Treatment Database

A sublingual low-dose cyclobenzaprine formulation FDA-approved for fibromyalgia in August 2025, the first new drug approved for the condition in over 15 years. Unlike oral cyclobenzaprine (a muscle relaxant), the sublingual route bypasses hepatic first-pass metabolism, reducing production of the long-acting metabolite norcyclobenzaprine and allowing a lower effective dose (5.6 mg vs 10–30 mg oral). Its proposed mechanism targets nonrestorative sleep, a core feature of fibromyalgia. Two of three phase 3 RCTs (RELIEF and RESILIENT; ~1,000 patients combined) met the primary endpoint of reduced daily pain at 14 weeks, with secondary endpoints including sleep quality and fatigue also significantly improved.