Description of underlying health problem
Fibromyalgia is a complex and heterogeneous condition.1 Symptoms are commonly multiple, tend to fluctuate and cannot be easily classified within known medical diagnostic categories.2 There are no imaging modalities of clinical laboratory investigations to confirm or refute the presence of fibromyalgia. Several classifications and diagnostic criteria have been proposed over the years. The 2016 revision of the 2010–1 criteria of the American College of Rheumatology (ACR) and the ACTTION-APS Pain Taxonomy diagnostic criteria are widely used for establishing a diagnosis of fibromyalgia.3,4 Fibromyalgia is usually diagnosed based on the presence of key elements such as widespread musculoskeletal pain, fatigue, non-refreshing sleep, cognitive complaints (e.g. trouble thinking, brain fog) and low mood.
Fibromyalgia affects 1.7 million adults in the UK, adversely impacting their daily functioning and health-related quality of life.5,6 Sleep disturbance is reported as one of the most common symptoms by 92% of those living with fibromyalgia.7,8 Nevertheless, fibromyalgia-related sleep problems are poorly managed in the NHS, with people continuing to seek help for improving their sleep for many years after their initial fibromyalgia diagnosis.6
The manifestation of sleep disturbances in fibromyalgia can be diverse and includes self-report of difficulty with sleep onset, frequent awakenings, feeling unrefreshed on waking and, overall, a perception of poor sleep quality. A meta-analysis of polysomnographic studies corroborates these reports, with evidence of shorter sleep duration, less time in deep sleep, lower sleep efficiency and more time spent awake after sleep onset in people with fibromyalgia, compared with controls.9 In terms of neurophysiology, these sleep disturbances are marked by reduced sleep spindles (12–14 Hz oscillations, a hallmark of sleep) during shallow sleep (N2 stage), intrusion of alpha activities (8–13 Hz oscillations, a marker of wakeful relaxation) during deep sleep (N3 stage) and increased rates of cyclical alternating pattern, which is a structural polysomnographic marker of sleep regulation instability. Although a unique signature of sleep disturbances specific to fibromyalgia is yet to be identified, there is an expert consensus backed by epidemiological data that alterations to normal sleep are a driver of pathological pain processing and central sensitisation, generating pain and cognitive–emotive symptoms that mimic those of fibromyalgia.10 Specific sleep disorders are highly prevalent among those with fibromyalgia; over 50% of people with a fibromyalgia diagnosis meet a clinical threshold or diagnostic criteria for chronic insomnia disorder, over 40% have been estimated to have comorbid restless leg syndrome and over a quarter exceed the clinical threshold for a diagnosis of obstructive sleep apnoea.11–13
Impact of health problem
Fibromyalgia has been shown to affect 2–3% of people in studies worldwide,14 although in the UK, and using more recent classification criteria, the prevalence was approximately 5%.15 Fatigue is one of the most disabling symptoms experienced by people with fibromyalgia. A study conducted in the USA reported that three-quarters of people with fibromyalgia showed clinically important levels of fatigue, which did not meaningfully improve over time, and that symptoms were strongly related to sleep disturbance.16,17
The toll of the problem on individuals is immense; our patient representative (DD) maintains that ‘sleep disturbance is torturous, being mentally, physically and emotionally exhausting at every level’. In addition to negative impacts on the individual, fibromyalgia-related sleep disturbances have also important health-economic consequences, with an estimated 150,000 general practitioner (GP) consultations per year in the UK.6 Fibromyalgia-related sleep disturbances are also associated with greater utilisation of ambulatory care services, increased drug prescriptions, including those not necessarily targeting sleep disturbances (e.g. muscle relaxants, antidepressants), and a higher risk of drug dependency and undesirable side effects (e.g. related to antidepressants, anticonvulsants and opioid use).18–20
Decision problem
The 2015 European guidelines for the management of fibromyalgia considered sleep as one of the key outcomes of interest.1 Although general recommendations were made for managing sleep disturbances, these were graded as ‘weak’ due to paucity of published evidence at that time. Additionally, sleep management was not the primary focus of the guidelines. Evidence reviews have recently informed National Institute of Health and Care Excellence (NICE) draft guidelines for the management of chronic pain; however, these cluster together a wide range of conditions (including osteoarthritis, mechanical back pain, fibromyalgia), and do not have a specific focus on sleep management.21 Given the increased number of published randomised controlled trials (RCTs) in this clinical area, there is a scope to conduct network meta-analyses of direct and indirect evidence to evaluate the comparative effectiveness of different interventions for the management of sleep problems in fibromyalgia.22,23 The results of the network meta-analysis (NMA) could be further enhanced by incorporating findings from a synthesis of qualitative evidence regarding the acceptability of different interventions from a patient perspective. A critical evaluation of measures used in trials to evaluate intervention performance is also essential to determine whether the outcomes that matter most to patients are being considered.
