title: Methylphenidate treatment in children with borderline IQ and mental retardation: analysis of three aggregated studies. Fenfluramine and methylphenidate in children with mental retardation and borderline IQ: clinical effects. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. A teacher rating scale for use in drug studies with children. Fenfluramine and methylphenidate in children with mental retardation and ADHD: clinical and side effects. 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 preschool children with developmental disabilities and ADHD. A controlled trial of stimulant medication in children with the fragile X syndrome. Double-blind administration of methylphenidate to mentally retarded children with attention deficit disorder; a preliminary study. Effects and noneffects of methylphenidate in children with mental retardation and ADHD. Efficacy of methylphenidate among mentally retarded children with attention deficit hyperactivity disorder. The effectiveness of methylphenidate in the management of Attention Deficit Hyperactivity Disorder (ADHD) in people with intellectual disabilities: A systematic review.
abstract: 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 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 BACKGROUND Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder ( ADHD ) , but no longer-term ( i.e. , > 4 months ) investigations have compared these 2 treatments or their combination . METHODS A group of 579 children with ADHD Combined Type , aged 7 to 9.9 years , were assigned to 14 months of medication management ( titration followed by monthly visits ) ; intensive behavioral treatment ( parent , school , and child components , with therapist involvement gradually reduced over time ) ; the two combined ; or st and ard community care ( treatments by community providers ) . Outcomes were assessed in multiple domains before and during treatment and at treatment end point ( with the combined treatment and medication management groups continuing medication at all assessment points ) . Data were analyzed through intent-to-treat r and om-effects regression procedures . RESULTS All 4 groups showed sizable reductions in symptoms over time , with significant differences among them in degrees of change . For most ADHD symptoms , children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care . Combined and medication management treatments did not differ significantly on any direct comparisons , but in several instances ( oppositional/aggressive symptoms , internalizing symptoms , teacher-rated social skills , parent-child relations , and reading achievement )  combined treatment proved superior to intensive behavioral treatment and /or community care while medication management did not . Study medication strategies were superior to community care treatments , despite the fact that two thirds of community-treated subjects received medication during the study period . CONCLUSIONS For ADHD symptoms , our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication . Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms , but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes The author describes and emphasizes the value of a symptom and behavior rating checklist for teachers ' use in drug studies with children . Factor analysis of the scale produced five factors that gave reliable subscales over a one-month period . A treatment study of dextroamphetamine with a group of children having learning and /or behavior disorders showed significant changes in all factors compared with a placebo group in a double-blind study Each of 28 nonautistic children with attention-deficit hyperactivity disorder and mental retardation received placebo , methylpheni date ( 0.4 mg/kg/day ) , and fenfluramine ( gradually increased to 1.5 mg/kg/day ) for 4 weeks each in a double-blind , crossover design . Teacher ratings indicated significant improvements with both active drugs on subscales design ated as Conduct Problem , Hyperactivity , and Irritability , but methylpheni date alone produced improvements on an Inattention subscale . Parent ratings indicated significant improvements with both drugs on subscales labeled Hyperactivity , Motor Excess , and Conduct Problem . Fenfluramine alone caused improved parent ratings on Irritability and Inappropriate Speech , and on Conners ' Abbreviated Symptom Question naire . Unlike a previous study , subgroup analyses failed to show a significantly better clinical response to methylpheni date for subjects with higher mental ages , although children with higher IQs responded better than those with IQs less than 45 . The active drugs had contrasting effects on heart rate and blood pressure .  Fenfluramine caused significant weight reductions relative to both placebo and methylpheni date . These findings suggest that both methylpheni date and fenfluramine have useful , but somewhat different , clinical effects in certain children with attention-deficit hyperactivity disorder and mental retardation 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 OBJECTIVE This was a double-blind , placebo-controlled , crossover design study of the safety and efficacy of methylpheni date ( MPH ) in 11 preschool children ( aged 4.0 - 5.11 years ) with developmental disabilities and attention-deficit hyperactivity disorder ( ADHD ) . METHOD MPH doses of 0.3 and 0.6 mg/kg per dose and a placebo were given . Drug response was evaluated via teacher-completed behavior checklists and clinic-based observations of activity level , attention , and compliance to adult requests . A side effects checklist was also completed by teachers and parents . RESULTS Significant improvement on teacher ratings of hyperactivity and inattention as well as clinic-based observations of activity level and compliance were associated with MPH . Eight of 11 preschool children were medication responders ( based on a minimum 