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Attention-deficit/hyperactivity disorder (ADHD) is a complex and heterogeneous neurodevelopmental disorder from a causal, clinical and prognostic perspective. Research reflects its multifactorial nature with a prominent role of genetic factors. Population studies have historically pointed to the involvement of numerous genetic variants of small effect size, which hardly by themselves increase the risk of presenting the disorder and hardly justify its high heritability. Many of them are present in more than 60% of the general population, suggesting their modulatory rather than causal role. However, after the irruption of new genetic techniques in the last 15 years, a greater number of cases are being identified with genetic disorders (many of them monogenic), whose genetic variants alone explain the presence of ADHD. A detailed study of the personal and family history, as well as a complete physical examination, can help to identify some of them. The identification of the cause in this group of cases has a crucial value in clinical counseling, genetic-familial counseling and prognostic anticipation, as well as in the performance or avoidance of complementary studies and in the design of the intervention plan.

Beyond the frequent coexistence of attention deficit hyperactivity disorder (ADHD) and reading disorder (dyslexia), the present review aims to examine the available empirical evidence on how ADHD negatively impacts on learning to read. Existing data suggest that the presence of the disorder (especially inattention symptoms), may affect i) the correct acquisition of reading, either directly or through its influence on the precursors to reading; ii) decoding skills themselves (reading accuracy and fluency), both directly and indirectly through its influence on cognitive processes such as distractibility or executive functions; and iii) reading comprehension, probably indirectly through the executive and verbal memory difficulties characteristic of ADHD. These findings have important implications for better characterizing and intervening on reading difficulties in ADHD, whether clinical or subclinical.

This study aims to contribute to a better understanding of attention deficit hyperactivity disorder (ADHD) by comprehensively examining the relationship between two of the main cognitive deficits of the disorder (attention and inhibitory control), symptomatology (inattention and hyperactivity/impulsivity) and functional impairment in 85 children and adolescents with ADHD without other comorbid disorders. We found, independent of general intellectual functioning and age, that i) greater attentional and inhibitory deficits predicted greater severity of ADHD symptoms, ii) greater attentional and inhibitory deficits predicted greater functional impairment, but not in a direct way but through symptoms, and iii) greater symptomatic severity predicted greater functional impairment. Beginning to explore and understand the complexity of ADHD is key to advance our knowledge of the disorder and for correct clinical decision making.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent disorders in the child and adolescent population, with a known impact on learning, social relations and quality of life. However, the lifestyle habits of patients with this disorder have been poorly studied., Material and Methods: A total of 160 children and adolescents, aged between 6 and 16 years, participated in the study. Half of them were treatment-naïve patients with a clinical diagnosis of ADHD according to DSM-IV-TR criteria, and without comorbidities. The remaining 80 participants were typically developing (TD) controls without known neurodevelopmental or psychiatric disorders. Parents of all participants completed a questionnaire about their children´s lifestyle habits (e.g, daily hours of sleep, media use and study)., Results: The groups had a similar socioeconomic background and did not differ with respect to age and sex distribution. However, patients with ADHD spent more time than TD children studying, and less time watching TV, playing video games, using computers and playing with other people. They also slept fewer hours per night than children and adolescents with TD. ADHD and TD groups spent similar time reading, listening to music and playing sports., Conclusions: The results of this study suggest that children and adolescents with ADHD have different lifestyle habits compared to age- and sex-matched controls. These findings are not explained by comorbid disorders or medication/ psychological treatment.

Attention deficit / hyperactivity disorder (ADHD) is one of the most prevalent disorders in the child-youth population, with a known impact on learning and school performance. Lack of attention, associated executive dysfunction and comorbid problems -particularly those related to learning and anxiety-, strongly determine this conceptual domain. Affected youths have more problems for taking notes, completion of homework, school programming and less motivation to study. Despite greater dedication to homework and greater use of support resources, school failure and nonachievement of curricular objectives are more frequent in these patients. The early diagnosis of ADHD and its comorbidities, the adequate and individualized psychoeducational and pharmacological intervention, have been shown to improve academic prognosis in the short and long term. For this purpose, the active participation of health and education professionals is essential.

