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Le TDAH chez les enfants et les adolescents, partie 2 : Le traitement
Abstract
Le trouble de déficit de l’attention/hyperactivité (TDAH) est un trouble neurodéveloppemental chronique. La Société canadienne de pédiatrie a préparé trois documents de principes après avoir effectué des analyses bibliographiques systématiques. Leurs objectifs s’établissent comme suit :
• 1) Résumer les données probantes cliniques à jour sur le TDAH.
• 2) Établir une norme pour les soins du TDAH.
• 3) Aider les cliniciens canadiens à prendre des décisions éclairées et fondées sur des données probantes pour rehausser la qualité des soins aux enfants et aux adolescents qui présentent cette affection.
La partie 2, axée sur le traitement, porte sur les données probantes et le contexte entourant diverses approches cliniques, la combinaison des interventions comportementales et pharmacologiques pour assurer un traitement plus efficace, le rôle de la formation des parents et des enseignants (ou des autres personnes qui s’occupent de l’enfant), le recours aux stimulants et aux non-stimulants, leurs effets et leurs risques, leur posologie et les protocoles de surveillance. Les recommandations thérapeutiques reposent sur les lignes directrices à jour, les données probantes tirées de publications scientifiques et le consensus d’experts.
... La psychoéducation fait partie des recommandations interna tionales [17] en première intention ou en accompagnement des stratégies médicamenteuses en fonction de la sévérité du trouble. Elle est destinée aux personnes présentant un TDAH quel que soit leur âge et à leur entourage. ...
Points essentiels
– Le trouble déficit de l'attention avec ou sans hyperactivité
(TDAH)se caractérise par des difficultés de régulation chez
les enfants et les adultes atteints : régulation de l'attention,
des émotions, du comportement et de la motivation.
– Avant d'envisager une prescription de méthylphénidate, les
recommandations d'experts insis tent sur la mise en place
de thérapies non médicamenteuses pour améliorer la qualité
de vie des sujets atteints et de celles de leurs proches.
– Cet article propose un aperçu desstratégiesthérapeutiques
qui existent chez l'enfant et chez l'adulte et qui pourront être
proposées après évaluation des besoins spécifiques : la
psychoéducation, les programmes d'entraînement aux
habiletés parentales, les programmes de thérapies
comportemen tales, cognitives et émotionnelles (TCCE) et
les programmes de remédiation cognitive.
Key points
Non-pharmacological management of ADHD
– Attention Deficit Disorder Hyperactivity (ADHD) is
characterized by difficulties in regulating the attention,
emotions, behavior and motivation of affected children and
adults. – Before considering prescribing methylphenidate,
expert recommendations insist on the use of
non-pharmacological treatment to improve the quality of life
of sufferers and their families. – This article provides an
overview of the therapeutic strategies available for children
and adults, which may be offered following an assessment of
specific needs: psychoeducation, parenting skills training
programs, behavioral, cognitive and emotional therapy (CBT)
programs and cognitive remediation programs.
... Toutefois, chez certains jeunes, des effets secondaires considérables associés à la prise de médication sont documentés tels que des troubles de l'humeur et du sommeil ainsi qu'une perte d'appétit importante (Feldman et al., 2018). À cet égard, le Journal de Québec a publié le 31 janvier 2019 une lettre signée par 45 pédiatres qui signalent la surmédication des jeunes ayant un diagnostic de TDAH au Québec (Dion-Viens, 2019). ...
L'étude présentée dans ce mémoire a pour objectif général d'explorer les effets perçus d'une formation en ligne ouverte à tous (MOOC) portant sur le trouble du déficit de l'attention/hyperactivité (TDAH). Plus précisément, elle vise à mesurer les effets perçus par les enseignants de ce MOOC sur leur sentiment d'efficacité personnelle (SEP) à enseigner aux élèves présentant un TDAH. Cette recherche vise également à explorer et documenter les besoins de formation des participants, la capacité du MOOC à y répondre, le niveau de satisfaction des participants, la contribution perçue des modalités de formation-accompagnement déployées sur le développement professionnel continu des participants et les effets perçus au regard des comportements des élèves visés par les interventions. Divisé en quatre modules répartis sur sept semaines, le MOOC Le point sur le TDAH : comprendre, soutenir et accompagner les jeunes propose un tour d'horizon du TDAH fondé sur la littérature scientifique récente afin de permettre aux enseignants de mieux comprendre ses symptômes et ses manifestations et d'explorer diverses approches d'intervention susceptibles de les aider à mieux soutenir leurs élèves dans leur développement et leurs apprentissages. Le MOOC a été évalué auprès d'enseignants ayant participé à la formation (n = 178) à l'aide d'un devis de recherche pré-expérimental à deux temps de mesure. Des analyses descriptives ainsi que des test-t pour groupes appariés ont été effectués afin d'atteindre les objectifs de la recherche. Les résultats mettent en évidence la satisfaction des participants et indiquent que la formation semble avoir contribué au développement du SEP et des connaissances des enseignants ainsi qu'à l'amélioration de leurs pratiques d'intervention envers les élèves présentant un TDAH. Par le fait même, les résultats obtenus montrent que les enseignants ont perçu une amélioration des comportements chez les élèves ciblés par les interventions déployées. Enfin, ce mémoire se conclut par une discussion portant sur les résultats, les limites de l'étude et les implications pour les futures recherches et les milieux scolaires.
Résumé
Les dispensateurs de soins pédiatriques sont souvent le premier point de contact des enfants et des adolescents aux prises avec des problèmes de santé mentale, mais ils ne possèdent pas nécessairement les ressources (p. ex., l’accès à une équipe multidisciplinaire) ni la formation nécessaires pour procéder à leur dépistage ou à leur prise en charge. Le présent document de principes conjoint décrit les principaux rôles et les principales compétences à maîtriser pour évaluer et traiter les problèmes de santé mentale chez les enfants et les adolescents, de même que les facteurs qui optimisent le plus possible l’évolution de la santé mentale dans ces groupes d’âge. Il contient des conseils fondés sur des données probantes à propos du dépistage des préoccupations en matière de santé mentale chez les jeunes et leur famille ainsi qu’à propos des échanges sur le sujet. Les interventions préventives et thérapeutiques dont l’efficacité est démontrée en milieu communautaire sont abordées. Le présent document de principes, qui est fondamental, traite également des changements à l’enseignement de la médecine ainsi qu’aux systèmes et aux politiques de santé qui s’imposent pour améliorer la pratique clinique et les efforts de revendications au Canada, y compris les modèles de rémunération appropriés, les approches des soins abordées étape par étape, le financement gouvernemental ciblé, l’enseignement et la formation professionnelle.
The purpose of this research was to update the series of articles on evidence-based treatment for children and adolescents with attention deficit/hyperactivity disorder that have appeared in this journal (Evans, Owens & Bunford, 2014; Pelham & Fabiano, 2008; Pelham, Wheeler, & Chronis, 1998). We completed a systematic review of the literature published between 2012 and 2016 to establish levels of evidence for psychosocial treatments for these youth. We identified articles using criteria established by the Society of Clinical Child and Adolescent Psychology using keyword searches of abstracts and titles. Articles were classified according to a modified version of the Division 12 task force guidelines that was used in other reviews in this series. The results revealed that findings are becoming increasingly nuanced with variations in levels of evidence related to ages of the children and characteristics of the specific treatment. In addition, we focused our critique on generalization of treatment effects across settings and time and on sample diversity (with regard to ethnicity and levels of parent education) in relation to the population. Children of parents with higher levels of education than average appear to be overrepresented in the literature. Implications for future treatment development and evaluation and for dissemination research are discussed.
Background:
The Multimodal Treatment Study (MTA) began as a 14-month randomized 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 assessments 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.
Previous studies have suggested that risk of psychotic events may be increased in children exposed to methylphenidate (MPH). However, this risk has not been fully examined and the possibility of confounding factors has not been excluded. Patients aged 6-19 years who received at least one MPH prescription were identified using Hong Kong population-based electronic medical records on the Clinical Data Analysis & Reporting System (2001-2014). Using the self-controlled case series design, relative incidence of psychotic events was calculated comparing periods when patients were exposed to MPH with non-exposed periods. Of 20 586 patients prescribed MPH, 103 had an incident psychotic event; 72 (69.9%) were male and 31 (30.1%) female. The mean age at commencement of observation was 6.95 years and the mean follow-up per participant was 10.16 years. On average, each participant was exposed to MPH for 2.17 years. The overall incidence of psychotic events during the MPH exposure period was 6.14 per 10 000 patient-years. No increased risk was found during MPH exposed compared to non-exposed periods (incidence rate ratio (IRR) 1.02 (0.53-1.97)). However, an increased risk was found during the pre-exposure period (IRR 4.64 (2.17-9.92)). Results were consistent across all sensitivity analyses. This study does not support the hypothesis that MPH increases risk of incident psychotic events. It does indicate an increased risk of psychotic events prior to the first prescription of MPH, which may be due to an association between psychotic events and the behavioural and attentional symptoms that led to psychiatric assessment and initiation of MPH treatment.
Study question Is methylphenidate beneficial or harmful for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents?
Methods Electronic databases were searched up to February 2015 for parallel and crossover randomised clinical trials comparing methylphenidate with placebo or no intervention in children and adolescents with ADHD. Meta-analyses and trial sequential analyses (TSA) were conducted. Quality was assessed using GRADE. Teachers, parents, and observers rated ADHD symptoms and general behaviour.
