title: Methylphenidate versus dexamphetamine in children with attention deficit hyperactivity disorder: A double-blind, crossover trial. Efficacy of Reboxetine in the Treatment of Attention-Deficit/Hyperactivity Disorder in Boys With Intolerance to Methylphenidate: An Open-Label, 8-Week, Methylphenidate-Controlled Trial Relative efficacy of long-acting stimulants on children with attention deficit-hyperactivity disorder: a comparison of standard methylphenidate, sustained-release methylphenidate, sustained-release dextroamphetamine, and pemoline. 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 European, randomized, phase 3 study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder Buspirone Versus Methylphenidate in the Treatment of Attention Deficit Hyperactivity Disorder: A Double-Blind and Randomized Trial 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 Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder: results from a randomized, controlled trial A Comparison of Ritalin and Adderall: Efficacy and Time-course in Children With Attention-deficit/Hyperactivity Disorder Dose effects and comparative effectiveness of extended release dexmethylphenidate and mixed amphetamine salts. A double-blind, placebo-controlled trial of dexmethylphenidate hydrochloride and d,l-threo-methylphenidate hydrochloride in children with attention-deficit/hyperactivity disorder. Memantine versus Methylphenidate in Children and Adolescents with Attention Deficit Hyperactivity Disorder: A Double-Blind, Randomized Clinical Trial Buspirone versus methylphenidate in the treatment of children with attention- deficit/ hyperactivity disorder: randomized double-blind study. Fenfluramine and dextroamphetamine treatment of childhood hyperactivity. Clinical and biochemical findings. Atomoxetine versus Methylphenidate in Paediatric Outpatients with Attention Deficit Hyperactivity Disorder: A Randomized, Double-Blind Comparison Trial Side effects of methylphenidate and dexamphetamine in children with attention deficit hyperactivity disorder: a double-blind, crossover trial. Modafinil as a treatment for Attention-Deficit/Hyperactivity Disorder in children and adolescents: A double blind, randomized clinical trial Effects of methylphenidate, desipramine, and l-dopa on attention and inhibition in children with Attention Deficit Hyperactivity Disorder Effects of atomoxetine and methylphenidate on sleep in children with ADHD. Efficacy of theophylline compared to methylphenidate for the treatment of attention-deficit hyperactivity disorder in children and adolescents: a pilot double-blind randomized trial. Selegiline in the treatment of attention deficit hyperactivity disorder in children: a double blind and randomized trial Double-blind, placebo-controlled study of single-dose amphetamine formulations in ADHD. Effect of Extended-Release Dexmethylphenidate and Mixed Amphetamine Salts on Sleep: A Double-Blind, Randomized, Crossover Study in Youth with Attention-Deficit Hyperactivity Disorder Combined Stimulant and Guanfacine Administration in Attention-Deficit/Hyperactivity Disorder: A Controlled, Comparative Study. Treatment of hyperactive children with monoamine oxidase inhibitors. I. Clinical efficacy. Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder. Methylphenidate vs dextroamphetamine vs caffeine in minimal brain dysfunction: controlled comparison by placebo washout design with Bayes' analysis. A Laboratory School Comparison of Mixed Amphetamine Salts Extended Release (Adderall XR®) and Atomoxetine (Strattera®) in School-Aged Children With Attention Deficit/Hyperactivity Disorder Methylphenidate and caffeine in the treatment of children with minimal brain dysfunction. Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis. Comparison of the effects of chlorpromazine, dextroamphetamine and methylphenidate on the behaviour and intellectual functioning of hyperactive children. Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial. Lisdexamfetamine Dimesylate and Mixed Amphetamine Salts Extended-Release in Children with ADHD: A Double-Blind, Placebo-Controlled, Crossover Analog Classroom Study Caffeine versus methylphenidate and d-amphetamine in minimal brain dysfunction: a double-blind comparison. A Comparative Study of the Efficacy of ACTH4–9 Analog, Methylphenidate, and Placebo on Attention Deficit Disorder with Hyperkinesis Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes. A randomized trial of edivoxetine in pediatric patients with attention-deficit/hyperactivity disorder. Levoamphetamine and dextroamphetamine: comparative efficacy in the hyperkinetic syndrome. Assessment by target symptoms. Selegiline in comparison with methylphenidate in attention deficit hyperactivity disorder children and adolescents in a double-blind, randomized clinical trial. Pindolol and methylphenidate in children with attention-deficit hyperactivity disorder. Clinical efficacy and side-effects. A comparison of morning-only and morning/late afternoon Adderall to morning-only, twice-daily, and three times-daily methylphenidate in children with attention-deficit/hyperactivity disorder. Bupropion versus methylphenidate in the treatment of children with attention-deficit/hyperactivity disorder: randomized double-blind study. Randomised controlled study-efficacy of clonidine versus carbamazepine in children with ADHD. Levoamphetamine vs dextroamphetamine in minimal brain dysfunction. Replication, time response, and differential effect by diagnostic group and family rating. Classroom academic performance: improvement with both methylphenidate and dextroamphetamine in ADHD boys. Pemoline, methylphenidate, and placebo in children with minimal brain dysfunction. A double-blind, placebo-controlled study of Adderall and methylphenidate in the treatment of attention-deficit/hyperactivity disorder.
abstract: OBJECTIVE To compare methylpheni date ( MPH ) and dexamphetamine ( DEX ) in a sample of children with attention deficit hyperactivity disorder ( ADHD ) . METHOD A total of 125 children with ADHD received both MPH ( 0.3 mg/kg twice daily ) and DEX ( 0.15 mg/kg twice daily ) for 2 weeks a double-blind , crossover study . Outcome measures were Conners ' Parent Rating Scale-Revised , Conners ' Teacher Rating Scale-Revised , a Parent Global Perceptions question naire , the Continuous Performance Test , and the Barkley Side Effects Rating Scale . RESULTS There were significant group mean improvements from baseline score on all measures for both stimulants . On the Conners ' Teacher Rating Scale-Revised , response was greater on MPH than DEX on the conduct problems and hyperactivity factors , as well as on the hyperactivity index . On the Conners ' Parent Rating Scale-Revised , anxiety was the only factor to differ significantly , in favor of MPH . Parents rated 73 % of subjects as globally improved on MPH and 69 % improved on DEX , compared with baseline . Overall , 46 % of parents chose MPH as the preferred drug , compared with 37 % who chose DEX . On the Continuous Performance Test , there was no difference in the number of correct responses or errors between the two drugs . CONCLUSIONS Most children with ADHD improve significantly on both MPH and DEX . There was a slight advantage to MPH on most measures Objective : Attention-deficit/hyperactivity disorder ( ADHD ) is the most common neurobehavioral disorder of childhood . Principal treatment options for ADHD today include the psychostimulants , mainly methylpheni date ( MPH ) . However , approximately 30 % to 50 % of children and adults with ADHD either do not respond to or do not tolerate treatment with stimulants . In this 8-week open-label , MPH-controlled , parallel group design study , we investigate the efficacy of reboxetine , a new selective norepinephrine reuptake inhibitor , in the treatment of boys with ADHD with a history of intolerance to MPH therapy . Method : Twenty-seven outpatient boys , aged 6 to 16 years , diagnosed with ADHD , participated in the study . Those with a history of intolerance to MPH therapy were assigned to treatment with reboxetine ( 2 - 8 mg/d ) , and the rest were assigned to treatment with MPH ( 10 - 20 mg/d ) as the control group . The primary outcome measure for this study was the change in rating scores on the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , ADHD Scale ( DAS ) that was assessed at baseline and at 8 weeks . Results : At the end of 8 weeks , both reboxetine and MPH treatment regimens result ed in significant improvement in ADHD symptoms . The change in the reduction in the total DAS score and the DAS subscale scores between the reboxetine group and the MPH group was not statistically significant in any of the scores . Conclusions : Although preliminary , results of this study indicate that the use of reboxetine , a new selective norepinephrine reuptake inhibitor , in the treatment of ADHD could increase treatment options