RESUMEN
BACKGROUND: In the treatment of major depressive disorder (MDD), it is not fully understood how individual symptoms improve over time (trajectory) in remitters. This study compared symptom improvement trajectories, as measured with the 17-item Hamilton Depression Rating Scale (HAM-D17), in remitters and nonremitters. METHODS: This analysis is based on 10 placebo-controlled, randomized, double-blind trials of duloxetine (40-60mg/day) for treatment of MDD from baseline up to week 8. Remission was defined as a HAM-D17 total score ≤7 at week 8 (last observation carried forward). Trajectories of HAM-D17 items were assessed by mixed model repeated measures analysis for treatment and remitter-nonremitter comparisons. Grouping of the trajectories was performed by factor analysis. Predictor analysis using HAM-D17 items was conducted by logistic regression. RESULTS: There were 1555 patients in the duloxetine group (489 [31.4%] remitters) and 1206 patients in the placebo group (290 [24.0%] remitters; P<.0001). For most items, the difference in trajectories between remitters and nonremitters appeared at early time points and increased over time. Treatment response trajectories were very similar for duloxetine and placebo remitters, while duloxetine nonremitters improved more than placebo nonremitters. For duloxetine remitters, we found 3 trajectory groups of HAM-D17 items. The predictor analysis showed that improvement in 6 individual items at week 1 or 2 was significantly associated with remission at week 8. LIMITATIONS: Generalizability of these results may be limited by the relatively short observation period used to define remission. CONCLUSIONS: Early monitoring of some symptoms of depression may prove useful in guiding treatment decisions.
Asunto(s)
Antidepresivos/administración & dosificación , Trastorno Depresivo Mayor/tratamiento farmacológico , Clorhidrato de Duloxetina/administración & dosificación , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
In treating Major Depressive Disorder with associated painful physical symptoms (PPS), the effect of duloxetine on PPS has been shown to decompose into a direct effect on PPS and an indirect effect on PPS via depressive symptoms (DS) improvement. To evaluate the changes in relative contributions of the direct and indirect effects over time, we analyzed pooled data from 3 randomized double-blind studies comparing duloxetine 60 mg/d with placebo in patients with major depressive disorder and PPS. Changes from baseline in Montgomery-Åsberg Depression Rating Scale total and Brief Pain Inventory-Short Form average pain score were assessed over 8 weeks. Path analysis examined the (1) direct effect of treatment on PPS and/or indirect effect on PPS via DS improvement and (2) direct effect of treatment on DS and/or indirect effect on DS via PPS improvement. At week 1, the direct effect of duloxetine on PPS (75.3%) was greater than the indirect effect through DS improvement (24.7%) but became less (22.6%) than the indirect effect (77.4%) by week 8. Initially, the direct effect of duloxetine on PPS was markedly greater than its indirect effect, whereas later the indirect effect predominated. Conversely, at week 1, the direct effect of treatment on DS (46.4%) was less than the indirect effect (53.6%), and by week 8 it superseded (62.6%) the indirect effect (37.4%). Thus, duloxetine would relieve PPS directly in the initial phase and indirectly via improving DS in the later phase.
Asunto(s)
Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/tratamiento farmacológico , Clorhidrato de Duloxetina/uso terapéutico , Dolor/diagnóstico , Dolor/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Analgésicos/uso terapéutico , Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/epidemiología , Método Doble Ciego , Humanos , Dolor/epidemiología , Dimensión del Dolor/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Knowing when to change pain-medication strategy is not well researched and remains a gap in treating chronic pain. OBJECTIVE: Our aim was to determine how long to treat osteoarthritis (OA) knee pain and chronic low back pain (CLBP) with duloxetine before considering a change in medication strategy. METHODS: We employed a post hoc analysis of changes in pain-severity data from placebo-controlled studies of duloxetine treatment in nondepressed patients with OA knee pain and CLBP. The studies were selected for inclusion in the analyses based on similarity of study design. Pain severity was recorded daily in patient diaries using an ordinal 11-point numerical rating scale (0 = no pain to 10 = most severe pain). The weekly means of the daily 24-hour average pain severity ratings from these diaries were pooled within disease states. Moderate response was defined as at least a 30% reduction from baseline in pain severity, and minimal improvement was defined as <10% reduction from baseline. The probability of achieving at least moderate pain reduction during 3 months treatment with duloxetine was estimated by Kaplan-Meier methods in patients with no or minimal improvement after 2, 4, and 6 weeks of treatment, as well as in all patients who had not yet achieved a moderate response (<30% reduction in pain severity). RESULTS: There were 239 OA patients and 541 CLBP patients who were randomly assigned to treatment with duloxetine 60/120 mg/d. OA and CLBP patients with minimal improvement at 2 weeks of treatment had <40% probability of achieving a moderate response, and at 4 weeks of treatment their chances were reduced to <30% in OA patients and <25% in CLBP patients. In patients showing <30% improvement at week 2 of treatment, OA patients had a 62% probability of achieving a moderate response, and CLBP patients had a 52% probability for a moderate response, and at 4 weeks of treatment, their chances were reduced to <50% in OA patients and <40% in CLBP patients. CONCLUSIONS: Patients taking duloxetine for OA or CLBP who have <10% reduction in pain after 4 weeks of treatment have limited possibility for eventually achieving even moderate pain reduction by the end of 12 weeks. ClinicalTrials.gov identifier: NCT00433290, NCT00408421, NCT00424593, NCT00408876, NCT00767806.
