Erratum to: Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies Common and unique therapeutic mechanisms of stimulant and nonstimulant treatments for attention-deficit/hyperactivity disorder. Long-term, open-label study of the safety and efficacy of atomoxetine in adults with attention-deficit/hyperactivity disorder: an interim analysis. Selegiline in the treatment of attention deficit hyperactivity disorder in children: a double blind and randomized trial Impact of comorbid autism spectrum disorders on stimulant response in children with attention deficit hyperactivity disorder: a retrospective and prospective effectiveness study. Methylphenidate-Elicited Dopamine Increases in Ventral Striatum Are Associated with Long-Term Symptom Improvement in Adults with Attention Deficit Hyperactivity Disorder A pilot study for augmenting atomoxetine with methylphenidate: safety of concomitant therapy in children with attention-deficit/hyperactivity disorder Young adult outcomes in the follow‐up of the multimodal treatment study of attention‐deficit/hyperactivity disorder: symptom persistence, source discrepancy, and height suppression Blood pressure changes associated with medication treatment of adults with attention-deficit/hyperactivity disorder. Long-term stimulant treatment of children with attention-deficit hyperactivity disorder symptoms. A randomized, double-blind, placebo-controlled trial. Stimulant treatment in children with attention-deficit/hyperactivity disorder moderates adolescent academic outcome. Long-term effectiveness and safety of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder. Adult outcome of hyperactive boys. Educational achievement, occupational rank, and psychiatric status. Childhood hyperactivity and psychostimulants: a review of extended treatment studies. Symptomatic improvement in children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment. A Systematic Review of Global Publication Trends Regarding Long-Term Outcomes of ADHD Clinical efficacy of methylphenidate in conduct disorder with and without attention deficit hyperactivity disorder. Management of adult attention deficit hyperactivity disorder in UK primary care: a survey of general practitioners Academic achievement and emotional status of children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment. Children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment: impact on parental practices. Do stimulants reduce the risk for cigarette smoking in youth with attention-deficit hyperactivity disorder? A prospective, long-term, open-label study of extended-release 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. Efficacy of theophylline compared to methylphenidate for the treatment of attention-deficit hyperactivity disorder in children and adolescents: a pilot double-blind randomized trial.
Background : The stimulant methylpheni date ( MPH ) has been a mainstay of treatment for attention-deficit/hyperactivity disorder ( ADHD ) for many years . Owing to the short half-life and the issues associated with multiple daily dosing of immediate-release MPH formulations , a new generation of long-acting MPH formulations has emerged . Direct head-to-head studies of these long-acting MPH formulations are important to facilitate an evaluation of their comparative pharmacokinetics and efficacy ; however , to date , relatively few head-to-head studies have been performed . The objective of this systematic review was to compare the evidence available from head-to-head studies of long-acting MPH formulations and provide information that can guide treatment selection . Methods : A systematic literature search was conducted in MEDLINE and PsycINFO in March 2012 using the MeSH terms : attention deficit disorder with hyperactivity/drug therapy ; methylpheni date /therapeutic use and All Fields : Concerta ; Ritalin LA ; OROS and ADHD ; Medikinet ; Equasym XL and ADHD ; long-acting methylpheni date ; Diffucaps and ADHD ; SODAS and methylpheni date . No filters were applied and no language , publication date or publication status limitations were imposed . Articles were selected if the title indicated a comparison of two or more long-acting MPH preparations in human subjects of any age ; non- systematic review articles and unpublished data were not included . Results : Of 15,295 references returned in the literature search and screened by title , 34 articles were identified for inclusion : nine articles from pharmacokinetic studies ( nine studies ) ; nine articles from laboratory school studies ( six studies ) ; two articles from r and omized controlled trials ( two studies ) ; three articles from switching studies ( two studies ) and three articles from one observational study . Conclusions : Emerging