***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE To evaluate the short-term efficacy and side effects associated with two methylpheni date hydrochloride ( MPH ) dosing patterns . METHODS Twenty-five boys with attention deficit hyperactivity disorder ( ADHD ) participated in a 5-week , triple-blind , placebo-controlled , crossover evaluation of MPH administered twice ( b.i.d . ) versus thrice ( t.i.d . ) per day ( mean dose = 8.8 + /- 5 mg , .30 + /- .1 mg/kg/dose ) . Four dosing conditions ( placebo , titration [ gradual increase to target dose ] , b.i.d . , and t.i.d . ) were used . Dependent measures obtained on a weekly basis included : parent and teacher ratings of child behavior , parent-child conflicts , parent report of stimulant side effects , child self-report of mood symptoms , a sleep log , laboratory measures of attention , and actigraphic recording of sleep activity . RESULTS All dosing conditions result ed in significant effects on ADHD symptoms when compared with baseline . Relative to placebo , t.i.d . dosing was characterized by improvement on the greatest number of behavioral measures , and both b.i.d . and t.i.d . were generally more effective than titration . Direct comparisons of b.i.d . and t.i.d . dosing revealed that t.i.d . was associated with greater improvement on the Conners Parent Rating Scale Impulsivity/Hyperactivity factor , with a similar marginally significant effect for the ADD-H Teacher Rating Scale Hyperactivity factor . The analysis of clinical ly significant change favored a three-times-a-day dosing schedule over placebo on both parent and teacher ratings of impulsivity/hyperactivity and attention . Compared with placebo , appetite suppression was rated , on average , as more severe in the t.i.d . and titration conditions , but not in the b.i.d . condition . However , the number of subjects who exhibited any or severe appetite suppression did not differ significantly between the b.i.d . and t.i.d . schedules . Although there was no difference in sleep duration for children on b.i.d . and t.i.d . schedules , total sleep time appeared to decrease slightly on t.i.d . relative to placebo according to both parent ratings and actigraphic assessment . There were no significant differences between b.i.d . and t.i.d . on any other side effects or sleep variables . CONCLUSIONS For many children with ADHD , t.i.d . dosing may be optimal . There are few differences in acute side effects between b.i.d . and t.i.d . MPH dosing . The dosing schedule should be selected according to the severity and time course of ADHD symptoms rather than in anticipation of dosing schedule-related side effects 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 Abstract Hypotheses concerning unexpected , psychostimulant-related effects reported in previous studies were examined by separating behavioral/physical complaints highly specific to methylpheni date ( MPH ) from those that ( a ) may mimic core/ secondary symptoms of the disorder , or ( b ) are commonly reported by unmedicated children in the general population . Sixty-five children with attention-deficit/hyperactivity disorder ( ADHD ) participated in a double-blind , placebo-controlled , within-subject ( crossover ) experimental design and received a placebo and four MPH doses in counterbalanced order following baseline assessment . Behavioral and physical complaints were significantly higher under baseline relative to placebo and the four immediate-release MPH conditions ( 5 mg , 10 mg , 15 mg , and 20 mg ) across three symptom categories : ADHD core/ secondary symptoms ; symptoms commonly reported in the general population , including unmedicated children with ADHD ; and symptoms highly specific to MPH . No significant differences were found among active drug conditions . Past unexpected findings of psychostimulant effects in ADHD may be due to the inclusion of scale items that reflect core/ secondary features of ADHD and normally occurring behavioral/physical complaints in children OBJECTIVE To evaluate the efficacy and safety of osmotic-release methylpheni date ( OROS-MPH ) compared with placebo for attention-deficit/hyperactivity disorder ( ADHD ) , and the impact on substance treatment outcomes in adolescents concurrently receiving cognitive-behavioral therapy ( CBT ) for substance use disorders ( SUD ) . METHOD This was a 16-week , r and omized , controlled , multi-site trial of OROS-MPH + CBT versus placebo + CBT in 303 adolescents ( aged 13 through 18 years ) meeting DSM-IV diagnostic criteria for ADHD and SUD . Primary outcome measures included the following : for ADHD , clinician-administered ADHD Rating Scale ( ADHD-RS ) , adolescent informant ; for substance use , adolescent-reported days of use in the past 28 days . Secondary outcome measures included parent ADHD-RS and weekly urine drug screens ( UDS ) . RESULTS There were no group differences on reduction in ADHD-RS scores  ( OROS-MPH : -19.2 , 95 % confidence interval [ CI ] , -17.1 to -21.2 ; placebo , -21.2 , 95 % CI , -19.1 to -23.2 ) or reduction in days of substance use ( OROS-MPH : -5.7 days , 95 % CI , 4.0 - 7.4 ; placebo : -5.2 days , 95 % CI , 3.5 - 7.0 ) . Some secondary outcomes favored OROS-MPH , including lower parent ADHD-RS scores at 8 ( mean difference = 4.4 , 95 % CI , 0.8 - 7.9 ) and 16 weeks ( mean difference = 6.9 ; 95 % CI , 2.9 - 10.9 ) and more negative UDS in OROS-MPH ( mean = 3.8 ) compared with placebo ( mean = 2.8 ; p = .04 ) . CONCLUSIONS OROS-MPH did not show greater efficacy than placebo for ADHD or on reduction in substance use in adolescents concurrently receiving