Reframing Fibromyalgia Care in 2025: Restricted Impact of TNX-102 SL’s Approval

For more than 15 years, fibromyalgia care has existed in a therapeutic holding pattern. Clinicians have relied on a small group of FDA-approved medications—duloxetine, milnacipran, and pregabalin—alongside off-label agents, nonpharmacologic strategies, and trial-and-error symptom management. While these approaches have helped subsets of patients, they have fallen short for many others, leaving fibromyalgia one of the most challenging chronic pain syndromes to manage in routine clinical practice.

That landscape shifted in August 2025, when the US Food and Drug Administration approved TNX-102 SL (Tonmya) for the treatment of adults with fibromyalgia, marking the first new drug approved for the indication in more than 15 years.1 The decision introduced not only a new therapeutic option, but also a different conceptual target: nonrestorative sleep, long recognized as a core driver of fibromyalgia symptoms but rarely addressed directly by approved therapies.

The approval arrives amid a broader transformation in pain medicine. Earlier in 2025, the FDA approved suzetrigine, a non-opioid pain signal inhibitor, as the first new drug class for acute pain in more than 2 decades.2 Together, these approvals signal renewed momentum in novel, non-opioid pain innovation, yet they also highlight how much work remains, particularly for complex, heterogeneous conditions like fibromyalgia.

Insights from clinicians across rheumatology, rehabilitation, and integrative pain care suggest that TNX-102 SL may meaningfully expand the fibromyalgia toolkit—but that its impact will depend on access, patient selection, expectations, and how it is integrated into broader, multimodal care strategies.

Targeting Nonrestorative Sleep in Fibromyalgia

Fibromyalgia is defined not by structural damage or overt inflammation, but by central nervous system dysregulation—a constellation of altered pain processing, sleep disruption, fatigue, and cognitive symptoms. This complexity has made it resistant to single-target pharmacologic solutions. The pain experienced in fibromyalgia cannot be fully explained by peripheral injury or inflammatory disease activity. Even in patients with well-controlled autoimmune or musculoskeletal disease, fibromyalgia symptoms may persist, reflecting what pain researchers now classify as nociplastic pain that is driven by altered neural processing rather than tissue damage. Sleep disturbance is a central part of this phenomenon.

TNX-102 SL is a sublingual formulation of cyclobenzaprine, designed to optimize overnight pharmacokinetics and target sleep-related mechanisms without residual daytime effects. Unlike oral cyclobenzaprine, the sublingual formulation bypasses first-pass hepatic metabolism, reducing formation of long-lived metabolites and allowing for a more controlled overnight exposure.1

The FDA approval was based on data from the phase 3 RESILIENT trial, which demonstrated statistically significant improvements in daily pain scores, sleep disturbance, fatigue, and sleep quality compared with placebo. The study included 457 patients with fibromyalgia receiving TNX-102 SL 5.6 mg administered before bedtime (n = 231) or placebo (n = 226). Participants were mostly female (n = 436; 95.4%) and were mostly White/Caucasian (n = 386; 84.5%). They had a mean duration of 9.2 years of fibromyalgia disease (standard deviation [SD], 9.0) and a mean 5.9 (SD, 1.1) numeric rating scale (NRS) pain score at baseline. Investigators found that TNX-102 SL demonstrated a highly statistically significant improvement in the primary endpoint of statistically significantly reducing daily NRS pain scores compared with placebo starting at week 1 and continuing until Week 14 (P <.0001), with an effect size of 0.38.3

Importantly, improvements were observed early and sustained across the study period, supporting the concept that targeting sleep physiology can influence core fibromyalgia symptoms. From a clinical perspective, this represents a meaningful shift. Rather than treating pain as an isolated symptom, TNX-102 SL aligns with a growing recognition that sleep dysfunction is a central driver of fibromyalgia, not merely a secondary complaint.

