title: Childhood methylphenidate treatment of ADHD and response to affective stimuli Methylphenidate treatment in children with borderline IQ and mental retardation: analysis of three aggregated studies. Methylphenidate and ADHD: influence of age, IQ and neurodevelopmental status. Positive Effects of Methylphenidate on Social Communication and Self-Regulation in Children with Pervasive Developmental Disorders and Hyperactivity Fenfluramine and methylphenidate in children with mental retardation and borderline IQ: clinical effects. Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Positive Effects of Methylphenidate on Inattention and Hyperactivity in Pervasive Developmental Disorders: An Analysis of Secondary Measures Epidemiology of autism spectrum disorders in adults in the community in England. Prediction of clinical response in children taking methylphenidate Effects of Stimulant Medication, Incentives, and Event Rate on Reaction Time Variability in Children With ADHD Randomized, placebo-controlled, crossover study of methylphenidate for attention-deficit/hyperactivity disorder symptoms in preschoolers with developmental disorders. Methylphenidate for pervasive developmental disorders: safety and efficacy of acute single dose test and ongoing therapy: an open-pilot study. A randomized, controlled effectiveness trial of OROS-methylphenidate compared to usual care with immediate-release methylphenidate in attention deficit-hyperactivity disorder. Randomized controlled double-blind trial of optimal dose methylphenidate in children and adolescents with severe attention deficit hyperactivity disorder and intellectual disability. Efficacy of Methylphenidate Among Children with Autism and Symptoms of Attention-Deficit Hyperactivity Disorder Effects of methylphenidate on quality of life in children with both developmental coordination disorder and ADHD. Misinterpreting Emotional Expressions in Attention-Deficit/Hyperactivity Disorder: Evidence for a Neural Marker and Stimulant Effects Impact of comorbid autism spectrum disorders on stimulant response in children with attention deficit hyperactivity disorder: a retrospective and prospective effectiveness study. Pharmacotherapy in early infantile autism. Improvement of facial affect recognition in children and adolescents with attention-deficit/hyperactivity disorder under methylphenidate. Use of methylphenidate in the treatment of children with autistic disorder Chelation for autism spectrum disorder (ASD).
abstract: Neural correlates of emotional dysregulation in attention-deficit/hyperactivity disorder ( ADHD ) and persisting influence of Methylpheni date ( MPH ) still remain insufficiently understood . Decreased activation in the subgenual cingulate and the ventral striatum were found during the perception of positive and negative affective pictures in drug-naïve males with ADHD during childhood ( n=10 ) . Males with ADHD during childhood treated with MPH ( n=10 ) did not show any significant differences compared to healthy controls ( n=10 ) . Further prospect i ve studies need to clarify direct and indirect mechanisms of MPH treatment that may contribute to emotional processing , which is dysfunctional in males without pharmacological treatment in childhood OBJECTIVE To determine response of low-IQ children with attention deficit hyperactivity disorder ( ADHD ) symptoms to methylpheni date ( MPH ) . METHODS An aggregated analysis was conducted in 90 children with low IQ who received the same dose regimen of MPH in three independent , placebo-controlled studies . Active drug and placebo were given from 2 to 4 weeks each . Outcome measures included teacher and parent ratings on st and ardized behavior scales ( mean n = 84 ) , performance on computer-controlled cognitive-motor tests ( n = 62 ) , and measures of cardiovascular response ( n = 85 ) . RESULTS Both teachers and parents rated the children consistently as being improved on subscales assessing attention , overactivity , and conduct problems . Some 44 % of the subjects showed at least a 30 % reduction compared with placebo on teacher ratings . MPH  improved accuracy on several cognitive tests , response speed was increased on some , and seat activity declined for one of three tests ; heart rate was mildly increased ( 3.9 beats/minute ) with MPH . Analyses of IQ and mental age as moderator variables suggested that lower functional level ( especially lower IQ ) may be associated with a less favorable response to MPH . CONCLUSIONS Children with low IQ and ADHD clearly respond to MPH , but their rate of beneficial response appears to be well under that of normal-IQ children and more varied . Different attentional mechanisms may moderate response to psychostimulants Sixty-nine children with attention deficit hyperactivity disorder ( ADHD ) underwent blind methylpheni date trials . 