title: Treatment of ADHD in children with tics: A randomized controlled trial Multisite controlled study of OROS methylphenidate in the treatment of adolescents with attention-deficit/hyperactivity disorder. Dose-response effects of methylphenidate on ecologically valid measures of academic performance and classroom behavior in adolescents with ADHD. Treatment effects of methylphenidate on behavioral adjustment in children with mental retardation and ADHD. Comparison of the clinical efficacy of twice-daily Ritalin® and once-daily Equasym™ XL with placebo in children with Attention Deficit/Hyperactivity Disorder A randomized controlled trial of clonidine added to psychostimulant medication for hyperactive and aggressive children. Long-acting methylphenidate has an effect on aggressive behavior in children with attention-deficit/hyperactivity disorder. Prevalence of Prescribed Attention-Deficit Hyperactivity Disorder Medications and Diagnosis among Canadian Preschoolers and School-Age Children: 1994–2007 A controlled trial of extended-release guanfacine and psychostimulants for attention-deficit/hyperactivity disorder. Clonidine benefits children with attention deficit disorder and hyperactivity: report of a double-blind placebo-crossover therapeutic trial. Transdermal methylphenidate, behavioral, and combined treatment for children with ADHD. Clonidine Extended-Release Tablets as Add-on Therapy to Psychostimulants in Children and Adolescents With ADHD Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes. Effects of Guanfacine Extended Release on Oppositional Symptoms in Children Aged 6–12 Years with Attention-Deficit Hyperactivity Disorder and Oppositional Symptoms Double-blind, placebo-controlled trial of clonidine in hyperactive children with mental retardation. Effect of Lisdexamfetamine Dimesylate on Parent-Rated Measures in Children Aged 6 to 12 Years With Attention-Deficit/Hyperactivity Disorder: A Secondary Analysis
abstract: Background The treatment of children with attention deficit hyperactivity disorder ( ADHD ) and Tourette syndrome ( TS ) has been problematic because methylpheni date (MPH)—the most commonly used drug to treat ADHD — has been reported to worsen tics and because clonidine (CLON)—the most commonly prescribed alternative — has unproven efficacy . Methods The authors conducted a multicenter , r and omized , double-blind clinical trial in which 136 children with ADHD and a chronic tic disorder were r and omly administered CLON alone , MPH alone , combined CLON + MPH , or placebo ( 2 × 2 factorial design ) . Each subject participated for 16 weeks ( weeks 1–4 CLON/placebo dose titration , weeks 5–8 added MPH/placebo dose titration , weeks 9–16 maintenance therapy ) . Results Thirty-seven children were administered MPH alone , 34 were administered CLON alone , 33 were administered CLON + MPH , and 32 were administered placebo . For our primary outcome measure of ADHD ( Conners Abbreviated Symptom Question naire – Teacher ) , significant improvement occurred for subjects assigned to CLON ( p < 0.002 ) and those assigned to MPH ( p < 0.003 ) . Compared with placebo , the greatest benefit occurred with combined CLON + MPH ( p < 0.0001 ) . CLON appeared to be most helpful for impulsivity and hyperactivity ; MPH appeared to be most helpful for inattention . The proportion of individual subjects reporting a worsening of tics as an adverse effect was no higher in those treated with MPH ( 20 % ) than those being administered CLON alone ( 26 % ) or placebo ( 22 % ) . Compared with placebo , measured tic severity lessened in all active treatment groups in the following order : CLON + MPH , CLON alone , MPH alone . Sedation was common with CLON treatment ( 28 % reported moderate or severe sedation ) , but otherwise the drugs were tolerated well , including absence of any evident cardiac toxicity . Conclusions Methylpheni date and clonidine ( particularly in combination ) are effective for ADHD in children with comorbid tics . Prior recommendations to avoid methylpheni date in these children because of concerns of worsening tics are unsupported by this trial BACKGROUND Despite the persistence of attention-deficit/hyperactivity disorder ( ADHD ) into adolescence , little is known about the efficacy and tolerability of stimulant medications in this age group . OBJECTIVE To report the results of a multisite controlled study among adolescents with ADHD evaluating the efficacy and tolerability of osmotic-release oral system ( OROS ) methylpheni date . DESIGN Adolescents ( N = 220 ) having a confirmed Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition diagnosis of ADHD underwent dose titration to identify dosages of OROS methylpheni date that improved symptoms to predefined criteria . Subjects successfully completing the dose titration phase ( n = 177 ) ( ie , tolerated and responded to treatment and adhered to the protocol ) were r and omized to receive 2 weeks ' treatment with their individualized dosage of OROS methylpheni date ( 18 , 36 , 54 , or 72 mg once daily ) or placebo .  