Objective: This study aimed to examine the influence of dopamine transporter gene ( DAT1) 3'UTR genotype on cingulate cortical thickness in a large sample of children and adolescents with ADHD., Method: Brain MRIs were acquired from 46 ADHD patients with homozygosity for the 10-repeat allele and 52 ADHD patients with a single copy or no copy of the allele. The cingulate cortex of each MRI scan was automatically parceled into sulci and gyri as well as into Brodmann areas (BA)., Results: There were no group differences in age, gender, full-scale intelligence quotient, symptom severity, treatment status, comorbidity, or mean overall cortical thickness. Sulcus/gyrus- and BA-based analyses revealed that patients homozygous for the 10-repeat allele showed significantly greater thickness in right cingulate gyrus and right BA 24 compared with 9-repeat carriers., Conclusion: These findings suggest that thickness of cingulate cortex is influenced by the presence of the 10-repeat allele in ADHD.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition in childhood (5.3% to 7.1% worldwide prevalence), with substantial overall financial burden to children/adolescents, their families, and society. The aims of this study were to describe the clinical characteristics of children and adolescents with ADHD in Spain, estimate the associated direct/indirect costs of the disorder, and assess whether the characteristics and financial costs differed between children/adolescents adequately responding to currently available pharmacotherapies compared with children/adolescents for whom pharmacotherapies failed., Methods: This was a multicenter, cross-sectional, descriptive analysis conducted in 15 health units representative of the overall Spanish population. Data on demographic characteristics, socio-occupational status, social relationships, clinical variables of the disease, and pharmacological and non-pharmacological treatments received were collected in 321 children and adolescents with ADHD. Direct and indirect costs were estimated over one year from both a health care system and a societal perspective., Results: The estimated average cost of ADHD per year per child/adolescent was €5733 in 2012 prices; direct costs accounted for 60.2% of the total costs (€3450). Support from a psychologist/educational psychologist represented 45.2% of direct costs and 27.2% of total costs. Pharmacotherapy accounted for 25.8% of direct costs and 15.5% of total costs. Among indirect costs (€2283), 65.2% was due to caregiver expenses. The total annual costs were significantly higher for children/adolescents who responded poorly to pharmacological treatment (€7654 versus €5517; P = 0.024), the difference being mainly due to significantly higher direct costs, particularly with larger expenses for non-pharmacological treatment (P = 0.012)., Conclusions: ADHD has a significant personal, familial, and financial impact on the Spanish health system and society. Successful pharmacological intervention was associated with lower overall expenses in the management of the disorder.

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in childhood, which is frequently maintained in adolescent and adult age. It presents great clinical heterogeneity, significantly affecting the functioning of those who suffer it. Although drug treatments obtain results by themselves, the approach should be multidisciplinary and be adapted to the specific needs of each patient and his/ her family. Given the variety of drugs currently available to treat ADHD, there are diverse opinions on the most effective way to approach this disorder. The objective of this work is to study the opinion of an expert clinical panel and to know the professional criteria used to define key concepts and therapeutic guidelines of ADHD in Spain., Methodology: The project was carried out in four phases: 1) Constitution of a Scientific Committee, responsible for the preliminary biographic review and the formulation of the questionnaire; 2) selection of an expert panel of specialists with special interest and/or experience in the treatment of ADHD; 3) Likert type structured survey (online platform) in two rounds with interim processing of opinions; and 4) collection and final analysis of results., Results: The experts’ panel achieved a consensus in 55 of the 58 items making up the questionnaire, finding 3 items in which sufficient unanimity of criteria was not achieved because of the high number of experts were found in positions of non-certainty., Conclusions: Overall, the experts of this study reached a high level of agreement in the criteria proposed in the survey, which could be generalized as indications for the clinical practice in the management of ADHD. Similarly, and given the dispersion of the results in some of the items and the lack of consensus in others, some points remain as object of discussion.

