Transition from methylphenidate or amphetamine to atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder--a preliminary tolerability and efficacy study. Common and unique therapeutic mechanisms of stimulant and nonstimulant treatments for attention-deficit/hyperactivity disorder. Randomized controlled double-blind trial of optimal dose methylphenidate in children and adolescents with severe attention deficit hyperactivity disorder and intellectual disability. Methylphenidate versus dexamphetamine in children with attention deficit hyperactivity disorder: A double-blind, crossover trial. Differential impact of methylphenidate and atomoxetine on sustained attention in youth with attention-deficit/hyperactivity disorder. Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: acute comparison and differential response. 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)* Atomoxetine versus Methylphenidate in Paediatric Outpatients with Attention Deficit Hyperactivity Disorder: A Randomized, Double-Blind Comparison Trial A Comparative Study of the Efficacy of ACTH4–9 Analog, Methylphenidate, and Placebo on Attention Deficit Disorder with Hyperkinesis Clinically Relevant Doses of Methylphenidate Significantly Occupy Norepinephrine Transporters in Humans In Vivo Clinical efficacy of methylphenidate in conduct disorder with and without attention deficit hyperactivity disorder. Effectiveness of atomoxetine and quality of life in children with attention-deficit/hyperactivity disorder as perceived by patients, parents, and physicians in an open-label study. Attention deficit disorder with and without hyperactivity: clinical response to three dose levels of methylphenidate. 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. Methylphenidate for pervasive developmental disorders: safety and efficacy of acute single dose test and ongoing therapy: an open-pilot study. Clinical gains from including both dextroamphetamine and methylphenidate in stimulant trials. Atomoxetine treatment in adolescents with attention-deficit/hyperactivity disorder.
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 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 BACKGROUND Attention deficit hyperactivity disorder is increased in children with intellectual disability . Previous research has suggested stimulants are less effective than in typically developing children but no studies have titrated medication for individual optimal dosing or tested the effects for longer than 4 weeks . METHOD One hundred and twenty two drug-free children aged 7 - 15 with hyperkinetic disorder and IQ 30 - 69 were recruited to a double-blind , placebo-controlled trial that r and omized participants using minimization by probability , stratified by referral source and IQ level in a one to one ratio .  Methylpheni date was compared with placebo . Dose titration comprised at least 1 week each of low ( 0.5 mg/kg/day ) , medium ( 1.0 mg/kg/day ) and high dose ( 1.5 mg/kg/day ) . Parent and teacher Attention deficit hyperactivity disorder ( ADHD ) index of the Conners Rating Scale-Short Version at 16 weeks provided the primary outcome measures . Clinical response was determined with the Clinical Global Impressions scale ( CGI-I ) . Adverse effects were evaluated by a parent-rated question naire , weight , pulse and blood pressure . Analyses were by intention to treat . TRIAL REGISTRATION IS RCT N 68384912 . RESULTS Methylpheni date was superior to placebo with effect sizes of 0.39 [ 95 % confidence intervals ( CIs ) 0.09 , 0.70 ] and 0.52 ( 95 % CIs 0.23 , 0.82 ) for the parent and teacher Conners ADHD index . Four ( 7 % ) children on placebo versus 24 ( 40 % ) of those on methylpheni date were judged improved or much improved on the CGI . IQ and autistic symptoms did not affect treatment efficacy . Active medication was associated with sleep difficulty , loss of appetite and weight loss but there were no significant differences in pulse or blood pressure . CONCLUSIONS Optimal dosing of methylpheni date is practical and effective in some children with hyperkinetic disorder and intellectual disability . Adverse effects typical of methylpheni date were seen and medication use may require close monitoring in this vulnerable group 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 BACKGROUND This study examined the effects of atomoxetine ( ATX ) and OROS methylpheni date ( MPH ) on laboratory measures of inhibitory control and attention in youth with attention-deficit/hyperactivity disorder ( ADHD ) . It was hypothesized that performance would be improved by both treatments , but response profiles would differ because the medications work via different mechanisms . METHODS One hundred and two youth ( 77 male ; mean age = 10.5 ± 2.7 years ) with ADHD received ATX ( 1.4 ± 0.5 mg/kg ) and MPH ( 52.4 ± 16.6 mg ) in a r and omized , double-blind , crossover design . Medication was titrated in 4 - 6-week blocks separated by a 2-week placebo washout  . Inhibitory control and attention measures were obtained at baseline , following washout , and at the end of each treatment using Conners ' Continuous Performance Test II ( CPT-II ) , which provided age-adjusted T-scores for reaction time ( RT ) , reaction time variability ( RT variability ) , and errors . Repeated- measures analyses of variance were performed , with Time ( premedication , postmedication ) and Treatment type ( ATX , MPH ) entered as within-subject factors . Data from the two treatment blocks were checked for order effects and combined if order effects were