Asunto(s)
Analgésicos/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Clorhidrato de Duloxetina/uso terapéutico , Dolor de la Región Lumbar/tratamiento farmacológico , Osteoartritis de la Rodilla/tratamiento farmacológico , Analgésicos/administración & dosificación , Método Doble Ciego , Esquema de Medicación , Clorhidrato de Duloxetina/administración & dosificación , Femenino , Humanos , Masculino , Dimensión del DolorRESUMEN
OBJECTIVES: To assess and compare direct medical costs and medication compliance between patients with fibromyalgia who initiated duloxetine and patients with fibromyalgia who initiated pregabalin in 2008. METHODS: A retrospective cohort study design was used based on a large US national commercial claims database (2006 to 2009). Patients with fibromyalgia aged 18 to 64 who initiated duloxetine or pregabalin in 2008 and who had continuous health insurance 1 year preceding and 1 year following the initiation were selected into duloxetine cohort or pregabalin cohort based on their initiated agent. Medication compliance was measured by total supply days, medication possession ratio (MPR), and proportion of patients with MPR ≥ 0.8. Direct medical costs were measured by annual costs per patient and compared between the cohorts in the year following the initiation. Propensity score stratification and bootstrapping methods were used to adjust for distribution bias, as well as cross-cohort differences in demographic, clinical and economic characteristics, and medication history prior to the initiation. RESULTS: Both the duloxetine (n = 3,033) and pregabalin (n = 4,838) cohorts had a mean initiation age around 49 years, 89% were women. During the postindex year, compared to the pregabalin cohort, the duloxetine cohort had higher totally annual supply days (273.5 vs. 176.6, P < 0.05), higher MPR (0.7 vs. 0.5, P < 0.05), and more patients with MPR ≥ 0.8 (45.1% vs. 29.4%, P < 0.05). Further, relative to pregabalin cohort, duloxetine cohort had lower inpatient costs ($2,994.9 vs. $4,949.6, P < 0.05), lower outpatient costs ($8,259.6 vs. $10,312.2, P < 0.05), similar medication costs ($5,214.6 vs. $5,290.8, P > 0.05), and lower total medical costs ($16,469.1 vs. $20,552.6, P < 0.05) in the postinitiation year. CONCLUSIONS: In a real-world setting, patients with fibromyalgia who initiated duloxetine in 2008 had better medication compliance and consumed less inpatient, outpatient, and total medical costs than those who initiated pregabalin.
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Fibromialgia/economía , Costos de la Atención en Salud , Cumplimiento de la Medicación , Tiofenos/economía , Ácido gamma-Aminobutírico/análogos & derivados , Adolescente , Adulto , Estudios de Cohortes , Bases de Datos Factuales/economía , Clorhidrato de Duloxetina , Femenino , Fibromialgia/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Pregabalina , Estudios Retrospectivos , Tiofenos/uso terapéutico , Adulto Joven , Ácido gamma-Aminobutírico/economía , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
BACKGROUND: Osteoarthritis (OA) knee pain is common in older patients and contributes to decreased quality of life. Older patients are generally at higher risk of adverse drug reactions due to age-related changes in physiology that affect drug disposition, metabolism, and response. These analyses examined efficacy and safety outcomes of older (≥65 years) versus younger patients from clinical trials of duloxetine in the management of OA knee pain. METHODS: This is a post hoc analysis of two 13-week studies, in which patients were randomized to duloxetine 60 mg/day or placebo. Both studies allowed potential dose changes after 7 weeks of dosing, with Study I re-randomizing duloxetine treated patients to either stay on 60 mg/day or increase to 120 mg/day; while Study II more closely mimicked clinical practice by escalating only non-responding patients to 120 mg/day. For all analyses patients were subgrouped by age: older (≥65 years) and younger (40-64 years). Overall efficacy and safety age-group comparisons of duloxetine versus placebo were performed using pooled data from both studies with all duloxetine dose levels combined. Safety analyses included discontinuation rates, treatment-emergent adverse events, and serious adverse events. To evaluate the effects of increasing the dose in non-responding patients, only Study II data were evaluated. Treatment arms were defined post hoc as placebo, duloxetine 60 mg/day, and duloxetine 60/120 mg/day. RESULTS: At study end, patients in each age group who were treated with duloxetine versus placebo had significantly greater improvement in pain (both, p<.05), and there was no significant effect of age on treatment (p=.72). Increasing the dose to 120 mg in non-responding patients was not found to have a significant advantage. Among treatment-emergent adverse events with duloxetine treatment, only dizziness had a significantly differential treatment effect (p=.02) with greater incidence over placebo in younger patients (6.6% versus 0.6%, p=.02), but not in older patients (1.0% versus 3.2%, p=.29). CONCLUSIONS: Duloxetine was efficacious and generally well tolerated for management of symptomatic knee OA in both older and younger patients, but increasing the dose to 120 mg in non-responding patients did not provide additional benefit.