Treatment effectiveness was measured using investigator , parent , and adolescent assessment s of ADHD . RESULTS A significant reduction from baseline in the investigator-rated ADHD Rating Scale , the primary efficacy measure , was found with OROS methylpheni date treatment compared with placebo . Similar findings were noted with parent- and adolescent-report measures . Based on a Clinical Global Impression improvement subscale score of much or very much improved , 52 % of subjects in the OROS methylpheni date group improved compared with 31 % receiving placebo . Thirty-seven percent of subjects required the maximum dosage of 72 mg/d . The incidence of drug-related adverse events was similar between the 2 study groups . CONCLUSION In adolescents , once-daily OROS methylpheni date significantly reduced ADHD symptoms and was well tolerated using dosages up to 72 mg/d The effects of methylpheni date on the academic performance and classroom behavior of 45 adolescents with attention deficit hyperactivity disorder were studied . During a 6-week , placebo-controlled medication assessment in the context of a summer treatment program , participants received a double-blind , crossover trial of 3 doses of methylpheni date . Dependent measures included note-taking quality , quiz and worksheet scores , written language usage and productivity , teacher ratings , on-task and disruptive behavior , and homework completion . Group data showed positive effects of methylpheni date on academic measures ; however , the greatest benefit came with the lowest dose . Although additional benefit did occur for some participants with higher doses , the largest increment of change usually occurred between the placebo and 10-mg dose . Many adolescents did not experience added benefit with increased dosages , and in some cases they experienced deterioration . Guidelines for assessment of medication effects are discussed OBJECTIVE The effects of stimulant medication treatment were investigated in children with mental retardation ( MR ) and attention-deficit/hyperactivity disorder ( ADHD ) . METHOD Parent and teacher behavioral ratings and reports of side effects were obtained for children ( N = 24 , mean age = 10.9 years , SD = 2.4 ) during a placebo-controlled , double-blind , crossover treatment trial with 0.15 mg/kg , 0.30 mg/kg , and 0.60 mg/kg b.i.d . dosages of methylpheni date . RESULTS The most significant improvements occurred at the 0.60 mg/kg methylpheni date dose for teacher ratings of inattention ( p = .024 ) , hyperactivity ( p < .001 ) , aggression ( p < .001 ) , and asocial behavior ( p = .009 ) . No significant improvements , relative to placebo , occurred at the 0.15 mg/kg dosage . Of interest , nearly all significant medication-related behavioral improvements were detected by teachers . However , parents were sensitive raters of side effects , noting more sleeping problems and loss of appetite at the 0.60 mg/kg dose compared with placebo . CONCLUSIONS These results suggest that symptoms of ADHD can be treated successfully in children with ADHD/MR , and consistent with MTA study results , higher doses were most effective . Furthermore , these improvements were not accompanied by increases in symptoms such as staring , social withdrawal , or anxiety Objective To compare the efficacy and safety of two methylpheni date ( MPH ) formulations — once-daily modified-release MPH ( EqXL , Equasym ™ XL ) and twice-daily immediate-release methylpheni date ( MPH-IR , Ritalin ® )— and placebo in children with Attention Deficit/Hyperactivity Disorder ( ADHD ) . Methods Children aged 6–12 years on a stable dose of MPH were r and omized into a double-blind , three-arm , parallel-group , multi-center study and received 3 weeks of EqXL ( 20 , 40 , or 60 mg qd ) , MPH-IR ( 10 , 20 , or 30 mg bid ) or placebo . Non-inferiority of EqXL to MPH-IR was assessed by the difference in the inattention/overactivity component of the overall teacher ’s IOWA Conners ’ Rating Scale on the last week of treatment ( per protocol population ) . Safety was monitored by adverse events , laboratory parameters , vital signs , physical exam , and a Side Effect Rating Scale . Results The lower 97.5 % confidence interval bound of the difference between MPH groups fell above the non-inferiority margin ( −1.5 points ) not only during the last