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1.
Headache ; 60(10): 2202-2219, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33063862

RESUMO

OBJECTIVE: This post hoc analysis evaluated the efficacy of galcanezumab for the prevention of migraine in patients with and without comorbid anxiety and/or depression. BACKGROUND: Patients with migraine have a higher risk of anxiety and/or depression. Given the high prevalence of psychiatric symptoms and their potential negative prognostic impact, determining the efficacy of migraine treatments in patients with these comorbidities is important. METHODS: The results of 2 phase 3 episodic migraine studies of patients with 4-14 migraine headache days (MHD) per month were pooled. A third chronic migraine study, which was evaluated separately, enrolled patients with ≥15 headache days per month, of which ≥8 had migraine-like features. Patients in all 3 studies were randomized 2:1:1 to placebo, galcanezumab 120 mg, or galcanezumab 240 mg. The efficacy of galcanezumab on migraine was measured in subgroups of patients with anxiety and/or depression (current or past) and patients without. A repeated measures model was used to compare treatment groups within each subgroup and to test for consistency of treatment effect across the anxiety/depression subgroups (subgroup-by-treatment interaction) during the double-blind treatment phases. RESULTS: Among 1773 intent-to-treat patients with episodic migraine, both doses of galcanezumab demonstrated statistically significant improvements relative to placebo in overall number of MHD for the subgroups of patients with anxiety and/or depression (mean change difference from placebo [95% CI]: -2.07 [-2.81, -1.33] for galcanezumab 120 mg [P < .001], -1.91 [-2.78, -1.04] for 240 mg [P < .001]) and without anxiety and/or depression (mean change difference from placebo [95% CI]: -1.92 [-2.36, -1.47] for 120 mg [P < .001], -1.77 [-2.20, -1.33] for 240 mg [P < .001]), as was observed for the secondary outcomes of MHD with acute medication use and functional impairment. Among 1113 intent-to-treat patients with chronic migraine, those with anxiety and/or depression had significant reductions in overall MHD frequency with the 240-mg dose (mean change difference from placebo [95% CI]: -1.92 [-3.52, -0.33]; P = .018), whereas significant reductions were observed at both the 120-mg (mean change difference from placebo [95% CI]: -2.29 [-3.26, -1.31]; P < .001) and 240-mg (-1.85 [-2.83, -0.87]; P < .001) doses in patients without anxiety and/or depressions. Significant reductions (P < .01) in MHD with acute medication use were observed at both doses within both anxiety/depression subgroups and for overall functional impairment for patients without anxiety and/or depression, though neither dose significantly reduced overall functional impairment beyond placebo in the subgroup with anxiety and/or depression. In the episodic and chronic migraine studies, the subgroup-by-treatment interaction was not statistically significant for MHD, MHD with acute medication use, or functional impairment (chronic study only), suggesting a lack of evidence of differential effect between subgroups. Furthermore, differences between subgroups in the mean change differences from placebo, as well as overlapping 95% confidence intervals for the subgroups, indicated lack of a clinical or statistical difference between subgroups for these outcome variables. There was a significantly higher percentage of patients with episodic migraine attaining ≥50%, ≥75%, and 100% reductions, and a higher percentage of patients with chronic migraine attaining ≥50% and ≥75% reductions from baseline with galcanezumab compared with placebo, regardless of medical history of anxiety and/or depression. CONCLUSIONS: A medical history of anxiety and/or depression does not seem to interfere with response to galcanezumab among patients with episodic migraine, and both doses of galcanezumab appear efficacious for these individuals regardless of this psychiatric history. Among patients with chronic migraine and comorbid anxiety and/or depression, the 240-mg dose, but not the 120-mg dose, significantly decreased overall MHD, but neither dose resulted in significantly greater functional improvement. Patients with migraine and comorbid anxiety and/or depression often require additional interventions, and this may be more important in chronic migraine.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Transtornos de Ansiedade , Transtorno Depressivo , Transtornos de Enxaqueca/prevenção & controle , Avaliação de Resultados em Cuidados de Saúde , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Transtornos de Ansiedade/epidemiologia , Comorbidade , Transtorno Depressivo/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/epidemiologia
2.
Curr Med Res Opin ; 36(10): 1653-1666, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32845740

