Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder (ADHD), and its safety and efficacy show significant differences in the pediatric population. This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme CYP2D6 of atomoxetine, and then from the perspective of therapeutic drug monitoring, this article summarizes the reference ranges of the effective concentration of atomoxetine in children with ADHD proposed by several studies. In general, there is an association between the peak plasma concentration of atomoxetine and clinical efficacy, but with a lack of data from the Chinese pediatric population. Therefore, it is necessary to establish related clinical indicators for atomoxetine exposure, define the therapeutic exposure range of children with ADHD in China, and combine CYP2D6 genotyping to provide support for the precision medication of atomoxetine.
Adult ; Child ; Humans ; Adrenergic Uptake Inhibitors/therapeutic use* ; Atomoxetine Hydrochloride/therapeutic use* ; Attention Deficit Disorder with Hyperactivity/genetics* ; Cytochrome P-450 CYP2D6/therapeutic use* ; Drug Monitoring ; Genetic Testing ; Propylamines/therapeutic use* ; Treatment Outcome

OBJECTIVE: To explore the clinical and genetic characteristics of a boy with isolated maternal uniparental disomy of chromosome 20 [UPD(20)mat]. METHODS: A child who was admitted to the Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology on April 8,2021. was selected as the study subject. Phenotypic and endocrinological findings of the child were retrospectively analyzed. Whole exome sequencing (WES) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were carried out for detecting the UPD sequences and copy number variations. Both of his parents were verified by Sanger sequencing. Relevant literature was systematically reviewed. RESULTS: The child, a 3-year-and-8-month-old boy born to a 41-year-old mother by Cesarean delivery at 36⁺² gestational weeks due to oligohydramia, had a birth weight of 2 300 g and length of 46 cm. He was admitted to the NICU for feeding difficulties which had persisted despite of clinical management. At the age of 3.75, he had a height of 92.5 cm (< 3rd percentile; 25th ~ 50th percentile at 2.5 years) and a weight of 10.8 kg (< 3rd percentile; 50th percentile at 15 months). He had also presented with growth retardation, short stature, attention deficit and hyperactivity disorder (ADHD), mild mental retardation, and speech and language development disorders. He had simian creases in both hands but no additional dysmorphic signs, and his motor development was normal. Serum insulin, thyroid-stimulating hormone, and insulin growth factor binding protein 3 levels were within the normal ranges, though insulin growth factor-1 (IGF-1) was slightly decreased. Since that time he had continuously used atomoxetine hydrochloride capsules to control his ADHD. WES and MS-MLPA revealed the existence of UPD (20)mat. CONCLUSION The UPD(20)mat syndrome is characterized by feeding difficulties, growth retardation and short stature. The child in our case has been accompanied by ADHD and speech and language development disorders, which required long-term treatment. For women with advanced maternal age and suggestive phenotypes, genetic testing and counseling should be conducted.
Male ; Pregnancy ; Humans ; Child ; Female ; Infant ; Adult ; Chromosomes, Human, Pair 20 ; DNA Copy Number Variations ; Retrospective Studies ; Uniparental Disomy/genetics* ; Atomoxetine Hydrochloride ; Dwarfism ; Intercellular Signaling Peptides and Proteins ; Language Development Disorders ; Growth Disorders ; Insulins