head-to-head studies provide important data on the comparative efficacy of the formulations available . At a group level , efficacy across the day generally follows the pharmacokinetic profile of the MPH formulation . No formulation is clearly superior to another ; careful consideration of patient needs and subtle differences between formulations is required to optimize treatment . For patients achieving suboptimal symptom control , switching long-acting MPH formulations may be beneficial . When switching formulations , it is usually appropriate to titrate the immediate-release component of the formulation ; a limitation of current studies is a focus on total daily dose rather than equivalent immediate-release components . Further studies are necessary to provide guidance in clinical practice , particularly in the treatment of adults and pre-school children and the impact of comorbidities and symptom severity on treatment response 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 ( ADHD ) is an early-onset neuropsychiatric disorder that affects 3 % to 7 % of school-age children and 4 % of adults . Its pathophysiology is thought to involve the dopaminergic and nor-adrenergic pathways associated with attention control and impulsivity . These symptoms have largely been defined in the childhood population , but the course of the condition and expression in the adult population are not as well characterized . METHOD This is an ongoing , 3-year , open-label study consisting of adults with DSM-IV ADHD who were previously enrolled in 1 of 2 double-blind , acute-treatment studies of atomoxetine .  The results of the interim analysis reported here were derived from the study of 384 patients at 31 sites who had been studied for a period of up to 97 weeks . The primary efficacy measure was the Conners ' Adult ADHD Rating Scale-Investigator Rated : Screening Version ( CAARS-Inv : SV ) total ADHD symptom score . In addition , safety , adverse events , and vital sign measurements were assessed . RESULTS Significant improvement was noted with atomoxetine therapy , with mean CAARS-Inv : SV total ADHD symptom scores decreasing 33.2 % from 29.2 ( baseline of open-label therapy ) to 19.5 ( endpoint of open-label therapy ) ( p < .001 ) . Similar and significant decreases were noted for the secondary efficacy measures . Adverse events consisted primarily of pharmacologically ( noradrenergic ) expected effects , such as increases in heart rate and blood pressure and a slight decrease in weight . CONCLUSION The results of this interim analysis of an ongoing , open-label study of adults with ADHD support the long-term efficacy , safety , and tolerability of atomoxetine for the treatment of adult ADHD Attention deficit hyperactivity disorder ( ADHD ) is a common disorder of childhood that affects 3 % to 6 % of school-age children . Conventional stimulant medications are recognized by both specialists and parents as useful symptomatic treatment . Nevertheless , approximately 30 % of ADHD children treated with them do not respond adequately or can not tolerate the associated adverse effects . Such difficulties highlight the need for alternative safe and effective medications in the treatment of this disorder . Selegiline is a type B monoamine oxidase inhibitor ( MAOI ) that is metabolized to amphetamine and methamphetamine stimulant compounds that may be useful in the treatment of ADHD . The authors undertook this study to further evaluate , under double-blind and controlled conditions , the efficacy of selegiline for ADHD in children . A total of 28 children with ADHD as defined by DSM IV were r and omized to selegiline or methylpheni date  dosed on an age and weight-adjusted basis at selegiline 5 mg/day ( under 5 years ) and 10 mg/day ( over 5 years ) ( Group 1 ) and methylpheni date 1 mg/kg/day ( Group 2 ) for a 4-week double-blind clinical trial . The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale . Patients were assessed by a child psychiatrist at baseline , 14 and 28 days after the medication started . No significant differences were observed between the two protocol s on the Parent and Teacher Rating Scale scores . Although the number of dropouts in the methylpheni date group was higher than in the selegiline group , there was no significant difference between the two protocol s in terms of the dropouts . Decreased appetite , difficulty falling asleep and headaches were observed more in the methylpheni date group . The results of this study must be considered preliminary , but they do suggest that selegiline may be beneficial in the treatment of ADHD . In addition , a tolerable side effect profile may be considered as one of the advantages of selegiline in the treatment of ADHD BACKGROUND In the