Dataset Information

Effects of methylphenidate on executive functioning in children and adolescents with ADHD after long-term use: a randomized, placebo-controlled discontinuation study.

ABSTRACT:

Background

Methylphenidate may improve executive functioning in children with attention-deficit/hyperactivity disorder (ADHD). However, it is unclear if there are still acute effects of methylphenidate on executive functioning after long-term use.

Methods

In a randomized double-blind, placebo-controlled discontinuation study, 94 children and adolescents (ages 8-18 years) who used methylphenidate beyond two years were either assigned to seven weeks of continued treatment with 36 or 54 mg of extended-release methylphenidate or to gradual withdrawal over three weeks to placebo for four weeks. Performance on neuropsychological tasks, measuring working memory, response inhibition, attentional flexibility and psychomotor speed was compared between both groups using mixed models for repeated measures. Additionally, we investigated within the discontinuation group if a deterioration on the investigator-rated Clinical Global Impressions Improvement scale after withdrawing to placebo was related to a worse performance on the neuropsychological tasks. This study was registered in the Netherlands Trial Register (www. Trialregister.nl) with identifier 5252.

Results

After withdrawal of methylphenidate, the discontinuation group made more errors on working memory (β = -1.62, SD = 0.56, t = -2.88, p = .01, Cohen's f2 = .14), independent from reaction time compared to baseline, in contrast to the continuation group. We did not find differences in changes in response inhibition, attentional flexibility and psychomotor speed between the two groups. Also, there were no significant differences in task measures between the participants who deteriorated clinically and those who did not.

Conclusions

Our study shows that methylphenidate has a beneficial effect on working memory after two years of use. Future studies should explore whether cognitive outcomes may aid clinical decision-making on the continued use of methylphenidate, given dissociation between cognitive and behavioural effects of stimulant medication.

SUBMITTER: Rosenau PT

PROVIDER: S-EPMC9292145 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Neurocognitive heterogeneity is increasingly recognized as a valid phenomenon in ADHD, with most estimates suggesting that executive dysfunction is present in only about 33%-50% of these children. However, recent critiques question the veracity of these estimates because our understanding of executive functioning in ADHD is based, in large part, on data from single tasks developed to detect gross neurological impairment rather than the specific executive processes hypothesized to underlie the ADHD phenotype. The current study is the first to comprehensively assess heterogeneity in all three primary executive functions in ADHD using a criterion battery that includes multiple tests per construct (working memory, inhibitory control, set shifting). Children ages 8-13 (M?=?10.37, SD?=?1.39) with and without ADHD (N?=?136; 64 girls; 62% Caucasian/Non-Hispanic) completed a counterbalanced series of executive function tests. Accounting for task unreliability, results indicated significantly improved sensitivity and specificity relative to prior estimates, with 89% of children with ADHD demonstrating objectively-defined impairment on at least one executive function (62% impaired working memory, 27% impaired inhibitory control, 38% impaired set shifting; 54% impaired on one executive function, 35% impaired on two or all three executive functions). Children with working memory deficits showed higher parent- and teacher-reported ADHD inattentive and hyperactive/impulsive symptoms (BF10?=?5.23?×?104), and were slightly younger (BF10?=?11.35) than children without working memory deficits. Children with vs. without set shifting or inhibitory control deficits did not differ on ADHD symptoms, age, gender, IQ, SES, or medication status. Taken together, these findings confirm that ADHD is characterized by neurocognitive heterogeneity, while suggesting that contemporary, cognitively-informed criteria may provide improved precision for identifying a smaller number of neuropsychologically-impaired subtypes than previously described.

Project description:IntroductionExecutive functions (EFs) training interventions aimed at ADHD-symptom reduction have yielded mixed results. Generally, these interventions focus on training a single cognitive domain (e.g., working memory [WM], inhibition, or cognitive-flexibility). However, evidence suggests that most children with ADHD show deficits on multiple EFs, and that these EFs are largely related to different brain regions. Therefore, training multiple EFs might be a potentially more effective strategy to reduce EF-related ADHD symptoms.MethodsEighty-nine children with a clinical diagnosis of ADHD (aged 8-12) were randomized to either a full-active-condition where visuospatial WM, inhibition and cognitive-flexibility were trained, a partially-active-condition where inhibition and cognitive-flexibility were trained and the WM-training task was presented in placebo-mode, or to a full placebo-condition. Short-term and long-term (3-months) effects of this gamified, 25-session, home-based computer-training were evaluated on multiple outcome domains.ResultsDuring training compliance was high (only 3% failed to meet compliance criteria). After training, only children in the full-active condition showed improvement on measures of visuospatial short-term-memory (STM) and WM. Inhibitory performance and interference control only improved in the full-active- and the partially-active condition. No Treatment-condition x Time interactions were found for cognitive-flexibility, verbal WM, complex-reasoning, nor for any parent-, teacher-, or child-rated ADHD behaviors, EF-behaviors, motivational behaviors, or general problem behaviors. Nonetheless, almost all measures showed main Time-effects, including the teacher-ratings.ConclusionsImprovements on inhibition and visuospatial STM and WM were specifically related to the type of treatment received. However, transfer to untrained EFs and behaviors was mostly nonspecific (i.e., only interference control improved exclusively in the two EF training conditions). As such, in this multiple EF-training, mainly nonspecific treatment factors - as opposed to the specific effects of training EFs-seem related to far transfer effects found on EF and behavior.Trial registrationtrialregister.nl NTR2728. Registry name: improving executive functioning in children with ADHD: training executive functions within the context of a computer game; registry number: NTR2728.