OBJECTIVES: The objective of this study was to investigate clinical and neuropsychological factors associated with treatment response and adverse events of atomoxetine in children with attention-deficit/hyperactivity disorder (ADHD) in Korea. METHODS: Children with ADHD were recruited at the Department of Psychiatry of Asan Medical Center from April 2015 to April 2018. Diagnoses of ADHD and comorbid psychiatric disorders were confirmed with the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version. The subjects were subsequently treated with atomoxetine for 12 weeks and illness severity was scored using the ADHD Rating Scale, Clinical Global Impression-Severity scale (CGI-S) and/or Improvement scale (CGI-I), at pre- and post-treatment. They also completed the Advanced Test of Attention (ATA), while their caregivers completed the Korean Personality Rating Scale for Children (KPRC) at pre- and post-treatment. Independent t-test, Fisher's exact test, χ2 test, mixed between-within analysis of variance and correlation analysis were used for statistical analysis. RESULTS: Sixty-five children with ADHD (mean age: 7.9±1.4 years, 57 boys) were enrolled, of which, 33 (50.8%) were treatment responders. Scores on the social dysfunction subscale of the KPRC (p=0.021) and commission errors on the visual ATA (p=0.036) at baseline were higher in treatment non-responders than in responders; however, the statistical significances disappeared after adjusting for multiple comparisons. Mood changes were also observed in 13 subjects (20.0%), and three of them discontinued atomoxetine due to this. Additionally, atomoxetine-emergent mood change was observed more frequently in girls (p=0.006), while the intelligence quotient (p=0.040) was higher in those subjects with mood changes than in those without. CONCLUSION: The results of our study suggest that clinical and neuropsychological factors could be associated with treatment response or adverse events of atomoxetine in children with ADHD. Further long-term studies with larger samples are needed.
Atomoxetine Hydrochloride ; Caregivers ; Child ; Chungcheongnam-do ; Diagnosis ; Female ; Humans ; Intelligence ; Korea ; Mood Disorders

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder defined by impairing levels of inattention, disorganization, and/or hyperactivity-impulsivity. ADHD often persists into adulthood, with resultant impairments of social, academic and occupational functioning. ADHD is a very common disease during childhood and, the pooled overall prevalence of ADHD was found to be 5.29%. When screening for ADHD, clinicians should try to develop rapport with patients and their caregivers to increase the likelihood that they will follow the diagnostic process and treatment. The current drugs that have received Food and Drug Administration-approval for ADHD include stimulants (methylphenidate and dextroamphetamine) and non-stimulants (atomoxetine, guanfacine, and clonidine). Stimulants improve inattention, hyperactivity, and impulsivity in addition to decreasing disruptive behaviors and promoting academic achievement and the maintenance of appropriate friendships. In order to enhance drug compliance, the use of long-acting stimulants is increasing. Atomoxetine is a selective norepinephrine reuptake blocker, the effects of which may take 2 to 6 weeks to be noticeable. Furthermore, α2 agonists may help to improve behavioral side effects, tics, and sleep problems during stimulant or atomoxetine use. Common side effects of stimulants and atomoxetine include headache, stomachache, and loss of appetite. Routine electorcardiography before medication is not recommended unless there is a specific indication. Methylphenidate and atomoxetine are safe as first line therapies, and their side effects are well tolerated.
Appetite ; Atomoxetine Hydrochloride ; Attention Deficit Disorder with Hyperactivity ; Caregivers ; Compliance ; Drug Therapy ; Friends ; Guanfacine ; Headache ; Humans ; Impulsive Behavior ; Mass Screening ; Methylphenidate ; Neurodevelopmental Disorders ; Norepinephrine ; Prevalence ; Problem Behavior ; Tics

A structured review study of drug interventions on sleep disorders in patients with autism spectrum disorders (ASD) has not been published to date. This systematic review aimed to investigate drug interventions for the treatment of sleep disorders in children with ASD. The Web of Science, PubMed, and Scopus databases were searched until March 2019. Study quality was assessed using the Delphi checklist. Due to the heterogeneity of the findings, a meta-analysis was not possible. Drug interventions for the treatment of sleep disorders in patients with ASD included melatonin, atomoxetine, and risperidone. Atomoxetine had no effect on sleep disorders in patients with ASD. A total of 10 studies were reviewed. Melatonin appears to be useful for the treatment of sleep problems in patients with ASD, but further studies are needed to determine the effects of other drugs.
Atomoxetine Hydrochloride ; Autism Spectrum Disorder ; Autistic Disorder ; Checklist ; Child ; Humans ; Melatonin ; Population Characteristics ; Risperidone ; Sleep Wake Disorders

