Safety Of Duloxetine In Patients Research Articles

A Randomized, Placebo-Controlled, Double-Blinded Trial of Duloxetine in the Treatment of General Fatigue in Patients With Chronic Fatigue Syndrome

To assess the efficacy and safety of duloxetine in patients with chronic fatigue syndrome. A 12-week, randomized, double-blind study was designed to compare duloxetine 60-120 mg/d (n = 30) with placebo (n = 30) for efficacy and safety in the treatment of patients with chronic fatigue syndrome. The primary outcome measure was the Multidimensional Fatigue Inventory general fatigue subscale (range: 4-20, with higher scores indicating greater fatigue). Secondary measures were the remaining Multidimensional Fatigue Inventory subscales, Brief Pain Inventory, Medical Outcomes Study Short Form-36, Hospital Anxiety and Depression Scale, Centers for Disease Control and Prevention Symptom Inventory, Patient Global Impression of Improvement, and Clinical Global Impression of Severity. The primary analysis of efficacy for continuous variables was a longitudinal analysis of the intent-to-treat sample, with treatment-by-time interaction as the measure of effect. The improvement in the Multidimensional Fatigue Inventory general fatigue scores for the duloxetine group was not significantly greater than for the placebo group (P = 0.23; estimated difference between groups at week 12 = -1.0 [95% CI: -2.8, 0.7]). The duloxetine group was significantly superior to the placebo group on the Multidimensional Fatigue Inventory mental fatigue score, Brief Pain Inventory average pain severity and interference scores, Short Form-36 bodily pain domain, and Clinical Global Impression of Severity score. Duloxetine was generally well tolerated. The primary efficacy measure of general fatigue did not significantly improve with duloxetine when compared with placebo. Significant improvement in secondary measures of mental fatigue, pain, and global measure of severity suggests that duloxetine may be efficacious for some chronic fatigue syndrome symptom domains, but larger controlled trials are needed to confirm these results.

Efficacy and Safety of Duloxetine in Patients with Chronic Low Back Pain Who Used versus Did Not Use Concomitant Nonsteroidal Anti-Inflammatory Drugs or Acetaminophen: A Post Hoc Pooled Analysis of 2 Randomized, Placebo-Controlled Trials.

This subgroup analysis assessed the efficacy of duloxetine in patients with chronic low back pain (CLBP) who did or did not use concomitant nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen (APAP). Data were pooled from two 13-week randomized trials in patients with CLBP who were stratified according to NSAID/APAP use at baseline: duloxetine NSAID/APAP user (n = 137), placebo NSAID/APAP user (n = 82), duloxetine NSAID/APAP nonuser (n = 206), and placebo NSAID/APAP nonuser (n = 156). NSAID/APAP users were those patients who took NSAID/APAP for at least 14 days per month during 3 months prior to study entry. An analysis of covariance model that included therapy, study, baseline NSAID/APAP use (yes/no), and therapy-by-NSAID/APAP subgroup interaction was used to assess the efficacy. The treatment-by-NSAID/APAP use interaction was not statistically significant (P = 0.31) suggesting no substantial evidence of differential efficacy for duloxetine over placebo on pain reduction or improvement in physical function between concomitant NSAID/APAP users and non-users.

P.2.c.009 Efficacy and safety of duloxetine in patients with melancholic depression

Randomised, placebo-controlled trials of treatments for depression typically collect outcomes data but traditionally only analyse data to demonstrate efficacy and safety. Additional post-hoc statistical techniques may reveal important insights about treatment variables useful when considering inter-individual differences amongst depressed patients. This paper aims to examine the Gradient Boosted Model (GBM), a statistical technique that uses regression tree analyses and can be applied to clinical trial data to identify and measure variables that may influence treatment outcomes.GBM was applied to pooled data from 12 randomised clinical trials of 4987 participants experiencing an acute depressive episode who were treated with duloxetine, an SSRI or placebo to predict treatment remission. Additional analyses were conducted on the same dataset using the logistic regression model for comparison between these two methods.With GBM, there were noticeable differences between treatments when identifying which and to what extent variables were associated with remission. A single logistic regression only revealed a decreasing or increasing relationship between predictors and remission while GBM was able to reveal a complex relationship between predictors and remission.These analyses were conducted post-hoc utilising clinical trials databases. The criteria for constructing the analyses data were based on the characteristics of the clinical trials.GBM can be used to identify and quantify patient variables that predict remission with specific treatments and has greater flexibility than the logistic regression model. GBM may provide new insights into inter-individual differences in treatment response that may be useful for selecting individualised treatments.IMPACT clinical trial number 3327; IMPACT clinical trial number 4091; IMPACT clinical trial number 4689; IMPACT clinical trial number 4298; NCT00071695; NCT00062673; NCT00036335; NCT00067912; NCT00073411; NCT00489775; NCT00536471; NCT00666757 (note that trials with IMPACT numbers predate mandatory clinical trial registration requirements)

