RESUMEN
OBJECTIVE: The efficacy and safety of atomoxetine was assessed in adult ADHD patients from Japan, Korea, and Taiwan in this first placebo-controlled Asian clinical study in adults of an ADHD medication. METHOD: Atomoxetine was compared with placebo (195 atomoxetine, 196 placebo) over 10 weeks. The change from baseline to endpoint and changes over time in the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version total score (CAARS-Inv: SV total score) were assessed along with changes in quality of life (QoL) and executive function. RESULTS: Atomoxetine treatment resulted in a mean reduction of -14.3 (placebo, -8.8) in CAARS-Inv: SV total score and a steady increase of between-group differences from Week 2. Improvements in QoL and executive functioning were also observed. Treatment-emergent adverse events leading to discontinuation were infrequent (atomoxetine: 5.2%, placebo: 1.5%). CONCLUSION: Atomoxetine was tolerable and effective in improving QoL and executive function as well as ameliorating core ADHD symptoms in adult Asian patients.
Asunto(s)
Inhibidores de Captación Adrenérgica/administración & dosificación , Clorhidrato de Atomoxetina/administración & dosificación , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Inhibidores de Captación Adrenérgica/efectos adversos , Adulto , Pueblo Asiatico/etnología , Clorhidrato de Atomoxetina/efectos adversos , Trastorno por Déficit de Atención con Hiperactividad/etnología , Método Doble Ciego , Esquema de Medicación , Sustitución de Medicamentos , Función Ejecutiva/efectos de los fármacos , Femenino , Humanos , Japón/etnología , Masculino , Calidad de Vida , República de Corea , Taiwán , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: There is a clinical need for a liquid formulation of atomoxetine. We assessed the safety and bioequivalence of an atomoxetine oral solution. METHODS: This was an open-label, randomized, crossover study. Healthy adult male Japanese subjects (n = 42) with a cytochrome P450 2D6 extensive (including intermediate and ultrarapid) metabolizer genotype were administered atomoxetine 50 mg as oral solution and capsules once each, with a washout period >5 days between doses. Blood samples were used to analyze pharmacokinetic parameters, particularly maximum observed drug concentration (C max) and area under the concentration vs. time curve from time zero to the last time point with a measurable concentration (AUC0-last). Bioequivalence was concluded if the 90 % confidence interval of the ratio of geometric means between formulations for both C max and AUC0-last were within the interval of 0.8-1.25. Safety assessments included determination of adverse events. Taste was evaluated via a five-item questionnaire immediately and 10 min after taking atomoxetine oral solution. RESULTS: Forty subjects completed the study. Plasma concentration-time profiles of atomoxetine oral solution and capsules were similar, and the statistical analysis of systemic exposure showed that the two formulations were bioequivalent. Adverse events were mild and similar in type and frequency between the formulations. For taste acceptability, only 7.1 % of subjects responded that the oral solution would be difficult to take every day. CONCLUSION: Atomoxetine oral solution is bioequivalent to atomoxetine capsules and potentially fulfills the need for an oral solution atomoxetine formulation that will facilitate treatment of children with attention-deficit hyperactivity disorder.
Asunto(s)
Clorhidrato de Atomoxetina/administración & dosificación , Adulto , Clorhidrato de Atomoxetina/farmacocinética , Cápsulas , Química Farmacéutica , Estudios Cruzados , Femenino , Genotipo , Humanos , Masculino , Equivalencia Terapéutica , Adulto JovenRESUMEN
OBJECTIVES: This study compared the sociodemographic characteristics, comorbidities, healthcare resource utilization, and work productivity among Japanese adults who reported being diagnosed with attention-deficit/hyperactivity disorder (ADHD) to those of a non-ADHD control population. METHODS: Data for this study were captured from an online survey of adults in Japan conducted by Kantar Health using consumer panels. A total of 84 survey participants reported they had received a diagnosis of ADHD from a physician. Survey responses pertaining to functional status and resource utilization from this ADHD group were compared to those from a non-ADHD control group of 100 participants. Comparisons between the ADHD and non-ADHD groups were made using chi-square tests for categorical variables and t-tests for continuous variables. RESULTS: Participants in the ADHD group were on average slightly younger with a higher proportion of males. ADHD respondents reported significantly more comorbid depression, sleep difficulties, headaches, and anxiety than non-ADHD controls. Over the previous 6 months, the ADHD group made more visits to healthcare providers and the emergency room, and had more hospitalizations than non-ADHD controls. The ADHD group also rated their overall health status lower than the non-ADHD control group. Respondents with ADHD reported a significantly higher degree of health-related work impairment compared to non-ADHD, with greater absenteeism and decreased work productivity. The ADHD group indicated their symptoms negatively impacted relationships, self-esteem, and regular daily activities. CONCLUSIONS: Japanese adults with ADHD face a substantial burden of illness, including lower overall health status, increased number of comorbidities, greater healthcare utilization, and significant health-related occupational impairment compared to those without ADHD. Additional research is needed to develop a better understanding of both the consequences and treatment approaches for Japanese adults with ADHD.