Asunto(s)
Analgésicos/uso terapéutico , Osteoartritis de la Rodilla/diagnóstico , Osteoartritis de la Rodilla/tratamiento farmacológico , Dolor/diagnóstico , Dolor/tratamiento farmacológico , Tiofenos/uso terapéutico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Analgésicos/efectos adversos , Mareo/inducido químicamente , Mareo/diagnóstico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Clorhidrato de Duloxetina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/métodos , Tiofenos/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: This post-hoc analysis was conducted to investigate if safety outcomes differed among race/ethnic subgroups of patients treated with duloxetine for chronic painful conditions. RESEARCH DESIGN AND METHODS: Pooled data from 15 placebo-controlled clinical trials were used to compare the safety outcomes of duloxetine among patients of Caucasian, Hispanic, Asian, and Black race/ethnic origins. Patients were randomized to receive placebo (n = 2199) or duloxetine (n = 3148) for treatment of diabetic peripheral neuropathic pain, fibromyalgia, osteoarthritis pain, or chronic low back pain. For categorical outcomes such as study discontinuation, adverse events leading to discontinuation, and treatment-emergent adverse events, incidence rates were summarized by race/ethnic subgroups. The Breslow-Day test was used to assess the homogeneity of treatment odds ratios across the four subgroups. For continuous outcomes such as changes in vital signs, body weight, and laboratory measures, an analysis of covariance or analysis of variance model was used and duloxetine effects were compared among race/ethnic subgroups based on the test of treatment-by-subgroup interaction. RESULTS: No significant differences were found among race/ethnic subgroups for discontinuation due to adverse events except for anxiety (p = 0.040). Rates of nausea and decreased appetite were significantly higher (p ≤ 0.05) in duloxetine-treated patients compared with placebo-treated patients within each race/ethnic subgroup. The Breslow-Day test was not significant for most safety outcomes, nor were treatment-by-race/ethnic subgroup interactions (p > 0.1), which suggested duloxetine effects were not significantly different among race/ethnic subgroups. CONCLUSION: Overall, these results detected only minimal differences among safety outcomes assessed in these race/ethnic subgroups in patients treated with duloxetine for chronic painful conditions. The unbalanced sample sizes among the race/ethnic subgroups may have limited the power to detect treatment by race subgroup interactions. These post-hoc subgroup analyses were of an exploratory nature and the results should be interpreted with appropriate caution.
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Analgésicos/administración & dosificación , Asiático , Negro o Afroamericano , Dolor Crónico/tratamiento farmacológico , Hispánicos o Latinos , Tiofenos/administración & dosificación , Población Blanca , Adolescente , Adulto , Analgésicos/efectos adversos , Clorhidrato de Duloxetina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiofenos/efectos adversosRESUMEN
OBJECTIVE: To assess the cost-effectiveness of duloxetine in the treatment of chronic low back pain (CLBP) from a US private payer perspective. METHODS: A cost-utility analysis was undertaken for duloxetine and seven oral post-first-line comparators, including nonsteroidal anti-inflammatory drugs (NSAIDs), weak and strong opioids, and an anticonvulsant. We created a Markov model on the basis of the National Institute for Health and Clinical Excellence model documented in its 2008 osteoarthritis clinical guidelines. Health states included treatment, death, and 12 states associated with serious adverse events (AEs). We estimated treatment-specific utilities by carrying out a meta-analysis of pain scores from CLBP clinical trials and developing a transfer-to-utility equation using duloxetine CLBP patient-level data. Probabilities of AEs were taken from the National Institute for Health and Clinical Excellence model or estimated from osteoarthritis clinical trials by using a novel maximum-likelihood simulation technique. Costs were gathered from Red Book, Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project database, the literature, and, for a limited number of inputs, expert opinion. The model performed one-way and probabilistic sensitivity analyses and generated incremental cost-effectiveness ratios (ICERs) and cost acceptability curves. RESULTS: The model estimated an ICER of $59,473 for duloxetine over naproxen. ICERs under $30,000 were estimated for duloxetine over non-NSAIDs, with duloxetine dominating all strong opioids. In subpopulations at a higher risk of NSAID-related AEs, the ICER over naproxen was $33,105 or lower. CONCLUSIONS: Duloxetine appears to be a cost-effective post-first-line treatment for CLBP compared with all but generic NSAIDs. In subpopulations at risk of NSAID-related AEs, it is particularly cost-effective.
