Intake Of Methylphenidate Research Articles

Role of environmental enrichment on social interaction, anxiety, locomotion, and memory in Wistar rats under chronic methylphenidate intake.

Chronic use of various compounds can have long-lasting effects on animal behavior, and some of these effects can be influenced by the environment. Many environmental enrichment protocols have the potential to induce behavioral changes. The aim of the present study was to investigate how environmental enrichment can mitigate the effects of chronic methylphenidate consumption on the behavior of Wistar rats. The animals were housed for 20 days under either an environmental enrichment protocol (which included tubes of different shapes) or standard housing conditions. After seven days, half of the rats received 13 days of oral administration of methylphenidate (2 mg/kg). After seven days, the rats underwent behavioral tests, including the elevated plus maze (anxiety), open field (locomotion), object-in-place recognition test (spatial memory), and a test for social interaction (social behavior). The results showed that the enriched environmental condition reversed the enhanced time in the open arms of the elevated plus maze induced by methylphenidate (F[1,43] = 4.275, p = 0.045). Methylphenidate also enhanced exploratory rearing in the open field (F[1,43] = 4.663, p = 0.036) and the time spent in the open area of the open field (H[3] = 8.786, p = 0.032). The enriched environment mitigated the inhibition of social interaction with peers induced by methylphenidate (H[3] = 16.755, p < 0.001) as well as the preference for single exploratory behavior (H[3] = 9.041, p = 0.029). These findings suggest that environmental enrichment can counteract some of the effects of methylphenidate. These results are relevant for the clinical treatment of the long-lasting secondary effects associated with methylphenidate pharmacological treatment.

Striatal dopamine dissociates methylphenidate effects on value-based versus surprise-based reversal learning

Psychostimulants such as methylphenidate are widely used for their cognitive enhancing effects, but there is large variability in the direction and extent of these effects. We tested the hypothesis that methylphenidate enhances or impairs reward/punishment-based reversal learning depending on baseline striatal dopamine levels and corticostriatal gating of reward/punishment-related representations in stimulus-specific sensory cortex. Young healthy adults (N = 100) were scanned with functional magnetic resonance imaging during a reward/punishment reversal learning task, after intake of methylphenidate or the selective D2/3-receptor antagonist sulpiride. Striatal dopamine synthesis capacity was indexed with [18F]DOPA positron emission tomography. Methylphenidate improved and sulpiride decreased overall accuracy and response speed. Both drugs boosted reward versus punishment learning signals to a greater degree in participants with higher dopamine synthesis capacity. By contrast, striatal and stimulus-specific sensory surprise signals were boosted in participants with lower dopamine synthesis. These results unravel the mechanisms by which methylphenidate gates both attention and reward learning.

Co-Evolution of the General Factor of Personality and the Big Five Factors: A Mathematical Model and Its Application to Methylphenidate

This study presents a generalization of a mathematical model, called the “bridge model” in Literature, to study the co-evolution or dynamical relationship between the General Factor of Personality (GFP) and the Big Five Factors (B5F) as a consequence of a stimulus. This generalization permits its application here to study such co-evolution after a dose intake of methylphenidate. On the one hand, a stimulus-response model, an integro-differential equation called the “response model,” predicts the short-term effects of a stimulus on the GFP and on the B5F. The fact that both the GFP and the B5F dynamics can be described by the response model is here referred as the “invariance principle.” On the other hand, the invariance principle leads to the derivation of the bridge model: a second order partial differential equation that relates every B5F to the GFP and time. The outcomes of both experimental designs permit the validation of the response model and of the new bridge model.

ASD with ADHD vs. ASD and ADHD alone: a study of the QbTest performance and single-dose methylphenidate responding in children and adolescents

