title: Treatment of ADHD in children with tics: A randomized controlled trial Increasing value and reducing waste in research design, conduct, and analysis Treatment effectiveness of combined medication/behavioural treatment with chinese ADHD children in routine practice. Symptomatic improvement in children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment. A pilot study for augmenting atomoxetine with methylphenidate: safety of concomitant therapy in children with attention-deficit/hyperactivity disorder The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. Effectiveness of an adaptive
  multimodal treatment in children
  with Attention–Deficit Hyperactivity
  Disorder – global outcome Variability in ADHD Care in Community-Based Pediatrics Better Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement Effects of a restricted elimination diet on the behaviour of children with attention-deficit hyperactivity disorder (INCA study): a randomised controlled trial Does brief, clinically based, intensive multimodal behavior therapy enhance the effects of methylphenidate in children with ADHD? A Pilot Study of Methyiphenidate, Clonidine, or the Combination in ADHD Comorbid with Aggressive Oppositional Defiant or Conduct Disorder GRADE guidelines: 3. Rating the quality of evidence. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials A controlled trial of extended-release guanfacine and psychostimulants for attention-deficit/hyperactivity disorder. Clonidine Extended-Release Tablets as Add-on Therapy to Psychostimulants in Children and Adolescents With ADHD Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes.
abstract: Background The treatment of children with attention deficit hyperactivity disorder ( ADHD ) and Tourette syndrome ( TS ) has been problematic because methylpheni date (MPH)—the most commonly used drug to treat ADHD — has been reported to worsen tics and because clonidine (CLON)—the most commonly prescribed alternative — has unproven efficacy . Methods The authors conducted a multicenter , r and omized , double-blind clinical trial in which 136 children with ADHD and a chronic tic disorder were r and omly administered CLON alone , MPH alone , combined CLON + MPH , or placebo ( 2 × 2 factorial design ) . Each subject participated for 16 weeks ( weeks 1–4 CLON/placebo dose titration , weeks 5–8 added MPH/placebo dose titration , weeks 9–16 maintenance therapy ) . Results Thirty-seven children were administered MPH alone , 34 were administered CLON alone , 33 were administered CLON + MPH , and 32 were administered placebo . For our primary outcome measure of ADHD ( Conners Abbreviated Symptom Question naire – Teacher ) , significant improvement occurred for subjects assigned to CLON ( p < 0.002 ) and those assigned to MPH ( p < 0.003 ) . Compared with placebo , the greatest benefit occurred with combined CLON + MPH ( p < 0.0001 ) . CLON appeared to be most helpful for impulsivity and hyperactivity ; MPH appeared to be most helpful for inattention . The proportion of individual subjects reporting a worsening of tics as an adverse effect was no higher in those treated with MPH ( 20 % ) than those being administered CLON alone ( 26 % ) or placebo ( 22 % ) . Compared with placebo , measured tic severity lessened in all active treatment groups in the following order : CLON + MPH , CLON alone , MPH alone . Sedation was common with CLON treatment ( 28 % reported moderate or severe sedation ) , but otherwise the drugs were tolerated well , including absence of any evident cardiac toxicity . Conclusions Methylpheni date and clonidine ( particularly in combination ) are effective for ADHD in children with comorbid tics . Prior recommendations to avoid methylpheni date in these children because of concerns of worsening tics are unsupported by this trial Correctable weaknesses in the design , conduct , and analysis of biomedical and public health research studies can produce misleading results and waste valuable re sources . Small effects can be difficult to distinguish from bias introduced by study design and analyses . An absence of detailed written protocol s and poor documentation of research is common . Information obtained might not be useful or important , and statistical precision or power is often too low or used in a misleading way . Insufficient consideration might be given to both previous and continuing studies . Arbitrary choice of analyses and an overemphasis on r and om extremes might affect the reported findings . Several problems relate to the research workforce , including failure to involve experienced statisticians and method ologists , failure to train clinical research ers and laboratory scientists in research methods and design , and the involvement of stakeholders with conflicts of interest . Inadequate emphasis is placed on recording of research decisions and on reproducibility of research . Finally , reward systems incentivise quantity more than quality , and novelty more than reliability . We propose potential solutions for these problems , including improvements in protocol s and