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Analgésicos Opioides/economía , Antiinflamatorios no Esteroideos/economía , Anticonvulsivantes/economía , Seguro de Salud/economía , Dolor de la Región Lumbar/economía , Inhibidores Selectivos de la Recaptación de Serotonina/economía , Tiofenos/economía , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Enfermedad Crónica , Análisis Costo-Beneficio , Clorhidrato de Duloxetina , Economía Farmacéutica , Humanos , Dolor de la Región Lumbar/tratamiento farmacológico , Cadenas de Markov , Metaanálisis como Asunto , Modelos Económicos , Años de Vida Ajustados por Calidad de Vida , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Tiofenos/uso terapéutico , Estados UnidosRESUMEN
OBJECTIVES: To determine the effect of duloxetine treatment on cognition in patients with fibromyalgia. METHODS: Cognitive testing was conducted in a subset of adult patients in a randomized, double-blind, placebo-controlled trial of duloxetine. Patients met the American College of Rheumatology criteria for fibromyalgia and had a score of 4 or higher on the Brief Pain Inventory 24-hour average pain severity item. Patients who consented to cognitive testing were randomized to duloxetine (n = 80) or placebo (n = 76). The primary end point was at Week 12. Speed of processing on tasks requiring visual attention, working memory, and executive function was assessed with a Symbol Digit Substitution Test and Trail-Making Test A and B. Episodic memory was tested using the Verbal Learning and Recall Test. The change from baseline to end point (last-observation-carried-forward analysis) was analyzed by an analysis of covariance model, which included baseline, treatment, investigator, and treatment-by-investigator interaction. RESULTS: Most of the patients were white (89%) women (92%), ranging in age from 21 to 88 years. Mean scores on the cognitive tests were within 2 SD of published scores for similar-aged participants in the general population, indicating no substantial impairment. Baseline-to-end point changes in cognitive scores did not differ significantly between duloxetine and placebo treatment groups. CONCLUSIONS: Although scores differed somewhat from norms for age, substantial cognitive impairment was not evident in patients with fibromyalgia as assessed by the Symbol Digit Substitution Test, Trail-Making Test, and Verbal Learning and Recall Test. Overall, duloxetine treatment had neither positive nor negative effects on cognition. TRIAL REGISTRATION: Clintrials.gov NCT00673452.
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Trastornos del Conocimiento/tratamiento farmacológico , Fibromialgia/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Tiofenos/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Atención/efectos de los fármacos , Trastornos del Conocimiento/etiología , Clorhidrato de Duloxetina , Función Ejecutiva/efectos de los fármacos , Femenino , Fibromialgia/complicaciones , Fibromialgia/psicología , Humanos , Masculino , Memoria Episódica , Memoria a Corto Plazo/efectos de los fármacos , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos , Dolor/tratamiento farmacológico , Dimensión del Dolor , Placebos , Tiempo de Reacción/efectos de los fármacos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Aprendizaje Verbal/efectos de los fármacos , Adulto JovenRESUMEN
INTRODUCTION: Fatigue is one of the most disabling symptoms associated with fibromyalgia that greatly impacts quality of life. Fatigue was assessed as a secondary objective in a 2-phase, 24-week study in outpatients with American College of Rheumatology-defined fibromyalgia. METHODS: Patients were randomized to duloxetine 60-120 mg/d (N = 263) or placebo (N = 267) for the 12-week acute phase. At Week 12, all placebo-treated patients were switched to double-blind treatment with duloxetine for the extension phase. Fatigue was assessed at baseline and every 4 weeks with the Multidimensional Fatigue Inventory (MFI) scales: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Activity, and Reduced Motivation. Other assessments that may be associated with fatigue included Brief Pain Inventory (BPI) average pain, numerical scales to rate anxiety, depressed mood, bothered by sleep difficulties, and musculoskeletal stiffness. Treatment-emergent fatigue-related events were also assessed. Changes from baseline to Week 12, and from Week 12 to Week 24, were analyzed by mixed-effects model repeated measures analysis. RESULTS: At Week 12, duloxetine versus placebo significantly (all p < .05) reduced ratings on each MFI scale, BPI pain, anxiety, depressed mood, and stiffness. Improvement in ratings of being bothered by sleep difficulties was significant only at Weeks 4 and 8. At Week 24, mean changes in all measures indicated improvement was maintained for patients who received duloxetine for all 24 weeks (n = 176). Placebo-treated patients switched to duloxetine (n = 187) had significant within-group improvement in Physical Fatigue (Weeks 16, 20, and 24); General Fatigue (Weeks 20 and 24); Mental Fatigue (Week 20); and Reduced Activity (Weeks 20 and 24). These patients also experienced significant within-group improvement in BPI pain, anxiety, depressed mood, bothered by sleep difficulties, and stiffness. Overall, the most common (> 5% incidence) fatigue-related treatment-emergent adverse events were fatigue, somnolence, and insomnia. CONCLUSIONS: Treatment with duloxetine significantly improved multiple dimensions of fatigue in patients with fibromyalgia, and improvement was maintained for up to 24 weeks. TRIAL REGISTRATION: ClinicalTrials.gov registry NCT00673452.