RESUMO

OBJECTIVE: Migraine is a chronic, disabling neurological disease affecting >1 billion people worldwide. Migraine remains undertreated in Asia, including Taiwan. Galcanezumab is a humanized monoclonal antibody that selectively binds calcitonin gene-related peptide, a peptide firmly established in the pathophysiology of migraine, with demonstrated efficacy and safety in patients with episodic or chronic migraine. Our objective was to evaluate the efficacy and safety of galcanezumab in Taiwanese patients with episodic or chronic migraine. METHODS: We conducted a sub-group analysis of the Taiwanese cohort from two double-blind, placebo-controlled, Phase 3 clinical trials of galcanezumab in the prevention of episodic and chronic migraine, EVOLVE-2 (NCT02614196) and REGAIN (NCT02614261), respectively. During the EVOLVE-2 and REGAIN double-blind periods, 2092 patients were randomly assigned to receive monthly injections of either placebo, 120 mg galcanezumab (240 mg loading dose), or 240 mg galcanezumab. In REGAIN, a 9-month open-label period followed. Post-hoc analysis on the Taiwanese population across both trials included 106 patients, 45 of whom continued into the open-label period in REGAIN. RESULTS: Our findings show that galcanezumab has similar efficacy and safety in the Taiwanese population, as compared to the "All Patients" population included in the study. Galcanezumab treatment reduced the number of monthly migraine headache days, determined a higher percentage of patients with a ≥ 50% response, and positively impacted quality of life. CONCLUSION: Galcanezumab is a promising therapeutic for the preventive treatment of migraine in the Taiwanese population.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Transtornos de Enxaqueca/prevenção & controle , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Doença Crônica , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/psicologia , Qualidade de Vida
3.
J Atten Disord ; 24(3): 363-372, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-27521574

RESUMO

Objective: This study examines the relationship between maintenance of improved executive functioning (EF) in adults with ADHD with long-term symptom improvement with atomoxetine. Method: Data were collected from a yearlong, double-blind, placebo-controlled clinical study on adult patients with ADHD receiving atomoxetine (80-100 mg/day) for 24 weeks. Patients were then randomized to continue atomoxetine or placebo for 6 months. Executive functioning was rated with Behavior Rating Inventory of Executive Function-Adult Version: Self-Report™ (BRIEF-A: Self-Report™), and the T-scores were determined. Results: Postrandomization T-scores for atomoxetine patients were significantly better than those of placebo patients (3 and 6 months postrandomization). Patients with greater improvements in EF were more likely to show worsening of EF and to relapse after atomoxetine discontinuation. The maintenance of improved EF was significantly associated with improved ADHD symptoms (Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version [CAARS-Inv:SV] with adult prompts). Conclusion: Treatment with atomoxetine improved EF during the treatment phases. Improved EF was maintained up to 6 months after discontinuation of atomoxetine.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Função Executiva , Inibidores da Captação Adrenérgica/uso terapêutico , Adulto , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Método Duplo-Cego , Humanos , Recidiva , Resultado do Tratamento
4.
J Headache Pain ; 20(1): 118, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881817

RESUMO

After publication of our article [1] we were notified that the data presented in the upper row of Fig. 7 was inadvertently the least square mean change from baseline (standard error) at Month 6 rather than the overall average of Month 3 and Month 6. The figure legend and discussion of the data in the text were and are correct. The error was only in the upper row of Fig. 7. The legend for Fig. 7 did not require revision.