Project description:IntroductionEarlier studies exploring the value of executive functioning (EF) indices for assessing treatment effectiveness and predicting treatment response in attention-deficit/hyperactivity disorder (ADHD) mainly focused on pharmacological treatment options and revealed rather heterogeneous results. Envisioning the long-term goal of personalized treatment selection and intervention planning, this study comparing methylphenidate treatment (MPH) and a home-based neurofeedback intervention (NF@Home) aimed to expand previous findings by assessing objective as well as subjectively reported EF indices and by analyzing their value as treatment and predictive markers.MethodsChildren and adolescents (n = 146 in the per protocol sample) aged 7-13 years with a formal diagnosis of an inattentive or combined presentation of ADHD were examined. We explored the EF performance profile using the Conners Continuous Performance Task (CPT) and the BRIEF self-report questionnaire within our prospective, multicenter, randomized, reference drug-controlled NEWROFEED study with sites in five European countries (France, Spain, Switzerland, Germany, and Belgium). As primary outcome for treatment response, the clinician-rated ADHD Rating Scale-IV was used. Patients participating in this non-inferiority trial were randomized to either NF@home (34-40 sessions of TBR or SMR NF depending on the pre-assessed individual alpha peak frequency) or MPH treatment (ratio: 3:2). Within a mixed-effects model framework, analyses of change were calculated to explore the predictive value of neurocognitive indices for ADHD symptom-related treatment response.ResultsFor a variety of neurocognitive indices, we found a significant pre-post change during treatment, mainly in the MPH group. However, the results of the current study reveal a rather limited prognostic value of neurocognitive indices for treatment response to either NF@Home or MPH treatment. Some significant effects emerged for parent-ratings only.DiscussionCurrent findings indicate a potential value of self-report (BRIEF global score) and some objectively measured neurocognitive indices (CPT commission errors and hit reaction time variability) as treatment markers (of change) for MPH. However, we found a rather limited prognostic value with regard to predicting treatment response not (yet) allowing recommendation for clinical use. Baseline symptom severity was revealed as the most relevant predictor, replicating robust findings from previous studies.

Project description:UnlabelledVery little is known about the psychological consequences of a cardiac arrest (CA) during childhood. Our aim was to assess long-term emotional and behavioral functioning, and its predictors, in survivors of CA in childhood. This long-term follow-up study involved all consecutive infants, children, and adolescents surviving CA in a tertiary-care university children's hospital between January 2002 and December 2011. Emotional and behavioral functioning was assessed with the Child Behavior Checklist (CBCL), Teacher's Report Form (TRF), and Youth Self-Report (YSR). Of the eligible 107 CA survivors, 52 patients, parents, and/or teachers filled out online questionnaires. Compared with normative data, parents and teachers reported significantly more attention and somatic problems (age range 6-18 years). Parents also reported more attention problems for age range 1.5-5 years. Twenty-eight percent of the children (n = 14) scored in the psychopathological range (i.e., for age range 1.5-18 years; p < 0.001) according to parent reports. Male gender, older age, and basic life support were significantly related to worse scores on the scales internalizing problems, externalizing problems, and total problems and subscale attention problems.ConclusionLong-term deficits in attention and somatic complaints were reported. Attention problems after childhood CA can interfere with school performance. Long-term follow-up with neuropsychological assessment should be organized.What is known• Critical illness has a significant influence on the presence of long-term emotional and behavioral problems. • Long-term emotional and behavioral problems have been described for various groups of critically ill children such as congenital heart disease, meningococcal septic shock, and neonatal asphyxia. What is new: • This is the first study that addresses long-term emotional and behavioral problems in a relatively large consecutive series of children and adolescents surviving cardiac arrest. • Long-term deficits in attention and somatic complaints were reported.