Asunto(s)
Fatiga/tratamiento farmacológico , Fatiga/etiología , Fibromialgia/complicaciones , Fibromialgia/tratamiento farmacológico , Tiofenos/administración & dosificación , Adulto , Antidepresivos/administración & dosificación , Ansiedad/tratamiento farmacológico , Ansiedad/etiología , Depresión/tratamiento farmacológico , Depresión/etiología , Clorhidrato de Duloxetina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Actividad Motora/efectos de los fármacos , Dolor Musculoesquelético/tratamiento farmacológico , Dolor Musculoesquelético/etiología , Umbral del Dolor/efectos de los fármacos , Satisfacción del Paciente , Placebos , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Trastornos del Sueño-Vigilia/etiología , Resultado del TratamientoRESUMEN
The objective of this paper is to better understand the relationship of pain and mood in patients with fibromyalgia and comorbid major depressive disorder (MDD). Pooled data from 4 double-blind, placebo-controlled, randomized trials of duloxetine hydrochloride 60-120mg/day in patients with fibromyalgia were included (N=1332). Of these, 350 (26% [147 placebo, 203 duloxetine]) had comorbid MDD (per Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision criteria) and were included in these analyses. Primary measures included Brief Pain Inventory average pain; Hamilton Depression Rating Scale or Beck Depression Inventory. Logistic regression was used to evaluate the consistency of treatment effect across various subgroups. Path analysis was used to assess the effect of duloxetine on improvement in pain in the presence of improvement in mood and vice versa. Results indicated that 69% of improvement in pain was a direct effect of treatment, with improvement in mood accounting for 31% of pain response. In conclusion, consistent with our hypothesis, duloxetine produced a substantial direct effect on pain improvement and change in mood exerted a modest indirect effect on pain improvements in patients with fibromyalgia and MDD. Hence, both direct and indirect analgesic and antidepressant properties appear to be relevant for the treatment of these comorbid patients with duloxetine.
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Afecto/efectos de los fármacos , Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor , Fibromialgia , Dolor/etiología , Tiofenos/uso terapéutico , Adulto , Comorbilidad , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/epidemiología , Método Doble Ciego , Clorhidrato de Duloxetina , Femenino , Fibromialgia/complicaciones , Fibromialgia/tratamiento farmacológico , Fibromialgia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Escalas de Valoración Psiquiátrica , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To investigate the efficacy of flexible dose duloxetine 60-120 mg/day on changes in fibromyalgia (FM) symptoms assessed by the Patient Global Impression of Improvement (PGI-I) scale. METHODS: Outpatients ≥ 18 years of age who met American College of Rheumatology criteria for FM, and had ≥ 4 score on the Brief Pain Inventory (BPI) average pain item, were randomized to duloxetine (n = 263) or placebo (n = 267) for 24 week double-blind treatment (primary endpoint at Week 12). Key secondary measures included BPI average pain severity, patient-rated scales assessing mood, anxiety, pain, sleep, and stiffness, Clinical Global Impression of Severity (CGI-S), Multidimensional Fatigue Inventory, Cognitive and Physical Functioning Questionnaire, Beck Depression Inventory (BDI), Beck Anxiety Inventory, and Medical Outcome Study Short-Form Health Survey (SF-36). RESULTS: At Week 12, duloxetine-treated patients reported significantly greater global improvement with mean PGI-I scores of 2.8 compared to 3.4 in the placebo group (p < 0.001). Significantly more duloxetine- versus placebo-treated patients (57% vs 32%; p < 0.001) reported feeling "much" or "very much better" (PGI-I score ≤ 2). There was significantly greater improvement with duloxetine versus placebo treatment in BPI average pain severity, mood (including BDI total), anxiety (patient-rated only), stiffness, CGI-S, fatigue, all SF-36 domains (except role-physical and physical component summary), and being less bothered by pain or sleep difficulties. Treatment-emergent adverse events occurring significantly more frequently with duloxetine included: nausea, headache, constipation, dry mouth, dizziness, diarrhea, and hyperhidrosis. CONCLUSION: Treatment with duloxetine 60, 90, and 120 mg/day was associated with feeling much better, pain reduction, being less bothered by sleep difficulties, and improvement in mood, stiffness, fatigue and functioning. (Clinical trial registry NCT00673452).
