Effects of pharmacological and non-pharmacological interventions for the management of sleep problems in people with fibromyalgia: a multi-methods evidence synthesis.

Background: Fibromyalgia is a chronic condition characterised by widespread musculoskeletal pain. Sleep problems are reported by 92% of people living with fibromyalgia. Objectives: To evaluate the effectiveness and safety of interventions for the management of fibromyalgia-related sleep problems; explore the experiences of people with fibromyalgia-related sleep problems and examine the content of patient-reported outcome measures for 'sleep quality'. Methods: We conducted: (1) a network meta-analysis of randomised controlled trials to compare the effectiveness of pharmacological and non-pharmacological interventions; (2) a systematic thematic synthesis of qualitative evidence; (3) a content analysis of existing patient-reported outcome measures validated in people with fibromyalgia. Major electronic databases were searched in November 2021. Results: One hundred and sixty-eight studies were included in the effectiveness synthesis. The network meta-analysis assessing sleep quality included 35 treatment categories from 65 studies (8247 participants). Most studies were at high overall risk of bias. There is some evidence that compared with placebo or sham treatments, some forms of exercise [i.e. land-based aerobic exercise training in combination with flexibility training (standardised mean difference -4.69, credible interval -8.14 to -1.28) and aquatic-based aerobic exercise training (standardised mean difference -2.63, credible interval -4.74 to -0.58)] may improve sleep. There is also a suggestion that land-based strengthening exercise, psychological and behavioural therapies with a focus on sleep, electrotherapy, weight loss, dental splints, antipsychotics and tricyclics may have a modest effect on sleep, but credible intervals are wide. For other interventions, there is no clear evidence of beneficial effects on sleep. Our certainty of current evidence was predominantly low to very low. The thematic synthesis highlighted the bidirectional relationship between sleep and pain. Twenty-one sleep domains were identified across five patient-reported outcome measures. The domain most frequently identified was sleep maintenance. The Pittsburgh Sleep Quality Index was the most comprehensive tool (15 domains), followed by the Medical Outcomes Study Sleep Scale (11 domains). Limitations: Quantitative studies varied considerably in terms of characteristics of interventions, control treatments and type of outcome measures. In the network, most interventions were compared with placebo, sham treatment or usual care and not with another active treatment. In general, studies were small, unblinded and of short duration (median 12 weeks). For the qualitative synthesis and patient-reported outcome measures analysis, it is unclear whether study participants are adequately representative of the wider population of fibromyalgia patients due to poor reporting of demographic data. Conclusions: Some forms of exercise may be effective for managing sleep problems in people with fibromyalgia. However, heterogeneity, imprecision and low quality of the current evidence base preclude any firm conclusions. Qualitative data indicate that poor sleep is a common, profoundly disabling problem for people with fibromyalgia that negatively affects their other symptoms (e.g. pain), health and well-being. While we found heterogeneity among the item content of the patient-reported outcome measures, all capture constructs associated with sleep quality and, conceptually, are similar enough to be combined in a synthesis. Future work: High-quality research is needed to investigate which interventions are more likely to be effective for treating fibromyalgia-related sleep problems. Future studies must be designed in collaboration with fibromyalgia patients and include an appropriate comparator treatment. Pre-registration of study protocols is essential. Study registration: This study is registered as PROSPERO CRD42021296922. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR132999) and is published in full in