available for children who have shown intolerance or who are unresponsive to MPH Twenty-two children with attention deficit-hyperactivity disorder underwent a double-blind , placebo-controlled , crossover evaluation of the efficacy of st and ard methylpheni date twice a day and comparable doses every morning of a sustained-release preparation of methylpheni date ( SR-20 Ritalin ) , a sustained-release form of dextroamphetamine ( Dexedrine Spansule ) , and pemoline . The children were participating in a summer treatment program in which they engaged in recreational and classroom activities . Dependent measures include evaluations of social behavior during group recreational activities , classroom performance , and performance on a continuous performance task . Results revealed generally equivalent and beneficial effects of all four medications . Dexedrine Spansule and pemoline tended to produce the most consistent effects and were recommended for 10 of the 15 children who were responders to medication . The continuous performance task results showed that all four medications had an effect within 2 hours of ingestion , and the effects lasted for 9 hours . The implication s of these results for the use of long-acting stimulant medication in children with attention deficit-hyperactivity disorder are discussed 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 This study evaluated the efficacy and safety of lisdexamfetamine dimesylate ( LDX ) compared with placebo in children and adolescents with attention-deficit/hyperactivity disorder ( ADHD ) in Europe .  Osmotic-release oral system methylpheni date ( OROS-MPH ) was included as a reference arm . Patients ( 6 - 17 years old ) with a baseline ADHD Rating Scale version IV ( ADHD-RS-IV ) total score ≥ 28 were r and omized ( 1:1:1 ) to dose-optimized LDX  ( 30 , 50 , or 70 mg/day ) , OROS-MPH ( 18 , 36 , or 54 mg/day ) or placebo for 7 weeks . Primary and key secondary efficacy measures were the investigator-rated ADHD-RS-IV and the Clinical Global Impressions-Improvement ( CGI-I ) rating , respectively . Safety assessment s included treatment-emergent adverse events ( TEAEs ) , electrocardiograms , and vital signs . Of 336 patients r and omized , 196 completed the study . The difference between LDX and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -18.6 ( 95 % confidence interval [ CI ] : -21.5 to -15.7 ) ( p<0.001 ; effect size , 1.80 ) . The difference between OROS-MPH and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -13.0 ( 95 % CI : -15.9 to -10.2 ) ( p<0.001 ; effect size , 1.26 ) . The proportions ( 95 % CI ) of patients showing improvement ( CGI-I of 1 or 2 ) at endpoint were 78 % ( 70 - 86 ) , 14 % ( 8 - 21 ) , and 61 % ( 51 - 70 ) for LDX , placebo , and OROS-MPH . The most common TEAEs for LDX were decreased appetite , headache , and insomnia . Mean changes in vital signs were modest and consistent with the known profile of LDX . LDX was effective and generally well tolerated in children and adolescents with ADHD The efficacy and side effects of buspirone compared with methylpheni date ( MPH ) in the treatment of children with attention-deficit/hyperactivity disorder ( ADHD ) . A total of 34 children with ADHD as defined by DSM-IV-TR were r and omized to buspirone or methylpheni date dosed on weight-adjusted basis at buspirone ( 0.5 mg/kg/day ) and methylpheni date ( 0.3–1 mg/kg/day ) for a 6-week double-blind clinical trial . The principle measures of outcome were the teacher and parent ADHD Rating Scale . The side effects were assessed by the special side effect checklist of each drug . In both groups , the scores of teacher and parent ADHD Rating Scale significantly declined on the 6th week as compared to baseline ( p = 0.001 ) . These effects were observed in the subscales too . No significant differences were observed between the two protocol s on the total scores of parent and teacher ADHD Rating Scale , but methylpheni date was superior to buspirone in decreasing the symptoms of inattention . The side effects of buspirone were mild and rare in comparison with MPH . Buspirone has a favorable side-effects profile . It also has clinical ly and statistically significant impacts on improving the ADHD symptoms in children . These preliminary findings of the efficacy of buspirone in children with ADHD need large and cross-over studies 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 Lisdexamfetamine dimesylate ( LDX ) is a long-acting , prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder ( ADHD ) . This r and omized placebo-controlled trial of an optimized daily dose of LDX ( 30 , 50 or 70 mg ) was conducted in children and adolescents ( aged 6–17 years ) with ADHD . To evaluate the efficacy of LDX throughout the day , symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners ’ Parent Rating Scale-Revised ( CPRS-R ) at 1000 , 1400 and 1800 hours following early morning dosing ( 0700 hours ) . Osmotic-release oral system methylpheni date ( OROS-MPH ) was included as a reference treatment , but the study was not design ed to support a statistical comparison between LDX and OROS-MPH . The full analysis set comprised 317 patients ( LDX , n = 104 ; placebo , n = 106 ; OROS-MPH , n = 107 ) . At baseline , CPRS-R total scores were similar across treatment groups . At endpoint , differences ( active treatment − placebo ) in least squares ( LS ) mean change from baseline CPRS-R total scores were statistically significant ( P < 0.001 ) throughout the day for LDX ( effect sizes : 1000 hours , 1.42 ; 1400 hours , 1.41 ; 1800 hours , 1.30 ) and OROS-MPH ( effect sizes : 1000 hours , 1.04 ; 1400 hours , 0.98 ; 1800 hours , 0.92 ) . Differences in LS mean change from baseline to endpoint were statistically significant ( P < 0.001 ) for both active treatments in all four subscales of the CPRS-R ( ADHD index , oppositional , hyperactivity and cognitive ) . In conclusion , improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening ( 1800 hours ) Objective . Very little research has focused on the efficacy of Adderall ( Shire-Richwood Inc , Florence , KY ) in the treatment of children with attention-deficit/hyperactivity disorder ( ADHD ) , and no studies have compared it with st and ardized doses of Ritalin ( Novartis Pharmaceuticals , East Hanover , NJ ) . It is thought that Adderall has a longer half-life than Ritalin and might minimize the loss of efficacy that occurs 4 or 5 hours after Ritalin ingestion . We compared two doses of Ritalin and Adderall in the treatment of ADHD in children in an acute study and assessed the medications ' time courses . Design . Within-subject , double-blind , placebo-controlled , crossover design lasting 6 weeks . As in our previous work , medication changes occurred on a daily basis in r and om order over days . Setting . Eight-week , weekday ( 9 hours daily )  summer treatment program at the State University of New York at Buffalo , using an intensive behavioral treatment program including a point system and parent training . Study Participants . Twenty-five children ( 21 boys and 4 girls ) diagnosed as ADHD using st and ardized structured interview and rating scales , mean age 9.6 years , 88 % Caucasian , of average intelligence , with no medical conditions that would preclude a trial of stimulant medication . Thirteen were comorbid for opposi-tional-defiant disorder and another 8 for conduct disorder . Interventions . Children received 10 mg of Ritalin , 17.5 mg of Ritalin , 7.5 mg of Adderall , 12.5 mg of Adderall , or placebo , twice a day ( 7:45 am and 12:15 pm ) , in r and om order with conditions changing daily for 24 days . Outcome Measures . Daily rates of behaviors in recreational and classroom setting s , and st and ardized ratings from counselors , teachers , and parents , were averaged across days within condition within child and compared . Within-subject relative sizes of the medication effects were computed by taking the placebo-minus-drug mean difference divided by the placebo st and ard deviation for each child , and were compared hourly between first daily ingestion ( 7:45am ) and 5:00 pm to assess the time course of the two drugs . Measures were taken at 12:00 pm ( recess rule violations ) and at 5:00 pm ( parent behavior ratings ) to determine whether Adderall was still effective at times when the effects of Ritalin should have worn off . Parent ratings were also made for evening behavior to assess possible rebound , and side effects ratings were obtained from parents , counselors , and teachers . Parents , counselors , and teachers also rated their perceptions of medication status and whether they recommended the continued use of the medication given that day . Finally , a clinical team made recommendations for treatment taking into account each child 's individual response . Results . Both drugs were routinely superior to placebo and produced dramatic improvements in