“I am aware that some rheumatologists have commented that it will just be an expensive version of generic, oral cyclobenzaprine, but the fact that it was able to show statistical separation from placebo and has a unique mechanism of action that yields more enduring effect during the nighttime’s sleep cycles, and that its bioavailability is greater, all add up to our wanting to use it,” Philip Mease, MD, director of Rheumatology Research at Providence Swedish Medical Center and clinical professor at the University of Washington School of Medicine, told HCPLive.

However, clinicians caution against viewing the approval as a cure or a comprehensive solution. Fibromyalgia remains a heterogeneous condition, and sleep-targeted therapy alone is unlikely to address all contributing mechanisms in every patient.

TNX-102 SL as a Tool, Not a Transformation for Fibromyalgia

Clinicians anticipate that TNX-102 SL will be used primarily in patients with persistent symptoms despite prior therapy, particularly those in whom sleep disruption is prominent and limiting. For patients who have cycled through existing approved medications or experienced waning benefit over time, a new mechanism of action offers a rationale for re-engagement with pharmacologic care.

“Especially with the patients who are dealing with high levels of pain and really limitations to function, where even conservative management we can only get so far, that's when the medical management really can make a big difference,” Nicole Zangoglia, PT, DPT, a physical therapist with a concierge practice, said.

At the same time, clinicians emphasize that real-world uptake will hinge on insurance coverage, prior authorization requirements, and patient cost-sharing. As with many specialty medications, administrative barriers could limit access, blunting the drug’s real-world impact despite positive trial data.

“Assuming that the cost to the patient will not be exorbitant, assuming insurance coverage, and that there will be a reasonably non-onerous prior authorization process, we do plan to prescribe TNX-102 SL in our practice, based on the efficacy and safety data demonstrated in the phase 3 trials,” Mease said.

While the approval has been widely described as a milestone, some clinicians urge restraint in characterizing it as a transformative moment for fibromyalgia care. From this perspective, TNX-102 SL represents an incremental advance rather than a paradigm shift.

Fibromyalgia management has long required multimodal care, including physical therapy, behavioral interventions, sleep hygiene, stress management, and patient education. Pharmacologic treatments can support function and symptom control, but they rarely address the full scope of autonomic, neurologic, and psychosocial dysregulation involved.

“In my practice we’re always trying to bridge the gap between conservative care and medical management, because there's a role for both. And a lot of the times, if one can only get so far, we need a little assistance from the other. So there's always, it's always exciting when there's other opportunities that are non conservative, so that we have some resources and some something else to try for patients who are still struggling. So I haven't seen too much of the effects of that yet, but I'd be definitely excited to see where that goes,” Zangoglia said.

There is concern that new medications, however welcome, risk being positioned as standalone solutions rather than integrated components of comprehensive care. In this view, fibromyalgia treatment has historically fallen into cycles of enthusiasm followed by disappointment, as new drugs fail to deliver durable, system-level change. It is necessary to reframe expectations for this new addition to the fibromyalgia landscape. TNX-102 SL may help patients function better, sleep more effectively, and reduce pain intensity—but it is unlikely to “reset” the underlying dysregulation that characterizes fibromyalgia for many individuals.

Limits of Pharmacology for Fibromyalgia

A recurring theme among clinicians is that fibromyalgia reflects a dysregulated autonomic and central nervous system, shaped by genetic vulnerability, stress exposure, illness, and chronic pain signaling. Once established, this dysregulation can become self-sustaining.

“This type of pain may need different approaches to effectively treat. So whilst immunomodulatory medicines may effectively treat inflammation and reduce classic nociceptive pain, adjunctive approaches may be needed to treat nociplastic pain. This may also reduce the tendency to keep changing the patient’s immunomodulatory medicine, if inflammation is well controlled. Along with this education, we are hoping to see measures of nociplastic pain used in clinical trials and in clinical practice to aid clinicians to navigate this complexity,” Mease said.

Pharmacologic agents can modulate symptoms within this system, but they may not fundamentally rewire it. This has fueled growing interest in nonpharmacologic neuromodulation approaches, including transcranial magnetic stimulation, vagus nerve stimulation, and other device-based therapies aimed at restoring autonomic balance.

