Drug treatments for fibromyalgia: systematic review and network meta-analysis of randomised trials.

Abstract

Objective: To compare the effectiveness of drug treatments for the management of fibromyalgia.

Design: Systematic review and network meta-analysis of randomised trials.

Data sources: Medline, Embase, AMED (Allied and Complementary Medicine Database), PsycInfo, CINAHL, and Cochrane CENTRAL (Cochrane Central Register of Controlled Trials), from inception to 13 January 2025.

Eligibility criteria for selecting studies: Parallel, crossover, and cluster randomised trials that enrolled adults (aged ≥18 years) with fibromyalgia, according to any published diagnostic criteria or as diagnosed by a physician. Trials compared commercially available, investigational, or discontinued drug treatments with another drug, the same drug at a different dose or regimen, placebo, or standard care. Treatments also included select vitamins and supplements, such as melatonin, vitamin D, vitamin B6, and omega 3 fatty acids.

Results: 151 eligible trials (32 592 participants) were included in this systematic review. Compared with placebo or usual care, low certainty evidence suggested that sodium oxybate, selective noradrenaline (norepinephrine) reuptake inhibitors (NRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), and gabapentinoids may increase the likelihood of patient reported meaningful improvement or recovery (risk difference 105 to 283 more per 1000 patients). Based on scores from the fibromyalgia impact questionnaire, low certainty evidence further suggested that sodium oxybate (mean difference -8.81, 95% confidence interval (CI) -11.78 to -5.84) and selective serotonin reuptake inhibitors (SSRIs) (mean difference -8.02, 95% CI -13.40 to -2.64) may reduce fibromyalgia symptoms, whereas tricyclic antidepressants, sodium oxybate, and gabapentinoids may improve sleep quality. No drug showed pooled effects on pain, physical health or mental health that met or exceeded a threshold for clinical importance. For sodium oxybate, selective NRIs, SNRIs, and cyclobenzaprine, responder analyses indicated that a potentially important proportion of patients achieved a reduction in pain of at least 30% (risk difference 111 to 202 more per 1000 patients). In addition, no drug increased the risk of discontinuing treatment or serious adverse events.

Conclusions: This systematic review and network meta-analysis provides low certainty evidence that sodium oxybate, selective NRIs, SNRIs, gabapentinoids, tricyclic antidepressants, and SSRIs may provide typically small benefits in select outcomes for people with fibromyalgia.

Systematic review registration: PROSPERO CRD42012003291.