36 had ADHD alone ( with or without a learning disability ) and 33 had additional neurodevelopmental disorders . Of the children with ADHD alone , 88 per cent improved significantly on methylpheni date . This did not differ significantly from the 69 per cent response rate for children with ADHD and other neurodevelopmental disorders . The results confirm and add to the research literature indicating that ADHD children who are of preschool age and /or who have co-existing neurological disorders may benefit from methylpheni date This report examined the effect of methylpheni date on social communication and self-regulation in children with pervasive developmental disorders and hyperactivity in a secondary analysis of RUPP Autism Network data . Participants were 33 children ( 29 boys ) between the ages of 5 and 13 years who participated in a four-week crossover trial of placebo and increasing doses of methylpheni date given in r and om order each for one week . Observational measures of certain aspects of children ’s social communication , self-regulation , and affective behavior were obtained each week . A significant positive effect of methylpheni date was seen on children ’s use of joint attention initiations , response to bids for joint attention , self-regulation , and regulated affective state . The results go beyond the recent literature and suggest that methylpheni date may have positive effects on social behaviors in children with PDD and hyperactivity A double-blind , placebo-controlled , crossover study of methylpheni date ( 0.4 mg/kgday ) and different doses of fenfluramine ( 1.0 , 1.5 , or 2.0 mg/g/day ) in children with mental retardation or borderline IQ and ADHD was conducted . Parents , teachers , examiners , and physicians rated the children . There were relatively few significant drug effects by condition . When the optimal fenfluramine dose for each child was compared with placebo and methylpheni date , significant improvements occurred for fenfluramine on several parent and teacher subscales ; teachers rated the children as somewhat improved with methylpheni date . The highest dose of fenfluramine produced more behavior compliance but apparently at the cost of cognitive efficiency . Most side effects ( drowsiness , dizziness , anorexia ) occurred with fenfluramine . Both drugs appear to be effective treatments for children with ADHD and mental retardation , although there is a possible neurotoxic action with fenfluramine . We recommend a gradual phase-in of fenfluramine dosage , up to 1.5 mg/kg/day , for most children CONTEXT Hyperactivity and inattention are common symptoms in children with autistic disorder and related pervasive developmental disorders , but studies of stimulants in these conditions have been inconclusive . OBJECTIVES To determine the efficacy and safety of methylpheni date hydrochloride in children with pervasive developmental disorders and hyperactivity . DESIGN Double-blind , placebo-controlled , crossover trial followed by open-label continuation . SETTING Five academic outpatient clinics . PARTICIPANTS Seventy-two drug-free children , aged 5 to 14 years , with pervasive developmental disorders accompanied by moderate to severe hyperactivity . INTERVENTIONS Prior to r and omization , subjects entered a 1-week test-dose phase in which each subject received placebo for 1 day followed by increasing doses of methylpheni date ( low , medium , and high doses ) that were each given for 2 days . The low , medium , and high doses of methylpheni date hydrochloride were based on weight , and they ranged from 7.5 mg/d to 50.0 mg/d in divided doses . Subjects who tolerated the test dose ( n = 66 ) were assigned to receive placebo for 1 week and then 3 methylpheni date doses in r and om order during a double-blind , crossover phase . Children responding to methylpheni date then entered 8 weeks of open-label treatment at the individually determined best dose . MAIN OUTCOME MEASURES The primary outcome measure was the teacher-rated hyperactivity subscale of the Aberrant Behavior Checklist . Response was defined as " much improved " or " very much improved " on the Clinical Global Impressions Improvement item coupled with considerable reductions in the parent-rated and /or teacher-rated Aberrant Behavior Checklist hyperactivity subscale score . RESULTS Methylpheni date was superior to placebo on the primary outcome measure , with effect sizes ranging from 0.20 to 0.54 depending on dose and rater . Thirty-five ( 49 % ) of 72 enrolled subjects were classified as methylpheni date responders . Adverse effects led to the discontinuation of study medication in 13 ( 18 % ) of 72 subjects . CONCLUSIONS Methylpheni date was often efficacious in treating hyperactivity associated