Asunto(s)
Fibromialgia/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Tiofenos/uso terapéutico , Adulto , Método Doble Ciego , Clorhidrato de Duloxetina , Femenino , Fibromialgia/fisiopatología , Humanos , Persona de Mediana Edad , Placebos , Índice de Severidad de la Enfermedad , Tiofenos/administración & dosificación , Resultado del TratamientoRESUMEN
INTRODUCTION: This study tested the hypothesis that baseline ratings of fatigue/tiredness would be negatively associated with the efficacy of duloxetine on measures of pain and functional ability in patients with fibromyalgia. METHODS: A post hoc analysis of pooled data from 4 double-blind, placebo-controlled studies of duloxetine in fibromyalgia was performed. The fibromyalgia impact questionnaire (FIQ) tiredness item score (0 to 10 scale) was used to define tiredness subgroups. Patients were stratified into 3 subgroups: mild (0 to 3), moderate (4 to 6), and severe (7 to 10) tiredness. Analysis of covariance models and logistic regressions were used to test treatment-by-tiredness subgroup interactions. RESULTS: Data from the first 3 months are included in this post hoc analysis (duloxetine N = 797, placebo N = 535). At baseline, the distribution of tiredness severity in the duloxetine and placebo groups respectively was 3.64% and 3.75% mild, 16.71% and 15.57% moderate, and 79.65% and 80.68% severe. Rates of clinically significant (≥30% and ≥50%) improvement in brief pain inventory (BPI) average pain were similar across the tiredness subgroups. Tiredness severity at baseline was not negatively associated with the effects of duloxetine on patients' reports of functional ability using the FIQ total score, FIQ measures of physical impairment, interference with work, pain, stiffness, and depression and the medical outcomes study short form-36 (SF-36). CONCLUSIONS: Studies of duloxetine in fibromyalgia have demonstrated clinically significant improvements in pain and functional ability (FIQ, SF-36). This post hoc analysis of data shows that the efficacy of duloxetine among patients with fibromyalgia does not vary as a function of baseline ratings of fatigue/tiredness.
Asunto(s)
Fatiga/tratamiento farmacológico , Fibromialgia/tratamiento farmacológico , Recuperación de la Función/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Tiofenos/uso terapéutico , Clorhidrato de Duloxetina , Humanos , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVES: This study examined the time course for minimal clinically significant improvement in pain severity during the initial 12 weeks of treatment in patients with fibromyalgia taking duloxetine. METHODS: Four double-blind, placebo-controlled trials of duloxetine were pooled. Patients received duloxetine 60 mg/d, 120 mg/d, or placebo. Clinically significant treatment response (>or=30% reduction in pain severity on the 24-hour average pain severity of the Brief Pain Inventory scale) was assessed over 12 weeks. RESULTS: At endpoint, 46.9% of duloxetine 60-mg-, 48.6% of duloxetine 120-mg-, and 32.1% of placebo-treated patients (P<0.001 for both doses) had >or=30% improvement on average pain from baseline. The probabilities of achieving >or=30% response at Weeks 1, 2, 4, 8, and 12 among duloxetine 60-mg-treated patients were 27%, 44%, 45%, 47%, and 49%, respectively, and among duloxetine 120-mg-treated patients were 35%, 43%, 53%, 53%, and 51%, respectively (P<0.01 vs. placebo at each week, for both doses). Among patients who did not respond by Weeks 1, 2, 4, and 8, the percentages of duloxetine 60-mg-treated patients who achieved a response by the endpoint of the study were 36.9%, 29.8%, 28.9%, and 26.9%, respectively. DISCUSSION: This article examines the time course for minimal clinically significant improvement in pain severity in duloxetine-treated patients with fibromyalgia. It provides information about continued treatment in patients who do not initially respond to duloxetine. This information could potentially help physicians facing clinical decisions about management of fibromyalgia with duloxetine.
