Methylphenidate Treatment In Children Research Articles

Attention deficit hyperactivity disorder, physical abuse and methylphenidate treatment in children

A growing number of studies show an association between attention deficit hyperactivity disorder and physical abuse in childhood. We examined temporal associations of physical abuse risk with methylphenidate treatment in children with attention deficit hyperactivity disorder. Using Hong Kong electronic medical records, we conducted a self-controlled case series study in 1,064 children (5–16 years old) who were treated with methylphenidate and also experienced physical abuse. Compared with non-medicated periods, a higher risk of abuse was observed shortly before treatment initiation (incidence rate ratio = 4.49; 95% confidence interval = 3.76–5.36). After treatment initiation, the risk was comparable to that in non-medicated periods (incidence rate ratio = 0.90; 95% confidence interval = 0.63–1.29), followed by a 37% reduction during subsequent treatment. These findings are consistent with the hypothesis that methylphenidate treatment in children with attention deficit hyperactivity disorder is associated with a reduced risk of becoming a victim of physical abuse. Man, Gao and colleagues find that methylphenidate treatment in children with attention deficit hyperactivity disorder is associated with reduced risk of physical abuse.

3.9 What Are the Benefits and Harms of Methylphenidate Treatment in Children and Adolescents With ADHD?

Stimulants are the recommended pharmacological treatment of choice for children and adolescents with ADHD, but there is no consensus in the field regarding the benefits and harms of methylphenidate. This Cochrane systematic review is an update of the first comprehensive systematic review on the topic conducted in 2015. The review is investigating the benefits and harms of methylphenidate treatment for children with ADHD.

Influence of COMT (rs4680) and DRD2 (rs1076560, rs1800497) Gene Polymorphisms on Safety and Efficacy of Methylphenidate Treatment in Children with Fetal Alcohol Spectrum Disorders

Fetal alcohol spectrum disorders (FASD) in a course of high prenatal alcohol exposure (hPAE) are among the most common causes of developmental disorders. The main reason for pharmacological treatment of FASD children is attention deficit hyperactivity disorder (ADHD), and methylphenidate (MPH) is the drug of choice. The aim of the study was to assess whether children born of hPAE with ADHD, with or without morphological FASD, differ in terms of catechol-O-methyltransferase (COMT) and dopamine receptor D2 (DRD2) gene polymorphisms, and if genetic predisposition affects response and safety of MPH treatment. The polymorphisms of COMT (rs4680) and DRD2 (rs1076560, rs1800497) were analyzed in DNA samples. A borderline significance was found for the correlation between MPH side effects and the G allele of COMT (rs4680) (p = 0.04994) in all ADHD children. No effect of COMT (rs4680) and DRD2 (rs1076560, rs1800497) polymorphisms and the treatment efficacy was observed. The analyzed DRD2 and COMT gene polymorphisms seem to play no role in MPH efficacy in ADHD children with hPAE, while low-activity COMT (Met158) variant carriers may be more intolerant to MPH. The MPH treatment is effective in ADHD independent of FASD, although the ADHD-FASD variant requires higher doses to be successful. These results may help in optimization and individualization in child psychiatry.

The effect of autistic traits on response to and side-effects of pharmacological ADHD treatment in children with ADHD: results from a prospective clinical cohort