with pervasive developmental disorders , but the magnitude of response was less than that seen in typically developing children with attention-deficit/hyperactivity disorder . Adverse effects were more frequent BACKGROUND Methylpheni date has been shown elsewhere to improve hyperactivity in about half of treated children who have pervasive developmental disorders ( PDD ) and significant hyperactive-inattentive symptoms . We present secondary analyses to better define the scope of effects of methylpheni date on symptoms that define attention-deficit/hyperactivity disorder ( ADHD ) and oppositional defiant disorder ( ODD ) , as well as the core autistic symptom domain of repetitive behavior . METHODS Sixty-six children ( mean age 7.5 y ) with autistic disorder , Asperger 's disorder , and PDD not otherwise specified , were r and omized to varying sequences of placebo and three different doses of methylpheni date during a 4-week blinded , crossover study . Methylpheni date doses used approximated .125 , .25 , and .5 mg/kg per dose , twice daily , with an additional half-dose in the late afternoon . Outcome measures included the Swanson , Nolan , and Pelham Question naire revised for DSM-IV ( ADHD and ODD scales ) and the Children 's Yale-Brown Obsessive Compulsive Scales for PDD . RESULTS Methylpheni date was associated with significant improvement that was most evident at the .25- and .5-mg/kg doses . Hyperactivity and impulsivity improved more than inattention . There were not significant effects on ODD or stereotyped and repetitive behavior . CONCLUSIONS Convergent evidence from different assessment s and raters confirms methylpheni date 's efficacy in relieving ADHD symptoms in some children with PDD . Optimal dose analyses suggested significant interindividual variability in dose response CONTEXT To our knowledge , there is no published information on the epidemiology of autism spectrum disorders ( ASDs ) in adults . If the prevalence of autism is increasing , rates in older adults would be expected to be lower than rates among younger adults . OBJECTIVE To estimate the prevalence and characteristics of adults with ASD living in the community in Engl and . DESIGN A stratified , multiphase r and om sample was used in the third national survey of psychiatric morbidity in adults in Engl and in 2007 . Survey data were weighted to take account of study design and nonresponse so that the results were representative of the household population . SETTING General community ( ie , private households ) in Engl and . PARTICIPANTS Adults ( people 16 years or older ) . MAIN OUTCOME MEASURES Autism Diagnostic Observation Schedule , Module 4 in phase 2 vali date d against the Autism Diagnostic Interview-Revised and Diagnostic Interview for Social and Communication Disorders in phase 3 . A 20-item subset of the Autism-Spectrum Quotient self-completion question naire was used in phase 1 to select respondents for phase 2 . Respondents also provided information on sociodemographics and their use of mental health services . RESULTS Of 7461 adult participants who provided a complete phase 1 interview , 618 completed phase 2 diagnostic assessment s. The weighted prevalence of ASD in adults was estimated to be 9.8 per 1000 ( 95 % confidence interval , 3.0 - 16.5 ) . Prevalence was not related to the respondent 's age . Rates were higher in men , those without educational qualifications , and those living in rented social ( government-financed ) housing . There was no evidence of increased use of services for mental health problems . CONCLUSIONS Conducting epidemiologic research on ASD in adults is feasible . The prevalence of ASD in this population is similar to that found in children . The lack of an association with age is consistent with there having been no increase in prevalence and with its causes being temporally constant . Adults with ASD living in the community are socially disadvantaged and tend to be unrecognized Twenty-six children having Attention Deficit Hyperaclivity Disorder were tested before and after treatment with methylpheni date . In addition to st and ardized parent and teacher rating scales , each child was assessed on a variety of psychomotor tests with an emphasis on attentional constructs . Relatively few of the performance tests , administered prior to medication , predicted clinical response to medication . However , chronological age and performance on a  memory distraction task and on the Graduated Holes Task ( Kløve , 1963 ) were moderately correlated with clinical outcome . Using stepwise multiple regression analyses to predict outcome , age and the psychomotor tasks predicted about 50 % of outcome variance . There was virtually no relationship between clinical change and change on the performance tests . Findings are discussed with respect to results from previous prediction studies , theoretical models of drug response , and clinical management This study examined the effects of methylpheni date ( MPH ) on reaction time ( RT ) variability in children with attention deficit hyperactivity disorder ( ADHD ) . Using a broad battery of computerized tasks , and both conventional and ex-Gaussian indicators of RT variability , in addition to within-task manipulations of incentive and event rate ( ER ) , this study comprehensively examined the breadth , specificity , and possible moderators of effects of MPH on RT variability .  