Several lines of evidence suggest that the dopamine transporter gene (DAT1) plays a crucial role in attention deficit hyperactivity disorder (ADHD). Concretely, recent data indicate that the 10-repeat (10R) DAT1 allele may mediate neuropsychological functioning, response to methylphenidate, and even brain function and structure in children with ADHD. This study aimed to investigate the influence of 10R DAT1 on thickness of the prefrontal cortex in children and adolescents with ADHD. To this end, brain magnetic resonance images were acquired from 33 patients with homozygosity for the 10R allele and 30 patients with a single copy or no copy of the allele. The prefrontal cortex of each MRI scan was automatically parceled into regions of interest (ROIs) based on Brodmann areas (BA). The two groups were matched for age, gender, IQ, ADHD subtype, symptom severity, comorbidity and medication status. However, patients with two copies of the 10R allele exhibited significantly decreased cortical thickness in right BA 46 relative to patients with one or fewer copies of the allele. No other prefrontal ROI differed significantly between the two groups. Present findings suggest that cortical thickness of right lateral prefrontal cortex (BA 46) is influenced by the presence of the DAT1 10 repeat allele in children and adolescents with ADHD., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction: The term adoption or adoptive filiation is understood as referring to the legal act by which family ties are created between two persons such that a relationship of fatherhood or motherhood is established between them. AIMS. The purpose of this study is to outline the problems derived from prenatal exposure to alcohol and other risk factors, from hypostimulation during the 'critical period' in institutionalised patients (especially those adopted from eastern European countries) and their relation with attention deficit hyperactivity disorder (ADHD). This work also seeks to take a deeper look into the diagnosis, prevention and treatment of these problems., Development: These children have problems in terms of psychosocial relationships, behavioural problems, delayed language or reading development and, above all, ADHD. In practice it is extremely difficult to separate the two factors during the assessment of children adopted from eastern European countries in neuropaediatric consultations. Exactly how all these factors are interrelated is not well understood., Conclusions: There is a close relationship between prenatal exposure to alcohol and the consequences of adoption. There is a need for placebo-controlled randomised studies, with larger population samples, that test the benefits and profile of side effects, both with psychostimulants and with atomoxetine in this group of patients.

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobiological disorders in childhood, and is characterized by inappropriate levels of inattention, hyperactivity and/or impulsiveness, with an estimated prevalence of 5.29%. ADHD can have a negative impact upon all areas of the life of the patient. The main clinical guides accept multimodal treatment, involving both pharmacological and psychological measures, as the best management approach in ADHD (psychoeducational, behavioural and academic). Lisdexamfetamine dimesylate (LDX) is a new drug for the treatment of ADHD. A multidiscipline expert document has been developed, compiling the scientific evidence referred to this new molecule. The study also addresses the existing shortcomings in current drug therapy for ADHD and the contributions of LDX to routine clinical practice, in an attempt to help and guide physicians in the use of this new treatment. This document is endorsed by the ADHD and Psychoeducational Development task Group of the Spanish Society of Primary Care Pediatrics (Grupo de TDAH y Desarrollo Psicoeducativo de la Asociación Española de Pediatría de Atención Primaria, AEPap), the Spanish Society of Pediatric Neurology (Sociedad Española de Neurología Pediátrica, SENEP) and the Spanish Society of Out-hospital Pediatrics and Primary Care (Sociedad Española de Pediatría Extrahospitalaria y Atención Primaria, SEPEAP).

Structural and functional brain studies on attention deficit/hyperactivity disorder (ADHD) have primarily examined anatomical abnormalities in the prefronto-striatal circuitry (especially, dorsal and lateral areas of the prefrontal cortex and dorsal striatum). There is, however, increased evidence that several temporal lobe regions could play an important role in ADHD. The present study used MRI-based measurements of cortical thickness to examine possible differences in both prefrontal and temporal lobe regions between medication-näive patients with ADHD (N = 50) and age- and sex-matched typically developing controls (N = 50). Subjects with ADHD exhibited significantly decreased cortical thickness in the right temporal pole and orbitofrontal cortex (OFC) relative to healthy comparison subjects. These differences remained significant after controlling for confounding effects of age, overall mean cortical thickness and comorbid externalizing conditions, such as oppositional defiant and conduct disorders. These results point to the involvement of the temporal pole and OFC in the neuropathology of ADHD. Moreover, present findings add evidence to the assumption that multiple brain regions and psychological processes are associated with ADHD., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Although, in everyday life, patients with attention deficit hyperactivity disorder (ADHD) are frequently distracted by goal-irrelevant affective stimuli, little is known about the neural and behavioral substrates underlying this emotional distractibility. Because some of the most important brain responses associated with the sudden onset of an emotional distracter are characterized by their early latency onset and short duration, we addressed this issue by using a temporally agile neural signal capable of detecting and distinguishing them. Specifically, scalp event-related potentials (ERPs) were recorded while 20 boys with ADHD combined type and 20 healthy comparison subjects performed a digit categorization task during the presentation of three types of irrelevant, distracting stimuli: arousing negative (A-), neutral (N) and arousing positive (A+). Behavioral data showed that emotional distracters (both A- and A+) were associated with longer reaction times than neutral ones in the ADHD group, whereas no differences were found in the control group. ERP data revealed that, compared with control subjects, boys with ADHD showed larger anterior N2 amplitudes for emotional than for neutral distracters. Furthermore, regression analyses between ERP data and subjects' emotional ratings of distracting stimuli showed that only in the ADHD group, emotional arousal (ranging from calming to arousing) was associated with anterior N2: its amplitude increased as the arousal content of the visual distracter increased. These results suggest that boys with ADHD are more vulnerable to the distracting effects of irrelevant emotional stimuli than control subjects. The present study provides first data on the neural substrates underlying emotional distractibility in ADHD., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The cardinal symptoms of attention deficit hyperactivity disorder (ADHD)--inattention, hyperactivity and impulsiveness--are not specific and may be found in the general population and in other disorders. These symptoms are present in over 50% of patients with autism spectrum disorders (ASD). It thus seems quite clear that both problems can coexist in these patients. The usual pharmacological treatments for ADHD, methylphenidate and atomoxetine, appear to be useful in reducing the above-mentioned symptoms in patients with ADHD and ASD. Effectiveness seems to be lower in patients with ASD and tolerance is slightly poorer. This may be conditioned by a number of variables, including: the complexity of ASD, association with mental retardation, polypharmacotherapy, and so on. Given the long-term tolerance profile of methylphenidate and atomoxetine, these treatments appear to be a good alternative with which to improve the problems of attention and self-control these patients have. Nevertheless, further controlled studies are needed to confirm this proposition.