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Inhibidores de Captación Adrenérgica/uso terapéutico , Fibromialgia/complicaciones , Dolor/tratamiento farmacológico , Dolor/etiología , Tiofenos/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Clorhidrato de Duloxetina , Femenino , Fibromialgia/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: To assess the long-term safety, tolerability, and efficacy of duloxetine in patients with fibromyalgia. METHODS: We report results from the 6-month extension phases of 2 randomized, double-blind, placebo-controlled clinical trials having 6-month placebo-controlled phases. In Study 1, all patients received duloxetine 120 mg/d after 28 weeks on placebo or duloxetine 60 or 120 mg/d. In Study 2, patients taking placebo were titrated to duloxetine 60 mg/d after 27 weeks on treatment, while duloxetine-treated patients remained on their dosages of 60 or 120 mg/d. Safety and tolerability were assessed via discontinuation rates, treatment-emergent adverse events (TEAEs), and changes in vital signs and laboratory measures. The primary efficacy measure was the Brief Pain Inventory average pain severity score. RESULTS: The percentage of patients entering and completing the extension phase was 56% (156/278) for Study 1 and 69% (140/204) for Study 2. Groups titrating from placebo to duloxetine showed the highest discontinuation rates due to an adverse event (Study 1, 25%; Study 2, 19%) and TEAE rates (Study 1, 82%; Study 2, 77%). The most common TEAEs were nausea and dry mouth. No significant within-group changes in blood pressure occurred in any group. Significant within-group mean increases in pulse (bpm) were observed in the placebo/duloxetine 120 mg group in Study 1 (3.7 [SD = 11.2], P Asunto(s)
Antidepresivos/uso terapéutico
, Fibromialgia/tratamiento farmacológico
, Tiofenos/uso terapéutico
, Depresión/tratamiento farmacológico
, Depresión/psicología
, Evaluación de la Discapacidad
, Método Doble Ciego
, Clorhidrato de Duloxetina
, Femenino
, Fibromialgia/fisiopatología
, Fibromialgia/psicología
, Estado de Salud
, Humanos
, Masculino
, Persona de Mediana Edad
, Dolor/tratamiento farmacológico
, Dolor/fisiopatología
, Dimensión del Dolor
, Resultado del Tratamiento
RESUMEN
OBJECTIVE: To investigate the efficacy of duloxetine in the treatment of pain and improvement in functional impairment and quality of life in patients with fibromyalgia from a pooled analysis of 4 placebo-controlled, double-blind, randomized trials. METHOD: Patients were eligible for inclusion in the studies if they were at least 18 years of age, met criteria for fibromyalgia as defined by the American College of Rheumatology, and had specified minimum pain severity scores. Across all studies, 797 patients received duloxetine 60-120 mg/d and 535 patients received placebo. Pain was assessed by the Brief Pain Inventory (BPI) 24-hour average pain severity score; other efficacy measures included the Clinical Global Impressions-Severity of Illness scale (CGI-S), Patient Global Impressions-Improvement scale (PGI-I), 17-item Hamilton Depression Rating Scale (HDRS-17), Fibromyalgia Impact Questionnaire (FIQ) total score, BPI pain interference items, Sheehan Disability Scale (SDS), and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) mental and physical components. Changes from baseline to endpoint (last observation carried forward) for most of the above efficacy measures were analyzed using an analysis-of-covariance model. RESULTS: After 12 weeks of treatment, pain was significantly reduced in patients treated with duloxetine (P < .001) compared with placebo. In addition, duloxetine was superior to placebo in improving CGI-S (P < .001); PGI-I (P < .001); FIQ total (P < .001); HDRS-17 total (P = .003); SDS global functioning (P < .001), work/school (P = .018), and family life (P < .001); SF-36 mental (P < .001) and physical (P = .026) component; and BPI pain interference (P < .001) scores. Treatment-by-subgroup interactions were not significant for sex (P = .320), age (P = .362), or race (P = .180). CONCLUSIONS: This pooled analysis provides evidence that 12 weeks of treatment with duloxetine 60-120 mg/d effectively improves fibromyalgia symptoms and may offer benefits beyond pain relief.
RESUMEN
OBJECTIVE: To investigate the relationship between changes in clinical rating scale items and endpoint Patient Global Impression of Improvement (PGI-I). METHODS: Data were pooled from 4 randomized, double-blind, placebo-controlled studies of duloxetine in patients with fibromyalgia (FM). Variables included in the analyses were those that assessed symptoms in FM domains of pain, fatigue, sleep, cognitive difficulties, emotional well-being, physical function, and impact on daily living. The association of endpoint PGI-I with changes from baseline in individual variables was assessed using Pearson product-moment correlations (r). Stepwise linear regression was used to identify those variables for which changes from baseline were statistically significant independent predictors of the endpoint PGI-I ratings. RESULTS: Changes in pain variables and interference of symptoms with the ability to work were highly correlated (r >or= 0.5 or r Asunto(s)
Antidepresivos/uso terapéutico
, Fibromialgia
, Dolor
, Tiofenos/uso terapéutico
, Clorhidrato de Duloxetina
, Fibromialgia/tratamiento farmacológico
, Fibromialgia/fisiopatología
, Fibromialgia/psicología
, Humanos
, Dolor/tratamiento farmacológico
, Dolor/psicología
, Dimensión del Dolor
, Ensayos Clínicos Controlados Aleatorios como Asunto
, Encuestas y Cuestionarios
RESUMEN
BACKGROUND: Evaluation and treatment of major depression (MDD) in elderly patients is frequently complicated by the presence of comorbid medical conditions, which can reduce the effect of depression treatment, leading to lower rates of depressive-symptom improvement and higher rates of relapse. OBJECTIVE: The authors investigated results of antidepressant concurrent with arthritis pain treatment in elderly patients. METHOD: Patients age 65 and over with recurrent MDD were stratified by arthritis status and randomized to duloxetine (a dual reuptake-inhibitor of serotonin and norepinephrine) or placebo treatment for 8 weeks (duloxetine, N=117; placebo, N=55). RESULTS: Duloxetine significantly reduced MDD symptom severity in elderly patients with and without arthritis, and produced significant reduction in several pain measures in those patients with comorbid arthritis. DISCUSSION: The magnitude and time-course of depressive symptom improvement did not differ significantly between patients with and without arthritis. Some studies have suggested that the severity of pain in arthritis patients may be linked to depression severity.
