Unlike other chronic conditions like diabetes or hypertension, which have specific prescription medications that target the disease, there is no single gold-standard “fibromyalgia medication” for treatment of the condition. Instead, people with fibromyalgia are often treated with a variety of medications from different disease categories, frequently with limited evidence.
Medication therapy is also not mandatory for the management of fibromyalgia, because of the limited efficacy of any one individual drug when it comes to pain reduction. In fibromyalgia patients treated with medication therapy, a reduction of 50% in pain severity score is generally achieved only by 10% to 25% of patients.1
However, improvement of the pain severity score isn’t the only outcome that matters to people with fibro. Quality of life is a frequently-measured outcome and important factor to general health. Some pharmacological treatments used to treat fibromyalgia significantly improve the quality of life for those who have the condition. Although their pain severity levels may not change, people with fibromyalgia taking medication can see improvements in their overall well-being that can impact how they live their best lives.2
Reviewing the Three FDA-Approved Medications for Fibromyalgia
Pregabalin, duloxetine, and milnacipran are the current first-line prescribed medications that are approved by the Food and Drug Administration (FDA), but have had a mostly modest effect in improving pain and other symptoms in patients with fibromyalgia. With a minority of patients expected to experience substantial benefit from these FDA-approved medications, most fibromyalgia patients will discontinue therapy because of either a lack of improvement in symptoms or due to the adverse side effects). Many non-FDA approved medication treatments have also undergone limited study and have had negative results.
This blog post will focus on the FDA-approved medications for fibromyalgia – what they are, how they work, and what to expect when taking them. Although some people may not want to take medications, and despite the available drugs being less than perfect, medication is a component of a holistic treatment strategy for many people with fibromyalgia, and knowledge about these options is power when discussing a treatment plan with your provider.
Pregabalin was approved by the FDA for the treatment of fibromyalgia in 2004. A generic version of the extended-release formulation is available in the United States as of April 2021. In 2020, it was the 78th most commonly prescribed medication in the United States, with more than 9 million prescriptions. In the US, pregabalin is a Schedule V controlled substance under the Controlled Substances Act of 1970.
Pregabalin is in a class of drugs commonly referred to as gabapentinoids. Chemically, pregabalin is a gamma-aminobutyric acid (GABA) analog, and acts by inhibiting specific calcium channels on nerve membranes. The receptor it binds to and inhibits is called the α2δ subunit of the calcium channel; when pregabalin binds to and blocks this channel, it reduces the ability for the nerve endings to release certain molecules that lead to increased pain signaling.3 Pregabalin has also been shown to promote changes within the brain by decreasing the excitability of certain areas known to increase pain transmission in fibromyalgia patients. 4
The starting FDA-approved dosage for pregabalin is at 150 mg daily; however, the drug may show a higher effectiveness when used at a doses from 300-600 mg/day.5 Many clinicians use lower pregabalin doses than those used in clinical trials because higher doses are more likely to cause significant side effects and not be well-tolerated by patients.6
Efficacy of Pregabalin for Fibromyalgia
A recent systematic review published in the Cochrane Database shows that a minority of people with moderate to severe pain due to fibromyalgia treated with a daily dose of 300 to 600 mg of pregabalin had a reduction of pain intensity over a follow-up period of 12 to 26 weeks, with tolerable adverse effects.7
In a review that I published in 20178, we found 8 studies on pregabalin in fibromyalgia patients that were found to be high-level well-conducted research (double-blinded, randomized-controlled trials) and supported the use of pregabalin for the treatment of fibromyalgia. 7 of these studies investigated pregabalin monotherapy at varying doses ranging from 150–600 mg/day and were found to have superior pain relief compared to placebo.
Side Effects of Pregabalin
Pregabalin can take a few weeks to start exerting its effects on the nervous system in order to reduce symptoms related to fibromyalgia. While there may be positive benefits that people with fibromyalgia get from this medication, there are also the possibilities of side effects. Pregabalin commonly can cause dizziness, sleepiness, and blurry vision. Taking pregabalin may also affect your ability to think clearly and one shouldn’t drive, use machinery, or do other tasks that require alertness until they know how this drug affects them.