rates of negative behavior , academic productivity , and staff/parent ratings of behavior . The doses of Adderall that were assessed produced greater improvement than did the assessed doses of Ritalin , particularly the lower dose of Ritalin , on numerous but not all measures . This result suggests that the doses of Adderall used were functionally more potent than those for Ritalin . Adderall was generally superior to the low dose of Ritalin when the effects of Ritalin were wearing off at midday and late afternoon/early evening . The lower dose of Adderall produced effects comparable to those of the higher dose of Ritalin . Both drugs produced low and comparable levels of clinical ly significant side effects . Staff clinical recommendations for continued medication favored Adderall three to one . Almost 25 % of the study participants were judged to be nonresponders by the clinical team , presumably because of their large beneficial response to the concurrent behavioral intervention and minimal incremental benefit from medication . Conclusions . This is the first investigation to assess comparable doses of Adderall and Ritalin directly . Results showed that Adderall is at least as effective as Ritalin in improving acutely the behavior and academic productivity of children with ADHD . These results show clearly that Adderall should be added to the armamentarium of effective treatment for ADHD , particularly for children in whom the effects of Ritalin dissipate rapidly and a longer acting medication is desired . Measures taken at times of the day when Ritalin is expected to have worn off—4 to 5 hours after ingestion — generally showed that Adderall was more effective than Ritalin at these times . The 7.5-mg twice-a-day dose of Adderall and the 17.5-mg twice-a-day dose of Ritalin produced equivalent behavioral changes . This indicates that a 5-mg dose of Adderall ( or slightly less ) is equivalent to a 10-mg dose of Ritalin , indicating that Adderall is twice as potent ; this potency ratio is similar to the well-known 1:2 ratio between d-amphetamine and methylpheni date . A higher dose of Adderall did not produce incremental improvement beyond that of the 7.5-mg dose , and parents were less likely to desire the continuation of the higher Adderall dose than the other medication conditions . Three-quarters of the responders to medication were recommended the lower rather than higher of the doses assessed . These findings are similar to our previous reports that there is a diminishing incremental value with stimulant medications beyond low to moderate doses , particularly when a behavioral intervention is concurrently implemented . Time-course results indicated that the afternoon dose of medication seemed to have a larger effect than the morning dose , raising the possibility that afternoon doses of stimulant medication may be able to be reduced relative to the morning dose without a corresponding reduction in efficacy . Although this practice is commonly used with some cases in clinical setting s , it is almost never used in empirical investigations and no studies have systematic ally investigated the practice . Our results suggest that systematic studies of a reduced midday dose are indicated . Further studies of dose equivalence and dose-response , including mg/kg dosing rather than absolute dosing , are necessary to firmly establish the  Adderall : Ritalin  dosing ratio and guidelines for clinical practice . Studies comparing Adderall to d-amphetamine should be conducted to determine whether the compound is superior to d-amphetamine alone . Further examinations of time-course are necessary to determine the length of action of  Adderall  — for example , whether a single morning dose will be sufficient to provide coverage throughout the school day OBJECTIVE To compare the dose effects of long-acting extended-release dexmethylpheni date ( ER d-MPH ) and ER mixed amphetamine salts ( ER MAS ) on attention-deficit/hyperactivity disorder ( ADHD ) symptom dimensions , global and specific impairments , and common adverse events associated with stimulants . METHODS Fifty-six children and adolescents with ADHD participated in an 8-week , double-blind , crossover study comparing ER d-MPH ( 10 , 20 , 25 - 30 mg ) and ER MAS ( 10 , 20 , 25 - 30 ) with a week of r and omized placebo within each drug period . Efficacy was assessed with the ADHD Rating Scale-IV ( ADHD-RS-IV ) , whereas global and specific domains of impairment were assessed with the Clinical Global Impressions Severity and Improvement Scales and the parent-completed Weiss Functional Impairment Scale , respectively . Insomnia and decreased appetite , common stimulant-related adverse events , were measured with the parent-completed Stimulant Side Effects Rating Scale . RESULTS Both ER d-MPH and ER MAS were associated with significant reductions in ADHD symptoms . Improvement in Total ADHD and Hyperactivity/Impulsivity symptoms were strongly associated with increasing dose , whereas improvements in Inattentive symptoms were only moderately associated with dose . About 80 % demonstrated reliable change on ADHD-RS-IV at the highest dose level of ER MAS compared with 79 % when receiving ER d-MPH .  Decreased appetite and insomnia were more common at higher dose levels for both stimulants . Approximately 43 % of the responders were preferential responders to only one of the stimulant formulations . CONCLUSIONS Dose level , rather than stimulant class , was strongly related to medication response OBJECTIVE To evaluate the efficacy and safety of dexmethylpheni date hydrochloride ( d-MPH , Focalin ) for the treatment of attention-deficit/hyperactivity disorder ( ADHD ) and to test an a priori hypothesis that d-MPH would have a longer duration of action than d , l-threo-methylpheni date ( d , l-MPH ) . METHOD This was a r and omized , double-blind study conducted at 12 U.S. centers . One hundred thirty-two subjects received d-MPH ( n=44 ) , d , l-MPH ( n=46 ) , or placebo ( n=42 ) twice daily for 4 weeks , with titration of the dose based on weekly clinic visits . The primary efficacy variable was change from baseline to last study visit on teacher-completed Swanson , Nolan , and Pelham Rating Scale ( Teacher SNAP ) . Secondary efficacy measures included the change on parent-completed SNAP ( Parent SNAP ) , Clinical Global Impressions Scale-Improvement ( CGI-I ) score , and Math Test performance . Assessment s at home in late afternoon were included to test the hypothesis that d-MPH would have a longer duration of efficacy than d , l-MPH . Safety was assessed through monitoring occurrence and severity of adverse events and discontinuations related to them . RESULTS Treatment with either d-MPH ( p=.0004 ) or d , l-MPH ( p=.0042 ) significantly improved Teacher SNAP ratings compared with placebo . The d-MPH group showed significant improvements compared with placebo on the afternoon Parent SNAP ratings ( p=.0003 ) and scores on the Math Test ( p=.0236 ) obtained late in the afternoon at 6:00 p.m. Sixty-seven percent of patients showed improvement on d-MPH and 49 % on d , l-MPH based on CGI-I scores . Both d-MPH and d , l-MPH were well tolerated , no patient in the d-MPH group and only two patients each in the d , l-MPH and placebo groups discontinued the study . CONCLUSIONS For the treatment of ADHD , an average titrated dose of 18.25 mg/day of d-MPH is as efficacious and safe as an average titrated dose of 32.14 mg/day of d , l-MPH . Both active treatments have large effect sizes . Thus , d-MPH and d , l-MPH appear to provide similar efficacy , and d-MPH may have longer duration of action after twice-daily dosing , but additional studies are needed to determine the statistical and clinical significance of this possibility Objectives : The aim of this r and omized clinical trial was to assess the efficacy of memantine versus methylpheni date in the treatment of children with attention deficit hyperactivity disorder . Method : Forty participants ( 34 boys and 6 girls ) aged 6 - 11 who were diagnosed with attention deficit hyperactivity disorder based on ( DSM-IV-TR ) criteria were selected for this study . The participants were r and omly assigned to two groups : group one ( n = 22 ) received memantine and the other group ( n = 18 ) received methylpheni date for six weeks . Treatment outcomes were assessed using the Attention Deficit Hyperactivity Rating Scale and Clinical Global Impression- Severity Scale administered at baseline and at weeks 3 and 6 following the treatment . Also , a two-way repeated measures analysis of variance ( time- treatment interaction ) was used . Results : At 6 weeks , methylpheni date produced a signiﬁcantly better outcome on the Parent Rating Scale scores and Clinical Global Impression- Severity than memantine . Side effects were observed more often in the memantine group . However , with respect to the frequency of side effects , the difference between the memantine and methylpheni date groups was not signiﬁcant . The most common side effects associated with memantine  are appetite suppression , headache , vomiting , nausea and fatigue . Conclusion : The results of this study revealed that although memantine was less effective than methylpheni date in the treatment of attention deficit hyperactivity disorder , it may be considered as an alternative treatment A recent r and omized clinical trial showed buspirone efficacy in the treatment of attention-deficit/hyperactivity disorder ( ADHD ) in children . However , results from a recent multi-site controlled clinical trial of transdermal buspirone failed to separate it from placebo in a large sample of children with ADHD . Therefore , due to these inconsistent findings , this study was design ed to assess the efficacy of buspirone in the treatment of children with ADHD compared to methylpheni date in a double blind r and omized clinical trial . Forty out patients with a DSM-IV-TR diagnosis of ADHD were study population of this trial . 