BackgroundThe continuous performance task (CPT) may help identify coexistent attention deficit hyperactivity disorder (ADHD) in autism spectrum disorder (ASD). The Quantified behavior Test (QbTest) combines a CPT and motion-tracking data to assess ADHD symptoms. This study aimed to evaluate the QbTest performance of children and adolescents with ASD plus ADHD, including estimating the effects of single-dose methylphenidate (MPH). To achieve these aims, (1) the QbTest performances were evaluated in ASD alone, ASD plus ADHD, and ADHD alone, and (2) the effects on the QbTest performance of single-dose MPH before and after intake were estimated across the groups. It was assumed that the ASD plus ADHD performance, including the MPH response, would preferably resemble the performance in ADHD alone, rather than ASD alone.MethodsRetrospective data were analyzed for 482 children and adolescents: 69 with ASD alone, 142 with ASD plus ADHD (ASD/ADHD), and 271 with ADHD alone. For 343 subjects, the QbTest was performed before and up to four hours after a single-dose MPH intake. A summary index of the CPT and motion-capture data was provided for QbTest cardinal parameters.ResultsOf 12 QbTest parameters assessed before given MPH, the ASD/ADHD group had scores in line with the ASD group regarding four parameters and the ADHD group regarding nine parameters. Significant differences between groups were seen with respect to QbInattention (p > 0.05); the lowest scores in ASD and the highest in ADHD. Those with ASD/ADHD and ADHD had similar QbActivity and QbImpulsivity scores, but significantly higher than those with ASD. After MPH intake, scores for QbActivity decreased similarly in ASD/ADHD and ADHD, as well as scores for QbImpulsivity. QbImpulsivity increased in ASD. QbInattention scores decreased similarly in all groups after MPH intake.ConclusionsChildren and adolescents with ASD plus ADHD exhibited more atypical QbTest performances than those with ASD alone, while most of their performances were similar to those observed in ADHD alone. In addition, a single dose of MPH mitigated attention deficits and decreased hyperactivity while improved impulsivity in these children. Prospective studies should further clarify the role of the QbTest in the diagnostic and therapeutic interventions in ASD with ADHD.

Two-month administration of methylphenidate improves olfactory sensitivity and suppresses appetite in individuals with obesity.

Olfaction contributes to feeding behaviour and is modulated by changes in dopamine levels. Methylphenidate (MPH) increases brain dopamine levels and has been shown to reduce appetite and promote weight loss in patients with attention deficit hyperactivity disorder. The objectives of this study were to test the effect of MPH on olfaction, appetite, energy intake, and body weight (BW) on individuals with obesity. In a randomized, double-blind study, 12 participants (age 28.9 ± 6.7 years) with a body mass index (BMI) of 36.1 ± 4.5kg/m2 were assigned to MPH (0.5mg/kg) (n= 5) or placebo (n= 7) twice daily for 2months. Appetite (visual analog scale), odour threshold (Sniffin' Sticks®), energy intake (food menu), and BW (DEXA scan) were measured at day1 and day60. MPH intake significantly increased odour threshold scores (6.3 ± 1.4 vs. 9.4 ± 2.1 and 7.9 ± 2.3 vs. 7.8 ± 1.9, respectively; p= 0.029) versus placebo. There was a significantly greater suppression of appetite sensations (desire to eat (p= 0.001), hunger (p= 0.008), prospective food consumption (p= 0.003)) and an increase in fullness (p= 0.028) over time in the MPH versus placebo. MPH suppressed appetite and improved olfactory sensitivity in individuals with obesity. These data provide novel findings on the favourable effects of MPH on appetite and weight regulation in individuals living with obesity.

Alterations in Rat’s Testicular Structure and Function following Simultaneous Administration of Nicotine and Methylphenidate: An in Vitro Dose-Response Study

Methylphenidate (MPH) and nicotine (NCT) have deleterious effects on testicular tissue, individually. Methylphenidate intake could increase the tendency to use NCT. In this study, the possible synergistic effects of MPH and NCTon the intensity of structural and functional changes of testicular tissue were evaluated using experimental animal study. Eighty male mature Wistar rats were used. MPH (5 and 10 mg/kg, IP) and NCT (2 and 4 mg/kg, IP) were administrated individually (MPH or NCT) or simultaneously (MPH + NCT) to eight treated groups of adult rats (n = 10/group) once a day for eight weeks. After the recording of body and testicular weight, the plasma level of pituitary gonadotropins, testosterone, and malondialdehyde (MDA) as lipid peroxidation index were measured. Also, testes samples were prepared for tissue lipid peroxidation assay, histomorphology, immunohistochemistry of p53 protein, and electron microscopy. Moreover, sperm analysis was performed on cauda epididymis. There was not any significant difference in initial and final body weight between groups. Testicular weight and testicular to body weight ratio were reduced in treated groups. LH, Testosterone, and plasma and tissue MDA were increased and FSH decreased dose-dependently in the most treated groups. Most of the histomorphometric, cell population, and sperm analysis parameters were decreased in treated groups in a dose-dependent manner. The light and electron micrographs showed various alterations in testicular tissue which were more obvious in higher doses of NCT or MPH and NCT + MPH groups. Immunostaining of testicular tissue revealed upregulation of p53 in treated groups, particularly in NCT + MPH groups. The results of this study showed that simultaneous administration of NCT and MPH could induce more alterations in the structure and function of testicular tissue compared to their individual administration.