OBJECTIVE: We aimed to investigate the long-term effects of atomoxetine on growth in Korean children and adolescents with attention-deficit/hyperactivity disorder (ADHD). METHODS: The medical records of 82 subjects (mean age, 9.0±2.0 years; 64 boys) with ADHD treated with atomoxetine for at least 1 year at the Department of Psychiatry at Asan Medical Center were retrospectively reviewed. Height and weight data were prospectively obtained and retrospectively gathered and converted to age- and gender-corrected z scores using norms from Korean youths. Growth changes were analyzed using random coefficients models with changes in height or weight z scores as the dependent variables. RESULTS: Height z scores significantly decreased during the treatment period (β=-0.054, p=0.024). Height z scores decreased during the 1st year of treatment (β=-0.086, p=0.003), but did not change after the 1st year. Weight z scores did not change significantly during treatment (β=0.004, p=0.925). CONCLUSION: Our results suggest that long-term atomoxetine treatment may be associated with deficits in height growth in Korean youths, although this effect was minor and tended to be attenuated over the first year. Because of the limitations of this study such as retrospective design and selection bias, further prospective studies are needed.
Adolescent* ; Atomoxetine Hydrochloride* ; Child* ; Chungcheongnam-do ; Humans ; Medical Records ; Prospective Studies ; Retrospective Studies* ; Selection Bias

OBJECTIVE: This study aimed to assess treatment persistence in Korean children and adolescents with attention deficit hyperactivity disorder (ADHD) and the factors influencing their adherence to ADHD pharmacotherapy. METHODS: The study included patients between 6 and 18 years of age with ADHD who were taking various formulations of methylphenidate and atomoxetine on June 1, 2014. Patients were dichotomized as “persistent” or “non-persistent”, depending on whether they continued ADHD therapy for 6 months (therapy persistence). We also investigated if the patients were taking the same medication(s) as before and also classified the patients as “medication persistent” or “non-persistent”. Patient' characteristics were correlated with therapy persistence and medication persistence. Multiple logistic regression analyses were performed to assess potential risk factors for treatment persistence. RESULTS: Overall, 3,317 patients were included in the analysis. A majority of patients were taking stimulants (82.0%), 16.2% were taking non-stimulants and 1.8% were taking a combination therapy of stimulants and non-stimulants. After 6 months, 2,290 patients (69.0%) continued to take medication for ADHD with 1,953 patients taking the same medication(s) as 6 months previously. Common positive factors for therapy persistence and medication persistence were identified as younger age, retardation, and developmental delay, and long-acting formulations of methylphenidate as either monotherapy or in a combination therapy may be used. CONCLUSION: ADHD medications were proven to improve academic performance and social skills of children. Collaboration between patients, parents, school staffs, and prescribers is required to improve the persistent use of ADHD medications.
Adolescent* ; Atomoxetine Hydrochloride ; Attention Deficit Disorder with Hyperactivity* ; Child* ; Cooperative Behavior ; Drug Therapy* ; Humans ; Korea* ; Logistic Models ; Medication Adherence ; Methylphenidate ; Parents ; Risk Factors ; Social Skills

