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.
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
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 .