5.
J Headache Pain ; 20(1): 75, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253091

RESUMO

BACKGROUND: Patients with high-frequency episodic migraine (HFEM) have a greater disease burden than those with low-frequency episodic migraine (LFEM). Acute treatment overuse increases the risk of migraine chronification in patients with HFEM. Galcanezumab, a humanized monoclonal antibody binding calcitonin gene-related peptide (CGRP), is effective for migraine prevention with a favorable safety profile. Here, we investigate whether there are differences in galcanezumab efficacy in patients with LFEM or with HFEM. METHODS: Data were pooled from two double-blind, placebo-controlled phase 3 trials; EVOLVE-1 and EVOLVE-2. Patients were 18-65 years old, experienced 4-14 monthly migraine headache days (MHDs) for ≥1 year prior, with onset at < 50 years of age. Migraine headaches were tracked via electronic patient-reported outcome system and randomization was stratified by low (LFEM; 4-7 monthly MHDs) or high (HFEM; 8-14 monthly MHDs) frequency. Subgroup analysis compared the HFEM and LFEM subgroups with a linear or generalized linear mixed model repeated measures approach. RESULTS: The intent-to-treat patients (N = 1773) had a mean age of 41.3 years, were mostly white (75%), female (85%), and 66% of patients had HFEM. In both the LFEM and HFEM subgroups, the overall (Months 1-6) and monthly changes from baseline in monthly MHDs and monthly MHDs with acute medication use compared with placebo were statistically significantly reduced for galcanezumab 120-mg and 240-mg. Galcanezumab (120-mg and 240-mg) significantly decreased the overall and monthly MHDs with nausea and/or vomiting, and with photophobia and phonophobia versus placebo in patients with LFEM or HFEM. In both subgroups, the mean overall (Months 1-6) and monthly percentages of patients with ≥50%, ≥75%, and 100% reduction in monthly MHDs from baseline were statistically significantly greater in patients receiving either dose of galcanezumab versus placebo. Galcanezumab (120-mg and 240-mg) significantly improved the Migraine-Specific Quality of Life Questionnaire role function-restrictive domain score as well as the Migraine Disability Assessment total score versus placebo for patients with LFEM or HFEM. There were no significant subgroup-by-treatment interactions. CONCLUSIONS: Galcanezumab was as effective in patients with HFEM as in those with LFEM. Associated symptoms, quality of life, and disability were similarly improved in patients with HFEM or LFEM. TRIAL REGISTRATION: NCT02614183 , NCT02614196 .


Assuntos
Anticorpos Monoclonais/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Feminino , Humanos , Hiperacusia/etiologia , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/diagnóstico , Náusea/etiologia , Fotofobia/etiologia , Placebos , Qualidade de Vida , Resultado do Tratamento , Vômito/etiologia , Adulto Jovem
6.
Atten Defic Hyperact Disord ; 9(4): 219-229, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28477289

RESUMO

We identified relapse/maintenance-of-response (MOR) predictors following discontinuation of long-term atomoxetine treatment in pediatric and adult patients with attention-deficit/hyperactivity disorder (ADHD) and assessed correlations between ADHD symptoms and quality of life (QoL). Post hoc analyses of data from two randomized, double-blind, placebo-controlled, phase 3 withdrawal studies in patients with ADHD meeting predefined response criteria before randomization. Study 1: patients (N = 163; 6-15 years) received atomoxetine (1.2-1.8 mg/kg/day) for 1 year, followed by randomization to atomoxetine (n = 81) or placebo (n = 82) for 6 months. Study 2: patients (N = 524; 18-50 years) received atomoxetine (80-100 mg/day) for ~6 months, followed by randomization to atomoxetine (n = 266) or placebo (n = 258) for ~6 months. Placebo patients were used for the analyses. Relapse: ≥50% worsening of prerandomization improvement in ADHD symptoms and ≥2 level severity increase on the Clinical Global Impression-Severity (CGI-S) scale at 2 consecutive visits; MOR: retaining ≥75% of prerandomization symptom improvement and CGI-S ≤ 2 at all visits (study 1); retaining ≥70% of prerandomization symptom improvement and CGI-S ≤ 3 at all visits (study 2). In adults, statistically significantly (P ≤ .05) increased likelihood of relapse was associated with prerandomization presence of Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator-Rated:Screening Version (CAARS-Inv:SV) items "difficulty awaiting turn" and "careless mistakes." In pediatric patients, less MOR was associated with prerandomization presence of ADHD Rating Scale-IV-Parent Version Investigator-Rated item "does not listen"; in adults, less MOR was associated with prerandomization presence of CAARS-Inv:SV items "loses things" and "difficulty awaiting turn." Changes in patients' QoL after withdrawal from atomoxetine moderately correlated with changes in ADHD symptoms in pediatric patients and mildly in adults.


