Currently, there are no medications approved for the treatment of juvenile fibromyalgia (JFM). We evaluated the safety and efficacy of duloxetine 30/60 mg once daily (QD) versus placebo in ...adolescents with JFM.
In this Phase 3b, multisite (US, Argentina, Puerto Rico, and India) trial, patients aged 13-17 years with JFM and a score of ≥4 on the Brief Pain Inventory-Modified Short Form: Adolescent Version (BPI) 24-h average pain severity score were randomized to duloxetine or placebo for the 13-week double-blind period. The starting duloxetine dose was 30 mg, with a target dose of 60 mg QD, as tolerated. The primary endpoint was the mean change in 24-h average pain severity of the Brief Pain Inventory (BPI) from baseline to Week 13, analyzed using mixed-model repeated measures (MMRM) technique. Secondary measures were BPI severity and interference scores; treatment response (≥30%, ≥50% reductions on BPI average pain severity); Pediatric Pain Questionnaire; Clinical Global Impression of Severity: Overall and Mental Illness scales; Functional Disability Inventory: child and parent versions; Children's Depression Inventory; Multidimensional Anxiety Scale for Children; and safety and tolerability. Continuous secondary efficacy measures were analyzed using analysis of covariance or MMRM, and categorical data using Cochran-Mantel-Haenszel test and Fisher's exact test, where appropriate.
A total of 184 patients with JFM received duloxetine (N = 91) or placebo (N = 93), of which 149 patients (81.0%) completed the 13-week double-blind treatment period. Baseline characteristics were comparable between groups; majority of the patients were Caucasian (77.17%) and females (75.0%), with a mean age of 15.53 years. For the primary measure, BPI average pain severity, the mean change was not statistically different between duloxetine and placebo (- 1.62 vs. -0.97, respectively; p = .052). For secondary efficacy outcomes, statistically significantly more duloxetine- versus placebo-treated patients had a treatment response (≥30% and ≥50% reductions on BPI average pain severity) and improvement of the general activity and relationships items on the BPI interference subscale. The percentage of patients reporting at least 1 treatment-emergent adverse event was higher in the duloxetine versus placebo groups (82.42% vs. 62.37%, respectively; p = .003). The overall safety profile of duloxetine in this study was similar to that reported previously in duloxetine pediatric trials of other indications.
The primary study outcome, mean change in 24-h BPI average pain severity rating from baseline to Week 13, did not significantly improve with duloxetine compared to placebo in patients with JFM. However, significantly more patients on duloxetine compared to placebo had a ≥30% and ≥50% reduction in pain severity. There were no new safety concerns related to duloxetine in the study population.
ClinicalTrials.gov Identifier: NCT01237587 . Registered 08 November, /2010.
A clinically significant change in functional disability for adolescents with fibromyalgia comprised an approximate 8-point reduction in disability scores and a reduction in disability grade after ...cognitive-behavioral treatment (CBT).
The primary objective of this study was to estimate a clinically significant and quantifiable change in functional disability to identify treatment responders in a clinical trial of cognitive-behavioral therapy (CBT) for youth with juvenile fibromyalgia (JFM). The second objective was to examine whether baseline functional disability (Functional Disability Inventory), pain intensity, depressive symptoms (Children’s Depression Inventory), coping self-efficacy (Pain Coping Questionnaire), and parental pain history predicted treatment response in disability at 6-month follow-up. Participants were 100 adolescents (11–18years of age) with JFM enrolled in a recently published clinical trial comparing CBT to a fibromyalgia education (FE) intervention. Patients were identified as achieving a clinically significant change in disability (ie, were considered treatment responders) if they achieved both a reliable magnitude of change (estimated as a ⩾7.8-point reduction on the FDI) using the Reliable Change Index, and a reduction in FDI disability grade based on established clinical reference points. Using this rigorous standard, 40% of patients who received CBT (20 of 50) were identified as treatment responders, compared to 28% who received FE (14 of 50). For CBT, patients with greater initial disability and higher coping efficacy were significantly more likely to achieve a clinically significant improvement in functioning. Pain intensity, depressive symptoms, and parent pain history did not significantly predict treatment response. Estimating clinically significant change for outcome measures in behavioral trials sets a high bar but is a potentially valuable approach to improve the quality of clinical trials, to enhance interpretability of treatment effects, and to challenge researchers to develop more potent and tailored interventions.