Study answer and limitations The analyses included 38 parallel group trials (n=5111, median treatment duration 49 days) and 147 crossover trials (n=7134, 14 days). The average age across all studies was 9.7 years. The analysis suggested a beneficial effect of methylphenidate on teacher rated symptoms in 19 parallel group trials (standardised mean difference (SMD) −0.77, n=1698), corresponding to a mean difference of −9.6 points on the ADHD rating scale. There was no evidence that methylphenidate was associated with an increase in serious adverse events (risk ratio 0.98, nine trials, n=1532; TSA adjusted intervention effect RR 0.91). Methylphenidate was associated with an increased risk of non-serious adverse events (1.29, 21 trials, n=3132; TSA adjusted RR 1.29). Teacher rated general behaviour seemed to improve with methylphenidate (SMD −0.87, five trials, n=668) A change of 7 points on the child health questionnaire (CHQ) has been deemed a minimal clinically relevant difference. The change reported in a meta-analysis of three trials corresponds to a mean difference of 8.0 points on the CHQ (range 0-100 points), which suggests that methylphenidate may improve parent reported quality of life (SMD 0.61, three trials, n=514). 96.8% of trials were considered high risk of bias trials according to the Cochrane guidelines. All outcomes were assessed very low quality according to GRADE.
What this study adds The results suggest that among children and adolescents with a diagnosis of ADHD, methylphenidate may improve teacher reported symptoms of ADHD and general behaviour and parent reported quality of life. However, given the risk of bias in the included studies, and the very low quality of outcomes, the magnitude of the effects is uncertain. Methylphenidate is associated with an increased risk of non-serious but not serious adverse events.
Funding, competing interests, data sharing Region Zealand Research Foundation and Copenhagen Trial Unit. Competing interests are given in the full paper on bmj.com. Full data are available in the version of this review published in The Cochrane Library.
Context:
Mixed findings exist on whether stimulant medications alter youth sleep.
Objective:
To determine the effect of stimulant medications on sleep.
Data studies:
Studies published through March 2015 were collected via CINAHL, PsycINFO, and PubMed. References of retrieved articles were reviewed.
Study selection:
Eligibility criteria included studies with children/adolescents who had attention-deficit/hyperactivity disorder (ADHD), random assignment to stimulants, and objective sleep measurement. Studies that did not include information about key variables were excluded.
Data extraction:
Study-level, child-level, and sleep data were extracted by 2 independent coders. Effect sizes were calculated by using random effects models. Potential moderators were examined by using mixed effect models.
Results:
A total of 9 articles (N = 246) were included. For sleep latency, the adjusted effect size (0.54) was significant, indicating that stimulants produce longer sleep latencies. Frequency of dose per day was a significant moderator. For sleep efficiency, the adjusted effect size (-0.32) was significant. Significant moderators included length of time on medication, number of nights of sleep assessed, polysomnography/actigraphy, and gender. Specifically, the effect of medication was less evident when youth were taking medication longer. For total sleep time, the effect size (-0.59) was significant, such that stimulants led to shorter sleep duration.
Limitations:
Limitations include few studies, limited methodologic variability, and lack of unpublished studies.
Conclusions:
Stimulant medication led to longer sleep latency, worse sleep efficiency, and shorter sleep duration. Overall, youth had worse sleep on stimulant medications. It is recommended that pediatricians carefully monitor sleep problems and adjust treatment to promote optimal sleep.
A new multilayer-bead formulation of extended-release methylphenidate hydrochloride (MPH-MLR) has been evaluated in pharmacokinetic studies in healthy adults and in Phase III efficacy/safety studies in children and adolescents with attention deficit hyperactivity disorder (ADHD). Using available data in healthy adults, a two-input, one-compartment, first-order elimination population pharmacokinetic model was developed using nonlinear mixed-effect modeling. The model was then extended to pediatric subjects, and was found to adequately describe plasma concentration-time data for this population. A pharmacokinetic/pharmacodynamic model was also developed using change from baseline in the ADHD Rating Scale (ADHD-RS)-IV total scores from a pediatric Phase III trial and simulated plasma concentration-time data. During simulations for each MPH-MLR dose level (10-80 mg), increased body weight resulted in decreased maximum concentration. Additionally, as maximum concentration increased, ADHD-RS-IV total score improved (decreased). Knowledge of the relationship between dose, body weight, and clinical response following the administration of MPH-MLR in children and adolescents may be useful for clinicians selecting initial dosing of MPH-MLR. Additional study is needed to confirm these results.
Objective The aim of this systematic review and meta-analysis was to examine the evidence for the effectiveness of exercise interventions on attention deficit hyperactivity disorder (ADHD)-related symptoms such as inattention, hyperactivity/impulsivity, anxiety and cognitive functions in children and adolescents.
Method Five databases covering the period up to November 2014 (PubMed, Scopus, EMBASE, EBSCO [E-journal, CINAHL, SportDiscus] and The Cochrane Library) were searched. Methodological quality was assessed using the Cochrane tool of bias. Standardized mean differences (SMD) and 95% confidence intervals were calculated, and the heterogeneity of the studies was estimated using Cochran’s Q-statistic.
Results Eight randomized controlled trials (n = 249) satisfied the inclusion criteria. The studies were grouped according to the intervention programme: aerobic and yoga exercise.The meta-analysis suggests that aerobic exercise had a moderate to large effect on core symptoms such as attention (SMD = 0.84), hyperactivity (SMD = 0.56) and impulsivity (SMD = 0.56) and related symptoms such as anxiety (SMD = 0.66), executive function (SMD = 0.58) and social disorders (SMD = 0.59) in children with ADHD. Yoga exercise suggests an improvement in the core symptoms of ADHD.
Conclusions The main cumulative evidence indicates that short-term aerobic exercise, based on several aerobic intervention formats, seems to be effective for mitigating symptoms such as attention, hyperactivity, impulsivity, anxiety, executive function and social disorders in children with ADHD.
Objective: the authors performed meta-analyses of randomized controlled trials to examine the effects of cognitive training on attention-deficit/hyperactivity disorder (ADHD) symptoms, neuropsychological deficits, and academic skills in children/adolescents with ADHD.
Method: the authors searched Pubmed, Ovid, Web of Science, ERIC, and CINAHAL databases through May 18, 2014. Data were aggregated using random-effects models. Studies were evaluated with the Cochrane risk of bias tool.
Results: sixteen of 695 nonduplicate records were analyzed (759 children with ADHD). When all types of training were considered together, there were significant effects on total ADHD (standardized mean difference [SMD] = 0.37, 95% CI = 0.09–0.66) and inattentive symptoms (SMD = 0.47, 95% CI = 0.14–0.80) for reports by raters most proximal to the treatment setting (i.e., typically unblinded). These figures decreased substantially when the outcomes were provided by probably blinded raters (ADHD total: SMD = 0.20, 95% CI = 0.01–0.40; inattention: SMD = 0.32, 95% CI = −0.01 to 0.66). Effects on hyperactivity/impulsivity symptoms were not significant. There were significant effects on laboratory tests of working memory (verbal: SMD = 0.52, 95% CI = 0.24–0.80; visual: SMD = 0.47, 95% CI = 0.23–0.70) and parent ratings of executive function (SMD = 0.35, 95% CI = 0.08–0.61). Effects on academic performance were not statistically significant. There were no effects of working memory training, specifically on ADHD symptoms. Interventions targeting multiple neuropsychological deficits had large effects on ADHD symptoms rated by most proximal assessors (SMD = 0.79, 95% CI = 0.46–1.12).
Conclusion: despite improving working memory performance, cognitive training had limited effects on ADHD symptoms according to assessments based on blinded measures. Approaches targeting multiple neuropsychological processes may optimize the transfer of effects from cognitive deficits to clinical symptoms
BACKGROUND AND OBJECTIVE: Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) are prone to sustaining trauma that requires emergency department (ED) admission. Methylphenidate (MPH) can reduce ADHD symptoms and may thus theoretically reduce the risk of trauma-related ED admission, but previous studies do not make this association clear. This study examines the association between MPH and trauma-related ED admission.
METHODS: A total of 17 381 patients aged 6 to 19 years who received MPH prescriptions were identified by using the Hong Kong population-based electronic medical records on the Clinical Data Analysis & Reporting System (2001–2013). Using a self-controlled case series study design, the relative incidence of trauma-related ED admissions was compared with periods of patient exposure and nonexposure to MPH.
RESULTS: Among 17 381 patients prescribed MPH, 4934 had at least 1 trauma-related ED admission. The rate of trauma-related ED admission was lower during exposed periods compared with nonexposed periods (incidence rate ratio [IRR]: 0.91 [95% confidence interval (CI): 0.86–0.97]). The findings were similar only when the incident trauma episode was assessed (IRR: 0.89 [95% CI: 0.82–0.96]). A similar protective association was found in both genders. In validation analysis using nontrauma-related ED admissions as a negative control outcome, no statistically significant association was found (IRR: 0.99 [95% CI: 0.95–1.02]). Sensitivity analysis testing for uncertainty over the precise period of MPH exposure demonstrated consistent results.
CONCLUSIONS: This study supports the hypothesis that MPH is associated with a reduced risk of trauma-related ED admission in children and adolescents. A similar protective association was found in both male and female patients. This protective association should be considered in clinical practice.
Objective: We undertook a meta-analysis of published Randomized Controlled Trials (RCT) with semi-active control and sham-NF groups to determine whether Electroencephalogram-neurofeedback (EEG-NF) significantly improves the overall symptoms, inattention and hyperactivity/impulsivity dimensions for probably unblinded assessment (parent assessment) and probably blinded assessment (teacher assessment) in children with Attention Deficit Hyperactivity Disorder (ADHD).
Data sources: A systematic review identified independent studies that were eligible for inclusion in a random effects meta-analysis.
