Clinical study on modified self-made Qingxin Buqi Pinggan Decoction combined with atomoxetine hydrochloride in the treatment of attention deficit hyperactivity disorder / 国际中医中药杂志

Objective:To evaluate the efficacy of modified self-made Qingxin Buqi Pinggan Decoction combined with atomoxetine hydrochloride in the treatment of attention deficit hyperactivity disorder (ADHD).Methods:Randomized controlled trial. A total of 200 children with ADHD admitted to our hospital from January 2020 to January 2022 were selected as observation subjects by prospective cohort study, and were divided into two groups according to the random number table method. The control group was given oral administration of atomoxetine hydrochloride capsules, and the observation group was given self-made Qingxin Buqi Pinggan Decoction on the basis of the control group. Both groups were treated continuously for 3 months. Before and after treatment, the Traditional Chinese Medicine symptoms were scored, and the core symptoms of the children were evaluated by Swanson Nolan and Pelham-versionⅣ (SNAP-Ⅳ), and the hyperactivity tendency was assessed by Parent Symptom Questionnaire (PSQ). The serum cortisol (COR) and adrenocorticotropic hormone (ACTH) levels were measured by chemiluminescence immunoassay. Adverse reactions during treatment were observed and clinical efficacy was evaluated.Results:The total effective rate was 97.0% (97/100) in observation group and 88.0% (88/100) in control group ( χ2=5.84, P=0.016). After treatment, the scores of restlessness, hyperactivity, unsteadiness, emaciation, lusterless complexion and restless sleep in the observation group were significantly lower than those in the control group ( t=17.90, 11.79, 10.01, 23.27, 11.79, 12.03, P<0.01). The scores of impulsivity factor, learning factor, hyperactivity factor, behavior factor, psychosomatic factor and anxiety factor were significantly lower than those in the control group ( t=4.65, 42.83, 10.01, 41.89, 39.42, 18.30, P<0.01). The scores of attention deficit, hyperactivity-impulsivity and behavior performance were significantly lower than those in the control group ( t=11.68, 9.69, 28.42, P<0.01). After treatment, the levels of serum COR [(337.26±17.22) nmol/L vs. (275.51±15.49) nmol/L, t=26.66] and ACTH [(24.47±1.12) ng/L vs. (19.23±1.43) ng/L, t=28.85] were significantly higher in observation group than those in the control group ( P<0.01). During treatment, the incidence rate of adverse reactions was 6.0% in observation group and 5.0% in control group ( χ2=0.10, P=0.756). Conclusion:Modified self-made Qingxin Buqi Pinggan Decoction combined with atomoxetine hydrochloride can improve the clinical symptoms of children with ADHD, reduce the degree of hyperactivity disorder, increase the levels of serum COR and ACTH, and enhance the clinical efficacy.

A precision medication study of atomoxetine in children with attention deficit hyperactivity disorder: CYP2D6 genetic testing and therapeutic drug monitoring / 中国当代儿科杂志

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.

Clinical efficacy of atomoxetine combined with cognitive behavior therapy on children with attention deficit hyperactivity disorder / 中华行为医学与脑科学杂志

