Fibromyalgia is a chronic nociplastic pain syndrome characterized by widespread musculoskeletal pain, fatigue, non-restorative sleep, and cognitive difficulties (often called “fibro fog”), frequently accompanied by other symptoms such as mood changes or overlapping conditions like irritable bowel syndrome. It arises primarily from altered central nervous system pain processing rather than peripheral tissue damage or inflammation.
Myth: Fibromyalgia is “all in the head” or purely psychological
Fact: While psychological factors and stress can influence symptoms, fibromyalgia has a clear biological basis. Recent research confirms it as a disorder of central sensitization and nociplastic pain, where the brain and spinal cord amplify pain signals even without ongoing tissue injury. Large genetic studies (analyzing millions of people) have identified dozens of risk loci linked mainly to neuronal function, supporting a neurological foundation. Additional evidence points to impaired descending pain inhibition, possible neuroimmune changes, gut microbiota contributions, and oxidative stress. Triggers such as infection, trauma, or emotional stress may interact with genetic predisposition, but the condition is not imaginary or solely psychosomatic.
Myth: There is no effective treatment
Fact: Management is multimodal and individualized, with non-pharmacological approaches as the foundation. Aerobic exercise (walking, swimming, cycling), graded physical activity, patient education, pain neuroscience education, cognitive behavioral therapy (CBT), and acceptance and commitment therapy (ACT) have strong evidence for reducing pain, fatigue, and improving function and sleep. Emerging neuromodulation options such as transcutaneous electrical nerve stimulation (TENS) added to physical therapy and home-based transcranial direct current stimulation (tDCS) combined with exercise have shown meaningful benefits for movement-evoked pain and disability in recent trials, with effects lasting months.
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Pharmacological options provide modest help for some patients:
- Established FDA-approved agents (pregabalin, duloxetine, milnacipran): Moderate evidence of substantial pain relief (at least 50 percent reduction) in roughly 1 in 10 patients with moderate-to-severe pain for 4 to 12 weeks; limited long-term data beyond 6 months and variable effects on other symptoms.
- New approval in August 2025: Tonmya (TNX-102 SL; sublingual cyclobenzaprine 5.6 mg once daily at bedtime). First new FDA-approved fibromyalgia medication in over 15 years. It targets non-restorative sleep. Two phase 3 trials (RELIEF and RESILIENT, nearly 1,000 patients) showed statistically significant reductions in daily pain scores vs. placebo at 14 weeks, higher rates of at least 30 percent pain improvement, and benefits on sleep/fatigue; generally well tolerated (sublingual route reduces first-pass metabolism and some side effects).
- Other/off-label or emerging:
- Low-dose naltrexone (LDN): Ongoing interest for possible neuroinflammation/central sensitization effects; recent data show limited or mixed efficacy and call for more rigorous trials.
- Cyclobenzaprine (oral, older use), certain antidepressants, gabapentinoids; limited or no strong support for opioids, most NSAIDs, or many anticonvulsants.
- Early-stage exploration of cannabinoids, certain psychedelics (e.g., psilocybin), intravenous lidocaine (selected refractory cases), nutraceuticals targeting oxidative stress/mitochondria, and other neuromodulators.
Myth: Ketamine infusions are a proven breakthrough for fibromyalgia pain
Fact: Ketamine (an NMDA receptor antagonist) is used off-label for refractory chronic pain, including fibromyalgia, because it can temporarily interrupt central sensitization. Systematic reviews of studies in fibromyalgia patients show short-term pain reduction, often lasting only hours after low-dose intravenous infusions, with side effects (dissociation, dizziness, nausea) that are usually transient. Some observational series and real-world reports describe longer-lasting relief in subsets of patients with repeated or higher-dose protocols, and sequential intravenous induction followed by oral maintenance has helped roughly half of one refractory cohort.
- Systematic reviews specific to fibromyalgia:
- A 2024 systematic review of 6 studies (115 patients) found short-term pain reduction (VAS scores often improved markedly right after infusion). Side effects were common during infusion but usually resolved quickly. The one study with 8-week follow-up did not show sustained benefit. Authors concluded short-term effectiveness and relative safety, but long-term data are lacking and bias risk is high.
- An earlier 2021 systematic review of 7 publications (118 patients) similarly noted only brief relief (hours) with single low-dose infusions. Case reports suggested higher total doses, longer infusions, or more frequent dosing might produce better or longer effects, but this remains unproven in controlled trials.
