Short-term efficacy and safety of sublingual cyclobenzaprine for fibromyalgia: A systematic review and meta-analysis

Fibromyalgia (FM) is a chronic nociplastic pain syndrome marked by widespread pain, nonrestorative sleep, fatigue, and functional impairment. TNX-102 SL (cyclobenzaprine HCl sublingual) is a once-nightly, non-opioid therapy designed to improve sleep and reduce multi-domain FM symptoms.

We identified randomised, double-blind, placebo-controlled trials of TNX-102 SL in adults with FM. Outcomes included the weekly average daily pain, achieving ≥ 30% and ≥ 50% pain reduction, Patient Global Impression of Change, Fibromyalgia Impact Questionnaire-Revised (FIQ-R), and safety. Random-effects meta-analyses were performed with risk of bias assessed by RoB 2.

Across four trials (total n = 1,684), TNX-102 SL significantly increased ≥ 30% pain responders (RR 1.44; 95% CI 1.15-1.81; I² = 2.6%) and ≥ 50% pain responders (RR 1.43; 95% CI 1.12-1.82; I² = 0%), and improved PGIC response (RR 1.52; 95% CI 1.29-1.79; I² = 8.5%), compared with placebo. Although the TNX-102 SL did not significantly improve FIQR. Treatment-emergent adverse events were more frequent with TNX-102 SL (RR 1.41; 95% CI 1.26-1.57; I² = 0%), driven by transient oral side effects: oral hypoesthesia (RR 38.11; 95% CI 18.55-78.29), oral paresthesia (RR 7.88; 95% CI 4.75-13.05), and abnormal taste (RR 10.92; 95% CI 6.74-17.69). Discontinuation rates were similar to placebo (RR 1.03; 95% CI 0.78-1.36; I² = 0%), and no deaths were reported.

This meta-analysis of TNX-102 SL for fibromyalgia found that once-nightly sublingual cyclobenzaprine produced consistent improvements in pain response and global impression compared to placebo, with a good tolerability profile. TNX-102 SL represents an essential new non-opioid option for fibromyalgia. Key Points • In a meta-analysis of four randomized, double-blind trials (n = 1,684), TNX-102 SL increased ≥ 30% and ≥ 50% pain responder rates versus placebo (RR 1.44 and 1.43; low heterogeneity). • TNX-102 SL improved Patient Global Impression of Change (RR 1.52), while FIQ-R scores -were not significantly different from placebo. • Treatment-emergent adverse events were more frequent and primarily transient oral effects (hypoesthesia, paresthesia, dysgeusia), with similar discontinuation rates and no reportd deaths.