documentation , consideration of evidence from studies in progress , st and ardisation of research efforts , optimisation and training of an experienced and non-conflicted scientific workforce , and reconsideration of scientific reward systems BACKGROUND The effectiveness of a combined methylpheni date /behavioural treatment ( BT ) versus methylpheni date -only for Chinese children with Attention-Deficit/Hyperactivity Disorder ( ADHD ) was tested in routine clinical practice in Hong Kong . METHODS A r and omized group comparison design was adopted with two treatment conditions ( methylpheni date -only ; methylpheni date /BT ) , which lasted for 6 months . There were four assessment time points ( pre-treatment , post-treatment , and 6-month and 12-month follow-ups ) , using the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviours ( SWAN ) Rating Scale . Parental attitude toward different treatment options of ADHD was also assessed at pre-treatment and post-treatment . Participants included 90 Chinese ADHD children ( mean age=8 years , SD=.95 ) . RESULTS The combination of BT and a low-dose methylpheni date was significantly more effective than methylpheni date -only in reducing ADHD and ODD symptoms at post-treatment . At follow-ups , the benefits of the combined treatment were maintained , while the methylpheni date -only group caught up in improvement in ADHD symptoms . Parents in both treatment conditions showed improved attitude toward medication after the 6-month treatment phase , while their attitude toward BT was positive all along . CONCLUSIONS This study supported the added benefits of BT , on top of medication , for Chinese ADHD children in routine practice with treatments conducted by regular medical and paramedical staffs 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 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 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field BACKGROUND Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder ( ADHD ) , but no longer-term ( i.e. , > 4 months ) investigations have compared these 2 treatments or their combination . METHODS A group of 579 children with ADHD Combined Type , aged 7 to 9.9 years , were assigned to 14 months of medication management ( titration followed by monthly visits ) ; intensive behavioral treatment ( parent , school , and child components , with therapist involvement gradually reduced over time ) ; the two combined ; or st and ard community care ( treatments by community providers ) . Outcomes were assessed in multiple domains before and during treatment and at treatment end point ( with the combined treatment and medication management groups continuing medication at all assessment points ) . Data were analyzed through intent-to-treat r and om-effects regression procedures . RESULTS All 4 groups showed sizable reductions in symptoms over time , with significant differences among them in degrees of change . For most ADHD symptoms , children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care . Combined and medication management treatments did not differ significantly on any direct comparisons , but in several instances ( oppositional/aggressive symptoms , internalizing symptoms , teacher-rated social skills , parent-child relations , and reading achievement )  combined treatment proved superior to intensive behavioral treatment and /or community care while medication management did not . Study medication strategies were superior to community care treatments , despite the fact that two thirds of community-treated subjects received medication during the study period . CONCLUSIONS For ADHD symptoms , our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication . Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms , but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes Abstract Background The meaning of different components within a multimodal treatment of ADHD remains to be further clarified . Objective To evaluate the effectiveness of  behaviour therapy  and drug treatment  within an adaptive and individually tailored multimodal treatment for children with ADHD . Method After an initial psychoeducation n = 75 school-children aged 6–10 years with a diagnosis of ADHD/HKD were assigned to either behaviour therapy ( including continued psychoeducation ) or medical management with methylpheni date plus psychoeducation . Depending on the effectiveness , the treatment was either terminated ( if totally effective ) with long – term aftercare and continuation of medication if needed , or ( if partially effective ) the other treatment component was added ( combined treatment ) , or ( if ineffective ) the treatment components were replaced . Thus a treatment rationale was applied which result ed in an adaptive and individually tailored therapy – similar to a strategy that may be useful in clinical practice . Results Of the children who started with behaviour therapy after initial psychoeducation 26 % received a combined treatment in later treatment stages . In most of the cases ( 82 % ) with initial medical management , behaviour