recent past , psychiatrists and paediatricians have avoided prescribing stimulant medication , such as methylpheni date and dexamphetamine to patients with autism spectrum disorders ( ASD ) because of both doubts about efficacy and concern that these medications make stereotypies worse . Recently , a number of small trials have suggested that methypheni date does have a role in the management of hyperactivity in children with autistic spectrum disorders . METHODS Children with ASD and attention deficit hyperactivity disorder ( ADHD ) , and children with ADHD without ASD received st and ard treatment with methypheni date from one specialist centre . A combination of st and ardized and novel outcome tools was used to allow both an exploratory retrospective study of 174 children and then a prospect i ve study of a further 52 children to be carried out . RESULTS After treatment with stimulants , the subjects in both groups showed statistically significant improvements in target symptoms of ' hyperactivity ' , ' impulsivity ' , ' inattention ' , ' oppositionality ' , ' aggression ' and ' intermittent explosive rage ' . The Clinical Global Impression-Improvement and efficacy index measures also improved in each group . In both the retrospective and the prospect i ve studies , there was no statistically significant difference in the degree of improvements between each group . Importantly , neither tics nor repetitive behaviours worsened in either group . Children in the ' ADHD-only ' group who were prescribed stimulants experienced significant ' nausea ' , ' giddiness ' , ' headaches ' and ' sleep difficulties ' , whereas sleep difficulties were the only side effect that emerged in children in the ASD with ADHD group . CONCLUSIONS Both studies presented here support previous findings from smaller studies that show children with autism and ADHD can respond as well to stimulants as children with ADHD alone . Although r and omized controlled trials remain the gold st and ard for efficacy studies , systems like this that allow clinicians to continue rigorous and consistent monitoring for many years have a valuable role to play . Furthermore , such monitoring systems which now exist electronically can easily accumulate large data sets and reveal details about long-term effectiveness and long-term side effects of medication that are unlikely to be discovered in short-term trials Stimulant medications , such as methylpheni date , which are effective treatments for attention deficit hyperactivity disorder ( ADHD ) , enhance brain dopamine signaling . However , the relationship between regional brain dopamine enhancement and treatment response has not been evaluated . Here , we assessed whether the dopamine increases elicited by methylpheni date are associated with long-term clinical response . We used a prospect i ve design to study 20 treatment-naive adults with ADHD who were evaluated before treatment initiation and after 12 months of clinical treatment with a titrated regimen of oral methylpheni date . Methylpheni date -induced dopamine changes were evaluated with positron emission tomography and [11C]raclopride ( D2/D3 receptor radiolig and sensitive to competition with endogenous dopamine ) . Clinical responses were assessed using the Conners ' Adult ADHD Rating Scale and revealed a significant reduction in symptoms of inattention and hyperactivity with long-term methylpheni date treatment . A challenge dose of 0.5 mg/kg intravenous methylpheni date significantly increased dopamine in striatum ( assessed as decreases in D2/D3 receptor availability ) . In the ventral striatum , these dopamine increases were associated with the reductions in ratings of symptoms of inattention with clinical treatment . Statistical parametric mapping additionally showed dopamine increases in prefrontal and temporal cortices with intravenous methylpheni date that were also associated with decreases in symptoms of inattention . Our findings indicate that dopamine enhancement in ventral striatum ( the brain region involved with reward and motivation ) was associated with therapeutic response to methylpheni date , further corroborating the relevance of the dopamine reward/motivation circuitry in ADHD . It also provides preliminary evidence that methylpheni date -elicited dopamine increases in prefrontal and temporal cortices may also contribute to the clinical response 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 BACKGROUND The Multimodal Treatment Study ( MTA ) began as a 14-month r and omized clinical trial of behavioral and pharmacological treatments of 579 children ( 7 - 10 years of age ) diagnosed with attention-deficit/hyperactivity disorder (ADHD)-combined type . It transitioned into an observational