Five-fold increase in national prevalence rates of attention-deficit/hyperactivity disorder medications for children and adolescents with autism spectrum disorder, attention-deficit/hyperactivity disorder, and other psychiatric disorders: a Danish register-based study. A pilot study for augmenting atomoxetine with methylphenidate: safety of concomitant therapy in children with attention-deficit/hyperactivity disorder A multi-centre, randomised, open-label study of atomoxetine compared with standard current therapy in UK children and adolescents with attention-deficit/hyperactivity disorder (ADHD)* Predictors of pharmacological treatment outcomes with atomoxetine or methylphenidate in patients with attention-deficit/hyperactivity disorder from China, Egypt, Lebanon, Russian Federation, Taiwan, and United Arab Emirates. Atomoxetine treatment in children and adolescents with attention-deficit hyperactivity disorder: what are the long-term health-related quality-of-life outcomes? Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: acute comparison and differential response. Atomoxetine versus Methylphenidate in Paediatric Outpatients with Attention Deficit Hyperactivity Disorder: A Randomized, Double-Blind Comparison Trial The effect of methylphenidate on oppositional defiant disorder comorbid with attention deficit/hyperactivity disorder. Common and unique therapeutic mechanisms of stimulant and nonstimulant treatments for attention-deficit/hyperactivity disorder. Improvement of facial affect recognition in children and adolescents with attention-deficit/hyperactivity disorder under methylphenidate. Neurofeedback for the treatment of children and adolescents with ADHD: a randomized and controlled clinical trial using parental reports Transition from methylphenidate or amphetamine to atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder--a preliminary tolerability and efficacy study. Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial. Clinical efficacy of methylphenidate in conduct disorder with and without attention deficit hyperactivity disorder. Effects of atomoxetine and methylphenidate on sleep in children with ADHD. Protocol investigating the clinical utility of an objective measure of activity and attention (QbTest) on diagnostic and treatment decision-making in children and young people with ADHD—‘Assessing QbTest Utility in ADHD’ (AQUA): a randomised controlled trial Management of adult attention deficit hyperactivity disorder in UK primary care: a survey of general practitioners Atomoxetine treatment in children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder. 3L, 5L, What the L? A NICE Conundrum Acetyl-L-Carnitine as an Adjunctive Therapy in the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: A Placebo-Controlled Trial Bupropion versus methylphenidate in the treatment of children with attention-deficit/hyperactivity disorder: randomized double-blind study. Methylphenidate versus dexamphetamine in children with attention deficit hyperactivity disorder: A double-blind, crossover trial. The effects of methylphenidate on neural systems of attention in attention deficit hyperactivity disorder.
OBJECTIVE The purpose of this study was to estimate the prevalence and time trends in prescriptions of methylpheni date , dexamphetamine , and atomoxetine in children and adolescents , within three diagnostic groups : 1 ) autism spectrum disorder ( ASD ) , 2 ) attention-deficit/hyperactivity disorder ( ADHD ) , and 3 ) other psychiatric disorders . METHODS Data from six different national registers were used and merged to identify a cohort of all children and adolescents born in Denmark between 1990 and 2001 ( n=852,711 ) . Sociodemographic covariates on cohort members and their parents and lifetime prescriptions of methylpheni date , dexamphetamine , and atomoxetine were extracted from the registers . Prescriptions were also stratified by duration ( < 6 months . vs.≥ 6 months ) . RESULTS Sixteen percent of 9698 children and adolescents with ASD ( n=1577 ) , 61 % of 11,553 children and adolescents with ADHD ( n=7021 ) and 3 % of 48,468 children and adolescents with other psychiatric disorders ( n=1537 ) were treated with one or more ADHD medications . There was a significant increase in prescription rates of these medications for all three groups . From 2003 to 2010 , youth 6 - 13 years of age with ASD , ADHD , and other psychiatric disorders had 4.7-fold ( 4.4 - 4.9 ) , 6.3-fold ( 6.0 - 6.4 ) , and 5.5-fold ( 5.0 - 5.9 ) increases , respectively , in prescription rates of ADHD medications . CONCLUSION This is the largest study to date assessing stimulant treatment in children and