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Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Eficiencia , Servicios de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud , Adulto , Ansiedad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Depresión/complicaciones , Femenino , Estado de Salud , Encuestas Epidemiológicas , Humanos , Japón , Masculino , Persona de Mediana Edad , Calidad de Vida , Trastornos del Sueño-Vigilia/complicacionesRESUMEN
Atomoxetine, which is indicated for treatment of attention-deficit hyperactivity disorder (ADHD), is predominantly metabolized by genetically polymorphic cytochrome P450 2D6 (CYP2D6). Based on identified CYP2D6 genotypes, individuals can be categorized into 4 phenotypic metabolizer groups as ultrarapid, extensive, intermediate, and poor. Previous studies have focused on observed differences between poor and extensive metabolizers, but it is not well understood whether the safety profile of intermediate metabolizers differs from that of ultrarapid and extensive metabolizers. This study compared safety and tolerability among the different CYP2D6 metabolizer groups in the 12-week open-label phase of an atomoxetine study in adult patients with ADHD. Genotyping identified 1039 patients as extensive/ultrarapid metabolizers, 780 patients as intermediate metabolizers, and 117 patients as poor metabolizers. Common (≥5% frequency) treatment-emergent adverse events did not significantly differ between extensive/ultrarapid and intermediate metabolizers (odds ratios were <2.0 or >0.5). Poor metabolizers had higher frequencies of dry mouth, erectile dysfunction, hyperhidrosis, insomnia, and urinary retention compared with the other metabolizer groups. There were no significant differences between extensive/ultrarapid and intermediate metabolizers in changes from baseline in vital signs. These results suggest that data from CYP2D6 intermediate and extensive/ultrarapid metabolizers can be combined when considering safety analyses related to atomoxetine.
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Inhibidores de Captación Adrenérgica/efectos adversos , Clorhidrato de Atomoxetina/efectos adversos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Citocromo P-450 CYP2D6/genética , Inhibidores de Captación Adrenérgica/farmacocinética , Inhibidores de Captación Adrenérgica/uso terapéutico , Adulto , Clorhidrato de Atomoxetina/farmacocinética , Clorhidrato de Atomoxetina/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/genética , Citocromo P-450 CYP2D6/metabolismo , Femenino , Genotipo , Humanos , Masculino , Fenotipo , Adulto JovenRESUMEN
INTRODUCTION: This article aims to assess the efficacy and safety of atomoxetine in Korean adults with attention-deficit hyperactivity disorder (ADHD). METHODS: This post hoc double-blind, placebo-controlled study of atomoxetine (40-120 mg/day) over 10 weeks in adults with ADHD at 45 Japanese, Korean, and Taiwanese study sites focused on patient data from Korea (atomoxetine, n = 37; placebo, n = 37). Primary efficacy outcome was change in baseline-to-endpoint Conners' Adult ADHD Rating Scale-Investigator-rated: Screening Version (CAARS-Inv:SV) Total ADHD Symptoms score. Secondary efficacy outcomes included changes in Adult ADHD Quality of Life (AAQoL) total, Behavior Rating Inventory of Executive Function-Adult Version Self-Report (BRIEF-A:Self-Report), and Clinical Global Impression-ADHD-Severity (CGI-ADHD-S) scale scores. RESULTS: Atomoxetine-treated patients demonstrated a mean 18.9-point reduction in CAARS-Inv:SV total ADHD Symptoms score, compared with the 7.45-point reduction in placebo-treated patients (P ≤ 0.01). Significantly greater improvement was found for atomoxetine versus placebo in CGI-ADHD-S (P ≤ 0.01), BRIEF-A:Self-Report global executive composite (P ≤ 0.05), and metacognition index (P ≤ 0.01) executive function scores. Nausea, decreased appetite, and dry mouth were reported with significantly greater frequency by atomoxetine-treated patients, and only one placebo-treated patient discontinued because of adverse event. A 2.1-kg reduction in weight and a 7.5-beat/minute increase in pulse rate were observed in atomoxetine-treated patients. DISCUSSION: These data support a significant benefit of 80- to 120-mg once daily atomoxetine versus placebo for treatment of ADHD in adult Korean patients. A high placebo response rate was observed in this adult Korean sample; a higher discontinuation rate was also observed in atomoxetine-treated patients. These observations warrant further investigation.