Objective: Atomoxetine's tolerance and efficacy were studied in 24 patients with pervasive developmental disorder and symptoms of ADHD., Method: Prospective, open-label, 16-week study was performed, using the variables of the Clinical Global Impression Scale and the Conners' Scale, among others., Results: A significant difference was found between pre- and posttreatment scores as well as a significant reduction was found on the scales used. Only five patients presented adverse events., Conclusion: Atomoxetine therefore appears to be a useful drug, pointing to the need for larger, randomized, controlled, double-blind studies to confirm its efficacy versus placebo and in comparison with other treatment options.

Background: The Internet is increasingly used as a source of health-related information. The objective of this study was to assess the quality of web-based information on treatments for attention-deficit/hyperactivity disorder (ADHD)., Methods: Sixteen expert health professionals in ADHD and 35 parents of paediatric patients with a recent diagnosis of ADHD assessed the information contained in the 10 highest ranked websites in Spanish, using the Spanish version of the DISCERN tool - a validated questionnaire designed to assess the quality and reliability of web-based information on treatment choices (rating scores from 15 to 75)., Results: DISCERN scores given by parents and experts were low (total mean scores [standard deviation]: 35.9 [13.1] and 43.4 [13.7], respectively) and inter-rater agreement was poor/moderate (weighted kappa for the global assessment between -0.69 and +0.93, average = 0.29). There was a significant change on the ADHD-knowledge and motivation for treatment (ADHD-KMT) basic knowledge sub-scale score after the assessment of the different websites by parents (total mean scores [standard deviation]: 49.09 [9.46] and 63.21 [9.45])., Conclusions: Despite a poor/moderate inter-rater agreement between parent and expert opinions, all agreed that the quality of the web-based information on treatment choices for ADHD is generally poor.

Objective: We have analyzed social and leadership abilities in children with ADHD and their relationship with execution of tasks involving sustained attention and inhibitory control., Patients and Methods: A retrospective analysis of 170 patients with ADHD was performed. We evaluated leadership and social abilities, measured through the Behavior Assessment System for Children (BASC) and their relations with the results of different neuropsychological tests, including Wechsler scale for children (WISC-IV) and Conners' continuous performance (CPT II)., Results: In the differential analysis between the IQ, results of the tests and their relation to BASC scores, a statistically significant relation was observed between attentional capacity expected according to the patient's intelligence and social skills scores (according to BASC filled out by mothers and teachers) and leadership (according to all informants) sections., Conclusions: Attentional difficulties are closely related to social competence in patients with ADHD, either by a direct cause-effect relationship or a shared dysexecutive substrate of this disorder.