Objective:To investigate the clinical efficacy of atomoxetine combined with cognitive-behavioral therapy (CBT) on children with attention deficit hyperactivity disorder (ADHD).Methods:Totally 104 children diagnosed with ADHD were randomly divided into atomoxetine group ( n=34), CBT group ( n=35) and atomoxetine combined with CBT group ( n=35). After 12 weeks of treatment, questionnaire-children with difficulties (QCD), Swanson child behavior checklist (SNAP-Ⅳ) and Conners parents rating scales (CPRS) were used to evaluate the efficacy and recorded the adverse reactions during the treatment. SPSS 23.0 software was used for statistical analysis. Paired sample t-test was used to compare the scores of the same group before and after treatment, and one-way ANOVA was used to compare the difference between the three groups after treatment. Results:(1)Compared with baseline, the score of QCD increased(32.96±3.01, 43.00±2.22) ( t=-13.35, P<0.01) , while the attention deficit(15.67±3.46, 6.07±1.73), hyperactivity/impulse(13.59±3.41, 7.30±2.43), opposition disobedience(9.85±3.98, 2.59±2.17) and total score(39.11±6.65, 16.59±3.91) of SNAP-Ⅳ decreased in atomoxetine combined with CBT group after treatment ( t=14.96, 10.87, 11.77, 21.49, all P<0.01). The factor scores of behavior problems(0.81±0.30, 0.70±0.26), learning problems(1.58±0.31, 0.32±0.13), psychosomatic disorders(0.22±0.25, 0.16±0.20), impulse hyperactivity(1.27±0.37, 0.71±0.18), anxiety(0.32±0.26, 0.23±0.17) and hyperactivity index(1.19±0.40, 0.79±0.22) of CPRS also decreased ( t=2.71, 21.23, 2.41, 8.87, 2.96, 6.19, all P<0.05) in atomoxetine combined with CBT group after treatment. (2) After treatment, the changes of QCD scores, attention deficit dimension in SNAP-Ⅳ scale, learning problems and impulse hyperactivity dimension in CPRS scale of the three groups before and after treatment were statistically significant (all P<0.05). (3) Post LSD comparison showed that the change in CBT group was significantly lower than that in atomoxetine group and atomoxetine combined CBT group in QCD score(both P<0.05). In the dimension of attention deficit of SNAP-Ⅳ, the difference in CBT group was significantly lower than that in atomoxetine combined CBT group ( P<0.01). In the learning problems and impulse hyperactivity dimensions of CPRS, the changes of atomoxetine combined with CBT group were significantly higher than those of atomoxetine group and CBT group (all P<0.01). Conclusion:Atomoxetine combined with CBT has better curative effect than atomoxetine or CBT alone in patients with ADHD. It can effectively improve the core symptoms and daily life function of ADHD children, and has high safety.

Trastorno por déficit de atención con o sin hiperactividad aislado en consulta de Neuropediatría. Serie de casos / Isolated attention deficit disorder with/without hyperactivity in clinical practice. Series of cases

El trastorno por déficit de atención e hiperactividad afecta al 5 % de los niños en edad escolar. Se presenta una serie de 82 niños con este trastorno no asociado a enfermedades neurológicas ni a discapacidad intelectual o trastorno del espectro autista, atendidos durante un período de 8 meses en Neuropediatría: 57 casos de tipo combinado, 23 de tipo inatento y 2 de predominio hiperactivo. Tiempo medio de seguimiento: 7 ± 2,8 años (rango: 4-14,6). Compartían seguimiento con Psiquiatría 16 pacientes. Nunca recibieron tratamiento por decisión parental 12 pacientes. De los 70 que recibieron, en 20, hubo demora en el inicio del tratamiento. Tiempo medio de demora: 20 meses ± 1,6 años (rango: 1 mes y 6 años). Tiempo medio de tratamiento: 44 meses ± 2,6 años (rango: 1 mes y 10,5 años). El 90 % de los pacientes (63) que iniciaron tratamiento continuaban tomándolo en la última revisión

Attention deficit disorder with hyperactivity has a high prevalence affecting 5 % of school-age children. We present a case series of 82 children with said disorder not associated with neurological diseases or intellectual disability or autism spectrum disorder, treated during a period of 8 months in a neuropediatrics clinic: 57 cases of combined type, 23 of inattentive type and 2 of overactive predominance. Average follow-up time: 7 ± 2.8 years (range: 4-14.6); 16 patients shared follow-up with Psychiatry; 12 patients never received treatment by parental decision. Of the 70 who received it, in 20 there was a delay in the start of treatment. Average delay time: 20 months ± 1.6 years (range: 1 month and 6 years). Average treatment time: 44 months ± 2.6 years (range: 1 month and 10.5 years); 90 % of the patients (63) who started treatment were under treatment at the last control

Tratamiento del trastorno por déficit de atención con hiperactividad en la práctica clínica habitual: Estudio retrospectivo / Treatment of attention-deficit/hyperactivity disorder in clinical practice. A retrospective study