Assuntos
Cloridrato de Atomoxetina/administração & dosagem , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Efeito Placebo , Adolescente , Adulto , Cloridrato de Atomoxetina/uso terapêutico , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Fatores de Risco , Adulto Jovem
7.
Ther Innov Regul Sci ; 50(1): 91-100, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30236022

RESUMO

BACKGROUND: This article describes follow-up work extended from Tanaka et al (2011) in defining the region in multiregional clinical trials (MRCTs). The previous paper advocated a systematic approach to defining regions and recommended the sponsor to think through carefully, prespecify, and justify any regional definitions as well as obtain regulatory concurrence prior to study conduct. Particular attention was advised for intrinsic and extrinsic factors such as race/ethnicity, disease epidemiology, medical practice, and geographic proximity. An analytical approach such as a cluster method to define region was introduced, and references on observed regional differences were provided. METHODS: A closer review of those references and others from a more comprehensive literature search was conducted to gain a deeper understanding of intrinsic and extrinsic factors in relation to the observed regional differences in the treatment effect. The application of a k-means cluster method to define region was explored, as well as the implication to regional sample size for MRCTs. RESULTS: Of extrinsic factors, diagnostic capabilities, medical/clinical practice such as aspirin use, patient care such as site's usual practice, intervention, capability, and concomitant medications were considered potential contributors to differences in clinical outcomes or measures. Commonly reported intrinsic factors were underlying etiology, epidemiology, genetics, and patient characteristics (age, ethnicity, race, risk factors). CONCLUSION: Using a checklist to identify intrinsic/extrinsic factors that might lead to differences in treatment effect allows one to scientifically define more meaningful regions from the identified factors, which will help with estimating the relative treatment outcome as well as exploring appropriate regional sample size.

8.
Postgrad Med ; 127(7): 677-85, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26329980

RESUMO

BACKGROUND: Adults with attention-deficit/hyperactivity disorder treated with atomoxetine were examined for time-to-onset and -resolution of common treatment-emergent adverse events (TEAEs) and male sexual dysfunction, and for changes in blood pressure (BP) and heart rate (HR) upon atomoxetine discontinuation. METHODS: 12-week open-label atomoxetine (40-100 mg/day) was followed by 12-week double-blind maintenance treatment (atomoxetine 80 or 100 mg/day). Responders were then randomized to atomoxetine (n = 266) or placebo (n = 258) for 25-week randomized withdrawal. Examined were (1) median time-to-onset and -resolution of TEAEs during atomoxetine treatment, and (2) within group, visitwise mean changes for sitting HR, systolic BP, and diastolic BP for the postrandomization placebo group. RESULTS: Common adverse events (AEs) appeared early, within week 1 of atomoxetine treatment. Some AEs resolve relatively rapidly, whereas others have a more lingering course of resolution (including male sexual side effects); median resolution times were 3 - 53 days. BP and HR increases during atomoxetine treatment returned to baseline upon atomoxetine discontinuation. CONCLUSION: Atomoxetine is associated with common AEs, with 3- to 53-day median resolution times. TRIAL REGISTRATION: ClincialTrials.gov - NCT00700427.


Assuntos
Cloridrato de Atomoxetina , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Doenças Cardiovasculares , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Disfunção Erétil , Inibidores da Captação Adrenérgica/administração & dosagem , Inibidores da Captação Adrenérgica/efeitos adversos , Adulto , Cloridrato de Atomoxetina/administração & dosagem , Cloridrato de Atomoxetina/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/fisiopatologia , Disfunção Erétil/induzido quimicamente , Disfunção Erétil/diagnóstico , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Fatores de Tempo , Resultado do Tratamento , Suspensão de Tratamento
9.
Int Psychogeriatr ; 27(9): 1533-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25925598