The more common side effects of pregabalin can include:
- trouble concentrating
- blurry vision
- dry mouth
- weight gain
- swelling of your hands or feet
If these effects are mild, they may go away within a few days or a couple of weeks. However, if they’re more severe or don’t go away, it’s important to talk to a clinician or pharmacist for more guidance.
Duloxetine and Milnacipran
There are two FDA approved antidepressants that are used to treat fibromyalgia – duloxetine and milnacipran. Duloxetine and milnacipran are serotonin and norepinephrine reuptake inhibitors (SNRIs). These drugs work to increase the amount of serotonin and norepinephrine in the central nervous system, which improves pain inhibition from the brain and can improve depressive symptoms that commonly occur in people with fibromyalgia.
Duloxetine was approved by the FDA for the treatment of fibromyalgia in June 2008. In 2020, it was the 27th most commonly prescribed medication in the United States, with more than 22 million prescriptions. Milnacipran was approved by the FDA in 2009 for patients with fibromyalgia.
Efficacy of Duloxetine and Milnacipran for Fibromyalgia
A recent Cochrane Database review evaluated the use of SNRIs across eighteen studies with a total of 7,903 adults diagnosed with fibromyalgia by considering various outcomes for SNRIs, including health-related quality of life, fatigue, sleep problems, pain and patient general impression, as well as safety and tolerability.9 Within these pooled studies, 52% percent of those receiving duloxetine and milnacipran had a clinically relevant benefit over placebo compared to 29% of those on placebo.
That being said, pain relief and reduction of fatigue was not clinically relevant for duloxetine and milnacipran in 50% or greater of patients, and did not improve their quality of life.10 Other outcomes of interest that did not find positive outcomes were reducing problems in sleep and overall, the potential general benefits of duloxetine and milnacipran were outweighed by their potential harms. The authors of this Cochrane Review concluded, however, that a minority of people with fibromyalgia might experience substantial symptom relief without clinically-relevant adverse events.
Digging deeper into the double-blinded, randomized-controlled studies that identified efficacy and best dosing paradigms, in the same review I discussed earlier that I published, we found numerous studies, many with large sample sizes, showing superior efficacy in pain reduction with milnacipran compared to placebo. Our review also found many studies on duloxetine demonstrating superior efficacy of duloxetine compared to placebo at varying dosages of the drug, with 60 to 120 mg being the most commonly studied. Three studies reported efficacy of duloxetine that was not superior to placebo (one studied a 30 mg dose, one studied a 60 mg dose, and one studied either 60 or 120 mg dose) .
Side Effects of Duloxetine and Milnacipran
Duloxetine and milnacipran may take 1 to 4 weeks or longer before patients feel the full benefit of the medication. Side effects may occur when taking these medications, but people should not stop taking duloxetine without talking to your doctor, as if one suddenly stops taking duloxetine or milnacipran, you may experience withdrawal symptoms such as nausea, vomiting, diarrhea, anxiety, dizziness, tiredness, headache, pain, burning, numbness, or tingling in the hands or feet, irritability, difficulty falling asleep or staying asleep, sweating, and nightmares.
Some of the common side effects of duloxetine and milnacipran will gradually improve as your body gets used to the treatment. These common side effects of duloxetine can happen in up to 1 in 10 people and include: feeling sick to your stomach (nausea and/or vomiting, dry mouth, blurry vision, dizziness, headaches, constipation, fatigue, sweating, decreased appetite, decreased sex drive, and difficulty sleeping. Speak to a clinician or pharmacist for advice on how to cope with side effects, or if serious adverse side effects occur.
Should I Take Medication for Fibromyalgia?