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Inhibidores de Captación Adrenérgica/administración & dosificación , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Propilaminas/administración & dosificación , Inhibidores de Captación Adrenérgica/efectos adversos , Adulto , Clorhidrato de Atomoxetina , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Propilaminas/efectos adversos , Calidad de Vida , República de Corea , Resultado del TratamientoRESUMEN
We assessed the executive function in adults with attention-deficit/hyperactivity disorder (ADHD) during atomoxetine treatment in a randomized withdrawal trial. Responders (Conners' ADHD Rating Scale-Investigator Rated: Screening Version [adult prompts] ≥30% reduction from baseline and Clinical Global Impression Scale-ADHD Severity score ≤3) to open-label atomoxetine (40-100 mg/d, 12 weeks) entered a 37-week double-blind maintenance period. Patients who maintained response (double-blind atomoxetine for 12 weeks) were randomized 1:1 to atomoxetine (80-100 mg/d, n = 266) or placebo (n = 258) for 25 weeks (total duration, 1 year). Patients and investigators were blinded to response criteria and randomization timing. Change in executive function was assessed with the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Self-Report and Informant T scores from the randomization to the last-observation-carried-forward postrandomization week 25 (after week 17). Of the enrolled patients (n = 2017; mean age, 33.2 years; male, 58.7%), 524 responders were randomized. During open-label atomoxetine, subscales and individual items on both BRIEF-A questionnaires showed significant improvement (P < 0.001). After randomization, the following T scores improved significantly (P ≤ 0.05) with patients in the atomoxetine group versus those in the placebo group: global executive composite, behavioral regulation, and metacognition indices; plan/organize, working memory, inhibit, task monitor and shift (both BRIEF-A questionnaires), emotional control and organization of materials (BRIEF-A Informant), and initiate (BRIEF-A Self-Report). Atomoxetine significantly improved the executive function compared with placebo, which was maintained for 25 weeks or more; the executive function of patients in the placebo group worsened but did not return to baseline levels after randomization.
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Inhibidores de Captación Adrenérgica/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/psicología , Función Ejecutiva/efectos de los fármacos , Propilaminas/uso terapéutico , Síndrome de Abstinencia a Sustancias/psicología , Inhibidores de Captación Adrenérgica/farmacología , Adulto , Clorhidrato de Atomoxetina , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Método Doble Ciego , Femenino , Humanos , Masculino , Propilaminas/farmacología , Síndrome de Abstinencia a Sustancias/diagnóstico , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: The primary aim of this study was to evaluate the long-term safety/tolerability of atomoxetine in Japanese adults with attention deficit hyperactivity disorder (ADHD). METHODS: This 48-week, open-label extension study involved participants with ADHD who completed a 10-week randomized controlled trial of atomoxetine. Participants received atomoxetine 40 mg/day, followed by step-wise titration to a maximum of 120 mg/day. The primary outcome was safety/tolerability. Secondary outcomes were symptoms of ADHD (Conners' Adult ADHD Rating Scales-Investigator Rated: Screening Version 18-item total score), quality of life (Adult Attention-Deficit/Hyperactivity Disorder Quality of Life scale), and executive function (Behavior Rating Inventory of Executive Function-Adult Version: Self-report). RESULTS: Of the 39.5% of participants overall who discontinued the study, 15.9% (37/233) of participants discontinued because of adverse events (AEs), primarily nausea (4.3%; 10/233). Overall, 93.6% (218/233) of participants experienced treatment-emergent AEs (TEAEs), most commonly nausea (56.2%; 131/233), nasopharyngitis (25.3%; 59/233), thirst (19.3%; 45/233), headache (17.2%; 40/233), and decreased appetite (16.3%; 38/233). Most TEAEs (70.8%; 165/233) were mild in intensity. Overall, 79.8% (186/233) of participants experienced ≥1 adverse drug reaction, primarily nausea (55.4%; 129/233). Five participants experienced serious AEs during the open-label extension; none was related/possibly related to treatment. There were statistically significant increases in vital signs and decreases in body weight that were not considered clinically significant. Symptoms of ADHD, quality of life, and executive function were significantly improved from baseline to endpoint (P < 0.05). DISCUSSION: Despite discontinuations due to the long-term, open-label design, AE related discontinuations were modest, suggesting that atomoxetine has acceptable long-term safety and tolerability in Japanese adults with ADHD. Symptoms of ADHD improved and remained improved throughout the study.