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 treatment using tablet of buspirone at a dose of 20 - 30 mg/day depending on weight ( 20 mg/day for < 30 kg and 30 mg/day for > 30 kg ) ( group 1 ) or methylpheni date at a dose of 20 - 30 mg/day depending on weight ( 20 mg/day for < 30 kg and 30 mg/day for > 30 kg ( group 2 ) for a 6 week double blind , r and omized clinical trial . 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 . Significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores . The changes at the endpoint compared to baseline were : -8.95±8.73 ( mean±SD ) and -15.60±7.81 ( mean±SD ) for buspirone and methypheni date , for Parent ADHD Rating Scale . The changes at the endpoint compared to baseline were : -9.80 ±7.06 ( mean±SD ) and -22.40±9.90 ( mean±SD ) for buspirone and methypheni date , respectively for Teacher ADHD Rating Scale . The difference between the buspirone and methylpheni date groups in the frequency of side effects was not significant except for decreased appetite , headache and insomnia that were observed more frequently in the methylpheni date group . The results of this study suggest that administration of buspirone was less effective than methylpheni date in the treatment of ADHD Twenty boys ( mean age , 9 + /- 2 years ) with attention deficit disorder with hyperactivity received three weeks each of dextroamphetamine sulfate ( 0.5 mg/kg/d ) , fenfluramine hydrochloride ( 0.6 mg/kg/d increased to 2.0 mg/kg/d ) , and placebo in a double-blind , r and om-order , crossover design . Half the boys also met criteria for conduct disorder .  Dextroamphetamine produced immediate and marked improvement in disruptive , overactive behaviors .  Fenfluramine had no effect on any behavioral measure at either the low or high dosage . Both drugs decreased levels of urinary norepinephrine , 3-methoxy-4-hydroxyphenylglycol ( MHPG ) , and vanillylm and elic acid .  Fenfluramine , however , also produced a significant decrease in plasma MHPG levels and a larger decrease in urinary norepinephrine levels . It reduced urinary epinephrine levels as well , an effect opposite to that of dextroamphetamine . These findings suggest that different mechanisms of action are involved in the ability of the two drugs to reduce levels of MHPG and vanillylm and elic acid . Fenfluramine increased plasma prolactin levels and decreased platelet serotonin levels . Despite the structural similarity of the two drugs , some common overall effects on catecholamine metabolism , and similar effects on weight , fenfluramine had none of the motor activity or therapeutic effects of dextroamphetamine Objective : To ( i ) test whether atomoxetine is non-inferior to methylpheni date in treating symptoms of attention deficit hyperactivity disorder ( ADHD ) in paediatric patients ; and ( ii ) determine the tolerability of the two drugs . Method : This double-blind study was conducted in 6- to 16-year-old out patients with ADHD ( DSM-IV ) in China , Korea and Mexico ( January – October 2004 ) . Patients were r and omly assigned to once-daily atomoxetine ( 0.8–1.8 mg kg−1 day−1 ; n = 164 ) or twice-daily methylpheni date ( 0.2–0.6 mg kg−1 day−1 ; n = 166 ) for ∼8 weeks . Primary efficacy assessment was the comparison of response rates ( ≥40 % reduction from baseline to end point in total score ) on the Attention Deficit Hyperactivity Disorder Rating Scale-IV-Parent Version : Investigator-Administered and -Scored . Tolerability measures included , but were not limited to , the assessment of treatment-emergent adverse events ( TEAEs ) and weight . Results : Atomoxetine was non-inferior to methylpheni date in improving ADHD symptoms based on response rates ( atomoxetine , 77.4 % ; methylpheni date , 81.5 % ; one-sided 95 % lower confidence limit = −11.7 % , p = 0.404 ) . Treatment-emergent adverse effects experienced significantly more frequently in the atomoxetine group , compared with the methylpheni date group , included anorexia ( 37.2 % vs. 25.3 % ; p = 0.024 ) , nausea ( 20.1 % vs. 10.2 % ; p = 0.014 ) , somnolence ( 26.2 % vs. 3.6 % ; p < 0.001 ) , dizziness ( 15.2 % vs. 7.2 % ; p = 0.024 ) and vomiting ( 11.6 % vs. 3.6 % ; p = 0.007 ) , most of which were of mild or moderate severity . Atomoxetine-treated patients experienced a small but significantly greater mean weight loss from baseline to end point than methylpheni date -treated patients ( −1.2 kg vs. −0.4 kg ; p < 0.001 ) . Conclusions : This study suggests that atomoxetine is non-inferior to methylpheni date in the improvement of ADHD symptoms in paediatric out patients . Although both of the drugs were well tolerated , atomoxetine was associated with a higher incidence of TEAEs than methylpheni date OBJECTIVE To compare the side effect profiles of methylpheni date ( MPH ) and dexamphetamine ( DEX ) in children with attention deficit hyperactivity disorder ( ADHD ) , as well as to determine which symptoms are genuine adverse effects of stimulant medication , as opposed to aspects of the child 's underlying behavioral phenotype . DESIGN Double-blind , crossover study . SETTING Pediatric teaching hospital ambulatory behavior clinic . SUBJECTS A total of 125 children with ADHD with a mean age of 104.8 months . INTERVENTIONS Subjects received DEX ( 0.15 mg/kg/dose ) and MPH ( 0.3 mg/kg/dose ) twice a day for 2 weeks each in a r and omized order . OUTCOME MEASURES The Barkley Side Effects Rating Scale ( 17 symptoms ; 0 = absent , severity rated from 1 to 9 ) was completed by parents at baseline and at the completion of each trial fortnight . RESULTS Subjects ' parents reported a significantly greater mean number ( 8.19 ) and mean severity ( 4.08 ) of " side effects " before commencing the trial than during the MPH period ( number 7.19 ; severity 3.24 ) , but not the DEX period ( number 7.64 , severity 3.73 ) . The mean severity ( but not mean number ) was greater on DEX than on MPH . DEX caused more severe insomnia and appetite suppression compared with the baseline rating . Appetite suppression was the only item rated more severe on MPH than at baseline . Six side effects were significantly more severe on DEX than MPH : insomnia , irritability , proneness to crying , anxiousness , sadness/unhappiness , and nightmares . None were more severe on MPH than DEX . Overall , both MPH and DEX were well tolerated by most subjects , with only four subjects discontinuing the trial period because of severe adverse effects ( 2 -1.6%- on each stimulant ) . CONCLUSIONS Many symptoms commonly attributed to stimulant medication are actually preexisting characteristics of children with ADHD and improve with stimulant treatment . At the doses investigated , both DEX and MPH caused appetite suppression , and DEX caused insomnia . Negative emotional symptoms were more severe on DEX than MPH 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 The objective of this study was to investigate the effects of methylpheni date ( MPH ) on attention and inhibition in children with Attention Deficit Hyperactivity Disorder ( ADHD ) and to establish what the relative contributions of the noradrenergic and dopaminergic systems to this effect were . In addition to MPH , two other drugs were administered in order to affect both transmitter systems more selectively , L-dopa ( dopamine ( DA ) agonist ) and desipramine ( DMI ) ( noradrenaline ( NA ) re-uptake inhibitor ) . Sixteen children with ADHD performed a stop-task , a laboratory task that measures the ability to inhibit an ongoing action , in a double-blind r and omized within-subjects design . Each child received an acute clinical dose of MPH , DMI , L-dopa , and placebo ;  measures of performance and plasma were determined . The results indicated that inhibition performance was improved under DMI but not under MPH or L-dopa . The response-time to the stop-signal was marginally