BackgroundAttention deficit hyperactivity disorder (ADHD) is a common childhood behavioral condition that globally affects an average of around 5% of children and is associated with several adverse life outcomes. Comorbidity with autism spectrum disorder (ASD) is highly prevalent. Pharmacological treatment for ADHD symptoms has been shown to be effective. However, the prevailing perception is that children with ADHD and concomitant ASD symptoms report poorer efficacy and more side effects. This has been supported by studies on this population, but prospective studies directly comparing children with ADHD and different levels of ASD symptoms are lacking. We aimed to assess if children with ADHD and concomitant ASD symptoms differ regarding effects and side-effects of pharmacological ADHD treatment compared to children with ADHD without ASD traits. This is to our knowledge the second study to directly compare the effect of ADHD medication between ADHD patients with different levels of ASD symptoms.MethodsIn a non-randomized, observational, prospective cohort study, 323 patients aged 6 to 17 years who were diagnosed with ADHD and starting pharmacological treatment were divided into two groups: one with high level of ASD symptoms (ASD group, N=71) and one with low level of ASD symptoms (non-ASD group, N = 252). Treatment outcome was measured as ADHD symptoms, and evaluated using the Swanson, Nolan and Pelham Teacher and Parent ADHD rating scale-version IV (SNAP-IV). Side-effects were evaluated using the Pediatric Side Effects Checklist (P-SEC), at 3 months follow-up.ResultsFrom baseline to 3 months, there was no significant difference in neither treatment effect nor number of clinically significant adverse events experienced between the ASD group and the non-ASD group.ConclusionsOur results did not implicate that ADHD patients with concomitant ASD symptoms have decreased treatment effect of ADHD medication than patients with ADHD without concomitant ASD symptoms. Neither did the results support that ADHD patients with ASD symptoms experienced significantly more side-effects than ADHD patients without ASD symptoms. Although, we did not analyze different medications separately, this is in line with the only previous study directly comparing methylphenidate treatment in children with or without ASD.Trial registrationNCT02136147, May 12, 2014.

A Case Study on EEG Analysis: Embedding Entropy Estimations Indicate the Decreased Neuro-Cortical Complexity Levels Mediated by Methylphenidate Treatment in Children with ADHD.

Objective: Complexity analysis is a method employed to understand the activity of the brain. The effect of methylphenidate (MPH) treatment on neuro-cortical complexity changes is still unknown. This study aimed to reveal how MPH treatment affects the brain complexity of children with attention deficit hyperactivity disorder (ADHD) using entropy-based quantitative EEG analysis. Three embedding entropy approaches were applied to short segments of both pre- and post- medication EEG series. EEG signals were recorded for 25 boys with combined type ADHD prior to the administration of MPH and at the end of the first month of the treatment. Results: In comparison to Approximate Entropy (ApEn) and Sample Entropy (SampEn), Permutation Entropy (PermEn) provided the most sensitive estimations in investigating the impact of MPH treatment. In detail, the considerable decrease in EEG complexity levels were observed at six cortical regions (F3, F4, P4, T3, T6, O2) with statistically significant level (p < .05). As well, PermEn provided the most meaningful associations at central lobes as follows: 1) The largeness of EEG complexity levels was moderately related to the severity of ADHD symptom detected at pre-treatment stage. 2) The percentage change in the severity of opposition as the symptom cluster was moderately reduced by the change in entropy. Conclusion: A significant decrease in entropy levels in the frontal region was detected in boys with combined type ADHD undergoing MPH treatment at resting-state mode. The changes in entropy correlated with pre-treatment general symptom severity of ADHD and conduct disorder symptom cluster severity.

Long-Term Treatment With Extended-Release Methylphenidate Treatment in Children Aged 4 to

To investigate long-term (12-month) safety and symptom control of extended-release methylphenidate (MPH-MLR) in children aged 4 to <6 years after treatment optimization. A total of 90 children aged 4 to <6 years with attention-deficit/hyperactivity disorder (ADHD) were enrolled from 2 MPH-MLR studies. Treatment-emergent adverse events (TEAEs) and ADHD symptom control were assessed in the safety population (n = 89) and modeled with mixed model analyses. Most TEAEs (89.9%) were rated by investigators as of mild or moderate severity. One serious AE was reported (unrelated to study drug). Ten children discontinued because of TEAEs. Two discontinued because of weight loss; no significant increase in the rate of underweight children from baseline to endpoint was observed. Overall, 18% lost weight and 18% reported decreased appetite. Weight and height z scores and obesity rates decreased significantly from baseline to endpoint. Insomnia was reported (9%); none of these children discontinued. Sleep quality did not change significantly. Hypertension was reported (6.7%); none of these children dropped out. Diastolic, but not systolic, blood pressure increased significantly during the follow-up. Control of ADHD symptoms was maintained throughout follow-up. These data contribute to the understanding of the long-term safety of an extended-release stimulant in children 4 to <6 years of age. The observed risk of a TEAE-related discontinuation was ∼11%. TEAEs were not dose related, and most were of mild to moderate severity. Symptom control was maintained through the year-long study. A 12-Month Open Label Safety Study of Aptensio XR® in Children Ages 4-5 Years Diagnosed With ADHD (EF004); https://clinicaltrials.gov; NCT02677519.

