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.

Topical diclofenac epolamine patch 1.3% for treatment of acute pain caused by soft tissue injury.

Acute pain caused by musculoskeletal disorders is very common and has a significant negative impact on quality-of-life and societal costs. Many types of acute pain have been managed with traditional oral non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitors (coxibs). Data from prospective, randomised controlled clinical trials and postmarketing surveillance indicate that use of oral traditional NSAIDs and coxibs is associated with an elevated risk of developing gastrointestinal, renovascular and/or cardiovascular adverse events (AEs). Increasing awareness of the AEs associated with NSAID therapy, including coxibs, has led many physicians and patients to reconsider use of these drugs and look for alternative treatment options. Treatment with NSAIDs via the topical route of administration has been shown to provide clinically effective analgesia at the site of application while minimising systemic absorption. The anti-inflammatory and analgesic potency of the traditional oral NSAID diclofenac, along with its physicochemical properties, makes it well suited for topical delivery. Several topical formulations of diclofenac have been developed. A topical patch containing diclofenac epolamine 1.3% (DETP, FLECTOR(®) Patch), approved for use in Europe in 1993, has recently been approved for use in the United States and is indicated for the treatment of acute pain caused by minor strains, sprains and contusions. In this article, we review the available clinical trial data for this product in the treatment of pain caused by soft tissue injury.

Antidepressants and Antiepileptic Drugs for Chronic Non-Cancer Pain

The development of newer classes of antidepressants and second-generation antiepileptic drugs has created unprecedented opportunities for the treatment of chronic pain. These drugs modulate pain transmission by interacting with specific neurotransmitters and ion channels. The actions of antidepressants and antiepileptic drugs differ in neuropathic and non-neuropathic pain; and agents within each medication class have varying degrees of efficacy. Tricyclic antidepressants (e.g.; amitriptyline; nortriptyline; desipramine) and certain novel antidepressants (i.e.; bupropion; venlafaxine; duloxetine) are effective in the treatment of neuropathic pain. The analgesic effect of these drugs is independent of their antidepressant effect and appears strongest in agents with mixed-receptor or predominantly noradrenergic activity; rather than serotoninergic activity. First-generation antiepileptic drugs (i.e.; carbamazepine; phenytoin) and second-generation antiepileptic drugs (e.g.; gabapentin; pregabalin) are effective in the treatment of neuropathic pain. The efficacy of antidepressants and antiepileptic drugs in the treatment of neuropathic pain is comparable; tolerability also is comparable; but safety and side effect profiles differ. Tricyclic antidepressants are the most cost-effective agents; but second-generation antiepileptic drugs are associated with fewer safety concerns in elderly patients. Tricyclic antidepressants have documented (although limited) efficacy in the treatment of fibromyalgia and chronic low back pain. Recent evidence suggests that duloxetine and pregabalin have modest efficacy in patients with fibromyalgia

Osteoarthritis. How to manage pain and improve patient function.

Osteoarthritis (OA) typically affects persons over age 60 and is often associated with pain and disability. Weight-bearing joints are most commonly affected. The goal of treatment is to minimize pain and its impact on patient function and quality of life. Patient education, psychological support, weight control, exercise, heat/cold application, and use of assistive devices are safe nonpharmacologic approaches. Pharmacologic therapies include acetaminophen, selected NSAIDs, and other analgesics, including opioids for moderate to severe pain. Topical agents, complementary products, viscosupplementation, and surgery may be useful in an individualized treatment plan.

