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Am Fam Physician. 2025;112(4):456

CLINICAL QUESTION

What are the most effective drugs for providing meaningful pain relief in adults with fibromyalgia?

BOTTOM LINE

In this synthesis of Cochrane Reviews, the authors found moderate- to good-quality evidence that duloxetine, milnacipran (Savella), and pregabalin were effective in meaningful pain relief at 4 to 12 weeks. Long-term effectiveness data are lacking. (Level of Evidence = 1a)

SYNOPSIS

The authors did an umbrella review—a synthesis of other systematic reviews and meta-analyses—of 21 Cochrane Reviews of pharmacologic treatments for fibromyalgia in adults. To be included, the analyses had to address outcomes 3 months after starting treatment. Because of the differences in outcomes and potential inclusion of randomized and nonrandomized trials, the authors chose not to pool data. Antidepressants were evaluated in seven of the Cochrane Reviews; anticonvulsants were evaluated in nine; and antipsychotics, cannabinoids, oxycodone, nonsteroidal anti-inflammatory drugs (NSAIDs), and combination therapy were evaluated in one. Overall, the reviews found no trials that included carbamazepine, clonazepam, lamotrigine, phenytoin, oxycodone, topiramate, or valproate. The authors identified very limited evidence on the effectiveness of antipsychotics, cannabinoids, combination therapy, gabapentin, lacosamide (Vimpat), monoamine oxidase inhibitors, and NSAIDs. They also found significant publication bias for studies of amitriptyline and selective serotonin reuptake inhibitors. More helpful, however, was the discovery of moderate- to good-quality evidence that for a 30% improvement in pain the number needed to treat [NNT] was 6 to 10 and for a 50% reduction in pain the NNT was 7 to 14 for duloxetine, milnacipran, and pregabalin. Patients taking duloxetine, milnacipran, or pregabalin were more likely than control patients to report meaningful global improvement (NNT = 5–22). The authors found no efficacy data beyond 6 months. The frequency of serious adverse effects was no different than with placebo.

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POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see https://www.essentialevidenceplus.com/Home/Loe?show=Sort.

Primary Care Update, a free podcast focused on POEMs, is available on Apple Podcasts and Spotify.

This series is coordinated by Natasha J. Pyzocha, DO, contributing editor.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.

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Copyright © 2025 by the American Academy of Family Physicians.

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