With no existing cure for fibromyalgia, a chronic pain syndrome, current treatments focus on managing the symptoms like pain, fatigue and poor sleep, with exercise being a key part of the recommendations. Otherwise, the only solutions available are cognitive therapies and antidepressants, due the variability of symptoms from patient to patient. The only FDA-approved drugs to treat fibromyalgia are antidepressants duloxetine (Cymbalta) and milnacipran (Savella), and antiepileptic pregabalin (Lyrica), and drug discovery efforts have had limited success in recent years.
The 2024 FDA fast-track ruling on Tonmya (cyclobenzaprine HCl sublingual tablets) has brought this underserved patient population back into the spotlight. Here, we take a look at the latest research into fibromyalgia therapies and whether a successful treatment might be on the horizon.
Fibromyalgia as an autoimmune disease
In 2021 a breakthrough study shed new light on fibromyalgia syndrome (FMS) by demonstrating that the symptoms are caused by antibodies that increase the activity of pain-sensing nerves throughout the body1. The research was led by the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, in collaboration with the University of Liverpool and the Karolinska Institute, Sweden.
The researchers injected mice with antibodies from people living with fibromyalgia and observed that the mice rapidly developed an increased sensitivity to pressure and cold, as well as displaying reduced movement grip strength. Furthermore, the mice injected with fibromyalgia antibodies recovered after a few weeks, when antibodies had been cleared from their system, which suggests that therapies which reduce antibody levels in patients are likely to be effective treatments. Such therapies are already available and are used to treat other disorders that are caused by autoantibodies.
Dr David Andersson, the study’s primary investigator from King’s IoPPN said: “The implications of this study are profound. Establishing that fibromyalgia is an autoimmune disorder will transform how we view the condition and should pave the way for more effective treatments for the millions of people affected. Our work has uncovered a whole new area of therapeutic options and should give real hope to fibromyalgia patients.”
Ketamine-based treatments
Several studies have explored the potential of ketamine, a cyclohexanone-derived general anaesthetic and NMDA receptor antagonist, as a treatment for fibromyalgia. Researchers in Brazil conducted a systematic review of the safety and efficacy of ketamine in fibromyalgia patients covering six articles2. They found that most short-term studies had a good response, though a study with eight weeks of follow-up did not observe a good response. Overall, they concluded that while the evidence suggests ketamine is safe and has a potential effect on fibromyalgia, more studies, including long-term follow-up studies, are still needed.
In a poster shared at the American Psychiatric Association Annual Meeting 2024, it was shown that intranasal esketamine given for treatment-resistant depression (TRD) had a positive impact on patients’ fibromyalgia symptoms3. The poster details a case in which TRD treatment with intranasal esketamine 84mg weekly was associated with major depressive disorder remission as well as sustained improvement in fibromyalgia pain through ten months of ongoing treatment and follow-up. The patient reported consistent and lasting relief from fibromyalgia pain of four to five points on a 10 point scale. She rated her baseline pain as seven to eight out of 10 daily, with exacerbations to nine or 10, but with esketamine she rated her pain as two to three out of 10 most days, with breakthrough as high as four out of 10 on day six or seven of the one-week inter-dose interval.
Medical cannabis
Medical cannabis has also demonstrated promise as a treatment for fibromyalgia, largely due to its potential role in pain management. In a 2020 study, fibromyalgia patients were prescribed two oil-diluted cannabis extracts: Bedrocan (22% THC, <1% CBD), and Bediol (6.3% THC, 8% CBD) and symptom severity was assessed using Fibromyalgia Impact Questionnaire (FIQR), Fibromyalgia Assessment Scale (FAS), FACIT-Fatigue score, Pittsburgh Sleep Quality Index (PSQI), and Zung Depression and Anxiety Scales4.
A significant improvement in the PSQI and FIQR was observed in respectively 44% and 33% of patients, while 50% showed a moderate improvement in the anxiety and depression scales. Multiple regression analysis showed a correlation between the body mass index (BMI) and FIQR improvement. Concomitant analgesic treatment was reduced or suspended in 47% of the patients. The authors conclude that further studies are needed to confirm these data, identify medical cannabis-responsive sub-groups of fibromyalgia patients, and establish the most appropriate posology and duration of the therapy.
A 2024 study by Singla et al assessed the use of cannabis as a symptom management strategy in fibromyalgia using an anonymous survey of patients treated at the Mayo Clinic in Rochester, Minnesota5. Nearly half of respondents reported cannabis use since their fibromyalgia diagnosis to address pain (98.9%), fatigue (96.2%), stress, anxiety, or depression (93.9%), and insomnia (93.6%). Improvement in pain symptoms with cannabis use was reported by 82.0%, and most reported that cannabis also improved symptoms of stress, anxiety, and depression and of insomnia.
