Efficacy and safety of duloxetine in Chinese patients with chronic pain due to osteoarthritis: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: We assessed the efficacy and safety of duloxetine (60 mg, once daily), compared with placebo, during a 13-week treatment period in Chinese patients with chronic pain due to osteoarthritis (OA). DESIGN: Patients were at least 40 years old (male or female) who met American College of Rheumatology clinical and radiographic criteria for the diagnosis of OA of the knee or hip. The primary efficacy measure in this phase 3, randomized, double-blind, placebo-controlled clinical trial was assessment of pain severity by the Brief Pain Inventory (BPI) 24-h Average Pain rating. The clinical trial was conducted at 17 study centers. Statistical approaches included mixed-effects model repeated measures and analysis of covariance. A Fisher exact test was applied to categorical variables. RESULTS: Of 407 patients randomized (duloxetine: N = 205; placebo: N = 202), 166 (81.0%) patients from the duloxetine group and 176 (87.1%) patients from the placebo group completed the 13-week treatment phase. The majority (76.4%) of patients was female; mean age was 60.5 years. Duloxetine-treated patients reported significant pain reduction, compared with placebo treatment, on the BPI 24-h Average Pain rating (least-squares mean (LS Mean) change from baseline to endpoint [95% confidence interval (CI)], duloxetine: -2.23; placebo: -1.73; difference = -0.50 [-0.80, -0.20]; P = 0.001). The incidence of discontinuations due to adverse events was 9.0% in duloxetine-treated patients and 4.5% in placebo-treated patients (P = 0.109). CONCLUSIONS: This study demonstrated the efficacy of duloxetine in Chinese patients with chronic pain due to OA. The safety profile of duloxetine observed in this study was consistent with that in previous duloxetine trials. This trial is registered with ClinicalTrials.gov (NCT01931475).

Predictive factors and clinical biomarkers for treatment in patients with chronic pain caused by osteoarthritis with a central sensitisation component.

AIMS: The aim of this non-systematic review was to provide a practical guide for clinicians on the evidence for central sensitisation in chronic osteoarthritis (OA) pain and how this pain mechanism can be addressed in terms of clinical diagnosis, investigation and treatment. METHODS: The authors undertook a non-systematic review of the literature including a MEDLINE search (search terms included central sensitisation, osteoarthritis, osteoarthrosis) for relevant and current clinical studies, systematic reviews and narrative reviews. Case reports, letters to the editor and similar literature sources were excluded. Information was organised to allow a pragmatic approach to the discussion of the evidence and generation of practical recommendations. RESULTS: There is good evidence for a role of central sensitisation in chronic OA pain in a subgroup of patients. Clinically, a central sensitisation component in chronic OA pain can be suspected based on characteristic pain features and non-pain features seen in other conditions involving central sensitisation. However, there are currently no diagnostic inventories for central sensitisation specific to OA. Biomarkers may be helpful for confirming the presence of central sensitisation, especially when there is diagnostic uncertainty. Several non-pharmacological and pharmacological treatments may be effective in OA patients with central sensitisation features. Multimodal therapy may be required to achieve control of symptoms. DISCUSSION: Clinicians should be aware of central sensitisation in patients with chronic OA pain, especially in patients presenting with severe pain with unusual features.

Treatment of patients with diabetic peripheral neuropathic pain in China: a double-blind randomised trial of duloxetine vs. placebo.

BACKGROUND: Duloxetine has been approved in the United States, European Union and some Asian countries for the treatment of diabetic peripheral neuropathic pain (DPNP). We assessed the efficacy and safety of duloxetine (60 mg once daily) compared with placebo in Chinese patients suffering from DPNP. METHODS: This was a phase 3, multicenter, randomised, double-blind, parallel, placebo-controlled, 12-week trial of the treatment of DPNP with duloxetine. Subjects were male and female outpatients ≥ 18 years of age with DPNP, as assessed by the Michigan Neuropathy Screening Instrument, and had a rating of ≥ 4 on the Brief Pain Inventory-Modified Short Form-Severity weekly average pain item. The primary efficacy measure was the reduction in pain severity from baseline to 12 weeks, as measured by the weekly mean of 24-h average pain ratings recorded in the patient's diary. Mean changes from baseline in efficacy measures were analysed by a restricted maximum likelihood-based, mixed-effects model repeated measures approach and by analysis of covariance. RESULTS: Of the 405 patients randomised, 203 patients were assigned to duloxetine 60 mg once daily and 202 patients were assigned to placebo. Duloxetine-treated patients showed significantly greater pain relief on 24-h average pain ratings compared with placebo-treated patients each week of the 12-week study period [week 12: least squares (LS) mean change duloxetine: -2.40, placebo: -1.97; LS mean change difference (95% confidence interval) = -0.43 (-0.82, -0.04), p = 0.030]. Compared with placebo, patients treated with duloxetine experienced higher rates of nausea (p = 0.010), somnolence (p < 0.001) and asthenia (p = 0.002). CONCLUSIONS: Duloxetine-treated patients showed significantly greater pain relief compared with placebo-treated patients over the 12-week study period. Duloxetine was shown in Chinese patients to have a safety profile similar to that found in previous duloxetine trials.

