Most effective treatments for fibromyalgia
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Making day-to-day life easier with fibromyalgia treatment
People living with fibromyalgia often have a lower quality of life because of widespread pain, poor sleep, fatigue, mood changes and memory problems. The condition resembles chronic fatigue syndrome and is defined by persistent, widespread pain. Its causes are still not fully understood, so treatment focuses on easing symptoms and improving daily function.
A 2022 analysis of 36 clinical trials with almost 12,000 patients compared the main fibromyalgia medications. Duloxetine (120 mg a day) brought the greatest improvement in pain and depression, while amitriptyline brought the greatest improvement in sleep, fatigue and overall quality of life. Amitriptyline was also the only medication that people did not stop more often than a placebo because of side effects. Pregabalin and milnacipran also helped. Benefits are generally modest, so the best choice depends on which symptoms bother you most.
Start with exercise and non-drug care
European (EULAR) and Canadian fibromyalgia guidelines agree that care should start with education and non-drug therapies, with medications added for severe pain or sleep problems. Exercise is the only treatment that received a strong recommendation in the European guidelines.
- Regular physical activity, including moderate aerobic exercise, strengthening, yoga, tai chi and pool exercise, can reduce pain and improve mood. Mind-body exercise such as yoga and tai chi, and combined exercise programs, also improve sleep.
- Cognitive behavioural therapy can help you build coping skills, especially if mood or sleep are affected.
- Mindfulness-based stress reduction and acupuncture may also help, alongside other treatments.
Fibromyalgia medications with proven benefit
- Duloxetine (Cymbalta), a serotonin-norepinephrine reuptake inhibitor (SNRI), is the most effective medication for pain and depression in fibromyalgia. A 2023 review of 11 trials found it better than placebo at every dose studied.
- Amitriptyline (Elavil), a tricyclic antidepressant taken at low doses, is the most effective for sleep, fatigue and quality of life, with a smaller effect on pain.
- Pregabalin (Lyrica), a medication that calms overactive nerve signals, reduces fibromyalgia pain and can improve sleep.
- Milnacipran (Savella), another SNRI, reduces pain. It is approved for fibromyalgia in the United States but is not available in Canada.
Treatments with limited or no proven benefit include SSRI antidepressants (fluoxetine, paroxetine), opioids (tramadol, oxycodone), cannabinoids, clonazepam (a benzodiazepine), phenytoin, intravenous lidocaine and growth hormone. Cyclobenzaprine, a muscle relaxant, has modest evidence and may help some people with sleep.
How your genes affect fibromyalgia medications
Genetic differences in liver enzymes can change how quickly you break down some medications. Faster metabolism can leave too little medication in your blood to work well, while slower metabolism can let it build up and cause side effects. A pharmacogenetic test shows whether you are a poor, intermediate, normal, rapid or ultrarapid metabolizer for these enzymes.
| Medication | Helps most with | Cleared by | What your genes mean |
|---|---|---|---|
| Amitriptyline (Elavil) | Sleep, fatigue, quality of life | CYP2C19 and CYP2D6 | At the low doses used for fibromyalgia, usually no dose change. CYP2D6 ultrarapid metabolizers may get too little effect, so another medication may be preferred. Poor and intermediate metabolizers should be watched for side effects. |
| Duloxetine (Cymbalta) | Pain, depression | CYP1A2 and CYP2D6 | CYP2D6 poor or ultrarapid metabolizers may have more side effects or a weaker response, but current guidelines do not give specific dose adjustments. Drug interactions also matter. |
| Pregabalin (Lyrica) | Pain, sleep | Kidneys | Not affected by genes. The dose depends on kidney function. |
| Milnacipran (Savella)* | Pain | Kidneys | Not affected by genes. |
*Not available in Canada.
The amitriptyline advice comes from the Clinical Pharmacogenetics Implementation Consortium (CPIC), which notes that dose changes based on genes are mainly needed at the higher doses used for depression. Your prescriber chooses the medication and dose with you.
How can I avoid drug interactions and side effects?
People with fibromyalgia often take more than one medication, so interactions matter:
- Amitriptyline with duloxetine, other SNRIs or SSRIs: these combinations need caution. Duloxetine can raise amitriptyline levels, and together they increase the risk of serotonin syndrome. Your prescriber may monitor you closely or choose another combination. Either medication can usually be combined with pregabalin.
- Duloxetine with strong CYP1A2 blockers: medications such as fluvoxamine can raise duloxetine levels about six-fold and should be avoided with duloxetine.
- Tramadol with antidepressants: tramadol adds to the risk of serotonin syndrome with SNRIs and SSRIs, and some antidepressants can stop it from working well. Learn more in Pain and depression drugs not working?
- Cannabinoids: cannabis products can affect the enzymes that break down amitriptyline (CYP2C19 and CYP3A4) and change its levels.
Knowledge is power
To understand how your body processes medications, you and your doctor can consider a pharmacogenetic test. Pillcheck includes a medication review by a clinical pharmacist, who provides recommendations based on your results and checks for drug interactions.
Summary
- Exercise and non-drug care are the first step in managing fibromyalgia.
- Duloxetine helps most with pain and depression, amitriptyline with sleep, fatigue and quality of life, and pregabalin with pain.
- Pharmacogenetic testing can show whether amitriptyline is likely to suit you, and a medication review can catch interactions between your medications.
Frequently asked questions
What is the most effective medication for fibromyalgia?
It depends on your main symptoms. In a large 2022 analysis, duloxetine helped most with pain and depression, and amitriptyline helped most with sleep, fatigue and quality of life.
Is exercise really a treatment for fibromyalgia?
Yes. Exercise is the only fibromyalgia treatment with a strong recommendation in the European guidelines, and both European and Canadian guidelines recommend starting with exercise and other non-drug care.
Do my genes affect fibromyalgia medications?
Mainly for amitriptyline, which is broken down by CYP2D6 and CYP2C19. Duloxetine is broken down by CYP1A2 and CYP2D6: CYP2D6 poor or ultrarapid metabolizers may have more side effects or a weaker response, although current guidelines do not give specific dose adjustments. Pregabalin and milnacipran are cleared by the kidneys.
Can I take amitriptyline and duloxetine together?
Only with caution and your prescriber's close monitoring, because duloxetine can raise amitriptyline levels and the combination increases the risk of serotonin syndrome.
References
Farag HM, Yunusa I, Goswami H, et al. Comparison of Amitriptyline and US Food and Drug Administration-Approved Treatments for Fibromyalgia: A Systematic Review and Network Meta-analysis. JAMA Netw Open. 2022;5(5):e2212939.
Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis. 2017;76(2):318-328.
Fitzcharles MA, Ste-Marie PA, Goldenberg DL, et al. 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia syndrome: executive summary. Pain Res Manag. 2013;18(3):119-126.
Hicks JK, Sangkuhl K, Swen JJ, et al. Clinical Pharmacogenetics Implementation Consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2017;102(1):37-44.
Tzadok R, Ablin JN. Current and Emerging Pharmacotherapy for Fibromyalgia. Pain Res Manag. 2020;2020:6541798.
Migliorini F, Maffulli N, Eschweiler J, et al. Duloxetine for fibromyalgia syndrome: a systematic review and meta-analysis. J Orthop Surg Res. 2023;18(1):504.
Cuenca-Martínez F, Suso-Martí L, Fernández-Carnero J, et al. Exercise-based interventions on sleep quality in patients with fibromyalgia syndrome: An umbrella and mapping review with meta-analysis. Semin Arthritis Rheum. 2023;61:152216.