Data extraction: Effect sizes for ADHD symptoms were expressed as standardized mean differences (SMD) with 95% confidence intervals.
Results: Five identified studies met eligibility criteria, 263 patients with ADHD were included, 146 patients were trained with EEG-NF. On parent assessment (probably unblinded assessment), the overall ADHD score (SMD = −0.49 [−0.74, −0.24]), the inattention score (SMD = −0.46 [−0.76, −0.15]) and the hyperactivity/impulsivity score (SMD = −0.34 [−0.59, −0.09]) were significantly improved in patients receiving EEG-NF compared to controls. On teacher assessment (probably blinded assessment), only the inattention score was significantly improved in patients receiving EEG-NF compared to controls (SMD = −0.30 [−0.58, −0.03]).
Conclusions: This meta-analysis of EEG-NF in children with ADHD highlights improvement in the inattention dimension of ADHD symptoms. Future investigations should pay greater attention to adequately blinded studies and EEG-NF protocols that carefully control the implementation and embedding of training.
Background and objective:
There is ongoing concern that stimulant medications may adversely affect growth. In a sample of attention-deficit/hyperactivity disorder (ADHD) cases and controls from a population-based birth cohort, we assessed growth and the association between stimulant treatment and growth.
Methods:
Subjects included childhood ADHD cases (N = 340) and controls (N = 680) from a 1976 to 1982 birth cohort (N = 5718). Height and stimulant treatment information were abstracted from medical records and obtained during a prospective, adult follow-up study. For each subject, a parametric penalized spline smoothing method modeled height over time, and the corresponding height velocity was calculated as the first derivative. Peak height velocity (PHV) age and magnitude were estimated from the velocity curves. Among stimulant-treated ADHD cases, we analyzed height Z scores at the beginning, at the end, and 24 months after the end of treatment.
Results:
Neither ADHD itself nor treatment with stimulants was associated with differences in magnitude of PHV or final adult height. Among boys treated with stimulants, there was a positive correlation between duration of stimulant usage before PHV and age at PHV (r = 0.21, P = .01). There was no significant correlation between duration of treatment and change in height Z scores (r = -0.08 for beginning vs end change, r = 0.01 for end vs 24 months later change). Among the 59 ADHD cases treated for ≥3 years, there was a clinically insignificant decrease in mean Z score from beginning (0.48) to end (0.33) of treatment (P = .06).
Conclusions:
Our findings suggest that ADHD treatment with stimulant medication is not associated with differences in adult height or significant changes in growth.
It is estimated that 2-3% of children in the US have hypertension (HTN) and 8% of children ages 4-17 carry the diagnosis of Attention Deficit Hyperactivity Disorder (ADHD). The prevalence of HTN and cardiovascular (CV) risk factors in children with ADHD on CNS stimulant treatment (stimulants) compared to no treatment and compared to their healthy counterparts is not well described. Using NHANES data, we examined demographic, BP and CV risk factors of 4,907 children aged 12-18 years with and without the diagnosis of ADHD, and further examined the CV risk in a subgroup of ADHD patients on stimulants. 383 (10.7%) children were reported to have ADHD; of whom 111 (3.4%) were on stimulants. Children with ADHD on stimulants were significantly younger, male, and white compared to those with ADHD not on medication and those without ADHD. BMI, eGFR, cholesterol, the prevalence of albuminuria and poverty were not significantly different between the three groups. 160 (2.7%) had BP in the hypertensive and 637 (12.4%) in the prehypertensive range. The prevalence of elevated BP (HTN and/or pre-HTN range) was not different between children with ADHD on stimulants compared to ADHD without medication and those without ADHD. Heart Rate (HR) was significantly higher in the ADHD group on stimulants vs. the groups ADHD on no stimulants and without ADHD. When the relationship between stimulants and the risk of abnormal BP was examined, there was a significant interaction between having BP in the HTN range and sex. After adjusting for BMI, race and age, females with ADHD on stimulants tended to be older and had significantly more BP in the hypertensive range. On the other hand, males were more likely to be of a white race and older, but not hypertensive. Children with ADHD on stimulants have significantly higher HR than children with ADHD on no stimulants and children without ADHD. On the other hand, the prevalence of abnormal BP classification is comparable between the three groups.
OBJECTIVE
Behavioral interventions are recommended as attention-deficit/hyperactivity disorder (ADHD) treatments. However, a recent meta-analysis found no effects on core ADHD symptoms when raters were probably blind to treatment allocation. The present analysis is extended to a broader range of child and parent outcomes.
METHOD
A systematic search in PubMed, Ovid, Web of Knowledge, ERIC, and CINAHAL databases (up to February 5, 2013) identified published randomized controlled trials measuring a range of patient and parent outcomes for children and adolescents diagnosed with ADHD (or who met validated cutoffs on rating scales).
RESULTS
Thirty-two of 2,057 nonduplicate screened records were analyzed. For assessments made by individuals closest to the treatment setting (usually unblinded), there were significant improvements in parenting quality (standardized mean difference [SMD] for positive parenting 0.68; SMD for negative parenting 0.57), parenting self-concept (SMD 0.37), and child ADHD (SMD 0.35), conduct problems (SMD 0.26), social skills (SMD 0.47), and academic performance (SMD 0.28). With probably blinded assessments, significant effects persisted for parenting (SMD for positive parenting 0.63; SMD for negative parenting 0.43) and conduct problems (SMD 0.31).
CONCLUSION
In contrast to the lack of blinded evidence of ADHD symptom decrease, behavioral interventions have positive effects on a range of other outcomes when used with patients with ADHD. There is blinded evidence that they improve parenting and decrease childhood conduct problems. These effects also may feed through into a more positive parenting self-concept but not improved parent mental well-being.
Unlabelled:
This review summarises research studies on the impact and beneficial effects of different types of exercise on childhood attention-deficit/hyperactivity disorder (ADHD) and provides recommendations for the scientific and therapeutic communities.
Conclusion:
Although the design and the exercise interventions featured in these studies varied considerably, all showed that exercise reduced the symptoms of ADHD and led to improvements in social behaviour, motor skills, strength and neuropsychological parameters.
Attention deficit hyperactivity disorder (ADHD) is a common condition with a high societal burden. The present guidelines summarise current literature, generating expert consensus recommendations for the treatment of ADHD in children and adults. These guidelines also provide a review of recent research in the fields of neuroimaging, neuropsychology and genetics of ADHD. Novel discoveries in these areas have informed physiological models for the disease. Since the publication of the previous British Association for Psychopharmacology guidelines in 2008, new drugs have been licensed and further compounds are being investigated. The publication of randomised controlled trials of psychological interventions has contributed to the range of treatment options for ADHD. As the disorder has been diagnosed more frequently there has been greater focus on comorbid conditions and how they impact treatment. Services have continued to develop for the treatment of ADHD in adults and care agreements have been introduced to facilitate access to treatment.
Recent guidelines for the diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) have claimed the possible benefits of psychoeducational techniques in the comprehensive management of ADHD. To evaluate the efficacy of a psychoeducation programme for parents of children and adolescents with ADHD in a clinical setting using a blind randomized trial. 81 children/adolescents with ADHD were randomly assigned for their families to receive either a well-structured psychoeducation programme (intervention group, n = 44), or a parent counselling and support intervention (control group, n = 37). Measures of child ADHD symptoms, psychopathology, quality of life and family stress were taken before and after intervention and after a year follow-up. Parents and evaluators were unaware of the condition received. Compared to the support control group, the psychoeducation group showed ADHD Index and cognitive/inattention levels significantly reduced after the intervention ended (Mann-Whitney U = 3.34; p = 0.001; Mann-Whitney U = 3.47; p = 0.001). An improvement in the pro-social domain was also observed after 1 year follow-up (Mann-Whitney U = -2.37; p = 0.018), and clinical global impression found a statistically significant effect for severity over the time. Differences were initially found for the impact of the disorder in the family in different domains, including emotional and social functioning; these differences were no longer significant after alpha correction. No significant differences in quality of life or family stress were found in comparison with the control group. This psychoeducation programme is a valuable treatment for parents/carers of children/adolescents with ADHD, which needs to be considered when evaluating different non-pharmacological treatment options. Psychoeducation and other kind of non-pharmacological approaches need to be regarded not as a substitute, but as a complementary treatment to medications; these approaches might help other very crucial aspects of ADHD including social and familiar outcomes.
The purpose of this research was to update the Pelham and Fabiano (2008) review of evidence-based practices for children and adolescents with attention-deficit/hyperactivity disorder. We completed a systematic review of the literature published between 2007 and 2013 to establish levels of evidence for psychosocial treatments for these youth. Our review included the identification of relevant articles using criteria established by the Society of Clinical Child and Adolescent Psychology (see Southam-Gerow & Prinstein, in press) using keyword searches and a review of tables of contents. We extend the conceptualization of treatment research by differentiating training interventions from behavior management and by reviewing the growing literature on training interventions. Consistent with the results of the previous review we conclude that behavioral parent training, behavioral classroom management, and behavioral peer interventions are well-established treatments. In addition, organization training met the criteria for a well-established treatment. Combined training programs met criteria for Level 2 (Probably Efficacious), neurofeedback training met criteria for Level 3 (Possibly Efficacious), and cognitive training met criteria for Level 4 (Experimental Treatments). The distinction between behavior management and training interventions provides a method for considering meaningful differences in the methods and possible mechanisms of action for treatments for these youth. Characteristics of treatments, participants, and measures, as well as the variability in methods for classifying levels of evidence for treatments, are reviewed in relation to their potential effect on outcomes and conclusions about treatments. Implications of these findings for future science and practice are discussed.