A total of 93 children with ADHD completed a 4-week within-subject , r and omized , double-blind , placebo-controlled crossover trial of MPH to identify an optimal dosage . Children were then r and omly assigned to receive either their optimal MPH dose or placebo after which they completed five neuropsychological tasks , each allowing trial-by-trial assessment of RTs . Stimulant effects on RT variability were observed on both measures of the total RT distribution ( ie , coefficient of variation ) as well as on an ex-Gaussian measure examining the exponential portion of the RT distribution ( ie , τ ) . There was minimal , if any , effect of MPH  on performance accuracy or RT speed . Within-task incentive and ER manipulations did not appreciably affect stimulant effects across the tasks . The pattern of significant and pervasive effects of MPH on RT variability , and few effects of MPH  on accuracy and RT speed suggest that MPH primarily affects RT variability . Given the magnitude and breadth of effects of MPH on RT variability as well as the apparent specificity of these effects of MPH on RT variability indicators , future research should focus on neurophysiological correlates of effects of MPH on RT variability in an effort to better define MPH pharmacodynamics OBJECTIVE The aim of this study was to investigate the short-term efficacy and safety of methylpheni date ( MPH ) to treat attention-deficit/hyperactivity disorder ( ADHD ) symptoms in an understudied population of preschoolers with pervasive developmental disorder ( PDD ) or intellectual disability ( ID ) . METHODS Fourteen preschoolers with developmental disorders ( DD , n = 14 ; PDD , n = 12 ; ID , n = 2 ) underwent MPH titration in a single-blind manner followed by a 4-week double-blind crossover phase . Each child was administered placebo for 2 weeks and " optimal dose " for 2 weeks . The primary outcome measure was the Diagnostic and Statistical Manual of Mental Disorders , 4(th ) edition ( DSM-IV ) ADHD subscale of the Conners ' Parent Rating Scale-Revised ( CPRS-R-DSM-IV-ADHD ) . RESULTS MPH improved parent-rated ADHD symptoms of the preschoolers ; 50 % were rated as responders . The CPRS-R-DSM-IV-ADHD subscale was significant for the PDD subgroup ( p = 0.005 , Cohen d = 0.97 ) and marginally significant for the entire DD sample ( p = 0.08 , Cohen d = 0.50 ) . Half of the preschoolers experienced side effects with MPH , including reports of increased stereotypic behavior , upset stomach , sleep-related difficulties , and emotional lability . One child discontinued during titration due to side effects . CONCLUSION The predominant direction of response in these preschoolers with both ADHD and PDD/ID favored MPH , even though the response was more subtle and variable than in older and typically developing children . Due to high rates of adverse effects , preschoolers should be monitored closely OBJECTIVE The aim of this study was to investigate the effects of ongoing methylpheni date ( MPH ) on ADHD-related and autistic symptoms in Pervasive Developmental Disorders ( PDD ) in children who did not present any adverse effects to an initial acute dose administered at the clinic . METHODS Participants included 13 subjects ( 12 males , with a mean age of 7.9 years ) with PDD and moderate to severe hyperactivity/impulsivity . The severity of the symptoms assessment was based on Clinical Global Impression ( CGI ) , Childhood Autism , Child Psychiatric and Conners Parent and Teacher Rating Scales ( CPRS ) . Scores at baseline , and after 1 and 3 months of treatment , were compared to intent-to-treat analyses . RESULTS One ( 1 ) hour after a single MPH dose ( 0.4 mg/kg ) , 5 subjects exhibited increased hyperactivity , stereotypes , dysphoria , or motor tics and were rated as minimally or much worse on the CGI Global Improvement Scale . They received no further treatment with MPH . Four ( 4 ) of the remaining subjects were rated as improved , and four as unchanged ; they proceeded to a 12-week open trial of MPH . Two children remained unchanged : they discontinued treatment after 1 week on maximally tolerated doses . However , in group analyses , behavioral measures of hyperactivity