Exercise Training May Help Improve Sleep in People With Fibromyalgia

Current interventions for sleep problems in people with fibromyalgia show only low levels of certainty of efficacy, although some forms of exercise training may be beneficial, according to a recent systematic review and meta-analysis.1

“Fibromyalgia is a chronic condition characterized by widespread musculoskeletal pain and fatigue. Almost everyone with fibromyalgia has sleep problems. We aimed to evaluate the effectiveness and safety of current interventions for the management of fibromyalgia-related sleep problems,” lead investigator Jemma Hudson, PhD, University of Aberdeen, United Kingdom, and colleagues wrote.1

Hudson and colleagues searched major electronic databases in November 2021 and identified 168 randomized controlled trials assessing pharmacologic and/or nonpharmacologic interventions in adults and children with fibromyalgia and sleep problems. They primarily looked at was sleep quality assessed using validated patient-reported outcome measures and also assessed the methodologic quality of included studies using the Cochrane Risk-of-Bias tool.

The investigators included 65 studies evaluating 35 treatment categories in 8,247 participants in a network meta-analyses (NMA). Notably, they found most studies had a high overall risk of bias. Hudson and colleagues found data supporting exercise’s positive effect on sleep.

Specifically, land-based aerobic exercise training in combination with flexibility training showed a standardized mean difference (SMD) of −4.69 (95% CI, -8.14 to -1.28) and aquatic-based aerobic exercise training showed a SMD of-2.63 (95% CI, -4.74 to -0.58) compared to placebo or sham. The investigators also found some suggesting that electrotherapy, weight loss, dental splints, antipsychotics, tricyclics, land-based strengthening exercise, and psychological and behavioral therapy with a focus on sleep, may moderately affect sleep.

“There is a low level of certainty surrounding the effectiveness of interventions for the management of sleep problems in people with fibromyalgia, but some forms of exercise training appear more likely to provide an improvement in sleep quality,” Hudson and colleagues concluded.1

Issues with sleep quality contribute greatly to the disease burden that fibromyalgia imposes on patients. One program in development, TNX-102 SL (cyclobenzaprine HCl sublingual tablets), is a 5.6 mg, non-opioid, centrally acting analgesic designed for chronic use that aims to address non-restorative sleep in fibromyalgia. The FDA accepted Tonix Pharmaceuticals’ a new drug application (NDA) for TNX-102 SL in December 2024, making the drug the first potential new first-line treatment for fibromyalgia in 15 years.2

The NDA submission included data from 2 14-week double-blind, randomized, placebo-controlled phase 3 trials evaluating the safety and efficacy of TNX-102 SL as a bedtime treatment for fibromyalgia. RELIEF, the first phase 3 trial completed in December 2020, met its primary endpoint of significantly reducing daily pain compared with placebo (P = .010). The second phase 3 trial, RESILIENT, was completed in December 2023 and demonstrated a significant reduction of daily pain compared with placebo (P = .00005). The most common treatment-emergent adverse events were mild tongue or mouth numbness at the administration site.2

REFERENCES

1. Hudson J, Imamura M, Robertson C, et al. Effects of Pharmacologic and Nonpharmacologic Interventions for the Management of Sleep Problems in People With Fibromyalgia: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. Arth. Care. Res. Pubished online February 10, 2025. Accessed April 25, 2025. doi: 10.1002/acr.25505

2. Tonix Pharmaceuticals Announces FDA Acceptance of the New Drug Application (NDA) for TNX-102 SL for Fibromyalgia. Globe Newswire. December 17, 2024. Accessed April 25, 2025. https://www.globenewswire.com/news-release/2024/12/17/2998199/28908/en/Tonix-Pharmaceuticals-Announces-FDA-Acceptance-of-the-New-Drug-Application-NDA-for-TNX-102-SL-for-Fibromyalgia.html.