Self-guided digital behavioural therapy versus active control for fibromyalgia (PROSPER-FM): a phase 3, multicentre, randomised controlled trial.

Background: International guidelines have recommended cognitive behavioural therapy, including acceptance and commitment therapy (ACT), as it offers validated benefits for managing fibromyalgia; however, it is inaccessible to most patients. We aimed to evaluate the effect of a 12-week, self-guided, smartphone-delivered digital ACT programme on fibromyalgia management.

Methods: In the PROSPER-FM randomised clinical trial conducted at 25 US community sites, adult participants aged 22-75 years with fibromyalgia were recruited and randomly assigned (1:1) to the digital ACT group or an active control group that offered daily symptom tracking and monitoring and access to health-related and fibromyalgia-related educational materials.

Self-guided digital acceptance and commitment therapy for fibromyalgia management: results of a randomized, active-controlled, phase II pilot clinical trial.

Although empirically validated for fibromyalgia (FM), cognitive and behavioral therapies, including Acceptance and Commitment Therapy (ACT), are inaccessible to many patients. A self-guided, smartphone-based ACT program would significantly improve accessibility. The SMART-FM study assessed the feasibility of conducting a predominantly virtual clinical trial in an FM population in addition to evaluating preliminary evidence for the safety and efficacy of a digital ACT program for FM (FM-ACT).

Randomized clinical trial of bedtime sublingual cyclobenzaprine (TNX-102 SL) in military-related PTSD and the role of sleep quality in treatment response.

Effective posttraumatic stress disorder (PTSD) pharmacotherapy is needed. This 12-week randomized multicenter trial evaluated efficacy and safety of TNX-102 SL, a bedtime sublingual formulation of cyclobenzaprine, in patients with military-related PTSD randomized to TNX-102 SL 2.8 mg or 5.

A famciclovir + celecoxib combination treatment is safe and efficacious in the treatment of fibromyalgia.

Objective: Infections and other stressors have been implicated in the development of fibromyalgia. We hypothesized that these stressors could result in recurrent reactivations of latent herpes virus infections, which could lead to the development of fibromyalgia. This study evaluated a famciclovir + celecoxib drug combination (IMC-1), active against suspected herpes virus reactivation and infection, for the treatment of fibromyalgia.

Milnacipran combined with pregabalin in fibromyalgia: a randomized, open-label study evaluating the safety and efficacy of adding milnacipran in patients with incomplete response to pregabalin.

Objective: To evaluate the safety, tolerability, and efficacy of adding milnacipran to pregabalin in patients with fibromyalgia who have experienced an incomplete response to pregabalin.

Methods: In this randomized, multicenter, open-label study, patients received pregabalin 300 or 450 mg/day during a 4- to 12-week run-in period. Patients with weekly recall visual analog scale (VAS) pain score of at least 40 and up to 90, Patient Global Impression of Severity score of at least 4, and Patient Global Impression of Change (PGIC) score of at least 3 were classified as incomplete responders and randomized to continue pregabalin alone (n = 180) or receive milnacipran 100 mg/day added to pregabalin (n = 184).

Relationships among pain, depressed mood, and global status in fibromyalgia patients: post hoc analyses of a randomized, placebo-controlled trial of milnacipran.

Background: Patients with fibromyalgia often experience depressive symptoms in addition to chronic pain and other characteristic symptoms associated with this disorder.

Objective: To examine the relationships among pain, depressive symptoms, and global status in a clinical trial of milnacipran for fibromyalgia.

Methods: Data from a randomized, double-blind study (milnacipran 100 mg/d, n = 516; placebo, n = 509) were analyzed.

Short-term (2-week) effects of discontinuing milnacipran in patients with fibromyalgia.

Objective: To examine the effects of abruptly withdrawing milnacipran during the 2-week discontinuation phase of a study in which FM patients had received 12 weeks of stable-dose treatment with milnacipran at 100 mg/day.

Research Design And Methods: The effects of withdrawing milnacipran were evaluated prospectively over a 2-week period (Weeks 12 to 14) using a randomized, placebo-controlled withdrawal design. Patients who had originally received milnacipran 100 mg/d for 12 weeks were re-randomized to continue milnacipran (n = 178) or switch directly to placebo (n = 178); patients originally receiving placebo continued placebo (n = 359).

