Functional outcomes from a head-to-head, randomized, double-blind trial of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder and an inadequate response to methylphenidate The Link Between Health-Related Quality of Life and Clinical Symptoms Among Children with Attention-Deficit Hyperactivity Disorder Bupropion versus methylphenidate in the treatment of children with attention-deficit/hyperactivity disorder: randomized double-blind study. Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial. Selegiline in comparison with methylphenidate in attention deficit hyperactivity disorder children and adolescents in a double-blind, randomized clinical trial. Efficacy and Safety of Lisdexamfetamine Dimesylate and Atomoxetine in the Treatment of Attention-Deficit/Hyperactivity Disorder: a Head-to-Head, Randomized, Double-Blind, Phase IIIb Study Erratum to: Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies A double-blind comparison of desipramine and placebo in children and adolescents with chronic tic disorder and comorbid attention-deficit/hyperactivity disorder. Modafinil as a treatment for Attention-Deficit/Hyperactivity Disorder in children and adolescents: A double blind, randomized clinical trial Long-acting methylphenidate has an effect on aggressive behavior in children with attention-deficit/hyperactivity disorder. Efficacy and safety of lisdexamfetamine dimesylate in adolescents with attention-deficit/hyperactivity disorder. Atomoxetine treatment in children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder. Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebo-controlled trial. Vitamin-mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial. A randomized controlled trial of pemoline for attention-deficit/hyperactivity disorder in substance-abusing adolescents. The effectiveness of methylphenidate in the management of Attention Deficit Hyperactivity Disorder (ADHD) in people with intellectual disabilities: A systematic review. A multicenter randomized placebo-controlled clinical trial of pramipexole for Tourette's syndrome. Multimodal treatment in children and adolescents with attention-deficit/hyperactivity disorder: a 6-month follow-up A randomized placebo-controlled trial of electroencephalographic (EEG) neurofeedback in children with attention-deficit/hyperactivity disorder. The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extension. Methylphenidate for attention deficit hyperactivity disorder and drug relapse in criminal offenders with substance dependence: a 24-week randomized placebo-controlled trial Efficacy and safety of atomoxetine hydrochloride in Korean adults with attention‐deficit hyperactivity disorder Urinary catecholamines in children with attention deficit hyperactivity disorder (ADHD): Modulation by a polyphenolic extract from pine bark (Pycnogenol®)
Attention-deficit/hyperactivity disorder ( ADHD ) is associated with functional impairments in multiple domains of patients ’ lives . A secondary objective of this r and omized , active-controlled , head-to-head , double-blind , dose-optimized clinical trial was to compare the effects of lisdexamfetamine dimesylate ( LDX ) and atomoxetine ( ATX ) on functional impairment in children and adolescents with ADHD . Patients aged 6–17 years with an ADHD Rating Scale IV total score ≥28 and an inadequate response to methylpheni date treatment ( judged by investigators ) were r and omized ( 1:1 ) to once-daily LDX or ATX for 9 weeks . Parents/guardians completed the Weiss Functional Impairment Rating Scale-Parent Report ( WFIRS-P ) at baseline and at week 9 or early termination . p values were nominal and not corrected for multiple comparisons . Of 267 r and omized patients , 200 completed the study ( LDX 99 , ATX 101 ) . At baseline , mean WFIRS-P total score in the LDX group was 0.95 [ st and ard deviation ( SD ) 0.474 ; 95 % confidence interval ( CI ) 0.87 , 1.03 ] and in the ATX group was 0.91 ( 0.513 ; 0.82 , 1.00 ) . Scores in all WFIRS-P domains improved from baseline to endpoint in both groups , with least-squares mean changes in total score of −0.35 ( 95 % CI −0.42 , −0.29 ) for LDX and −0.27 ( −0.33 , −0.20 ) for ATX . The difference between LDX and ATX was statistically significant ( p < 0.05 ) for the Learning and School ( effect size of LDX vs ATX , 0.43 ) and Social Activities ( 0.34 ) domains and for total score ( 0.27 ) . Both treatments reduced functional impairment in children and adolescents with ADHD ; LDX was statistically significantly more effective than ATX in two of six domains and in total score ABSTRACT . Clinical research on attention-deficit hyperactivity disorder ( ADHD ) has begun to integrate measures of health-related quality of life ( HRQL ) as part of the overall assessment of treatment outcomes . This study examines the association