and impulsivity improved significantly , while autism core symptom measures were unaffected . No significant adverse effects were observed in any of the 8 subjects . CONCLUSIONS Administering a single MPH test dose may be useful in identifying children with PDD who may benefit from prolonged therapy BACKGROUND The thrice daily dosing regimen of immediate release methylpheni date ( IR-MPH ) for Attention Deficit/Hyperactivity Disorder ( ADHD ) requires in-school dosing , leading to issues surrounding dispensing and storage of controlled substances by school personnel and concerns over children?s privacy and the embarrassment associated with taking medication in public at school . OROS-methylpheni date ( OROS-MPH ) is a once-daily controlled-release formulation of methylpheni date ( MPH ) developed to overcome some of the limitations associated with IR-MPH and first-generation sustained-release formulations . R and omized , controlled trials ( RCTs ) that focus on treatment efficacy provide the best evidence for demonstrating whether an intervention works , but under ideal conditions one can not discount the importance of efficacy study results . However , the most useful information to clinicians comes from an effectiveness study design . OBJECTIVES To evaluate the effectiveness and tolerability of OROS-MPH versus usual care with IR-MPH in children aged 6 to 12 years with ADHD . METHODS This 8 week , multicentre , open-label study r and omized 147 subjects to either once-daily OROS-MPH or usual care with IR-MPH .  Subjects were titrated to a clinical ly effective dose of either study medication over 4 weeks and maintained on that dose for an additional 4 weeks . The SNAP-IV parent-rating scale was used to assess effectiveness . RESULTS OROS-MPH showed statistically significant superiority to IR-MPH in remission rate based on the 18 ADHD symptoms ( p=0.0002 , X2=13.8 , df=1 ) and severity of ADHD and ODD symptoms ( p=0.004 , F=8.4 , df=1,127 ) , as well as on the following secondary assessment s : IOWA Conners , Conners Parent Rating Scale ( short version ) , Parent Stress Index , ( short version ) ; Visual Analogue Scale for social play ; Clinical Global Impression-Severity , Clinical Global Impression-Improvement and Parent Satisfaction with treatment .  OROS-MPH and IR-MPH were both well tolerated with a similar side effect profile . CONCLUSIONS Once-daily OROS-MPH is significantly more effective than usual care with IR-MPH based on multiple outcome measures including remission rate BACKGROUND Attention deficit hyperactivity disorder is increased in children with intellectual disability . Previous research has suggested stimulants are less effective than in typically developing children but no studies have titrated medication for individual optimal dosing or tested the effects for longer than 4 weeks . METHOD One hundred and twenty two drug-free children aged 7 - 15 with hyperkinetic disorder and IQ 30 - 69 were recruited to a double-blind , placebo-controlled trial that r and omized participants using minimization by probability , stratified by referral source and IQ level in a one to one ratio .  Methylpheni date was compared with placebo . Dose titration comprised at least 1 week each of low ( 0.5 mg/kg/day ) , medium ( 1.0 mg/kg/day ) and high dose ( 1.5 mg/kg/day ) . Parent and teacher Attention deficit hyperactivity disorder ( ADHD ) index of the Conners Rating Scale-Short Version at 16 weeks provided the primary outcome measures . Clinical response was determined with the Clinical Global Impressions scale ( CGI-I ) . Adverse effects were evaluated by a parent-rated question naire , weight , pulse and blood pressure . Analyses were by intention to treat . TRIAL REGISTRATION IS RCT N 68384912 . RESULTS Methylpheni date was superior to placebo with effect sizes of 0.39 [ 95 % confidence intervals ( CIs ) 0.09 , 0.70 ] and 0.52 ( 95 % CIs 0.23 , 0.82 ) for the parent and teacher Conners ADHD index . Four ( 7 % ) children on placebo versus 24 ( 40 % ) of those on methylpheni date were judged improved or much improved on the CGI . IQ and autistic symptoms did not affect treatment efficacy . Active medication was associated with sleep difficulty , loss of appetite and weight loss but there were no significant differences in pulse or blood pressure . CONCLUSIONS Optimal dosing of methylpheni date is practical and effective in some children with hyperkinetic disorder and intellectual disability . Adverse effects typical of methylpheni date were seen and medication use may require close monitoring in this vulnerable group Thirteen children ( ages 5.6 to 11.2 years ) with autism and symptoms of attention-deficit hyperactivity disorder ( ADHD ) participated in a double-blind , placebo-controlled crossover study of methylpheni date ( 0.3 