not present . CLINICAL TRIAL REGISTRATION Clinical trials.gov : NCT00183391 . RESULTS Main effects for Time on RT ( p = .03 ) , RTSD ( p = .001 ) , and omission errors ( p = .01 ) were significant . A significant Drug × Time interaction indicated  that MPH improved RT , RTSD , and omission errors  more than ATX ( p < .05 ) . Changes in performance with treatment did not correlate with changes in ADHD symptoms . CONCLUSIONS MPH has greater effects  than ATX on CPT measures of sustained attention in youth with ADHD . However , the dissociation of cognitive and behavioral change with treatment indicates that CPT measures can not be considered proxies for symptomatic improvement . Further research on the dissociation of cognitive and behavioral endpoints for ADHD is indicated 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 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 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 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 BACKGROUND Attention-deficit/hyperactivity disorder is a psychiatric disorder that starts in childhood . The mechanism of action of methylpheni date , the most common treatment for attention deficit hyperactivity disorder , is unclear . In vitro , the affinity of methylpheni date for the norepinephrine transporter ( NET ) is higher than that for the dopamine transporter ( DAT ) . The goal of this study was to use positron emission tomography to measure the occupancy of brain norepinephrine transporter by methylpheni date in vivo in humans . METHODS We used (S , S)-[¹¹C ] methylreboxetine ( [¹¹C]MRB ) to determine the effective dose 50 ( ED₅₀ ) of methylpheni date for NET . In a within-subject design , healthy subjects ( n = 11 ) received oral , single-blind placebo and 2.5 , 10 , and 40 mg of methylpheni date 75 min before [¹¹C]MRB injection . Dynamic positron emission tomography imaging was performed for 2 hours with the High Resolution Research Tomograph . The multilinear reference tissue model with occipital cortex as the reference region was used to estimate binding potential non-displaceable ( BP(ND ) ) in the thalamus and other NET-rich regions . RESULTS BP(ND ) was reduced by methylpheni date in a dose-dependent manner in thalamus and other NET-rich regions . The global ED₅₀ was estimated to be .14 mg/kg ; therefore , the average clinical maintenance dose of methylpheni date ( .35-.55 mg/kg ) produces 70 % to 80 % occupancy of NET . CONCLUSIONS For the first time in humans , we demonstrate that oral methylpheni date significantly occupies NET at clinical ly relevant doses . The ED₅₀ is lower than that for DAT ( .25 mg/kg ) , suggesting the potential relevance of NET inhibition in the therapeutic effects of methylpheni date in attention-deficit/hyperactivity disorder 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 OBJECTIVES Health-related quality of life in children with attention-deficit/hyperactivity disorder ( ADHD ) may improve with atomoxetine treatment . However , the degree of improvement may be perceived differently by patients , parents , and physicians . The primary aim of this study was to investigate ADHD-related difficulties as perceived from these three perspectives and to compare the perspectives . The degree of perceived difficulties was taken to reflect the health-related quality of life of patients in the study . A second objective was to assess the effectiveness of atomoxetine in children with ADHD in an open-label setting . METHODS Children aged 6 - 11 years with ADHD were treated for 24 weeks with atomoxetine at a target dose of 0.5 - 1.2 mg/kg per day . ADHD-related difficulties were assessed after 8 and 24 weeks of treatment using the newly devised Global Impression of Perceived Difficulties ( GIPD ) scale . This instrument , that has not yet been psychometrically vali date d , reflects patient quality of life from the three perspectives . Agreement among the perspectives was determined using Cohen 's kappa . RESULTS A total of 262 patients was treated with atomoxetine .  The mean dose for the respective visit intervals ranged between 1.15 and 1.17 mg/kg per day . Quality of life as reflected by the degree of perceived difficulties improved over time . Change in GIPD scores was greatest within the first 2 weeks . The course of the mean GIPD total scores over time showed a similar pattern among the three different rater perspectives . However , patients perceived the degree of difficulties as significantly less compared to parents and physicians . Agreement of ratings was highest between physicians and parents . CONCLUSIONS Results from the GIPD suggest that patient quality of life improves with time on atomoxetine . The effectiveness of atomoxetine in an open-label study was very similar to the effectiveness shown in placebo-controlled trials The response of 23 children with attention deficit disorder ( ADD ) with hyperactivity ( + H ) and 17 children with ADD without hyperactivity ( -H ) to three doses of methylpheni date ( 5 , 10 , and 15 mg twice a day ) was evaluated in a triple-blind , placebo-controlled cross-over design using parent and teacher ratings of behavior , laboratory tests of ADD symptoms , and behavioral observations during academic performance . Results indicated that the children with ADD+H were rated as having more pervasive behavioral problems at home and more pervasive and severe conduct problems at school than the children with ADD-H. Laboratory tests found the children with ADD+H to be impaired in behavioral inhibition and vigilance