40 % decrease between placebo and one drug condition on either the teacher-rated Conners Hyperactivity Index or the Hyperactive-Distractible subscale of the Preschool Behavior Question naire ) . Five children exhibited significant adverse drug side effects such as severe social withdrawal , increased crying , and irritability , especially at the higher dose ( 0.6 mg/kg ) . CONCLUSIONS Results suggest that preschool children with developmental disabilities and ADHD respond to MPH at rates similar to those of school-age children with mental retardation and ADHD . However , this population appears to be especially susceptible to adverse drug side effects Attentional deficits and hyperactivity frequently are major problems for fra(X ) boys . This study evaluated the effectiveness of 2 stimulant medications , methylpheni date and dextroamphetamine compared to placebo in 15 children ( 13 males , 2 females ) with the fra(X ) syndrome . A double-blind crossover design was used with outcome measures which included parent and teacher behavior checklists , a controlled observation period , continuous performance tasks and an actometer measure of movement . When the children were treated with methylpheni date only , improvement was seen in socialization skills and attention span according to teacher checklists .  Ten children were clinical ly considered responders and treatment was continued after the study was completed Ten children with IQs ranging from 48 to 77 who were living at home and attending special education programs in public schools were involved in an outpatient , double-blind , active drug and placebo cross-over study using methylpheni date . These children were considered to have symptoms of the  attention deficit disorder  as well as being mentally retarded . Five of the 10 children responded positively to active medication as measured by improvement in the Conners ' rating forms for parents and teachers . We concluded that retarded children with high activity levels and attention disorders are positively affected by stimulant medication but that careful and controlled observational and behavioral assessment is required on an individual basis Stimulant medication efficacy was evaluated in 14 children with attention-deficit hyperactivity disorder and IQs of 48 to 74 in a double-blind crossover study of two methylpheni date doses and placebo . Dependent measures included behavioral ratings , work output , measures of learning , attention and impulsivity , and direct observation of peer social interactions . Nine children ( 64 % ) were methylpheni date -responders , based upon the Conners Hyperactivity Index . Significant gains in on-task behavior and attentional skills were noted with methylpheni date in comparison to placebo . No improvement on measures of learning or social interactions were observed . Results extend and replicate previous research conducted by the authors Twelve children with IQ scores of 50 to 74 ( educable mental retardation ) who met rigorous diagnostic criteria for attention deficit hyperactivity disorder participated in a double-blind crossover study of the efficacy of two doses of methylpheni date compared with placebo . Dependent measures included behavioral ratings , classroom work output , laboratory measures of attention and learning , and direct observations of social behavior . Improvement with medication on the Conners Hyperactivity Index was observed in 75 % of subjects . Significant increases in work output , on-task behavior , and attentional skills were associated with methylpheni date . However , gains in measures of attention were not associated with improvement in learning , as measured by a paired associate learning task . Additionally , no significant increases in appropriate social interactions during free play were associated with methylpheni date . The results suggest that mentally retarded children with attention deficit hyperactivity disorder respond to methylpheni date at similar rates and in similar domains to that of the nonretarded population BACKGROUND The effectiveness of psychostimulants , primarily methylpheni date ( MPH ) , in the treatment of Attention Deficit Hyperactivity Disorder ( ADHD ) in the general population of typically growing children and adolescents is well established through many R and omised Controlled Trials ( RCTs ) . AIMS AND METHODS We carried out a systematic review of all the RCTs in people with intellectual disabilities ( ID ) that assessed effectiveness of MPH on the core ADHD symptoms . OUTCOMES AND RESULTS We included 15 papers from 13 studies that were all on children and adolescents with ID ( 315 participants were on MPH and placebo respectively ) , 12 of which used a cross over design , and one used a parallel design . On average around 40 - 50 % responded to MPH in the ID group whereas around 70 - 80 % response rate is reported among the non-ID children . Because of the heterogeneity of the outcome data it was not possible to carry out a meta- analysis . Significant adverse events included sleep difficulties and poor appetite along with weight loss and also irritability , social withdrawal and increased motor activities including tic . CONCLUSIONS AND IMPLEMENTATION On the basis of the poor quality evidence that is available , it seems that MPH may be effective in some but not all children and adolescents with ID and ADHD
target: Our study suggests that methylpheni date retains its efficacy in children with ADHD and borderline intellectual functioning or ID
background: Attention-deficit/hyperactivity disorder ( ADHD ) frequently co-occurs with intellectual disability in children , and may further compromise learning .
  Methylpheni date is a first-line treatment for ADHD , however no previous meta- analysis has evaluated its overall efficacy for ADHD in children with comorbid intellectual disability ( ID ) or borderline intellectual functioning .