between HRQL and measures of clinical symptoms of ADHD . Data were gathered from 297 children and adolescents in an 8-week , r and omized , double-blind , placebo-controlled , clinical trial of atomoxetine treatment for ADHD . HRQL was assessed with the Child Health Question naire 50-item Parent Form . ADHD symptoms were assessed with the ADHD Rating Scale-IV ; Parent Version and Clinical Global Impressions-ADHD-Severity . Associations between HRQL and clinical symptoms were assessed with correlations , analyses of variance with post hoc comparisons , and t tests . The Child Health Question naire 50-item Parent Form scales assessing psychosocial domains of HRQL were significantly negatively correlated with clinical measures . Improvement in clinical symptoms was associated with corresponding improvement in psychosocial aspects of HRQL . The findings suggest that HRQL instruments can add important information to efficacy measures in clinical trials of ADHD treatment OBJECTIVE To compare the safety and efficacy of bupropion with methylpheni date in children and adolescents with attention-deficit/hyperactivity disorder ( ADHD ) . METHODS In a 6-week r and omized double-blind study , 44 patients with a DSM-IV-TR diagnosis of ADHD were r and omly assigned to receive bupropion 100 - 150 mg/day ( 100 mg/day for < 30 kg and 150 mg/day for > 30 kg ) or methylpheni date 20 - 30 mg/day . Symptoms were assessed using Teacher and Parent Attention-Deficit/Hyperactivity Disorder Rating Scale-IV ( ADHD-RS-IV ) at baseline and weeks 3 and 6 . RESULTS Forty patients had at least one post-baseline measurement , and 38 patients completed the trial . No significant difference was found between the two groups on the Parent and Teacher ADHD-RS-IV scores ( [ F(1 , 38 ) = 0.266 , p = 0.609 ] and [ F(1 , 38 ) = 0.001 , p = 0.972 ] , respectively ) . By week 6 , 18 patients ( 90 % ) in each group achieved response on the Parent scale ( Fisher 's exact test p-value = 1.0 ) . With the Teacher ADHD-RS-IV used , eight ( 40 % ) patients in the bupropion group and 12 ( 60 % ) patients in the methylpheni date group achieved response by week 6 ( χ(2 ) ( 1 ) = 1.600 , p = 0.206 ) . Headache was observed more frequently in the methylpheni date group . Frequency of other side effects was not significantly different between the two groups . CONCLUSIONS Bupropion has a comparable safety and efficacy profile with methylpheni date in children and adolescents with ADHD OBJECTIVE The aim of the present study was to further evaluate , under double blind and controlled conditions , the efficacy of amantadine for attention-deficit/hyperactivity disorder ( ADHD ) in children and adolescents as compared to methylpheni date . METHODS This was a 6-week r and omized clinical trial . Forty patients ( 28 boys and 12 girls ) with a DSM-IV-TR diagnosis of ADHD were the study population of this trial . All study subjects were r and omly assigned to receive the treatment using capsule of amantadine at a dose of 100 - 150 mg/day depending on weight ( 100 mg/day for < 30 kg and 150 mg/day for > 30 kg ) or methylpheni date at a dose of 20 - 30 mg/day for a 6-week double blind , r and omized clinical trial . The principal measure of outcome was the Teacher and Parent Attention deficit/hyperactivity disorder Rating Scale-IV . RESULTS No significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores ( df = 1 ; F = 0.02 ; p = 0.86 and df = 1 ; F = 0.01 ; p = 0.89 , respectively ) . Side effects of decreased appetite and restlessness were observed more frequently in the methylpheni date group . CONCLUSION The results of this study indicate that amantadine significantly improved symptoms of ADHD and was well tolerated and it may be beneficial in the treatment of children with ADHD . Nevertheless , the present results do not constitute proof of efficacy OBJECTIVES The aim of this study was to examine the selegiline treatment compared to methylpheni date ( MPH ) in children and adolescents with attention deficit hyperactivity disorder ( ADHD ) . METHOD Forty subjects , aged 6 - 15 years , boys and girls , who were diagnosed as having ADHD , using the criteria of the Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition ( DSM-IV ) , were r and omly assigned to receive either selegiline or MPH for 60 days . Treatment outcomes were assessed using the Attention Deficit Hyperactivity Scale ( ADHS ) administered at baseline and on days 14 , 28 , 42 , and 60 following the commencement of treatment . Side effects were also rated . RESULTS There were no significant differences between sex , age , weight , and ethnicity of participants in the 2 groups . Both groups showed a significant improvement over the 60 days of treatment result ing from the teachers ' and parents ' ADHS scores across the treatment . CONCLUSION