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1.
Curr Med Res Opin ; 35(10): 1825-1835, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31284771

RESUMO

Objective: To investigate the efficacy and safety of mirogabalin, an α2δ ligand, in patients with fibromyalgia (FM). Methods: In three 13-week, multicenter, double-blind, phase 3 studies (studies A, B, and C), patients with FM (n = 1293, 1270, and 1301, respectively) were randomized (1:1:1:1) to placebo, pregabalin 150 mg twice daily, mirogabalin 15 mg once daily or mirogabalin 15 mg twice daily. The primary endpoint was the change in weekly average daily worst pain score (ADPS) at week 13. Key secondary endpoints included Patient Global Impression of Change and change in the Fibromyalgia Impact Questionnaire total score. Long-term safety of mirogabalin was assessed in a 52-week extension study. Results: Neither mirogabalin dose demonstrated a significant ADPS reduction from baseline vs. placebo at week 13 in any of the three studies. Pregabalin significantly reduced ADPS from baseline vs. placebo in studies B and C (p = .0008 and .0001, respectively). The effect of mirogabalin compared with placebo on key secondary endpoints was variable across the studies. Mirogabalin was well tolerated by most patients in the phase 3 studies; no unexpected adverse events occurring during the 52-week extension study. Conclusion: While both mirogabalin doses were well tolerated by most patients and showed potential for reducing pain associated with FM, the primary endpoint of significant pain reduction in patients on mirogabalin compared with placebo was not achieved in any of the three randomized controlled studies. Clinical trial registration: NCT02146430; NCT02187159; NCT02187471; and NCT02234583 (extension study).

2.
Pediatr Rheumatol Online J ; 17(1): 27, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138224

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01237587 . Registered 08 November, /2010.

4.
Pain ; 160(2): 433-441, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30335681

RESUMO

Juvenile-onset fibromyalgia (JFM) is typically diagnosed in adolescence and characterized by widespread pain and marked functional impairment. The long-term impact of JFM into adulthood is poorly understood. The objectives of this study were to describe physical and psychosocial outcomes of youth diagnosed with JFM in early adulthood (∼8-year follow-up), examine longitudinal trajectories of pain and depressive symptoms from adolescence to young adulthood, and examine the impact of pain and depressive symptoms on physical functioning over time. Participants were 97 youth with JFM enrolled in a prospective longitudinal study in which pain symptoms, and physical and psychosocial functioning were assessed at 4 time points over approximately 8 years. At the time 4 follow-up (Mage = 24.2 years), the majority continued to suffer from pain and impairment in physical, social, and psychological domains. However, trajectories of pain and emotional symptoms showed varying patterns. Longitudinal analysis using growth mixture modeling revealed 2 pain trajectories (Steady Improvement and Rapid Rebounding Improvement), whereas depressive symptoms followed 3 distinct trajectories (Low-Stable, Improving, and Worsening). Membership in the Worsening Depressive symptoms group was associated with poorer physical functioning over time (P < 0.001) compared with the Low-Stable and Improving groups. This study offers evidence that although JFM symptoms persist for most individuals, pain severity tends to decrease over time. However, depressive symptoms follow distinct trajectories that indicate subgroups of JFM. In particular, JFM patients with worsening depressive symptoms showed decreasing physical functioning and may require more intensive and consistent intervention to prevent long-term disability.


Assuntos
Depressão/etiologia , Exercício/fisiologia , Fibromialgia/complicações , Fibromialgia/psicologia , Dor/etiologia , Adolescente , Idade de Início , Criança , Estudos de Coortes , Progressão da Doença , Feminino , Fibromialgia/diagnóstico , Humanos , Masculino , Dor/psicologia , Medição da Dor , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Escalas de Graduação Psiquiátrica , Adulto Jovem
5.
J Pain ; 20(6): 611-628, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30453109