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Inhibidores de Captación Adrenérgica , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Propilaminas , Inhibidores de Captación Adrenérgica/administración & dosificación , Inhibidores de Captación Adrenérgica/efectos adversos , Inhibidores de Captación Adrenérgica/farmacología , Adulto , Clorhidrato de Atomoxetina , Femenino , Humanos , Japón , Masculino , Propilaminas/administración & dosificación , Propilaminas/efectos adversos , Propilaminas/farmacología , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: The primary objective of this study was to assess the overall safety and tolerability of atomoxetine in Korean, Chinese, and Taiwanese adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: A total of 44 patients aged ≥18 years who met the Conners' Adult ADHD Diagnostic Interview for DSM-IV diagnostic criteria for ADHD were enrolled from China, Korea, and Taiwan. In this open-label, dose-escalation study, patients received atomoxetine orally once daily over a period of eight weeks, starting at 40 mg/day (one week) up to a maximum dosage of 120 mg/day. Tolerability was evaluated by rate of discontinuation due to adverse events. Safety was assessed by recording all adverse events, laboratory tests, vital signs, and electrocardiograms. ADHD symptoms were evaluated by the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) for efficacy assessment. RESULTS: Thirty-four patients (77.3%) completed the study. Atomoxetine was well tolerated with a discontinuation rate of 2.3% (1/44) due to adverse events. The most commonly reported adverse events were nausea, dizziness, and somnolence. The mean change from baseline to endpoint in CAARS-Inv:SV total ADHD symptom score was -12.5 (P < 0.001). A significant reduction in the CAARS-Inv:SV subscales (inattentive, hyperactive/impulsive, and ADHD index score, P < 0.001) was observed. DISCUSSION: This is the first atomoxetine clinical trial in adult patients with ADHD in China, Korea, and Taiwan. Atomoxetine was well tolerated in doses of up to 120 mg/day with no unknown safety concerns.
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Inhibidores de Captación Adrenérgica/administración & dosificación , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Propilaminas/administración & dosificación , Administración Oral , Inhibidores de Captación Adrenérgica/efectos adversos , Adulto , Anciano , Clorhidrato de Atomoxetina , Trastorno por Déficit de Atención con Hiperactividad/etnología , China/etnología , Esquema de Medicación , Femenino , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Propilaminas/efectos adversos , República de Corea , Taiwán/etnología , Resultado del TratamientoRESUMEN
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.
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Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Escalas de Valoración Psiquiátrica , Adolescente , Adulto , Argentina , Clorhidrato de Atomoxetina , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , América del Norte , Propilaminas/uso terapéutico , Reproducibilidad de los Resultados , Federación de RusiaRESUMEN
AIMS: The main purpose of this first atomoxetine study in Japanese adults with attention-deficit/hyperactivity disorder (ADHD) was to investigate the tolerability of an 8-week treatment regimen. METHODS: This was an open-label, dose escalation study conducted in 45 Japanese patients aged at least 18 years with DSM-IV-defined ADHD. Patients received atomoxetine orally for 8 weeks. Atomoxetine administration was started at 40 mg/day (7 days), and subsequently increased to a maximum dose of 120 mg/day. Tolerability was assessed by discontinuation rate due to adverse events. Adverse events, laboratory tests, vital signs and electrocardiograms were collected. In addition, ADHD symptoms were assessed by using the Japanese version of the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) scores. RESULTS: Thirty-nine patients completed the study period. Atomoxetine was well tolerated with a 6.7% (3/45) discontinuation rate due to nausea, malaise and anorexia. The most commonly reported adverse events were nausea, nasopharyngitis and headache; there were no unexpected safety concerns. No deaths or serious adverse events were reported. Mean CAARS-Inv:SV-J total ADHD symptom scores decreased in a time-dependent manner; the mean change from baseline to endpoint was -15.0 (P<0.001). CONCLUSIONS: This study showed that atomoxetine was well tolerated in these patients and suggested that atomoxetine at a maximum dose of 120 mg/day would be safe in Japanese ADHD patients.