long-term follow-up of 515 cases consented for continuation and 289 classmates ( 258 without ADHD ) added as a local normative comparison group ( LNCG ) , with assessment s 2 - 16 years after baseline . METHODS Primary ( symptom severity ) and secondary ( adult height ) outcomes in adulthood were specified . Treatment was monitored to age 18 , and naturalistic subgroups were formed based on three patterns of long-term use of stimulant medication ( Consistent , Inconsistent , and Negligible ) . For the follow-up , hypothesis-generating analyses were performed on outcomes in early adulthood ( at 25 years of age ) . Planned comparisons were used to estimate ADHD-LNCG differences reflecting persistence of symptoms and naturalistic subgroup differences reflecting benefit ( symptom reduction ) and cost ( height suppression ) associated with extended use of medication . RESULTS For ratings of symptom severity , the ADHD-LNCG comparison was statistically significant for the parent/self-report average ( 0.51 ± 0.04 , p < .0001 , d = 1.11 ) , documenting symptom persistence , and for the parent/self-report difference ( 0.21 ± 0.04 , p < .0001 , d = .60 ) , documenting source discrepancy , but the comparisons of naturalistic subgroups reflecting medication effects were not significant . For adult height , the ADHD group was 1.29 ± 0.55 cm shorter than the LNCG ( p < .01 , d = .21 ) , and the comparisons of the naturalistic subgroups were significant : the treated group with the Consistent or Inconsistent pattern was 2.55 ± 0.73 cm shorter than the subgroup with the Negligible pattern ( p < .0005 , d = .42 ) , and within the treated group , the subgroup with the Consistent pattern was 2.36 ± 1.13 cm shorter than the subgroup with the Inconsistent pattern ( p < .04 , d = .38 ) . CONCLUSIONS In the MTA follow-up into adulthood , the ADHD group showed symptom persistence compared to local norms from the LNCG . Within naturalistic subgroups of ADHD cases , extended use of medication was associated with suppression of adult height but not with reduction of symptom severity OBJECTIVE To evaluate the effects of medications used in the treatment of adults with attention-deficit/hyperactivity disorder ( ADHD ) on blood pressure and pulse . METHOD Subjects were those with DSM-III-R-/DSM-IV-diagnosed ADHD enrolled in placebo-controlled studies of 5 different medications for ADHD . Cardiovascular data from these studies of both stimulants ( methylpheni date , amphetamine compounds , pemoline ) and nonstimulants ( bupropion , desipramine ) were reanalyzed for baseline-to-endpoint active-treatment or placebo effects on blood pressure and heart rate . RESULTS There were 125 subjects with a mean + /- SD age of 39 + /- 9 years . In general , active drug treatment for ADHD compared to baseline was associated with several statistically significant changes in systolic blood pressure ( bupropion : + 5.9 mm Hg , p < .05 by paired t test ; amphetamine : + 5.4 mm Hg , p < .05 ) , diastolic blood pressure ( desipramine : + 7.1 mm Hg , p < .05 ) , and heart rate ( bupropion : + 6.9 mm Hg , p < .05 ; amphetamine : + 7.3 mm Hg , p < .05 ; methylpheni date : + 4.5 mm Hg , p < .05 ) . New-onset cases of systolic or diastolic hypertension ( blood pressure > or = 140/90 ) were recorded in 8 % ( 7/89 ) of placebo-treated subjects and 10 % ( 9/89 ) of subjects receiving active medication , regardless of the class ( stimulant , nonstimulant ) . CONCLUSION Both stimulant and nonstimulant catecholaminergic medications used in adults with ADHD are associated with minor , but statistically significant , changes in heart rate and blood pressure that were often observed in those receiving placebo . Given the minor pressor and chronotropic effect of these medications , adults with ADHD should have their blood pressure and heart rate checked at baseline and periodically during treatment BACKGROUND We wanted to study the effects of amphetamine on symptoms of attention-deficit hyperactivity disorder ( ADHD ) over a longer period than has been reported in previous studies of central stimulants in this condition . METHODS Sixty-two children , aged 6 to 11 years , meeting DSM-III-R symptom criteria for ADHD participated in a parallel-group design , r and omized , double-blind , placebo-controlled study of amphetamine treatment . Treatment was not restricted to children with " pure " ADHD , ie , some had comorbid diagnoses . In the amphetamine group , children received active treatment for 15 months . RESULTS Amphetamine was clearly superior to placebo in reducing inattention , hyperactivity , and other disruptive behavior problems and tended to lead to improved results on the Wechsler Intelligence Scale for Children -- Revised . Treatment failure rate