RESUMO

BACKGROUND: The Generalized Anxiety Inventory (GAI) has been developed for use in the assessment of anxiety symptoms in older adults (≥ 65 years), but previous validation work has not examined the psychometric qualities of the instrument in relation to treatment. The objective of this study was to examine the performance of the GAI for its internal reliability, convergent and divergent validity, and its sensitivity to treatment. METHODS: Elderly patients with generalized anxiety disorder (GAD) participated in a 10-week double-blind study of duloxetine treatment for patients with GAD. Anxiety symptoms were assessed with the Hamilton Anxiety Rating Scale (HAMA), the Hospital Anxiety and Depression Scale (HADS) anxiety and depression subscales, and the GAI. Internal reliability of the GAI was assessed with Cronbach's α. Correlations among the HAMA, HADS, and GAI scores were analyzed to determine convergent and divergent validity. Patients were also compared on remission status using recommended cut-off scores for the GAI. RESULTS: Patients with GAD, who were at least 65 years of age, were randomly assigned to double-blind treatment with either duloxetine (N = 151) or placebo (N = 140) for 10 weeks acute therapy. The mean change on the GAI was significantly greater with duloxetine compared with placebo treatment (-8.36 vs. -4.96, respectively, p ≤ 0.001). The GAI demonstrated good internal consistency, good convergent and divergent validity, but suggested cut-off values for caseness with the GAI did not correspond to remission status as measured by the HAMA. CONCLUSIONS: Within an elderly patient population with GAD, the GAI demonstrated sound psychometric qualities and sensitivity to change with treatment.


Assuntos
Antidepressivos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Ansiedade/diagnóstico , Depressão/diagnóstico , Cloridrato de Duloxetina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Argentina , Áustria , Canadá , Método Duplo-Cego , Feminino , Alemanha , Humanos , Masculino , México , Polônia , Escalas de Graduação Psiquiátrica , Psicometria , Reprodutibilidade dos Testes , Espanha , Resultado do Tratamento , Reino Unido , Estados Unidos
10.
Atten Defic Hyperact Disord ; 7(2): 141-50, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25563210

RESUMO

The adult attention-deficit/hyperactivity disorder (ADHD) quality-of-life (AAQoL) scale was previously validated in adult patients in the USA; here, the AAQoL is validated in adult European patients. Data from a 12-week open-label acute treatment period with atomoxetine (80-100 mg/day) in adults with ADHD were used. Patients (≥ 18 to ≤ 50 years old) had a score ≥ 2 on ≥ 6 items on the inattentive or hyperactive core subscales of Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV); a CAARS-Inv:SV 18-item total ADHD symptom score ≥ 20; and Conners' Adult ADHD Rating Scale-Observer: Screening Version 6-item inattentive or hyperactive core subscale scores ≥ 2. Data were stratified based on patients' geographic region (Europe vs USA). Scale validation psychometric properties results were very similar between European (n = 1,217; 57.7 % male; mean age 33.0 years) and US (n = 602; 62.1 % male; mean age 33.5 years) patients, including factor loading, internal consistency, convergent and discriminant validity, and responsiveness. Exploratory factor analysis confirmed four AAQoL subscales. Internal consistency was acceptable (Cronbach's alpha > 0.70 for all subscales). The AAQoL total score showed moderate convergent validity with CAARS-Inv:SV 18-item total ADHD symptom and clinical global impression-ADHD-severity (CGI-ADHD-S) scores; and strong convergent validity with Behavior Rating Inventory of Executive Function-Adult Version: Self-Report Global-Executive-Composite Index scores. Mean AAQoL total scores were significantly different among patients grouped by CGI-ADHD-S scores, suggesting good discriminant validity. The AAQoL total and subscale scores presented good responsiveness from baseline to 12 weeks. The AAQoL scale shows comparable validity in European and US adults with ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Escalas de Graduação Psiquiátrica/normas , Qualidade de Vida/psicologia , Adolescente , Inibidores da Captação Adrenérgica/uso terapêutico , Adulto , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Europa (Continente) , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Psicometria , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos , Adulto Jovem
11.
J Child Adolesc Psychopharmacol ; 25(10): 799-809, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25265343