adolescents with ASD , and is the first prospect i ve study quantifying the change over time in the prevalence of treatment with ADHD medications in a population -based national cohort of children and adolescents with ASD . The prevalence of stimulant treatment in youth with ASD of 16 % is consistent with earlier studies . The past decade has witnessed a clear and progressive increase in the prescription rates of medications typically used to treat ADHD in children and adolescents in Denmark . This increase is not limited to only those with ADHD , but includes others with neuropsychiatric disorders , including ASD . The risks and benefits of this practice await further study Background This study examined augmenting atomoxetine with extended-release methylpheni date in children whose attention-deficit/hyperactivity disorder ( ADHD ) previously failed to respond adequately to stimulant medication . Methods Children with ADHD and prior stimulant treatment ( N = 25 ) received atomoxetine ( 1.2 mg/kg/day ) plus placebo . After 4 weeks , patients who were responders ( n = 4 ) were continued on atomoxetine/placebo while remaining patients were r and omly assigned to either methylpheni date ( ATX/MPH ) ( 1.1 mg/kg/day ) or placebo augmentation ( ATX/PB ) for another 6 weeks . Patients and sites were blind to timing of active augmentation . Safety measures included vital signs , weight , and adverse events . Efficacy was assessed by ADHD rating scales . Results Categorical increases in vital signs occurred for 5 patients ( 3 patients in ATX/MPH , 2 patients in ATX/PBO ) . Sixteen percent discontinued the study due to AE , but no difference between augmentation groups . Atomoxetine treatment was efficacious on outcome measures ( P ≤ .001 ) , but methylpheni date did not enhance response . Conclusion Methylpheni date appears to be safely combined with atomoxetine , but conclusions limited by small sample . With atomoxetine treatment , 43 % of patients achieved normalization on ADHD ratings ABSTRACT Objective : To assess the broader efficacy ( i.e. , improvements in quality of life/functional outcomes ) of atomoxetine compared with st and ard current therapy ( SCT ) in UK paediatric patients with ADHD and to explore clinician/parent/child perceptions of ADHD . Research design and methods : A total of 201 patients with ADHD were r and omised into this multi-centre , open-label study to receive atomoxetine ( n = 104 ) or SCT ( n = 97 ) for 10 weeks . Broader efficacy was assessed using the parent-rated Child Health and Illness Profile-Child Edition ( CHIP‑CE ) total ( global ) t-score . Secondary outcome measures included the five CHIP‑CE domains ; parent-rated Family Burden of Illness Module ( FBIM ) ; investigator-rated ADHD‑Rating Scale ; investigator-rated Clinical Global Impression (CGI)-Severity/Improvement scales ; and child-rated Harter Self-Perception Profile ( HSPP ) . Results : Quality of life of children/adolescents with ADHD was extremely compromised at baseline ( CHIP‑CE total t-scores : atomoxetine , 23.2 ± 12.2 ; SCT , 23.9 ± 11.0 ) , and improved during the 10-week study for both groups ; the CHIP‑CE score was statistically significantly higher for patients treated with atomoxetine ( 38.4 ± 1.3 ) compared with SCT ( 30.8 ± 1.3 ) at week 10 ( p < 0.001 ) . ADHD‑RS , CGI-Severity , and CGI-Improvement scores were significantly different between the groups in favour of atomoxetine ( p < 0.001 ) . There was a statistically significant difference between the groups in the HSPP Social Acceptance domain in favour of atomoxetine , but not in the five other HSPP domains or FBIM total score . Atomoxetine was well-tolerated . Conclusions : Results from this open-label trial show that atomoxetine is superior to SCT in addressing broader efficacy and functional outcomes in UK children/adolescents with ADHD . This study contributes to the underst and ing of broader efficacy in children with ADHD , and is timely in light of recent NICE guidance BACKGROUND The reduced availability of data from non-Western countries limits our ability to underst and attention-deficit/hyperactivity disorder ( ADHD ) treatment outcomes , specifically , adherence and persistence of ADHD in children and adolescents . This analysis assessed predictors of treatment outcomes in a non-Western cohort of patients with ADHD treated with atomoxetine or methylpheni date .  