Efficacy and Safety of Duloxetine in Patients With Chronic Low Back Pain

This was a randomized, double-blind, placebo-controlled clinical trial. To assess the efficacy and safety of duloxetine in the treatment of chronic low back pain (CLBP). Imbalance of serotonin and norepinephrine within modulatory pain pathways has been implicated in the development and maintenance of chronic pain. Duloxetine, a selective reuptake inhibitor of serotonin and norepinephrine, has demonstrated clinical efficacy in 3 distinct chronic pain conditions: diabetic peripheral neuropathic pain, fibromyalgia, and chronic pain because of osteoarthritis. In this randomized double-blind trial, adult nondepressed patients with a non-neuropathic CLBP and a weekly mean of the 24-hour average pain score>or=4 at baseline (0-10 scale) were treated with either duloxetine or placebo for 13 weeks. The dose of duloxetine during first 7 weeks was 60 mg once daily. At week 7, patients reporting<30% pain reduction had their dose increased to 120 mg. The primary outcome measure was the Brief Pain Inventory (BPI) 24-hour average pain rating. Secondary measures included Roland-Morris Disability Questionnaire-24; Patient's Global Impressions of Improvement; Clinical Global Impressions-Severity (CGI-S); BPI-Severity and -Interference (BPI-I); and weekly means of the 24-hour average pain, night pain, and worst pain scores from patient diaries. Quality-of-life, safety, and tolerability outcomes were also assessed. Compared with placebo-treated patients (least-squares mean change of -1.50), patients on duloxetine (least-squares mean change of -2.32) had a significantly greater reduction in the BPI 24-hour average pain from baseline to endpoint (P=0.004 at week 13). Additionally, the duloxetine group significantly improved on Patient's Global Impressions of Improvement; Roland-Morris Disability Questionnaire-24; BPI-Severity and average BPI-Interference; weekly mean of the 24-hour average pain, night pain, and worst pain. Significantly more patients in the duloxetine group (13.9%) compared with placebo (5.8%) discontinued because of adverse events (P=0.047). The most common treatment-emergent adverse events in the duloxetine group included nausea, dry mouth, fatigue, diarrhea, hyperhidrosis, dizziness, and constipation. Duloxetine significantly reduced pain and improved functioning in patients with CLBP. The safety and tolerability were similar to those reported in earlier studies.

Efficacy and Safety of Duloxetine in Patients With Chronic Low Back Pain

From the Departments of Family Medicine and Medicine, Oregon Health and Science University, Portland, OR. The device(s)/drug(s) that is/are the subject of this manuscript is/are not FDA-approved for this indication and is/are commercially available in the United States. No funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript. Address correspondence and reprint requests to Richard A. Deyo, MD, MPH, Department of Family Medicine (FM), Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239-3098; E-mail: [email protected].

Duloxetine Versus Placebo in Patients With Chronic Low Back Pain: A 12-Week, Fixed-Dose, Randomized, Double-Blind Trial

This randomized, double-blind, placebo-controlled study assessed efficacy and safety of duloxetine in patients with chronic low back pain (CLBP). Adults (n = 401) with a nonneuropathic CLBP and average pain intensity of ≥ 4 on an 11-point numerical scale (Brief Pain Inventory [BPI]) were treated with either duloxetine 60 mg once daily or placebo for 12 weeks. The primary measure was BPI average pain. Secondary endpoints included Patient's Global Impressions of Improvement (PGI-I), Roland Morris Disability Questionnaire (RMDQ-24), BPI-Severity (BPI-S), BPI-Interference (BPI-I), and response rates (either ≥ 30% or ≥ 50% BPI average pain reduction at endpoint). Health outcomes included Short Form-36, European Quality of Life-5 Dimensions, and the Work Productivity and Activity Impairment questionnaire. Safety and tolerability were assessed. Compared with placebo-treated patients, duloxetine-treated patients reported a significantly greater reduction in BPI average pain (P ≤ .001). Similarly, duloxetine-treated patients reported significantly greater improvements in PGI-I, BPI-S, BPI-I, 50% response rates, and some health outcomes. The RMDQ and 30% response rate showed numerical improvements with duloxetine treatment. Significantly more patients in the duloxetine group (15.2%) than patients in the placebo group (5.4%) discontinued because of adverse events (P = .002). Nausea and dry mouth were the most common treatment-emergent adverse events with rates significantly higher in duloxetine-treated patients. This study provides clinical evidence of the efficacy and safety of duloxetine at a fixed dose of 60 mg once daily in the treatment of chronic low back pain (CLBP). As of December 2009, duloxetine has not received regulatory approval for the treatment of CLBP.

Safety and tolerability of duloxetine treatment of diabetic peripheral neuropathic pain between patients with and without cardiovascular conditions

Background Diabetic patients are predisposed to cardiovascular (CV) disease and other chronic medical conditions. We compared the safety of duloxetine in patients with (CV-positive) and without (CV-negative) historical/comorbid cardiovascular conditions at study entry. Methods Data were pooled from three double-blind studies in which patients (age ≥18 years) with diabetic peripheral neuropathic pain (DPNP) were randomized to 12 weeks of duloxetine (DLX) 60 mg qd ( n=344), 60 mg bid ( n=341), or placebo (PBO, n=339). Safety assessments included discontinuation rates, spontaneously reported treatment-emergent adverse events (TEAEs), changes in vital signs, and changes in lab analytes. Results Mean age of CV-positive patients ( n=762) vs. CV-negative patients ( n=262) was 61.1 vs. 56.1 years. The most common historical or comorbid CV conditions were hypertension, coronary artery disease, and myocardial infarction. Discontinuation due to adverse events was higher for DLX than for PBO in both CV-positive and CV-negative patients (13.5% DLX, 6.0% PBO, and 14.3% DLX, 3.4% PBO, respectively). Rates of CV-related TEAEs in CV-positive (8.4% DLX; 9.9% PBO) and CV-negative (8.6% DLX; 5.7% PBO) patients were similar ( P>.1). Mean changes in blood pressure for each DLX dose vs. PBO between CV-positive and CV-negative patients were not statistically significant ( P>.1), nor were sustained hypertension rates between CV-positive (2.4% DLX; 2.8% PBO) and CV-negative (2.9% DLX; 4.7% PBO) patients. Conclusions In this analysis, the safety of duloxetine in patients with DPNP was not found to be significantly different between patients with and without historical or comorbid CV conditions.