Behavioral and Neurophysiological Markers of ADHD in Children, Adolescents, and Adults: A Large-Scale Clinical Study.

This study aimed to re-evaluate the possible differences between attention-deficit/hyperactivity disorder (ADHD) subjects and healthy controls in the context of a standard Go/NoGo task (visual continuous performance test [VCPT]), frequently used to measure executive functions. In contrast to many previous studies, our sample comprises children, adolescents, and adults. We analyzed data from 447 ADHD patients and 227 healthy controls. By applying multivariate linear regression analyses, we controlled the group differences between ADHD patients and controls for age and sex. As dependent variables we used behavioral (number of omission and commission errors, reaction time, and reaction time variability) and neurophysiological measures (event-related potentials [ERPs]). In summary, we successfully replicated the deviations of ADHD subjects from healthy controls. The differences are small to moderate when expressed as effect size measures (number of omission errors: d = 0.60, reaction time variability: d = 0.56, contingent negative variation (CNV) and P3 amplitudes: −0.35 < d < −0.47, ERP latencies: 0.21 < d < 0.29). Further analyses revealed no substantial differences between ADHD subtypes (combined, inattentive, and hyperactive/impulsive presentation), subgroups according to high- and low-symptomatic burden or methylphenidate intake for their daily routine. We successfully replicated known differences between ADHD subjects and controls for the behavioral and neurophysiological variables. However, the small-to-moderate effect sizes limit their utility as biomarkers in the diagnostic procedure. The incongruence of self-reported symptomatic burden and clinical diagnosis emphasizes the challenges of the present clinical diagnosis with low reliability, which partially accounts for the low degree of discrimination between ADHD subjects and controls.

The Impact of Methylphenidate on QbTest Performance of Children with ADHD: A Retrospective Clinical Study.

IntroductionThe Quantified behavior Test (QbTest), which combines a continuous performance task (CPT) and motion tracking, provides data for the core signs of attention-deficit/hyperactivity disorder (ADHD): attention, hyperactivity, and impulsivity. This study aimed to evaluate the performance of children and adolescents with ADHD on the QbTest before and after a single methylphenidate (MPH) dose.Subjects and MethodsThis retrospective chart review study included data from 149 children and 215 adolescents who completed the QbTest. A summary index of the CPT and motion capture data on the QbTest is provided by three cardinal parameters: QbActivity, QbImpulsivity, and QbInattention. The test was performed twice on the same day, before and up to three hours after MPH intake. A decrease by ≥ 0.5 in a cardinal parameter score was considered an improvement, whereas an increase by ≥ 0.5 a deterioration.ResultsQbActivity improvement after MPH intake was present in 71.7% and 76.2% of the children and adolescents, respectively. QbImpulsivity improvement was observed in 50.4% of the children and 44.7% of the adolescents, and QbInattention improvement in 85.1% and 91.1% of the children and adolescents, respectively. All three parameters improved simultaneously in 27.7% of the children and 28.7% of the adolescents. The likelihood that one parameter deteriorated after MPH use was greater if that parameter was within the normal range before medication. This was most pronounced for QbImpulsivity. Among male adolescents, QbInattention improvement was often accompanied by QbImpulsivity deterioration.ConclusionThe QbTest inattention and motor activity parameters improved markedly after a single MPH dose in children and adolescents with ADHD, while less so for impulsivity. Improvement of one parameter is not necessarily associated with improvement of the other two, and deterioration, especially regarding impulsivity, may occur. If confirmed, these results highlight the need for optimization and individualization of MPH treatment, while monitoring all aspects of the ADHD symptomatology based on the QbTest performance.

Effects of 12-Week Methylphenidate Treatment on Neurometabolism in Adult Patients with ADHD: The First Double-Blind Placebo-Controlled MR Spectroscopy Study.

