Sleep and Fibromyalgia

Fibromyalgia is a complex chronic condition associated with pain, myalgias, and arthralgias, as well as a constitution of other debilitating symptoms such as fatigue and cognitive, gastrointestinal, sleep, and mood issues.¹ Sleep disturbances are a hallmark feature of the condition and have a significant bidirectional relationship with other symptomatology, especially pain.² Diagnostic criteria have slight variation between defining bodies such as the American College of Rheumatology, but generally include widespread pain across multiple sites in the body, along with sleep, fatigue, and other aforementioned associated symptoms all occurring for at least three months, without other physical exam, radiological, or laboratory explanations.

Exact etiologies of fibromyalgia remain debated, but inflammatory, neuroendocrine, and autoimmune causes are speculated to interact with an array of biopsychosocial factors contributing to dysregulation of central nervous system mechanisms, resulting in hypersensitivity to pain.³ Due to the interconnection of etiological factors, progressive models for the treatment of fibromyalgia thus involve a multifaceted approach to address potential contributors. Exercise, counseling, stress reduction techniques, and potentially pharmacotherapy for mood and pain (typically in the form of tricyclic antidepressants, selective serotonin and norepinephrine reuptake inhibitors, or anti-epileptic drugs) are supported as part of a global therapeutic approach.⁴ Addressing sleep issues is a crucial component of fibromyalgia management, both in terms of mitigating the sleep-related symptoms associated with the condition as well as sleep being a target for improving other symptoms such as pain and mood.

Sleep and Pain

Sleep, a necessary and conserved process across nearly all species, impacts practically every human biological system. Its role in maintaining sound cognitive, mood, endocrine, and immune function has been well documented.^5-7 Factors contributing to pain and pain perception are complex, with contributions across multiple of these systems. Poor sleep has been shown to dysregulate components of these processes, resulting in increased sensitivity to pain.² Alternatively, having pain can worsen sleep quality and duration, perhaps leading to somewhat of an amplification feedback loop in fibromyalgia. This interaction between sleep and pain, with poor sleep having the ability to potentiate pain and pain contributing to disrupted sleep, is a key concept with multiple implications in the condition of fibromyalgia.

Subjective and Objective Sleep Findings and Co-morbidities 

Sleep complaints in fibromyalgia can be diverse and varied, but issues with sleep onset, sleep maintenance, and sleep being non-restorative are consistently reported,⁸ with the majority of individuals with fibromyalgia (potentially as high as 90%)⁹ reporting some degree of sleep disturbance or quality impact. In addition to insomnia, other comorbid sleep disorders can further compound sleep disturbance and may be seen at a higher rate in fibromyalgia. Restless legs syndrome (RLS) has been reported to occur in approximately 38% of patients with fibromyalgia,¹⁰ with medications used for mood and pain, such as SSRIs, SNRIs, and TCAs, also serving to potentially exacerbate RLS. The presence of RLS in fibromyalgia has been shown to worsen sleep quality, daytime sleepiness, and quality of life as measured by the Pittsburgh Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Fibromyalgia Impact Questionnaire (FIQ) when compared to fibromyalgia patients without RLS.¹¹ Obstructive sleep apnea (OSA) has been reported to be as high as 45%-65%, 9% in patients with fibromyalgia,^12,13 with retrospective analysis also supporting OSA/fibromyalgia association and recommending evaluation via sleep study in all patients with fibromyalgia.¹⁴

While opioids are not routinely prescribed for fibromyalgia, if given for pain, they have the potential to precipitate respiratory depression and central sleep apnea as well as worsen daytime somnolence. Substantial evidence has not been reported on an association between fibromyalgia and central disorders of hypersomnolence, such as narcolepsy, but if present, symptom burden may be even greater in these patients.

Polysomnography findings have been, in part, inconclusive in capturing a universal picture of patients with fibromyalgia; however, several studies have reported decreased sleep efficiency (SE), as well as increased sleep fragmentation, wake after sleep onset (WASO), and light sleep (N1) in this population.^15,16 Quantitative EEG during polysomnography has reported significant differences in the ratio of delta to alpha frequency power in patients with fibromyalgia compared to controls, citing a ratio of ≤1 being 95% specific for fibromyalgia,¹³ perhaps serve as a marker for altered sleep function in fibromyalgia.

Management Considerations

Due to the burden of sleep-related associated symptoms, potentially increased co-morbidity of other sleep disorders, and sleep’s ability to modulate pain and mood, attention to evaluating and optimizing sleep should be a routine part of fibromyalgia treatment.

Sleep hygiene and utilization of cognitive behavioral therapy for insomnia (CBT-I) when appropriate can not only improve sleep but may have a positive impact on other aspects of fibromyalgia, such as mental health and quality of life.

Exercise, one of the consistently supported recommendations for fibromyalgia, has benefits for pain, mood, and sleep.¹⁷

Stress management and addressing any comorbid anxiety and depression can improve sleep as well as other symptomatology of fibromyalgia.

Sleep evaluation and treatment for any underlying sleep disorders should be a consistent aspect of management.