METHODS Data from a 12-month , prospect i ve , observational study in out patients aged 6 - 17 years treated with atomoxetine ( N = 234 ) or methylpheni date ( N = 221 ) were analysed post hoc to determine potential predictors of treatment outcomes . Participating countries included the Russian Federation , China , Taiwan , Egypt , United Arab Emirates and Lebanon . Factors associated with remission were analysed with stepwise multiple logistic regression and classification and regression trees ( CART ) . Cox proportional hazards models with propensity score adjustment assessed differences in atomoxetine persistence among initial-dose cohorts . RESULTS In patients treated with atomoxetine who had available dosing information ( N = 134 ) , Cox proportional hazards revealed lower ( < 0.5 mg/kg ) initial dose was significantly associated with shorter medication persistence ( p < 0.01 ) . multiple logistic regression analysis revealed greater rates of remission for  atomoxetine-treated patients were associated with age ( older ) , country ( United Arab Emirates ) and gender ( female ) ( all p < 0.05 ) . CART analysis confirmed older age and lack of specific phobias were associated with greater remission rates . For methylpheni date , greater baseline weight ( highly correlated with the age factor found for atomoxetine ) and prior atomoxetine use were associated with greater remission rates . CONCLUSIONS These findings may help clinicians assess factors upon initiation of ADHD treatment to improve course prediction , proper dosing and treatment adherence and persistence . TRIAL REGISTRATION Observational study , therefore no registration OBJECTIVE Numerous investigations have examined the efficacy of pharmacological treatment for attention-deficit/hyperactivity disorder ( ADHD ) in children . However , relatively few studies have addressed the impact of treatment on long-term subjective , psychosocial outcomes , such as health-related quality of life ( HRQL ) . This study examines the long-term effects of pharmacological treatment with atomoxetine on HRQL in children and adolescents with ADHD . METHODS Participants included 6- to 17-year-old children and adolescents ( n = 912 ) with ADHD enrolled in a 24-month , multicenter , open-label trial of atomoxetine . Outcomes included clinician ratings of ADHD , parent ratings of ADHD , and a widely used measure of HRQL ( The Child Health Question naire ( CHQ ) ) . Treatment response rates were calculated based on a CHQ improvement of at least 1 st and ard error of measurement . RESULTS Significant improvements in HRQL were found following both acute and long-term treatment for psychosocial but not physical health . Of participants who completed treatment ( n = 312 or 34.2 % of those enrolled ) , 81 % responded to acute treatment and 78 % responded to long-term treatment . Improvements noted after acute treatment were maintained during long-term treatment with the majority of participants ( 86 % ) continuing to respond to treatment . CONCLUSIONS Atomoxetine is associated with improvements in HRQL , and the improvements are generally stable over time OBJECTIVE Response to atomoxetine , a nonstimulant norepinephrine-specific reuptake inhibitor , was compared with the effect of osmotic-release oral methylpheni date , a long-acting methylpheni date preparation , in patients with attention deficit hyperactivity disorder ( ADHD ) . METHOD In a large placebo-controlled , double-blind study , patients ages 6 - 16 with ADHD , any subtype , were r and omly assigned to receive 0.8 - 1.8 mg/kg per day of atomoxetine ( N=222 ) , 18 - 54 mg/day of osmotically released methylpheni date ( N=220 ) , or placebo ( N=74 ) for 6 weeks . The a priori specified primary analysis compared response ( at least 40 % decrease in ADHD Rating Scale total score ) to osmotically released methylpheni date with response to atomoxetine and placebo . After 6 weeks , patients treated with methylpheni date were switched to atomoxetine under double-blind conditions . RESULTS The response rates for both atomoxetine ( 45 % ) and methylpheni date ( 56 % ) were markedly superior to that for placebo ( 24 % ) , but the response to osmotically released methylpheni date was superior to that for atomoxetine . Each medication was well tolerated , with completion rates and discontinuations for adverse events not significantly different from those for placebo . Of the 70 subjects who did not respond to methylpheni date , 30 ( 43 % ) subsequently responded to atomoxetine . Likewise , 29 ( 42 % ) of the 69 patients who did not respond to atomoxetine had previously responded to osmotically released methylpheni date . CONCLUSION Response was significantly greater with osmotically released methylpheni date than with atomoxetine . One-third of patients who received methylpheni date followed by atomoxetine responded better to one or the other , suggesting that there may be preferential