Methylphenidate Treatment Adherence and Persistence in Children in the Netherlands.

Objectives: Numerous studies have examined determinants contributing to methylphenidate adherence and persistence, but these were mainly conducted in adults. These determinants are likely to be different in children as they usually rely on their parents to provide them with the care they need. The objective was to study child and family characteristics as determinants of methylphenidate adherence and persistence in children. Methods: The study population consists of 307 children from the Generation R Study in the Netherlands, who had at least one dispensing record of methylphenidate until the age of 16 years. Adherence was defined as a medication possession ratio ≥0.80 up to 2 years after treatment initiation. Persistence was defined as the duration of treatment until a discontinuation period of ≥6 months. Family and child characteristics were tested as determinants of adherence with multivariable logistic regression analysis. Persistence was evaluated using a Kaplan-Meier analysis. Results: Children of mothers with one child (adjusted odds ratio [OR]: 2.31, 95% confidence interval [CI]: 1.17-4.54) or of mothers with an average household income (compared to high) were more likely to be adherent (adjusted OR: 3.45, 95% CI: 1.43-8.31). Children who started treatment at the age of 12-16 years (compared to <12 years) (adjusted hazard ratio [HR]: 3.55, 95% CI: 2.54-4.98) and girls (adjusted HR: 1.44, 95% CI: 1.07-1.95) were more often nonpersistent. Conclusion: Both child and family characteristics may play a role in methylphenidate treatment adherence. Furthermore, gender and the start age of treatment were found to be associated with nonpersistence. These findings may be important for health care professionals when initiating methylphenidate treatment in children.

Continued Benefits of Methylphenidate in ADHD After 2 Years in Clinical Practice: A Randomized Placebo-Controlled Discontinuation Study.

The benefits of long-term use of methylphenidate treatment in children and adolescents with attention deficit hyperactivity disorder (ADHD), as frequently prescribed in clinical practice, are unclear. The authors investigated whether methylphenidate remains beneficial after 2 years of use. Ninety-four children and adolescents (ages 8-18 years) who had been treated in regular care with methylphenidate for more than 2 years were randomly assigned to double-blind continuation of treatment for 7 weeks (36 or 54 mg/day of extended-release methylphenidate) or gradual withdrawal over 3 weeks, to 4 weeks of placebo. The primary outcome measure was the investigator-rated ADHD Rating Scale (ADHD-RS); secondary outcome measures were the investigator-rated Clinical Global Impressions improvement scale (CGI-I) and the Conners' Teacher Rating Scale-Revised: Short Form (CTRS-R:S). Continuous ratings were analyzed with mixed model for repeated measures analyses, and the CGI-I with a chi-square test. The mean ADHD-RS scores at baseline for the continuation and discontinuation groups, respectively, were 21.4 (SD=9.7) and 19.6 (SD=8.9); after 7 weeks, the mean scores were 21.9 (SD=10.8) and 24.7 (SD=11.4), with a significant between-group difference in change over time of -4.6 (95% CI=-8.7, -0.56) in favor of the group that continued methylphenidate treatment. The ADHD-RS inattention subscale and the CTRS-R:S ADHD index and hyperactivity subscale also deteriorated significantly more in the discontinuation group. The CGI-I indicated worsening in 40.4% of the discontinuation group, compared with 15.9% of the continuation group. Continued treatment with methylphenidate remains effective after long-term use. Some individual patients may, however, be withdrawn from methylphenidate without deterioration. This finding supports guideline recommendations that patients be assessed periodically to determine whether there is a continued need for methylphenidate treatment.

Effect of Methylphenidate on State Anxiety in Children With ADHD-A Single Dose, Placebo Controlled, Crossover Study.