therapy was added . ADHD symptoms , individually defined behaviour problems and comorbid symptoms were significantly reduced during the course of treatment . On core measures large pre – post effect sizes were found . On teacher ratings  combined treatment was more effective than behaviour therapy . Conclusions Both , behaviour therapy and combined treatment are effective interventions within an adaptive and individually tailored multimodal treatment strategy BACKGROUND : Although many efforts have been made to improve the quality of care delivered to children with attention-deficit/hyperactivity disorder ( ADHD ) in community-based pediatric setting s , little is known about typical ADHD care in these setting s other than rates garnered through pediatrician self-report . METHODS : Rates of evidence -based ADHD care and sources of variability ( practice -level , pediatrician-level , patient-level ) were determined by chart review s of a r and om sample of 1594 patient charts across 188 pediatricians at 50 different practice s. In addition , the associations of Medicaid-status and practice setting ( ie , urban , suburban , and rural ) with the quality of ADHD care were examined . RESULTS :  Parent- and teacher-rating scales were used during ADHD assessment with approximately half of patients . The use of Diagnostic and Statistical Manual of Mental Disorders criteria was documented in 70.4 % of patients . The vast majority ( 93.4 % ) of patients with ADHD were receiving medication and only 13.0 % were receiving psychosocial treatment .  Parent- and teacher-ratings were rarely collected to monitor treatment response or side effects . Further , fewer than half ( 47.4 % ) of children prescribed medication had contact with their pediatrician within the first month of prescribing . Most variability in pediatrician-delivered ADHD care was accounted for at the patient level ; however , pediatricians and practice s also accounted for significant variability on specific ADHD care behaviors . CONCLUSIONS : There is great need to improve the quality of ADHD care received by children in community-based pediatric setting s. Improvements will likely require systematic interventions at the practice and policy levels to promote change Reporting harms may cause more trouble and discredit than the fame and glory associated with successful reporting of benefits ( 1 ) . The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement , a checklist ( Table 1 ) flow diagram first published in 1996 and revised 5 years later ( 2 , 3 ) , is an effort to st and ardize , and thereby improve , published reports of r and omized , controlled trials ( RCTs ) . One of the additions to the 2001 revision was an item about reporting adverse events . This single item did not do full justice to the importance of harms-related issues . The CONSORT Group met in September 2001 to discuss how to correct this deficiency . We aim ed to provide evidence -based guidance on the reporting of harms in RCTs . First , we search ed MEDLINE , EMBASE , Web of Science , and the Cochrane Library using a wide array of terms related to harms and identified pertinent evidence . We also communicated with experts and review ed bibliographies of identified articles to find additional studies . At a meeting in Montebello , Quebec , Canada , in May 2003 , CONSORT Group members , including several journal editors and additional experts in related fields , held a structured discussion of recommendations about reporting of harms-related issues in RCTs . The discussion s led to a written document that we circulated among the team members for comment . The present manuscript describes our recommendations on the appropriate reporting of harms in RCTs . Table 1 . Original CONSORT Checklist The terminology of harms-related issues in RCTs is confusing and often misleading or misused ( see Glossary ) ( 4 , 5 ) . Safety is a reassuring term that may obscure the real and potentially major harms that drugs and other interventions may cause . We encourage authors to use the term harms instead of safety . In addition to misused terminology , reporting of harms in RCTs has received less attention than reporting of efficacy and effectiveness and is often inadequate ( 6 - 14 ) . In short , both scientific evidence and ethical necessity call for action to improve the quality of reporting of harms in RCTs ( 15 , 16 ) . Here , we present a set of recommendations and accompanying explanations for the proper reporting of harms in RCTs . These recommendations should complement the existing CONSORT statement ( Table 2 ) . Examples are presented on the Annals and CONSORT ( www.consort-statement.org ) Web sites . Table 2 . Checklist of Items To Include When Reporting Harms in R and omized , Controlled Trials Recommendations Title and Abstract Recommendation 1 . If the study collected data on harms and benefits , the title or abstract should so state . The title should mention harms if the study of harms was a key trial objective . Many phase I and phase II trials , some phase II/III trials , and most phase IV