Attention deficit hyperactivity disorder (ADHD) is a frequent neurodevelopmental disorder that often persists into adulthood. Methylphenidate (MPH) is the first-line treatment for ADHD; however, despite its wide usage, little is known about its neurometabolic effects. Until now, no randomized and blinded clinical trials have been conducted addressing the neurometabolic signals of MPH administration in adults with ADHD. In the current study, the authors investigated how MPH intake and group psychotherapy (GPT) influence brain neurometabolism over the course of three months. The authors hypothesized a decrease in the anterior cingulate cortex (ACC) glutamate concentration following MPH administration. This study was part of a double-blind multicenter trial (Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS)) investigating the effects of MPH and GPT in patients with adult ADHD. Using single-voxel magnetic resonance spectroscopy (MRS) of the pregenual ACC and the left cerebellar hemisphere (CHL), we investigated the concentration of glutamate plus glutamine (Glx), N-acetyl-aspartate, creatine, total choline containing compounds, and myo-inositol in patients before and after 12 weeks of treatment. Neither MPH nor GPT significantly influenced the Glx concentration or any of the other metabolite concentrations in the ACC and CHL after 12 weeks. Therefore, contrary to the hypothesis, no change in the prefrontal Glx signal was detected after MPH treatment. Given that MRS does not differentiate between glutamate in the synaptic cleft and in neuronal tissue, MPH-induced down-regulation of glutamatergic neurotransmission in the ACC might only affect the concentration of glutamate in the synaptic cleft, while the general availability of glutamate in the respective neuronal tissue might be unaffected by MPH intake. The observed lack of any MPH-induced normalization in metabolite concentrations is less surprising, considering that the baseline sample did not significantly differ from a healthy control group. Future studies of other regions, such as the basal ganglia, and the use of novel methods, such as whole brain MRS and multimodal imaging approaches, are necessary.

The interactive effects of test-retest and methylphenidate administration on cognitive performance in youth with ADHD: A double-blind placebo-controlled crossover study

Studies have shown that Methylphenidate (MPH) affects cognitive performance on the neuropsychological tests and clinical symptoms of individuals diagnosed with attention deficit/hyperactivity disorder (ADHD). This study investigated the acute effects of MPH on neuropsychological tests to explore the interaction between MPH and test-retest effects. Twenty youths with ADHD were tested before and after MPH intake in a double-blind placebo-controlled crossover design and compared to twenty matched controls. Participants were tested on a range of standardized tasks including sustained attention to response, N-Back, and Word/Color Stroop. Identical tasks were administered twice each testing day, before and 1 hour after MPH/Placebo administration. Healthy controls were tested similarly with no intervention. Decreases in response time (RT) variability across tasks and in commission errors were found in ADHD after MPH. Conversely, a significant increase in RT variability and increase in omission errors were observed after the placebo. In the control group, RT variability and omission errors increased whereas commission errors decreased, suggesting fatigue and practice effects, respectively. Test-retest reliability was higher in controls than ADHD. It is suggested that cognitive tests are sensitive objective measures for the assessment of responses to MPH in ADHD but are also affected by repetition and fatigue.

Long-term Effects of Multimodal Treatment on Adult Attention-Deficit/Hyperactivity Disorder Symptoms