responders 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 assess the effect of methylpheni date on the diagnosis of oppositional-defiant disorder ( ODD ) comorbid with attention-deficit hyperactivity disorder ( ADHD ) . METHOD We conducted an open-label study in which 10 children and adolescents with a dual diagnosis of ODD and ADHD were assessed for their ODD symptoms and treated with methylpheni date . At least one month after ADHD symptoms were under control , ODD symptoms were reevaluated with the Parent form of the Children Interview for Psychiatric Syndromes ( P-ChIPS ) . RESULTS Nine of the 10 patients no longer fulfilled diagnostic criteria for ODD after they were treated with methylpheni date for ADHD . CONCLUSION Methylpheni date seems to be an effective treatment for ODD , as well as for ADHD itself . The implication s for the treatment of patients with ODD not comorbid with ADHD needs further investigation CONTEXT Attention-deficit/hyperactivity disorder ( ADHD ) is a highly prevalent and impairing psychiatric disorder that affects both children and adults . There are Food and Drug Administration-approved stimulant and nonstimulant medications for treating ADHD ; however , little is known about the mechanisms by which these different treatments exert their therapeutic effects . OBJECTIVE To contrast changes in brain activation related to symptomatic improvement with use of the stimulant methylpheni date hydrochloride vs the nonstimulant atomoxetine hydrochloride . DESIGN Functional magnetic resonance imaging before and after 6 to 8 weeks of treatment with methylpheni date ( n = 18 ) or atomoxetine ( n = 18 ) using a parallel-groups design . SETTING Specialized ADHD clinical research program at Mount Sinai School of Medicine , New York , New York . PARTICIPANTS Thirty-six youth with ADHD ( mean [ SD ] age , 11.2 [ 2.7 ] years ; 27 boys ) recruited from r and omized clinical trials . MAIN OUTCOME MEASURES Changes in brain activation during a go/no-go test of response inhibition and investigator-completed ratings on the ADHD Rating Scale-IV-Parent Version . RESULTS Treatment with methylpheni date vs atomoxetine was associated with comparable improvements in both response inhibition on the go/no-go test and mean ( SD ) improvements in ratings of ADHD symptoms ( 55 % [ 30 % ] vs 57 % [ 25 % ] ) . Improvement in ADHD symptoms was associated with common reductions in bilateral motor cortex activation for both treatments . Symptomatic improvement was also differentially related to gains in task-related activation for atomoxetine and reductions in activation for methylpheni date in the right inferior frontal gyrus , left anterior cingulate/supplementary motor area , and bilateral posterior cingulate cortex . These findings were not attributable to baseline differences in activation . CONCLUSIONS Treatment with methylpheni date and atomoxetine produces symptomatic improvement via both common and divergent neurophysiologic actions in frontoparietal regions that have been implicated in the pathophysiology of ADHD . These results represent a first step in delineating the neurobiological basis of differential response to stimulant and nonstimulant medications for ADHD INTRODUCTION AND HYPOTHESIS Some authors draw a connection between the dopaminergic pathways and emotional perception . The present study is based on that association and addresses the question whether methylpheni date and the result ing amelioration of the disturbed dopamine metabolism lead to an improvement of the facial affect recognition abilities in children with attention-deficit/hyperactivity disorder ( ADHD ) . METHODS A computer test was conducted on 21 participants , aged 7 - 14 years and with a diagnosis of ADHD - some with comorbid oppositional defiant disorder - conducted the FEFA ( Frankfurt Test and Training of Facial Affect ) , a computer test to examine their facial affect recognition abilities . It consists of two subtests , one with faces and one with eye pairs . All participants were tested in a double-blind cross-over study , once under placebo and once under methylpheni date . RESULTS AND DISCUSSION The collected data showed that methylpheni date leads to amelioration of facial affect recognition abilities , but not on a significant level . Reasons for missing significance may be the small sample size or the fact that there exists some overlapping in cerebral connections and metabolic pathways of the site of action of methylpheni date and the affected dopaminergic areas in ADHD . However , consistent with the endophenotype concept , certain gene locations of the dopaminergic metabolism as both an