“I'm a very big fan of the holistic approach… creating medications that seemingly just band aid the issue is kind of my point of contention… I understand where it fits in… however, that kind of band aid like effect… has fallen short, as we see with the other handful of medications that we have that are FDA approved, which are not too robust,” Andrew Sharobeem, DO, a rheumatologist at Arizona Arthritis & Rheumatology Associates, told HCPLive.

While these approaches remain investigational or limited in availability, they reflect a broader recognition that fibromyalgia likely requires multi-level intervention, spanning sleep, neural processing, physical function, and psychological resilience.

Against this backdrop, TNX-102 SL may serve as a supportive therapy—one that helps stabilize sleep and reduce symptom intensity while other modalities address deeper contributors to disease persistence.

Fibromyalgia in the Context of 2025 Pain Innovation

The approval of TNX-102 SL does not stand alone. In January 2025, the FDA approved suzetrigine, a selective NaV1.8 sodium channel inhibitor, for moderate to severe acute pain, marking the first new drug class for acute pain in more than 20 years.2

Suzetrigine’s approval reflects a broader regulatory and scientific push toward non-opioid pain therapies that target specific biological mechanisms rather than broadly suppressing pain perception. Although suzetrigine is approved for acute pain and TNX-102 SL for chronic fibromyalgia, both approvals underscore renewed momentum in pain drug development after years of stagnation.

Importantly, these agents address different domains of pain biology. Suzetrigine targets peripheral nociceptive signaling, while TNX-102 SL targets sleep-related central sensitization. Together, they illustrate how pain medicine is moving away from one-size-fits-all approaches toward more mechanism-specific interventions.

Fibromyalgia’s Future: Progress With Perspective

The approval of TNX-102 SL in 2025 represents a meaningful step forward for fibromyalgia care, offering a novel, non-opioid option that directly targets a core feature of the disease: nonrestorative sleep. For patients who have cycled through existing therapies with limited success, it provides a new avenue worth exploring.

“I look forward to seeing RWE from long term clinical registries, to see if addition of this medication makes a difference, in settings not as controlled as clinical trials, with even more complex patients, there is improvement of pain, fatigue, and sleep disturbance. [In terms of other investigations with] long COVID and PTSD... there is overlapping pathophysiology with FM, including features of pain, fatigue and sleep disturbance, so I think it is worthwhile to consider use of this drug in these and other conditions that are at least partially characterized as central sensitization,” Mease said.

Clinicians agreed: no single medication is likely to resolve a condition defined by central sensitization, autonomic imbalance, and multifactorial symptom drivers. TNX-102 SL may improve quality of life for some patients, but it does not eliminate the need for comprehensive, multidisciplinary care—or for continued innovation beyond symptom management.

“It's great to have something like [TNX-102 SL] to avoid, certain medications that we know are not going to be great, like opioids, and are going to cause way more side effects than they do benefit. But, it's not that big splash that I'm looking forward to,” Sharobeem said.

Viewed alongside other 2025 pain approvals such as suzetrigine, TNX-102 SL reflects a broader reawakening in pain drug development. The challenge now is to ensure that these advances are integrated thoughtfully, equitably, and realistically into care models that recognize both the biology and the lived experience of chronic pain.

References

1. Johnson V. FDA Approves TNX-102 SL, First New Fibromyalgia Therapy in 15 Years. Article. HCPLive. August 15, 2025. https://www.hcplive.com/view/fda-approves-tnx-102-sl-first-new-fibromyalgia-therapy-in-15-years

2. Johnson V. FDA Approves Suzetrigine, a Non-Opioid Option, for Treatment of Acute Pain. Article. HCPLive. January 30, 2025. https://www.hcplive.com/view/fda-approves-suzetrigine-a-non-opioid-option-for-treatment-of-acute-pain

3. Iglehart III I, Sullivan G, Lederman S. Advancing Fibromyalgia Treatment: Transmucosal Sublingual Cyclobenzaprine (Tnx-102 SL) Targets Nonrestorative Sleep and Provides Sustained Pain Reduction.