Introduction: Non-adherence to efficacious pharmacotherapy is a major obstacle in the treatment of children suffering from attention deficit hyperactive disorder (ADHD). Some hold the position that pharmacotherapy induces anxiety, and that this is one of the reasons for this non-adherence. Previous studies have pointed to the opposite, a moderating effect of methylphenidate (MPH) on state anxiety in patients with ADHD. This has been shown in continuous treatment in children, but not on a single dose. We hypothesized that a single dose might have a different effect.Method: Twenty children with ADHD were given single doses of MPH in a randomized, controlled, crossover, double blind study. State anxiety using The Spielberger State-Trait Anxiety Inventory (STAI) and a continuous performance test were assessed.Results: As a group, no change was detected in state anxiety with MPH or placebo. However, children who were given MPH during the first session as opposed to those who received placebo first, demonstrated deterioration in baseline state anxiety in the second session [t(2.485), p < 0.05].Conclusion: Our findings show a possible delayed anxiety-provoking effect of a single dose of MPH. This may be relevant to the understanding of difficulties in adherence with MPH treatment in children with ADHD.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01798459

Effects of methylphenidate treatment in children with ADHD: a multimodal EEG/fNIRS approach

OBJECTIVEIn this study we investigated the stimulant methylphenidate (MPH) effects in Attention deficit hyperactivity disorder (ADHD) from neuroimaging and neurophysiological perspective by simultaneous recording functional near infrared spectroscopy (fNIRS) and electroencephalography (EEG) during attention task.METHODSUsing fNIRS we obtained frontal cortex hemodynamic responses and using event related potentials (ERP) we obtained amplitude values of P3 component of 18 children with ADHD and gender matched 18 healthy controls performing an oddball task. Same recordings were repeated 3 months after extended-release MPH (OROS-MPH) administration for ADHD group. Prefrontal cortex oxygenation and P3 amplitude were compared between control and pre-MPH ADHD groups and between Pre-MPH and post-MPH ADHD groups.RESULTSfNIRS indicated that the healthy controls exhibited higher right prefrontal activation than pre-MPH children with ADHD. Reduced P3 amplitude values were found in children with ADHD compared the control group. Reduced right prefrontal activation and P3 amplitude was normalized in ADHD group after MPH therapy.CONCLUSIONRecently multimodal neuroimaging which combine signals from different brain modalities have started to be considered as a potential to improve the accuracy of diagnosis. The current study provides MPH effect assessment in children with ADHD using multimodal EEG/fNIRS system for the first time. This study suggests combination of neuroimaging and electrophysiological parameters is a promising approach to investigate MPH effect assessment in children with ADHD.

Hallucinations and other psychotic symptoms in response to methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder: a Cochrane systematic review with meta-analysis and trial sequential analysis.

Background:There is little evidence in the literature on the association between methylphenidate treatment and psychotic symptoms in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).Objective:We examine the occurrence of psychotic symptoms during methylphenidate treatment of children and adolescents with ADHD. The data arise from our two Cochrane systematic reviews on methylphenidate, reported elsewhere.Methods:Electronic databases were searched up to January 2016 (for observational studies) and March 2017 (for randomized trials). We summarized data as risk ratios and pooled prevalences. Trial Sequential Analysis was used to control for random errors. We assessed the risk of bias and the quality of evidence according to Cochrane guidelines.Results:Ten randomized trials (1103 participants), 17 non-randomized studies (76,237 participants) and 12 patient reports or series (18 patients) were identified. In the randomized trials, there was no significant difference in the risk of developing psychotic symptoms [10 of 654 (pooled prevalence, 2.5%) methylphenidate versus 1 of 508 (pooled prevalence, 1.7%) placebo patients; risk ratio, 2.07; 95% confidence interval, 0.58 to 7.35]. Nine of 10 trials had a high risk of bias, and according to the Trial Sequential Analysis, the required information size was not achieved, that is, the meta-analysis was considerably underpowered. There were 873 instances of psychotic symptoms in the non-randomized studies among 55,603 participants (pooled prevalence, 1.2%; 95% confidence interval, 0.7 to 2.4). In the comparative cohort study, methylphenidate significantly increased the risk for any psychotic disorder by 36% (risk ratio, 1.36; 95% confidence interval, 1.17 to 1.57). The overall risk of bias was rated as critical for this study.Conclusions:Because of sparse data and low quality of evidence, we cannot confirm or refute whether methylphenidate increases the risk of psychotic symptoms in children and adolescents with ADHD. This possible adverse event may affect 1.1% to 2.5%, and physicians, patients and caregivers should be aware of this to ensure proper treatment in case of occurrence during methylphenidate treatment.