trials ( 17 , 18 ) target harms as primary outcomes . Yet , the title and abstract seldom contain the word harm . Among 375143 entries in the Cochrane Central Register of Controlled Trials ( Cochrane Library , issue 3 , 2003 ) , search ing titles with the search terms harm or harms yielded 337 references ( compared with 55374 for efficacy and 23415 for safety ) . Of the 337 , excluding several irrelevant articles on self-harm or harm reduction , only 3 trial reports and 2 abstract s contained the word harm in their titles . Authors should present information on harms in the abstract . If no important harms occurred , authors should so state . Explicit reference to the reporting of adverse events in the title or abstract is also important for appropriate data base indexing and information retrieval ( 19 ) . Introduction Background Recommendation 2 . If the trial addresses both harms and benefits , the introduction should so state . The introduction states the scientific background and rationale of an RCT . This requires a balanced presentation whereby the possible benefits of the intervention under investigation are outlined along with the possible harms associated with the treatment . R and omized , controlled trials that focus primarily on harms should clearly state this interest when describing the study objectives in the Introduction and in defining these objectives in the Methods . Methods Outcomes Recommendation 3 . List addressed adverse events with definitions for each ( with attention , when relevant , to grading , expected vs. unexpected events , reference to st and ardized and vali date d definitions , and description of new definitions ) . The Methods section should succinctly define the recorded adverse events ( clinical and laboratory ) . Authors should clarify whether the reported adverse events encompass all the recorded adverse events or a selected sample . They should explain how , why , and who selected adverse events for reporting . In trials that do not mention harms-related data , the Methods section should briefly explain the reason for the omission ( for example , the design did not include the collection of any information on harms ) . Authors should also be explicit about separately reporting anticipated and unexpected adverse events . Expectation may influence the incidence of reported or ascertained adverse events . Making participants aware in the consent form of the possibility of a specific adverse event ( priming ) may increase the reporting rate of the event ( 20 ) . Another example of priming is the finding that the rates of withdrawals due to adverse events and the rates of specific adverse events were significantly higher in trials of aspirin , diclofenac , or indomethacin with comparator drugs compared with placebo-controlled trials ( 21 ) . Presumably , participants were more eager to come forth and report an adverse event or to withdraw from treatment when they knew they could not be receiving inactive placebo . Authors should report whether they used st and ardized and vali date d measurement instruments for adverse events . Several medical fields have developed st and ardized scales ( 22 - 32 ) . Use of nonvali date d scales is common . The source document for well-established definitions and scales should be referenced . New definitions for adverse events should be explicit and clear . Authors should describe how they developed and vali date d new scales . For interventions that target healthy individuals ( for example , many preventive interventions ) , any harm , however minor , may be important to capture and report because the balance of harms and benefits may easily lean toward harms in a low-risk population . For other population s and for interventions that improve major outcomes ( for example , survival ) , severe and life-threatening adverse events may be the only ones that are important in the balance of benefits and harms . Recommendation 4 . Clarify how harms-related information was collected ( mode of data collection , timing , attribution methods , intensity of ascertainment , and harms-related monitoring and stopping rules , if pertinent ) . It is important to describe the question naires , interviews , and tests used to collect information on harms , as well as their timing during follow-up . Passive surveillance of harms leads to fewer recorded adverse events than active surveillance ( 4 ) . Open-ended questions may yield different information , both quantitatively and qualitatively , than structured question naires ( 33 ) . Studies of nonsteroidal , anti-inflammatory drugs ( NSAIDs ) exemplify how data collection methods can affect the detection and reporting of harms . When selective NSAIDs with fewer gastrointestinal adverse events became available , trials reported more than 10 times as many ulcers when comparing these drugs with older NSAIDs as when older NSAIDs were compared with placebo . In the newer trials , more ulcers were detected because participants had regular endoscopy , and the case definition of ulcers was more sensitive ( 34 ) . Authors should