As you can see, there is a lot to think about when it comes to medication therapy for fibromyalgia. These FDA-approved therapies can be considered for fibromyalgia treatment, along with non-FDA approved medications and non-drug therapies like behavioral treatment and movement.
A multimodal, personalized approach to fibromyalgia treatment can help improve symptoms and pain relief. Swing Care is here to comprehensively review your journey with fibromyalgia and identify if you are a good candidate for treatment with these and other evidence-based treatments.
1 Maffei ME. Fibromyalgia: Recent Advances in Diagnosis, Classification, Pharmacotherapy and Alternative Remedies. Int J Mol Sci. 2020 Oct 23;21(21):7877. doi: 10.3390/ijms21217877. PMID: 33114203; PMCID: PMC7660651.
2 Espejo JA, García-Escudero M, Oltra E. Unraveling the Molecular Determinants of Manual Therapy: An Approach to Integrative Therapeutics for the Treatment of Fibromyalgia and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Int J Mol Sci. 2018 Sep 9;19(9):2673. doi: 10.3390/ijms19092673. PMID: 30205597; PMCID: PMC6164741.
3 Micheva KD, Buchanan J, Holz RW, Smith SJ. Retrograde regulation of synaptic vesicle endocytosis and recycling. Nat Neurosci. 2003 Sep;6(9):925-32. doi: 10.1038/nn1114. PMID: 12910242.
4 Deitos A, Soldatelli MD, Dussán-Sarria JA, Souza A, da Silva Torres IL, Fregni F, Caumo W. Novel Insights of Effects of Pregabalin on Neural Mechanisms of Intracortical Disinhibition in Physiopathology of Fibromyalgia: An Explanatory, Randomized, Double-Blind Crossover Study. Front Hum Neurosci. 2018 Nov 19;12:406. doi: 10.3389/fnhum.2018.00406. PMID: 30510505; PMCID: PMC6252339.
5 Hirakata M, Yoshida S, Tanaka-Mizuno S, Kuwauchi A, Kawakami K. Pregabalin Prescription for Neuropathic Pain and Fibromyalgia: A Descriptive Study Using Administrative Database in Japan. Pain Res Manag. 2018 Jun 5;2018:2786151. doi: 10.1155/2018/2786151. PMID: 29973966; PMCID: PMC6008692.
6 Asomaning K, Abramsky S, Liu Q, Zhou X, Sobel RE, Watt S. Pregabalin prescriptions in the United Kingdom: a drug utilisation study of The Health Improvement Network (THIN) primary care database. Int J Clin Pract. 2016 May;70(5):380-8. doi: 10.1111/ijcp.12791. Epub 2016 Mar 29. PMID: 27028939.
7 Derry S, Cording M, Wiffen PJ, Law S, Phillips T, Moore RA. Pregabalin for pain in fibromyalgia in adults. Cochrane Database Syst Rev. 2016 Sep 29;9(9):CD011790. doi: 10.1002/14651858.CD011790.pub2. PMID: 27684492; PMCID: PMC6457745.
8 Nicol AL, Hurley RW, Benzon HT. Alternatives to Opioids in the Pharmacologic Management of Chronic Pain Syndromes: A Narrative Review of Randomized, Controlled, and Blinded Clinical Trials. Anesth Analg. 2017 Nov;125(5):1682-1703. doi: 10.1213/ANE.0000000000002426. PMID: 29049114; PMCID: PMC5785237.
9 Welsch P, Üçeyler N, Klose P, Walitt B, Häuser W. Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia. Cochrane Database Syst Rev. 2018 Feb 28;2(2):CD010292. doi: 10.1002/14651858.CD010292.pub2. PMID: 29489029; PMCID: PMC5846183.
10 Grubišić F. Are serotonin and noradrenaline reuptake inhibitors effective, tolerable, and safe for adults with fibromyalgia? A Cochrane Review summary with commentary. J Musculoskelet Neuronal Interact. 2018 Dec 1;18(4):404-406. PMID: 30511944; PMCID: PMC6313046.