individual CBT for co-occurring SUD . However , OROS-MPH was relatively well tolerated and was associated with modestly greater clinical improvement on some secondary ADHD and substance outcome measures . Clinical Trial Registration Information-Attention Deficit Hyperactivity Disorder ( ADHD ) in Adolescents with Substance Use Disorders ( SUD ) ; http://www . clinical trials.gov ; NCT00264797 The frequency and severity of 17 side effects presumably associated with stimulant medication were assessed during a rigorous , triple-blind , placebo-controlled , crossover evaluation of methylpheni date , 0.3 and 0.5 mg/kg twice a day , in 83 children with attention deficit hyperactivity disorder . Side effects were rated by parents and teachers at the end of each weekly drug condition . Three children ( 3.6 % ) had side effects that were sufficiently serious to warrant immediate discontinuation of medication . Parent ratings indicated that only the side effects of decreased appetite , insomnia , stomachaches , and headaches increased significantly in frequency and severity during the two active medication doses as compared with the placebo condition . Fewer than half of the children experienced these side effects and among those who did , ratings of mean severity remained in the mild range . Teacher ratings showed little change over drug conditions , except on ratings of staring , sadness , and anxiety , which declined with increasing dose of medication . Parent ratings indicated that only the side effects of decreased appetite , insomnia , stomachaches , and headaches increased significantly in frequency and severity during the two active medication doses as compared with the placebo condition . Fewer than half of the children experienced these side effects and among those who did , ratings of mean severity remained in the mild range . Teacher ratings showed little change over drug conditions , except on ratings of staring , sadness , and anxiety , which declined with increasing dose of medication . Surprisingly , a high frequency of these behavior side effects were reported during the placebo condition . Stimulant medication within this therapeutic range , therefore , results in few , generally mild side effects . ( ABSTRACT TRUNCATED AT 250 WORDS In clinical sample s , juvenile bipolar disorder ( JBPD ) is frequently accompanied by co-morbid attention-deficit/hyperactivity disorder ( ADHD ) . Clinical trials assessing combined psychopharmacological interventions in this population are scarce , and methylpheni date ( MPH ) may worsen manic symptoms . We conducted a r and omized crossover trial with MPH and placebo ( 2 weeks each ) combined with aripiprazole in children and adolescents ( n = 16 ; 8 - 17 years old ) with JBPD and ADHD who had a significant response in manic symptoms with aripiprazole but still presented clinical ly significant symptoms of ADHD .  ADHD , manic , and depressive symptoms were assessed by means of st and ard scales . Fourteen out of the 16 subjects completed the trial . No significant differences between the effects of methylpheni date and placebo were detected in ADHD ( F(1 , 43.22 ) = 0.00 ; p = 0.97 ) or manic ( F(1 , 40.19 ) = 0.93 ; p = 0.34 ) symptoms . Significant improvement in depressive symptoms was observed in the MPH group ( F(1,19.03 ) = 7.75 ; p = 0.01 ) according to a secondary self-reported outcome measure . One patient using aripiprazole  and MPH discontinued the trial due to the onset of a severe mixed episode . No other significant adverse events were observed . Although MPH did not worsen manic symptoms , it was not more effective than placebo in improving ADHD symptoms in children and adolescents with JBPD co-morbid with ADHD stabilized with aripiprazole . Further investigations are warranted . This study is registered at www . clinical trials.gov under the identifier NCT00305370 OBJECTIVE The purpose of this study was to investigate clinical gains from including both dextroamphetamine and methylpheni date in stimulant trials . METHOD Thirty-six medication-naïve children ages 9 - 14 years diagnosed with attention-deficit/hyperactivity disorder ( ADHD ) were enrolled for 6 weeks in a crossover trial , with 2 weeks of methylpheni date , dextroamphetamine , and placebo , in a r and omly assigned , counterbalanced sequence . Outcome measures constituted a computer-based continuous performance test combined with a motion tracking system ( Qb Test ) and an ADHD question naire rated by parents and teachers . RESULTS Group analyses found significant treatment effects of similar size for the two stimulants on both outcome measures . Single-subject analyses revealed that each stimulant produced a favourable response in 26 children ; however , an individual child frequently responded qualitatively or quantitatively differently to the two stimulants . By including both stimulants in the trial , the number of favorable responders increased from 26 ( 72 % ) to 33 ( 92 % ) . In children with favorable responses of unequal strength to the two stimulants , a shift from inferior drug to best drug was associated with a 64 % mean increase in the overall response strength score , as measured by the ADHD question naire . CONCLUSIONS The likelihood of a favorable response and optimal response strength is increased by including both stimulants in the stimulant trial . The study was first registered in clinical trials 28 September 2010 . Clinical Trials.gov Identifier : NCT01220440 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 
    Output:
    
Methylpheni date 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