and 0.6 mg/kg per dose ) . Eight subjects responded positively , based upon a minimum 50 % decrease on the Conners Hyperactivity Index . Ratings of stereotypy and inappropriate speech , which are often associated with autistic core features , also decreased . However , no changes were found on the Child Autism Rating Scale , a global assessment of autistic symptomotology . Significant adverse side effects occurred in some children including social withdrawal and irritability , especially at the 0.6 mg/kg dose . Results suggest that methylpheni date can be efficacious for children with autism and ADHD symptoms . However , this group of children seems to be particularly susceptible to adverse side effects Measurement of health-related quality of life ( HRQOL ) in attention-deficit-hyperactivity disorder ( ADHD ) gives a more complete picture of day-to-day functioning and treatment effects than behavioural rating alone . The aim of this pilot study was to investigate the impact of the combined diagnoses of developmental coordination disorder ( DCD ) and ADHD on HRQOL , and the effectiveness of methylpheni date ( MPH ) on HRQOL . HRQOL was established using the Dutch-Child-AZL-TNO- Quality -of-Life ( DUX-25 ) and the TNO-AZL-Child- Quality -of-Life ( TACQOL ) question naires , completed by children and parents . HRQOL of these children was compared with that of 23 age- and sex-matched healthy controls . Twenty-three children ( 21 males , two females ; mean age 8 y 6 mo , [ SD 3 mo ] range 7 y-10 y 8 mo ) with ADHD/DCD entered a 4-week , open-label MPH study , after MPH-sensitivity was established , in a double-blind , placebo-controlled trial . In these children 's self- and proxy reports , impact of both DCD and ADHD was reflected in lower general well-being ( self and proxy report p=0.001 ) due to lower functioning in motor ( selfp=0.026 ; proxy 0.001 ) , autonomic ( self p<0.001 ; proxy p=0.047 ) , cognitive ( self p=0.001 ; proxy p=0.01 ) , and social ( self and proxy p<0.001 ) domains . HRQOL scores improved in 18 children receiving MPH ( p=0.001 ) versus controls . The ADHD /DCD group also demonstrated a significant improvement in ADHD symptoms ( p<0.001 ) and motor functioning ( p<0.001 ) . Additional motor therapy will still be needed in about half of the children with ADHD/DCD receiving MPH , within multimodal treatment including educational and psychosocial assistance BACKGROUND In addition to cognitive impairment , there are disruptions to mood and emotion processing in attention-deficit/hyperactivity disorder ( ADHD ) but little is known about their neural basis . We examined ADHD disturbances in mood and emotion recognition and underlying neural systems before and after treatment with stimulant medication . METHODS Participants were 51 unmedicated ADHD adolescents and 51 matched healthy control subjects rated for depressed and anxious mood and accuracy for identifying facial expressions of basic emotion . Brain function was recorded using event-related potentials ( ERPs ) while subjects viewed these expressions . ADHD subjects were retested after 4 weeks , following treatment with methylpheni date ( MPH ) . RESULTS ADHD subjects showed a profile of emotion-related impairment : higher depression and anxiety , deficits in identifying threat-related emotional expressions in particular , and alterations in ERPs . There was a pronounced reduction in occipital activity during the early perceptual analysis of emotional expression ( within 120 msec ) , followed by an exaggeration of activity associated with structural encoding ( 120 - 220 msec ) and subsequent reduction and slowing of temporal brain activity subserving context processing ( 300 - 400 msec ) . Methylpheni date normalized neural activity and produced some improvement of emotion recognition but had no impact on negative mood . Improvements in neural activity with MPH were consistent predictors of improvement in clinical features of emotional lability and hyperactivity . CONCLUSIONS Objective behavioral and brain function measures of emotion processing may provide a valuable addition to the clinical armamentarium for assessing emotional disturbances in ADHD and the efficacy of stimulants for treating these disturbances BACKGROUND In the recent past , psychiatrists and paediatricians have avoided prescribing stimulant medication , such as methylpheni date and dexamphetamine to patients with autism spectrum disorders ( ASD ) because of both doubts about efficacy and concern that these medications make stereotypies worse . Recently , a number of small trials have suggested that methypheni date does have a role in the management of hyperactivity in children with autistic spectrum disorders . METHODS Children with ASD and attention deficit hyperactivity disorder ( ADHD ) , and