Attention deficit hyperactivity disorder (ADHD) is a remarkably heterogeneous neurobiological disorder. This characteristic is aetiologically mediated by genetic and environmental factors. Numerous studies have shown that different genes play a moderate but complex role in the aetiology of ADHD. Significant associations have been identified with several candidate genes for this disorder, including DAT1, DRD4, DRD5, 5HTT, HTR1B or SNAP25. The neurocognitive models of ADHD have been largely based on the findings from neuroimaging studies conducted in patients with ADHD, when establishing hypotheses capable of explaining the clinical features that are observed. From a neurobiological point of view, the genetic architecture of these patients or the interaction of the above-mentioned genes should at least partially account for the neuroanatomical and neuropsychological findings observed, which explains the axiomatic antithesis in the title. Nevertheless, the results of studies into the relationship between the genotyping and the neuroimaging or psychological findings are scarce and contradictory. The methodological differences in the volumetric analyses, the sizes of the populations studied, the neuropsychological batteries that are used, the presence of previous pharmacological treatment or comorbidity could account for these results.

Fetal alcohol syndrome represents the classic and most severe manifestation of epigenetic changes induced by exposure to alcohol during pregnancy. Often these patients develop attention deficit hyperactivity disorder. We analyzed cortical thickness in 20 children and adolescents with fetal alcohol syndrome and attention deficit hyperactivity disorder (group 1), in 20 patients without fetal alcohol syndrome (group 2), and in 20 control cases. The first group revealed total cortical thickness significantly superior to those of the other two groups. In per-lobe analyses of cortical thickness, group 1 demonstrated greater cortical thickness in the frontal, occipital, and right temporal and left frontal lobes compared with the second group, and in both temporal lobes and the right frontal lobe compared with the control group. This study demonstrated greater cortical thickness in patients with attention deficit hyperactivity disorder and heavy prenatal exposure to alcohol, probably as an expression of immature or abnormal brain development., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Numerous studies have documented that children with attention deficit hyperactivity disorder (ADHD) show a low social competence., Objective: To compare the symptomatic severity of ADHD, as well as associations to different subtypes, sex and comorbidities, with social functioning ("ability" and "leadership") estimated through a Behavior Assessment System for Children (BASC) for parents and teachers., Patients and Methods: We have retrospectively analyzed 170 patients with ADHD, diagnosed between 2007 and 2010. Social "ability," "leadership," "hyperactivity" and "attention deficit" sections of BASC and cardinal symptoms of ADHD measured through a Spanish scale for de evaluation of DHD (E-DHD) were registered. Results of these variables are analyzed according to the normative data by age and sex, and processed in Z values., Results: The ratings for social skills were significantly lower in patients with conduct disorder or oppositional defiant disorder as informed by parents (p<0.05). Symptomatic intensity of ADHD showed significant (p<0,001) and inverse relation with social "ability" as parents. "Attention-deficit" scores were related with social "ability" and "leadership" as parents and teachers., Conclusions: Intensity of attention deficit was the only variable that showed a significant relation with the social skills and leadership according to the BASC scores, independently of the informer.

The study objective was to assess the efficacy and tolerability of atomoxetine in the treatment of attention deficit hyperactivity disorder symptoms in patients with mental retardation. In a 16-week, open-label, prospective study, 48 children with mental retardation and attention deficit hyperactivity disorder were recruited; the patients received atomoxetine, with a single final dose of 1.2 mg/kg per day reached at 3 weeks. The measure of efficacy was scores on Clinical Global Impression Severity scale (CGI-S), Conners, and Attention Deficit Hyperactivity Disorder Rating Scale ADHDRS-IV. A statistically significant difference was documented between the mean CGI-S scores before and after treatment: baseline CGI-S = 5.31 (S.D. = 0.85); post-treatment CGI-S = 4.13 (S.D. = 0.97), with a difference of 1.18 points (S.D. = 0.84) and a 95% confidence interval for the difference of 0.92-1.43 (P < 0.001). A statistically significant reduction (P < 0.01) was observed with respect to all the variables of the ADHDRS-IV and Conners scales. Slightly less than one third of the patients (31%) presented adverse events, the majority of which were mild, with irritability being the most frequent event. Atomoxetine appears to be to useful in improving attention deficit hyperactivity disorder symptoms in mentally retarded patients. Larger, randomized, controlled, double-blind studies are required to confirm the efficacy observed in this first study., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Much attention has been paid in recent years to the role of prenatal exposure to alcohol. Fetal alcohol syndrome is one of the most severe afflictions resulting from such exposure. The present report documents the cases of adopted children diagnosed with fetal alcohol syndrome who developed both Tourette syndrome and attention deficit-hyperactivity disorder. Out of a population of 138 adopted children with behavior issues whose clinical histories were reviewed retrospectively, 9 children (6.5%) presented this constellation. Epidemiologic data, clinical data, neurologic examination findings, complementary testing, and developmental data were recorded. All nine patients studied had initial psychomotor retardation, despite the frequent case of subsequent intelligence quotient normalization. From a behavioral perspective, half of the cases presented obsessive-compulsive disorder and problems with social relations. Aggressive behavior was common. These cases also presented a high degree of severity of both tics and hyperactivity. The most common drug treatment was methylphenidate. This constellation of fetal alcohol syndrome, Tourette syndrome, and attention deficit-hyperactivity disorder is scantly reported in the literature and is likely underdiagnosed. This particular constellation poses its own prognosis and requires its own treatment., (Copyright 2010 Elsevier Inc. All rights reserved.)