Following the trial , MPH did not effect greater mean improvement as a result of the parents ' or teachers ' ADHS scores than selegiline . Thus , selegiline appears to be effective and well tolerated for ADHD in children and adolescents Objectives The aim of this study was to compare the efficacy and safety of the prodrug psychostimulant lisdexamfetamine dimesylate ( LDX ) and the non-stimulant noradrenergic compound atomoxetine ( ATX ) in children and adolescents with attention-deficit/hyperactivity disorder ( ADHD ) who had previously responded inadequately to methylpheni date ( MPH ) . Methods This 9-week , head-to-head , r and omized , double-blind , active-controlled study ( SPD489 - 317 ; Clinical Trials.gov NCT01106430 ) enrolled patients ( aged 6–17 years ) with at least moderately symptomatic ADHD and an inadequate response to previous MPH therapy . Patients were r and omized ( 1:1 ) to an optimized daily dose of LDX ( 30 , 50 or 70 mg ) or ATX ( patients < 70 kg , 0.5–1.2 mg/kg with total daily dose not to exceed 1.4 mg/kg ; patients ≥70 kg , 40 , 80 or 100 mg ) . The primary efficacy outcome was time ( days ) to first clinical response . Clinical response was defined as a Clinical Global Impressions-Improvement ( CGI-I ) score of 1 ( very much improved ) or 2 ( much improved ) . Secondary efficacy outcomes included the proportion of responders at each study visit and the change from baseline in ADHD Rating Scale ( ADHD-RS-IV ) and CGI-Severity scores . Tolerability and safety were assessed by monitoring treatment-emergent adverse events ( TEAEs ) , height and weight , vital signs and electrocardiogram parameters . Endpoint was defined as the last post-baseline , on-treatment visit with a valid assessment . Results Of 267 patients r and omized ( LDX , n = 133 ; ATX , n = 134 ) , 200 ( 74.9 % ) completed the study . The median time to first clinical response [ 95 % confidence interval ( CI ) ] was significantly shorter for patients receiving LDX [ 12.0 days ( 8.0–16.0 ) ] than for those receiving ATX [ 21.0 days ( 15.0–23.0 ) ] ( p = 0.001 ) . By week 9 , 81.7 % ( 95 % CI 75.0–88.5 ) of patients receiving LDX had responded to treatment compared with 63.6 % ( 95 % CI 55.4–71.8 ) of those receiving ATX ( p = 0.001 ) . Also by week 9 , the difference between LDX and ATX in least-squares mean change from baseline ( 95 % CI ) was significant in favour of LDX for the ADHD-RS-IV total score [ −6.5 ( −9.3 to −3.6 ) ; p < 0.001 ; effect size 0.56 ] , inattentiveness subscale score [ −3.4 ( −4.9 to −1.8 ) ; p < 0.001 ; effect size 0.53 ] and the hyperactivity/impulsivity subscale score [ −3.2 ( −4.6 to −1.7 ) ; p < 0.001 ; effect size 0.53 ] . TEAEs were reported by 71.9 and 70.9 % of patients receiving LDX and ATX , respectively . At endpoint , both treatments were associated with mean ( st and ard deviation ) increases in systolic blood pressure [ LDX , + 0.7 mmHg ( 9.08 ) ; ATX , + 0.6 mmHg ( 7.96 ) ] , diastolic blood pressure [ LDX , + 0.1 mmHg ( 8.33 ) ; ATX , + 1.3 mmHg ( 8.24 ) ] and pulse rate [ LDX , + 3.6 bpm ( 10.49 ) ; ATX , + 3.7 bpm ( 10.75 ) ] , and decreases in weight [ LDX , −1.30 kg ( 1.806 ) ; ATX , −0.15 kg ( 1.434 ) ] . Conclusions LDX was associated with a faster and more robust treatment response than ATX in children and adolescents with at least moderately symptomatic ADHD who had previously responded inadequately to MPH . Both treatments displayed safety profiles consistent with findings from previous clinical trials Background : The stimulant methylpheni date ( MPH ) has been a mainstay of treatment for attention-deficit/hyperactivity disorder ( ADHD ) for many years . Owing to the short half-life and the issues associated with multiple daily dosing of immediate-release MPH formulations , a new generation of long-acting MPH formulations has emerged . Direct head-to-head studies of these long-acting MPH formulations are important to facilitate an evaluation of their comparative pharmacokinetics and efficacy ; however , to date , relatively few head-to-head studies have been performed . The objective of this systematic review was to compare the evidence available from head-to-head studies of long-acting MPH formulations and provide information that can guide treatment selection . Methods : A systematic literature search was conducted in MEDLINE and PsycINFO in March 2012 using the MeSH terms : attention deficit disorder with hyperactivity/drug therapy ; methylpheni date /therapeutic use and All Fields : Concerta ; Ritalin LA ; OROS and ADHD ; Medikinet ; Equasym XL and ADHD ; long-acting methylpheni date ; Diffucaps and ADHD ; SODAS and methylpheni date . No filters were applied and no language , publication date or publication status limitations were imposed . Articles were selected if the title indicated a comparison of two