El trastorno por déficit de atención e hiperactividad (TDAH) es un trastorno del neurodesarrollo complejo y heterogéneo, de carácter crónico, de etiología multifactorial, principalmente debida a factores genéticos y ambientales. Realizamos un estudio analítico retrospectivo del tratamiento de niños diagnosticados de TDAH. Se estudió una muestra de 82 niños diagnosticados de TDAH (74.4% niños y 25.6% niñas). El 96.3% de los casos presentaba algún trastorno asociado. El tratamiento farmacológico fue el tratamiento de elección (90.2%). El 46.0% recibía metilfenidato de liberación inmediata, un 51.4% metilfenidato de liberación sostenida y la atomoxetina solo se recetó en un 2.7% de los casos. El 20.3% de la muestra abandonó en algún momento el tratamiento farmacológico. El tratamiento farmacológico fue la opción más utilizada en nuestra muestra, y el metilfenidato de liberación inmediata el fármaco de elección para inicio del tratamiento. Se utilizan poco las alternativas a los estimulantes. No se encontraron diferencias significativas entre el tipo de tratamiento y el subtipo de TDAH o el género, aunque sí en cuanto a la edad de inicio del tratamiento.

Attention deficit hyperactivity disorder (ADHD) is a complex and heterogeneous neurodevelopmental disorder, of a chronic nature, of multifactorial etiology, mainly due to genetic and environmental factors. We conducted a retrospective analytical study of the t herapeutic management of children diagnosed with ADHD. A sample of 82 children diagnosed with ADHD (74.4% children and 25.6% girls) was studied. 96.3% of the cases presented some associated disorder. Pharmacological treatment was the treatment of choice (90.2%). 46.0% received immediate release methylphenidate, 51.4% sustained release methylphenidate and atomoxetine was only prescribed in 2.7% of patients. 20.3% of the sample abandoned pharmacological treatment at some point. Pharmacological treatment was the most frequent option in our sample, and methylphenidate immediate release the drug of choice for treatment initiation. The alternatives to stimulants are used in very low percentage of the patient. No significant differences were found between the type of treatment regarding the subtype of ADHD or gender, but we found significant difference in relation with the age of onset of treatment.

Pharmacotherapy for attention-deficit/hyperactivity disorder

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.

Clinical and Neuropsychological Factors Associated with Treatment Response and Adverse Events of Atomoxetine in Children with Attention-Deficit/Hyperactivity Disorder

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.

Process improvement on the synthesis of atomoxetine / 中国药科大学学报

@#Atomoxetine is a highly selective norepinephrine reuptake inhibitor. Based on the analysis of the literature methods, the synthesis process of atomoxetine was improved. Using 3-chloropropiophenone-1 as the raw material, optically pure target product was obtained by asymmetric reduction, Mitsunobu reaction and condensation reaction in three steps, with a total yield of 26%. The third-step methylation sealing operation was changed to the reaction under normal pressure, which increased the feasibility of industrialization. The improved process operation was simplified and the reaction conditions were mild, which would provide a new method for the preparation of atomoxetine.

Patterns and Persistence of Pharmacotherapy for Children and Adolescents with Attention Deficit Hyperactivity Disorder in South Korea

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.

Effects of Atomoxetine on Height and Weight in Korean Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Retrospective Chart Review

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.

Trastorno por uso de sustancias en pacientes con trastorno por déficit de atención e hiperactividad que reciben estimulantes / Substance use disorder in patients with attention deficit hyperactivity disorder receiving stimulants

RESUMEN El trastorno por déficit de atención e hiperactividad (TDAH) es la alteración neuroconductual más frecuente en la consulta pediátrica y su tratamiento comprende la terapia comportamental y el empleo de fármacos. Existe una preocupación latente por el eventual desarrollo del trastorno por el uso de sustancias (TUS) en los pacientes con TDAH tratados con estimulantes. La evidencia médica sugiere un efecto protector con respecto al consumo de sustancias psicoactivas, pero también alerta sobre el potencial abuso por parte de los pacientes y las personas alrededor. En este artículo se revisan sistemáticamente las virtudes y los riesgos de desarrollar TUS en los pacientes con TDAH en tratamiento con estimulantes.