week of treatment but during all three treatment weeks . Both MPH-treatment groups experienced superior benefit when compared to placebo during all treatment weeks ( P < 0.001 ) . All treatments were well tolerated . Conclusions EqXL given once-daily was non-inferior to MPH-IR given twice-daily . Both treatments were superior to placebo in reducing ADHD symptoms OBJECTIVE To compare clonidine with placebo added to ongoing psychostimulant therapy for the treatment of attention-deficit/hyperactivity disorder with comorbid oppositional defiant disorder or conduct disorder . METHOD Children 6 to 14 years of age recruited through 2000 to 2001 were r and omized to receive clonidine syrup 0.10 to 0.20 mg/day ( n = 38 ) or placebo ( n = 29 ) for 6 weeks . Primary outcome measures were the Conduct and Hyperactive Index subscales of the parent-report Conners Behavior Checklist . Side effects were monitored using physiological measures and the Barkley Side Effect Rating Scale . RESULTS Evaluable patient analysis showed that significantly more clonidine-treated children than controls were responders on the Conduct scale ( 21 of 37 versus 6 of 29 ; chi2(1 ) = 8.75 , p < .01 ) but not the Hyperactive Index ( 13 of 37 versus 5 of 29 ) . Compared with placebo , clonidine was associated with a greater reduction in systolic blood pressure measured st and ing and with transient sedation and dizziness .  Clonidine-treated individuals had a greater reduction in a number of unwanted effects associated with psychostimulant treatment compared with placebo . CONCLUSIONS The findings support the continued use of clonidine in combination with psychostimulant medication to reduce conduct symptoms associated with attention-deficit/hyperactivity disorder . Treatment is well tolerated and unwanted effects are transient INTRODUCTION Aggression is frequently observed in children and adolescents with attention-deficit/hyperactivity disorder ( ADHD ) . The aim of this study was to assess the efficacy with regard to oppositional and aggressive behavior of a new long-acting methylpheni date preparation ( Medikinet retard , MPH-MR ) , with equal portions of the immediate-release and the sustained-release active substance , and especially to look at correlations between either teacher or parent assessment of aggression and ADHD sub-symptomatology . METHODS Eighty five children and adolescents ( 6 - 16 years ) were investigated in a double-blind , r and omized , clinical trial over 5 weeks under a treatment with MPH-MR  using symptom checklists for ADHD , oppositional-defiant and conduct disorder according to the Diagnostic and Statistical Manual of Mental Disorders , 4th edition ( DSM-IV ) . RESULTS A total of 64.9 % of the children showed oppositional defiant disorder/conduct disorder ( ODD/CD ) symptoms . A statistically significant effect was found in the group treated with MPH ( verum-group ) . On the basis of Cohen 's criteria , high effects were found for aggressive symptoms in school ( d = 1.0 ) , but not in the afternoon ( d = 0.4 ) . There were also lower effect sizes for more severe aggressive symptoms . We found characteristic correlations between ODD/CD symptoms and the ADHD subscale hyperactivity/impulsivity compared to the subscale inattention . CONCLUSIONS Long-acting MPH is effective in the treatment of oppositional-defiant and aggressive behavior , especially concerning milder symptoms . The expected correlation between impulsivity and aggressiveness could be confirmed Objective : To describe trends in the prevalence of prescribed attention-deficit hyperactivity disorder ( ADHD ) medication by Canadian preschoolers and school-age children and to compare these with trends in the prevalence of the ADHD diagnosis between 1994 and 2007 . Methods : Subjects participated in the National Longitudinal Survey on Children and Youth , a Canadian prospect i ve survey collecting data biennially . Three cross-sectional sample s of nonreferred children , aged 3 to 9 years and representative of Canadian children for 1994–1995 ( n = 12 595 ) , 2000–2001 ( n = 13 904 ) , and 2006–2007 ( n = 14 655 ) , were selected for the analyses . Information on prescribed medications and ADHD diagnosis was reported by each child 's parents . Prevalence was estimated at each cycle , taking the child 's age and sex into account . Results : The estimated prevalence of prescribed medications and ADHD diagnosis in Canada was generally low ( less than 3 % ) , but higher for boys ( less than 4 % ) and school-age children ( less than 5 % ) .  