Good Evidence That Duloxetine, Milnacipran, and Pregabalin Provide Meaningful Pain Reduction in Adults With Fibromyalgia

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

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)

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.

Study design: Meta-analysis (other)

Funding source: Government

Setting: Various (meta-analysis)

Reference: Moore A, Bidonde J, Fisher E, et al. Effectiveness of pharmacological therapies for fibromyalgia syndrome in adults: an overview of Cochrane Reviews. Rheumatology (Oxford). 2025;64(5):2385-2394.