aetiological factor for ADHD and the deficient facial affect recognition abilities with these individuals were considered . Consulting current literature they were found to be not concordant . Therefore , we conclude that the lacking significance of the methylpheni date affect on facial affect recognition is based on this fact Background A r and omized and controlled clinical study was performed to evaluate the use of neurofeedback ( NF ) to treat  attention-deficit/hyperactivity disorder ( ADHD ) in children and adolescents . Methods The ADHD population was selected from an outpatient clinic for Child and Adolescent Mental Health in Norway . Ninety-one of the 275 children and adolescents ranging in age from 6 to 18 years ( 10.5 years ) participated in 30 sessions of an intensive NF program . The reinforcement contingency was based on the subjects ’ production of cortical beta1 activity ( 15–18 Hz ) . The ADHD participants were r and omized into three groups , with 30 in the NF group , 31 controls in a group that was given methylpheni date , and 30 in a group that received NF and methylpheni date .  ADHD core symptoms were reported by parents using the parent form of the Clinician ’s Manual for Assessment by Russell A. Barkley . Results Ninety-one children and adolescents were effectively r and omized by age , sex , intelligence and distribution of ADHD core symptoms . The parents reported significant effects of the treatments , but no significant differences between the treatment groups were observed . Conclusions NF was as effective as methylpheni date at treating the attentional and hyperactivity symptoms of ADHD , based on parental reports . Trial registration Current Controlled Trials BACKGROUND The primary treatment for attention-deficit/hyperactivity disorder ( ADHD ) has been psychostimulants . Recently developed nonpsychostimulant treatments have allowed certain patients to switch from a psychostimulant to a nonpsychostimulant . However , the outcomes of such switches have not been systematic ally studied . OBJECTIVE The purpose of this pilot study was to assess treatment tolerance and efficacy during a cross-taper transition from methylpheni date or amphetamine to atomoxetine among children and adolescents with ADHD . METHODS This pilot study was conducted in patients ( aged 6 - 17 years ) with incomplete responses ( failure to obtain full reduction/elimination of symptoms ) or intolerance of adverse events ( AEs ) during psychostimulant treatment . Patients continued ongoing psychostimulant treatment during the first week of the study . Transition to atomoxetine began by administering atomoxetine 0.5 mg/kg . d plus full-dose psychostimulant for 1 week , followed in the second week by 1.2 mg/kg . d atomoxetine plus half-dose psychostimulant . Patients remained on 1.2 mg/kg . d atomoxetine monotherapy for the remaining 5 weeks . This stepwise transition was enacted due to the difference in pharmacodynamics between the psychostimulants and atomoxetine . Applying a stepwise cross-titration allowed for better control of ADHD symptoms during the intervening period . Change in ADHD symptoms , as measured by the mean change in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version : Investigator-administered and -scored ( ADHDRS-IV-Parent : Inv ) , was assessed from baseline to end point . RESULTS Of the 62 subjects enrolled in the study , 39 ( 62.9 % ) were diagnosed as ADHD-combined type . Similar proportions were receiving methylpheni date ( 51.6 % ) and amphetamine ( 48.4 % ) . Slightly more wished to switch due to inadequate response ( 53.2 % ) than intolerability ( 46.8 % ) . Nine subjects discontinued at various times during the course of the study ( patient or parent/caregiver decision [ 4 ] , AE [ 2 ] , protocol violation [ 2 ] , and lack of efficacy [ 1 ] ) . Mean ( SD ) ADHDRS-IV-Parent : Inv total scores ( n = 59 , last-observation-carried-forward ) improved significantly from baseline ( visit 2 ) to an end point ( 32.1 [ 10.5 ] vs 22.6 [ 14.0 ] ; P < 0.001 ) . Of the 58 subjects answering in the atomoxetine  monotherapy phase , 38 ( 65.5 % ) reported a preference for atomoxetine treatment over their previous psychostimulant .  