Knowledge about the long-term effects of multimodal treatment in adult attention-deficit/hyperactivity disorder (ADHD) is much needed. To evaluate the long-term efficacy of multimodal treatment for adult ADHD. This observer-masked, 1.5-year follow-up of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), a prospective, multicenter randomized clinical trial, compared cognitive behavioral group psychotherapy (GPT) with individual clinical management (CM) and methylphenidate (MPH) with placebo (2 × 2 factorial design). Recruitment started January 2007 and ended August 2010, and treatments were finalized in August 2011 with follow-up through March 2013. Overall, 433 adults with ADHD participated in the trial, and 256 (59.1%) participated in the follow-up assessment. Analysis began in November 2013 and was completed in February 2018. After 1-year treatment with GPT or CM and MPH or placebo, no further treatment restrictions were imposed. The primary outcome was change in the observer-masked ADHD Index of Conners Adult ADHD Rating Scale score from baseline to follow-up. Secondary outcomes included further ADHD rating scale scores, observer-masked ratings of the Clinical Global Impression scale, and self-ratings of depression on the Beck Depression Inventory. At follow-up, 256 of 433 randomized patients (baseline measured in 419 individuals) participated. Of the 256 patients participating in follow-up, the observer-masked ADHD Index of Conners Adult ADHD Rating Scale score was assessed for 251; the mean (SD) baseline age was 36.3 (10.1) years; 125 patients (49.8%) were men; and the sample was well-balanced with respect to prior randomization (GPT and MPH: 64 of 107; GPT and placebo: 67 of 109; CM and MPH: 70 of 110; and CM and placebo: 55 of 107). At baseline, the all-group mean ADHD Index of Conners Adult ADHD Rating Scale score was 20.6, which improved to adjusted means of 14.2 for the GPT arm and 14.7 for the CM arm at follow-up with no significant difference between groups (difference, -0.5; 95% CI, -1.9 to 0.9; P = .48). The adjusted mean decreased to 13.8 for the MPH arm and 15.2 for the placebo arm (difference, -1.4; 95% CI, -2.8 to -0.1; P = .04). As in the core study, MPH was associated with a larger reduction in symptoms than placebo at follow-up. These results remained unchanged when accounting for MPH intake at follow-up. Compared with participants in the CM arm, patients who participated in group psychotherapy were associated with less severe symptoms as measured by the self-reported ADHD Symptoms Total Score according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) of Conners Adult ADHD Rating Scale (AMD, -2.1; 95% CI, -4.2 to -0.1; P = .04) and in the subscale of reducing pure hyperactive symptoms, measured via the Diagnostic Checklist for the diagnosis of ADHD in adults (AMD, -1.3; 95% CI, -2.8 to 0.1; P = .08). Regarding the Clinical Global Impression scale assessment of effectiveness, the difference between GPT and CM remained significant at follow-up (odds ratio, 1.63; 95% CI, 1.03-2.59; P = .04). No differences were found for any comparison concerning depression as measured with the Beck Depression Inventory. Results from COMPAS demonstrate a maintained improvement in ADHD symptoms for adults 1.5 years after the end of a 52-week controlled multimodal treatment period. The results indicate that MPH treatment combined with GPT or CM provides a benefit lasting 1.5 years. Confirming the results of the core study, GPT was not associated with better results regarding the primary outcome compared with CM. isrctn.org Identifier: ISRCTN54096201.

Childhood methylphenidate adherence as a predictor of antidepressants use during adolescence.

Methylphenidate (MPH) is a common and effective treatment for attention deficit hyperactivity disorder (ADHD), but little is known about the relationship between early childhood intake of MPH and onset of antidepressant treatment during adolescence. The study aimed to examine whether adherence to MPH during early childhood predicts the initiation of antidepressants during adolescence. This is a 12-year historical prospective nationwide cohort study of children enrolled in an integrated care system who were first prescribed MPH between the ages of 6 and 8years (N = 6830). We tested for an association between their adherence to MPH during early childhood (as indicated by medication possession ratio from MPH onset through the age of twelve) and the likelihood of being prescribed any antidepressant during adolescence (age 13-18). As all country citizens are covered by mandatory health insurance, and full services are provided by one of the four integrated care systems, data regarding patients' diagnoses, prescriptions, and medical purchases are well documented. Logistic regression analysis indicated that those with higher adherence to MPH had a 50% higher risk (95% CI 1.16-1.93) of receiving antidepressants during adolescence when controlling for other comorbid psychiatric conditions and parental use of antidepressants. In this large-scale longitudinal study, MPH adherence during early childhood emerged as a predictor for antidepressant treatment during adolescence, which may reflect increased emotional and behavioral dysregulation in this group. The highly adherent patients are at higher risk and should be clinically monitored more closely, particularly into adolescence.

Does methylphenidate cause liver damage? An analysis of ad hoc reports to the "Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM)"

Does methylphenidate cause liver damage? An analysis of ad hoc reports to the "Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM)" Abstract. Ad hoc reports to the "Bundesinstitut für Arzneimittel und Medizinprodukte" (BfArM, the German Federal Institute for Drugs and Medical Devices) were analyzed concerning liver injuring stemming from therapy with methylphenidate (MPH). Clinical criteria were used to assess suspected cases of causal association. The BfArM database on adverse drug reactions (ADRs) recorded suspected cases from Germany over the period from 1 January 2006 to 23 May 2016. Using the Standardized MedDRA Queries (SMQ) search strategy, we searched the database for "MPH" and its potential ADRs "Hepatic Disorder." The ad hoc reports were checked for completeness and assessed clinically according to the Uppsala Monitoring Centre criteria. 60 suspected cases of liver damages by MPH were recorded in the database. In 15 thereof, an assessment was not possible because of insufficient documentation; in 25 cases, a link between the intake of MPH and the occurrence of liver injury was considered "unlikely." A "possible" causality was assessed in 11 cases, a "probable/likely" causality in 9 cases: 1 patient with fulminant hepatitis, 1 with increased size of benign liver tumor, and 18 cases of (reversible) hepatic enzyme elevation. According to our evaluation, MPH is well-tolerated with regard to liver and gall bladder diseases. For patients with hepatic impairment or other risk factors, regular monitoring of liver values is recommended.