shortened after intake of DMI . MPH decreased omission and choice-errors and caused faster reaction times to the trials without the stop-tone . No effects of L-dopa whatsoever were noted . Prolactin levels were increased and 5-HIAA levels were lowered under DMI relative to placebo . It is suggested that the effects of MPH on attention are due to a combination of noradrenergic and dopaminergic mechanisms . The improved inhibition under DMI could be serotonergically mediated STUDY OBJECTIVES This study compared the effects of atomoxetine and methylpheni date on the sleep of children with attention-deficit/hyperactivity disorder ( ADHD ) . This study also compared the efficacy of these medications for treating ADHD in these children . DESIGN R and omized , double-blind , crossover trial . SETTING Two sleep disorders centers in the United States ; 1 in a private- practice setting and 1 in a hospital setting . PATIENTS 85 children diagnosed with ADHD . INTERVENTIONS Twice-daily atomoxetine and thrice-daily methylpheni date , each for approximately 7 weeks . MEASUREMENTS AND RESULTS Relative to baseline , the actigraphy data indicated that methylpheni date increased sleep-onset latency significantly more than did atomoxetine ( 39.2 vs 12.1 minutes , p < .001 ) . These results were consistent with the polysomnography data . Child diaries indicated that it was easier to get up in the morning , it took less time to fall asleep , and the children slept better with atomoxetine , compared with methylpheni date . Parents reported that it was less difficult getting their children up and getting them ready in the morning and that the children were less irritable , had less difficulty getting ready for bed , and had less difficulty falling asleep with atomoxetine , compared with methylpheni date . There were no significant differences between medications using the main measures of efficacy for ADHD treatment . Atomoxetine was superior on some secondary ADHD treatment-efficacy measures , based on parent reports . The only significant differences in treatment-emergent adverse events were greater incidence of decreased appetite and greater incidence of insomnia with methylpheni date . CONCLUSIONS Patients receiving twice-daily atomoxetine had shorter sleep-onset latencies , relative to thrice-daily methylpheni date , based on objective actigraphy and polysomnography data . Although both medications decreased nighttime awakenings , the decrease was greater for methylpheni date Attention-deficit hyperactivity disorder ( ADHD ) is a common disorder of childhood that affects 3 - 6 % of school children . Conventional stimulant medications are recognized as useful symptomatic treatments by both specialists and parents . Nevertheless , approximately 30 % of ADHD children treated with them do not respond adequately or can not tolerate the associated adverse effects . Such difficulties highlight the need for alternative , safe and effective medications in the treatment of this disorder . Theophylline is a psychomotor stimulant most widely used as a broncodilator . Purinergic modulation may be therapeutically beneficial in the treatment of psychiatric disorders . We hypothesized that theophylline would be beneficial for the treatment of ADHD and report results of a trial of theophylline compared with methylpheni date for the treatment of ADHD . A total of 32 children with ADHD as defined by DSM IV were r and omized to theophylline and methylpheni date dosed on an age and weight-adjusted basis at 4 mg/kg/day ( under 12 years ) and 3 mg/kg/day theophylline ( over 12 years ) ( group 1 ) and 1 mg/kg/day methylpheni date ( group 2 ) for a 6-week double-blind and r and omized clinical trial . The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale . Patients were assessed by a child psychiatrist , at baseline and at 14 , 28 and 42 days after start of the medication . No significant differences were observed between theophylline and methylpheni date on the Parent and Teacher Rating Scale scores over the trial ( t = 0.49 , d.f . = 24 P = 0.62 and t = 0.19 , d.f . = 24 P = 0.54 respectively ) . Although the number of dropouts in the methylpheni date group was higher than the theophylline group , there was no significant difference between the two protocol s in terms of the dropouts . In addition , headaches were observed more often in the methylpheni date group . The results suggest that theophylline may be a useful for the treatment of ADHD . In addition , a tolerable side-effect profile is one of the advantages of theophylline in the treatment of ADHD . Nevertheless , our study is small and our results would need to be confirmed in a larger study Attention deficit hyperactivity disorder ( ADHD ) is a common disorder of childhood that affects 3 % to 6 % of school-age children . Conventional stimulant medications are recognized by both specialists and parents as useful symptomatic treatment . Nevertheless , approximately 30 % of ADHD children treated with them do not respond adequately or can not tolerate the associated adverse effects . Such difficulties highlight the need for alternative safe and effective medications in the treatment of this disorder . Selegiline is a type B monoamine oxidase inhibitor ( MAOI ) that is metabolized to amphetamine and methamphetamine stimulant compounds that may be useful in the treatment of ADHD . The authors undertook this study to further evaluate , under double-blind and controlled conditions , the efficacy of selegiline for ADHD in children . A total of 28 children with ADHD as defined by DSM IV were r and omized to selegiline or methylpheni date  dosed on an age and weight-adjusted basis at selegiline 5 mg/day ( under 5 years ) and 10 mg/day ( over 5 years ) ( Group 1 ) and methylpheni date 1 mg/kg/day ( Group 2 ) for a 4-week double-blind clinical trial . The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale . Patients were assessed by a child psychiatrist at baseline , 14 and 28 days after the medication started . No significant differences were observed between the two protocol s on the Parent and Teacher Rating Scale scores . Although the number of dropouts in the methylpheni date group was higher than in the selegiline group , there was no significant difference between the two protocol s in terms of the dropouts . Decreased appetite , difficulty falling asleep and headaches were observed more in the methylpheni date group . The results of this study must be considered preliminary , but they do suggest that selegiline may be beneficial in the treatment of ADHD . In addition , a tolerable side effect profile may be considered as one of the advantages of selegiline in the treatment of ADHD OBJECTIVE To compare the efficacy and time course of single morning doses of Adderall , extended-release , and immediate-release dextroamphetamine sulfate . METHOD Thirty-five children with attention-deficit/hyperactivity disorder , combined type , were given Adderall , immediate-release dextroamphetamine , dextroamphetamine Spansules , and placebo in a r and omized , double-blind , crossover study . Behavior ratings , locomotor activity measurements , and academic measures were obtained over a period of 8 weeks . RESULTS All three drugs exhibited robust efficacy versus placebo on nearly all measures . The effects of dextroamphetamine Spansules were less robust in the morning , particularly compared with Adderall , but they lasted 3 to 6 hours longer , depending on the measure . Although parent behavior ratings and locomotor activity showed improvements up to 12 hours after single doses of all three drugs , the number of math problems attempted and completed correctly 4 hours after dosing were only robustly increased by Spansules . CONCLUSIONS Both immediate-release amphetamines demonstrated earlier onset of effects , but dextroamphetamine Spansules showed more sustained effects that were present on a wider range of measures Objective We sought to determine the dose-response effects of extended-release ( ER ) dexmethylpheni date ( d-MPH ) and ER mixed amphetamine salts ( MAS ) on objective measures of sleep . Methods This was an 8-week , double-blind , placebo-controlled , r and omized , two period , crossover study of youth with attention-deficit hyperactivity disorder ( ADHD ) as confirmed by the Kiddie Schedule for Affective Disorders for School-Age Children – Present and Lifetime version ( K-SADS-PL ) . Children aged 10–17 years were recruited from clinical practice , colleague referrals , and flyers . Participants were r and omized to initially receive either d-MPH or MAS . During each 4-week drug period , children received three dose levels ( 10 , 20 , and 25/30 mg ) in ascending order , with placebo substituted for active medication in a r and omized fashion during 1 week of the study . After 4 weeks , participants were switched to the alternative medication for another 4 weeks of treatment . The main outcome measure was sleep duration as measured by actigraphy . Children , parents , and research ers were blinded to drug , dose , and placebo status . Results Sixty-five participants met the inclusion criteria and were enrolled in the study . Of these , 37 participants with sufficient sleep data for analysis were included .  