or more long-acting MPH preparations in human subjects of any age ; non- systematic review articles and unpublished data were not included . Results : Of 15,295 references returned in the literature search and screened by title , 34 articles were identified for inclusion : nine articles from pharmacokinetic studies ( nine studies ) ; nine articles from laboratory school studies ( six studies ) ; two articles from r and omized controlled trials ( two studies ) ; three articles from switching studies ( two studies ) and three articles from one observational study . Conclusions : Emerging head-to-head studies provide important data on the comparative efficacy of the formulations available . At a group level , efficacy across the day generally follows the pharmacokinetic profile of the MPH formulation . No formulation is clearly superior to another ; careful consideration of patient needs and subtle differences between formulations is required to optimize treatment . For patients achieving suboptimal symptom control , switching long-acting MPH formulations may be beneficial . When switching formulations , it is usually appropriate to titrate the immediate-release component of the formulation ; a limitation of current studies is a focus on total daily dose rather than equivalent immediate-release components . Further studies are necessary to provide guidance in clinical practice , particularly in the treatment of adults and pre-school children and the impact of comorbidities and symptom severity on treatment response BACKGROUND Currently , there is no consensus on the best therapeutic approach to chronic tic disorders and comorbid attention-deficit/hyperactivity disorder ( ADHD ) . To address this issue , we evaluated the tolerability and efficacy of the noradrenergic tricyclic antidepressant desipramine hydrochloride in the treatment of children and adolescents with chronic tic disorders and comorbid ADHD . METHODS Forty-one children and adolescents with chronic tic disorders , including Tourette disorder and comorbid ADHD , were studied in a 6-week , double-blind , placebo-controlled , parallel trial . Desipramine was titrated weekly up to 3.5 mg/kg per day . We rated ADHD and tic symptoms weekly and monitored adverse effects , laboratory findings , and cardiovascular parameters . RESULTS Treatment with desipramine ( mean total daily dose , 3.4 mg/kg per day ) was well tolerated without meaningful adverse effects . Desipramine significantly reduced core symptoms of ADHD ( ADHD Rating Scale ; 42 % decrease from baseline relative to placebo , P<.001 ) , with equal response in inattentive symptoms and hyperactive/impulsive symptoms ( P<.001 for both ) . The ADHD response rate was robust ( 71 % vs 0 % ; desipramine vs placebo , P<.001 ) . Likewise , desipramine significantly reduced tic symptoms ( Yale Global Tic Severity Scale ; 30 % decrease from baseline relative to placebo , P<.001 ) , with equal response in motor and phonic tic symptoms ( P<.01 for both ) . The tic response rate was substantial ( 58 % vs 5 % ; desipramine vs placebo , P<.001 ) . There were small but statistically significant differences between desipramine and placebo in heart rate and blood pressure . CONCLUSIONS Treatment with desipramine was well tolerated and was associated with robust clinical ly significant reductions in tic and ADHD symptoms in children and adolescents with chronic tic disorders and ADHD diagnoses Attention-Deficit/Hyperactivity Disorder ( ADHD ) is the most prevalent psychiatric disorder currently afflicting children and is among the most common chronic conditions affecting school-age children . Modafinil is structurally different from the psychostimulants that are typically used to treat ADHD and has been reported to be effective in improving the symptoms of ADHD . The aim of the present study was to further evaluate , under double blind and controlled conditions , the efficacy of modafinil for ADHD in children and adolescents as compared to methylpheni date .  Patients included 60 out patients , children ( 47 boys and 13 girls ) between the ages of 6 - 15 who clearly met the DSM-IV-TR diagnostic criteria for ADHD . Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind , r and omized clinical trial . All study subjects were r and omly assigned to receive either treatment with modafinil film coated tablet ( in doses of 200 - 300 mg/day ) depending on weight ( 200 mg/day for < 30 kg and 300 mg/day for > 30 kg ) ( group 1 ) or methylpheni date ( in doses of 20 - 30 mg/day ) depending on weight ( 20 mg/day for < 30 kg and 30 mg/day for > 30 kg ) ( group 2 ) . The principal measure of outcome was the Teacher and Parent ADHD Rating Scale-IV . Patients were assessed at baseline and at 21 and 42 days after the medication started . No significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores . Side effects of decreased appetite and difficulty falling asleep were observed more in the methylpheni date group . The results of this study indicate that modafinil significantly improved symptoms of ADHD and was well tolerated and it is beneficial in the treatment of children with ADHD 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 examine lisdexamfetamine dimesylate ( LDX ) efficacy and safety versus placebo in adolescents with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD Adolescents ( 13 through 17 ) with at least moderately symptomatic ADHD ( ADHD Rating Scale IV : Clinician Version [ ADHD-RS-IV ] score ≥28 ) were r and omized to placebo or LDX ( 30 , 50 , or 70 mg/d ) in a 4-week , forced-dose titration , double-blind study . Primary and secondary efficacy measures were the ADHD-RS-IV , Clinical Global Impressions-Improvement ( CGI-I ) , and Youth QOL- Research Version ( YQOL-R ) . Safety assessment s included treatment-emergent adverse events ( TEAEs ) , vital signs , laboratory findings , physical examinations , and ECG . RESULTS Overall , 314 participants were r and omized ; 309 were in efficacy analyses and 49 withdrew ( 11 due to TEAEs ) . Least squares mean ( SE ) change from baseline at endpoint in ADHD-RS-IV total scores were -18.3 ( 1.25 ) , -21.1 ( 1.28 ) , -20.7 ( 1.25 ) for 30 , 50 , and 70 mg/d LDX , respectively ; -12.8 ( 1.25 ) for placebo ( p ≤ .0056 versus placebo for each ) . Differences in ADHD-RS-IV total scores favored all LDX doses versus placebo at all weeks ( p ≤ .0076 ) . On the CGI-I , 69.1 % of participants were rated very much/much improved at endpoint with LDX all doses versus placebo ( 39.5 % ) ( p < .0001 ) . YQOL-R changes at endpoint scores for LDX groups versus placebo were not significant . Commonly reported LDX ( all doses combined ) TEAEs ( ≥5 % ) were decreased appetite , headache , insomnia , decreased weight , and irritability . Small mean increases in pulse and blood pressure and no clinical ly meaningful trends in ECG changes were noted with LDX . CONCLUSIONS LDX at all doses was effective versus placebo in treating adolescent ADHD and demonstrated a safety profile consistent with previous LDX studies . CLINICAL TRIALS REGISTRY INFORMATION : Efficacy and Safety of Lisdexamfetamine Dimesylate ( LDX ) in Adolescents With Attention-Deficit/Hyperactivity Disorder ( ADHD ) ; http://www . clinical trials.gov ; NCT00735371 OBJECTIVE To examine ( 1 ) moderating effects of oppositional defiant disorder ( ODD ) on attention-deficit/hyperactivity disorder ( ADHD ) treatment response and ( 2 ) responses of ODD symptoms to atomoxetine . METHOD Children and adolescents ( ages 8 - 18 ) with ADHD were treated for approximately 8 weeks with placebo or atomoxetine ( fixed dosing : 0.5 , 1.2 , or 1.8 mg/kg/day , b.i.d . ) under r and omized , double-blind conditions . Among patients with lifetime diagnostic information ( n = 293 ) , 39 % were diagnosed with comorbid ODD and 61 % were not . Treatment-group differences and differences between patients with and without comorbid ODD were examined post hoc for changes on the Attention-Deficit/Hyperactivity Disorder Rating Scale IV-Parent version , investigator-administered and -scored ; Conners ' Parent Rating Scale-Revised Short Form ; Clinical Global Impressions Severity of ADHD Scale ; and the parent-rated Child Health Question naire . RESULTS Youths with ADHD and comorbid ODD showed statistically significant improvement in ADHD , ODD , and quality -of-life measures . Treatment response was similar in youths with and without ODD , except that the comorbid group showed improvement compared with placebo at 1.8 mg/kg/day but not 1.2 mg/kg/day . In contrast , youths without ODD showed improvement at 1.2 mg/kg/day and no incremental benefit at 1.8 mg/kg/day . CONCLUSIONS Atomoxetine treatment improves ADHD and ODD symptoms in youths with ADHD and ODD , although the comorbid group may require higher doses OBJECTIVE This study compared the efficacy of guanfacine extended release ( GXR ) , a selective alpha(2A)-adrenoceptor agonist , with placebo in children and adolescents with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD This double-blind , 9-week , dose-ranging , parallel- design , multicenter trial r and omized 6- to 17-year-olds with ADHD to once-daily oral GXR in 1- , 2- , 3- , and 4-mg doses or placebo . Primary outcome was change in total ADHD Rating Scale-IV score from baseline to endpoint . Secondary outcomes included changes in scores of hyperactive/impulsive and inattentive subscales ; clinician and parent ratings ; duration of clinical effect ; and safety measures . RESULTS Statistically significant reductions in ADHD Rating Scale-IV scores were observed from baseline to endpoint at all doses of GXR , with