Preschoolers ' prevalence of both prescribed medications and ADHD diagnosis stayed stable between 1994 and 2007 ( 1 % or less ) , while that of school-age children increased nearly 2-fold . Boys ' prevalence was higher than that of girls , but girls show the steepest increase over time , up to 2.1-fold . The association between prescribed medications and ADHD diagnosis has strengthened during the 2000s : a greater number of medications were used for children with ADHD ( from 43 % in 2000 to 59 % in 2007 ) while off-label use of prescribed medications decreased among school-age children . Conclusions : The upward trend in the prevalence of prescribed ADHD medications and ADHD diagnosis currently observed in contemporary societies is also occurring in Canada , except with preschoolers OBJECTIVE To examine efficacy , tolerability , and safety of guanfacine extended release ( GXR ; ≤4 mg/d ) adjunctive to a long-acting psychostimulant for the treatment of attention-deficit/hyperactivity disorder ( ADHD ) in children and adolescents 6 to 17 years of age with suboptimal , but partial , response to psychostimulant alone . METHOD In this multicenter , 9-week , double-blind , placebo-controlled , dose-optimization study , subjects ( N = 461 ) continued their stable dose of psychostimulant given in the morning and were r and omized to receive GXR in the morning ( GXR AM ) , GXR in the evening ( GXR PM ) , or placebo .  Efficacy measures included ADHD Rating Scale IV ( ADHD-RS-IV ) and Clinical Global Impressions of Severity of Illness ( CGI-S ) and Improvement ( CGI-I ) scales . Safety measures included adverse events ( AEs ) , vital signs , electrocardiograms , and laboratory evaluations . RESULTS At endpoint , GXR treatment groups showed significantly greater improvement from baseline ADHD-RS-IV total scores compared with placebo plus psychostimulant ( GXR AM , p = .002 ; GXR PM , p < .001 ) . Significant benefits of GXR treatment versus placebo plus psychostimulant were observed on the CGI-S ( GXR AM , p = .013 ; GXR PM , p < .001 ) and CGI-I ( GXR AM , p = .024 ; GXR PM , p = .003 ) . At endpoint , small mean decreases in pulse , systolic , and diastolic blood pressure were observed in GXR treatment groups versus placebo plus psychostimulant . No new safety signals emerged following administration of GXR with psychostimulants versus psychostimulants alone . Most AEs were mild to moderate in severity . CONCLUSIONS Morning or evening GXR administered adjunctively to a psychostimulant showed significantly greater improvement over placebo plus psychostimulant in ADHD symptoms and generated no new safety signals . Clinical trial registration information-Efficacy and Safety of SPD503 in Combination With Psychostimulants ; http://www . clinical trials.gov ; NCT00734578 Ten children ages 8–13 years with attention deficit disorder and hyperactivity ( ADDH ) completed a double-blind placebo-controlled crossover trial consisting of clonidine for 8 weeks and placebo for 4 weeks . The diagnosis was established through a st and ardized clinical interview with parents and children by two child psychiatrists and behavior ratings by parents and teachers . Parents ' behavior ratings showed that 7 of the 10 children clearly benefited from clonidine .  The total score of behavior ratings on Conners ' Scale for the group diminished from pretreatment levels of 66.85 ± 5.75 ( mean ± S.E. ) to 43.00 ± 6.29 by the end of active clonidine treatment ( p = 0.001 ) . Parents rated as the greatest improvement in factors comprising the Hyperactivity Index , and Conduct Problems . Of the 8 children on whom teachers ' ratings were completed , 7 improved with clonidine . Teachers ' overall ratings for the ADDH group before clondidine were 49.00 ± 5.2 and decreased to 25.79 ± 1.3 by the last 2 weeks of active treatment ( p = 0.001 ) . Teachers ' ratings of the " Hyperactivity Index " decreased even more significantly ( 1.99 ± 0.16 ) to 1.12 ± 0.06 by the end of active clondidine treatment ( p = 0.001 ) . The major side effect was sleepiness , which diminished in all but one child by the third week of treatment . Clonidine appears to be a safe , effective medication for a subgroup of children with symptoms of ADDH . Its effectiveness suggests the importance of the norepinephrine system in the pathophysiology of the cognitive and behavioral disturbances in some children with ADDH . Journal of the American Academy of Child Psychiatry , 24 , 5:617–629 , 1985 Stimulant medication and behavioral treatments are evidence -based for children with attention-deficit/hyperactivity disorder , but the combination of the 2 treatments has been understudied . In this investigation , methylpheni date ( MPH ) was crossed with 2 levels of behavior modification ( BMOD ) in a summer treatment program .  