RESUMO

Fibromyalgia (FM) is a common chronic pain disorder that presents diagnostic challenges for clinicians. Several classification, diagnostic and screening criteria have been developed over the years, but there continues to be a need to develop criteria that reflect the current understanding of FM and are practical for use by clinicians and researchers. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration (FDA) and the American Pain Society (APS) initiated the ACTTION-APS Pain Taxonomy (AAPT) to develop a diagnostic system that would be clinically useful and consistent across chronic pain disorders. The AAPT established an international FM working group consisting of clinicians and researchers with expertise in FM to generate core diagnostic criteria for FM and apply the multidimensional diagnostic framework adopted by AAPT to FM. The process for developing the AAPT criteria and dimensions included literature reviews and synthesis, consensus discussions, and analyses of data from large population-based studies conducted in the United Kingdom. The FM working group established a revised diagnosis of FM and identified risk factors, course, prognosis, and pathophysiology of FM. Future studies will assess the criteria for feasibility, reliability, and validity. Revisions of the dimensions will also be required as research advances our understanding of FM. PERSPECTIVE: The ACTTION-APS FM taxonomy provides an evidence-based diagnostic system for FM. The taxonomy includes diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms. This approach might improve the recognition of FM in clinical practice.

6.
Curr Med Res Opin ; 34(8): 1397-1409, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29519159

RESUMO

OBJECTIVES: Pregabalin, an α2-δ agonist, is approved for the treatment of fibromyalgia (FM) in the United States, Japan, and 37 other countries. The purpose of this article was to provide an in-depth, evidence-based summary of pregabalin for FM as demonstrated in randomized, placebo-controlled clinical studies, including open-label extensions, meta-analyses, combination studies and post-hoc analyses of clinical study data. METHODS: PubMed was searched using the term "pregabalin AND fibromyalgia" and the Cochrane Library with the term "pregabalin". Both searches were conducted on 2 March 2017 with no other date limits set. RESULTS: Eleven randomized, double-blind, placebo-controlled clinical studies were identified including parallel group, two-way crossover and randomized withdrawal designs. One was a neuroimaging study. Five open-label extensions were also identified. Evidence of efficacy was demonstrated across the studies identified with significant and clinically relevant improvements in pain, sleep quality and patient status. The safety and tolerability profile of pregabalin is consistent across all the studies identified, including in adolescents, with dizziness and somnolence the most common adverse events reported. These efficacy and safety data are supported by meta-analyses (13 studies). Pregabalin in combination with other pharmacotherapies (7 studies) is also efficacious. Post-hoc analyses have demonstrated the onset of pregabalin efficacy as early as 1-2 days after starting treatment, examined the effect of pregabalin on other aspects of sleep beyond quality, and shown it is effective irrespective of the presence of a wide variety of patient demographic and clinical characteristics. CONCLUSIONS: Pregabalin is a treatment option for FM; its clinical utility has been comprehensively demonstrated.


Assuntos
Analgésicos/uso terapêutico , Fibromialgia/tratamento farmacológico , Pregabalina/uso terapêutico , Estudos Cross-Over , Método Duplo-Cego , Humanos , Pregabalina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Postgrad Med ; 129(8): 921-933, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28967801

RESUMO

OBJECTIVES: The pregabalin dose-response for pain, Patient Global Impression of Change (PGIC), and sleep quality measures in painful diabetic peripheral neuropathy (pDPN), postherpetic neuralgia (PHN), and fibromyalgia (FM) is relevant for physicians treating these patients. This analysis aimed to demonstrate the dose-response of pregabalin for each indication and describe the onset (incidence), onset/continuation (prevalence), and resolution of adverse events (AEs) occurring during treatment. METHODS: Data from 14 placebo-controlled, fixed-dose pregabalin trials in pDPN, PHN, and FM were pooled within each indication. Patients had mean baseline pain scores ≥6 on an 11-point numeric rating scale. A hyperbolic Emax dose-response model examined the dose-response of pregabalin for pain, PGIC, and sleep quality. Safety assessments included onset and prevalence of common AEs each week, and resolution in the first 2 months of treatment. RESULTS: In all indications, the likelihood of patients experiencing pain relief and improvements in PGIC and sleep quality increased in a dose-dependent manner with increasing doses. In all indications, new incidences of dizziness and somnolence were highest after 1 week of treatment, with few subsequent new reports at a given dose. Prevalence rates decreased steadily after 1 week of treatment. In FM, new onset weight gain emerged 6-8 weeks following treatment; prevalence rates generally increased then remained steady over time. With the exception of weight gain, many AEs resolved in month 1. CONCLUSION: The dose-response of pregabalin for pain, PGIC, and sleep quality was demonstrated, highlighting the benefit of achieving the maximum recommended dose of 300 mg/day for pDPN, 300-600 mg/day for PHN, and 300-450 mg/day for FM. Common AEs are generally seen within 1 week of starting treatment, with few subsequent new reports at a given dose. New onset weight gain occurs after 6 weeks of treatment, reinforcing the need for regular monitoring of weight.