Tolerability results were as follows : 26 ( 44.1 % ) of 59 patients reported > or=1 AE , the most common being somnolence ( 4 [ 6.8 % ] ) , fatigue ( 3 [ 5.1 % ] ) , decreased appetite ( 3 [ 5.1 % ] ) , cough ( 3 [ 5.1 % ] ) , headache ( 3 [ 5.1 % ] ) , and contact dermatitis ( 2 [ 3.4 % ] ) . No clinical ly severe AEs were reported . Both mean ( SD ) diastolic ( 2.4 [ 7.8 ] mm Hg ; P = 0.031 ) and systolic ( 2.4 [ 7.9 ] mm Hg ; P = 0.029 ) blood pressures increased significantly from baseline to end point . Electrocardiography revealed a significant increase in mean ( SD ) heart rate ( 9.2 [ 11.6 ] bpm ; P < 0.001 ) and a corresponding decrease in mean ( SD ) RR interval ( -77.8 [ 98.2 ] ms ; P < 0.001 ) . Statistically significant , but mild , increases in diastolic pressure and heart rate were observed . CONCLUSION These children and adolescent patients were successfully switched from methylpheni date or amphetamine to atomoxetine treatment , with result ing improvement in ADHD symptom severity from baseline in this pilot study 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 Stimulants are not considered appropriate for the treatment of children with conduct disorders ( CDs ) . The postulated differences in stimulant effect between children with attention deficit hyperactivity disorder ( ADHD ) and CD led to the hypothesis that methylpheni date hydrochloride , which is effective in ADHD , would not significantly improve symptoms of CD . METHODS We r and omly assigned 84 children with CD , between the ages of 6 and 15 years , to receive methylpheni date hydrochloride ( up to 60 mg/d ) or placebo for 5 weeks . Behavior was evaluated by parent , teacher , and clinician reports and by direct classroom observations . Two thirds of the children also met criteria for ADHD . RESULTS Contrary to prediction , ratings of antisocial behaviors specific to CD were significantly reduced by methylpheni date treatment . The magnitude of methylpheni date effect indicated meaningful clinical benefit . Partialling out severity of ADHD did not alter the significant superiority of methylpheni date on CD ratings specifically ( P < .001 ) . CONCLUSIONS Methylpheni date has short-term positive effects on children and adolescents with CD . Key aspects of antisocial adjustment appear to be treatment responsive . This effect was independent of severity of the children 's initial ADHD symptoms 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 Introduction The National Institute for Health and Care Excellence ( NICE ) guidelines for attention deficit/hyperactivity disorder ( ADHD ) state that young people need to have access to the best evidence -based care to improve outcome . The current ‘ gold st and ard ’ ADHD diagnostic assessment combines clinical observation with subjective parent , teacher and self-reports . In routine practice , reports from multiple informants may be unavailable or contradictory , leading to diagnostic uncertainty and delay . The addition of objective tests of attention and activity may help reduce diagnostic uncertainty and delays in initiating treatment leading to improved outcomes . This trial investigates whether providing clinicians with an objective report of levels of attention , impulsivity and activity can lead to an earlier , and more accurate , clinical diagnosis and improved patient outcome . Methods and analysis This multisite r and omised controlled trial will recruit young people ( aged 6–17 years old ) who have been referred for an ADHD diagnostic assessment at Child and Adolescent Mental Health Services ( CAMHS ) and Community Paediatric clinics across Engl and . Routine clinical assessment will be augmented by the QbTest , incorporating a continuous performance test ( CPT ) and infrared motion tracking of activity . The participant will be r and omised into one of two study arms : QbOpen ( clinician has immediate access to a QbTest report ) : QbBlind ( report is withheld until the study end ) . Primary outcomes are time to diagnosis and diagnostic accuracy . Secondary outcomes include clinician 's diagnostic confidence and routine clinical outcome measures . Cost-effective analysis will be conducted , alongside a qualitative assessment of the feasibility and acceptability of incorporating QbTest in routine practice . Ethics and dissemination The findings from the study will inform commissioners , clinicians and managers about the feasibility , acceptability , clinical utility and cost-effectiveness of incorporating QbTest into routine diagnostic assessment of young people with ADHD . The results will be su bmi tted for publication in peer- review ed journals . The study has received ethical approval . Trial registration number NCT02209116 Background Compared to existing literature on childhood attention deficit hyperactivity disorder ( ADHD ) , little published adult data are available , particularly outside of the United States . Using General Practitioner ( GP ) question naires from the United Kingdom , this study aim ed to examine a number of issues related to ADHD in adults , across three cohorts of patients , adults who