The placebo effect and its determinants in fibromyalgia: meta-analysis of randomized controlled trials

The aims of this study were to determine whether placebo treatment in randomised controlled trials (RCTs) is effective for fibromyalgia and to identify possible determinants of the magnitude of any such placebo effect. A systematic literature search was undertaken for RCTs in people with fibromyalgia that included a placebo and/or a no-treatment (observation only or waiting list) control group. Placebo effect size (ES) for pain and other outcomes was measured as the improvement of each outcome from baseline divided by the standard deviation of the change from baseline. This effect was compared with changes in the no-treatment control groups. Meta-analysis was undertaken to combine data from different studies. Subgroup analysis was conducted to identify possible determinants of the placebo ES. A total of 3912 studies were identified from the literature search. After scrutiny, 229 trials met the inclusion criteria. Participants who received placebo in the RCTs experienced significantly better improvements in pain, fatigue, sleep quality, physical function, and other main outcomes than those receiving no treatment. The ES of placebo for pain relief was clinically moderate (0.53, 95%CI 0.48 to 0.57). The ES increased with increasing strength of the active treatment, increasing participant age and higher baseline pain severity, but decreased in RCTS with more women and with longer duration of fibromyalgia. In addition, placebo treatment in RCTs is effective in fibromyalgia. A number of factors (expected strength of treatment, age, gender, disease duration) appear to influence the magnitude of the placebo effect in this condition

Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesPersistent insomnia is among the most frequent complaints in general practice. To identify genetic factors for insomnia complaints, we performed a genome-wide association study (GWAS) and a genome-wide gene-based association study (GWGAS) in 113,006 individuals. We identify three loci and seven genes associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample (n = 7,565). Our top association (MEIS1, P < 5 × 10-8) has previously been implicated in restless legs syndrome (RLS). Additional analyses favor the hypothesis that MEIS1 exhibits pleiotropy for insomnia and RLS and show that the observed association with insomnia complaints cannot be explained only by the presence of an RLS subgroup within the cases. Sex-specific analyses suggest that there are different genetic architectures between the sexes in addition to shared genetic factors. We show substantial positive genetic correlation of insomnia complaints with internalizing personality traits and metabolic traits and negative correlation with subjective well-being and educational attainment. These findings provide new insight into the genetic architecture of insomnia.Netherlands Organization for Scientific Research NWO Brain & Cognition 433-09-228 European Research Council ERC-ADG-2014-671084 INSOMNIA Netherlands Scientific Organization (NWO) VU University (Amsterdam, the Netherlands) Dutch Brain Foundation Helmholtz Zentrum Munchen - German Federal Ministry of Education and Research state of Bavaria German Migraine & Headache Society (DMKG) Almirall AstraZeneca Berlin Chemie Boehringer Boots Health Care GlaxoSmithKline Janssen Cilag McNeil Pharma MSD Sharp Dohme Pfizer Institute of Epidemiology and Social Medicine at the University of Munster German Ministry of Education and Research (BMBF) German Restless Legs Patient Organisation (RLS Deutsche Restless Legs Vereinigung) Swiss RLS Patient Association (Schweizerische Restless Legs Selbsthilfegruppe

Nonpharmacologic treatment of chronic insomnia. An American Academy of Sleep Medicine review.

This paper reviews the evidence regarding the efficacy of nonpharmacological treatments for primary chronic insomnia. It is based on a review of 48 clinical trials and two meta-analyses conducted by a task force appointed by the American Academy of Sleep Medicine to develop practice parameters on non-drug therapies for the clinical management of insomnia. The findings indicate that nonpharmacological therapies produce reliable and durable changes in several sleep parameters of chronic insomnia sufferers. The data indicate that between 70% and 80% of patients treated with nonpharmacological interventions benefit from treatment. For the typical patient with persistent primary insomnia, treatment is likely to reduce the main target symptoms of sleep onset latency and/or wake time after sleep onset below or near the 30-min criterion initially used to define insomnia severity. Sleep duration is also increased by a modest 30 minutes and sleep quality and patient's satisfaction with sleep patterns are significantly enhanced. Sleep improvements achieved with these behavioral interventions are sustained for at least 6 months after treatment completion. However, there is no clear evidence that improved sleep leads to meaningful changes in daytime well-being or performance. Three treatments meet the American Psychological Association (APA) criteria for empirically-supported psychological treatments for insomnia: Stimulus control, progressive muscle relaxation, and paradoxical intention; and three additional treatments meet APA criteria for probably efficacious treatments: Sleep restriction, biofeedback, and multifaceted cognitive-behavior therapy. Additional outcome research is needed to examine the effectiveness of treatment when it is implemented in clinical settings (primary care, family practice), by non-sleep specialists, and with insomnia patients presenting medical or psychiatric comorbidity

Psychological and behavioral treatment of insomnia: Update of the recent evidence (1998-2004)