effect sizes ranging from 0.43 to 0.62 . In subjects receiving GXR , mean heart rate and systolic and diastolic blood pressure decreased as the dose of GXR increased and then returned toward baseline during the dose-maintenance and dose-tapering phases of the trial . Most frequent treatment-emergent adverse events ( > or = 5 % ) were somnolence , headache , fatigue , sedation , dizziness , irritability , upper abdominal pain , and nausea . Somnolence , sedation , and fatigue adverse events emerged within the first 2 weeks of dosing and generally resolved by study end . CONCLUSIONS : Guanfacine extended-release was effective in reducing symptoms of ADHD . Adverse events were mild to moderate , did not interfere with improvements in attention , and rarely led to discontinuation BACKGROUND The role of nutrition in the treatment of  attention-deficit hyperactivity disorder ( ADHD )  is gaining international attention ; however , treatments have generally focused only on diet restriction or supplementing with one nutrient at a time . AIMS To investigate the efficacy and safety of a broad-based micronutrient formula consisting mainly of vitamins and minerals , without omega fatty acids , in the treatment of ADHD in adults . METHOD This double-blind r and omised controlled trial assigned 80 adults with ADHD in a 1:1 ratio to either micronutrients  ( n = 42 ) or  placebo ( n = 38 ) for 8 weeks ( trial registered with the Australian New Zeal and Clinical Trials Registry : ACTRN12609000308291 ) . RESULTS Intent-to-treat analyses showed significant between-group differences favouring active treatment on self- and observer- but not clinician-ADHD rating scales . However , clinicians rated those receiving micronutrients as more improved than those on placebo both globally and on ADHD symptoms . Post hoc analyses showed that for those with moderate/severe depression  at baseline , there was a greater change in mood favouring active treatment over placebo . There were no group differences in adverse events . CONCLUSIONS This study provides preliminary evidence of efficacy for micronutrients in the treatment of  ADHD symptoms in adults , with a reassuring safety profile OBJECTIVE In adolescents with substance use disorder ( SUD ) , comorbid attention-deficit/hyperactivity disorder ( ADHD ) is associated with greater severity of substance abuse , conduct problems , and worse treatment outcomes . Although many controlled trials have established the efficacy of psychostimulants , including pemoline , for ADHD in children and adolescents , none have been conducted in adolescents with SUD . This r and omized , placebo-controlled trial , conducted between 1996 and 2000 , evaluated the safety and efficacy of pemoline on substance abuse and conduct problems . METHOD Sixty-nine adolescents ( aged 13 - 19 ) with conduct disorder ( CD ) , SUD , and ADHD were recruited from the community and r and omly assigned to a 12-week clinical trial of pemoline ( n = 35 ) or placebo ( n = 34 ) , titrated over 4 weeks to a single morning dose of 75 to 112.5 mg as tolerated . RESULTS Pemoline had greater efficacy than placebo for ADHD as determined by significantly more Clinician 's Global Impression-Improvement ( CGI-I ) ratings of 1 ( very much improved ) or 2 ( much improved ) at the study endpoint ( n = 69 ; p < .05 ) . There was also greater reduction in ADHD severity on the parent-rated Conners Hyperactivity-Impulsivity scale in pemoline-treated study completers compared to placebo-treated completers ( pemoline , n = 17 ; placebo , n = 16 ; p < .01 ) , but no difference between groups in the intent-to-treat analysis ( n = 68 ; p < .13 ) . Substance use did not decline in either group , and there was no difference between groups in baseline to study endpoint change in substance use or CD symptoms . Overall , pemoline was well tolerated , demonstrating a good safety profile and no elevation in liver enzyme levels . CONCLUSIONS Pemoline was efficacious for ADHD but did not have an impact on CD or substance abuse in the absence of specific treatment for SUD 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 BACKGROUND Dopamine agonists could theoretically normalize the suspected central dopamine hypersensitivity in Tourette 's syndrome . METHODS There was a multicenter r and omized , placebo-controlled , double-blind clinical trial of pramipexole given for 6 weeks in 63 children and adolescents with Tourette 's syndrome . RESULTS There were no significant differences in the adjusted mean change in the Total Tic Score of the Yale Global Tic Severity Scale for patients treated with pramipexole ( -7.16 ) and placebo ( -7.17 ) . There were no significant treatment effects on change from baseline in the Global Severity score of the Yale Scale and parent- and investigator-scored Clinical Global Impression of Improvement . In patients with attention deficit hyperactivity disorder , there was improvement in DuPaul ADHD scale scores for patients receiving pramipexole compared with placebo . CONCLUSIONS There was no evidence that pramipexole has efficacy in suppressing tics .  