specify the time frame of surveillance for adverse events . Some investigators stop recording adverse events at the end of the intervention period or a certain number of days afterward ( for example , 30 days after discontinuation of drug therapy ) and miss events with long latency ( 35 ) . Surgical trials often capture only the adverse events that occur intraoperatively . Several important surgical complications are likely to occur later . Finally , in crossover trials , delayed events might occur while the patient is taking a subsequent assigned treatment . Attribution is the process of deciding whether an adverse event is related to the intervention . Whenever authors filter events through an attribution process , they should state who makes the attribution ( investigators , participants , sponsors , or combinations ) , whether the process is blinded to assigned treatment , and what definitions of adverse events they use ( 4 ) . Discontinuations and withdrawals due to adverse events are especially important because they reflect the ultimate decision of the participant and /or physician to discontinue treatment . Although treatment may occasionally be discontinued for mild or moderate adverse events , attributing discontinuation to a specific reason ( to toxicity , lack of efficacy , other reasons , or combinations of reasons ) may be difficult . For example , in psychopharmacology , dropouts may reflect treatment ineffectiveness as much as toxicity-related intolerance ( 36 ) . Trial reports should specify who gave the reasons for discontinuation ( participants or physicians ) and whether attribution was blinded to the assigned treatment . For example , even in blinded trials , participants and their clinicians are often unblinded before they decide whether to discontinue the intervention . It is important to report participants who are nonadherent or lost to follow-up because their actions may reflect their inability to tolerate the intervention . Moreover , authors should specify how they h and led withdrawals in the analyses of the data . R and omized , controlled trials should report any plan for monitoring for harms and rules for stopping the trial because of harms ( 37 ) . They should clarify whether stopping guidelines examine benefits and harms BACKGROUND The effects of a restricted elimination diet in children with attention-deficit hyperactivity disorder ( ADHD ) have mainly been investigated in selected subgroups of patients . We aim ed to investigate whether there is a connection between diet and behaviour in an unselected group of children . METHODS The Impact of Nutrition on Children with ADHD ( INCA ) study was a r and omised controlled trial that consisted of an open-label phase with masked measurements followed by a double-blind crossover phase . Patients in the Netherl and s and Belgium were enrolled via announcements in medical health centres and through media announcements . R and omisation in both phases was individually done by r and om sampling . In the open-label phase ( first phase ) , children aged 4 - 8 years who were diagnosed with ADHD were r and omly assigned to 5 weeks of a restricted elimination diet ( diet group ) or to instructions for a healthy diet ( control group ) . Thereafter , the clinical responders ( those with an improvement of at least 40 % on the ADHD rating scale [ ARS ] ) from the diet group proceeded with a 4-week double-blind crossover food challenge phase ( second phase ) , in which high-IgG or low-IgG foods ( classified on the basis of every child 's individual IgG blood test results ) were added to the diet . During the first phase , only the assessing paediatrician was masked to group allocation . During the second phase ( challenge phase ) , all persons involved were masked to challenge allocation . Primary endpoints were the change in ARS score between baseline and the end of the first phase ( masked paediatrician ) and between the end of the first phase and the second phase ( double-blind ) , and the abbreviated Conners ' scale ( ACS ) score ( unmasked ) between the same timepoints . Secondary endpoints included food-specific IgG levels at baseline related to the behaviour of the diet group responders after IgG-based food challenges . The primary analyses were intention to treat for the first phase and per protocol for the second phase . INCA is registered as an International St and ard R and omised Controlled Trial , number IS RCT N 76063113 . FINDINGS Between Nov 4 , 2008 , and Sept 29 , 2009 , 100 children were enrolled and r and omly assigned to the control group ( n=50 ) or the diet group ( n=50 ) . Between baseline and the end of the first phase , the difference between the diet group and the control group in the mean ARS total score was 23·7 ( 95 % CI 18·6 - 28·8 ; p<0·0001 ) according to the masked ratings . The difference between groups in the mean ACS score between the same timepoints was 11·8 ( 95 % CI 9·2 - 14·5 ; p<0·0001 ) . The ARS total score increased in clinical responders after the challenge by 20·8 ( 95 % CI 14·3 - 27·3 ; p<0·0001 ) and the ACS