Clinical factors associated with decision to recommend methylphenidate treatment for children with ADHD in France

European guidelines advise on best practices for the diagnosis and non-pharmacological and pharmacological treatment of attention-deficit hyperactivity disorder (ADHD). This study aimed to (1) assess whether clinician's decisions to initiate methylphenidate treatment in children diagnosed with ADHD are in accordance with European guidelines and (2) identify clinical factors associated with the decision to recommend methylphenidate prescription. 5 to 13-year-old patients with an ADHD diagnosis were consecutively evaluated in an outpatient child and adolescent psychiatry clinic in France. Patients underwent a multidisciplinary evaluation including a diagnostic interview, symptom severity assessments with parent questionnaires, and IQ testing. We compared children with (n=105) and without (n=55) recommended methylphenidate treatment using Student's t test or Wilcoxon Mann-Whitney test and Chi-square or Fisher's test. Multivariate logistic regression was implemented to determine the respective influence of each variable on treatment recommendation. Recommendation to initiate methylphenidate treatment was associated with (1) ADHD combined presentation, (2) co-occurring Oppositional Defiant Disorder/Conduct Disorder (ODD/CD), Developmental Coordination Disorder (DCD) and Learning Disorder (LD), (3) clinical severity and impairment indicated on parent questionnaires, and (4) reduced perceptual reasoning. Using a multivariate regression model, ADHD combined presentation [combined versus predominantly hyperactive/impulsive and unspecified OR 4.52 (1.23-16.55), p=0.023], age [OR 1.46 (1.14-1.88), p=0.003], ODD/CD [OR 5.53 (2.19-14.01), p<0.001], DCD [OR 4.22 (1.70-10.48), p=0.002], PRI [OR 0.97 (0.94-0.99), p=0.01] were significantly associated with recommendation of methylphenidate treatment. Our results indicate that clinicians' treatment decision-making complies with European guidelines and is furthermore associated with the type and severity of ADHD symptoms but also with co-occurring disorders.

Influence of Written Informed Consent for Methylphenidate on Medicine Persistence Rates in Children with Attention-Deficit Hyperactivity Disorder

To assess the influence of written informed consent on nonpersistence with methylphenidate treatment in children with attention-deficit hyperactivity disorder (ADHD). We undertook a cohort study including 141 children with ADHD who started treatment with methylphenidate, with a follow-up of 6 months. The main outcome variable was nonpersistence, defined as discontinuation of treatment by the patient. Two groups were analyzed with and without written informed consent. Use of this consent was the decision of the prescribing physician because the law allows its use on a voluntary basis. The homogeneity of both groups was verified by evaluating sex, type of ADHD, methylphenidate dosage, age, severity, and other psychiatric disorders. To assess the influence of consent on nonpersistence, bootstrapping was used to determine relative risk reduction (RRR) and number needed to treat (NNT). Among the participants who completed follow-up, 67 provided written informed consent and 63 did not. We found the following nonpersistence frequencies in each group: (1) with written informed consent: 5 (7.5%) and (2) without written informed consent: 15 (23.8%). The clinically significant results were RRR, 0.67 ± 0.17; NNT, 7 (5-9). The use of written informed consent yielded higher persistence rates. Further studies are needed to determine whether we can use this procedure routinely in clinical practice.

Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials.

ObjectivesTo study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review.Methods and findingsWe use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors.Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes.ConclusionMethylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found.