OBJECTIVES: The objective of this study was to investigate the effect of pharmacological treatments for attention-deficit hyperactivity disorder (ADHD) on motor coordination, using the Developmental Coordination Disorder Questionnaire (DCDQ). METHODS: The participants were recruited from April 2015 to November 2016 from the Department of Psychiatry of Asan Medical Center and were treated for 3 months with methylphenidate or atomoxetine. The illness severity at baseline and 3 months were scored using the ADHD Rating Scale (ARS), Clinical Global Impression-Severity Scale (CGI-S) and/or Clinical Global Impression-Improvement Scale (CGI-I). A total of 39 children with ADHD (age 8.0±1.4 years, 36 boys) completed the Advanced Test of Attention (ATA) and their parents completed the DCDQ at baseline and 3 months. The paired t-test, mixed between-within analysis of variance and correlation analysis were used. RESULTS: The CGI-S (p<0.001), ARS (p<0.001), and fine motor/hand writing (p=0.005) on the DCDQ were significantly changed between pre-treatment and post-treatment. When the participants were divided into those who were suspected of having developmental coordination disorder (DCD) (n=23) and those who probably did not (n=16), the control during movement, fine motor/hand writing and general coordination scores on the DCDQ showed the main effects for group (p<0.001, p<0.001 and p<0.001, respectively). The fine motor/hand writing on the DCDQ has a significant main effect for time [F(1,37)=7.31, p=0.010, η2=0.405] and the interaction effect between group and time was also significant [F(1,37)=4.63, p=0.038, η2=0.111]. The baseline visual commission error on the ATA is significantly correlated with the changes in the DCDQ total scores (r=0.330, p=0.040). CONCLUSION: Our results provide preliminary evidence that pharmacological treatment for ADHD improves not only the core symptoms of ADHD, but also the motor coordination. Further studies are needed to confirm the effect of the pharmacological treatment for ADHD on the motor coordination.
Atomoxetine Hydrochloride ; Child ; Chungcheongnam-do ; Drug Therapy ; Humans ; Methylphenidate ; Motor Skills Disorders ; Parents ; Writing

OBJECTIVE: Several factors, such as male gender, older age, type of insurance, comorbid conditions, and medication type, have been associated with attention-deficit/hyperactivity disorder (ADHD) medication adherence rates, but the results have been inconsistent. We analyzed data to answer several questions: 1) How old were patients who first refilled their treatment medications used primarily for ADHD, regardless of the medication type? 2) What socio-demographic factors are associated with medication adherence? 3) What medical conditions, such as medication type and comorbid diagnosis, influence adherence? METHODS: We analyzed National Health Insurance data, which comprised continuously enrolled Korean National Medical Insurance children (6–18 years) with at least 2 ADHD prescription claims (January 2008–December 2011). The persistence of use regarding the days of continuous therapy without a 30-day gap were measured continuously and dichotomously. Adherence, using a medication possession ratio (MPR), was measured dichotomously (80% cut-off). RESULTS: The cumulative incidence of index cases that initiated medication refills for ADHD treatment during the 4 year period was 0.85%. The patients who exhibited a MPR greater than 80 comprised approximately 66%. The medication type, high school age groups, physician speciality, treatment at a private clinic, and comorbid conditions were associated with medication adherence during continuous treatment using a multivariate analysis. CONCLUSION: A better understanding of ADHD treatment patterns may lead to initiatives targeted at the improvement of treatment adherence and persistence. Other factors, including the severity, family history, costs, type of comorbidities, and switching patterns, will be analyzed in future studies.
Adolescent* ; Atomoxetine Hydrochloride ; Child* ; Cohort Studies* ; Comorbidity ; Compliance ; Diagnosis ; Humans ; Incidence ; Insurance ; Insurance, Health* ; Male ; Medication Adherence ; Multivariate Analysis ; National Health Programs ; Prescriptions ; Retrospective Studies*

The objective of this review is the revision of the Korean practice parameters for the pharmacological treatment of attention-deficit hyperactivity disorder (ADHD) based on the change in the diagnostic system from DSM-IV-TR to DSM-5 and psychopharmacological developments. For the evidence-based approach, the authors conducted a review of the literature, including controlled clinical trials, studies of the side effects of drugs, toxicology and meta-analyses from the United States and Europe, as well as recent research conducted in Korea. The review committee composed of Korean experts on ADHD reviewed the revised parameters. This revised version reveals how to use central nervous system psychostimulants, non-stimulants such as atomoxetine and alpha2 agonists, and other medication for ADHD, and how to manage the adverse effects of such medication. At the end of this revised version, the authors propose recommendations for the pharmacotherapy of ADHD.
Advisory Committees ; Atomoxetine Hydrochloride ; Central Nervous System ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Europe ; Korea ; Toxicology ; United States