score increased by 11·6 ( 7·7 - 15·4 ; p<0·0001 ) . In the challenge phase , after challenges with either high-IgG or low-IgG foods , relapse of ADHD symptoms occurred in 19 of 30 ( 63 % ) children , independent of the IgG blood levels . There were no harms or adverse events reported in both phases . INTERPRETATION A strictly supervised restricted elimination diet is a valuable instrument to assess whether ADHD is induced by food . The prescription of diets on the basis of IgG blood tests should be discouraged . FUNDING Foundation of Child and Behaviour , Foundation Nuts Ohra , Foundation for Children 's Welfare Stamps Netherl and s , and the KF Hein Foundation Objective The additional value of a short-term , clinical ly based , intensive multimodal behavior therapy to optimally titrated methylpheni date in children with attention-deficit hyperactivity disorder ( ADHD ) was investigated . Method Fifty children with ADHD ( ages 8–12 ) were r and omized to treatment of methylpheni date or treatment with methylpheni date combined with 10 weeks of multimodal behavior therapy . The multimodal behavior therapy consisted of a child and parent behavioral therapy and a teacher behavioral training . Assessment s included parent , teacher and child ratings of ADHD symptoms , oppositional and conduct behavior , social skills , parenting stress , anxiety and self-worth . Results Both treatment conditions yielded significant improvements on all outcome domains . No significant differences were found between both treatments . Conclusions No evidence was found for the additive effect of multimodal behavior therapy next to optimally titrated methylpheni date . Clinical implication sThis study does not support the expectation that optimally dosed stimulant treated children with ADHD should routinely receive psychosocial treatment to further reduce ADHD- and related symptoms A pilot comparison of the safety and efficacy of methylpheni date ( MPH ) combined with clonidine , clonidine monotherapy , or MPH monotherapy in 6to 16-year-old children diagnosed with attention deficit hyperactivity disorder ( ADHD ) and comorbid aggressive oppositional defiant disorder or conduct disorder was completed . Study design was a 3-month , r and omized , blinded , group comparison with eight subjects per group . No placebo comparison was used . All three treatment groups showed significant improvements in attention deficits , impulsivity , oppositional , and conduct disordered symptoms as assessed by parent and teacher rating scales and laboratory measures . Significant differences among treatment groups were found only on a few measures . Only the clonidine monotherapy group showed significantly decreased fine motor speed . These results suggest the safety and efficacy of clonidine alone or in combination with MPH for the treatment of ADHD and aggressive oppositional and conduct disorders This article introduces the approach of GRADE to rating  quality of evidence .  GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials OBJECTIVE To examine efficacy , tolerability , and safety of guanfacine extended release ( GXR ; ≤4 mg/d ) adjunctive to a long-acting psychostimulant for the treatment of attention-deficit/hyperactivity disorder ( ADHD ) in children and adolescents 6 to 17 years of age with suboptimal , but partial , response to psychostimulant alone . METHOD In this multicenter , 9-week , double-blind , placebo-controlled , dose-optimization study , subjects ( N = 461 ) continued their stable dose of psychostimulant given in the morning and were r and omized to receive GXR in the morning ( GXR AM ) , GXR in the evening ( GXR PM ) , or placebo .  Efficacy measures included ADHD Rating Scale IV ( ADHD-RS-IV ) and Clinical Global Impressions of Severity of Illness ( CGI-S ) and Improvement ( CGI-I ) scales . Safety measures included adverse events ( AEs ) , vital signs , electrocardiograms , and laboratory evaluations . RESULTS At endpoint , GXR treatment groups showed significantly greater improvement from baseline ADHD-RS-IV total scores compared with placebo plus psychostimulant ( GXR AM , p = .002 ; GXR PM , p < .001 ) . Significant benefits of GXR treatment versus placebo plus psychostimulant were observed on the CGI-S ( GXR AM , p = .013 ; GXR PM , p < .001 ) and CGI-I ( GXR AM , p = .024 ; GXR PM , p = .003 ) . At endpoint , small mean decreases in pulse , systolic , and diastolic blood pressure were observed in GXR treatment groups versus placebo plus psychostimulant . No new safety signals emerged following administration of GXR with psychostimulants versus psychostimulants alone . Most AEs were mild to moderate in severity . CONCLUSIONS Morning or evening GXR administered adjunctively to a psychostimulant showed significantly greater improvement over placebo plus psychostimulant in ADHD symptoms and generated no new safety signals . Clinical trial registration information-Efficacy and Safety of SPD503 in Combination With Psychostimulants ; http://www . clinical trials.gov ; NCT00734578 OBJECTIVE : To assess the efficacy and safety of clonidine