Assuntos
Analgésicos/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Fibromialgia/tratamento farmacológico , Neuralgia Pós-Herpética/tratamento farmacológico , Pregabalina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pregabalina/administração & dosagem , Pregabalina/efeitos adversos , Sono/efeitos dos fármacos , Adulto Jovem
8.
Postgrad Med ; 129(7): 709-714, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28562155

RESUMO

The current diagnostic and treatment pathway for patients with fibromyalgia (FM) is lengthy, complex, and characterized by multiple physician visits with an average 2-year wait until diagnosis. It is clear that effective identification and appropriate treatment of FM remain a challenge in current clinical practice. Ideally, FM management involves a multidisciplinary approach with the preferable patient pathway originating in primary care but supported by a range of health care providers, including referral to specialist care when necessary. After the publication of individual clinical studies, high-quality reviews, and meta-analyses, recently published FM treatment guidelines have transitioned from an expert consensus to an evidence-based approach. Evidence-based guidelines provide a framework for ensuring early diagnosis and timely adoption of appropriate treatment. However, for successful outcomes, FM treatments must adopt a more holistic approach, which addresses more than just pain. Impact on the associated symptoms of fatigue and cognitive problems, sleep and mood disturbances, and lowered functional status are also important in judging the success of FM therapy. Recently published guidelines recommend the adoption of a symptom-based approach to guide pharmacologic treatment. Emerging treatment options for FM may be best differentiated on the basis of their effect on comorbid symptoms that are often associated with pain (e.g. sleep disturbance, mood, fatigue). The current review discusses the most recently published Canadian guidelines and the implications of the recent European League Against Rheumatism (EULAR) recommendations, with a focus on the challenges of implementing these guidelines in current clinical practice.


Assuntos
Prática Clínica Baseada em Evidências/normas , Fibromialgia/diagnóstico , Fibromialgia/tratamento farmacológico , Manejo da Dor/métodos , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Pediatr Rheumatol Online J ; 14(1): 46, 2016 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-27475753

RESUMO

BACKGROUND: Fibromyalgia (FM) is a common pain condition characterized by widespread musculoskeletal pain and tenderness. Pregabalin is an approved treatment for adults in the United States, but there are no approved treatments for adolescents with FM. METHODS: This was a 15-week, randomized, double-blind, placebo-controlled study and 6-month open-label safety trial of flexible-dose pregabalin (75-450 mg/day) for the treatment of adolescents (12-17 years) with FM. Primary outcome was change in mean pain score at endpoint (scored from 0-10, with 24-h recall). Secondary outcomes included global assessments and measures of pain, sleep, and FM impact. RESULTS: A total of 107 subjects were randomized to treatment (54 pregabalin, 53 placebo) and 80 completed the study (44 pregabalin, 36 placebo). Improvement in mean pain score at endpoint with pregabalin versus placebo was not statistically significant, treatment difference (95 % CI), -0.66 (-1.51, 0.18), P = 0.121. There were significant improvements with pregabalin versus placebo in secondary outcomes of change in pain score by week (P < 0.05 for 10 of 15 weeks); change in pain score at week 15 (1-week recall), treatment difference (95 % CI), -0.87 (-1.68, -0.05), P = 0.037; and patient global impression of change, 53.1 % versus 29.5 % very much or much improved (P = 0.013). Trends toward improvement with pregabalin in other secondary outcomes measuring pain, sleep, and FM impact were not significant. Safety was consistent with the known profile of pregabalin in adults with FM. CONCLUSION: Pregabalin did not significantly improve the mean pain score in adolescents with FM. There were significant improvements in secondary outcomes measuring pain and impression of change. TRIAL REGISTRATIONS: NCT01020474 ; NCT01020526 .


