Efficacy of Selective Serotonin Reuptake Inhibitors for the Treatment of Chronic Pain and Comorbid Depression in Individuals With Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Fibromyalgia causes symptoms like chronic widespread pain, fatigue, and cognitive difficulties, often alongside depression and chronic pain, complicating treatment. While selective serotonin reuptake inhibitors (SSRIs) are prescribed for fibromyalgia-related depression and pain, their effectiveness is unclear. This systematic review and meta-analysis evaluated SSRI efficacy in fibromyalgia patients with comorbid depression and chronic pain. This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Ovid, and Google Scholar. We included randomized controlled trials (RCTs) using formal fibromyalgia criteria and reporting depression or pain outcomes. Non-RCTs, studies with non-adults, or non-SSRI comparisons without isolating SSRI effects were excluded. The Cochrane risk-of-bias tool for randomized trials (RoB-2) was used to assess the risk of bias in this study. Four reviewers independently screened titles and abstracts; four assessed full-texts with disagreements resolved by a senior reviewer. Outcome data were converted to mean change scores from baseline where not directly reported. The standardized mean difference (SMD) was used for the meta-analysis to pool data across different scales. Nine RCTs (n = 461 participants, predominantly female, mean ages across studies ranged from 32.7 to 52.9 years) were analyzed. Compared to placebo, SSRIs significantly reduced pain (eight RCTs, n = 421; SMD -0.53, 95% confidence interval (CI): -0.92 to -0.14, p = 0.007) and improved depression (six RCTs, n = 265; SMD -0.67, 95% CI: -1.14 to -0.20, p = 0.005). SSRIs also significantly improved quality of life (QOL) versus placebo (five RCTs, n = 301; SMD -0.30, 95% CI: -0.55 to -0.04, p = 0.02). Compared to other non-pharmacological interventions (acupuncture and aerobic exercise), SSRIs showed non-significant improvement in depression (two RCTs, n = 70; SMD -0.39, 95% CI: -1.32 to 0.54, p = 0.41). Common side effects included gastrointestinal issues, dry mouth, sedation, sexual dysfunction, and headaches; SSRI groups reported more adverse events and higher dropout rates. SSRIs showed statistically significant benefits for pain, depression, and QOL in fibromyalgia compared to placebo. However, the overall evidence quality was found to be very low to low due to heterogeneity and risk of bias. Future RCT designs should adhere to a strict methodology in order to strengthen the available evidence on the efficacy of SSRIs in treating fibromyalgia.