title: A pilot study for augmenting atomoxetine with methylphenidate: safety of concomitant therapy in children with attention-deficit/hyperactivity disorder Dosage effects of methylphenidate on the social behavior of adolescents diagnosed with attention-deficit hyperactivity disorder. Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: acute comparison and differential response. A randomized crossover clinical study showing that methylphenidate-SODAS improves attention-deficit/hyperactivity disorder symptoms in adolescents with substance use disorder. Methylphenidate in the treatment of children and adolescents with bipolar disorder and attention-deficit/hyperactivity disorder. Can Parent Reports Serve as a Proxy for Teacher Ratings in Medication Management of Attention-Deficit Hyperactivity Disorder? Effectiveness of methylphenidate in Native American children with fetal alcohol syndrome and attention deficit/hyperactivity disorder: a controlled pilot study. Which boys respond to stimulant medication? A controlled trial of methylphenidate in boys with disruptive behaviour. The effect of methylphenidate on prefrontal cognitive functioning, inattention, and hyperactivity in velocardiofacial syndrome. Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes. Concordance Among Physical Educators’, Teachers’, and Parents’ Perceptions of Attention Problems in Children Cytogenetic assessment of methylphenidate treatment in pediatric patients treated for attention deficit hyperactivity disorder. Influence of Reported Study Design Characteristics on Intervention Effect Estimates From Randomized, Controlled Trials
abstract: Background This study examined augmenting atomoxetine with extended-release methylpheni date in children whose attention-deficit/hyperactivity disorder ( ADHD ) previously failed to respond adequately to stimulant medication . Methods Children with ADHD and prior stimulant treatment ( N = 25 ) received atomoxetine ( 1.2 mg/kg/day ) plus placebo . After 4 weeks , patients who were responders ( n = 4 ) were continued on atomoxetine/placebo while remaining patients were r and omly assigned to either methylpheni date ( ATX/MPH ) ( 1.1 mg/kg/day ) or placebo augmentation ( ATX/PB ) for another 6 weeks . Patients and sites were blind to timing of active augmentation . Safety measures included vital signs , weight , and adverse events . Efficacy was assessed by ADHD rating scales . Results Categorical increases in vital signs occurred for 5 patients ( 3 patients in ATX/MPH , 2 patients in ATX/PBO ) . Sixteen percent discontinued the study due to AE , but no difference between augmentation groups . Atomoxetine treatment was efficacious on outcome measures ( P ≤ .001 ) , but methylpheni date did not enhance response . Conclusion Methylpheni date appears to be safely combined with atomoxetine , but conclusions limited by small sample . With atomoxetine treatment , 43 % of patients achieved normalization on ADHD ratings Research participants were 46 adolescents ( mean age = 13.8 years ) who completed an intensive summer treatment program including a  placebo-controlled , double-blind , crossover trial of 3 doses of methylpheni date ( MPH ) totaling 25 , 50 , or 75 mg per day . Dependent measures focused on social behavior and included observed behavior frequencies and ratings completed by counselors and parents , including side effects . Multiple data analytic methods were used with the goal of ( a ) describing the shape of the dose-response curves across multiple measures of social functioning , ( b ) determining the percentage of adolescents whose social behavior improved in response to MPH , and ( c ) assessing the incremental gains that result from increases in dose . The results show that ( a ) the shape of the dose-response curve is influenced by the measurement method , ( b ) the majority of adolescents exhibited improved social behavior when treated with MPH , ( c ) the bulk of the positive effects of MPH were achieved at the lowest dose , and ( d ) there appear to be diminishing positive effects and an increased risk of negative effects with successively higher doses OBJECTIVE Response to atomoxetine , a nonstimulant norepinephrine-specific reuptake inhibitor , was compared with the effect of osmotic-release oral methylpheni date , a long-acting methylpheni date preparation , in patients with attention deficit hyperactivity disorder ( ADHD ) . METHOD In a large placebo-controlled , double-blind study , patients ages 6 - 16 with ADHD , any subtype , were r and omly assigned to receive 0.8 - 1.8 mg/kg per day of atomoxetine ( N=222 ) , 18 - 54 mg/day of osmotically released methylpheni date ( N=220 ) , or placebo ( N=74 ) for 6 weeks . The a priori specified primary analysis compared response ( at least 40 % decrease in ADHD Rating Scale total score ) to osmotically released methylpheni date with response to atomoxetine