Objectives:
To describe the association between parents' attention-deficit/hyperactivity disorder (ADHD) treatment preferences and goals and treatment initiation.
Methods:
Parents/guardians of children aged 6 to 12 years diagnosed with ADHD in the past 18 months and not currently receiving combined treatment (both medication and behavior therapy [BT]) were recruited from 8 primary care sites and an ADHD treatment center. Parents completed the ADHD Preference and Goal Instrument, a validated measure, and reported treatment receipt at 6 months. Logistic regression was used to analyze the association of baseline preferences and goals with treatment initiation. Using linear regression, we compared the change in preferences and goals over 6 months for children who initiated treatment versus others.
Results:
The study included 148 parents/guardians. Baseline medication and BT preference were associated with treatment initiation (odds ratio [OR]: 2.6 [95% confidence interval (CI):1.2-5.5] and 2.2 [95% CI: 1.0-5.1], respectively). The goal of academic achievement was associated with medication initiation (OR: 2.1 [95% CI: 1.3-3.4]) and the goal of behavioral compliance with initiation of BT (OR: 1.6 [95% CI: 1.1-2.4]). At 6 months, parents whose children initiated medication or BT compared with others had decreased academic and behavioral goals, suggesting their goals were attained. However, only those initiating BT had diminished interpersonal relationship goals.
Conclusions:
Parental treatment preferences were associated with treatment initiation, and those with distinct goals selected different treatments. Results support the formal measurement of preferences and goals in practice as prioritized in recent national guidelines for ADHD management.
The aim of this study was to compare the efficacy and safety of the prodrug psychostimulant lisdexamfetamine dimesylate (LDX) and the non-stimulant noradrenergic compound atomoxetine (ATX) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) who had previously responded inadequately to methylphenidate (MPH).
This 9-week, head-to-head, randomized, double-blind, active-controlled study (SPD489-317; ClinicalTrials.gov NCT01106430) enrolled patients (aged 6-17 years) with at least moderately symptomatic ADHD and an inadequate response to previous MPH therapy. Patients were randomized (1:1) to an optimized daily dose of LDX (30, 50 or 70 mg) or ATX (patients <70 kg, 0.5-1.2 mg/kg with total daily dose not to exceed 1.4 mg/kg; patients ≥70 kg, 40, 80 or 100 mg). The primary efficacy outcome was time (days) to first clinical response. Clinical response was defined as a Clinical Global Impressions-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved). Secondary efficacy outcomes included the proportion of responders at each study visit and the change from baseline in ADHD Rating Scale (ADHD-RS-IV) and CGI-Severity scores. Tolerability and safety were assessed by monitoring treatment-emergent adverse events (TEAEs), height and weight, vital signs and electrocardiogram parameters. Endpoint was defined as the last post-baseline, on-treatment visit with a valid assessment.
Of 267 patients randomized (LDX, n = 133; ATX, n = 134), 200 (74.9 %) completed the study. The median time to first clinical response [95 % confidence interval (CI)] was significantly shorter for patients receiving LDX [12.0 days (8.0-16.0)] than for those receiving ATX [21.0 days (15.0-23.0)] (p = 0.001). By week 9, 81.7 % (95 % CI 75.0-88.5) of patients receiving LDX had responded to treatment compared with 63.6 % (95 % CI 55.4-71.8) of those receiving ATX (p = 0.001). Also by week 9, the difference between LDX and ATX in least-squares mean change from baseline (95 % CI) was significant in favour of LDX for the ADHD-RS-IV total score [-6.5 (-9.3 to -3.6); p < 0.001; effect size 0.56], inattentiveness subscale score [-3.4 (-4.9 to -1.8); p < 0.001; effect size 0.53] and the hyperactivity/impulsivity subscale score [-3.2 (-4.6 to -1.7); p < 0.001; effect size 0.53]. TEAEs were reported by 71.9 and 70.9 % of patients receiving LDX and ATX, respectively. At endpoint, both treatments were associated with mean (standard deviation) increases in systolic blood pressure [LDX, +0.7 mmHg (9.08); ATX, +0.6 mmHg (7.96)], diastolic blood pressure [LDX, +0.1 mmHg (8.33); ATX, +1.3 mmHg (8.24)] and pulse rate [LDX, +3.6 bpm (10.49); ATX, +3.7 bpm (10.75)], and decreases in weight [LDX, -1.30 kg (1.806); ATX, -0.15 kg (1.434)].
LDX was associated with a faster and more robust treatment response than ATX in children and adolescents with at least moderately symptomatic ADHD who had previously responded inadequately to MPH. Both treatments displayed safety profiles consistent with findings from previous clinical trials.
Background
Optimal management of attention deficit hyperactivity disorder (ADHD) aims not only to ameliorate patients’ symptoms, but also to improve health-related quality of life (HRQL) and functioning. A pivotal, 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in ten European countries demonstrated that the stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well-tolerated treatment for symptoms of ADHD.
Objective
The aim of this study was to assess HRQL and functional impairment outcomes in this clinical trial, using the Child Health and Illness Profile-Child Edition: Parent Report Form (CHIP-CE:PRF) and the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P), respectively.
Methods
Patients (aged 6–17 years) with diagnosed ADHD and a baseline ADHD Rating Scale IV total score ≥28 were randomized (1:1:1) to 7 weeks of double-blind treatment with once-daily LDX, placebo or the reference treatment, osmotic-release oral system methylphenidate (OROS-MPH). Participants’ parents (or legally authorized representatives) completed the CHIP-CE:PRF and WFIRS-P questionnaires at baseline, at weeks 4 and 7, and/or at early termination. Endpoint was defined as the last on-treatment visit with valid data (≤30 % missing items). The CHIP-CE:PRF Achievement domain was pre-specified as the primary HRQL outcome.
Results
The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107), the majority of whom completed the study (LDX, n = 77; placebo, n = 42; OROS-MPH, n = 72). Baseline CHIP-CE:PRF T-scores in four of the five domains were ≥1 standard deviation below norms (US community samples). Compared with placebo, LDX was associated with statistically significantly improved T-scores from baseline to endpoint in these four domains, with effect sizes of 1.280 (p
Safe and effective medication for attention deficit hyperactivity disorder (ADHD) is available and recommended as first-line treatment for the core symptoms of inattention, overactivity and impulsiveness. Despite impaired functioning during adolescence, many discontinue medication treatment. For children, healthcare decisions are usually made by the parent; older youth make their own decisions. Beliefs and attitudes may differ widely. Some families understand that ADHD is a neurobiological condition and accept that medication is indicated, for others, such treatment is unacceptable. Converging evidence describes negative perceptions of the burden associated with medication use as well as concerns about potential short and long term adverse effects. Indeed experiences of adverse effects are a frequent explanation for discontinuation among youth. Ways to improve shared decision making among practitioners, parents and youth, and to monitor effectiveness, safety and new onset of concurrent difficulties are likely to optimize outcomes.
Objective:
The purpose of this article was to systematically review the literature on stimulant and atomoxetine combination therapy, in particular: 1) Characteristics of patients with attention-deficit/hyperactivity disorder (ADHD) given combination therapy, 2) treatment strategies used, 3) efficacy and effectiveness, and 4) safety and tolerability.
Methods:
Literature databases (MEDLINE(®), EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, and SciVerse Scopus) were systematically searched using prespecified criteria. Publications describing stimulant and atomoxetine combination therapy in patients with ADHD or healthy volunteers were selected for review. Exclusion criteria were comorbid psychosis, bipolar disorder, epilepsy, or other psychiatric/neurologic diseases that could confound ADHD symptom assessment, or other concomitant medication(s) to treat ADHD symptoms.
Results:
Of the 16 publications included for review, 14 reported findings from 3 prospective studies (4 publications), 7 retrospective studies, and 3 narrative reviews/medication algorithms of patients with ADHD. The other two publications reported findings from two prospective studies of healthy volunteers. The main reason for prescribing combination therapy was inadequate response to previous treatment. In the studies of patients with ADHD, if reported, 1) most patients were children/adolescents and male, and had a combined ADHD subtype; 2) methylphenidate was most often used in combination with atomoxetine for treatment augmentation or switch; 3) ADHD symptom control was improved in some, but not all, patients; and 4) there were no serious adverse events.
Conclusions:
Published evidence of the off-label use of stimulant and atomoxetine combination therapy is limited because of the small number of publications, heterogeneous study designs (there was only one prospective, randomized controlled trial), small sample sizes, and geographic bias. Existing evidence suggests, but does not confirm, that this drug combination may benefit some, but not all, patients who have tried several ADHD medications without success.