was considerably lower and time to treatment failure was longer in the amphetamine group . Adverse effects were few and relatively mild . CONCLUSION The results of this long-term , placebo-controlled study of the central stimulant amphetamine in the treatment of ADHD indicate that there are remaining positive effects of the drug 15 months after starting treatment Treatment with psychostimulant medication has been shown to improve scholastic functioning in children with attention-deficit/hyperactivity disorder ( ADHD ) . However , the extent to which long-term academic gains are apparent in those having received such treatment remains elusive . This study examined prospect ively the relationship of childhood stimulant treatment to academic functioning during adolescence . Children ( n = 169 ) were initially recruited and diagnosed with ADHD when they were 7 - 11 years old . A sub sample of those with childhood ADHD ( n = 90 ) was reevaluated on average 9.13 ( SD = 1.5 ) years later . Prob and s who did and did not receive treatment with stimulant medication were compared to each other and to a never-ADHD comparison group ( n = 80 ) on three subtests from the Wechsler Individual Achievement Test-II ( WIAT-II ) , as well as high school grade point average ( GPA ) and number of retentions in school as derived from school records . Analyses of covariance controlling for severity of childhood ADHD symptoms indicated that prob and s treated with psychostimulant medication achieved better academic outcomes , as measured by WIAT-II subtests and high school GPA , than those not treated with psychostimulants ( p < .05 ) . However , treated prob and s did not fare as well as the never-ADHD comparison group . Psychostimulant treatment for children with ADHD may benefit long-term adolescent academic performance , although the extent of improvement is likely to vary as a function of multiple factors INTRODUCTION Lisdexamfetamine dimesylate ( LDX ) , a prodrug stimulant , is indicated for attention-deficit/hyperactivity disorder ( ADHD ) in children 6 - 12 years of age and in adults . In short-term studies , once-daily LDX provided efficacy throughout the day . This study presented here was conducted to assess the long-term safety , tolerability , and effectiveness of LDX in 6- to 12-year-olds with ADHD . METHODS This open-label , multicenter , single-arm study enrolled children with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition-Text Revision criteria for ADHD . Following 1-week screening and washout periods , subjects were titrated to LDX 30 , 50 , or 70 mg/day over 4 weeks and placed on maintenance treatment for 11 months . The ADHD Rating Scale and Clinical Global Impression-Improvement scale measured effectiveness . RESULTS Of 272 subjects receiving LDX , 147 completed the study . Most adverse events were mild to moderate and occurred during the first 4 weeks . There were no clinical ly meaningful changes in blood pressure or electrocardiographic parameters . From baseline to endpoint , mean ADHD Rating Scale scores improved by 27.2 points ( P<.0001 ) . Improvements occurred during each of the first 4 weeks , and were maintained throughout . Based on Clinical Global Impression-Improvement scale scores , > 80 % of subjects at endpoint and > 95 % of completers at 12 months were rated " improved . " CONCLUSION Long-term 30 , 50 , and 70 mg/day LDX was generally well tolerated and effective in children with ADHD OBJECTIVE The paucity of data concerning the long-term natural history of attention-deficit hyperactivity disorder ( ADHD ) , a common childhood psychiatric disorder , prompted a longitudinal study to investigate the adult sequelae of the childhood disorder . DESIGN Prospect i ve study , follow-up intervals ranging from 13 to 19 years ( mean , 16 years ) , with blind systematic clinical assessment s. SUBJECTS Ninety-one white males ( mean age , 26 years ) , representing 88 % of a cohort systematic ally diagnosed as hyperactive in childhood , and 95 ( 95 % ) of comparison cases of similar race , gender , age , whose teachers had voiced no complaints about their school behavior in childhood . RESULTS Prob and s had significantly higher rates than comparisons of ADHD symptoms ( 11 % vs 1 % ) , antisocial personality disorders ( 18 % vs 2 % ) , and drug abuse disorders ( 16 % vs 4 % ) . Significant comorbidity occurred between antisocial and drug disorders . Educational and occupational achievements were significantly compromised in the prob and s. These disadvantages were independent of psychiatric status . We did not find increased rates of affective or anxiety disorders in the prob and s. CONCLUSIONS Childhood ADHD predicts specific adult psychiatric disorders , namely antisocial