPH and those who received a placebo. However, significant differences were found between subjects who assumed they had received MPH or had no opinion, and those who assumed they had received a placebo. At three minutes, one hour, and one day after memorizing ten lists of 20 words, those who assumed they had received MPH recalled 54%, 58%, and 54% of the words, respectively, whereas those who assumed they had received placebo only recalled 35%, 37%, and 34%.ConclusionHealthy, partially sleep-deprived young students who assume they have received 20 mg of MPH experience a substantial placebo effect that improves consolidation of information into long-term memory. This is independent of any pharmacologic effects of MPH, which had no significant effects on verbal memory in this study. This information may be used to dissuade students from taking stimulants such as MPH during examination periods, thus avoiding subsequent abuse and addiction.

Methylphenidate Disrupts Social Play Behavior in Adolescent Rats

Methylphenidate is the first-choice treatment for attention-deficit/hyperactivity disorder (ADHD), but its mechanism of action is incompletely understood. The cognitive effects of methylphenidate have been extensively studied, but little is known about its effects on spontaneous social behavior. During adolescence, rats display a characteristic, highly vigorous form of social behavior, termed social play behavior, which is of critical importance for social and cognitive development. We investigated the neurobehavioral mechanisms by which methylphenidate affects social play behavior in rats. Methylphenidate (0.3-3.0 mg/kg, s.c. or p.o.) abolished social play behavior, without altering general social interest. This effect of methylphenidate did not depend upon the baseline level of social play and was not secondary to changes in locomotion. Furthermore, the play-suppressant effect of methylphenidate was not subject to tolerance or sensitization. Methylphenidate blocked both the initiation to play and the responsivity to play initiation. The effect of methylphenidate was mimicked by the noradrenaline reuptake inhibitor atomoxetine, which is also used for the treatment of ADHD, and was blocked by an alpha-2 adrenoceptor antagonist. In addition, combined administration of subeffective doses of methylphenidate and atomoxetine suppressed social play. However, blockade of alpha-1 adrenoceptors, beta-adrenoceptors, or dopamine receptors did not alter the effect of methylphenidate. These data show that methylphenidate selectively blocks the most vigorous part of the behavioral repertoire of adolescent rats through a noradrenergic mechanism. We suggest that the effect of methylphenidate on social play is a reflection of its therapeutic effect in ADHD, that is, improved behavioral inhibition. However, given the importance of social play for development, these findings may also indicate an adverse side effect of methylphenidate.

Clinical and cognitive effects of methylphenidate on children with attention deficit disorder as a function of aggression/oppositionality and age.

Clinical and cognitive effects of methylphenidate on children with attention deficit disorder as a function of aggression/oppositionality and age.