Research into interventions for managing sleep problems in people with fibromyalgia is still a top priority of the James Lind Alliance Priority Setting Partnerships initiative.24 The importance of this is amplified by a compelling body of literature demonstrating associations between sleep disturbances and exacerbation of other fibromyalgia symptoms. Disturbed sleep is an adverse prognostic factor, with evidence of dose-dependent relationships with pain intensity, worse physical and cognitive functioning, low mood, anxiety, catastrophising, low self-efficacy and poor quality of life.25 Sleep problems have also been implicated in the development of depression among those with persistent pain.26 The potential of sleep as a particularly salient management target is bolstered by large-scale population-based cohort studies identifying sleep disturbance as an independent factor that increases the risk of developing fibromyalgia by two- to fourfold, with a follow-up period of up to 12 years.27,28 Conversely, and perhaps more importantly, having restorative sleep has been found to prospectively predict successful resolution of chronic widespread pain.29
Description of interventions under assessment
Broadly, the interventions for management of fibromyalgia can be divided into pharmacological and non-pharmacological interventions. Pharmacological interventions may include:30
- Simple and opioid analgesics – for example paracetamol +/− opioids, tramadol (opioid with serotonin and norepinephrine reuptake inhibitor activity)
- Tricyclic antidepressants – for example amitriptyline, cyclobenzaprine (5-HT2 receptor blocker)
- Selective serotonin reuptake inhibitors (SSRIs) – for example citalopram, escitalopram, fluoxetine, paroxetine
- Serotonin reuptake inhibitors (SRIs) – for example duloxetine, es-reboxetine, milnacipran
- Gabapentinoid – gabapentin, pregabalin
- N-methyl-D-aspartate receptor antagonists – ketamine, memantine
- Cannabinoids – dronabinol, nabilone.
Non-pharmacological intervention may be classified as:31
- Exercise – this includes aerobic exercise, flexibility exercises, strengthening exercises, Mind–body exercise (mind–body Ex) (e.g. Tai Chi), or mixed exercise. Exercise could take place in water or on land.
- Psychological and behavioural interventions such as cognitive–behavioural therapy (CBT); mindfulness; acceptance and commitment therapy (ACT) and attachment-based compassion therapy.
- Relaxation or meditation, such as relaxation, meditation, hypnosis, guided imagery.
- Balneotherapy – defined as aquatic therapy that uses a natural thermal mineral water. This includes all aquatic interventions that involved adopting a static position in water with different minerals or in sea water.
- Manual therapy (Manual T) such as massage, physical therapy (e.g. mobilisation).
- Electrical therapy such as electrotherapy (Electro T), specifically neuromuscular electric stimulation, transcutaneous electrical nerve stimulation (TENS), laser therapy, and neuromodulation, such as transcranial direct-current stimulation (tDCS).32
- Complementary and non-mainstream interventions such as traditional acupuncture, magnetotherapy, homeopathy, cupping therapy, hyperbaric oxygen therapy, cryotherapy, whole body vibration.
- Dietary/nutrition interventions, such as nutritional supplements.
- Education.
Population and relevant subgroups
People of any age living with fibromyalgia.
Setting/context
Any relevant clinical setting (e.g. primary care, secondary care, community care).
Overall aim and objectives of this assessment
The overarching aim is to provide useful information to help patients’ self-management, aid clinical decision-making and guide future research by assessing the existing quantitative and qualitative evidence on interventions that may be used for the management of fibromyalgia-related sleep problems.
Specific objectives
- To undertake a comprehensive evidence synthesis to assess the clinical effectiveness and adverse effects of pharmacological and non-pharmacological treatments for the management of fibromyalgia-related sleep problems (quantitative evidence synthesis).
- To update and enhance a previously published qualitative evidence synthesis33 to ascertain the experiences and expectations of people who receive treatments for fibromyalgia-related sleep problems (qualitative evidence synthesis).
- To examine item content of existing patient-reported outcome measures (PROMs) related to sleep in people with fibromyalgia to assess heterogeneity and patient relevance (PROMs analysis).
- To provide an overview of current quantitative and qualitative evidence including evidence on PROMs.