Objective: honpharmacological treatments are available for attention deficit hyperactivity disorder (ADHD), although their efficacy remains uncertain. The authors undertook meta-analyses of the efficacy of dietary (restricted elimination diets, artificial food color exclusions, and free fatty acid supplementation) and psychological (cognitive training, neurofeedback, and behavioral interventions) ADHD treatments. Method: using a common systematic search and a rigorous coding and data extraction strategy across domains, the authors searched electronic databases to identify published randomized controlled trials that involved individuals who were diagnosed with ADHD (or who met a validated cutoff on a recognized rating scale) and that included an ADHD outcome. Results: fifty-four of the 2,904 nonduplicate screened records were included in the analyses. Two different analyses were performed. When the outcome measure was based on ADHD assessments by raters closest to the therapeutic setting, all dietary (standardized mean differences=0.21–0.48) and psychological (standardized mean differences=0.40–0.64) treatments produced statistically significant effects. However, when the best probably blinded assessment was employed, effects remained significant for free fatty acid supplementation (standardized mean difference=0.16) and artificial food color exclusion (standardized mean difference=0.42) but were substantially attenuated to nonsignificant levels for other treatments. Conclusions: free fatty acid supplementation produced small but significant reductions in ADHD symptoms even with probably blinded assessments, although the clinical significance of these effects remains to be determined. Artificial food color exclusion produced larger effects but often in individuals selected for food sensitivities. Better evidence for efficacy from blinded assessments is required for behavioral interventions, neurofeedback, cognitive training, and restricted elimination diets before they can be supported as treatments for core ADHD symptoms
Attention-deficit hyperactivity disorder (ADHD) has a significant impact on children's classroom behaviour, daily functioning and experience of school life. However, the effects of drug treatment for ADHD on learning and academic achievement are not fully understood. This review was undertaken to describe the effects of methylphenidate, dexamfetamine, mixed amfetamine salts and atomoxetine on children's on-task behaviour and their academic performance, and to perform a meta-analysis to quantify these effects. Nine electronic databases were systematically searched for randomized controlled trials comparing drug treatment for ADHD against (i) no drug treatment, (ii) baseline (in crossover trials), or (iii) placebo; reporting outcomes encompassing measures of educational achievement within the classroom environment. Forty-three studies involving a pooled total of 2,110 participants were identified for inclusion. Drug treatment benefited children in the amount of school work that they completed, by up to 15 %, and less consistently improved children's accuracy in specific types of academic assignments, such as arithmetic. Similar improvements were seen in classroom behaviour, with up to 14 % more of children's time spent "on task". Methylphenidate, dexamfetamine and mixed amfetamine formulations all showed beneficial effects on children's on-task behaviour and academic work completion. Atomoxetine was examined in two studies, and was found to have no significant effect. These review findings suggest that medication for ADHD has the potential to improve children's learning and academic achievement.
Background:
Attention deficit hyperactivity disorder (ADHD) in children is associated with hyperactivity and impulsivity, attention problems, and difficulties with social interactions. Pharmacological treatment may alleviate the symptoms of ADHD but this rarely solves difficulties with social interactions. Children with ADHD may benefit from interventions designed to improve their social skills. We examined the benefits and harms of social skills training on social skills, emotional competencies, general behaviour, ADHD symptoms, performance in school of children with ADHD, and adverse events.
Objectives:
To assess the beneficial and harmful effects of social skills training in children and adolescents with ADHD.
Search methods:
In July 2018, we searched CENTRAL, MEDLINE, Embase, PsycINFO, 4 other databases and two trials registers.We also searched online conference abstracts, and contacted experts in the field for information about unpublished or ongoing randomised clinical trials. We did not limit our searches by language, year of publication, or type or status of publication, and we sought translation of the relevant sections of non-English language articles.
Selection criteria:
Randomised clinical trials investigating social skills training versus either no intervention or waiting-list control, with or without pharmacological treatment of both comparison groups of children and adolescents with ADHD.
Data collection and analysis:
We conducted the review in accordance with the Cochrane Handbook for Systematic Reviews of Intervention. We performed the analyses using Review Manager 5 software and Trial Sequential Analysis. We assessed bias according to domains for systematic errors. We assessed the certainty of the evidence with the GRADE approach.
Main results:
We included 25 randomised clinical trials described in 45 reports. The trials included a total of 2690 participants aged between five and 17 years. In 17 trials, participants were also diagnosed with various comorbidities.The social skills interventions were described as: 1) social skills training, 2) cognitive behavioural therapy, 3) multimodal behavioural/psychosocial therapy, 4) child life and attention skills treatment, 5) life skills training, 6) the "challenging horizon programme", 7) verbal self-instruction, 8) meta-cognitive training, 9) behavioural therapy, 10) behavioural and social skills treatment, and 11) psychosocial treatment. The control interventions were no intervention or waiting list.The duration of the interventions ranged from five weeks to two years. We considered the content of the social skills interventions to be comparable and based on a cognitive-behavioural model. Most of the trials compared child social skills training or parent training combined with medication versus medication alone. Some of the experimental interventions also included teacher consultations.More than half of the trials were at high risk of bias for generation of the allocation sequence and allocation concealment. No trial reported on blinding of participants and personnel. Most of the trials did not report on differences between groups in medication for comorbid disorders. We used all eligible trials in the meta-analyses, but downgraded the certainty of the evidence to low or very low.We found no clinically relevant treatment effect of social skills interventions on the primary outcome measures: teacher-rated social skills at end of treatment (standardised mean difference (SMD) 0.11, 95% confidence interval (CI) 0.00 to 0.22; 11 trials, 1271 participants; I2 = 0%; P = 0.05); teacher-rated emotional competencies at end of treatment (SMD -0.02, 95% CI -0.72 to 0.68; two trials, 129 participants; I2 = 74%; P = 0.96); or on teacher-rated general behaviour (SMD -0.06 (negative value better), 95% CI -0.19 to 0.06; eight trials, 1002 participants; I2 = 0%; P = 0.33). The effect on the primary outcome, teacher-rated social skills at end of treatment, corresponds to a MD of 1.22 points on the social skills rating system (SSRS) scale (95% CI 0.09 to 2.36). The minimal clinical relevant difference (10%) on the SSRS is 10.0 points (range 0 to 102 points on SSRS).We found evidence in favour of social skills training on teacher-rated core ADHD symptoms at end of treatment for all eligible trials (SMD -0.26, 95% CI -0.47 to -0.05; 14 trials, 1379 participants; I2= 69%; P = 0.02), but the finding is questionable due to lack of support from sensitivity analyses, high risk of bias, lack of clinical significance, high heterogeneity, and low certainty.The studies did not report any serious or non-serious adverse events.
Authors' conclusions:
The review suggests that there is little evidence to support or refute social skills training for children and adolescents with ADHD. We may need more trials that are at low risk of bias and a sufficient number of participants to determine the efficacy of social skills training versus no training for ADHD. The evidence base regarding adolescents is especially weak.
Objective:
To compare educational, occupational, legal, emotional, substance use disorder, and sexual behavior outcomes in young adults with persistent and desistent attention-deficit/hyperactivity disorder (ADHD) symptoms and a local normative comparison group (LNCG) in the Multimodal Treatment Study of Children with ADHD (MTA).
Method:
Data were collected 12, 14, and 16 years postbaseline (mean age 24.7 years at 16 years postbaseline) from 476 participants with ADHD diagnosed at age 7 to 9 years, and 241 age- and sex-matched classmates. Probands were subgrouped on persistence versus desistence of DSM-5 symptom count. Orthogonal comparisons contrasted ADHD versus LNCG and symptom-persistent (50%) versus symptom-desistent (50%) subgroups. Functional outcomes were measured with standardized and demographic instruments.
Results:
Three patterns of functional outcomes emerged. Post-secondary education, times fired/quit a job, current income, receiving public assistance, and risky sexual behavior showed the most common pattern: the LNCG group fared best, symptom-persistent ADHD group worst, and symptom-desistent ADHD group between, with the largest effect sizes between LNCG and symptom-persistent ADHD. In the second pattern, seen with emotional outcomes (emotional lability, neuroticism, anxiety disorder, mood disorder) and substance use outcomes, the LNCG and symptom-desistent ADHD group did not differ, but both fared better than the symptom-persistent ADHD group. In the third pattern, noted with jail time (rare), alcohol use disorder (common), and number of jobs held, group differences were not significant. The ADHD group had 10 deaths compared to one death in the LNCG.
Conclusion:
Adult functioning after childhood ADHD varies by domain and is generally worse when ADHD symptoms persist. It is important to identify factors and interventions that promote better functional outcomes.
Objective:
The aim of the study was to synthesize the evidence of parent training (PT) as an early intervention for preschool children aged 2.5 to 6 years with ADHD or ADHD symptoms.
Method:
A systematic review and meta-analysis was conducted.
Results:
Sixteen studies including 1,003 children were analyzed. Parent-rated outcomes revealed moderate effect sizes (ESs; Hedges' g) of 0.51 for ADHD symptoms, 0.40 for conduct problems, and 0.64 for negative parenting. Based on independent assessment, results were only significant for negative parenting. Parent-rated outcomes were sustained at follow-ups of 3 to 12 months. Program type, intervention modality, and child diagnostic status did not moderate the effect.
Conclusion:
PT was partially supported as an efficacious intervention for preschool children with ADHD or ADHD symptoms with moderate ESs on parent-rated outcomes, but no significant results on independently assessed ADHD symptoms.
Aim:
To describe the prescription of medications for Attention-Deficit Hyperactivity Disorder (ADHD) in the UK between 1995 and 2015.
Methods:
Using the Clinical Practice Research Datalink (CPRD), we defined a cohort of all patients aged 6 to 45 years, registered with a general practitioner between January 1995 and September 2015. All prescriptions of methylphenidate, dexamphetamine/lisdexamphetamine, and atomoxetine were identified and annual prescription rates of ADHD were estimated using Poisson regression.
Results:
Within a cohort of 7,432,735 patients, we identified 698,148 prescriptions of ADHD medications during 41,171,528 person-years of follow-up. Usage was relatively low until the year 2000 during which the prescription rate was 42.7 (95% confidence interval (CI) 20.9 to 87.2) prescriptions per 10,000 persons, increasing to 394.4 (95% CI 296.7 to 524.2) in 2015, corresponding to an almost 800% increase (rate ratio 8.87; 95% CI 7.10 to 11.09). The increase was seen in all age groups and in both sexes but was steepest in boys aged 10 to 14 years. The prescription rate in males was almost 5 times that of females. Methylphenidate remained the most prescribed drug during the 20-year study period, representing 88.9% of all prescriptions in the 6-24 years old, and 63.5% of all prescriptions in adults (25-45 years old).