Twenty-seven children with attention-deficit/hyperactivity disorder , aged 6 - 12 , participated . Children received placebo and 3 doses of transdermal MPH ( 12.5 cm(2 ) , 25.0 cm(2 ) , and 37.5 cm(2 ) ) . BMOD was implemented on alternating weeks . Both treatments produced large and significant effects . Combined treatment was superior to either treatment alone . The effects of transdermal MPH were comparable to those found in this setting in previous studies with multiple stimulant medications and formulations . Consistent with other research , low doses of MPH -- even lower than in previous studies --yielded enhanced effects in combination with behavior modification OBJECTIVE : To assess the efficacy and safety of clonidine hydrochloride extended-release tablets ( CLON-XR ) combined with stimulants ( ie , methylpheni date or amphetamine ) for attention-deficit/hyperactivity disorder ( ADHD ) . PATIENTS AND METHODS : In this phase 3 , double-blind , placebo-controlled trial , children and adolescents with hyperactive- or combined-subtype ADHD who had an inadequate response to their stable stimulant regimen were r and omized to receive CLON-XR or placebo in combination with their baseline stimulant medication . Predefined efficacy measures evaluated change from baseline to week 5 . Safety was assessed by spontaneously reported adverse events , vital signs , electrocardiogram recordings , and clinical laboratory values . Improvement from baseline for all efficacy measures was evaluated using analysis of covariance . RESULTS : Of 198 patients r and omized , 102 received CLON-XR plus stimulant and 96 received placebo plus stimulant . At week 5 , greater improvement from baseline in ADHD Rating Scale IV ( ADHD-RS-IV ) total score ( 95 % confidence interval : −7.83 to −1.13 ; P = .009 ) , ADHD-RS-IV hyperactivity and inattention subscale scores ( P = .014 and P = .017 , respectively ) , Conners ' Parent Rating Scale scores ( P < .062 ) , Clinical Global Impression of Severity ( P = .021 ) , Clinical Global Impression of Improvement ( P = .006 ) , and Parent Global Assessment ( P = .001 ) was observed in the CLON-XR plus stimulant group versus the placebo plus stimulant group . Adverse events and changes in vital signs in the CLON-XR group were generally mild . CONCLUSIONS : The results of this study suggest that CLON-XR in combination with stimulants is useful in reducing ADHD in children and adolescents with partial response to stimulants 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 Abstract Objective : To evaluate the efficacy and safety of guanfacine extended release ( XR , Intuniv ™ ; Shire Development Inc. , Wayne , PA , USA ) in the treatment of oppositional symptoms in children aged 6–12 years with a diagnosis of attention-deficit hyperactivity disorder ( ADHD ) and the presence of oppositional symptoms . Subjects and Methods : In this r and omized , double-blind , placebo-controlled , multicentre , flexible-dose , dose-optimization study , children aged 6–12 years were r and omized to receive guanfacine XR ( 1–4mg/day ) or placebo for 9 weeks . Screening and washout periods were followed by a 5-week dose-optimization period , a 3-week dose-maintenance period and a 1-week tapering period . The primary efficacy measure was change from baseline to endpoint in the oppositional subscale of the Conners ’ Parent Rating Scale-Revised : Long Form ( CPRS-R : L ) score . Change in ADHD Rating Scale IV ( ADHD-RS-IV ) total score was a secondary efficacy measure . Safety assessment s included adverse events ( AEs ) , vital signs , ECG readings and laboratory studies . Results : A total of 217 children were enrolled : 138 were r and omized to receive guanfacine XR and 79 to receive placebo .  Least-squares mean reductions from baseline to endpoint in CPRS-R : L oppositional subscale scores were 10.9 in the guanfacine XR group compared with 6.8 in the placebo group ( p<0.001 ; effect size = 0.59 ) . A significantly greater reduction in ADHD-RS-IV total score from baseline to endpoint was also seen in the guanfacine-treated group compared with the placebo group ( 23.8 vs 11.5 , respectively ; p<0.001 ; effect size = 0.92 ) . A post hoc correlation analysis between percentage reduction from baseline to endpoint in CPRS-R : L oppositional subscale and ADHD-RS-IV total scores indicated that the decreases in oppositional symptoms and ADHD symptoms were highly correlated ( r = 0.74).The most commonly reported , treatment-emergent AEs ( TEAEs ) in the guanfacine XR group were somnolence ( 50.7 % ) , headache ( 22.1 % ) , sedation ( 13.2 % ) , upper abdominal pain ( 11.8 % ) and fatigue ( 11.0 % ) and most were mild or moderate in severity . TEAEs of sedation , somnolence or hypersomnia were experienced