whereas children with ADD-H were more impaired in the consistent retrieval of verbally learned material Drug effects were noted on the parent and teacher ratings and on most laboratory measures , with all three doses typically producing significant changes but rarely differing among themselves in effectiveness . The groups were not found to differ significantly on any measures in their response to methylpheni date . However , more children with ADD-H were clinical ly judged as having either no clinical response ( 24 % ) or responding best to the low dose ( 35 % ) of medication . In contrast , most ADD+H ( 95 % ) children were judged to be positive responders and most were recommended to receive the moderate to high dose ( 71 % ) 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 OBJECTIVE The aim of this study was to investigate the effects of ongoing methylpheni date ( MPH ) on ADHD-related and autistic symptoms in Pervasive Developmental Disorders ( PDD ) in children who did not present any adverse effects to an initial acute dose administered at the clinic . METHODS Participants included 13 subjects ( 12 males , with a mean age of 7.9 years ) with PDD and moderate to severe hyperactivity/impulsivity . The severity of the symptoms assessment was based on Clinical Global Impression ( CGI ) , Childhood Autism , Child Psychiatric and Conners Parent and Teacher Rating Scales ( CPRS ) . Scores at baseline , and after 1 and 3 months of treatment , were compared to intent-to-treat analyses . RESULTS One ( 1 ) hour after a single MPH dose ( 0.4 mg/kg ) , 5 subjects exhibited increased hyperactivity , stereotypes , dysphoria , or motor tics and were rated as minimally or much worse on the CGI Global Improvement Scale . They received no further treatment with MPH . Four ( 4 ) of the remaining subjects were rated as improved , and four as unchanged ; they proceeded to a 12-week open trial of MPH . Two children remained unchanged : they discontinued treatment after 1 week on maximally tolerated doses . However , in group analyses , behavioral measures of hyperactivity and impulsivity improved significantly , while autism core symptom measures were unaffected . No significant adverse effects were observed in any of the 8 subjects . CONCLUSIONS Administering a single MPH test dose may be useful in identifying children with PDD who may benefit from prolonged therapy OBJECTIVE The purpose of this study was to investigate clinical gains from including both dextroamphetamine and methylpheni date in stimulant trials . METHOD Thirty-six medication-naïve children ages 9 - 14 years diagnosed with attention-deficit/hyperactivity disorder ( ADHD ) were enrolled for 6 weeks in a crossover trial , with 2 weeks of methylpheni date , dextroamphetamine , and placebo , in a r and omly assigned , counterbalanced sequence . Outcome measures constituted a computer-based continuous performance test combined with a motion tracking system ( Qb Test ) and an ADHD question naire rated by parents and teachers . RESULTS Group analyses found significant treatment effects of similar size for the two stimulants on both outcome measures . Single-subject analyses revealed that each stimulant produced a favourable response in 26 children ; however , an individual child frequently responded qualitatively or quantitatively differently to the two stimulants . By including both stimulants in the trial , the number of favorable responders increased from 26 ( 72 % ) to 33 ( 92 % ) . In children with favorable responses of unequal strength to the two stimulants , a shift from inferior drug to best drug was associated with a 64 % mean increase in the overall response strength score , as measured by the ADHD question naire . CONCLUSIONS The likelihood of a favorable response and optimal response strength is increased by including both stimulants in the stimulant trial . The study was first registered in clinical trials 28 September 2010 . Clinical Trials.gov Identifier : NCT01220440 INTRODUCTION This study compared two atomoxetine titration dosing schedules and two atomoxetine maintenance doses for treating adolescent attention-deficit/hyperactivity disorder ( ADHD ) inattention and hyperactivity/impulsivity .  METHODS Adolescents ( N = 267 ) were r and omized to a slow or fast titration schedule . Patients who responded continued on a 40-week maintenance treatment , r and omized to either 0.8 or 1.4 mg/kg/day . RESULTS During the acute period , significant benefit was demonstrated with both titration schedules on the ADHD Rating Scale total score . Although patients in both groups maintained benefit relative to week 0 , statistically significant loss of benefit was found for patients maintained on 0.8 mg/kg/day but not on 1.4 mg/kg/day . A similar pattern was observed on the Clinical Global Impressions-ADHD-Severity scores and Life Participation Scale for ADHD-Child Version scores . Mean grade s for most subjects improved for patients in both maintenance treatment groups although most improvements were not statistically significant . CONCLUSIONS In adolescents with ADHD , treatment benefit at 8 weeks was better maintained long-term with 1.4 mg/kg/day than with 0.8 mg/kg/day . Improvement in adaptive functioning and age-appropriate developmental function was also demonstrated . Atomoxetine 0.8 and 1.4 mg/kg/day were equally well tolerated . CLINICAL TRIALS REGISTRY Maintenance of benefit with atomoxetine hydrochloride in adolescents with ADHD , NCT00191035
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 .