This manuscript, developed by a group of chronic pain researchers and clinicians from around the world, aims to address the state of knowledge about fibromyalgia (FM) and identify ongoing challenges ...in the field of FM and other chronic pain syndromes that may be characterized by pain centralization/amplification/hypersensitivity. There have been many exciting developments in research studies of the pathophysiology and treatment of FM and related syndromes that have the potential to improve the recognition and management of patients with FM and other conditions with FM-like pain. However, much of the new information has not reached all clinicians, especially primary care clinicians, who have the greatest potential to use this new knowledge to positively impact their patients’ lives. Furthermore, there are persistent misconceptions about FM and a lack of consensus regarding the diagnosis and treatment of FM. This paper presents a framework for future global efforts to improve the understanding and treatment of FM and other associated chronic pain syndromes, disseminate research findings, identify ways to enhance advocacy for these patients, and improve global efforts to collaborate and reach consensus about key issues related to FM and chronic pain in general.
This prospective longitudinal study examined the long-term physical and psychosocial outcomes of adolescents with juvenile-onset fibromyalgia (JFM), compared with healthy control subjects, into early ...adulthood.
Adolescent patients with JFM initially seen at a pediatric rheumatology clinic (n = 94) and age- and gender-matched healthy control subjects (n = 33) completed online measures of demographic characteristics, pain, physical functioning, mood symptoms, and health care utilization at ∼6 years' follow-up (mean age: 21 years). A standard in-person tender-point examination was conducted.
Patients with JFM had significantly higher pain (P < .001), poorer physical function (P < .001), greater anxiety (P < .001) and depressive symptoms (P < .001), and more medical visits (P < .001)than control subjects. The majority (>80%) of JFM patients continued to experience fibromyalgia symptoms into early adulthood, and 51.1% of the JFM sample met American College of Rheumatology criteria for adult fibromyalgia at follow-up. Patients with JFM were more likely than control subjects to be married and less likely to obtain a college education.
Adolescent patients with JFM have a high likelihood of continued fibromyalgia symptoms into young adulthood. Those who met criteria for fibromyalgia in adulthood exhibited the highest levels of physical and emotional impairment. Emerging differences in educational attainment and marital status were also found in the JFM group. JFM is likely to be a long-term condition for many patients, and this study for the first time describes the wide-ranging impact of JFM on a variety of physical and psychosocial outcomes that seem to diverge from their same-age peers.
Research in fibromyalgia has increased understanding of the possible genetic and environmental factors that could be involved in the etiology of fibromyalgia. There is now substantial evidence for ...augmentation of central pain processing in fibromyalgia. Because the clinical presentation of fibromyalgia is heterogeneous, treatment recommendations must be individualized for each patient. The rapid growth of trials in fibromyalgia in recent years has resulted in new evidence-based approaches to pharmacological and nonpharmacological treatment.
Summary Pregabalin is approved for the treatment of a variety of clinical conditions and its analgesic, anxiolytic and anticonvulsant properties are well documented. Pregabalin's effects on sleep, ...however, are less well known. This review summarizes the published data on the effects of pregabalin on sleep disturbance associated with neuropathic pain, fibromyalgia, restless legs syndrome, partial onset seizures and general anxiety disorder. The data demonstrate that pregabalin has a positive benefit on sleep disturbance associated with several different clinical conditions. Polysomnographic data reveal that pregabalin primarily affects sleep maintenance. The evidence indicates that pregabalin has a direct effect on sleep that is distinct from its analgesic, anxiolytic and anticonvulsant effects.
The presentation and course of bipolar disorder differs between women and men. The onset of bipolar disorder tends to occur later in women than men, and women more often have a seasonal pattern of ...the mood disturbance. Women experience depressive episodes, mixed mania, and rapid cycling more often than men. Bipolar II disorder, which is predominated by depressive episodes, also appears to be more common in women than men. Comorbidity of medical and psychiatric disorders is more common in women than men and adversely affects recovery from bipolar disorder more often in women. Comorbidity, particularly thyroid disease, migraine, obesity, and anxiety disorders occur more frequently in women than men, whereas substance use disorders are more common in men. Although the course and clinical features of bipolar disorder differ between women and men, there is no evidence that gender affects treatment response to mood stabilizers. However, women may be more susceptible to delayed diagnosis and treatment. Treatment of women during pregnancy and lactation is challenging because available mood stabilizers pose potential risks to the developing fetus and infant. Pregnancy neither protects nor exacerbates bipolar disorder, and many women require continuation of medication during the pregnancy. The postpartum period is a time of high risk for onset and recurrence of bipolar disorder in women, and prophylaxis with mood stabilizers might be needed. Individualized risk/benefit assessments of pregnant and postpartum women with bipolar disorder are required to promote the health of the woman and avoid or limit exposure of the fetus or infant to potential adverse effects of medication.