Conclusions:
Prescription rates of ADHD medications have increased dramatically in the past two decades. This may be due, at least in part, to both an increase in the number of patients diagnosed with ADHD over time and a higher percentage of those patients treated with medication.
Behavioral and pharmacological treatments for children with attention deficit/hyperactivity disorder (ADHD) were evaluated to address whether endpoint outcomes are better depending on which treatment is initiated first and, in case of insufficient response to initial treatment, whether increasing dose of initial treatment or adding the other treatment modality is superior. Children with ADHD (ages 5–12, N = 146, 76% male) were treated for 1 school year. Children were randomized to initiate treatment with low doses of either (a) behavioral parent training (8 group sessions) and brief teacher consultation to establish a Daily Report Card or (b) extended-release methylphenidate (equivalent to .15 mg/kg/dose bid). After 8 weeks or at later monthly intervals as necessary, insufficient responders were rerandomized to secondary interventions that either increased the dose/intensity of the initial treatment or added the other treatment modality, with adaptive adjustments monthly as needed to these secondary treatments. The group beginning with behavioral treatment displayed significantly lower rates of observed classroom rule violations (the primary outcome) at study endpoint and tended to have fewer out-of-class disciplinary events. Further, adding medication secondary to initial behavior modification resulted in better outcomes on the primary outcomes and parent/teacher ratings of oppositional behavior than adding behavior modification to initial medication. Normalization rates on teacher and parent ratings were generally high. Parents who began treatment with behavioral parent training had substantially better attendance than those assigned to receive training following medication. Beginning treatment with behavioral intervention produced better outcomes overall than beginning treatment with medication.
Injuries represent the largest disease burden and most common cause of death in children. Attention deficit hyperactivity disorder (ADHD) is associated with increased mortality, with accidents being the most common cause of death in ADHD. However, it is not known whether pharmacological treatment has any modifying effect on the risk of injuries in children and adolescents with ADHD.
Using Danish national registers, we followed a cohort of 710 120 individuals, including 4557 individuals diagnosed with ADHD before age 10 years. Using a quasi-experimental, difference-in-difference design, we estimated the odds ratios (ORs) for injuries and the mean change in prevalence rates of injuries and emergency ward visits before and after treatment, with matched untreated children with ADHD at the same age serving as controls.
Children with ADHD were more likely to sustain injuries, compared with children without ADHD, at age 10 years (adjusted OR=1·29, 95% CI 1·22-1·37) and at age 12 years (adjusted OR=1·30, 1·23-1·37). From age 5 to 10 years, the prevalence of injuries in children with ADHD who were treated with ADHD drugs decreased from 19% to 14%, compared with a prevalence of about 17% in non-treated children with ADHD. This corresponded to an adjusted difference-in-difference reduction in prevalence of injuries at age 10 years of 31·5% (8·2-54·8) and 43·5% (18·1-69·0) at age 12 years due to treatment. Pharmacological treatment also reduced the prevalence of emergency ward visits at age 10 years (28·2%, 6·3-50·1) and age 12 years (45·7%, 25·8-65·7).
Children with ADHD had an increased risk of injuries compared with other children. Treatment with ADHD drugs reduced the risk of injuries by up to 43% and emergency ward visits by up to 45% in children with ADHD. Taken together with previous findings of accidents being the most common cause of death in individuals with ADHD, these results are of major public health importance.
The Lundbeck Foundation, the Danish Council for Independent Research, Centre For Integrated Register-based Research at Aarhus University, the Region of Southern Denmark Research Foundation, and Wørzner's Foundation.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials.
We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics.
We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials.
Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant use, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.
Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
To develop evidence-based guidelines on pharmacotherapy for severe disruptive and aggressive behaviour in children and adolescents with attention-deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), or conduct disorder (CD). The guidelines assume that psychosocial interventions have been pursued but did not achieve sufficient improvement.
A multidisciplinary consensus group used the Grading of Recommendations Assessment, Development and Evaluation approach for rating evidence quality and for grading recommendations. We conducted a systematic review of medications studied in placebo-controlled trials for treating disruptive and aggressive behaviour in children and adolescents with ADHD, ODD, or CD. We followed consensus procedures to make 1 of 4 recommendations for each medication: strong, in favour (↑↑); conditional, in favour (↑?); conditional, against (↓?); and strong, against (↓↓).
For children and adolescents with disruptive or aggressive behaviour associated with ADHD, psychostimulants received a strong recommendation in favour of use, while atomoxetine and alpha-2 agonists received a conditional recommendation in favour of use. If these patients do poorly with ADHD medications, the medication with the most evidence is risperidone. Risperidone also has the most evidence for treating disruptive or aggressive behaviour in the absence of ADHD. However, given risperidone's major adverse effects, it received only a conditional recommendation in favour of use. We recommended against using quetiapine, haloperidol, lithium, or carbamazepine because of the poor quality of evidence and their major adverse effects.
When severe disruptive or aggressive behaviour occurs with ADHD, medications for ADHD should be used first. Other medications have major adverse effects and, with the exception of risperidone, very limited evidence to support their use.
Attention deficit hyperactivity disorder (ADHD) is a common mental disorder associated with factors that are likely to increase mortality, such as oppositional defiant disorder or conduct disorder, criminality, accidents, and substance misuse. However, whether ADHD itself is associated with increased mortality remains unknown. We aimed to assess ADHD-related mortality in a large cohort of Danish individuals.
By use of the Danish national registers, we followed up 1·92 million individuals, including 32 061 with ADHD, from their first birthday through to 2013. We estimated mortality rate ratios (MRRs), adjusted for calendar year, age, sex, family history of psychiatric disorders, maternal and paternal age, and parental educational and employment status, by Poisson regression, to compare individuals with and without ADHD.
During follow-up (24·9 million person-years), 5580 cohort members died. The mortality rate per 10 000 person-years was 5·85 among individuals with ADHD compared with 2·21 in those without (corresponding to a fully adjusted MRR of 2·07, 95% CI 1·70-2·50; p<0·0001). Accidents were the most common cause of death. Compared with individuals without ADHD, the fully adjusted MRR for individuals diagnosed with ADHD at ages younger than 6 years was 1·86 (95% CI 0·93-3·27), and it was 1·58 (1·21-2·03) for those aged 6-17 years, and 4·25 (3·05-5·78) for those aged 18 years or older. After exclusion of individuals with oppositional defiant disorder, conduct disorder, and substance use disorder, ADHD remained associated with increased mortality (fully adjusted MRR 1·50, 1·11-1·98), and was higher in girls and women (2·85, 1·56-4·71) than in boys and men (1·27, 0·89-1·76).
ADHD was associated with significantly increased mortality rates. People diagnosed with ADHD in adulthood had a higher MRR than did those diagnosed in childhood and adolescence. Comorbid oppositional defiant disorder, conduct disorder, and substance use disorder increased the MRR even further. However, when adjusted for these comorbidities, ADHD remained associated with excess mortality, with higher MRRs in girls and women with ADHD than in boys and men with ADHD. The excess mortality in ADHD was mainly driven by deaths from unnatural causes, especially accidents.
This study was supported by a grant from the Lundbeck Foundation.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Background:
The findings from case reports and patient questionnaire surveys have been interpreted as indicating that administration of stimulants is ill-advised for the treatment of attention-deficit hyperactivity disorder in children with tic disorder.
Methods:
Thirty-four prepubertal children with attention-deficit hyperactivity disorder and tic disorder received placebo and three dosages of methylphenidate hydrochloride (0.1, 0.3, and 0.5 mg/kg) twice daily for 2 weeks each, under double-blind conditions. Treatment effects were assessed using direct observations of child behavior in a simulated (clinic-based) classroom and using rating scales completed by the parents, teachers, and physician.
Results:
Methylphenidate effectively suppressed hyperactive, disruptive, and aggressive behavior. There was no evidence that methylphenidate altered the severity of tic disorder, but it may have a weak effect on the frequency of motor (increase) and vocal (decrease) tics.
Conclusion:
Methylphenidate appears to be a safe and effective treatment for attention-deficit hyperactivity disorder in the majority of children with comorbid tic disorder.
Background:
It has been shown that Attention Deficit Hyperactivity Disorder (ADHD) lowers the Quality of Life (QoL) of patients and their families. Medication as part of the treatment has a favourable effect on symptoms as well as functioning. Evidence on the impact of pharmacological treatment on symptoms of ADHD and the QoL of the patient and their family is still limited. There is a need for further research on QoL in ADHD as well as the relationship between ADHD and the impact on families rather than solely on patients.
Aims of the study:
Measure QoL of children with ADHD and their parents and explore the association of QoL with treatment response.
Methods:
A cross-sectional survey was performed using an online questionnaire to collect QoL data of children with ADHD (based on proxy reporting of parents) and their parents in a sample of members of an ADHD parent association. QoL was measured by EQ-5D and KIDSCREEN-10. Treatment response was based on descriptions by experts, based on compliance and functioning.
Results:
Analyses were based on 618 questionnaires (treatment responder n=428, treatment non-responder n=190). Mean age of the children was 11.8 years (82.4% male). QoL according to EQ-5D utility was 0.83 and 0.74 for responders and non-responders, respectively (p<0.001). For KIDSCREEN-10 the index was 42.24 and 40.33 for responders and non-responders, respectively (p<0.001). EQ-5D utility scores of the parents were 0.83 on average; no association with their child's treatment response could be established. A significant positive correlation between EQ-5D utility of the children and EQ-5D utility of the parents (R2=0.207, p<0.001) was found. The association between treatment response and children's QoL was significantly influenced by age category, having a sibling with ADHD, and presence of comorbidity.