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Antidepresivos/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Tiofenos/uso terapéutico , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Artritis/complicaciones , Trastorno Depresivo/complicaciones , Método Doble Ciego , Clorhidrato de Duloxetina , Femenino , Humanos , Masculino , Placebos , Recurrencia , Resultado del TratamientoRESUMEN
The purpose of this report is to describe the overall safety profile of both short- and longer-term duloxetine treatment of fibromyalgia. Data from four double-blind, randomized, placebo-controlled studies (two with 6-month open-label extension phases) and a 1-year, open-label safety study were included. Safety measures included treatment-emergent adverse events (TEAEs), adverse events leading to discontinuation, serious adverse events (SAEs), clinical laboratory tests, vital signs, and electrocardiograms. The most common TEAEs for short-term treatment with duloxetine were nausea (29.3%), headache (20.0%), dry mouth (18.2%), insomnia (14.5%), fatigue (13.5%), constipation (14.5%), diarrhea (11.6%), and dizziness (11.0%; all p < 0.05 vs. placebo). Most TEAEs emerged early and were mild to moderate in severity. The profile of adverse events in patients enrolled at least 6 months, and for patients in the 1-year study, was similar to that found in the short-term treatment studies, with no new adverse events emerging at a notable rate. About 20% of patients discontinued due to adverse events in the short-term treatment studies and in the 1-year study. SAEs were uncommon, and none occurred at a significantly higher frequency for duloxetine compared with placebo. Mean changes in vital signs and weight were small. Rates of treatment-emergent potentially clinically significant (PCS) vital sign, laboratory, and electrocardiogram measures were low, with only PCS rates of alanine aminotransferase being significantly higher for duloxetine compared with placebo in the placebo-controlled treatment studies. In the 1-year study, four patients (1.1%) had suicide-related behavior. The data provided here summarize short- and long-term safety from five clinical studies in patients treated with duloxetine for fibromyalgia. In addition, postmarketing surveillance continues for adverse events reported with duloxetine in fibromyalgia, as in other indications.
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Antidepresivos/administración & dosificación , Antidepresivos/efectos adversos , Fibromialgia/tratamiento farmacológico , Tiofenos/administración & dosificación , Tiofenos/efectos adversos , Clorhidrato de Duloxetina , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
OBJECTIVES: To investigate whether comorbid major depressive disorder (MDD) influenced the efficacy and safety of duloxetine in treating fibromyalgia (FM). METHODS: This was a post-hoc analysis using pooled data from 4 double-blind, placebo-controlled studies of patients with American College of Rheumatology-defined primary FM with or without MDD. Patients were randomized to duloxetine [60 or 120 mg/d (N=797)] or placebo (N=535) for approximately 3 months. Efficacy measures included the Brief Pain Inventory average pain score, 17-item Hamilton Depression Rating Scale, Fibromyalgia Impact Questionnaire, and Patient's/Clinician's Global Impressions of Improvement/Severity scales. RESULTS: At baseline, 26% of patients met diagnostic criteria for MDD. At endpoint (3 mo or last observation), duloxetine showed significantly (P<0.05) greater improvement versus placebo on the Brief Pain Inventory, Fibromyalgia Impact Questionnaire, Patient's Global Impressions of Improvement scale, and Clinician's Global Impressions of Severity scale in patients with and without comorbid MDD. The effect of duloxetine on these efficacy measures was consistent across FM patients with or without MDD (P>0.1 for treatment-by-strata interaction). On the 17-item Hamilton Depression Rating Scale, duloxetine showed significantly (P<0.05) greater improvement versus placebo in patients with comorbid MDD. The safety profile of duloxetine versus placebo with respect to serious adverse events and discontinuation owing to adverse events was similar for FM patients with versus without MDD (P>0.1 treatment-by-strata interaction). DISCUSSION: Duloxetine was effective in reducing pain and other symptoms in FM patients with and without MDD and demonstrated a similar safety profile for both groups.