Assuntos
Analgésicos/uso terapêutico , Fibromialgia/tratamento farmacológico , Pregabalina/uso terapêutico , Adolescente , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Medição da Dor , Resultado do Tratamento
11.
Clin J Pain ; 32(9): 737-46, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27022674

RESUMO

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.


Assuntos
Dor Crônica , Fibromialgia , Dor Crônica/diagnóstico , Dor Crônica/fisiopatologia , Dor Crônica/terapia , Fibromialgia/diagnóstico , Fibromialgia/fisiopatologia , Fibromialgia/terapia , Humanos
12.
Curr Rheumatol Rep ; 18(4): 19, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26984803

RESUMO

While a majority of research has focused on adult fibromyalgia (FM), recent evidence has provided insights into the presence and impact of FM in children and adolescents. Commonly referred as juvenile fibromyalgia (JFM), youths, particularly adolescent girls, present with persistent widespread pain and cardinal symptoms observed in adult FM. A majority of youth with JFM continue to experience symptoms into adulthood, which highlights the importance of early recognition and intervention. Some differences are observed between adult and juvenile-onset FM syndrome with regard to comorbidities (e.g., joint hypermobility is common in JFM). Psychological comorbidities are common but less severe in JFM. Compared to adult FM, approved pharmacological treatments for JFM are lacking, but non-pharmacologic approaches (e.g., cognitive-behavioral therapy and exercise) show promise. A number of conceptual issues still remain including (1) directly comparing similarities and differences in symptoms and (2) identifying shared and unique mechanisms underlying FM in adults and youths.


Assuntos
Dor Crônica/diagnóstico , Fibromialgia/diagnóstico , Fatores Etários , Dor Crônica/epidemiologia , Dor Crônica/psicologia , Dor Crônica/terapia , Fibromialgia/epidemiologia , Fibromialgia/psicologia , Fibromialgia/terapia , Humanos , Prognóstico
13.
J Rheumatol ; 42(12): 2427-33, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26373565

RESUMO

OBJECTIVE: Adolescents with juvenile-onset fibromyalgia (JFM) have increased rates of psychiatric disorders, but to our knowledge no studies have examined psychiatric disorders in adolescents with JFM when they enter young adulthood. This study examined the prevalence of psychiatric disorders in young adults diagnosed with JFM during adolescence and the relationship between mental health diagnoses and physical functioning. METHODS: Ninety-one young adults (mean age 21.60, SD 1.96) with a history of JFM being followed as part of a prospective longitudinal study and 30 matched healthy controls (mean age 21.57, SD 1.55) completed a structured interview of psychiatric diagnoses and a self-report measure of physical impairment. RESULTS: Young adults with a history of JFM were more likely to have current and lifetime histories of anxiety disorders (70.3% and 76.9%, respectively) compared with controls (33.3% for both, both p < 0.001). Individuals with JFM were also more likely to have current and lifetime histories of major mood disorders (29.7% and 76.9%, respectively) compared with controls (10% and 40%, p < 0.05). The presence of a current major mood disorder was significantly related to impairment in physical functioning [F (1, 89) = 8.30, p < 0.01] and role limitations attributable to a physical condition [F (1, 89) = 7.09, p < 0.01]. CONCLUSION: Psychiatric disorders are prevalent in young adulthood for individuals with a history of JFM, and a current major mood disorder is associated with greater physical impairment. Greater attention to early identification and treatment of mood disorders in patients with JFM is warranted.


Assuntos
Transtornos de Ansiedade/epidemiologia , Fibromialgia/epidemiologia , Fibromialgia/psicologia , Transtornos do Humor/epidemiologia , Medição da Dor , Adolescente , Distribuição por Idade , Idade de Início , Análise de Variância , Transtornos de Ansiedade/fisiopatologia , Estudos de Casos e Controles , Comorbidade , Feminino , Fibromialgia/diagnóstico , Humanos , Estudos Longitudinais , Masculino , Monitorização Fisiológica , Transtornos do Humor/fisiopatologia , Análise Multivariada , Testes Neuropsicológicos , Prevalência , Prognóstico , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Perfil de Impacto da Doença , Fatores de Tempo , Estados Unidos , Adulto Jovem
14.
Pediatr Rheumatol Online J ; 13: 27, 2015 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-26112278