and drug abuse disorders . In the adolescent outcome of this cohort , we found that these disturbances were dependent on the continuation of ADHD symptoms . In contrast , in adulthood , antisocial and drug disorders appeared , in part , independent of sustained ADHD . In addition , regardless of psychiatric status , ADHD placed children at relative risk for educational and vocational disadvantage . The results do not support a relationship between childhood ADHD and adult mood or anxiety disorders ABSTRACT Clinical trials with a treatment duration of at least 3 months were review ed to determine the effect of psychostimulants on the core symptoms of attention-deficit hyperactivity disorder ( ADHD ) and on its commonly associated features . Eighteen studies were identified : 17 were studies of  methylpheni date  , 1 was a study of dextroamphetamine , and none involved  pemoline  or  slow-release stimulants . Eleven of these studies were r and omized controlled trials , whereas seven employed quasi-experimental design s without r and omization . The results of r and omized controlled trials showed that psychostimulants provided greater benefit than did the nonr and omized trials , suggesting that the efficacy of extended treatment may have been underestimated because more seriously disturbed children were assigned to medication treatment than to control treatments in nonr and omized trials . Evidence from the more definitive r and omized controlled trials indicates that stimulants are more effective in ameliorating the core behavioral symptoms of ADHD ( restlessness , inattentiveness , impulsiveness ) than placebos , nonpharmacological therapies , or no treatment-at least in 3 - 7-month trials . During extended psychostimulant treatment , few children become symptom-free , clinical effects may diminish with time , and improvement dissipates rapidly upon discontinuation of medication . There is minimal evidence that extended stimulant treatment improves cognitive deficits or associated problems such as conduct disturbance , low self-esteem , poor peer relationships , or academic underachievement . The belief that stimulants do not improve the long-term prognosis of  children with ADHD  may be based on weakly design ed studies that focus on associated rather than core symptoms . A failure to assign patients of similar clinical severity to different treatment conditions may also have contributed to obscuring the efficacy of extended psychostimulant treatments OBJECTIVE To test the hypotheses that in children with attention-deficit/hyperactivity disorder ( ADHD ) ( 1 ) symptoms of ADHD , oppositional defiant disorder , and overall functioning are significantly improved by methylpheni date combined with intensive multimodal psychosocial treatment compared with methylpheni date alone and with methylpheni date plus attention control and ( 2 ) more children receiving combined treatment can be taken off methylpheni date . METHOD One hundred three children with ADHD ( ages 7 - 9 ) , free of conduct and learning disorders , who responded to short-term methylpheni date were r and omized for 2 years to ( 1 ) methylpheni date alone ; ( 2 ) methylpheni date plus psychosocial treatment that included parent training and counseling , social skills training , psychotherapy , and academic assistance , or ( 3 ) methylpheni date plus attention psychosocial control treatment . Assessment s included parent , teacher , and psychiatrist ratings , and observations in academic and gym classes . RESULTS Combination treatment did not lead to superior functioning and did not facilitate methylpheni date discontinuation . Significant improvement occurred across all treatments and continued over 2 years . CONCLUSIONS In stimulant-responsive children with ADHD , there is no support for adding ambitious long-term psychosocial intervention to improve ADHD and oppositional defiant disorder symptoms . Significant benefits from methylpheni date were stable over 2 years There is increased global recognition of attention deficit hyperactivity disorder ( ADHD ) as a serious medical condition with long-term consequences . Although originally conceived of as a childhood disorder , ADHD is being increasingly recognized in adults . Individual geographic regions may have specific interests and objectives for the study of ADHD . A systematic review of  long-term outcomes ( LTOs ) in ADHD was conducted to evaluate research on ADHD LTOs  on a global scale . Studies that were at least 2 years in duration were examined . A total of 351 studies were identified in the final analysis . We identified nine outcomes of interest and classified studies by specific geographical regions , age groups studied and study design by region and over time . Published studies of LTOs in ADHD have increased in all geographical regions over the past three decades , with a peak number of 42 publications in 2008 . This rise in publications on ADHD LTOs may reflect a rise in global interest and recognition of consequences and impairment associated with ADHD . Although many world regions have published on ADHD LTOs , the majority of studies have emerged from the US and Canada , followed by Europe . While investigators in the US and Canada were predominantly interested in drug addiction as a LTO , European research ers were more interested in antisocial behavior , and Eastern Asian investigators focused on both of these LTOs as well as self-esteem . Geographical differences in the focus of ADHD LTO studies may reflect regional variations in cultural values . Proportionally fewer prospect i ve longitudinal studies and proportionally more retrospective and cross-sectional studies have been published in more recent decades . Finally , more studies focusing on ADHD in adolescents and adults have been conducted in recent years , and particularly adolescents in Eastern Asia . These changes in basic study design may reflect an increase in the recognition that ADHD is a lifetime chronic disorder . This systematic review analysis of publication trends in ADHD LTOs reflects geographically based interests that change over time 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 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 test the hypothesis that intensive multimodal psychosocial intervention ( that includes academic assistance and psychotherapy ) combined with methylpheni date significantly enhances the academic performance and emotional status of children with attention-deficit/hyperactivity disorder ( ADHD ) compared with methylpheni date alone and with methylpheni date combined with nonspecific psychosocial treatment ( attention control ) . METHOD One hundred three children with ADHD ( ages 7 - 9 ) , free of conduct and learning disorders , who responded to short-term methylpheni date were r and omized for 2 years to receive one of three treatments : ( 1 ) methylpheni date alone , ( 2 ) methylpheni date plus psychosocial treatment that included academic remediation , organizational skills training , and psychotherapy as well as parent training and counseling and social skills training , or ( 3 ) methylpheni date plus attention control treatment . Children 's function was assessed through academic testing , parent ratings of homework problems , and self-ratings of depression and self-esteem . RESULTS No advantage was found on any measure of academic performance or emotional status for the combination treatment over methylpheni date alone and over methylpheni date plus attention control . Significant improvement occurred across all treatments and was maintained over 2 years . CONCLUSIONS In stimulant-responsive young children with ADHD without learning and conduct disorders , there is no support for academic assistance and psychotherapy to enhance academic achievement or emotional adjustment . Significant short-term improvements were maintained over 2 years OBJECTIVE To test the hypothesis that multimodal psychosocial intervention , which includes parent training , combined with methylpheni date significantly enhances the behavior of parents of children with attention-deficit/hyperactivity disorder ( ADHD ) , compared with methylpheni date alone and compared with methylpheni date and nonspecific psychosocial treatment ( attention control ) . METHOD One hundred three children with ADHD ( ages 7 - 9 ) , free of conduct and learning disorders , who responded to short-term methylpheni date therapy were r and omized for 2 years to receive either ( 1 ) methylpheni date treatment alone ; ( 2 ) methylpheni date plus psychosocial treatment that included parent training and counseling , social skills training , academic assistance , and psychotherapy ; or ( 3 ) methylpheni date plus attention control treatment . Parents rated their knowledge of parenting principles and negative and positive parenting behavior . Children rated their parents ' behavior . RESULTS Psychosocial treatment led to significantly better knowledge of parenting principles but did not enhance parenting practice s , as rated by parents and children . Significant improvement in mothers ' negative parenting occurred across all treatments and was maintained . CONCLUSIONS In nonconduct-disordered , stimulant-treated children with ADHD , parent training does not improve self-rated parental behavior . The benefits of brief stimulant treatment for negative parental behavior are sustained with extended treatment OBJECTIVE Although attention-deficit hyperactivity disorder ( ADHD ) is a well-known risk factor for cigarette smoking , prospect i ve studies aim ed at reducing smoking risk in this population are critically needed . STUDY DESIGN This was a 2-year , prospect i ve , open-label clinical trial of extended-release methylpheni date for smoking prevention in adolescents with ADHD ( n = 154 ) .  