Efficacy and Safety of Pregabalin-Tizanidine vs Pregabalin in Patients with Fibromyalgia: Study Protocol for a...

The global prevalence of fibromyalgia (FM) in the general population is estimated to range from 2% to 4%. Pregabalin, a gamma-aminobutyric acid (GABA) analogue, is one of the most widely prescribed medications for FM. However, at therapeutic doses, its limited efficacy and/or unacceptable side effects mean that many patients derive only partial benefit, often leading to treatment discontinuation. Cyclobenzaprine is a centrally acting muscle relaxant. In August 2025, the United States Food and Drug Administration approved a sublingual formulation of cyclobenzaprine hydrochloride for treating FM in adults. However, its availability is largely confined to North America. Tizanidine, like cyclobenzaprine, is also a muscle relaxant with a central mechanism; however, there is no codified posology for FM treatment with tizanidine.

This study aims to recruit 164 adult patients diagnosed with FM. Participants will be randomly assigned in a 1:1 ratio to either the intervention group (pregabalin plus tizanidine) or the control group (pregabalin monotherapy). The primary outcome is the change from baseline to week 12 in average pain intensity (during the last 7 days) assessed using the first item of the symptom domain of the Revised Fibromyalgia Impact Questionnaire (FIQR). Secondary outcomes, assessed at weeks 4, 8, 12, 16, 20, and 24, will include: widespread pain, symptom severity, functional performance, balance, muscle strength and power, psychological functioning, sleep quality, self-efficacy, treatment durability, and health-related quality of life.

This study was approved by the Institutional Review Board of Beijing Tiantan Hospital (KY2025-217-03-08) and was registered with ClinicalTrials.gov (NCT07382921). All study procedures will be conducted in accordance with the Declaration of Helsinki (1964) and its subsequent amendments (7th revision, Fortaleza, Brazil, 2013).

This trial will provide evidence for the efficacy and safety of pregabalin combined with tizanidine in the treatment of FM.