RESUMO

BACKGROUND: There are no approved medications for juvenile fibromyalgia (JFM), a disorder that is often under-diagnosed. The effects of milnacipran, a drug approved for the management of fibromyalgia (FM) in adults, was assessed in a clinical trial program for JFM. METHODS: Patients, ages 13-17 years who met the Yunus and Masi criteria for JFM and/or 1990 American College of Rheumatology criteria for FM, were enrolled in a responder-enriched, randomized withdrawal trial. After receiving open-label milnacipran (8 weeks), patients with ≥50 % improvement in pain underwent double-blind randomization (1:2) to either placebo or continuing treatment with milnacipran (8 weeks). All patients, including those who did not meet the randomization criteria for double-blind withdrawal, were allowed to enter an extension study with open-label milnacipran (up to 52 weeks). The primary endpoint was loss of therapeutic response (LTR) during the double-blind period. Additional outcome measures included the Patient Global Impression of Severity (PGIS), Pediatric Quality of Life Inventory (PedsQL: Generic Core Scales, Multidimensional Fatigue Scale), and Multidimensional Anxiety Scale for Children (MASC). Safety assessments included adverse events (AEs), vital signs, electrocardiograms, and laboratory tests. RESULTS: The milnacipran program was terminated early due to low enrollment. Because only 20 patients were randomized into the double-blind withdrawal period, statistical analyses were not conducted for the LTR endpoint. However, 116 patients entered the open-label period of the initial study and 57 participated in the open-label extension study. Their experience provides preliminary information about the use of milnacipran in JFM patients. During both open-label periods, there were mean improvements in pain severity, PGIC, PedsQL, and MASC scores. No unexpected safety issues were detected. The most commonly reported treatment-emergent AEs were nausea, headache, vomiting, and dizziness. Mean increases in heart rate and blood pressure were observed, and were consistent with the AE profile in adults with FM. CONCLUSIONS: The open-label findings provide preliminary evidence that milnacipran may improve symptoms of JFM, with a safety and tolerability profile that is consistent with the experience in adult FM patients. Future trial designs for JFM should consider the relatively low recognition of this condition compared to adult FM and the difficulties with enrollment. TRIAL REGISTRATION: NCT01328002 ; NCT01331109.


Assuntos
Inibidores da Captação Adrenérgica/uso terapêutico , Ciclopropanos/uso terapêutico , Fibromialgia/tratamento farmacológico , Adolescente , Inibidores da Captação Adrenérgica/efeitos adversos , Ciclopropanos/efeitos adversos , Método Duplo-Cego , Término Precoce de Ensaios Clínicos , Feminino , Humanos , Masculino , Milnaciprano , Resultado do Tratamento
15.
J Rheumatol ; 42(7): 1237-44, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26034150

RESUMO

OBJECTIVE: To assess pregabalin efficacy and safety in patients with fibromyalgia (FM) with comorbid depression taking concurrent antidepressant medication. METHODS: This randomized, placebo-controlled, double-blind, 2-period, 2-way crossover study was composed of two 6-week treatment periods separated by a 2-week taper/washout phase. Patients with FM (aged ≥ 18 yrs) taking a stable dose of a selective serotonin reuptake inhibitor (SSRI) or a serotonin/norepinephrine reuptake inhibitor (SNRI) for depression were randomized 1:1 to receive pregabalin/placebo or placebo/pregabalin (optimized to 300 or 450 mg/day). Antidepressant medication was continued throughout the study. The primary efficacy outcome was the mean pain score on an 11-point numerical rating scale. Secondary efficacy outcomes included measures of anxiety, depression, patient function, and sleep. RESULTS: Of 197 patients randomized to treatment, 181 and 177 received ≥ 1 dose of pregabalin and placebo, respectively. At baseline, 52.3% of patients were taking an SSRI and 47.7% an SNRI, and mean pain score was 6.7. Mean pain scores at endpoint were statistically significantly reduced with pregabalin (least squares mean difference from placebo -0.61, 95% CI -0.91 - -0.31, p = 0.0001). Pregabalin significantly improved Hospital Anxiety and Depression Scale-Anxiety (difference -0.95, p < 0.0001) and -Depression (difference -0.88, p = 0.0005) scores, Fibromyalgia Impact Questionnaire total score (difference -6.60, p < 0.0001), and sleep quality (difference 0.57, p < 0.0001), but not EuroQol 5-Dimensions score (difference 0.02, p = 0.3854). Pregabalin safety was consistent with previous studies and current product labeling. CONCLUSION: Compared with placebo, pregabalin statistically significantly improved FM pain and other symptoms in patients taking antidepressant medication for comorbid depression. ClinicalTrials.gov identifier: NCT01432236.