Discussion:
Strengths of this study are its sample size and the inclusion of QoL of parents, which has not been reported simultaneously before. The facts that data were derived from members of the ADHD parent association, the data for children were based on parents' report, and lack of possibility for confirmation of the clinical diagnosis are the main study limitations.
Implications for health care provision and use:
QoL of children with ADHD was shown to be significantly positively associated with response to treatment and negatively affected by comorbidity. In determining the treatment effects in ADHD, QoL and family overall well-being should be a standard consideration as well as an integrated part of health policy discussions on ADHD.
Implications for health policies:
Policymakers in the field of ADHD should focus on QoL of the patient, but also on the broader effects of effective treatment on the well-being of the parents.
Implications for further research:
Suggestions for further research include the repetition of this study including a control group and obtaining children's self-report on QoL and clinicians report on diagnosis.
This article reviews the literature concerning attention-deficit/hyperactivity disorder (ADHD) medication misuse, abuse, dependence, diversion, and malingering. The review covers nonmedical use (NMU) of both stimulant (methylphenidate and amphetamine) and nonstimulant (α-adrenergic agonists and atomoxetine) prescription medications, and provides a discussion on the relevance for ADHD treatment today. The neural basis for ADHD medication mechanisms of action (increased norepinephrine and dopamine signaling) and their neurobiochemical relationship to the abuse potential is explored. Regionally-specific, stimulant-induced elevations in brain dopamine appear to be integral to both efficacy in ADHD and potential for abuse. In addition to the prevalence of misuse and diversion, additional topics discussed include the potential safety concerns associated with NMU of prescription ADHD medications and the cost to payers of prescription drug diversion (eg, increased emergency department visits associated with misuse). The evidence describing the difficulty in detecting malingering for the purpose of illicit access to ADHD medications for subsequent misuse or diversion is also summarized. Moreover, the effect of ADHD medications in patients with comorbid substance use disorder and the controversial potential linkage of stimulant prescription use with subsequent substance use disorder are explored. Overall, the data suggest that ADHD medication misuse and diversion are common health care problems for stimulant medications, with the prevalence believed to be approximately 5% to 10% of high school students and 5% to 35% of college students, depending on the study. Stimulant effectiveness and speed of action are deemed desirable to enhance attention and focus performance for activities like studying, but stimulants are also misused recreationally. Conversely, the data suggest a lack of abuse potential and lack of actual medication misuse for the nonstimulant medications. Although they can be efficacious for the treatment of ADHD, the nonstimulants lack a mechanism of action linked to the abuse potential and they lack the desirable effects (speed of action, stimulant feel) that make stimulants susceptible to NMU. In light of these findings, the data suggest a need for close screening and therapeutic monitoring of ADHD medication use. In addition, nonstimulants might be an appropriate alternative for patients with concern about abuse and physicians concerned with general misuse and diversion.
Oral psychostimulant (PS) drugs, the pharmacologic treatment of choice for attention-deficit/hyperactivity disorder (ADHD), have been associated with diseases of abnormal sensitivity to cold (DASC) such as Raynaud phenomenon and acrocyanosis.
In a cohort of pediatric patients with DASC, we sought to identify prevalence and clinical features of patients on PS drugs.
A 6-year retrospective chart review (2005-2011) of Ste-Justine University Hospital Center DASC patients with and without exposure to PS drugs was performed. Clinical data were analyzed with descriptive statistical methods.
Of 43 patients with DASC, 11 (25%) were exposed to PS drugs. In this group males were overrepresented, there was no evidence of collagen vascular diseases, serologic findings were not significant and the mean duration of PS intake was of 2.5 years. DASC age of onset was similar in both exposed and nonexposed patients. The incidence of more than one DASC type was greater in teenager patients with a positive family history of autoimmune and/or collagen vascular diseases.
This study is limited by its small population size, short follow-up period and its retrospective nature.
Physicians should be aware of PS drugs as possible triggers for DASC.
© 2014 Canadian Dermatology Association.
Considerable scientific effort has been directed at developing effective treatments for attention-deficit/hyperactivity disorder (ADHD). Among alternative treatment approaches, neurofeedback has gained some promising empirical support in recent years from controlled studies as a treatment of core ADHD symptoms. However, a recent stringent meta-analysis of 8 randomized controlled trials published in 2013 found that the effects were stronger for unblinded measures and 3 recent subsequently published well-controlled trials found no effects for the most blinded ADHD outcome. Firmer conclusions must await upcoming evidence from larger controlled studies and future meta-analyses contrasting different forms of neurofeedback and different outcome measures.
There has been an increasing interest in and the use of computer-based cognitive training as a treatment of attention-deficit/hyperactivity disorder (ADHD). The authors' review of current evidence, based partly on a stringent meta-analysis of 6 randomized controlled trials (RCTs) published in 2013, and an overview of 8 recently published RCTs highlights the inconsistency of findings between trials and across blinded and nonblinded ADHD measures within trials. Based on this, they conclude that more evidence from well-blinded studies is required before cognitive training can be supported as a frontline treatment of core ADHD symptoms.
Dietary and herbal interventions for attention-deficit/hyperactivity disorder (ADHD) have been proposed by practitioners of Western medicine and traditional Chinese medicine. Children who are suspected to have nutritional deficiencies, insufficiencies, and/or food allergies should be evaluated and, if the suspicion is confirmed, treated with supplementation or specific food elimination as part of standard care. Limited research exists on the efficacy and safety of dietary intervention as an adjunct to conventional medication; thus, improvement and side effects should be closely monitored.
Using a previously developed population pharmacokinetic model, an exposure-response (ER) model was successfully developed to describe guanfacine plasma concentrations and changes in heart rate (HR) and the QT interval. Guanfacine exposure was associated with small decreases in HR and a small prolongation of the population-corrected QT (QTcP) interval. Based on the final ER model for effect of guanfacine on HR, the estimated population typical decrease in HR would be 2.3% (2.1-2.7%) of the baseline circadian HR for every 1 ng/mL of guanfacine exposure. A QTcP was developed for the analysis using the sampled population. An effect of sex on baseline-corrected QT (BQTP) was the only covariate effect in the final ER model for QTcP, its inclusion resulting in a typical baseline QTcP estimate that is 9 (5-13) ms higher for females. There was no evidence of QT-RR hysteresis. A linear model was used to relate guanfacine plasma concentrations to QTcP. The typical (95% confidence interval) slope parameter was estimated to be 0.941 (0.62-1.25) ms/ng/mL. The final model predicted an approximate 1-ms increase from baseline for every 1 ng/mL of guanfacine in plasma. The main predictor of QTcP prolongation was guanfacine exposure, which decreased with body weight and increased with dose.
Objectives:
The US Agency for Healthcare Research and Quality sponsored a comparative effectiveness review of interventions for preschoolers at risk for attention-deficit/hyperactivity disorder (ADHD).
Methods:
Medline, Cochrane CENTRAL, Embase, PsycInfo, and Education Resources Information Center were searched from 1980 to November 24, 2011. Selected studies were comparative, and enrolled children <6 years with clinically significant disruptive behavior, including ADHD. The interventions evaluated were parent behavior training (PBT), combined home and school/day care interventions, and methylphenidate use. Data were extracted by using customized software. Two independent raters evaluated studies as good, fair, or poor by using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies Risk of Bias. Overall strength of evidence (SOE) was rated for each intervention's effectiveness, accounting for study design, systematic error, consistency of results, directness of evidence, and certainty regarding outcome.
Results:
Fifty-five studies were examined. Only studies examining PBT interventions could be pooled statistically using meta-analysis. Eight "good" studies examined PBT, total n = 424; SOE was high for improved child behavior, standardized mean difference = -0.68 (95% confidence interval: -0.88 to -0.47), with minimal heterogeneity among studies. Only 1 good study evaluated methylphenidate, total n = 114; therefore, SOE for methylphenidate was low. Combined home and school/day care interventions showed inconsistent results. The literature reported adverse effects for methylphenidate but not for PBT.
Conclusions:
With more studies consistently documenting effectiveness, PBT interventions have greater evidence of effectiveness than methylphenidate for treatment of preschoolers at risk for ADHD.
Objective:
To review the association of priapism with stimulant medications and atomoxetine commonly used in the treatment of attention-deficit/hyperactivity disorder (ADHD).
Data sources:
A comprehensive literature search was conducted through PubMed (1966-May 15, 2014) using the search terms priapism, methylphenidate, amphetamine, atomoxetine, attention-deficit disorder with hyperactivity, and pediatrics. Google Scholar, Scopus, and the Food and Drug Administration (FDA) Web site were also searched. References from identified literature were also reviewed.
Study selection and data extraction:
All identified literature focused on ADHD treatment. Literature regarding priapism caused by methylphenidate, amphetamines, and atomoxetine were included.
Data synthesis:
Stimulant medications and atomoxetine have been linked to the occurrence of priapism in children. Specifically, methylphenidate has been implicated in a recent FDA safety announcement warning as a result of 15 case reports (mean age = 12.5 years), and thus, the drug label and medication guides have been updated to reflect this concern. Prolonged erections and priapism occurred with immediate- and long-acting products, dose increases, and drug withdrawal periods. Priapism has also occurred in 4 patients taking amphetamines and one 11-year-old patient taking atomoxetine for ADHD.
Conclusions:
Priapism has been associated with stimulants, amphetamines, and atomoxetine use for ADHD in children. Providers and health care practitioners should educate male patients prescribed these ADHD medications as well as caregivers regarding the signs, symptoms, and complications with priapism. Discontinuation and evaluation of the medication is warranted if this adverse drug reaction occurs. Depending on the priapism subtype, other products may be initiated or medications not associated with priapism may be utilized.