The primary objectives of this study were to assess the efficacy and safety of duloxetine for reducing pain severity in fibromyalgia patients with or without current major depressive disorder. This ...was a 6-month, multicenter, randomized, double-blind, placebo-controlled study. In total, 520 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to duloxetine (20
mg/day, 60
mg/day, or 120
mg/day) or placebo, administered once daily, for 6 months (after 3 months, the duloxetine 20-mg/day group titrated to 60
mg/day). The co-primary outcome measures were the Brief Pain Inventory (BPI) average pain severity score and Patient Global Impressions of Improvement (PGI-I) score. Safety was assessed via treatment-emergent adverse events, and changes in vital sign, laboratory, and ECG measures. Compared with placebo-treated patients, those patients treated with duloxetine 120
mg/day improved significantly more on the co-primary outcome measures at 3 months (change in BPI score −2.31 vs −1.39,
P
<
0.001 and PGI-I 2.89 vs 3.39,
P
=
0.004) and at 6 months (change in BPI −2.26 vs −1.43,
P
=
0.003 and PGI-I 2.93 vs 3.37,
P
=
0.012). Compared with placebo, treatment with duloxetine 60
mg/day also significantly improved the co-primary measures at 3 months and BPI at 6 months. Duloxetine was efficacious in patients both with and without major depressive disorder. There were no clinically significant differences between treatment groups in changes in vital signs, laboratory measures, or ECG measures. Study results demonstrated that duloxetine at doses of 60
mg/day and 120
mg/day appears to be safe and efficacious in patients with fibromyalgia.
According to the American College of Rheumatology, fibromyalgia is widespread pain of at least 3 months' duration in combination with pain at 11 or more of 18 specific tender point sites on the body. ...Many individuals with fibromyalgia also have comorbid psychiatric disorders, which can present diagnostic dilemmas and require additional treatment considerations to optimize patient outcomes. Fibromyalgia has been found to be strongly associated with depressive and anxiety symptoms, a personal or family history of depression, and accompanying antidepressant treatment. Psychiatric comorbidities negatively impact the severity and course of fibromyalgia. Pharmacotherapy can be employed to control fibromyalgia and comorbid mood and anxiety disorders. Additionally, nonpharmacologic therapies for fibromyalgia and comorbid psychiatric disorders include cognitive-behavioral therapy and aerobic exercise. The efficacy of pharmacologic and nonpharmacologic treatments is examined in this article, as well as the diagnostic difficulties that comorbid disorders present.
This was a 12-week, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, in 354 female ...patients with primary fibromyalgia, with or without current major depressive disorder. Patients (90% Caucasian; mean age, 49.6 years; 26% with current major depressive disorder) received duloxetine 60
mg once daily (QD) (
N=118), duloxetine 60
mg twice daily (BID) (
N=116), or placebo (
N=120). The primary outcome was the Brief Pain Inventory average pain severity score. Response to treatment was defined as ≥30% reduction in this score. Compared with placebo, both duloxetine-treated groups improved significantly more (
P<0.001) on the Brief Pain Inventory average pain severity score. A significantly higher percentage of duloxetine-treated patients had a decrease of ≥30% in this score (duloxetine 60
mg QD (55%;
P<0.001); duloxetine 60
mg BID (54%;
P=0.002); placebo (33%)). The treatment effect of duloxetine on pain reduction was independent of the effect on mood and the presence of major depressive disorder. Compared with patients on placebo, patients treated with duloxetine 60
mg QD or duloxetine 60
mg BID had significantly greater improvement in remaining Brief Pain Inventory pain severity and interference scores, Fibromyalgia Impact Questionnaire, Clinical Global Impression of Severity, Patient Global Impression of Improvement, and several quality-of-life measures. Both doses of duloxetine were safely administered and well tolerated. In conclusion, both duloxetine 60
mg QD and duloxetine 60
mg BID were effective and safe in the treatment of fibromyalgia in female patients with or without major depressive disorder.
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