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

Abstract

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.

Brain and psychological determinants of placebo pill response in chronic pain patients

“…of the placebo pill ingestion were 0.62 for treatment 1 and 0.73 for treatment 2 (Supplementary Figure 4 ), which are comparable with E.S. reported in the placebo literature in chronic pain patients 29 , 30 .…”

The placebo response in myasthenia gravis assessed by quantitative myasthenia gravis score: A meta‐analysis

“…In the present study, we show that placebo responses in MG are quite small when assessed through QMG scores, a quantitative finding that parallels other conditions, such as cancer, obsessive‐compulsive disorder, insomnia, and hypertension . These conditions differ from others such as pain, Parkinson's disease, depression, fibromyalgia, epilepsy, and dermatological conditions, thereby emphasizing the need to map placebo responses across diseases.…”

“…Since the beginning of randomized placebo‐controlled clinical trials (RCTs) in pharmacology, placebo responses have received great attention. More recently, placebo effects have been investigated in their own right and meta‐analyses on the magnitude of placebo effects have been conducted in several clinical conditions such as pain, fibromyalgia, psychiatric disorders, Parkinson's disease, epilepsy, gastrointestinal disorders, dermatological conditions, insomnia, and hypertension …”

Clinical relevance of contextual factors as triggers of placebo and nocebo effects in musculoskeletal pain

“…Different studies have measured the magnitude of placebo and nocebo effects induced by CFs in different musculoskeletal pain conditions commonly encounter in daily setting [ 117 , 133 ]. Indeed the clinical effectiveness of placebo analgesia was demonstrated in specific complaints such as fibromyalgia [ 128 ] and osteoarthritis [ 118 ] with an effect size (ES) over 0.5. Also, nocebo hyperalgesia measured as dropout rate due to adverse event were present in fibromyalgia (9.6%) [ 134 ] and osteoarthritis (4.8%) [ 135 ].…”