received ADHD drug treatment in childhood/adolescence but stopped prior to adulthood ; adults who received ADHD drug treatment in childhood/adolescence and continued treatment into adulthood and adults who started ADHD drug treatment in adulthood . Methods Patients with a diagnosis of ADHD and prescribed methylpheni date , dexamfetamine or atomoxetine were identified using data from The Health Improvement Network ( THIN ) . Date s when these drugs started and stopped were used to classify patients into the three cohorts . From each cohort , 50 patients were r and omly selected and question naires were sent via THIN to their GPs . GPs returned completed question naires to THIN who forwarded anonymised copies to the research ers . Data sets were analysed using descriptive statistics . Results Overall response rate was 89 % ( 133/150 ) . GPs stated that in 19 cases , the patient did not meet the criteria of that group ; the number of valid question naires returned was 114 ( 76 % ) . The following broad trends were observed : 1 ) GPs were not aware of the reason for treatment cessation in 43 % of cases , 2 ) patient choice was the most common reason for discontinuation ( 56 % ) , 3 ) 7 % of patients who stopped pharmacological treatment subsequently reported experiencing ADHD symptoms , 4 ) 58 % of patients who started pharmacological treatment for ADHD in adulthood received pharmacological treatment for other mental health conditions prior to the ADHD being diagnosed . Conclusion This study presents some key findings relating to ADHD ; GPs were often not aware of the reason for patients stopping ADHD treatment in childhood or adolescence . Patient choice was identified as the most common reason for treatment cessation . For patients who started pharmacological treatment in adulthood , many patients received pharmacological treatment for comorbidities before a diagnosis of ADHD was made 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 For many years , the National Institute for Health and Care Excellence ( NICE ) has recommended use of the EQ-5D-3L ( 3L ) [ 1 ] and its value set for the UK [ 2 ] . Since 2011 , an exp and ed-level instrument , the EQ-5D-5L ( 5L ) , has been available [ 3 ] and value sets now exist to support its use , including a value set for Engl and [ 4 , 5 ] . This poses a challenge for NICE . Should it recommend the 5L rather than the 3L ? This is neither a trivial nor merely academic matter : the choice of whether to use the 5L ( and English value set ) or the 3L ( and UK value set ) is likely to impact estimates of quality -adjusted life-years ( QALYs ) and incremental cost-effectiveness ratios ( ICERs ) . The size and direction of that impact will depend on the disease and the nature of the health problems . In general , where technologies improve self-reported health , estimates of QALY gains will often be smaller with the 5L [ 6 ] . In contrast , where technologies extend the length of life , estimates of QALY gains will be higher ( to varying degrees ) : each year of additional life is assigned a higher utility . The ultimate impact on health technology assessment ( HTA ) will depend on whether the differences between the 3L and 5L push ICERs from one side of the cost-effectiveness threshold to the other . Given the implication s for NICE ’s technology appraisal process , and other decisions informed by EQ-5D data , the Department of Health for Engl and has called for an independent validation of the 5L value set , given its relevance to policy [ 7 ] . In 2017 , NICE released a ‘ position statement ’ [ 8 ] stating that : The 3L value set continues to be used for reference-case analyses . Where 5L data have been collected , reference-case analyses should calculate utilities by mapping the 5L descriptive system data onto the 3L value set , using the van Hout et al. [ 9 ] mapping function . NICE supports sponsors of prospect i ve clinical studies continuing to use the 5L to collect data on quality of life . A further position statement is planned for August 2018 , to be informed by evidence from various studies underway . These include studies commissioned by the English Department of Health to investigate the implication s for past NICE technology appraisal s had the 5L been used , and to collect 3L and 5L data in parallel to further improve functions for mapping from one to the other . Other studies , funded by the EuroQol Group , are also underway , investigating various aspects of the relationship between the 3L and 5L across disease areas . The 3L and its UK value set has occupied a special place in NICE ’s technology appraisal process since its inception , therefore