Pramipexole may decrease symptoms of associated attention deficit hyperactivity disorder Abstract Background : Different treatment approaches aim ed at reducing attention-deficit/hyperactivity disorder ( ADHD ) core symptoms are available . However , factors such as intolerance , side-effects , lack of efficacy , high new technology costs , and placebo effect have spurred on an increasing interest in alternative or complementary treatment . Aim : The aim of this study is to explore efficacy of multimodal treatment consisting of st and ard stimulant medication ( methylpheni date ) and neurofeedback ( NF ) in combination , and to compare it with the single treatment in 6-month follow-up in ADHD children and adolescents . Methods : This r and omized controlled trial with 6-month follow-up comprised three treatment arms : multimodal treatment ( NF + MED ) , MED alone , and NF alone .  A total of 130 ADHD children/adolescents participated , and 62 % completed the study .  ADHD core symptoms were recorded pre-/post-treatment , using parents ’ and teachers ’ forms taken from Barkley ’s Defiant Children : A Clinician ’s Manual for Assessment and Parent Training , and a self-report question naire . Results : Significant ADHD core symptom improvements were reported 6 months after treatment completion by parents , teachers , and participants in all three groups , with marked improvement in inattention in all groups . However , no significant improvements in hyperactivity or academic performance were reported by teachers or self-reported by children/adolescents , respectively , in the three groups . Changes obtained with multimodal treatment at 6-month follow-up were comparable to those with single medication treatment , as reported by all participants . Conclusions : Multimodal treatment using combined stimulant medication and NF showed 6-month efficacy in ADHD treatment . More research is needed to explore whether multimodal treatment is suitable for ADHD children and adolescents who showed a poor response to single medication treatment , and for those who want to reduce the use of stimulant medication OBJECTIVE A double-blind , r and omized , placebo-controlled study was design ed to assess the efficacy and safety of electroencephalographic ( EEG ) neurofeedback in children with attention-deficit/hyperactivity disorder ( ADHD ) . The study started in August 2008 and ended in July 2012 and was conducted at Karakter Child and Adolescent Psychiatry University Centre in Nijmegen , The Netherl and s. METHOD Forty-one children ( aged 8 - 15 years ) with a DSM-IV-TR diagnosis of ADHD were r and omly assigned to treatment with either EEG neurofeedback ( n = 22 ) or placebo neurofeedback ( n = 19 ) for 30 sessions , given as 2 sessions per week . The children were stratified by age , electrophysiologic state of arousal , and medication use . Everyone involved in the study , except the neurofeedback therapist and the principal investigator , was blinded to treatment assignment . The primary outcome was severity of ADHD symptoms on the ADHD Rating Scale IV , scored at baseline , during treatment , and at study end . Clinical improvement as measured by the Clinical Global Impressions-Improvement scale ( CGI-I ) was a secondary outcome . RESULTS While total ADHD symptoms improved over time in both groups ( F1,39 = 26.56 , P < .001 ) , there was no significant treatment effect , ie , group × time interaction ( F1,39 = 0.36 , P = .554 ) ; the same was true for clinical improvement as measured by the CGI-I ( P = .092 ) . No clinical ly relevant side effects were observed . Among the children and their parents , guessing treatment assignment was not better than chance level ( P = .224 for children , P = .643 for parents ) . CONCLUSION EEG neurofeedback was not superior to placebo neurofeedback in improving ADHD symptoms in children with ADHD . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00723684 OBJECTIVE To study the efficacy and safety of phosphatidylserine ( PS ) containing Omega3 long-chain polyunsaturated fatty acids attached to its backbone ( PS-Omega3 ) in reducing attention-deficit/ hyperactivity disorder ( ADHD ) symptoms in children . METHOD A 15-week , double-blind , placebo-controlled phase followed by an open-label extension of additional 15 weeks . Two hundred ADHD children were r and omized to receive either PS-Omega3 or placebo , out of them , 150 children continued into the extension .  