RESUMO

OBJECTIVES: This extrapolation analysis qualitatively compared the efficacy and safety profile of atomoxetine from Lilly clinical trial data in 6-7-year-old patients with attention-deficit/hyperactivity disorder (ADHD) with that of published literature in 4-5-year-old patients with ADHD (two open-label [4-5-year-old patients] and one placebo-controlled study [5-year-old patients]). METHODS: The main efficacy analyses included placebo-controlled Lilly data and the placebo-controlled external study (5-year-old patients) data. The primary efficacy variables used in these studies were the ADHD Rating Scale-IV Parent Version, Investigator Administered (ADHD-RS-IV-Parent:Inv) total score, or the Swanson, Nolan and Pelham (SNAP-IV) scale score. Safety analyses included treatment-emergent adverse events (TEAEs) and vital signs. Descriptive statistics (means, percentages) are presented. RESULTS: Acute atomoxetine treatment improved core ADHD symptoms in both 6-7-year-old patients (n=565) and 5-year-old patients (n=37) (treatment effect: -10.16 and -7.42). In an analysis of placebo-controlled groups, the mean duration of exposure to atomoxetine was ∼ 7 weeks for 6-7-year-old patients and 9 weeks for 5-year-old patients. Decreased appetite was the most common TEAE in atomoxetine-treated patients. The TEAEs observed at a higher rate in 5-year-old versus 6-7-year-old patients were irritability (36.8% vs. 3.6%) and other mood-related events (6.9% each vs. <3.0%). Blood pressure and pulse increased in both 4-5-year-old patients and 6-7-year-old patients, whereas a weight increase was seen only in the 6-7-year-old patients. CONCLUSIONS: Although limited by the small sample size of the external studies, these analyses suggest that in 5-year-old patients with ADHD, atomoxetine may improve ADHD symptoms, but possibly to a lesser extent than in older children, with some adverse events occurring at a higher rate in 5-year-old patients.


Assuntos
Inibidores da Captação Adrenérgica/uso terapêutico , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Inibidores da Captação Adrenérgica/efeitos adversos , Fatores Etários , Cloridrato de Atomoxetina/efeitos adversos , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança
12.
Int Clin Psychopharmacol ; 28(6): 330-8, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23873291

RESUMO

The aim of this study was to evaluate the relationship between painful physical symptoms (PPS) and outcomes in major depressive disorder (MDD). Post-hoc analysis of two identically designed 8-week trials compared the efficacy of 60 mg/day duloxetine (N=523) with that of placebo (N=532) in treating PPS associated with MDD. The Montgomery-Åsberg Depression Rating Scale (MADRS) total score, the Brief Pain Inventory (BPI) average pain score, and the Sheehan Disability Scale global functional impairment score assessed depression symptoms, pain, and functioning, respectively. Remission was defined as a MADRS score of 10 or less, and the BPI response subgroup was defined as a 50% or greater reduction from baseline. Path analyses assessed relationships among variables. Duloxetine-treated patients who had a 50% or greater reduction in BPI score at endpoint had higher rates of remission. Path analysis indicated that 16% of likelihood of remission in depression symptoms was because of the direct effect of treatment, 41% because of pain reduction, and 43% because of functional improvement. Path analysis also indicated that 51% of improvement in functioning was attributed to pain improvement and 43% to mood improvement. Results demonstrate that improvement in pain and mood contributes to functional improvement, and pain reduction and functional improvement increase the likelihood of remission of depressive symptoms with duloxetine treatment in patients with both MDD and PPS at baseline.


Assuntos
Analgésicos/uso terapêutico , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Dor/tratamento farmacológico , Tiofenos/uso terapêutico , Adulto , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Método Duplo-Cego , Cloridrato de Duloxetina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Dor/epidemiologia , Estatística como Assunto/métodos
13.
Artigo em Inglês | MEDLINE | ID: mdl-23313564

RESUMO

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression and anxiety, but has not been examined systematically in generalized anxiety disorder (GAD). The objective of this study was to examine the relationship between baseline BDNF level and treatment response in patients with GAD. METHODS: Patients (N=168) were from China, met criteria for DSM-IV GAD, had a Hospital Anxiety and Depression Rating Anxiety (HADS-A) subscale score ≥10, and a Sheehan Disability Scale (SDS) global functioning total score ≥12 at baseline. Study design was double-blind therapy for 15 weeks with duloxetine 60-120 mg or placebo. Efficacy measures included the HADS-A and Hamilton Anxiety Rating Scale (HAMA) total score. Change from baseline to endpoint for BDNF by treatment group was analyzed using ANCOVA models with baseline BDNF level as a covariate. RESULTS: No significant association was found between baseline plasma BDNF levels and anxiety illness severity. Patients who received duloxetine (n=88) had a significantly greater mean increase in plasma BDNF level (957.80 picograms/ml) compared with patients who received placebo (n=80; 469.93 pg/mL) (P=.007). Patients who met response and remission criteria (with either treatment) had greater mean increases in BDNF at endpoint from baseline (P≤.05) but when compared with nonresponders and nonremitters, respectively, the differences in mean increase were not statistically significant between groups. CONCLUSIONS: BDNF levels significantly increased with duloxetine treatment for GAD, but response and remission outcomes were not clearly related to an increase in plasma BDNF level.