Assuntos
Analgésicos/uso terapêutico , Antidepressivos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Fibromialgia/tratamento farmacológico , Pregabalina/uso terapêutico , Adulto , Analgésicos/efeitos adversos , Estudos Cross-Over , Transtorno Depressivo/complicações , Relação Dose-Resposta a Droga , Método Duplo-Cego , Interações de Medicamentos , Feminino , Fibromialgia/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Pregabalina/efeitos adversos , Resultado do Tratamento
16.
Psychosomatics ; 56(3): 242-53, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25660434

RESUMO

OBJECTIVE: To assess the efficacy and safety of duloxetine in patients with chronic fatigue syndrome. METHODS: 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. RESULTS: 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. CONCLUSION: 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.


Assuntos
Cloridrato de Duloxetina/uso terapêutico , Síndrome de Fadiga Crônica/tratamento farmacológico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Fadiga Mental , Pessoa de Meia-Idade , Dor , Resultado do Tratamento
17.
Pain Med ; 16(1): 176-85, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25529830

RESUMO

OBJECTIVE: To determine the time to immediate and sustained clinical improvement in pain and sleep quality with pregabalin in patients with fibromyalgia. DESIGN: A post hoc analysis of four 8- to 14-week phase 2-3, placebo-controlled trials of fixed-dose pregabalin (150-600 mg/day) for fibromyalgia, comprising 12 pregabalin and four placebo treatment arms. PATIENTS: A total of 2,747 patients with fibromyalgia, aged 18-82 years. METHODS: Pain and sleep quality scores, recorded daily on 11-point numeric rating scales (NRSs), were analyzed to determine time to immediate improvement with pregabalin, defined as the first of ≥2 consecutive days when the mean NRS score was significantly lower for pregabalin vs placebo in those treatment arms with a significant improvement at endpoint, and time to sustained clinical improvement with pregabalin, defined as a ≥1-point reduction of the baseline NRS score of patient responders who had a ≥30% improvement on the pain NRS, sleep NRS, or Fibromyalgia Impact Questionnaire (FIQ) from baseline to endpoint, or who reported "much improved" or "very much improved" on the Patient Global Impression of Change (PGIC) at endpoint. RESULTS: Significant improvements in pain and sleep quality scores at endpoint vs placebo were seen in 8/12 and 11/12 pregabalin treatment arms, respectively (P < 0.05). In these arms, time to immediate improvements in pain or sleep occurred by day 1 or 2. Time to sustained clinical improvement occurred significantly earlier in pain, sleep, PGIC, and FIQ responders (P < 0.02) with pregabalin vs placebo. CONCLUSIONS: Both immediate and sustained clinical improvements in pain and sleep quality occurred faster with pregabalin vs placebo.


Assuntos
Analgésicos/uso terapêutico , Fibromialgia/complicações , Dor/tratamento farmacológico , Pregabalina/uso terapêutico , Sono/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibromialgia/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Fatores de Tempo , Adulto Jovem
18.
Health Qual Life Outcomes ; 12: 111, 2014 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-25017455