The effect of methylphenidate intake on brain structure in adults with ADHD in a placebo-controlled randomized trial

Based on animal research several authors have warned that the application of methylphenidate, the first-line drug for the treatment of attention-deficit/hyperactivity disorder (ADHD), might have neurotoxic effects potentially harming the brain. We investigated whether methylphenidate application, over a 1-year period, results in cerebral volume decrease. We acquired structural MRIs in a double-blind study comparing methylphenidate to placebo. Global and regional brain volumes were analyzed at baseline, after 3 months and after 12 months using diffeomorphic anatomic registration through exponentiated lie algebra. We included 131 adult patients with ADHD into the baseline sample, 98 into the 3-month sample (54 in the methylphenidate cohort and 44 in the placebo cohort) and 76 into the 1-year sample (37 in the methylphenidate cohort and 29 in the placebo cohort). Methylphenidate intake compared with placebo did not lead to any detectable cerebral volume loss; there was a trend toward bilateral cerebellar grey matter increase. Detecting possible neurotoxic effects of methylphenidate might require a longer observation period. There is no evidence of grey matter volume loss after 1 year of methylphenidate treatment in adult patients with ADHD.

Suicide Attempt with High Dose Long Acting Methylphenidate Ingestion: A Case Presentation

Attention Deficit and Hyperactivity Disorder (ADHD) is among the most commonly encountered neurodevelopmental disorders in childhood with its reported worldwide prevalance as 5%. Among the recommended treatment regimens as stimulants, the most frequently advised ones are methylphenidate (MPH) preparates. Among long acting MPH preparates, the form that contains an osmotic release oral system (MPH-OROS) is frequently used in clinical practice. Studies about risks, causes and outcomes regarding high dose MPH intake and effects of high dose MPH preparates in humans are limited. This article presents the clinical picture of a 12 year old boy who attempted suicide by ingesting 15 tablets of 36- mg MPH OROS. Exposure to an overdose of MPH-OROS exhibited acute sympathomimetic toxicity but no life-threatening symptoms in this patient. This case report might suggest that higher doses of MPH-OROS could be tolerated well under fine clinical observation and management; although more larger scale studies in this field would be required.

Long-term methylphenidate intake in chronic fatigue syndrome

Objective: Concentration disturbances are frequent in chronic fatigue syndrome (CFS). In a placebo-controlled double-blind crossover study, methylphenidate over 4 weeks was superior to placebo in the relief of fatigue and concentration disturbance. This observational study describes the effect of long-term methylphenidate intake on fatigue, concentration, and daily life activities, as reported by the patients themselves.Methods: A questionnaire was sent to all CFS patients who were prescribed methylphenidate at the general internal medicine department of a university hospital between August 2004 and February 2007, for possible improvement of concentration difficulties and fatigue.Results: Out of 194 consecutive patients, 149 (76.8%) sent the questionnaire back. At the time of the questionnaire, 65.3% had stopped the intake of methylphenidate, 34.7% still took it daily or occasionally. Among the patients who continued methylphenidate, 48% reported an at least 50% improvement of fatigue, and 62% reported an at least 50% improvement of concentration difficulties. This continued intake of methylphenidate resulted in more working hours in these patients. Side effects (agitation, palpitations, and dry mouth) were reported significantly more in patients who had stopped methylphenidate than in those who still took it.Conclusion: The long-term intake of methylphenidate by CFS patients with concentration difficulties has a positive effect in about one out of three patients.

Cytogenetic Effects of Chronic Methylphenidate Treatment and Chronic Social Stress in Adults with Attention-Deficit/Hyperactivity Disorder.