SUMMARY The attention deficit with hyperactivity disorder is the most frequent disorder in pediatric outpatient services and its treatment involves behavioral therapy and drugs. However, there is concerning about develop substances use disorder once upon treatment with stimulants. Medicine based evidence suggests a preventive effect about psychoactive substance consumption but also warns potential abuse by patients and people around. In this paper, we systematically review worths and risks of SUD in stimulant - treated ADHD patients.

Multi-spectroscopic characterization of bovine serum albumin upon interaction with atomoxetine / 药物分析学报

The quenching interaction of atomoxetine (ATX) with bovine serum albumin (BSA) was studied in vitro under optimal physiological condition (pH=7.4) by multi-spectroscopic techniques. The mechanism of ATX-BSA system was a dynamic quenching process and was confirmed by the fluorescence spectra and lifetime measurements. The number of binding sites, binding constants and other binding characteristics were computed. Thermodynamic parameters ΔH0 and ΔS0 indicated that intermolecular hydrophobic forces predominantly stabilized the drug-protein system. The average binding distance between BSA and ATX was studied by F?rsters theory. UV-absorption, Fourier transform infrared spectroscopy (FT-IR), circular dichroism (CD), synchronous spectra and three-dimensional (3D) fluorescence spectral results revealed the changes in micro-environment of secondary structure of protein upon the interaction with ATX. Displacement of site probes and the effects of some common metal ions on the binding of ATX with BSA interaction were also studied.

Factors that Affect the Adherence to ADHD Medications during a Treatment Continuation Period in Children and Adolescents: A Nationwide Retrospective Cohort Study Using Korean Health Insurance Data from 2007 to 2011

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.

Prescribing patterns for attention deficit hyperactivity disorder medications among children and adolescents in Korea, 2007-2011 / 한국역학회지

OBJECTIVES: This study analyzed the prevalence of attention deficit hyperactivity disorder (ADHD) medication use among children and adolescents in Korea between January 1, 2007 and December 31, 2011. METHODS: Using the Korea National Health Insurance claims database, we identified patients between one and 17 years of age who had at least one medical claim for the diagnosis of ADHD (International Classification of Diseases, 10th revision: F90.0). The annual prevalence of ADHD diagnoses was calculated, using national census data from Statistics Korea on the population aged between one and 17 years as the denominator. The prevalence was age-standardized using the 2010 population as the standard population. The number of patients who were treated with methylphenidate and/or atomoxetine and the prevalence of total patients with ADHD that were treated with either drug were also calculated for each year. All analyses were stratified according to gender and age group (1-5 years, 6-12 years, and 13-17 years). RESULTS: The number of patients diagnosed with ADHD increased from 72,704 persons (0.71%) in 2007 to 85,468 persons (0.93%) in 2011. The annual age-standardized prevalence of ADHD diagnoses increased from 0.67% in 2007 to 0.94% in 2011. The prevalence of methylphenidate use among children and adolescents with ADHD decreased from 73.91% in 2007 to 70.33% in 2011, whereas that of atomoxetine use increased from 5.77% in 2009 to 13.09% in 2011. CONCLUSIONS: While methylphenidate remains the most commonly prescribed ADHD drug, the use of atomoxetine has increased.

Advanced Test of Attention in Children with Attention-Deficit/Hyperactivity Disorder in Japan for Evaluation of Methylphenidate and Atomoxetine Effects

OBJECTIVE: This study was conducted to validate the Advanced Test of Attention (ATA) of the visual attention version of Japanese children with attention deficit/hyperactivity disorder (ADHD) and to evaluate the efficacy of methylphenidate (OROS-MPH) and atomoxetine medications. METHODS: To assess pharmacotherapy efficacy, the visual version of ATA was administered to 42 children with ADHD. Results were assessed using discriminant analysis, ANOVA for indices of ATA before and after medication treatment, and correlation analysis between the improvement of indices of ATA and clinical symptoms during medication treatment. RESULTS: Discriminant analysis showed that 69.0% of ADHD children were assigned correctly. The T score of commission errors increased as the trial progressed on the medication-off condition. T scores of commission errors and standard deviation of response times on medication-on condition were low compared to the medication-off condition. A few significant correlations were found between the improvements of indices of ATA and ADHD-Rating Scale (RS) during treatment. CONCLUSION: The performance of the visual version of ATA on medication-off condition reflected the features of ADHD. Furthermore, the medication treatment effects were confirmed sufficiently. In addition, results suggest that indices of ATA reflected aspects of ADHD symptoms that are difficult to elucidate for ADHD-RS. For assessing symptoms and effects of medical treatment in children with ADHD, ATA might be a useful assessment tool.

Differences in Utilization Patterns among Medications in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: a 36-Month Retrospective Study Using the Korean Health Insurance Review and Assessment Claims Database

We evaluated the differences in utilization patterns including persistence and adherence among medications in children and adolescents with attention deficit hyperactivity disorder (ADHD). The current study was performed using data from the Korean Health Insurance Review and Assessment claims database from January 1, 2009 to December 31, 2013. Our study sample consisted of 10,343 children and adolescents with ADHD who were not given their newly prescribed medication in 360 days before the initial claim in 2010. Data were followed up from the initiation of treatment with ADHD medications in 2010 to December 31, 2013. Discontinuation rates for 4 ADHD medications in our sample ranged from 97.7% for immediate-release methylphenidate to 99.4% for atomoxetine using refill gap more than 30 days and from 56.7% for immediate-release methylphenidate to 62.3% for extended-release methylphenidate using refill gap more than 60 days. In the number of discontinued, we found significant differences among medications using refill gap more than 30 days. Among 4 ADHD medications, extended-release methylphenidate and atomoxetine had more days than immediate-release methylphenidate and osmotic-controlled oral delivery system methylphenidate. In logistic regression analyses, extended-release methylphenidate, osmotic-controlled oral delivery system methylphenidate, and atomoxetine showed less discontinuation compared to immediate-release methylphenidate group when a refill gap more than 30 days was used. In logistic regression analysis of adherence, we could not find any differences among 4 medication types. We suggest that the utilization patterns should be assessed regularly in order to improve future outcomes in children and adolescents with ADHD.

Differences in Utilization Patterns among Medications in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: a 36-Month Retrospective Study Using the Korean Health Insurance Review and Assessment Claims Database

We evaluated the differences in utilization patterns including persistence and adherence among medications in children and adolescents with attention deficit hyperactivity disorder (ADHD). The current study was performed using data from the Korean Health Insurance Review and Assessment claims database from January 1, 2009 to December 31, 2013. Our study sample consisted of 10,343 children and adolescents with ADHD who were not given their newly prescribed medication in 360 days before the initial claim in 2010. Data were followed up from the initiation of treatment with ADHD medications in 2010 to December 31, 2013. Discontinuation rates for 4 ADHD medications in our sample ranged from 97.7% for immediate-release methylphenidate to 99.4% for atomoxetine using refill gap more than 30 days and from 56.7% for immediate-release methylphenidate to 62.3% for extended-release methylphenidate using refill gap more than 60 days. In the number of discontinued, we found significant differences among medications using refill gap more than 30 days. Among 4 ADHD medications, extended-release methylphenidate and atomoxetine had more days than immediate-release methylphenidate and osmotic-controlled oral delivery system methylphenidate. In logistic regression analyses, extended-release methylphenidate, osmotic-controlled oral delivery system methylphenidate, and atomoxetine showed less discontinuation compared to immediate-release methylphenidate group when a refill gap more than 30 days was used. In logistic regression analysis of adherence, we could not find any differences among 4 medication types. We suggest that the utilization patterns should be assessed regularly in order to improve future outcomes in children and adolescents with ADHD.

Acute Dystonia Following a Switch in Treatment from Atomoxetine to Low-dose Aripiprazole

The present report describes the cases of a 17-year-old male patient and a 13-year-old female patient who developed acute dystonia following the administration of low-dose aripiprazole (5 mg/day) after the cessation of atomoxetine treatment. Although aripiprazole-induced dystonia has been previously reported in the literature, it is rare, and most of these cases were associated with doses higher than 5 mg/day. Furthermore, both of the patients in the present study discontinued atomoxetine prior to the initiation of aripiprazole treatment; thus, this report also discussed the possible mechanisms underlying the manifestation of dystonia from the perspective of neurotransmitter activity.

Association of better atomoxetine response with polymorphisms of CYP2D6 gene in the treatment of attention-deficit/hyperactivity disorder / 中国心理卫生杂志

Objective:To explore the association between CYP2D6 gene polymorphism of cytochrome and clinical response to atomoxetinein children with attention-deficit/hyperactivity disorder.Methods:Totally 111 Han Chinese boys meeting criteria for ADHD in the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edi-tion (DSM-IV)were recruited.Atomoxetine treatment was given in titrated doses in order to achieve optimal re-sponse.Behavior changes were measured with the ADHD Rating Scale (ADHD-RS)at baseline and after optimal doses were reached.The decrease of ADHD-RS scores were primary measures of the treatment effect,the scores of the items in the ADHD-RS was less than or equal to 1 for the remission criteria.The three SNPs of CYP2D6 genes(rs1080985,rs1065852,rs16947)were genotyped by polymerase chain reaction (PCR).Results:There was no asso-ciation between single polymorphisms andatomoxetine after adjusting for baseline rating scores (P >0.05).In con-trast,haplotype analysis revealed that some patients with GAC haplotype achieved significant remission [remission vs.non-remission haplotype frequency (rate):5 /56 (8.9%)vs.3 /164(1.8%),P <0.05 ].After multiple testing correction still existed significant trend(P =0.082)and also found correlation trends after correlation analysis be-tween GAC haplotype and clinical response to atomoxetine (P =0.078),8 patients with GAC haplotype carriers were all effective response to treatment,non-responders without this haplotype.Conclusion:These results suggest association between polymorphisms of CYP2D6 gene and ADHD better clinical improvement with atomoxetine treatment,it is worth further exploration in a large sample.

Efficacy of Methylphenidate Hydrochloride controlled-release tablets on Attention-Deficit Hyperactivity Disorder in Children / 医药导报

Objective To observe the therapeutic effect of methylphenidate hydrochloride controlled-release tablets (OROS-MPH) on attention-deficit hyperactivity disorder (ADHD). Methods Seventy-two cases of children with ADHD were randomly divided into treatment group (40) and control group (32). Cases of treatment group were given 0.8-1.0 mg??kg-1 of OROS-MPH for three months. Cases of control group were given 1.2-1.4 mg??kg-1 of atomoxetine hydrochloride for three months. After 12 weeks treatment, children were evaluated by Wechsler intelligence test, Integrated visual and auditory continuous performance test (IVA-CPT), the SNAP-Ⅳ effect assessment scale and TESS scale. Results The treatment efficiency was similar in both groups. Attention deficit and hyperactivity in both groups were improved obviously. Wechsler intelligence score was significantly elevated ( P<0. 05), SNAP-Ⅳ score was significantly decreased ( P<0. 05), and IVA-CPT score was increased significantly after treatment ( P<0.05) . The changes of scores on hyperactivity, auditory attention and visual attention were more in OROS-MPH group than those in atomoxetine group(P<0.05). There was loss of appetite in 10 children of OROS-MPH group and in 14 children of atomoxetine group. There was drowsiness in 1 child of OROS-MPH group and in 5 children of atomoxetine group, as well as difficulty to fall asleep in 6 children of OROS-MPH group and 1 child of atomoxetine group (P<0.05). One child developed a transient spasm after 4-month treatment. Conclusion Both of OROS-MPH and atomoxetine hydrochloride can improve learning ability and the symptom of attention deficit and hyperactivity, and they are similarly effective and safe in children with ADHD, but OROS-MPH can work faster.