by 62.5 % of subjects in the guanfacine XR group . These events were most common during the dose-titration period but most ( 63.5 % ) resolved prior to the taper period . TEAEs of fatigue , lethargy and asthenia were reported in 11.0 % , 3.7 % and 0.0 % of subjects in the guanfacine XR group , respectively . Most subjects receiving guanfacine XR demonstrated modest changes in blood pressure , pulse rate and ECG readings that were not considered clinical ly significant . Conclusions : In this population of children aged 6–12 years with ADHD and the presence of oppositional symptoms , significant reductions in CPRS-R : L oppositional subscale and ADHD-RS-IV total scores were observed with guanfacine XR treatment compared with placebo . Treatment with guanfacine XR at optimized doses was associated with mostly mild or moderate TEAEs . The findings of this study support the efficacy of guanfacine XR in the treatment of children with ADHD and the presence of oppositional symptoms . Clinical Trial Registration Number : NCT00367835 A 12-week , double-blind , r and omized , placebo-controlled trial of oral clonidine in three fixed doses ( 4 , 6 , and 8 mcg/kg/day ) using a crossover design was conducted with 10 children who had hyperkinetic disorder ( mean age 7.6 years + /-.54 ) . All had comorbid mental retardation . Both parents ' ratings on the Parent Symptom Question naire and clinicians ' ratings on the Hillside Behaviour Rating Scale showed a marked dose-related response to clonidine in hyperactivity , impulsivity , and inattention . Drowsiness was a common side effect of clonidine . It wore off by the 2nd to 4th week in most cases . Thus , clonidine is a safe and effective medication in young hyperkinetic children with comorbid mental retardation Objective : To evaluate the efficacy of lisdexamfetamine dimesylate ( LDX ) in school-aged children with attention-deficit/hyperactivity disorder ( ADHD ) , using the Conners ' Parent Rating Scale , Revised Short Version ( CPRS-R : S ) and its subscales . Methods : This was a secondary post hoc analysis of data from a placebo-controlled , double-blind , parallel-group , forced doseescalation trial . Boys and girls aged 6 to 12 years with a primary diagnosis of ADHD were r and omly assigned to LDX ( 30 , 50 , or 70 mg/d ) or placebo . Improvement on the CPRS-R : S and its subscales ( ADHD Index , hyperactivity , appositional , and cognition ) at 10 : 00 AM , 2 : 00 PM , and 6 : 00 PM was analyzed . Safety assessment s included the identification of adverse events and were conducted throughout the study . Results : Of the 290 patients r and omized , 285 were included in the intent-to-treat population . Parents noted significant improvements at all 3 assessment times on the CPRS-R : S total score and for the CPRS-R : S ADHD Index , hyperactivity , and cognition subscales , regardless of the subject baseline disease severity . For the CPRS-R : S appositional subscale , significant improvement was noted at 10 : 00 AM and 2 : 00 PM ( P < 0.01 ) , and overall , significant improvement occurred in subjects who were more severely ill at baseline . The tolerability of LDX was comparable to that of other stimulants . Conclusion : Once-daily treatment with LDX was associated with significant improvement in parent-rated assessment s of AD HO-related behavior throughout the day at approximately 10 : 00 AM , 2 : 00 PM , and 6 : 00 PM . Lisdexamfetamine dimesylate was effective and well tolerated in this study population of children aged 6 to 12 years with ADHD
target: There is very-low- quality evidence that clonidine has a small effect on oppositional behaviour and conduct problems in youth with ADHD , with and without ODD or CD .
  There is moderate- quality evidence that guanfacine has a small-to-moderate effect on oppositional behaviour in youth with ADHD , with and without ODD .
  There is high- quality evidence that atomoxetine has a small effect on oppositional behaviour in youth with ADHD , with and without ODD or CD .
  Conclusions : Evidence indicates that psychostimulants , alpha-2 agonists , and atomoxetine can be beneficial for disruptive and aggressive behaviours in addition to core ADHD symptoms ; however , psychostimulants generally provide the most benefit
background: Objective : Children with attention-deficit hyperactivity disorder ( ADHD ) may have oppositional behaviour , conduct problems , and aggression .
  These symptoms vary in severity , and may be related to a comorbid diagnosis of oppositional defiant disorder ( ODD ) or conduct disorder ( CD ) .
  Critical evaluation of the efficacy of ADHD medications may guide the clinician regarding the usefulness of medications for these symptoms .