Evidence- and consensus-based practice guidelines for the diagnosis of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) presents a significant diagnostic and management challenge for primary care practitioners. Improving the accuracy and timeliness of diagnosis may result in improved quality and efficiency of care. OBJECTIVE: To systematically appraise the existing diagnostic criteria and combine the evidence with expert opinion to derive evidence- and consensus-based guidelines for a diagnostic approach to patients with suspected IBS. METHODS: We performed a systematic literature review (January 1966-April 2000) of computerized bibliographic databases. Articles meeting explicit inclusion criteria for diagnostic studies in IBS were subjected to critical appraisal, which formed the basis of guideline statements presented to an expert panel. To develop a diagnostic algorithm, an expert panel of specialists and primary care physicians was used to fill in gaps in the literature. Consensus was developed using a modified Delphi technique. RESULTS: The systematic literature review identified only 13 published studies regarding the effectiveness of competing diagnostic approaches for IBS, the accuracy of diagnostic tests, and the internal validity of current diagnostic symptom criteria. Few studies met accepted methodological criteria. While symptom criteria have been validated, the utility of endoscopic and other diagnostic interventions remains unknown. An analysis of the literature, combined with consensus from experienced clinicians, resulted in the development of a diagnostic algorithm relevant to primary care that emphasizes a symptom-based diagnostic approach, refers patients with alarm symptoms to subspecialists, and reserves radiographic, endoscopic, and other tests for referral cases. The resulting algorithm highlights the reliance on symptom criteria and comprises a primary module, 3 submodules based on the predominant symptom pattern (constipation, diarrhea, and pain) and severity level, and a subspecialist referral module. CONCLUSIONS: The dearth of available evidence highlights the need for more rigorous scientific validation to identify the most accurate methods of diagnosing IBS. Until such time, the diagnostic algorithm presented herein could inform decision making for a range of providers caring for primary care patients with abdominal discomfort or pain and altered bowel function suggestive of IBS.

Long-acting opioids for chronic pain: pharmacotherapeutic opportunities to enhance compliance, quality of life, and analgesia.

Effective management of chronic pain has become an increasingly critical issue in health care. Opioid agonists are among the most effective analgesics available for reducing pain perception; however, their chronic use is controversial. This is primarily due to regulatory barriers, misunderstandings about pain management among primary caregivers, fear of adverse side effects, and misconceptions about the potential risks of addiction. Short-acting opioids provide effective analgesia for acute pain but should be avoided as primary analgesics for chronic pain management. Long-acting opioids have greater utility than short-acting opioids in treating chronic pain in patients with consistent pain levels. Results of studies show that improved quality of life is directly related to the use of long-acting opioids in patients with chronic pain of both cancer and noncancer etiology. Short-acting opioids may be used during the initial dose titration period of long-acting formulations and as rescue medication for episodes of breakthrough pain. Clinical experience reveals that selection of an effective pain regimen for the patient with chronic pain, combined with aggressive management of side effects, leads to improved overall functioning and quality of life.

Chronic pain management in a health maintenance organization.

OBJECTIVE: The purpose of this study is to investigate the management of chronic pain in a large health maintenance organization using cognitive-behavioral techniques and a blinded control group. DESIGN: Subjects were randomized into two groups. All participants completed a self-administered baseline questionnaire and were mailed a self-administered 6-month follow-up questionnaire. SETTING: This study examines chronic pain management in a large, established health maintenance organization. PATIENTS: Patients were members of a health maintenance organization, had pain for at least 6 months, and had failed all known treatment regimens. INTERVENTIONS: The treatment group participated in a 16-hour, 8-week class teaching cognitive-behavioral techniques, the relaxation response, meditation, and stress management. The minimal treatment group received a home-study manual. OUTCOME MEASURES: Behavioral outcomes, function, and pain severity and also patient satisfaction were measured. RESULTS: Both the treatment and minimal treatment groups exhibited improvement in pain severity, negative mood, pain affect, and pain interference with the patient's life. CONCLUSION: Gains were achieved in pain severity, negative mood, pain affect, self-control, and pain interference with the patient's life. Other behavioral variables and activity did not improve. Except in self-control, pain affect, and distracting responses from their significant others, the blinded minimal treatment group demonstrated similar findings. Patient satisfaction with treatment strongly favored the treatment group with over 78% of the treatment participants satisfied with the care provided.