Sleep schedule measures showed a significant effect for dose on sleep start time ( F(1,36 ) = 6.284 ; p < 0.05 ) , with a significantly later sleep start time when children were receiving 20- or 30-mg doses , compared with placebo ( p < 0.05 ) . A significant dose effect was found on actual sleep duration ( F(1,36 ) = 8.112 ; p < 0.05 ) , with significantly shorter actual sleep duration for subjects receiving 30 mg compared with those receiving placebo ( p < 0.05 ) . There were no significant differences on sleep duration or sleep schedule between the two stimulant medications . The trial is complete and closed to follow-up . Conclusions Higher stimulant doses were associated with reduced sleep duration and later sleep start times , regardless of medication class . Trial registration Clinical Trials.gov : NCT00393042 OBJECTIVE Because models of attention-deficit/hyperactivity disorder ( ADHD ) therapeutics emphasize benefits of both enhanced dopaminergic and noradrenergic signaling , strategies to enhance D1 and α2A agonism may yield enhanced clinical and cognitive responses . This study tested the hypothesis that combined effects of a dopamine and noradrenergic agonist , d-methylpheni date extended-release ( DMPH ) with guanfacine ( GUAN ) , an α2A receptor agonist , would be clinical ly superior to either monotherapy and would have equal tolerability . METHOD An 8-week , double-blind , 3-arm , comparative trial r and omized 7- to 14-year-olds with DSM-IV ADHD to GUAN ( 1 - 3 mg/day ) , DMPH ( 5 - 20 mg/day ) , or a combination ( COMB )  with fixed-flexible dosing . Outcome measures were the ADHD Rating Scale IV ( ADHD-RS-IV ) and the Clinical Global Impression-Improvement ( CGI-I ) scale . Data on adverse events and safety measures were obtained . RESULTS A total of 207 participants were r and omized and received drug . Analyses showed significant treatment group main effects for ADHD-RS-IV ADHD total ( p = .0001 ) and inattentive symptoms ( p = .0001 ) . COMB demonstrated small but consistently greater reductions in ADHD-RS-IV Inattentive subscale scores versus monotherapies ( DMPH : p = .05 ; f(2 ) = .02 ; and GUAN : p = .02 ; f(2 ) = .02 ) , and was associated with a greater positive response rate by CGI-I ( p = .01 ) . No serious cardiovascular events occurred . Sedation , somnolence , lethargy , and fatigue were greater in both guanfacine groups . All treatments were well tolerated . CONCLUSION COMB showed consistent evidence of clinical benefits over monotherapies , possibly reflecting advantages of greater combined dopaminergic and α2A agonism . Adverse events were generally mild to moderate , and COMB treatment showed no differences in safety or tolerability . CLINICAL TRIAL REGISTRATION INFORMATION Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder ( Project1 ) ; http:// clinical trials.gov/ ; NCT00429273 Fourteen boys ( mean age , 9.2 + /- 1.5 years ) with Attention Deficit Disorder ( ADD ) With Hyperactivity were treated with dextroamphetamine sulfate or a monoamine oxidase inhibitor ( MAOI ) ( six received clorgyline , eight received tranylcypromine sulfate ) for four weeks each in a double-blind , cross-over study that included a two-week placebo washout between active drug periods . The MAOIs had immediate , clinical ly significant benefit and were clinical ly indistinguishable from dextroamphetamine . Most children responded to both stimulant and MAOI . These findings of equivalent efficacy of MAOIs in ADD are in contrast to our previous studies with neurotransmitter system selective agents , which showed only weak effects , and suggest that multiple neurotransmitter alterations may be required for stimulant drug effects in ADD . The immediate response to MAOIs indicates a different mechanism from that mediating antidepressant effect . The MAOIs may be useful alternate treatments in selected cases of ADD OBJECTIVE In the treatment of attention-deficit hyperactivity disorder ( ADHD ) , the efficacy of the tricyclic antidepressants and monoamine oxidase inhibitor antidepressants has been compared with that of both placebo and the stimulants ( methylpheni date and /or dextroamphetamine ) . However , the effectiveness of bupropion has been contrasted only with placebo . The primary aim of this study was to contrast the efficacy of bupropion with that of methylpheni date in the treatment of ADHD . METHOD A double-blind , crossover design was used in this study . After a 14-day medication washout period , 15 ADHD subjects ( 7 to 17 years old ) were r and omized to either methylpheni date or bupropion for 6 weeks , washed out for an additional 2 weeks , and then " crossed over " to the other drug . Methylpheni date was titrated to the maximum effective dose of 0.4 to 1.3 mg/kg per day ( mean 0.7 mg/kg per day ) and bupropion was titrated to an effective dose ranging from 1.4 to 5.7 mg/kg per day ( mean 3.3 mg/kg per day ) . RESULTS Both methylpheni date and bupropion produced significantly greater ( p < .001 ) and equivalent improvement on the Iowa-Conners Teacher 's Rating Scale according to both the subjects ' parents and teachers . The same pattern of improvement was also noted for improvement on the Clinical Global Impression Scale , Kagan 's Matching Familiar Figures Test , Continuous Performance Test , Children 's Depression Inventory , Children 's Manifest Anxiety Scale , and Rey Auditory-Verbal Learning Test . CONCLUSIONS In this double-blind , crossover trial , bupropion and methylpheni date were both effective and did not differ in their overall efficacy as treatments for ADHD Double-blind crossover comparison of methylpheni date hydrochloride , dextroamphetamine sulfate , and caffeine after placebo washout in 29 children with minimal brain dysfunction ( MBD ) showed on six ratings that methylpheni date and dextroamphetamine were significantly ( P less than .05 to P less than .001 ) better than placebo and caffeine , but not significantly ( P less than .05 ) different from each other . Placebo , caffeine , and ratings before drug did not differ significantly . Of 26 drug responders , 12 responded best to dextroamphetamine , ten to methylpheni date , and one to caffeine . The latter child showed no improvement at all with either prescription stimulant . Methylpheni date and dextroamphetamine were each efficacious for six children who did not respond to the other stimulant . All three drugs showed significant ( P less than .05 ) weight loss and cardiovascular side effects , the latter possibly spurious . Dextroamphetamine showed a significant ( P less than .05 ) decrease from placebo in " tummyaches . Mixed amphetamine salts extended release ( MAS XR ; Adderall XR ® ) and atomoxetine ( Strattera ® ) were compared in children 6 to 12 years old with attention deficit/hyperactivity disorder ( ADHD ) combined or hyperactive/impulsive type in a r and omized , double-blind , multicenter , parallel-group , forced-dose-escalation laboratory school study . Primary efficacy measure was the SKAMP ( Swanson , Kotkin , Agler , M-Flynn , and Pelham ) behavioral rating scale . Changes in mean SKAMP deportment scores from baseline were significantly greater for MAS XR ( n = 102 ) than for atomoxetine ( n = 101 ) overall ( -0.56 and -0.13 , respectively ; p < .0001 ) and at each week ( p < .001 ) . Adverse events were similar for both treatment groups . The extended time course of action and greater therapeutic efficacy  of MAS XR suggests that it is more effective than atomoxetine in children with ADHD In this double-blind , crossover study of 8 boys with minimal brain dysfunction , 20 mg of methylpheni date daily was significantly better than 160 mg of caffeine in controlling behavior , especially impulsivity and hyperactivity , and methylpheni date alone was superior to decaffeinated coffee and placebo . The tentative results of this study confirm the primary position of sympathomimetics in the pharmacotherapy of minimal brain dysfunction and , in addition , suggest the involvement of dopamine pathways in this disorder . The authors urge further study of this hypothesis OBJECTIVE To examine the safety and tolerability of clonidine used alone or with methylpheni date in children with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD In a 16-week multicenter , double-blind trial , 122 children with ADHD were r and omly assigned to clonidine ( n = 31 ) , methylpheni date ( n = 29 ) , clonidine and methylpheni date ( n = 32 ) , or placebo ( n = 30 ) . Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylpheni date ( both with divided dosing ) . Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs . RESULTS There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine ( 17.5 % versus 3.4 % ; p = .02 ) , but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes . There were no suggestions of interactions between clonidine and methylpheni date regarding cardiovascular outcomes . Moderate or severe adverse events were more common in subjects on clonidine ( 79.4 % versus 49.2 % ; p = .0006 ) but not associated with higher rates of early study withdrawal . Drowsiness was common on clonidine , but generally resolved by 6 to 8 weeks . CONCLUSIONS Clonidine , used alone or with methylpheni date , appears safe and well tolerated in childhood ADHD . Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness Chlorpromazine , dextroamphetamine and methylpheni date were significantly superior to placebo in producing overall improvement in the behaviour of hyperactive children .  Chlorpromazine was effective for the majority of the children , but reduced only hyperactivity , having no demonstrable effect on distractibility , aggressivity or excitability . Both stimulants produced more goal -oriented behaviour and reduced distractibility .  Methylpheni date was the most effective of the drugs in prpducing exceptional improvement . All three active drugs had to be discontinued in a few of the children because of side effects . Not all hyperactive children were benefited by the drugs . No background variables ( with the exception of mother-child relationship ) were found in the present studies to predict favourable response to the drugs . Methylpheni date became our drug of choice for this group of hyperactive children 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 BACKGROUND Lisdexamfetamine dimesylate is a therapeutically inactive prodrug in which d-amphetamine is covalently bound to l-lysine , a naturally occurring amino acid . Pharmacologically active d-amphetamine is released from lisdexamfetamine following oral ingestion . METHODS This phase 2 , r and omized , double-blind , placebo- and active-controlled crossover study compared the efficacy and safety of lisdexamfetamine ( LDX : 30 , 50 , or 70 mg ) with placebo , with mixed amphetamine salts extended-release ( MAS XR : 10 , 20 , or 30 mg ) included as a reference arm of the study , in 52 children aged 6 to 12 years with attention-deficit/hyperactivity disorder ( ADHD ) in an analog classroom setting . The primary efficacy measure was the Swanson , Kotkin , Agler , M-Flynn , and Pelham ( SKAMP ) Rating Scale ; secondary efficacy measures included the Permanent Product Measure of Performance ( PERMP ) Derived Measures , and the Clinical Global Impression ( CGI ) Scale . RESULTS LDX treatment significantly improved scores on SKAMP-deportment , SKAMP-attention , PERMP-attempted , PERMP-correct , and CGI-improvement from baseline . Adverse events were similar for both active treatments . CONCLUSIONS In a laboratory classroom environment , LDX significantly improved ADHD symptoms versus placebo in school-age children with ADHD The authors compared the efficacy of caffeine , methylpheni date , and d-amphetamine in children with minimal brain dysfunction using a double-blind crossover design . The slight improvement with caffeine was not significantly better than placebo . Both prescription drugs result ed in significant improvement and were significantly superior to caffeine . The authors suggest that the discrepancy between these results and an earlier , more optimistic report mat stem from the use in this study of pure caffeine rather than whole coffee The present study compared the behavioral performance of 30 children with attention deficit disorder with hyperkinesis ( HK ) on electrophysiological , biochemical , behavioral , and psychometric measurements . HK children were partitioned into cells of 10 and were then treated with placebo , methylpheni date , and adrenocorticotropic hormone fractions ( ACTH4–9 analog ) , respectively , in a double-blind r and omized cell sequence according to body weight . The results revealed that HK children on methylpheni date manifested a significantly greater vasomotor reactivity , behavioral improvement , and learning receptivity than did HK children taking ACTH4–9 analog and /or placebo . Future research implication s with ACTH4–9 and HK children are discussed 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 OBJECTIVE The purpose of this study was to assess the efficacy and safety of edivoxetine ( LY2216684 ) , a selective norepinephrine reuptake inhibitor , in pediatric patients with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD A fixed-dose , r and omized , double-blind , 8 week study was conducted in patients 6 - 17 years of age , who were r and omized by two strata : 1 ) Patients with prior stimulant use r and omized to placebo , edivoxetine 0.1 mg/kg/day , 0.2 mg/kg/day , or 0.3 mg/kg/day arms in a 1:1:1:1 ratio ; 2 ) Stimulant-naïve patients r and omized to placebo , edivoxetine 0.1mg/kg/day , 0.2 mg/kg/day , 0.3 mg/kg/day , or osmotic-release oral system methylpheni date ( OROS MPH ) ( 18 - 54 mg/day based on body weight ) arms in a 1:1:1:1:1 ratio . The primary efficacy measure was baseline-to-week 8 change of ADHD Rating Scale ( ADHD-RS ) total score for edivoxetine 0.2 mg/kg/day and 0.3 mg/kg/day . RESULTS A total of 340 patients were r and omized to placebo ( n=78 ) ; edivoxetine 0.1 mg/kg/day ( n=76 ) , 0.2 mg/kg/day ( n=75 ) , or 0.3 mg/kg/day ( n=75 ) ; or OROS MPH ( n=36 ) . In the stimulant-naïve stratum , the positive control , OROS MPH , was significantly superior to placebo in mean ADHD-RS total score change at end-point ( -19.46 , p=0.015 ) . The edivoxetine 0.2 mg/kg/day and 0.3 mg/kg/day arms had statistically significantly greater improvement than the placebo arm in mean ADHD-RS total score change at end-point ( placebo -10.35 ; edivoxetine 0.2 mg/kg/day -16.09 , p<0.010 ; edivoxetine 0.3 mg/kg/day -16.39 , p<0.010 ) and Clinical Global Impressions-Improvement score  ( placebo 3.05 ; edivoxetine 0.1 mg/kg/day 3.01 , p=0.860 ; edivoxetine 0.2 mg/kg/day 2.54 , p=0.013 ; edivoxetine 0.3 mg/kg/day 2.53 , p=0.013 ) . In the overall efficacy-analyses data set ( n=270 ) , the effect size estimates for edivoxetine doses 0.1 mg/kg/day , 0.2 mg/kg/day and 0.3 mg/kg/day at the week 8 time point were 0.17 , 0.51 , and 0.54 , respectively ( for the stimulant-naïve stratum , the effect size estimate for OROS MPH was 0.69 ) . Compared with placebo , edivoxetine treatment was associated with statistically significant increases in blood pressure and pulse ( p<0.050 ) , and a smaller increase or slight decrease in weight .  CONCLUSIONS Edivoxetine at doses of 0.2 mg/kg/day and 0.3 mg/kg/day demonstrated efficacy in ADHD treatment , despite the presence of a sizeable placebo response . No unexpected adverse events were identified . Clinical Trial Registry identifier : NCT00922636 In a nine-week double-blind crossover comparison of dextroamphetamine , levoamphetamine ( Cydril ) , and placebo with 11 hyperkinetic children , effects were assessed by an established teacher rating scale , a parent rating scale , and a new tool , weekly quantification of parent-selected target symptoms . Both active drugs were significantly more effective than placebo . Dextroamphetamine seemed consistently superior to levoamphetamine , though not to a significant degree ( on this size sample ) . Levoamphetamine seemed " slower starting , " requiring three weeks to show significant benefit on target symptoms , whereas dextroamphetamine showed nearly its maximum benefit the first week . Levoamphetamine seemed better for hyperactivity and aggressiveness than for inattentiveness , whereas dextroamphetamine seemed equally beneficial for all three . These data are consistent with the possibility that therapeutic effects of amphetamine on hyperkinetic children are mediated , at least in some , by dopaminergic systems 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 The purpose of this study was to examine the efficacy and side-effects of pindolol , a beta-blocker , in children with attention-deficit hyperactivity disorder ( ADHD ) . Fifty-two ADHD children , 7 - 13 years old , participated in a prospect i ve double-blind placebo-controlled comparison of pindolol and methylpheni date ( MPH ) . Active treatment was pindolol and MPH : pindolol 20 mg b.i.d . or MPH 10 mg b.i.d . for 4 weeks . The outcome was assessed on the basis of the Abbreviated Conners Rating Scales ( ACRS ) completed by parents , teachers , and by a psychologist during psychological testing . Pindolol treatment was associated with a higher incidence of paraesthesias and with more intense nightmares and hallucinations than MPH or placebo treatment . These side-effects led to an interim change in design by ending pindolol treatment after 32 participants . Pindolol proved to be just as effective as MPH in decreasing hyperactivity and conduct problems at home , and hyperactivity problems at school .  