any transition will inevitably pose challenges ; for example , reconciling potential inconsistencies between past and future decisions . Given that evidence will continue to be su bmi tted using both the 3L and 5L for years to come , if both value sets are able to be used , there is a risk of inconsistency between decisions being made in the future . HTA in other countries may also face similar issues . Given the difficulties with any transition away from the 3L , is there a case for NICE to adopt the 5L as its preferred instrument ? Papers in this issue of Pharmacoeconomics , which are cited in this commentary , address that question by investigating comparative performance of the 3L and 5L The objective of this study was to test whether a previous observed Acetyl-L-carnitine ( ALC ) treatment effect could be repeated in an ALC adjunctive therapy treatment trial of attention-deficit/hyperactivity disorder ( ADHD ) in children and adolescents . This was a six-week , r and omized clinical trial undertaken in an outpatient child and adolescent clinic . Subjects included 40 out patients ( 28 boys and 12 girls ) between the ages of 7–13 who met the DSM-IV-TR diagnostic criteria for ADHD . All study subjects were r and omly assigned to receive treatment using capsules of ALC doses ranging from 500 to 1,500 mg/day depending on the weight of the child plus methylpheni date at a dose of 20–30 mg/day depending on weight or Placebo plus methylpheni date at a dose of 20–30 mg/day depending on weight . The principal measure of outcome was the Teacher and Parent attention deficit/hyperactivity disorder Rating Scale- IV . No difference was observed between the two groups on the Parent and Teacher Rating Scale scores ( df = 1 ; F = 0.10 ; P = 0.74 and df = 1 ; F = 0.22 ; P = 0.63 respectively ) . Side effects consisting of headache and irritability were observed more frequently in the methylpheni date plus placebo group . The results of this study do not support the application of ALC as an adjunctive therapy to methylpheni date in children and adolescents with ADHD 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 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 Recent studies have suggested that attention deficit hyperactivity disorder ( ADHD ) is associated with abnormalities in basal ganglia and prefrontal cortical functioning . However , these studies have primarily relied upon cognitive tasks that reflect impulse control rather than attentional mechanisms . METHOD The authors used functional magnetic resonance imaging to investigate the neural correlates of selective and divided attention in a r and omized , double-blind , placebo-controlled pharmacological challenge with methylpheni date in 15 adolescents with ADHD ( ages 14 - 17 ) , eight adolescents with reading disorder ( ages 12 - 17 ) , and four adolescents with both reading disorder and ADHD ( ages 14 - 18 ) who were scanned during both a methylpheni date and a placebo session . Fourteen healthy comparison subjects ( ages 12 - 20 ) who were not given methylpheni date served as the primary comparison group . RESULTS During the divided attention task , unmedicated subjects with ADHD or reading disorder  recruited the left ventral basal ganglia significantly less than the healthy comparison subjects . Methylpheni date led to an increase in activation in this region but had no effect on task performance .  Subjects with ADHD also recruited the middle temporal gyrus significantly less than the comparison subjects , but methylpheni date did not have a direct effect on activation in this region . CONCLUSIONS These results suggest that ADHD is associated with abnormal processing in attentional networks , with specific dysfunction in striatal circuitry . Methylpheni date may act to normalize activity within this network
Results The technology assessment was unable to differentiate between the various drugs in terms of efficacy , and its economic model was ultimately driven by cost differences .
While the assessment concluded that the economic model " clearly identified an optimal treatment strategy " with first-line dexamphetamine , the NICE appraisal committee subsequently found it impossible to distinguish between the different strategies on grounds of cost-effectiveness .
Background Health technology assessment s ( HTAs ) by the National Institute for Health and Clinical Excellence ( NICE ) enjoy high levels of international attention .
The present analysis addresses NICE 's appraisal of methylpheni date , atomoxetine and dexamphetamine for attention-deficit/hyperactivity disorder ( ADHD ) in children and adolescents , published in March 2006 .