children with ADHD without ASD received st and ard treatment with methypheni date from one specialist centre . A combination of st and ardized and novel outcome tools was used to allow both an exploratory retrospective study of 174 children and then a prospect i ve study of a further 52 children to be carried out . RESULTS After treatment with stimulants , the subjects in both groups showed statistically significant improvements in target symptoms of ' hyperactivity ' , ' impulsivity ' , ' inattention ' , ' oppositionality ' , ' aggression ' and ' intermittent explosive rage ' . The Clinical Global Impression-Improvement and efficacy index measures also improved in each group . In both the retrospective and the prospect i ve studies , there was no statistically significant difference in the degree of improvements between each group . Importantly , neither tics nor repetitive behaviours worsened in either group . Children in the ' ADHD-only ' group who were prescribed stimulants experienced significant ' nausea ' , ' giddiness ' , ' headaches ' and ' sleep difficulties ' , whereas sleep difficulties were the only side effect that emerged in children in the ASD with ADHD group . CONCLUSIONS Both studies presented here support previous findings from smaller studies that show children with autism and ADHD can respond as well to stimulants as children with ADHD alone . Although r and omized controlled trials remain the gold st and ard for efficacy studies , systems like this that allow clinicians to continue rigorous and consistent monitoring for many years have a valuable role to play . Furthermore , such monitoring systems which now exist electronically can easily accumulate large data sets and reveal details about long-term effectiveness and long-term side effects of medication that are unlikely to be discovered in short-term trials An up-to- date review of drug treatment in psychoses of early childhood is presented . At the present time , of all biological interventions in these developmental disorders , drug treatment alone remains a valuable addition or an essential treatment modality of the total treatment . Experience has shown that a therapeutically effective potent drug can make the autistic child more amenable to other therapies , including special education . However , knowledge is lacking about the effect of various psychoactive agents on cognition in this patient population as well as their influence on growth , weight , endocrine systems , and organs . Drugs currently in use treat symptoms , not diseases . A great need for classification in this area persists . The same symptoms may be caused by a variety of etiologic factors , and autism may or may not be the earliest expression of childhood schizophrenia . It is suggested that clinical distinctions be correlated or even improved by certain biochemical , neuroendocrine , and physiological criteria ; this also may be of considerable value in predicting whether a child can benefit from a specific drug INTRODUCTION AND HYPOTHESIS Some authors draw a connection between the dopaminergic pathways and emotional perception . The present study is based on that association and addresses the question whether methylpheni date and the result ing amelioration of the disturbed dopamine metabolism lead to an improvement of the facial affect recognition abilities in children with attention-deficit/hyperactivity disorder ( ADHD ) . METHODS A computer test was conducted on 21 participants , aged 7 - 14 years and with a diagnosis of ADHD - some with comorbid oppositional defiant disorder - conducted the FEFA ( Frankfurt Test and Training of Facial Affect ) , a computer test to examine their facial affect recognition abilities . It consists of two subtests , one with faces and one with eye pairs . All participants were tested in a double-blind cross-over study , once under placebo and once under methylpheni date . RESULTS AND DISCUSSION The collected data showed that methylpheni date leads to amelioration of facial affect recognition abilities , but not on a significant level . Reasons for missing significance may be the small sample size or the fact that there exists some overlapping in cerebral connections and metabolic pathways of the site of action of methylpheni date and the affected dopaminergic areas in ADHD . However , consistent with the endophenotype concept , certain gene locations of the dopaminergic metabolism as both an aetiological factor for ADHD and the deficient facial affect recognition abilities with these individuals were considered . Consulting current literature they were found to be not concordant . Therefore , we conclude that the lacking significance of the methylpheni date affect on facial affect recognition is based on this fact The use of psychostimulants in autistic