Methylphenidate (MPH) is widely used to treat childhood and adult attention-deficit/hyperactivity disorder (ADHD). However, there are still safety concerns about side effects in long-term treatment. The aim of this study was to assess cytogenetic effects of chronic MPH treatment in adult ADHD and to find out if chronic social stress is attenuated by medication and to investigate whether chronic psychosocial stress leads to mutagenic effects by itself. Lymphocytes for micronucleus assay and saliva samples for cortisol measurement were collected from adult ADHD patients and healthy controls. Stress exposure of the last 3 months was assessed by TICS (Trier Inventory for Chronic Stress). We could not detect an influence of MPH treatment on cytogenetic markers. ADHD patients displayed significantly higher chronic stress levels measured by TICS compared to healthy controls which were influenced by duration of MPH treatment. ADHD patients also showed significantly lower basal cortisol levels. We could corroborate that there are neither cytogenetic effects of chronic stress nor of chronic MPH intake even after several years of treatment.

Does Test Dose of Central Stimulant Influence Continuous Performance Test (CPT) and Activity in Boys with Attention Deficit Hyperactivity Disorder?

Background: Monitoring the effect of medication by using an objective measure would bring new perspectives to the work with patients suffering from Attention Deficit Hyperactivity Disorder (ADHD). Objective: In order to objectify and monitor treatment efficiency, a Continuous Performance Test (the QB Test) was used and evaluated in daily clinical practice. Method: A total of 12 boys aged 8-12 fulfilling diagnostic criteria for ADHD were tested using the QB Test before and after intake of methylphenidate. Findings: One hour after intake of test dose of medicine, there were significant improvements on numbers of omissions (p=0.014), reaction time (p=0.038), correct responses (p=0.031) and activity (p=0.045). Nonsignificant improvements in reaction time variability (p=0.190) and correct non-responses (p=0.764) were found. Number of guesses and errors of commission were unchanged after medication. Conclusions: The QB Test can be used to track effects of medication, showing greatest improvement in the most inattentive and hyperactive/impulsive children.

Influence of Methylphenidate on the Frequency of Stuttering: A Randomized Controlled Trial.

Recently, a case report described a decrease in frequency of stuttering after intake of methylphenidate (MPH). This study was undertaken to investigate if this effect could again be reproduced in a population of young healthy male adult persons with developmental stuttering. A double-blind randomized crossover trial, with a 2-week washout period, including 15 Dutch-speaking young healthy persons with developmental stuttering, assessed the effects of a single dose of 20 mg MPH compared with placebo on stuttering. Dependent and 1-sample t tests were used to detect significant differences. The end point was the number of stutter moments and self-perceived improvement. MPH yielded a significant decrease in the number of stutter moments when reading and speaking (P = 0.002), which was not the case with placebo (P = 0.090). There was a significant improvement from baseline after intake of MPH as compared with placebo (P = 0.003). Self-perceived improvement with MPH was not significantly better as compared with placebo (P = 0.28). This study showed that the participants had an objective statistically significant decrease in the frequency of stuttering with MPH, and this was not the case with placebo. This was also the case for a reduction in stutter moments when reading out loud and speaking spontaneously. However, this result was not subjectively perceived by the participants.

The effects of methylphenidate on whole brain intrinsic functional connectivity.

Methylphenidate (MPH) is an indirect dopaminergic and noradrenergic agonist that is used to treat attention deficit hyperactivity disorder and that has shown therapeutic potential in neuropsychiatric diseases such as depression, dementia, and Parkinson's disease. While effects of MPH on task-induced brain activation have been investigated, little is known about how MPH influences the resting brain. To investigate the effects of 40 mg of oral MPH on intrinsic functional connectivity, we used resting state fMRI in 54 healthy male subjects in a double-blind, randomized, placebo-controlled study. Functional connectivity analysis employing ICA revealed seven resting state networks (RSN) of interest. Connectivity strength between the dorsal attention network and the thalamus was increased after MPH intake. Other RSN located in association cortex areas, such as the left and right frontoparietal networks and the executive control network, showed MPH-induced connectivity increase to sensory-motor and visual cortex regions and connectivity decrease to cortical and subcortical components of cortico-striato-thalamo-cortical circuits (CST). RSN located in sensory-motor cortex areas showed the opposite pattern with MPH-induced connectivity increase to CST components and connectivity decrease to sensory-motor and visual cortex regions. Our results provide evidence that MPH does not only alter intrinsic connectivity between brain areas involved in sustained attention, but that it also induces significant changes in the cortico-cortical and cortico-subcortical connectivity of many other cognitive and sensory-motor RSN.