Toward development of a fibromyalgia responder index and disease activity score: OMERACT module update.

Following development of the core domain set for fibromyalgia (FM) in Outcome Measures in Rheumatology Clinical Trials (OMERACT) meetings 7 to 9, the FM working group has progressed toward the development of an FM responder index and a disease activity score based on these domains, utilizing outcome indices of these domains from archived randomized clinical trials in FM. Possible clinical domains that could be included in a responder index and disease activity score include pain, fatigue, sleep disturbance, cognitive dysfunction, mood disturbance, tenderness, stiffness, and functional impairment. Outcome measures for these domains demonstrate good to adequate psychometric properties, although measures of cognitive dysfunction need to be further developed.

A pooled analysis of two randomized, double-blind, placebo-controlled trials of milnacipran monotherapy in the treatment of fibromyalgia.

Milnacipran has been shown to significantly improve the pain, global well-being, and physical function of fibromyalgia (FM), and is approved by the U.S. Food and Drug Administration for the management of this disorder.

Role and rationale for the use of milnacipran in the management of fibromyalgia.

Fibromyalgia (FM) is a complex syndrome characterized by chronic widespread musculoskeletal pain which is often accompanied by multiple other symptoms, including fatigue, sleep disturbances, decreased physical functioning, and dyscognition. Due to these multiple symptoms, as well as high rates of comorbidity with other related disorders, patients with FM often report a reduced quality of life. Although the pathophysiology of FM is not completely understood, patients with FM experience pain differently from the general population, most likely due to dysfunctional pain processing in the central nervous system leading to both hyperalgesia and allodynia.

Efficacy and safety of milnacipran 100 mg/day in patients with fibromyalgia: results of a randomized, double-blind, placebo-controlled trial.

Objective: To assess the efficacy and safety of milnacipran at a dosage of 100 mg/day (50 mg twice daily) for monotherapy treatment of fibromyalgia.

Methods: A double-blind, placebo-controlled trial was performed to assess 1,025 patients with fibromyalgia who were randomized to receive milnacipran 100 mg/day (n = 516) or placebo (n = 509). Patients underwent 4-6 weeks of flexible dose escalation followed by 12 weeks of stable-dose treatment.

Contributions of change in clinical status parameters to Patient Global Impression of Change (PGIC) scores among persons with fibromyalgia treated with milnacipran.

Clinical trials on the treatment of pain syndromes have adopted Patient Global Impression of Change (PGIC) as a primary outcome. However, little is known about how change in clinical status influences these ratings. The present study examined relationships between changes in pain, depressed mood, physical functioning, vitality, sleep disturbance, cognitive complaints, and PGIC ratings among 1260 participants with fibromyalgia (FM) who completed one of two trials examining the safety and efficacy of milnacipran.

Durability of therapeutic response to milnacipran treatment for fibromyalgia. Results of a randomized, double-blind, monotherapy 6-month extension study.

Objective: To evaluate the durability of improvement and long-term efficacy of milnacipran treatment in fibromyalgia, to assess efficacy in patients re-randomized from placebo to milnacipran, and to collect additional information on the tolerability and efficacy of long-term treatment with milnacipran.

Design: A total of 449 patients who successfully completed a 6-month lead-in study enrolled in this 6-month extension study (87.7% of eligible subjects).

The efficacy and safety of milnacipran for treatment of fibromyalgia. a randomized, double-blind, placebo-controlled trial.

Objective: To evaluate the safety and efficacy of milnacipran, a dual norepinephrine and serotonin reuptake inhibitor, in the treatment of fibromyalgia (FM).

Methods: A 27-week, randomized, double-blind, multicenter study compared milnacipran 100 and 200 mg/day with placebo in the treatment of 888 patients with FM. Two composite responder definitions were used to classify each patient's individual response to therapy.

Milnacipran for the treatment of fibromyalgia in adults: a 15-week, multicenter, randomized, double-blind, placebo-controlled, multiple-dose clinical trial.

Background: Preclinical and clinical studies have suggested that milnacipran, a dual norepinephrine-serotonin reuptake inhibitor, may be efficacious in the treatment of fibromyalgia (FM).