Assuntos
Antidepressivos/uso terapêutico , Transtornos de Ansiedade/sangue , Transtornos de Ansiedade/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/sangue , Tiofenos/uso terapêutico , Adolescente , Adulto , Idoso , Agorafobia/sangue , Agorafobia/tratamento farmacológico , Análise de Variância , China , Manual Diagnóstico e Estatístico de Transtornos Mentais , Avaliação da Deficiência , Método Duplo-Cego , Cloridrato de Duloxetina , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/sangue , Transtorno de Pânico/tratamento farmacológico , Transtornos Fóbicos/sangue , Transtornos Fóbicos/tratamento farmacológico , Escalas de Graduação Psiquiátrica , Estresse Psicológico/complicações , Estresse Psicológico/psicologia , Resultado do Tratamento , Adulto Jovem
14.
Pain Res Treat ; 2012: 898347, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22973509

RESUMO

We summarize efficacy and safety findings from 4 double-blind, placebo-controlled, 12-week studies and 1 open-label, uncontrolled, 34-week maintenance-of-effect (MOE) study that examine duloxetine 40 and 60 mg once daily (QD) in patients with diabetic peripheral neuropathic pain (DPNP). In all placebo-controlled studies, duloxetine showed significantly (P ≤ .01) greater reduction in pain severity (weekly mean of 24-hour average pain severity ratings, primary outcome measure) compared with placebo. In all placebo-controlled studies, duloxetine showed significantly (P ≤ .05) greater improvement on brief pain inventory-Interference ratings. Patient global impression of improvement ratings were superior to placebo (P ≤ .01) for duloxetine patients in all placebo-controlled studies. Response rates (based on 30% pain reduction) ranged from 57% to 68% for duloxetine and from 35% to 47% for placebo and were statistically significantly different (P ≤ .01) between treatment groups in 3 out of 4 studies. The open-label study showed maintenance of analgesic effect of duloxetine in DPNP. In the duloxetine groups, 4.3% to 14.9% of patients discontinued because of adverse events (placebo groups: 2.6% to 7.4%). Most commonly reported treatment-emergent adverse events were nausea, somnolence, and headache. Duloxetine 40 and 60 mg QD was efficacious and well tolerated in the management of DPNP.

15.
Curr Drug Saf ; 4(1): 22-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19149522

RESUMO

OBJECTIVE: We present a post-hoc analysis of the safety and efficacy of duloxetine, a selective serotonin/norepinephrine reuptake inhibitor, for treatment of diabetic peripheral neuropathic pain (DPNP) in older patients. METHODS: Data from three double-blind, placebo-controlled trials in adult patients with DPNP were pooled and stratified by age (<65, >or=65 years). Patients were randomized to duloxetine (DLX) 60 mg once-daily, 60 mg twice-daily, or placebo for 12 weeks, followed by a 52-week extension phase (re-randomization to routine care or DLX 120 mg/day). Intent-to-treat analyses were used for safety and efficacy assessment. RESULTS: In the acute phase, overall TEAE rates did not differ significantly by age. A greater percentage of older patients discontinued due to TEAEs (P<0.001), regardless of treatment group. Duloxetine improved weekly mean 24-hour average pain scores versus placebo in both age groups (P<0.01). In the extension phase, a significant therapy-by-age interaction (P<0.05) was observed in overall TEAE rate; with routine care, 86.6% of older patients had >or=1 TEAE versus 74.6% of younger patients. CONCLUSIONS: Although TEAEs more frequently lead to discontinuation in older patients, duloxetine was well tolerated and efficacious for treatment of DPNP regardless of age. These data suggest duloxetine may be beneficial for treatment of DPNP in patients>or=65.


Assuntos
Neuropatias Diabéticas/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Tiofenos/uso terapêutico , Fatores Etários , Idoso , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Cloridrato de Duloxetina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Tiofenos/efeitos adversos , Resultado do Tratamento
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