Weight change with long-term duloxetine use in chronic painful conditions: an analysis of 16 clinical studies.

AIMS: Report weight change baseline up to 12-15 months in duloxetine-treated patients during clinical trials of chronic painful conditions of diabetic peripheral neuropathic pain (DPNP), fibromyalgia, chronic low back pain (CLBP) and chronic knee pain as a result of osteoarthritis. METHODS: Weight change data from 16 duloxetine studies in chronic painful conditions were pooled by pain condition and duration, creating 10 datasets. Datasets included placebo-controlled, open-label and routine-care-controlled designs. Assessments included mean weight change from baseline, baseline body mass index category, potentially clinically significant (PCS) weight change and weight-related treatment-emergent adverse events. RESULTS: Total number of patients was 5111 with mean baseline weight ranging from 70 to 97 kg. All duloxetine groups had significant mean weight loss compared with placebo at acute phase completion (p ≤ 0.001). In studies > 3 months, patients from fibromyalgia and CLBP studies had overall mean weight increase (up to 1.1 kg), whereas patients in DPNP studies had overall mean weight loss (-0.33 to -1.7 kg) at end-point. Overall, the percentage of patients with PCS weight gain was 0.4-16% and PCS weight loss was 2.5-9.9%. DISCUSSION: Weight change data in clinical trials of patients with fibromyalgia or CLBP treated with duloxetine for up to 15 months were consistent with data reported in 10 clinical trials of patients with major depressive disorder (MDD) using duloxetine up to 52 weeks. Patients with DPNP had weight loss at end-point. CONCLUSION: Mean weight changes and percentages of patients with PCS weight loss and weight gain observed in DPNP, fibromyalgia and CLBP with long-term duloxetine treatment were consistent with those reported previously for MDD studies.

Improvement of psychic and somatic symptoms in adult patients with generalized anxiety disorder: examination from a duloxetine, venlafaxine extended-release and placebo-controlled trial.

BACKGROUND: This study examined the efficacy and tolerability of duloxetine and venlafaxine extended-release (XR) treatment for generalized anxiety disorder (GAD), with a secondary focus on psychic and somatic symptoms within GAD. METHOD: The design was a 10-week, multi-center, double-blind placebo-controlled study of duloxetine (20 mg or 60-120 mg once daily) and venlafaxine XR (75-225 mg once daily) treatment. Efficacy was measured using the Hamilton Anxiety Rating Scale (HAMA), which includes psychic and somatic factor scores. Tolerability was measured by occurrence of treatment-emergent adverse events (TEAEs) and discontinuation rates. RESULTS: Adult out-patients (mean age 42.8 years; 57.1% women) with DSM-IV-defined GAD were randomly assigned to placebo (n=170), duloxetine 20 mg (n=84), duloxetine 60-120 mg (n=158) or venlafaxine XR 75-225 mg (n=169) treatment. Each of the three active treatment groups had significantly greater improvements on HAMA total score from baseline to endpoint compared with placebo (p=0.01-0.001). For the HAMA psychic factor score, both duloxetine treatment arms and venlafaxine XR demonstrated significantly greater improvement compared with placebo (p=0.01-0.001). For the HAMA somatic factor score, the mean improvement in the duloxetine 60-120 mg and venlafaxine XR groups was significantly greater than placebo (p0.05 and p0.01 respectively), whose mean improvement did not differ from the duloxetine 20 mg group (p=0.07). Groups did not differ in study discontinuation rate due to adverse events. CONCLUSIONS: Duloxetine and venlafaxine treatment were each efficacious for improvement of core psychic anxiety symptoms and associated somatic symptoms for adults with GAD.

Pediatric concussions in sports; a simple and rapid assessment tool for concussive injury in children and adults.

BACKGROUND: We established a routine protocol for concussion evaluation in athletes for nonmedical personnel. The evaluation, management guidelines, and return-to-play recommendations were summarized with a memorable mnemonic on a convenient handheld card. MATERIALS AND METHODS: The ability to remember the return-to-play mnemonic and effectively apply it to corresponding guidelines was evaluated in 194 sports personnel without medical training. The participants were given three clinical scenarios, each including age, pertinent history, sporting event, description of an injury, symptoms, signs, and a brief neurological exam. Subsequently, the subject's ability to recall the return-to-play mnemonic and the Standard Assessment of Concussion, to describe the corresponding guidelines, and to advise return-to-play was evaluated. CONCLUSION: Our "return-to-play" mnemonic was found to be simple and memorable, allowing for a high recall percentage and accurate evaluation of concussion cases. High intersubject agreement suggests that this method has both standardization and generalization potential.