Objective:
The purpose of this study was to assess the effect of guanfacine extended release (GXR) adjunctive to a psychostimulant on oppositional symptoms in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).
Methods:
A multicenter, double-blind, placebo-controlled dose-optimization study of GXR (1-4 mg/d) or placebo administered morning (a.m.) or evening (p.m.) adjunctive to psychostimulant was conducted in subjects ages 6-17 with suboptimal response to psychostimulant alone. Suboptimal response was defined as treatment with a stable dose of psychostimulant for ≥4 weeks with ADHD Rating Scale IV total score ≥24 and Clinical Global Impressions-Severity of Illness score ≥3, as well as investigator opinion. Primary efficacy and safety results have been reported previously. Secondary efficacy measures included the oppositional subscale of the Conners' Parent Rating Scale-Revised: Long Form (CPRS-R:L); these are reported herein.
Results:
Significant reductions from baseline to the final on-treatment assessment on the oppositional subscale of the CPRS-R:L were seen with GXR plus psychostimulant compared with placebo plus psychostimulant, both in the overall study population (placebo-adjusted least squares [LS] mean change from baseline to the final on-treatment assessment: GXR a.m.+psychostimulant, -2.4, p=0.001; GXR p.m.+psychostimulant, -2.2, p=0.003) as well as in the subgroup of subjects with significant baseline oppositional symptoms (GXR a.m.+psychostimulant, -3.6, p=0.001; GXR p.m.+psychostimulant, -2.7, p=0.013). Treatment-emergent adverse events were reported by 77.3%, 76.3%, and 63.4% of subjects in the GXR a.m., GXR p.m., and placebo groups, respectively, in the overall study population.
Conclusions:
GXR adjunctive to a psychostimulant significantly reduced oppositional symptoms compared with placebo plus a psychostimulant in subjects with ADHD and a suboptimal response to psychostimulant alone.
The efficacy of three dietary treatments for ADHD has been repeatedly tested in randomized controlled trials (RCTs). These interventions are restricted elimination diets (RED), artificial food colour elimination (AFCE) and supplementation with free fatty acids (SFFA). There have been three systematic reviews and associated meta-analyses of the RCTs for each of these treatments.
The aim of this review is to critically appraise the studies on the dietary treatments of ADHD, to compare the various meta-analyses of their efficacy that have been published and to identify where the design of such RCTs could be improved and where further investigations are needed.
The meta-analyses differ in the inclusion and exclusion criteria applied to potentially eligible studies. The range of average effect sizes in standard deviation units is RED (0.29-1.2), AFCE (0.18-0.42) and SFFA (0.17-0.31). The methodology of many of the trials on which the meta-analyses are based is weak.
Nevertheless, there is evidence from well-conducted studies for a small effect of SFFA. Restricted elimination diets may be beneficial, but large-scale studies are needed on unselected children, using blind assessment and including assessment of long-term outcome. Artificial food colour elimination is a potentially valuable treatment but its effect size remains uncertain, as does the type of child for whom it is likely to be efficacious. There are additional dietary supplements that have been used with children with ADHD. A systematic search identified 11 RCTs that investigated the effects of these food supplements. Despite positive results for some individual trials, more studies are required before conclusions can be reached on the value in reducing ADHD symptoms of any of these additional supplements.
To comprehensively evaluate the efficacy and safety of atomoxetine (ATX) in pediatric attention-deficit/hyperactivity disorder (ADHD).
Meta-analysis of all double-blind randomized controlled trials (DBRCTs) evaluating the efficacy and tolerability of ATX for ADHD. Pooled, random-effects analyses were conducted, calculating standardized mean difference (SMD), yielding effect sizes (ES), relative risk (RR), and number-needed-to-treat/harm (NNT/NNH).Moderator/mediator analyses were also conducted, including metaregression.
Across 25 DBRCTs (56 treatment arms, N = 3,928), ATX outperformed placebo regarding overall ADHD symptoms (ES = -0.64, 95% confidence interval [CI] = -0.56 to -0.71, p < 0.0001), hyperactivity/impulsivity (ES = -0.67, CI = -0.53 to -0.81, p < 0.0001), and inattention (ES = -0.59, CI = -0.51 to -0.67, p < 0.0001). Altogether, 44.4% versus 21.4% of patients improved by ≥40% (NNT = 4), whereas 39.9% versus 65.9% improved by <25% (NNT = 4). Oppositional defiant disorder symptoms (ES = -0.33) and quality-of-life-related outcomes (ES = -0.48 to -0.25) improved somewhat less. A higher percentage of treatment-naïve patients moderated the efficacy of ATX for overall ADHD symptoms (p = 0.017). All-cause discontinuation with ATX was similar to that for placebo (p = 1.00), with lower discontinuation because of inefficacy (relative risk [RR] = 0.51, CI = 0.36-0.74, p < 0.0001, NNT = 34), but higher discontinuation because of adverse effects (AEs) (RR = 1.89, CI = 1.08-3.31, p = 0.03, NNH = 50) with ATX. At least 1 adverse effect (AE) (70.4% versus 56.1%, p < 0.01, NNH = 6) and ≥1 psychiatric AE (21.5% versus 7.4%, NNH = 7, p < 0.01) were more frequent with ATX, whereas serious AEs (1.5% versus 1.0%), aggression (7.5% versus 6.0%), and suicidal ideation (1.3% versus 0.9%) were not different from placebo.
Short-term ATX treatment is safe and superior to placebo for overall ADHD symptoms and key secondary outcomes, with a medium ES. However, a relevant patient subgroup (40%) continues to have significant symptomatology, requiring additional clinical attention.
To meta-analyze the efficacy and safety of α-2 agonists in pediatric attention-deficit/hyperactivity disorder (ADHD).
We searched MEDLINE, EMBASE, Cochrane Library, CINAHL, and PsycINFO until May 2013 for randomized trials comparing α-2 agonists with placebo in ADHD youth. Primary outcome was reduction in overall ADHD symptoms. Secondary outcomes included hyperactivity/impulsivity, inattentiveness, oppositional defiant disorder symptoms (ODD symptoms), all-cause discontinuation, specific-cause discontinuation, and adverse effects. Standardized mean differences (SMD), relative risk (RR), and number-needed-to-treat/number-needed-to-harm (NNT/NNH) were calculated. Data were analyzed separately in monotherapy and as add-on to psychostimulants.
Altogether, 12 studies (N = 2,276) were included. Across 9 studies (n = 1,550), α-2 agonist monotherapy significantly reduced overall ADHD symptoms (SMD = -0.59, p < .00001), hyperactivity/impulsivity (SMD = -0.56, p < .00001), inattention (SMD = -0.57, p < .00001), and ODD symptoms (SMD = -0.44, p = .0004). Similarly, α-2 agonist add-on treatment (3 studies, n = 726) significantly reduced overall ADHD symptoms (SMD = -0.36, p < .0001), hyperactivity/impulsivity (SMD = -0.33, p < .0001), and inattention (SMD = -0.34, p < .0001), but effect sizes were lower than in monotherapy trials (p = .03-0.04). As monotherapy, α-2 agonists had lower all-cause (RR = 0.70, p = .01, NNT = 10) and inefficacy-related (RR = 0.39, p < .0001) discontinuations than did placebo; however, intolerability-related discontinuation was similar, despite significantly more common fatigue (NNH = 10), sedation (NNH = 17), and somnolence (NNH = 4) and significantly greater hypotensive (clonidine-IR), bradycardic (clonidine-IR), and QTc prolonging (guanfacine-XR) effects. Added to stimulants, α-2 agonists had all-cause and specific-cause discontinuations that were comparable to those of placebo, but somnolence (NNH = 10) was more common, and hypotensive and bradycardic effects (clonidine-XR and guanfacine-XR) were greater than with placebo.
α-2 Agonist monotherapy and, possibly to a lesser extent, co-treatment, are significantly superior to placebo for overall, hyperactivity, and inattentive ADHD symptoms. Efficacy advantages need to be balanced against fatigue, somnolence/sedation, hypotension, bradycardia, and possibly QTc prolongation.
Abstract Background: Attention-deficit/hyperactivity disorder (ADHD) is a pediatric psychological condition commonly treated with stimulant medications. Negative media reports and stigmatizing societal attitudes surrounding the use of these medications make it difficult for parents of affected children to accept stimulant treatment, despite it being first line therapy. Objective: The purpose of this study was to identify factors that influence parental decision making regarding stimulant treatment for ADHD. Methods: A systematic review of the literature was conducted to identify studies: 1) that employed qualitative methodology, 2) that highlighted treatment decision(s) about stimulant medication, 3) in which the decision(s) were made by the parent of a child with an official ADHD diagnosis, and 4) that examined the factors affecting the decision(s) made. Individual factors influencing parental treatment decision making, and the major themes encompassing these factors, were identified and followed by a thematic analysis. Results: Eleven studies reporting on the experiences of 335 parents of children with ADHD were included. Four major themes encompassing influences on parents' decisions were derived from the thematic analysis performed: confronting the diagnosis, external influences, apprehension regarding therapy, and experience with the healthcare system. Conclusions: The findings of this systematic review reveal that there are multiple factors that influence parents' decisions about stimulant therapy. This information can assist clinicians in enhancing information delivery to parents of children with ADHD, and help reduce parental ambivalence surrounding stimulant medication use. Future work needs to address parental concerns about stimulants, and increase their involvement in shared decision making with clinicians to empower them to make the most appropriate treatment decision for their child.