Smoking outcomes were assessed with the Fagerstrom Tolerance Question naire . Comparisons were made using data from a historical , naturalistic sample of ADHD ( n = 103 ) and non-ADHD comparators ( n = 188 ) of similar age and sex assessed with the same assessment battery as that used in subjects participating in the clinical trial . RESULTS The smoking rate at endpoint ( mean , 10 months of methylpheni date treatment ) was low in the clinical trial subjects and not significantly different from that in the non-ADHD comparators or the ADHD comparators receiving stimulants naturalistically ( 7.1 % vs 8.0 % vs 10.9 % ; P > .20 ) . In contrast , the smoking rate was significantly lower in the clinical trial subjects than in the naturalistic sample of ADHD comparators who were not receiving stimulant treatment ( 7.1 % vs 19.6 % ; P = .009 [ not significant ] , adjusting for comorbid conduct disorder and alcohol and drug abuse ) . CONCLUSION Although considered preliminary until replicated in future r and omized clinical trials , the findings from this single-site , open-label study suggest that stimulant treatment may contribute to a decreased risk for smoking  in adolescents with ADHD . If confirmed , this finding would have significant clinical and public health impacts 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 Attention-deficit hyperactivity disorder ( ADHD ) is a common disorder of childhood that affects 3 - 6 % of school children . Conventional stimulant medications are recognized as useful symptomatic treatments by both specialists and parents . Nevertheless , approximately 30 % of ADHD children treated with them do not respond adequately or can not tolerate the associated adverse effects . Such difficulties highlight the need for alternative , safe and effective medications in the treatment of this disorder . Theophylline is a psychomotor stimulant most widely used as a broncodilator . Purinergic modulation may be therapeutically beneficial in the treatment of psychiatric disorders . We hypothesized that theophylline would be beneficial for the treatment of ADHD and report results of a trial of theophylline compared with methylpheni date for the treatment of ADHD . A total of 32 children with ADHD as defined by DSM IV were r and omized to theophylline and methylpheni date dosed on an age and weight-adjusted basis at 4 mg/kg/day ( under 12 years ) and 3 mg/kg/day theophylline ( over 12 years ) ( group 1 ) and 1 mg/kg/day methylpheni date ( group 2 ) for a 6-week double-blind and r and omized clinical trial . The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale . Patients were assessed by a child psychiatrist , at baseline and at 14 , 28 and 42 days after start of the medication . No significant differences were observed between theophylline and methylpheni date on the Parent and Teacher Rating Scale scores over the trial ( t = 0.49 , d.f . = 24 P = 0.62 and t = 0.19 , d.f . = 24 P = 0.54 respectively ) . Although the number of dropouts in the methylpheni date group was higher than the theophylline group , there was no significant difference between the two protocol s in terms of the dropouts . In addition , headaches were observed more often in the methylpheni date group . The results suggest that theophylline may be a useful for the treatment of ADHD . In addition , a tolerable side-effect profile is one of the advantages of theophylline in the treatment of ADHD . Nevertheless , our study is small and our results would need to be confirmed in a larger study
These observational studies also showed positive correlations between early recognition of the disorder , stimulant treatment during childhood and favorable long-term outcome in adult ADHD patients .
In conclusion , stimulant therapy of ADHD has long-term beneficial effects and is well tolerated .
Attention-deficit/hyperactivity disorder ( ADHD ) is a common disorder of childhood that often persists into adulthood .
Although stimulant medications are recommended as the first-line treatment for ADHD because of their documented short-term effects in children and adults , less is known about their effects on long-term outcome in adults .
Here we review the long-term efficacy and safety of the stimulant drugs methylpheni date and amphetamine , as well as the related compound atomoxetine .
We performed a systematic review to identify direct and indirect effects of stimulant therapy on long-term outcome in adults .