BACKGROUND: Recognition that psychological and behavioral factors play an important role in insomnia has led to increased interest in therapies targeting these factors. A review paper published in 1999 summarized the evidence regarding the efficacy of psychological and behavioral treatments for persistent insomnia. The present review provides an update of the evidence published since the original paper. As with the original paper, this review was conducted by a task force commissioned by the American Academy of Sleep Medicine in order to update its practice parameters on psychological and behavioral therapies for insomnia. METHODS: A systematic review was conducted on 37 treatment studies (N = 2246 subjects/patients) published between 1998 and 2004 inclusively and identified through Psyclnfo and Medline searches. Each study was systematically reviewed with a standard coding sheet and the following information was extracted: Study design, sample (number of participants, age, gender), diagnosis, type of treatments and controls, primary and secondary outcome measures, and main findings. Criteria for inclusion of a study were as follows: (a) the main sleep diagnosis was insomnia (primary or comorbid), (b) at least 1 treatment condition was psychological or behavioral in content, (c) the study design was a randomized controlled trial, a nonrandomized group design, a clinical case series or a single subject experimental design with a minimum of 10 subjects, and (d) the study included at least 1 of the following as dependent variables: sleep onset latency, number and/or duration of awakenings, total sleep time, sleep efficiency, or sleep quality. RESULTS: Psychological and behavioral therapies produced reliable changes in several sleep parameters of individuals with either primary insomnia or insomnia associated with medical and psychiatric disorders. Nine studies documented the benefits of insomnia treatment in older adults or for facilitating discontinuation of medication among chronic hypnotic users. Sleep improvements achieved with treatment were well sustained over time; however, with the exception of reduced psychological symptoms/ distress, there was limited evidence that improved sleep led to clinically meaningful changes in other indices of morbidity (e.g., daytime fatigue). Five treatments met criteria for empirically-supported psychological treatments for insomnia: Stimulus control therapy, relaxation, paradoxical intention, sleep restriction, and cognitive-behavior therapy. DISCUSSION: These updated findings provide additional evidence in support of the original review's conclusions as to the efficacy and generalizability of psychological and behavioral therapies for persistent insomnia. Nonetheless, further research is needed to develop therapies that would optimize outcomes and reduce morbidity, as would studies of treatment mechanisms, mediators, and moderators of outcomes. Effectiveness studies are also needed to validate those therapies when implemented in clinical settings (primary care), by non-sleep specialists. There is also a need to disseminate more effectively the available evidence in support of psychological and behavioral interventions to health-care practitioners working on the front line

Nonpharmacologic treatment of chronic insomnia

This paper reviews the evidence regarding the efficacy of nonpharmacological treatments for primary chronic insomnia. It is based on a review of 48 clinical trials and two meta-analyses conducted by a task force appointed by the American Academy of Sleep Medicine to develop practice parameters on non-drug therapies for the clinical management of insomnia. The findings indicate that nonpharmacological therapies produce reliable and durable changes in several sleep parameters of chronic insomnia sufferers. The data indicate that between 70% and 80% of patients treated with nonpharmacological interventions benefit from treatment. For the typical patient with persistent primary insomnia, treatment is likely to reduce the main target symptoms of sleep onset latency and/or wake time after sleep onset below or near the 30-min criterion initially used to define insomnia severity. Sleep duration is also increased by a modest 30 minutes and sleep quality and patient's satisfaction with sleep patterns are significantly enhanced. Sleep improvements achieved with these behavioral interventions are sustained for at least 6 months after treatment completion. However, there is no clear evidence that improved sleep leads to meaningful changes in daytime well-being or performance. Three treatments meet the American Psychological Association (APA) criteria for empirically-supported psychological treatments for insomnia: Stimulus control, progressive muscle relaxation, and paradoxical intention; and three additional treatments meet APA criteria for probably efficacious treatments: Sleep restriction, biofeedback, and multifaceted cognitive-behavior therapy. Additional outcome research is needed to examine the effectiveness of treatment when it is implemented in clinical settings (primary care, family practice), by non-sleep specialists, and with insomnia patients presenting medical or psychiatric comorbidity

Derivation of research diagnostic criteria for insomnia: Report of an American Academy of Sleep Medicine Work Group

Insomnia is a highly prevalent, often debilitating, and economically burdensome form of sleep disturbance caused by various situational, medical, emotional, environmental and behavioral factors. Although several consensually-derived nosologies have described numerous insomnia phenotypes, research concerning these phenotypes has been greatly hampered by a lack of widely accepted operational research diagnostic criteria (RDC) for their definition. The lack of RDC has, in turn, led to inconsistent research findings for most phenotypes largely due to the variable definitions used for their ascertainment. Given this problem, the American Academy of Sleep Medicine (AASM) commissioned a Work Group (WG) to review the literature and identify those insomnia phenotypes that appear most valid and tenable. In addition, this WG was asked to derive standardized RDC for these phenotypes and recommend assessment procedures for their ascertainment. This report outlines the WG's findings, the insomnia RDC derived, and research assessment procedures the WG recommends for identifying study participants who meet these RDC