Results of safety and efficacy of sublingual cyclobenzaprine (TNX-102) in patients with fibromyalgia

A recent study has stated that the treatment with sublingual cyclobenzaprine (TNX-102 SL) was safe and well-tolerated in patients with fibromyalgia. The study findings have been published in the journal Arthritis & Research.

Dr. Lederman and his colleagues conducted a double-blind, randomized, placebo-controlled trial to evaluate pain reduction in fibromyalgia patients using TNX-102 SL. This study, which included 503 patients, reported a significant decrease in daily pain with TNX-102 after 14 weeks (approximately 3 months) in the study group. However, at week 14, the Patient Global Impression of Change did not show significant improvement due to TNX-102 SL. Nonetheless, there was an improvement in Fibromyalgia Impact Questionnaire-Revised scores, Patient-Reported Outcomes Measurement Information System, and daily sleep quality. The most frequently reported treatment-emergent adverse events overall by patients receiving TNX-102 SL and placebo were oral hypoesthesia (17.3% with TNX-102 SL vs. 0.4% with placebo), oral paresthesia (5.6% vs. 0.4%), and altered product taste (4.4% vs. 0.4%).

A 2021 placebo-controlled multicenter efficacy and safety trial showed reduced daily pain using TNX at the 5.6 mg dose during bedtime. It also showed improvement in sleep, fatigue, and other fibromyalgia symptoms. A 30% pain reduction responder analysis showed 46.8% TNX responders compared to 34.9% on placebo (p=0.006). According to Patient Global Impression of Change, 29.4% of those on the placebo had responders versus 37.5% of those using TNX (P=0.058). TNX demonstrated higher separation from placebo in terms of FIQ-R symptoms (p=0.007), function (p=0.009), PROMIS sleep disturbance (P <0.001), fatigue (P=0.018), and daily diary sleep quality (p<0.001).

In conclusion, the findings from these studies indicate that TNX-102 SL has a primary impact on sleep quality, which in turn may lead to a reduction in central sensitization. This improvement at the syndromal level is reflected in the broad-spectrum activity observed in fibromyalgia symptoms.


  1. Lederman S, Arnold LM, Vaughn B, Kelley M, Sullivan GM. Efficacy and Safety of TNX‐102 SL (Sublingual Cyclobenzaprine) for the Treatment of Fibromyalgia: Results From the Randomized, Placebo‐Controlled RELIEF Trial. Arthritis Care & Research. 2023 May 11.
  2. Sullivan G, Kelley M, Iserson A, Peters P, Peters A, Flint C, et al. TNX-102 SL (Sublingual Cyclobenzaprine) for the Treatment of Fibromyalgia in the RELIEF Study: Positive Results of a Phase 3 Randomized, Double-Blind, Placebo-Controlled Multicenter Efficacy and Safety Trial [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9).