and placebo . After 6 weeks , patients treated with methylpheni date were switched to atomoxetine under double-blind conditions . RESULTS The response rates for both atomoxetine ( 45 % ) and methylpheni date ( 56 % ) were markedly superior to that for placebo ( 24 % ) , but the response to osmotically released methylpheni date was superior to that for atomoxetine . Each medication was well tolerated , with completion rates and discontinuations for adverse events not significantly different from those for placebo . Of the 70 subjects who did not respond to methylpheni date , 30 ( 43 % ) subsequently responded to atomoxetine . Likewise , 29 ( 42 % ) of the 69 patients who did not respond to atomoxetine had previously responded to osmotically released methylpheni date . CONCLUSION Response was significantly greater with osmotically released methylpheni date than with atomoxetine . One-third of patients who received methylpheni date followed by atomoxetine responded better to one or the other , suggesting that there may be preferential responders Our objective was to evaluate the effectiveness of a long-acting formulation of methylpheni date ( MPH-SODAS ) on attention-deficit/hyperactivity disorder ( ADHD ) symptoms in an outpatient sample of adolescents with ADHD and substance use disorders ( SUD ) . Secondary goals were to evaluate the tolerability and impact on drug use of MPH-SODAS . This was a 6-week , single-blind , placebo-controlled crossover study assessing efficacy of escalated doses of MPH-SODAS on ADHD symptoms in 16 adolescents with ADHD/SUD . Participants were r and omly allocated to either group A ( weeks 1 - 3 on MPH-SODAS , weeks 4 - 6 on placebo ) or group B ( reverse order ) . The primary outcome measures were the Swanson , Nolan and Pelham Scale , version IV ( SNAP-IV ) and the Clinical Global Impression Scale ( CGI ) . We also evaluated the adverse effects of MPH-SODAS using the Barkley Side Effect Rating Scale and subject reports of drug use during the study . The sample consisted of marijuana ( N = 16 ; 100 % ) and cocaine users ( N = 7 ; 43.8 % ) . Subjects had a significantly greater reduction in SNAP-IV and CGI scores ( P < 0.001 for all analyses ) during MPH-SODAS treatment compared to placebo . No significant effects for period or sequence were found in analyses with the SNAP-IV and CGI scales . There was no significant effect on drug use .  MPH-SODAS was well tolerated but was associated with more severe appetite reduction than placebo ( P < 0.001 ) . MPH-SODAS was more effective than placebo in reducing ADHD symptoms in a non-abstinent outpatient sample of adolescents with comorbid SUD . R and omized clinical trials , with larger sample s and SUD intervention , are recommended OBJECTIVE To examine the short-term efficacy of methylpheni date in the treatment of youths with bipolar disorder ( BD ) and comorbid attention deficit/hyperactivity disorder ( ADHD ) . METHOD A 4-week double-blind , placebo-controlled trial in youths ages 5 to 17 years was conducted . Subjects met DSM-IV criteria for bipolar disorder and ADHD , were currently receiving a stable dose of at least one thymoleptic , and while euthymic continued to have clinical ly significant symptoms of ADHD . Patients received 1 week each of placebo , methylpheni date 5 mg twice daily , methylpheni date 10 mg twice daily , and methylpheni date 15 mg twice daily using a crossover design . Subjects were r and omly assigned to receive one of six possible dosing orders . At study 's end , and before the blind being broken , a " best dose week " for each subject was determined . The primary outcome measure was the total score on the parent-completed ADHD Rating Scale-IV . RESULTS Sixteen patients , with a mean age of 10.43 ( SD 3.14 ) years completed the trial . Lower scores during best dose treatment compared to the week of placebo treatment were found on the ADHD Rating Scale-IV ( p < .05 ) , suggesting a therapeutic benefit . A large effect size ( Cohen 's d = 0.90 ) was found for methylpheni date . Treatment was generally well tolerated . CONCLUSIONS Euthymic youths with bipolar disorder and ADHD may benefit from short-term concomitant treatment with methylpheni date Objective : While American Academy of Pediatrics guidelines recommend obtaining symptom reports from both parents and teachers when treating children with attention-deficit hyperactivity disorder ( ADHD ) , information from parents is easier to obtain and practitioners may prefer to rely solely on parent report when managing medications . There are , however , few empirical data on the relationship between parent and teacher reports during medication management of ADHD . This study examined the relationship between parent and teacher reports of symptoms of ADHD during a clinical trial . Methods : A study to improve medication management of ADHD was conducted in 24 pediatric practice s