Efficacy was assessed using Conners ' parent and teacher rating scales ( CRS-P , T ) , Strengths and Difficulties Question naire ( SDQ ) , and Child Health Question naire ( CHQ ) . Safety evaluation included adverse events monitoring . RESULTS The key finding of the double-blind phase was the significant reduction in the Global : Restless/impulsive subscale of CRS-P and the significant improvement in Parent impact-emotional ( PE ) subscale of the CHQ , both in the PS-Omega3 group . Exploratory subgroup analysis of children with a more pronounced hyperactive/impulsive behavior , as well as mood and behavior-dysregulation , revealed a significant reduction in the ADHD-Index and hyperactive components . Data from the open-label extension indicated sustained efficacy for children who continued to receive PS-Omega3 . Children that switched to PS-Omega3 treatment from placebo showed a significant reduction in subscales scores of both CRS-P and the CRS-T , as compare to baseline scores . The treatment was well tolerated . CONCLUSIONS The results of this 30-week study suggest that PS-Omega3 may reduce ADHD symptoms in children . Preliminary analysis suggests that this treatment may be especially effective in a subgroup of hyperactive-impulsive , emotionally and behaviorally-dysregulated ADHD children Aim To test the efficacy and safety of osmotic release oral system ( OROS ) methylpheni date ( MPH ) in doses up to 180 mg/day to treat attention deficit hyperactivity disorder ( ADHD ) and prevent any drug relapse in individuals with a co-diagnosis of ADHD and amphetamine dependence . Design R and omized placebo-controlled 24-week double-blind trial with parallel groups design . Setting Participants were recruited from medium security prisons in Sweden . The medication started within 2 weeks before release from prison and continued in out-patient care with twice-weekly visits , including once-weekly cognitive behavioural therapy . Participants Fifty-four men with a mean age of 42 years , currently incarcerated , meeting DSM-IV criteria for ADHD and amphetamine dependence . Measurements Change in self-reported ADHD symptoms , relapse to any drug use ( amphetamine and other drugs ) measured by urine toxicology , retention to treatment , craving and time to relapse . Findings The MPH-treated group reduced their ADHD symptoms during the trial ( P = 0.011 ) and had a significantly higher proportion of drug-negative urines compared with the placebo group ( P = 0.047 ) , including more amphetamine-negative urines ( P = 0.019 ) and better retention to treatment ( P = 0.032 ) . Conclusions Methylpheni date treatment reduces attention deficit hyperactivity disorder symptoms and the risk for relapse to substance use in criminal offenders with attention deficit hyperactivity disorder and substance dependence This article aims to assess the efficacy and safety of atomoxetine in Korean adults with attention‐deficit hyperactivity disorder ( ADHD ) Abstract Our study tested the hypothesis that treatment with a potent polyphenol complex not only reduces hyperactivity of children , but also catecholamine excretion and oxidative stress . Urine catecholamine concentrations were measured in attention deficit hyperactivity disorder ( ADHD ) children and healthy controls . ADHD children received either placebo ( PL ) or Pycnogenol ® ( Pyc ) , a bioflavonoid extract from the pine bark , for one month . The study was performed in a r and omized , double-blind , PL controlled design . Concentrations of catecholamines were higher in urine of ADHD patients compared to those of healthy children . Moreover , noradrenaline ( NA ) concentrations positively correlated with degree of hyperactivity of ADHD children . In ADHD patients , adrenaline ( A ) and NA concentrations positively correlated with plasma levels of oxidized glutathione . The treatment of ADHD children with Pyc caused decrease of dopamine ( D ) and trend of A and NA decrase and increased GSH/GSSG ratio . In conclusion , the data provide further evidence for the overactivity of the noradrenergic system in ADHD and demonstrate that A release may be increased , as well . Treatment of ADHD children  with Pyc  normalized catecholamine concentrations , leading to less hyperactivity , and , consequently , to reduced oxidative stress
On the CGI-I scale , the analysis revealed that MPH was more effective than ATX and GXR .
For any adverse events , RBX ( 89 % ) was the safest alternative .
Network meta- analysis offered a broader overview on the available treatments for ADHD , especially for safety issues , and contributes towards evidence gathering and clinical practice decisions .
The aim of this study is to gather evidence of head-to-head double-blind r and omized-controlled trials on the efficacy and safety of available treatments for attention deficit hyperactivity disorder ( ADHD ) in children and adolescents .