Introduction: The objective of the study was to assess the efficacy of extended-release methylphenidate (Mph-ER) (Medikinet; MEDICE Arzneimittel Pütter GmbH & Co KG, Iserlohn, Germany) in the pediatric population with attention deficit/hyperactivity disorder (ADHD); a parallel analysis of the validity of various tools for monitoring short-term clinical response to treatment was made., Methods: This was a retrospective analysis of 94 children with ADHD who received treatment with Mph-ER. The ADHD Rating Scale-IV (ADHD-RS) was used to assess clinical efficacy. The following neuropsychological tests were used to assess cognitive-attentional efficacy: the faces test, the D2 test, the Magallanes visual attention scale (EMAV; Escalas Magallanes de Attencion Visual), and the Conners' Continuous Performance Test II (CPT-II). The ADHD-RS scale was completed by the parents at the time of diagnosis and after 3 months of treatment. The tests were taken by patients both without treatment and under the effects of treatment. The results of these variables were transformed into Z values for subsequent analysis., Results: In all, 84% of the patients lowered their ADHD-RS score with Mph-ER. Regarding the neuropsychological tests, a significant change was seen when the results of patients without treatment were compared with their later results with treatment. When the order of test conditions was reversed (with and then without treatment), the CPT-II was the only test for which there was still a significant difference., Conclusion: Mph-ER improved attention and self-control from a clinical and cognitive point of view. Of those studied, the CPT-II was the most effective neuropsychological test for monitoring efficacy of Mph in the short-term.

Background: Striatal cholinergic dysfunction may be important in tics and attention-deficit/hyperactivity disorder (ADHD)., Objective: The purpose of this study was to determine the safety profile of donepezil and whether it improves chronic tics in young patients with comorbid ADHD., Methods: This 18-week (14 weeks of open treatment followed by a 4-week washout period), single-center, dose-escalating, prospective, open-label trial was conducted in patients aged 7 to 17 years with tics, including chronic motor or vocal tics and Tourette's syndrome, and ADHD. Patients were treated with once-daily oral donepezil doses of 2.5 mg for 2 weeks, 5 mg for the next 6 weeks, and 10 mg for the last 6 weeks, followed by a 4-week washout period. Patients were evaluated using the Children's Global Assessment Scale; the Yale Global Tic Severity Scale (YGTSS); the Revised Conners' Parent Rating Scale; the Symbol and Digit Wisconsin Card Sorting Test; the Stroop black/white, color, and interference tests; the Rey Complex Figure Test; and the Children's Yale-Brown Obsessive Compulsive Scale at 4 visits: baseline, week 8 (5-mg dose), week 14 (10-mg dose), and week 18 (washout)., Results: Seventeen males and 3 females (mean [SD] age, 11.3 [1.9] years [range, 8-14 years]; tic duration, 5.3 [1.9] years; ADHD duration, 6.5 [1.7] years) were included in this study. Tics were significantly reduced at the 10-mg (week-14) donepezil visit compared with the baseline and washout visits based on the total mean (SD) tic score of the YGTSS (18.6 [9.3] vs 12.2 [11.0]; P = 0.006). Fifty percent of patients withdrew and 65% experienced adverse events., Conclusions: These preliminary results suggest that donepezil significantly reduced tics in these children and adolescents with comorbid ADHD who completed the study. No significant improvement in the symptoms of comorbid ADHD was found with the use of donepezil 10 mg. Donepezil 5 and 10 mg were not well tolerated in these children and adolescents.