Effectiveness and adverse effects of methylphenidate treatment in children diagnosed with disruptive mood dysregulation disorder and attention-deficit hyperactivity disorder: a preliminary report

ABSTRACTObjective: Comorbidity with attention deficit hyperactivity disorder (ADHD) and disruptive mood dysregulation disorders (DMDD) is very common in children and adolescents In this study, we aimed to present a retrospective study of methylphenidate (MPH) treatment in 12 cases who were diagnosed with DMDD and ADHD.Method: All patients were followed-up in our outpatient clinic and the effectiveness and side effects of MPH were explored. Mood Symptom Questionnaire (MSQ-7) and Clinical Global Impression-Severity (CGI-S) were used for assessing the mood symptoms and their severity.Results: The differences between initiation time and the end-point time in CGI-S and MSQ-7 scores were statistically significant.Conclusion: In this present study, the usage of MPH was found to lead to an increase in irritability in children with ADHD and DMDD evidently.

Telephone‐assisted self‐help for parents of children with attention‐deficit/hyperactivity disorder who have residual functional impairment despite methylphenidate treatment: a randomized controlled trial

Self-help parenting interventions have been shown to be effective in the management of children with attention-deficit/hyperactivity disorder (ADHD) and may be useful when there are barriers to face-to-face therapist-led parent trainings. Previous studies indicate that behavioral interventions might be a useful adjunct to medication in children with residual ADHD symptoms, and regarding comorbid oppositional symptoms and multiple domains of functional impairment. In the present study, we examined whether a telephone-assisted self-help (TASH) parenting behavioral intervention (written materials plus telephone counseling) enhanced the effects of methylphenidate treatment in children with ADHD. In this randomized controlled trial, parents of 103 school-aged children with ADHD and residual functional impairment despite methylphenidate treatment were randomly assigned to either the enhancement group, which received the TASH intervention as adjunct to routine clinical care (including continued medication), or to the active control group, which received routine clinical care only (including continued medication). Parent-completed outcome measures at baseline and at 12months (postassessment) included functional impairment, ADHD symptoms, oppositional defiant disorder (ODD) symptoms, parenting behavior, and parental satisfaction with the intervention (ClinicalTrials.gov: NCT01660425; URL: https://clinicaltrials.gov/ct2/show/NCT01660425). Intention-to-treat analyses of covariance (ANCOVAs), which controlled for baseline data, revealed significant and moderate intervention effects for ODD symptoms and negative parenting behavior at the postassessment, whereas per-protocol analyses additionally showed significant and moderate effects on functional impairment (primary outcome). Parents expressed high satisfaction with the program. The TASH program enhances effects of methylphenidate treatment in families who complete the intervention. Thediscontinuation rate of about 30% and comparison between completing and discontinuing families suggest that the program may be more suitable for families with a higher educational level and fewer additional stresses.

Methylphenidate treatment in children with attention deficit hyperactivity disorder and comorbid social phobia

The aim of this study was to assess the response of social phobia (SP) symptoms to methylphenidate (MPH) treatment in children with attention deficit hyperactivity disorder (ADHD). Twenty-one ADHD patients with SP, aged between 8 and 18 years, received 12 weeks of MPH treatment. The severity of SP symptoms were assessed by the Liebowitz Social Anxiety Scale for Children and Adolescents (LSAS-CA), and the severity of ADHD symptoms was assessed by the ADHD Rating Scale at baseline and at endpoint. MPH treatment was associated with a significant decrease in the ADHD Rating Scale scores (P<0.0001) and in the total LSAS-CA scores (P=0.013), as well as the school-related items of LSAS-CA (P=0.011). A significant correlation was found between the reductions in ADHD score and total LSAS-CA score (P=0.038), especially in school-related SP. The improvement in ADHD symptoms because of MPH treatment correlates with a parallel improvement in SP. MPH treatment appears to be safe and effective in ADHD/SP children.