with 270 children . Children meeting criteria for ADHD were r and omized by practice to treatment-as-usual or specialized care groups , with data combined from the groups to examine parent-teacher agreement . Parent and teacher reports on the ADHD Rating Scale-IV  were obtained at pretreatment , 4 months , and 12 months follow-up . Results : At each assessment , correlations between parent and teacher ratings were statistically significant , but the magnitudes of the correlations were low , accounting for no more than approximately 17 % of the variance between measures . Correlations between change scores on parent and teacher ratings were statistically significant but low for Total and Inattentive scales and not significant for the Hyperactive-Impulsive scale . For agreement on extreme scores , 6 of 9 kappas were statistically significant but all were unacceptably low . Conclusions : Agreement between parent and teacher ratings of symptoms of ADHD is too low for clinicians to rely on parent reports while managing medications . Teacher reports are still needed to ensure optimal management This pilot study was design ed to assess the short-term effectiveness and side effects of methylpheni date in treating symptoms of attention deficit hyperactivity disorder ( ADHD ) in Native American children ( 5 to 12 years old ) with documented fetal alcohol syndrome ( FAS ) or partial fetal alcohol syndrome . Using strict criteria for the diagnosis of FAS and ADHD , a r and omized double-blind cross-over study of two placebos and a fixed dose of methylpheni date was completed in 4 Native American children in a residential school . Each treatment condition lasted 5 days , and daily observational outcome measures , the Conners Parent Rating Scale ( CPRS-48 ) , and the Conners Teacher Rating Scale ( CTRS-39 ) , were employed . Methylpheni date significantly improved scores of the Hyperactivity Index Scale on the CPRS-48 and the CTRS-39 but not the Daydreaming-Attention score on the CTRS-39 . Side effects were similar to those traditionally found in other population s. The promising preliminary results suggest that a more definitive study of methylpheni date in Native and non-Native children with FAS and ADHD is warranted Thirty-eight boys , referred for psychiatric treatment because of serious problems of behaviour , underwent a double-blind , placebo-controlled , crossover trial of methylpheni date and placebo . Methylpheni date was an effective treatment over a 3-week period . A good response to methylpheni date was predicted by higher levels of inattentive and restless behaviour , impaired performance on tests of attention , clumsiness , younger age and by the absence of symptoms of overt emotional disorder . DSM-III and ICD-9 diagnoses of ' hyperactivity ' were not good predictors . The results support the validity of a construct of hyperactivity in describing childhood psychopathology , but emphasize the need for a refinement of diagnostic criteria OBJECTIVE Methylpheni date ( MPH ) is commonly used to treat attention-deficit/hyperactivity disorder ( ADHD ) in all children , including those with velocardiofacial syndrome ( VCFS ) . Yet concerns have been raised regarding its safety and efficacy in VCFS . The goal of this study was to examine the safety and efficacy of MPH in children with VCFS . METHODS Thirty-four children and adolescents with VCFS and ADHD participated in a r and omized , controlled trial with a 2:1 ratio of MPH versus placebo . All subjects underwent a cardiological evaluation before and after MPH administration . The primary outcome measure was prefrontal cognitive performance following a single dose of MPH or placebo . A follow-up assessment was conducted after a 6-month treatment with MPH . RESULTS Compared with placebo , single MPH administration was associated with a more robust improvement in prefrontal cognitive performance , including achievements in the Hearts and Flowers executive function task and the visual continuous performance task . After 6 months of treatment , a 40 % reduction in severity of ADHD symptoms was reported by parents on the Revised Conners Rating Scale . All subjects treated with MPH reported at least one side effect , but it did not necessitate discontinuation of treatment . MPH induced an increase in heart rate and blood pressure that was usually minor , but was clinical ly significant in two cases . No differences in response to MPH were observed between catechol-O-methyltransferase Met versus Val carriers . CONCLUSION The use of MPH in children with VCFS appears to be effective and relatively safe . A comprehensive cardiovascular evaluation for children with VCFS before and during stimulant treatment is recommended OBJECTIVE To determine the efficacy and safety of clonidine , used alone or in combination with methylpheni date , in treating attention-deficit/hyperactivity disorder ( ADHD ) . METHOD A 16-week , r and omized , double-blind , placebo-controlled clinical trial was conducted in 122 children , ages 7 to 12 , with any subtype of ADHD , r and omly assigned to clonidine , methylpheni date , clonidine in combination with methylpheni date , or placebo according to a 2 x 2 factorial design . In two successive 4-week titration periods , clonidine ( or matching placebo ) and added methylpheni date ( or matching placebo ) were adjusted to optimal doses and then continued for 8 weeks . The primary efficacy outcome was changed from baseline to week 16 on the Conners Teachers Abbreviated Symptom Question naire . Secondary outcomes included the Conners Abbreviated Symptom Question naire for Parents and the Children 's Global Assessment Scale . RESULTS On the Conners Teachers Abbreviated Symptom Question naire , clonidine was not found to improve ADHD symptoms , whereas subjects treated with methylpheni date showed significant improvement compared to those not treated with methylpheni date . Subjects treated with clonidine had greater improvements on the Conners Abbreviated Symptom Question naire for Parents and Children 's Global Assessment Scale , but also a higher rate of sedation compared with subjects not treated with clonidine . CONCLUSIONS Based on the Conners Teachers Abbreviated Symptom Question naire , methylpheni date offers the best combination of efficacy and tolerability for ADHD . Clonidine was well tolerated despite the frequency of sedation and did offer some benefit Objective : The study examined the concordance among rating sources on attention problems of elementary school – aged children . Method : A r and omly selected sample ( N = 841 ) of children was rated by the physical educators , the teachers ,  and the parents  , using the  Attention Scales of the Motor Behavior Checklist ( MBC ) , the Teacher Report Form , the Child Behavior Checklist , and the ADHD – Rating Scale – IV ( ADHD-RS-IV ) . Results : Convergent validity of the Lack of Attention Scale of the MBC with the corresponding subscales was supported . Correlations were higher between teachers ’ ratings and between physical educators ’ and teachers ’ ratings than between physical educators ’ and parents ’ ratings or between teachers ’ and parents ’ ratings . Conclusion : Findings underscore the importance of taking the child ’s setting s and observer influences into account and suggest that MBC is a new promising instrument for screening attention problems in school setting Methylpheni date ( MPH , Ritalin ) , has been prescribed to treat attention deficit/hyperactivity disorder ( ADHD ) since its approval by the FDA over 50 years ago . Diagnoses of pediatric patients with ADHD and the administration of MPH to treat the symptoms have increased in prevalence in recent years . A 2005 study by El-Zein et al. reported statistically significant increases in cytogenetic anomalies including chromosomal aberrations ( CA ) , micronuclei ( MN ) and sister chromatid exchanges ( SCEs ) in peripheral blood lymphocytes cultured from pediatric patients treated for 3 months with MPH .  These findings led to wide-spread concern regarding the potential for genotoxic risks associated with prolonged administration of MPH . The study described in the present paper was design ed to repeat the El-Zein effort with a much larger sample size . The subjects ( N = 109 ) were r and omized into two groups : one treated with MPH as well as behavior therapy , the other was a control group that received behavior therapy only . We evaluated CAs , MN , and SCEs in peripheral blood lymphocytes in sample s obtained prior to therapy and after 3 months of treatment with MPH . The data were analyzed using a Poisson regression model with a generalized estimating equation method adjusted for several covariates including time , treatment-by-time interaction , sex , and age group . The log(e ) rate ratios of the MPH plus behavior therapy and behavior therapy groups were compared . The frequencies of CAs , MN , and SCEs were not increased in the MPH plus behavior therapy group when compared to the behavior therapy group only ( p = 0.53 , 0.28 , 0.81 , respectively ) . These results provide evidence in a large cohort that MPH does not induce cytogenetic anomalies in children , in contrast to the findings of the El-Zein study Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes
target: What this study adds The results suggest that among children and adolescents with a diagnosis of ADHD , methylpheni date may improve teacher reported symptoms of ADHD and general behaviour and parent reported quality of life .
  Methylpheni date is associated with an increased risk of non-serious but not serious adverse events .
background: Study question Is methylpheni date beneficial or harmful for the treatment of attention-deficit/hyperactivity disorder ( ADHD ) in children and adolescents ?