Objective: This study was conducted to evaluate the efficacy and tolerability of milnacipran in treating the multiple domains of FM.

Methods: This was a multicenter, double-blind, placebo-controlled trial.

Assessment of the test-retest reliability of laboratory polysomnography.

Statement Of The Problem: When conducting a treatment intervention study, it is assumed that a level of reliability can be obtained from the measurement tool such that the outcome can be reasonably assessed.

Purpose Of Study: Investigate the reliability of laboratory polysomnography, the gold standard for assessment of treatment outcomes for obstructive sleep apnea, at a 1-month interval.

Materials And Methods: In a clinical trial of 118 patients recruited to assess the effects of a pharmaceutical treatment intervention, a subset of 20 patients designated as placebo controls completed two polysomnography studies, one at baseline and one at least one month later.

Two randomized placebo-controlled trials to evaluate the efficacy and tolerability of mirtazapine for the treatment of obstructive sleep apnea.

Objective: Mirtazapine is an a2A antagonist and mixed 5-HT2/5-HT3 antagonist that has been proposed as a potential treatment for obstructive sleep apnea (OSA). A small, randomized, controlled trial has previously found an approximate halving in the severity of OSA with daily doses of 4.5 and 15 mg.

Fibromyalgia syndrome.

The objectives of the first OMERACT Fibromyalgia Syndrome (FM) Workshop were to identify and prioritize symptom domains that should be consistently evaluated in FM clinical trials, and to identify aspects of domains and outcome measures that should be part of a concerted research agenda of FM researchers. Such an effort will help standardize and improve the quality of outcomes research in FM. A principal assumption in this workshop has been that there exists a clinical syndrome, generally known as FM, characterized by chronic widespread pain typically associated with fatigue, sleep disturbance, mood disturbance, and other symptoms and signs, and considered to be related to central neuromodulatory dysregulation.

Characterization and consequences of pain variability in individuals with fibromyalgia.

Objective: A growing body of evidence suggests that real-time electronic assessments of pain are preferable to traditional paper-and-pencil measures. We used electronic assessment data derived from a study of patients with fibromyalgia (FM) to examine variability of pain over time and to investigate the implications of pain fluctuation in the context of a clinical trial.

Methods: The study group comprised 125 patients with FM who were enrolled in a randomized, placebo-controlled trial of milnacipran.

Efficacy of milnacipran in patients with fibromyalgia.

Objective: Fibromyalgia (FM) is a common musculoskeletal condition characterized by widespread pain, tenderness, and a variety of other somatic symptoms. Current treatments are modestly effective. Arguably, the best studied and most effective compounds are tricyclic antidepressants (TCA).

A double-blind placebo-controlled trial of milnacipran in the treatment of fibromyalgia.

Fibromyalgia syndrome is a systemic disorder of widespread pain which is thought to result from abnormal pain processing within the central nervous system. There are no currently approved treatments for this indication. Antidepressants appear, however, to be effective, especially those with an action on noradrenergic neurotransmission.

Pain assessment in patients with fibromyalgia syndrome: a consideration of methods for clinical trials.

Objective: This study was designed to compare 3 commonly used methodologies for assessing clinical pain during trials involving patients diagnosed with fibromyalgia syndrome. Baseline characteristics, characteristics over time, and compliance were evaluated for each of the methods.

Methods: Fourteen patients diagnosed with fibromyalgia syndrome were asked to monitor their symptoms of pain using 3 different strategies over a 12-week period: 1) real-time pain reports were collected on an electronic diary using randomly-scheduled audible prompts; 2) end-of-week reports asked patients to rate their mean pain over the past week on the electronic diary; and 3) monthly in-clinic reports asked patients to rate their mean pain for the week using a traditional paper and pencil diary.

Measuring clinical pain in chronic widespread pain: selected methodological issues.

Assessing clinical pain is an important task in clinical practice and research. A large empirical literature has documented that patients' pain reports can be systematically biased by a number of methodological factors. This chapter reviews a selection of methodological issues that can affect pain ratings, including: the impact of recall bias, the use of paper and electronic diaries to assess pain experiences, ecological momentary assessment methods as a way of capturing real-time pain data in the real world, and pain scaling and data analysis considerations.