Weight loss drugs
As it has been shown that weight loss can improve fibromyalgia symptoms, weight loss drugs like GLP-1 receptor agonists could be helpful to patients. In one case study, Mounjaro (tire patients), a once-weekly dual GIP receptor and GLP-1 receptor agonist, alleviated a patient’s symptoms of endometriosis and fibromyalgia. The patient has been on Mounjaro since the end of May 2024 and had lost six stone overall. Due to the significant improvement in her fibromyalgia and endometriosis symptoms the study reports she is considering staying on maintenance treatment with tirzepatide.
Fibromyalgia and the microbiome
Due to the fact that many fibromyalgia patients also suffer with inflammatory bowel conditions and the composition of the gut microbiota in individuals with fibromyalgia differs from that of healthy controls, recent studies have looked at the role of the gut microbiome in the disease.
A 2025 study showed that faecal microbiota transplantation from fibromyalgia patients into germ-free mice induces pain and numerous molecular phenotypes that parallel known changes in fibromyalgia patients, including immune activation and metabolomic profile alterations6. They found that replacing the fibromyalgia microbiota with a healthy microbiota substantially alleviated pain in mice. Then, as part of the same study, an open-label trial in women with fibromyalgia showed that transplantation of a healthy microbiota is associated with reduced pain and improved quality of life. The authors reach the conclusion that altered gut microbiota has a role in fibromyalgia pain and highlight it as a promising target for therapeutic interventions.
Drugs for addiction
Treatments indicated for alcohol-use or opioid-use disorder have also been posited as possible options for fibromyalgia. Naltrexone is approved in the US to treat opioid or alcohol use disorder and opioid dependence, but is being increasingly used off-label at low doses to alleviate fibromyalgia symptoms. However, the evidence is mixed, with one study supporting its use7, and another finding no benefit at all for patients’ pain, though some indications of improvements in memory loss8.
Astellas’ novel GABAB receptor positive allosteric modulator, ASP8062, was shown to exert analgesic effects in a rat model of fibromyalgia10. The findings were followed up in a Phase II trial by the manufacturer, but unfortunately this showed no statistically significant improvement compared to placebo11.
New approaches
ASP0819 is a novel, non-opioid KCa3.1 channel opener, also developed by Astellas, that reverses abnormal nerve firing of primary sensory afferent nerves. It was assessed as a treatment for fibromyalgia in a Phase IIa, double-blind trial in 20179.
The results revealed there was no statistically significant difference between ASP0819 and placebo for the primary endpoint at Week 8, though ASP0819 versus placebo significantly improved daily average pain at Weeks 2, 6, and 7. Numerical improvements were observed on the FIQR total score and several sleep items showed statistically significant improvements with ASP0819 versus placebo. However, as the drug did not meet its primary endpoint, no further studies were conducted.
Tonmya (cyclobenzaprine tablets)
By far the most promising new drug for fibromyalgia is Tonmya (cyclobenzaprine HCl sublingual tablets) by Tonix Pharmaceuticals. In July 2024, the FDA granted Fast Track designation to the non-opioid, centrally-acting analgesic drug. Seth Lederman, Chief Executive Officer of Tonix Pharmaceuticals, said: “The designation underscores the importance of addressing the unmet needs of fibromyalgia patients, who report dissatisfaction with current treatment options. If approved by the FDA, we expect Tonmya to become the first new pharmacotherapy for fibromyalgia in over 15 years. The NDA being prepared supports Tonmya’s potential position as a first line therapy for fibromyalgia, indicated for long-term daily use at bedtime.”
Tonmya is believed to utilise a trimodal mechanism of action, potentially serving as a functional antagonist to improve sleep quality and reduce pain in fibromyalgia patients. Antagonism of the Serotonin-2A receptor is thought to increase restorative slow wave sleep and to decrease the frequency of waking-after-sleep onset, while antagonism of the Alpha-1-adrenergic receptor is found to reduce trauma-related nightmares and other forms of sleep disturbances, and antagonism of the Histamine-1 receptor promotes a decrease in wakefulness and increase in restorative slow wave sleep in preclinical studies.
In December 2023, the company announced highly statistically significant and clinically meaningful topline results in RESILIENT, the second pivotal Phase III clinical trial of Tonmya for the management of fibromyalgia. In the study, Tonmya met its pre-specified primary endpoint, significantly reducing daily pain compared to placebo in participants with fibromyalgia. Statistically significant and clinically meaningful results were also seen in all six key secondary endpoints related to improving sleep quality, reducing fatigue and improving overall fibromyalgia symptoms and function.
References
- Goebel A, Krock E, Gentry C, et al. Passive transfer of fibromyalgia symptoms from patients to mice. JClin Invest 2021;131(13):e144201.
- de Carvalho JF, de Sena EP. Ketamine in fibromyalgia: a systematic review. Advances in Rheumatology 2024;64:54.