RESUMO

OBJECTIVES: Sleep disturbance is a common experience in fibromyalgia (FM). The field lacks a sleep specific patient reported outcome (PRO) measure developed and validated in a FM population. The study objective is to gain an in-depth understanding of sleep in FM and to develop a PRO measure of it. METHODS: Research involved the following stages: 1) A literature review conducted to identify key concepts associated with FM patient experience of sleep and PRO measures that have been used to assess this; 2) Qualitative interviews with therapeutic area experts; 3) Focus groups with FM patients who experienced sleep disturbance; 4) Development of a conceptual framework and the Fibromyalgia Sleep Diary (FMSD); and 5) Cognitive interviews with patients to explore content validity of the FMSD. RESULTS: The literature review and expert interviews supported sleep disturbance being an important aspect of the FM patient experience, and underscored the need for a new FM specific sleep PRO measure. Results from the focus groups demonstrated that FM patients experience sleep disturbances that they attribute to their FM symptoms, such as pain and stiffness, confirming the importance of understanding more about sleep changes. Aspects of sleep raised by FM patients included poor sleep quality and insufficient quantity including difficulty with falling asleep, getting comfortable, and staying asleep; restlessness; light sleep; not feeling rested upon awakening; and difficulty starting the day. Cognitive interview results showed that the 8-item FMSD, developed to reflect the concepts identified above, was relevant to FM patients with content that was interpreted as intended. CONCLUSIONS: The FMSD was developed in line with the recommendations of the FDA PRO guidance and ISPOR PRO Task Force. The qualitative evidence generated thus far strongly supports the content validity of the FMSD as a PRO measure of sleep disturbance in FM populations. Psychometric evaluation of the FMSD to demonstrate reliability, validity and sensitivity to change is recommended as a next step.


Assuntos
Fibromialgia/complicações , Indicadores Básicos de Saúde , Registros Médicos , Avaliação de Resultados da Assistência ao Paciente , Autorrelato , Transtornos do Sono-Vigília/diagnóstico , Adulto , Idoso , Feminino , Fibromialgia/psicologia , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Pesquisa Qualitativa , Qualidade de Vida , Reprodutibilidade dos Testes , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/psicologia , Inquéritos e Questionários
19.
Curr Med Res Opin ; 30(10): 2069-83, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24867298

RESUMO

OBJECTIVE: Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design. RESEARCH DESIGN AND METHODS: This multicenter study included 6 week single-blind pregabalin CR treatment followed by 13 week double-blind treatment with placebo or pregabalin CR. The starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495 mg/day based on efficacy and tolerability. Patients with ≥50% reduction in average daily pain score at the end of the single-blind phase were randomized to continue pregabalin CR at the optimized dose (330-495 mg/day) or to placebo. The primary endpoint was time to loss of therapeutic response (LTR), defined as <30% pain reduction relative to single-blind baseline or discontinuation owing to lack of efficacy or adverse event (AE). Secondary endpoints included measures of pain severity, global assessment, functional status, tiredness/fatigue, and sleep. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01271933. RESULTS: A total of 441 patients entered the single-blind phase, and 63 were randomized to pregabalin CR and 58 to placebo. The median time to LTR (Kaplan-Meier analysis) was significantly longer in the pregabalin CR group than placebo (58 vs. 22 days, p = 0.02). By trial end, 34/63 (54.0%) pregabalin CR and 41/58 (70.7%) placebo patients experienced LTR. Significantly more patients reported 'benefit from treatment' (Benefit, Satisfaction, and Willingness to Continue Scale) in the pregabalin CR group; no other secondary endpoints were statistically significant. Most AEs were mild to moderate in severity (most frequent: dizziness, somnolence). The percentage of pregabalin CR patients discontinuing because of AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively (placebo, 0%). CONCLUSIONS: Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance of response. Pregabalin CR was well tolerated in most patients. Generalizability may be limited by study duration and selective population.


Assuntos
Fibromialgia , Distúrbios do Início e da Manutenção do Sono , Ácido gama-Aminobutírico/análogos & derivados , Adulto , Idoso , Analgésicos/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Método Duplo-Cego , Cálculos da Dosagem de Medicamento , Feminino , Fibromialgia/complicações , Fibromialgia/diagnóstico , Fibromialgia/tratamento farmacológico , Fibromialgia/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Medição da Dor , Pregabalina , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/etiologia , Resultado do Tratamento , Ácido gama-Aminobutírico/administração & dosagem
20.
Pain ; 155(7): 1206-12, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24650858

RESUMO

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 (11-18 years 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 (i.e., were considered treatment responders) if they achieved both a reliable magnitude of change (estimated as a > or = 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.


Assuntos
Adaptação Psicológica , Terapia Cognitivo-Comportamental , Depressão/psicologia , Fibromialgia/terapia , Autoeficácia , Adolescente , Criança , Avaliação da Deficiência , Feminino , Fibromialgia/fisiopatologia , Fibromialgia/psicologia , Humanos , Masculino , Medição da Dor , Resultado do Tratamento
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