Parental quality of life and depressive mood following methylphenidate treatment of children with attention-deficit hyperactivity disorder

This naturalistic study investigated the associations between quality of life and depressive mood in parents and symptom changes in attention-deficit hyperactivity disorder (ADHD) children. At baseline and at weeks 4 and 8, the parents evaluated their children, who were receiving treatment with osmotic-release oral system methylphenidate (mean dosage 36.3 ± 15.5 mg/day), using the Swanson, Nolan, and Pelham - Fourth Edition (SNAP-IV-18) scale. The parents evaluated themselves using the Beck Depression Inventory (BDI) and the World Health Organization Quality of Life Assessment, Brief Version (WHOQOL-BREF). A significant reduction in SNAP-IV-18 scores and improvements in parental BDI scores and parental WHOQOL-BREF scores were observed. The decrease in BDI scores from baseline to 8 weeks was significantly associated with increases in WHOQOL-BREF sub-domain scores from baseline to 8 weeks, with a greater decrease at 4 weeks and after. The decrease in the SNAP-IV-18 hyperactivity-impulsivity score was significantly associated with increases in WHOQOL social sub-domain scores from baseline to 8 weeks. For those patients who showed a 25% or greater decrease in the SNAP-IV-18 total scores from baseline to 8 weeks, the decreases in the SNAP-IV-18 total score and in the inattention and hyperactivity-impulsivity scores were significantly associated with a decrease in BDI scores from baseline to 8 weeks. Methylphenidate treatment for ADHD was associated with both symptom alleviation in children with ADHD and improvement in parental depressive mood and quality of life, suggesting that the effects of treatment could go beyond symptom improvement in ADHD.

Norepinephrine Genes Predict Response Time Variability and Methylphenidate-Induced Changes in Neuropsychological Function in Attention Deficit Hyperactivity Disorder

Noradrenergic dysfunction may be associated with cognitive impairments in attention-deficit/hyperactivity disorder (ADHD), including increased response time variability, which has been proposed as a leading endophenotype for ADHD. The aim of this study was to examine the relationship between polymorphisms in the α-2A-adrenergic receptor (ADRA2A) and norepinephrine transporter (SLC6A2) genes and attentional performance in ADHD children before and after pharmacological treatment.One hundred one medication-naive ADHD children were included. All subjects were administered methylphenidate (MPH)-OROS for 12 weeks. The subjects underwent a computerized comprehensive attention test to measure the response time variability at baseline before MPH treatment and after 12 weeks. Additive regression analyses controlling for ADHD symptom severity, age, sex, IQ, and final dose of MPH examined the association between response time variability on the comprehensive attention test measures and allelic variations in single-nucleotide polymorphisms of the ADRA2A and SLC6A2 before and after MPH treatment.Increasing possession of an A allele at the G1287A polymorphism of SLC6A2 was significantly related to heightened response time variability at baseline in the sustained (P = 2.0 × 10) and auditory selective attention (P = 1.0 × 10) tasks. Response time variability at baseline increased additively with possession of the T allele at the DraI polymorphism of the ADRA2A gene in the auditory selective attention task (P = 2.0 × 10). After medication, increasing possession of a G allele at the MspI polymorphism of the ADRA2A gene was associated with increased MPH-related change in response time variability in the flanker task (P = 1.0 × 10).Our study suggested an association between norepinephrine gene variants and response time variability measured at baseline and after MPH treatment in children with ADHD. Our results add to a growing body of evidence, suggesting that response time variability is a viable endophenotype for ADHD and suggesting its utility as a surrogate end point for measuring stimulant response in pharmacogenetic studies.

Parents’ attitudes toward methylphenidate using n-of-1 trial: a pilot study

To compare parents' attitudes toward methylphenidate treatment in children with attention deficit hyperactivity disorder employing two approaches: (1) a 2-week double-blind placebo-drug trial (n-of-1 trial), (2) a traditional prescription approach. The study group (N-50) and a comparison group (N-45) were recruited. The Abbreviated Acceptability Rating Profile was administered prior to and following the pediatricians' consultation, and in 2, 4, and 8weeks after prescription. Complete data set was available for 21 children in each group. While initial attitudes were similar, a significantly more favorable attitude following the performance of an n-of-1 trial and throughout the follow-up in the study group only was noted. Adherence was significantly correlated with attitude score in the study group only. An individual n-of-1 trial with methylphenidate appears to positively affect parents' attitudes toward drug treatment and may also help adherence with this treatment.