hydrochloride extended-release tablets ( CLON-XR ) combined with stimulants ( ie , methylpheni date or amphetamine ) for attention-deficit/hyperactivity disorder ( ADHD ) . PATIENTS AND METHODS : In this phase 3 , double-blind , placebo-controlled trial , children and adolescents with hyperactive- or combined-subtype ADHD who had an inadequate response to their stable stimulant regimen were r and omized to receive CLON-XR or placebo in combination with their baseline stimulant medication . Predefined efficacy measures evaluated change from baseline to week 5 . Safety was assessed by spontaneously reported adverse events , vital signs , electrocardiogram recordings , and clinical laboratory values . Improvement from baseline for all efficacy measures was evaluated using analysis of covariance . RESULTS : Of 198 patients r and omized , 102 received CLON-XR plus stimulant and 96 received placebo plus stimulant . At week 5 , greater improvement from baseline in ADHD Rating Scale IV ( ADHD-RS-IV ) total score ( 95 % confidence interval : −7.83 to −1.13 ; P = .009 ) , ADHD-RS-IV hyperactivity and inattention subscale scores ( P = .014 and P = .017 , respectively ) , Conners ' Parent Rating Scale scores ( P < .062 ) , Clinical Global Impression of Severity ( P = .021 ) , Clinical Global Impression of Improvement ( P = .006 ) , and Parent Global Assessment ( P = .001 ) was observed in the CLON-XR plus stimulant group versus the placebo plus stimulant group . Adverse events and changes in vital signs in the CLON-XR group were generally mild . CONCLUSIONS : The results of this study suggest that CLON-XR in combination with stimulants is useful in reducing ADHD in children and adolescents with partial response to stimulants OBJECTIVE To determine the efficacy and safety of clonidine , used alone or in combination with methylpheni date , in treating attention-deficit/hyperactivity disorder ( ADHD ) . METHOD A 16-week , r and omized , double-blind , placebo-controlled clinical trial was conducted in 122 children , ages 7 to 12 , with any subtype of ADHD , r and omly assigned to clonidine , methylpheni date , clonidine in combination with methylpheni date , or placebo according to a 2 x 2 factorial design . In two successive 4-week titration periods , clonidine ( or matching placebo ) and added methylpheni date ( or matching placebo ) were adjusted to optimal doses and then continued for 8 weeks . The primary efficacy outcome was changed from baseline to week 16 on the Conners Teachers Abbreviated Symptom Question naire . Secondary outcomes included the Conners Abbreviated Symptom Question naire for Parents and the Children 's Global Assessment Scale . RESULTS On the Conners Teachers Abbreviated Symptom Question naire , clonidine was not found to improve ADHD symptoms , whereas subjects treated with methylpheni date showed significant improvement compared to those not treated with methylpheni date . Subjects treated with clonidine had greater improvements on the Conners Abbreviated Symptom Question naire for Parents and Children 's Global Assessment Scale , but also a higher rate of sedation compared with subjects not treated with clonidine . CONCLUSIONS Based on the Conners Teachers Abbreviated Symptom Question naire , methylpheni date offers the best combination of efficacy and tolerability for ADHD . Clonidine was well tolerated despite the frequency of sedation and did offer some benefit
target: At the class level , behavioural therapy ( alone or in combination with stimulants ) , stimulants , and non-stimulant seemed significantly more efficacious than placebo .
  Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants .
  Stimulants seemed superior to behavioural therapy , cognitive training and non-stimulants .
  Behavioural therapy , stimulants and their combination showed the best profile of acceptability .
  Stimulants and non-stimulants seemed well tolerated .
  Among medications , methylpheni date , amphetamine , atomoxetine , guanfacine and clonidine seemed significantly more efficacious than placebo .
  Methylpheni date and amphetamine seemed more efficacious than atomoxetine and guanfacine .
  Methylpheni date and clonidine seemed better accepted than placebo and atomoxetine .
  Most of the efficacious pharmacological treatments were associated with harms ( anorexia , weight loss and insomnia ) , but an increased risk of serious adverse events was not observed .
  There is lack of evidence for cognitive training , neurofeedback , antidepressants , antipsychotics , dietary therapy , fatty acids , and other complementary and alternative medicine .
  Clinical differences may exist between the pharmacological and non-pharmacological treatment used for the management of ADHD .
background: BACKGROUND Attention deficit hyperactivity disorder ( ADHD ) is one of the most commonly diagnosed psychiatric disorders in childhood .
  A wide variety of treatments have been used for the management of ADHD .
  We aim ed to compare the efficacy and safety of pharmacological , psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents .