Pharmacological treatment for obstructive sleep apnea: A systematic review and meta-analysis.

OBJECTIVE: Summarize the evidence on drug therapies for obstructive sleep apnea. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed, Embase, Scopus, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched on February 17th, 2023. A search strategy retrieved randomized clinical trials comparing the Apnea-Hypopnea Index (AHI) in pharmacotherapies. Studies were selected and data was extracted by two authors independently. The risk of bias was assessed using the Cochrane Risk of Bias tool. RevMan 5.4. was used for data synthesis. RESULTS: 4930 articles were obtained, 68 met inclusion criteria, and 29 studies (involving 11 drugs) were combined in a meta-analysis. Atomoxetine plus oxybutynin vs placebo in AHI mean difference of -7.71 (-10.59, -4.83) [Fixed, 95 % CI, I2 = 50 %, overall effect: Z = 5.25, p < 0.001]. Donepezil vs placebo in AHI mean difference of -8.56 (-15.78, -1.33) [Fixed, 95 % CI, I2 = 21 %, overall effect: Z = 2.32, p = 0.02]. Sodium oxybate vs placebo in AHI mean difference of -5.50 (-9.28, -1.73) [Fixed, 95 % CI, I2 = 32 %, overall effect: Z = 2.86, p = 0.004]. Trazodone vs placebo in AHI mean difference of -12.75 (-21.30, -4.19) [Fixed, 95 % CI, I2 = 0 %, overall effect: Z = 2.92, p = 0.003]. CONCLUSION: The combination of noradrenergic and antimuscarinic drugs shows promising results. Identifying endotypes may be the key to future drug therapies for obstructive sleep apnea. Moreover, studies with longer follow-up assessing the safety and sustained effects of these treatments are needed. PROSPERO REGISTRATION NUMBER: CRD42022362639.

[Attention deficit hyperactivity: pharmacotherapy through life]. / Déficit de atención con hiperactividad: farmacoterapia a través de la vida.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder of biological origin with a 70 to 80% genetic basis, which affects 5% of children and adolescents and 2.5% of adults, whose main symptoms are inattention, hyperactivity, and impulsivity. For many years it was thought that it only affected children; currently in the DSM 5 it is accepted that it can be diagnosed in adolescents and adults. Treatment must be individualized, the main objectives are to improve the core symptoms of people with ADHD, and their quality of life. The therapeutic approach is psychological, behavioral, and pharmacological. Medications are classified as stimulants and nonstimulants, with stimulants such as methylphenidate, lisdexamfetamine, and dexamphetamine being the first line. Non-stimulants include guanfacine and atomoxetine. Treatment is essential because it improves the quality of life of the person at the family, educational, work, and social levels.

El Trastorno por déficit de atención con hiperactividad (TDAH) es un trastorno del neurodesarrollo de origen biológico con una base genética del 70 al 80%, que afecta al 5% de niños y adolescentes y a un 2.5% de los adultos, cuyos síntomas principales son la inatención, hiperactividad e impulsividad. Por muchos años se pensó que afectaba solo a los niños; actualmente en el DSM 5 se acepta que se puede diagnosticar en adolescentes y adultos. El tratamiento debe ser individualizado, los objetivos principales son mejorar los síntomas centrales de las personas con TDAH, y su calidad de vida. El abordaje terapéutico es psicológico, conductual y farmacológico. Los medicamentos se clasifican en estimulantes y no estimulantes, siendo los de primera línea los estimulantes tales como el metilfenidato, lisdexanfetamina y dexanfetamina. Entre los no estimulantes se cuentan a la guanfacina y atomoxetina. El tratamiento es fundamental porque mejora la calidad de vida de la persona a nivel familiar, educativo, laboral y social.

Atomoxetine promotes incentive value of modafinil and sensitizes exploratory behavior.

Substance dependence is a disorder that alters the functioning of the nervous system due to frequent abuse of drugs. The role of dopamine in the addictive effect of psychostimulants is well known; however, the involvement of the noradrenergic system is still unclear and poorly understood, though drugs like cocaine and amphetamines are known to exert significant activity on this system. The drug modafinil (MOD) has no proven addictive effect. It promotes wakefulness by acting mainly on the dopaminergic system and, to a lesser degree, the noradrenergic (NOR) system. Atomoxetine (ATX) is a non-stimulant drug that acts only on the NOR system, enhancing its activity. The aims of the present study were to analyze the effect of co-activating the DA and NOR systems (with MOD and ATX, respectively) on motor activity and exploratory behavior, and to examine the possible emergence of rewarding properties of MOD and an MOD+ATX mixture. Male Wistar rats at postnatal day 60 were treated chronically (16 days) with either monotherapy with 2ATX, 4ATX, or 60MOD mg/kg, two combinations of these substances -60MOD + 2ATX and 60MOD + 4ATX- or a vehicle. The rats co-administered with 60MOD + 4ATX reduced the rearing behavior frequency induced by MOD, but this behavior was sensitized by self-administration of the MOD+ATX mixture after chronic treatment. The rats pre-treated with 60MOD + 4ATX showed higher self-administration of MOD and greater activity on an operant task to obtain the MOD+ATX mixture. In addition, the 60MOD, 2ATX, and 60MOD + 2ATX groups showed sensitization of exploratory behavior after ingesting the mixture. Results suggest that the noradrenergic system enhances the incentive value of MOD and a MOD+ATX mixture, while also playing an important role in the sensitization of exploratory behavior.

Association between sleep pattern and pharmacological treatment in children with attention deficit disorder with hyperactivity: a systematic review.

OBJECTIVE: The aim of this study was to analyze the effect of the pharmacological treatment on the sleep patterns of children with attention deficit hyperactivity disorder (ADHD). DATA SOURCE: A high-sensitivity electronic search was performed in the following databases: Cochrane Library, MEDLINE via PubMed, LILACS via the Regional Health Portal (BVS), Embase, Scopus, CINAHL, and Web of Science, as recommended by the Cochrane Handbook, and which has undergone peer review according to the PRESS Guide. DATA SYNTHESIS: The studies contemplated the use of the drugs atomoxetine, guanfacine, methylphenidate, dasotraline, L-theanine, and lisdexamfetamine. They showed efficiency in reducing the symptoms of ADHD, although all, except atomoxetine, affected sleep quality, such as by reducing total rapid eye movement (REM), non-REM phase, slow-wave sleep time, and longer sleep-onset latency. CONCLUSIONS: The drugs used in the treatment of ADHD seem to have negative repercussions on the sleep quality of children, with the drug atomoxetine showing lesser effects on this variable.

Atomoxetine Decreases Mitochondrial Biogenesis, Fission and Fusion In Human Neuron-like Cells But Does Not Alter Antioxidant Defences.

Atomoxetine (ATX) is a presynaptic norepinephrine transporter (NET) inhibitor widely prescribed for attention-deficit/hyperactivity disorder (ADHD) due to its low abuse potential and absence of psychostimulant effects. While NET inhibition is implicated in the clinical response, several additional pharmacoactivities may contribute to clinical efficacy or unwanted side effects. We recently reported that ATX can dose-dependently alter mitochondrial function and cellular redox status. Here, we assessed potential alterations in mitochondrial biogenesis, mitochondrial dynamics and cellular antioxidant capacity following high- and low-dose ATX treatment of differentiated human neuroblastoma cells. Human SH-SY5Y neuroblastoma cells were treated with ATX (1, 5, 10, 20 and 50 µM) for 7 days under differentiation culture conditions. Changes in the expression levels of protein markers for mitochondrial biogenesis, fusion and fission as well as of antioxidant proteins were analysed by Western blot. High-dose ATX (50 µM) reduced while low-dose ATX (10 µM) increased mitochondrial biogenesis as evidenced by parallel changes in SDHA, COX-I, PGC1α and TFAM expression. High-dose ATX also reduced mitochondrial fusion as evidenced by OPA1 and MFN2 downregulation, and mitochondrial fission as indicated by DRP1 and Fis1 downregulation. In contrast, ATX did not alter expression of the antioxidant enzymes SOD1 and catalase, the phase II transcription factor Nfr2, or the Nfr2-regulated antioxidant enzyme NQO1. Clinical responses and side effects of ATX may be mediated by dose-dependent modulation of mitochondrial biogenesis and dynamics as well as NET inhibition.

Therapeutic Approaches for ADHD by Developmental Stage and Clinical Presentation.

Attention Deficit Hyperactivity Disorder is a neurodevelopmental disorder with three presentations: inattentive, hyperactive/impulsive and combined. These may represent an independent disease entity. Therefore, the therapeutic approach must be focused on their neurobiological, psychological and social characteristics. To date, there is no comprehensive analysis of the efficacy of different treatments for each presentation of ADHD and each stage of development. This is as narrative overview of scientific papers that summarize the most recent findings and identify the most effective pharmacological and psychosocial treatments by ADHD presentation and age range. Evidence suggests that methylphenidate is the safest and most effective drug for the clinical management of children, adolescents and adults. Atomoxetine is effective in preschoolers and maintains similar efficacy to methylphenidate in adults, whereas guanfacine has proven to be an effective monotherapy for adults and is a worthy adjuvant for the management of cognitive symptoms. The psychosocial treatments with the best results in preschoolers are behavioral interventions that include training of primary caregivers. In adolescents, the combination of cognitive and cognitive-behavioral therapies has shown the best results, whereas cognitive-behavioral interventions are the most effective in adults. Pharmacological and psychosocial treatments must be adjusted to the ADHD presentation and its neurocognitive characteristics through the patient's development.

National clinical guideline for assessment and treatment of ADHD in children and young people: quick guide

Professional observers are independent persons who have in-depth knowledge of both children's normal behaviour and development and of ADHD, and who take a multidisciplinary approach to ADHD in their daily work. The observation must be geared to the specific problem with the child in question

Commentary: Identifying individualized predictions of response in ADHD pharmacotherapy - a commentary on Rodrigues et al. (2020).

In this issue, Rodrigues et al. (2020) present a systematic review with meta-analyses that reports the efficacy of five treatments for children with attention-deficit hyperactivity disorder symptoms in the context of autism spectrum disorder - (a) methylphenidate; (b) atomoxetine; (c) guanfacine; (d) aripiprazole; and (e) risperidone. In this commentary, we highlight the contrast between the scarce evidence base of treatment for ADHD in the context of autism and other subpopulations, such as tic disorders and intellectual disability, and the extensive evidence base of treatment for ADHD in general. The commentary weighs about the conundrum clinicians face of whether to rely on the limited evidence base of treatment for ADHD in subpopulation, or to derive conclusions from the larger body of evidence of treatment for ADHD in general. The commentary also discusses potential avenues for future research to address this clinical problem.

Atomoxetine Reestablishes Long Term Potentiation in a Mouse Model of Attention Deficit/Hyperactivity Disorder.

Attention deficit/hyperactivity disorder (ADHD) is the most prevalent psychiatric childhood disorder, characterized by hyperactivity, impulsivity and impaired attention, treated most frequently with methylphenidate (MPH). For children and adults with ADHD who do not respond satisfactorily or do not tolerate well stimulants such as MPH or D-Amphetamine, for them the alternative is to use Atomoxetine (ATX), a norepinephrine (NE) transporter inhibitor that increase extracellular NE. We examined the effects of ATX on behavior and hippocampal synaptic plasticity in the murine prenatal nicotine exposure (PNE) model of ADHD. ADHD symptoms were measured using behavioral tests, open field for hyperactivity and the Y-maze for spatial working memory. Further, ATX effects on long-term potentiation (LTP) in hippocampal slices at the CA3-CA1 synapse were assessed. PNE mice exhibited the behavioral deficits of ADHD, hyperactivity and spatial memory impairment. Intraperitoneal injection of ATX (2 mg/kg/day) normalized these behaviors significantly after 7 days. In PNE mice LTP was reduced (110.6 ±â€¯4.5% %; n = 7) compared to controls (148.9 ±â€¯5.2%; n = 7; p < 0.05). ATX administration (5 µM) reestablished the LTP in PNE mice to levels similar to the controls (157.7 ±â€¯6.3%; n = 7). Paired-pulse ratios (PPR) were not significantly different for any condition. These results indicate that administration of ATX in a PNE model of ADHD reestablishes TBS-dependent LTP in CA3-CA1 synapses. The results suggest postsynaptic changes in synaptic plasticity as part of the mechanisms that underlie improvement of ADHD symptoms induced by ATX.

Atomoxetine produces oxidative stress and alters mitochondrial function in human neuron-like cells.

Atomoxetine (ATX) is a non-stimulant drug used in the treatment of attention-deficit/hyperactivity disorder (ADHD) and is a selective norepinephrine reuptake inhibitor. It has been shown that ATX has additional effects beyond the inhibition of norepinephrine reuptake, affecting several signal transduction pathways and alters gene expression. Here, we study alterations in oxidative stress and mitochondrial function in human differentiated SH-SY5Y cells exposed over a range of concentrations of ATX. We found that the highest concentrations of ATX in neuron-like cells, caused cell death and an increase in cytosolic and mitochondrial reactive oxygen species, and alterations in mitochondrial mass, membrane potential and autophagy. Interestingly, the dose of 10 µM ATX increased mitochondrial mass and decreased autophagy, despite the induction of cytosolic and mitochondrial reactive oxygen species. Thus, ATX has a dual effect depending on the dose used, indicating that ATX produces additional active therapeutic effects on oxidative stress and on mitochondrial function beyond the inhibition of norepinephrine reuptake.

Using Cell Cultures for the Investigation of Treatments for Attention Deficit Hyperactivity Disorder: A Systematic Review.

BACKGROUND: Advances in basic and molecular biology have promoted the use of cell cultures in a wide range of areas, including the evaluation of drug efficacy, safety and toxicity. OBJECTIVE: This article aims to provide a general overview of the methodological parameters of cell cultures used to investigate therapeutic options for Attention Deficit Hyperactivity Disorder. METHOD: A systematic search was performed in the electronic databases PubMed, Scopus, and DOAJ. In vitro experimental studies using cell cultures were included. RESULTS: A total of 328 studies were initially identified, with 16 included for qualitative synthesis. Seven studies used neuronal cells (SH-SY5Y neuroblastoma and PC12 cell line) and nine used nonneuronal cells. All the studies described the culture conditions, but most studies were inconsistent with regard to reporting results and raw data. Only one-third of the studies performed cell viability assays, while a further 30% conducted gene expression analysis. Other additional tests included electrophysiological evaluation and transporter activity. More than 50% of the studies evaluated the effects of drugs such as methylphenidate and atomoxetine, while plant extracts were assessed in four studies and polyunsaturated fatty acids in one. CONCLUSION: We suggested a flowchart to guide the planning and execution of studies, and a checklist to be completed by authors to allow the standardized reporting of results. This may guide the elaboration of laboratory protocols and further in vitro studies.

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.

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

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.

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.

Safety of Treatments for ADHD in Adults: Pairwise and Network Meta-Analyses.

OBJECTIVE: The aim of the study was to analyze evidence comparing the profile of drugs used to treat ADHD in adult patients. METHOD: Systematic searches were conducted in electronic databases. Randomized, double-blind, parallel controlled trials that evaluated the safety of drugs in ADHD were included. The statistical analyses were conducted by pairwise meta-analyses and mixed treatment comparison (MTC). RESULTS: Ten ( n = 3006) trials were included in the analyses. We observed statistical differences for the following outcomes: decreased appetite between atomoxetine and placebo (odds ratio [OR] = 0.15, 95% credibility interval [CrI] = [0.05, 0.38]) and extended-release mixed amphetamine salts and placebo (OR = 0.06, 95% CrI = [0.00, 0.51]); insomnia between atomoxetine and placebo (OR = 0.48, 95% CrI = [0.27, 0.88]) and extended-release mixed amphetamine salts and placebo (OR = 0.23, 95% CrI = [0.06, 0.76]); sleepiness between atomoxetine and methylphenidate OROS (OR = 0.24, 95% CrI = [0.06, 0.97]); and decreased libido between atomoxetine and placebo (OR = 0.28, 95% CrI = [0.08, 0.90]). CONCLUSION: It was possible to generate evidence about the safety profile of different ADHD drugs.

Atomoxetine prevents working memory loss in hyperactive rats, mediating plastic changes in prefrontal cortex pyramidal neurons.

Attention Deficit Hyperactivity Disorder (ADHD) causes impaired visuospatial working memory (VWM), which primarily maps to the prefrontal cortex. However, little is known about the synaptic processes underlying cognitive loss in ADHD, or those ultimately involved in the preventive effect observed through the clinical use of Atomoxetine (ATX). To investigate the plasticity underlying ADHD related cognitive loss, and that potentially involved in the preventive action of Atomoxetine, allocentric VWM was assessed, as well as the dendritic spine number and proportional density on pyramidal neurons in the prefrontal cerebral cortex layer III of neonatal 6-hydroxydopamine-lesioned rats. The effect of acute ATX treatment was also assessed at 28 days of age. 6-OHDA induced lesions produced increased motor activity and a loss of VWM, concomitant with a reduction in thin spine density. ATX administration reversed cognitive loss, in conjunction with a decrease in thin spines and an increase in mushroom spines. A reduction in the proportion of spines involved in learning in hyperactive animals could account for the loss in cognitive function observed. Considering thin spine density was also reduced after ATX administration, we hypothesized that the restoration in cognitive function recorded could be brought about by an increase in memory related mushroom spines.

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.

Validity of conners' adult attention-deficit/hyperactivity disorder rating Scale-investigator rated: screening version in patients from within and outside of Europe.

In adult patients with attention-deficit/hyperactivity disorder from within and outside of Europe, Conners' Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Rating Scale-Investigator Rated: Screening Version showed good internal consistency (Cronbach's α=0.930 and 0.938, respectively) and convergent validity with the Clinical (Pearson's correlation coefficients: 0.65-0.82, P<0.001) Global Impression-ADHD-Severity scale over 12 weeks of pharmacological treatment.

Atomoxetine treatment of attention-deficit/hyperactivity disorder in young adults with assessment of functional outcomes: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with significant impairment in multiple functional domains. This trial evaluated efficacy in ADHD symptoms and functional outcomes in young adults treated with atomoxetine. METHODS: Young adults (18-30 years old) with ADHD were randomized to 12 weeks of double-blind treatment with atomoxetine (n = 220) or placebo (n = 225). The primary efficacy measure of ADHD symptom change was Conners' Adult ADHD Rating Scale (CAARS): Investigator-Rated: Screening Version Total ADHD Symptoms score with adult prompts. Secondary outcomes scales included the Adult ADHD Quality of Life-29, Clinical Global Impression-ADHD-Severity, Patient Global Impression-Improvement, CAARS Self-Report, Behavior Rating Inventory of Executive Function-Adult Version Self-Report, and assessments of depression, anxiety, sleepiness, driving behaviors, social adaptation, and substance use. RESULTS: Atomoxetine was superior to placebo on CAARS: Investigator-Rated: Screening Version (atomoxetine [least-squares mean ± SE, -13.6 ± 0.8] vs placebo [-9.3 ± 0.8], 95% confidence interval [-6.35 to -2.37], P < 0.001), Clinical Global Impression-ADHD-Severity (atomoxetine [-1.1 ± 0.1] vs placebo [-0.7 ± 0.1], 95% confidence interval [-0.63 to -0.24], P < 0.001), and CAARS Self-Report (atomoxetine [-11.9 ± 0.8] vs placebo [-7.8 ± 0.7], 95% confidence interval [-5.94 to -2.15], P < 0.001) but not on Patient Global Impression-Improvement. In addition, atomoxetine was superior to placebo on Adult ADHD Quality of Life-29 and Behavior Rating Inventory of Executive Function-Adult Version Self-Report. Additional assessments failed to detect significant differences (P ≥ 0.05) between atomoxetine and placebo. The adverse event profile was similar to that observed in other atomoxetine studies. Nausea, decreased appetite, insomnia, dry mouth, irritability, dizziness, and dyspepsia were reported significantly more often with atomoxetine than with placebo. CONCLUSIONS: Atomoxetine reduced ADHD symptoms and improved quality of life and executive functioning deficits in young adults compared with placebo. Atomoxetine was also generally well tolerated.

Academic outcomes in Asian children aged 8-11 years with attention-deficit/hyperactivity disorder treated with atomoxetine hydrochloride.

OBJECTIVE: To investigate the relationship between changes in attention-deficit/hyperactivity disorder (ADHD) core symptoms and changes in academic outcome of Asian children treated with atomoxetine. METHODS: This open-label study enrolled patients aged 8-11 years with DSM-IV-TR-defined ADHD, who were naïve to ADHD medications and met the symptomatic severity threshold of 1.5 standard deviations above the age and gender norm for the ADHDRS-IV-Parent:Inv (ADHDRS) total score. Data collection occurred for 24 weeks and included academic outcome, measured by the school grade average (SGA). RESULTS: Of 228 patients enrolled from China (n = 82), Taiwan (n = 76), and Korea (n = 70), 77.2% completed the study. Statistically significant (P < 0.001) baseline to last observation improvements in ADHDRS and SGA scores were observed. However, no linear correlation between change in ADHDRS total score and SGA (-0.083, P = 0.293) was observed. CONCLUSIONS: Despite significant independent improvements in core ADHD symptoms and academic grades over 24 weeks, the mean improvements observed in these measures did not appear to be correlated.

Electrochemical behavior of atomoxetine and its voltammetric determination in capsules.

In this work, the electrochemical behavior and the analytical application of atomoxetine, a selective noradrenaline reuptake inhibitor, are studied. Atomoxetine, studied by differential pulse voltammetry and cyclic voltammetry on a glassy carbon electrode, exhibited an anodic response in aqueous media with pH between 1.5 and 7. In non-aqueous medium (acetonitrile), the drug exhibited two irreversible oxidation peaks that are diffusion controlled. From chronocoulometric studies in acetonitrile, it was determined that each oxidation signal involves two and four electrons, respectively. For analytical purposes, a differential pulse voltammetry technique in 0.1 mol L(-1) perchloric acid was selected, which exhibited adequate figures of merit. The percent recovery was 96.6+/-1.2 and the detection and quantitation limits were 6.9 x 10(-5) and 1.0 x 10(-4) mol L(-1), respectively. Also, results indicate that excipients do not interfere with the oxidation signal of atomoxetine, which leads to the conclusion that the developed method is satisfactorily selective for atomoxetine quantification in pharmaceuticals with no prior separation or extraction necessary. Finally, the proposed voltammetric method was successfully applied to both the assay and the uniformity content of atomoxetine in capsules. For comparison, high-performance liquid chromatography analysis was also performed.