Pindolol , however , had less therapeutic effects than MPH during psychological testing , and failed to affect conduct problems in school . In sum , pindolol was modestly effective in the treatment of ADHD . Safety concerns on troubling side-effects clearly limit the use of it OBJECTIVE 1 ) To compare st and ard twice-daily methylpheni date ( MPH ) dosing with a single morning dose of MPH and of Adderall during a typical school-day time period , and 2 ) to conduct a dose-response study of the effects of a late-afternoon ( 3:30 PM ) dose of MPH and Adderall on evening behavior and side effects . DESIGN Within-subject , placebo-controlled , crossover design . SETTING Intensive summer treatment program with a comprehensive behavioral approach . STUDY PARTICIPANTS Twenty-one children with attention-deficit/hyperactivity disorder ( 19 boys and 2 girls ) , between the ages of 6 and 12 years . INTERVENTIONS Children received , in r and om order with daily crossovers , each of the following conditions : 1 ) placebo , 2 ) 0.3 mg/kg of MPH received 3 times , 3 ) 0.3 mg/kg of MPH received twice ( 7:30 AM and 11:30 AM ) with 0.15 mg/kg received at 3:30 PM , 4 ) 0.3 mg/kg of MPH received once in the morning only , 5 ) 0.3 mg/kg of Adderall received at 7:30 AM and at 3:30 PM , 6 ) 0.3 mg/kg of Adderall once in the morning with 0.15 mg/kg received at 3:30 PM , 7 ) 0.3 mg/kg of Adderall received in the morning only . OUTCOME MEASURES Daily rates of behaviors in social and academic setting s , and st and ardized ratings from counselors and teachers , were assessed for the hours between 8:00 AM and 3:30 PM ( a typical school-day ) . Relative sizes of the medication effects were compared hourly between first daily ingestion ( 7:30 AM ) and 4:45 PM to assess the time course of the 2 drugs . Effects of the 3:30 PM doses on functioning in the evenings at home were evaluated using parent ratings of behavioral and side effects . RESULTS A single morning dose of Adderall produced equivalent behavioral effects to those of MPH received twice-daily and behavioral effects of that single morning dose lasted throughout the school-day period . One morning dose of MPH was less effective than either 2 daily doses of MPH or 1 dose of Adderall , and seemed to wear off in the early to mid-afternoon . For some children a single morning dose of MPH maintained their behavior for an entire school day in the context of the summer treatment program . On parent ratings of evening behavior , 0.3 mg/kg of MPH at 3:30 PM was superior to 0.15 mg/kg at 3:30 PM , but there was no difference between the 2 doses of Adderall . Compared with placebo at 3:30 PM , only the 0.3 mg/kg dose of MPH caused significant improvement in parent ratings . In placebo versus Adderall comparisons , all doses , even the condition that consisted of Adderall in the morning and placebo at 3:30 PM , produced a significant change in evening behavior . CONCLUSIONS The results show that , at least in the context of an intensive behavioral intervention , a single morning dose of Adderall had behavioral effects throughout an entire school day period that were equivalent to st and ard twice-daily MPH dosing . These results indicate that Adderall may be used as a long-acting stimulant for children for whom midday dosing is a problem . Further study including dose-response comparisons , effects in regular school setting s , and direct comparisons with comparable doses of MPH and d-amphetamine will help to clarify the time course and relative advantages of Adderall 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 BACKGROUND Attention deficit hyperactivity disorder ( ADHD ) is one of the most common childhood psychiatric disorder with a prevalence of 8 - 12 % . Even though psychostimulants remain the treatment of choice , its cost and availability in developing countries limits the usage of the drug . In view of free availability and low cost , a R and omized controlled study was carried out using two second line drugs ( clonidine and carbamazepine ) in a tertiary care hospital , Pondicherry , South India . OBJECTIVE To compare the efficacy of clonidine and carbamazepine in children with ADHD . METHOD With approval of ethics committee , a prospect i ve , Double-blind , R and omized controlled study of clonidine and carbamazepine was conducted with 50 children with ADHD ( age group 4 - 12 years ) , over a period of 2 years ( 2005 - 07 ) in a tertiary care hospital , Pondicherry , South India . RESULTS Clonidine was effective in improving the hyperactivity and impulsivity symptoms in children with ADHD as compared to carbamazepine . Statistical significant improvement was not noted with respect to inattention symptoms and other comorbid conditions . CONCLUSION Clonidine can be a safer and cheaper alternative in treatment of children with ADHD , with a predominant effect on their hyperactivity and impulsivity symptoms Double-blind crossover r and omized Latin square comparison of placebo , dextroamphetamine , and levoamphetamine in 31 consecutively diagnosed children with minimal brain dysfunction ( MBD ) replicated a smaller nonr and om study . Both isomers showed significantly more benefit than placebo but were not significantly different from each other . Dextroamphetamine showed a nonsignificant trend of superiority over levoamphetamine . Of 25 subjects who responded well to drugs , three responded only to levoamphetamine , five only to dextroamphetamine , and 17 to both . This study seems to confirm the efficacy of levoamphetamine in MBD . An unsocialized aggressive subgroup ( 308.4 ) showed a nonsignificant trend for  levoamphetamine superiority , in contrast to the hyperkinetic ( 308.0 ) and overanxious ( 308.2 ) subgroups . Those who responded best to levoamphetamine tended ( not significantly ) to be from poorer functioning families . Parents ' ratings , but not teachers ' or psychiatrists ' ratings , showed significant placebo effect Daily academic classroom performance was recorded in a day hospital school using a commonly employed reading and math series as part of an 11-week double-blind , placebo controlled , crossover comparison of dextroamphetamine ( d-AMPH ) and methylpheni date ( MPH ) in 33 hyperactive boys . Students attempted more math and reading tasks while on either active drug . The percent correct and the number of attempted problems of the reading series improved with both drugs while the percent correct for the math series occurred with d-AMPH only . No dose-response relationship was found for either stimulant . Moderate , transient adverse effects were common for both drugs An eight-week double-blind comparison between pemoline ( Cylert ) , methylpheni date ( Ritalin ) hydrochloride , and placebo was carried out on 60 hyperactive children . Measurements of home , school , achievement , cognitive function , and global clinical status were made at baseline , midtreatment , end of treatment , and posttreatment . Both drugs produced improvement in all areas except the achievement measures . One major difference between drugs was the apparently longer action of pemoline , since its effects at home and school tended to persist when the drug was withdrawn , whereas the patients receiving methylpheni date tended to regress to their baseline levels OBJECTIVE While Adderall has been available for the treatment of attention-deficit/hyperactivity disorder ( ADHD ) for several years , there are few controlled studies comparing it to methylpheni date . METHOD Fifty-eight children with ADHD ( mean age 8.1 + /- 1.4 years ) were r and omly assigned to receive placebo , methylpheni date , or Adderall in a double-blind , parallel-group design for 3 weeks . Dosage was adjusted at the end of weeks 1 and 2 via an algorithm based on teacher and parent ratings . Final doses were 12.5 + /- 4.1 mg/day for Adderall and 25.2 + /- 13.1 mg/day for methylpheni date .  Teacher and parent ratings , as well as the psychiatrist 's Clinical Global Impression ( CGI ) , were the final outcome measures at the end of week 3 . RESULTS Both medications were superior to placebo at reducing inattentive and oppositional symptoms in the classroom and on the CGI . Adderall produced significantly more improvements on teacher ratings and the CGI than methylpheni date , although the algorithm may have limited dosing in the methylpheni date group . Seventy percent of children in the Adderall group were given medication once a day , compared with 15 % of the subjects receiving methylpheni date . CONCLUSIONS Adderall compared favorably to methylpheni date , and the behavioral effects of Adderall appear to persist longer than those of methylpheni date after individual doses
target: 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 .
background: 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 .