disorder has not received extensive evaluation . Furthermore , their use for the symptomatic control of autistic disorder has been felt to be contraindicated . This study investigates the use of methylpheni date ( MPH ) for the treatment of selected symptoms of autistic disorder . Ten children , ages 7–11 , with a DSM-III-R diagnosis of autistic disorder participated in a double-blind crossover study using placebo and two MPH doses ( 10 mg or 20 mg bid ) . Subjects showed modest but statistically significant improvement on MPH over placebo . No significant side effects including worsening stereotypic movements occurred on either dose . Improvement in hyperactivity and lack of adverse effects suggest that MPH may be useful in the treatment of hyperactive autistic children BACKGROUND It has been suggested that the severity of autism spectrum disorder ( ASD ) symptoms is positively correlated with the level of circulating or stored toxic metals , and that excretion of these heavy metals , brought about by the use of pharmaceutical chelating agents , results in improved symptoms . OBJECTIVES To assess the potential benefits and adverse effects of pharmaceutical chelating agents ( referred to as chelation therapy throughout this review ) for autism spectrum disorder ( ASD ) symptoms . SEARCH METHODS We search ed the following data bases on 6 November 2014 : CENTRAL , Ovid MEDLINE , Ovid MEDLINE In-Process , Embase , PsycINFO , Cumulative Index to Nursing and Allied Health Literature ( CINAHL ) and 15 other data bases , including three trials registers . In addition we checked references lists and contacted experts . SELECTION CRITERIA All r and omised controlled trials of pharmaceutical chelating agents compared with placebo in individuals with ASD . DATA COLLECTION AND ANALYSIS Two review authors independently selected studies , assessed them for risk of bias and extracted relevant data . We did not conduct a meta- analysis , as only one study was included . MAIN RESULTS We excluded nine studies because they were non-r and omised trials or were withdrawn before enrolment . We included one study , which was conducted in two phases . During the first phase of the study , 77 children with ASD were r and omly assigned to receive seven days of glutathione lotion or placebo lotion , followed by three days of oral dimercaptosuccinic acid ( DMSA ) .  Forty-nine children who were found to be high excreters of heavy metals during phase one continued on to phase two to receive three days of oral DMSA or placebo followed by 11 days off , with the cycle repeated up to six times . The second phase thus assessed the effectiveness of multiple doses of oral DMSA compared with placebo in children who were high excreters of heavy metals and who received a three-day course of oral DMSA . Overall , no evidence suggests that multiple rounds of oral DMSA had an effect on ASD symptoms . AUTHORS ' CONCLUSIONS This review included data from only one study , which had method ological limitations . As such , no clinical trial evidence was found to suggest that pharmaceutical chelation is an effective intervention for ASD . Given prior reports of serious adverse events , such as hypocalcaemia , renal impairment and reported death , the risks of using chelation for ASD currently outweigh proven benefits . Before further trials are conducted , evidence that supports a causal link between heavy metals and autism and methods that ensure the safety of participants are needed
target: No trials reported serious adverse events .
  Subgroup analysis by dose did not identify any significant differences in effect on our primary outcomes between low- , medium- or high-dose ranges .
  We found that short-term use of methylpheni date might improve symptoms of hyperactivity and possibly inattention in children with ASD who are tolerant of the medication , although the low quality of evidence means that we can not be certain of the true magnitude of any effect .
  There was no evidence that methylpheni date has a negative impact on the core symptoms of ASD , or that it improves social interaction , stereotypical behaviours , or overall ASD .
background: BACKGROUND Children with autistic spectrum disorder ( ASD ) frequently present with inattention , impulsivity and hyperactivity , which are the cardinal symptoms of attention deficit hyperactivity disorder ( ADHD ) .
  The effectiveness of methylpheni date , a commonly used ADHD treatment , is therefore of interest in these children .
  OBJECTIVES To assess the effects of methylpheni date for symptoms of ADHD ( inattention , impulsivity and hyperactivity ) and ASD ( impairments in social interaction and communication , and repetitive , restricted or stereotypical behaviours ) in children and adolescents aged 6 to 18 years with ASD .