Pharmacotherapy for fibromyalgia ideally should take sleep quality into consideration, with several agents typically used in the treatment of fibromyalgia, such as duloxetine and pregabalin, also potentially improving sleep as well as pain.¹⁸ While hypnotic pharmacotherapy is not necessarily routinely recommended, studies on several agents have demonstrated additional benefits in fibromyalgia. Orexin receptor agonist, suvorexant, demonstrated increased total sleep time and reduction in pain sensitivity in patients with fibromyalgia.¹⁹ Sodium oxybate has demonstrated improvements in symptoms of pain and fatigue, as well as reduction of alpha intrusion and sleep onset latency,²⁰ although it was denied FDA approval in 2010 for fibromyalgia due to concerns about safety and misuse.

Appreciation of the complex bidirectional relationship between sleep and fibromyalgia is crucial to improving symptom burden. Care coordination models where sleep providers and rheumatologists collaborate both for diagnosis and treatment are likely the ideal approach and should be able to provide better patient outcomes than either specialty can accomplish alone, even for the symptoms typically within their respective realms of care. Research into sleep and fibromyalgia remains ongoing, offering hope for better management and relief for those living with the chronic and debilitating condition of fibromyalgia.

Joshua Roland, MD, is a board-certified sleep physician who is currently serving as the medical director for Sanusom. He is an advocate for healthy sleep and its role in physical and mental well-being.This article first appeared in SleepWorld Magazine Nov/Dec 2023 issue.

References

1. Chinn, S., W. Caldwell, and K. Gritsenko, Fibromyalgia Pathogenesis and Treatment Options Update. Curr Pain Headache Rep, 2016. 20(4): p. 25.
2. Roehrs, T. and T. Roth, Sleep and pain: interaction of two vital functions. Semin Neurol, 2005. 25(1): p. 106-16.
3. Bradley, L.A., Pathophysiology of fibromyalgia. Am J Med, 2009. 122(12 Suppl): p. S22-30.
4. Clauw, D.J., Fibromyalgia: a clinical review. JAMA, 2014. 311(15): p. 1547-55.
5. Walker, M.P., The role of sleep-in cognition and emotion. Ann N Y Acad Sci, 2009. 1156: p. 168-97.
6. Spiegel, K., R. Leproult, and E. Van Cauter, Impact of sleep debt on metabolic and endocrine function. Lancet, 1999. 354(9188): p. 1435-9.
7. Besedovsky, L., T. Lange, and J. Born, Sleep and immune function. Pflugers Arch, 2012. 463(1): p. 121-37.
8. Wu, Y.L., et al., Sleep disturbances in fibromyalgia: A meta-analysis of case-control studies. J Psychosom Res, 2017. 96: p. 89-97.
9. Liedberg, G.M., M. Bjork, and B. Borsbo, Self-reported nonrestorative sleep in fibromyalgia – relationship to impairments of body functions, personal function factors, and quality of life. J Pain Res, 2015. 8: p. 499-505.
10. Padhan, P., D. Maikap, and M. Pathak, Restless leg syndrome in rheumatic conditions: Its prevalence and risk factors, a meta-analysis. Int J Rheum Dis, 2023. 26(6): p. 1111-1119.
11. Civelek, G.M., P.O. Ciftkaya, and M. Karatas, Evaluation of restless legs syndrome in fibromyalgia syndrome: an analysis of quality of sleep and life. J Back Musculoskelet Rehabil, 2014. 27(4): p. 537-44.
12. Mutlu, P., et al., Prevalence of obstructive sleep apnea in female patients with fibromyalgia. Saudi Med J, 2020. 41(7): p. 740-745.
13. Rosenfeld, V.W., D.N. Rutledge, and J.M. Stern, Polysomnography with quantitative EEG in patients with and without fibromyalgia. J Clin Neurophysiol, 2015. 32(2): p. 164-70.
14. Meresh, E.S., et al., Obstructive sleep apnea co-morbidity in patients with fibromyalgia: a single-center retrospective analysis and literature review. Open Access Rheumatol, 2019. 11: p. 103-109.
15. Diaz-Piedra, C., et al., Sleep disturbances of adult women suffering from fibromyalgia: a systematic review of observational studies. Sleep Med Rev, 2015. 21: p. 86-99.
16. Cetin, B., et al., Comparison of sleep structure in patients with fibromyalgia and healthy controls. Sleep Breath, 2020. 24(4): p. 1591-1598.
17. Estevez-Lopez, F., et al., Effectiveness of Exercise on Fatigue and Sleep Quality in Fibromyalgia: A Systematic Review and Meta-analysis of Randomized Trials. Arch Phys Med Rehabil, 2021. 102(4): p. 752-761.
18. Roth, T., et al., Effect of pregabalin on sleep in patients with fibromyalgia and sleep maintenance disturbance: a randomized, placebo-controlled, 2-way crossover polysomnography study. Arthritis Care Res (Hoboken), 2012. 64(4): p. 597-606.
19. Roehrs, T., et al., Sleep and pain in humans with fibromyalgia and comorbid insomnia: double-blind, crossover study of suvorexant 20 mg versus placebo. J Clin Sleep Med, 2020. 16(3): p. 415-421.
20. Scharf, M.B., M. Baumann, and D.V. Berkowitz, The effects of sodium oxybate on clinical symptoms and sleep patterns in patients with fibromyalgia. J Rheumatol, 2003. 30(5): p. 1070-4.