Background/Purpose: Fibromyalgia (FM) is a multifaceted disorder defined by chronic widespread pain, sleep disruption, fatigue, and cognitive difficulties. Although the predominant theory behind FM pathogenesis involves central sensitization and altered neurotransmitter signaling (e.g., serotonin, norepinephrine, glutamate), emerging evidence suggests peripheral contributors such as increased intramuscular pressure may also play a role. Elevated muscle tension has been correlated with poor sleep quality and higher pain levels, suggesting a cyclical relationship between sleep disturbance and muscular abnormalities. While tricyclic antidepressants (TCAs) have demonstrated some success in relieving FM-related symptoms – particularly sleep and mood disturbances – their use as monotherapy remains insufficient. Furthermore, despite literature on multimodal pharmacologic approaches, no studies to date have examined a combination of TCAs in a dose high enough to achieve uninterrupted sleep and muscle relaxants (MRs) as a targeted therapy for FM. This study explores whether this combination can effectively alleviate symptoms in a clinical population of FM patients.

Methods: We conducted a prospective study of 31 patients (25 females and 6 males) diagnosed with FM using the American College of Rheumatology (ACR) diagnostic criteria. All participants were prescribed a low dose TCA (amitriptyline, doxepin, or trazodone) in the early evening, titrated as needed to induce deep sleep. Once patients reported improved sleep, a nightly muscle relaxant – either cyclobenzaprine or tizanidine – was introduced and gradually increased based on tolerability, up to 30 mg or 24 mg respectively. Visual Analog Scales (VAS) were used to assess changes in pain (0–10), sleep quality (1 = excellent sleep, 10 = no sleep), and energy levels (1 = no energy, 10 = abundant energy) before and after the treatment regimen.

Results: Following treatment, 23 of 31 patients (74%) reported symptomatic improvement. Pain scores onVAS decreased from a pre-treatment mean of 7.81 to 5.25 post-treatment. Sleep quality improved significantly, with average sleep disruption scores declining from 5.7 to 2.69. Patient-reported energy levels increased from a mean of 2.34 to 4.77. See Figure 1. Eight patients (26%) reported no improvement, and an equal number experienced sedation as a side effect, though no other adverse events were reported. All results were statistically significant with a p-value < 0.01.

Conclusion: This study introduces a novel multimodal pharmacologic regimen combining tricyclic antidepressants and muscle relaxants to target both central and peripheral mechanisms contributing to FM symptomatology. Results suggest that such a combination can improve pain, sleep, and energy in a substantial portion of FM patients, with minimal side effects. Given the limitations of existing monotherapies and the heterogeneity of FM symptoms, this approach warrants further exploration in larger randomized controlled trials. Future studies should also evaluate long-term outcomes and compare this regimen directly with currently approved FM treatments such as duloxetine and pregabalin.

Figure 1. Fibromyalgia Symptom Severity Pre- and Post-Treatment

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/relax-the-body-dual-agent-nighttime-therapy-for-fibromyalgia-symptom-reduction-using-tricyclic-antidepressants-and-muscle-relaxants/