- Broader chronic pain evidence:
- A 2025 Cochrane review of NMDA antagonists (including ketamine) for chronic pain found no clear evidence of benefit across intermediate, short-, or medium-term outcomes versus placebo. Evidence quality was low to very low. Intravenous ketamine increased risk of psychotomimetic effects (delusions, delirium, paranoia), nausea, and vomiting. The review explicitly included conditions such as fibromyalgia.
- Observational and real-world data:
- Some larger retrospective series (including mixed chronic pain cohorts with fibromyalgia patients) report pain reductions lasting weeks to months in subsets of patients (e.g., about 30 to 50 percent achieving at least 30 to 50 percent relief in selected reports), with repeated infusions every few months. One single-day infusion cohort of refractory fibromyalgia patients showed median pain scores dropping from 8 to 5 and remaining stable out to 24 months in responders, though not everyone benefited.
- A large Cleveland Clinic series (over 1,000 chronic pain patients on a standardized low-dose protocol) found high completion rates, no serious adverse events, and modest improvements in pain interference, fatigue, and function lasting up to 6 months in a portion of patients.
- Sequential IV induction followed by oral ketamine maintenance showed complete or partial response in about half of one fibromyalgia cohort, with generally mild side effects.
Common side effects during/shortly after infusion include dissociation, hallucinations, dizziness, nausea, and blood pressure/heart rate changes. Serious events are uncommon at sub-anesthetic doses in monitored settings, but long-term risks (cognitive effects, bladder issues with repeated high exposure, dependence potential) are incompletely studied. Protocols vary widely (dose, duration, frequency), making results hard to compare.
Bottom line: Ketamine infusion can produce temporary pain relief in some people with fibromyalgia, particularly refractory cases, and may be considered in specialized pain clinics under close monitoring. However, high-quality evidence does not support consistent or durable benefit, and the 2025 Cochrane review highlights the overall lack of clear efficacy for chronic pain along with increased adverse-effect risk. Larger, rigorous randomized trials with long-term follow-up are still needed. Any decision should be individualized with a pain specialist after optimizing standard therapies.
Myth: One treatment works for everyone
Fact: Response is highly individual. Best outcomes usually come from combining education, consistent physical activity, psychological support, sleep optimization, and carefully selected medications or neuromodulation when needed. Opioids are not recommended. Ongoing research into gut microbiota, neuroimmune pathways, genetics, low-dose naltrexone, and other neuromodulatory approaches continues to refine options.
In summary, fibromyalgia is a legitimate, biologically grounded chronic pain condition. Progress in understanding its mechanisms and expanding treatment choices (from exercise and behavioral therapies to newer medications like Tonmya and selective use of tools such as TENS or, in refractory cases, carefully monitored ketamine) offers real hope. A personalized, multidisciplinary approach remains the most effective path forward. Anyone experiencing symptoms should work with a knowledgeable clinician to develop an evidence-based plan tailored to their needs.
Kayvan Haddadan is a physiatrist and pain management physician, and president and medical director of Advanced Pain Diagnostic & Solutions, a multidisciplinary pain management practice in California that he founded in 2012. A physician and surgeon licensed by the Medical Board of California, he is double board-certified in pain medicine and physical medicine and rehabilitation. He is also certified in controlled substance registration through the DEA and serves as a qualified medical examiner through California’s Department of Industrial Relations Division of Workers’ Compensation.
Dr. Haddadan earned his Bachelor of Science degree from the College of Alborz in Tehran, Iran, and his medical degree from Shahid Beheshti University of Medical Sciences. He later received his Educational Commission for Foreign Medical Graduates certification in Philadelphia, completed an internship in medical surgery at Loyola University Medical Center’s Stritch School of Medicine in Illinois, and finished his residency in physical medicine and rehabilitation at the same institution. He completed his fellowship in pain medicine at California Pacific Medical Center’s Pacific Pain Treatment Center and also trained in medical acupuncture for physicians at the University of California, Los Angeles David Geffen School of Medicine.
Dr. Haddadan has contributed to 29 research publications across multiple specialties, including pain management, cardiology, pulmonology, endocrinology, gastroenterology, and infectious disease. His work has examined topics such as hyperlipidemia in high cardiovascular risk patients, hyperuricemia and gout management, type 2 diabetes and hypertension, chronic obstructive pulmonary disease and asthma therapies, influenza treatment, irritable bowel syndrome, and opioid related complications in chronic pain care. His research has also included clinical outcome studies in spinal cord stimulation and award-winning presentations on neuropathic pain management and neuromuscular disorders.
