OBJECTIVES : To determine the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in treatment of fibromyalgia syndrome (FMS) by performing a meta-analysis of randomized controlled trials (RCTs).

METHODS A comprehensive search was performed on PubMed, EMBASE, and Cochrane Library from inception to November 2020. Title/abstract and full-text screening was performed on the web-based software called Covidence. The inclusion criteria included RCTs in adults (age ≥18 years) reporting the results of pain, sleep, depression, fatigue, and health-related quality of life (HRQoL), comparing SSRIs and/or SNRIs treatments with placebo using the diagnostic guidelines published by the American College of Rheumatology (ACR) in 1990, 2010 and 2016. The study quality was assessed using the JADAD score. Three authors independently extracted the data on pain, sleep, depression, fatigue, and quality of life outcomes. As all the primary outcomes represent the continuous data, effects were summarized using the standardized mean differences (SMDs) by a random-effects model.

RESULTS Twenty-one randomized controlled trials (median duration, 12 weeks) involving 6953 participants were included. There was strong evidence for an association of SSRIs and SNRIs with reduction in pain (SMD, −0.384; 95% confidence interval [95% CI], (−0.495 to −0.272), fatigue (SMD, −0.171; 95% CI, −0.229 to −0.113), depressed mood (SMD, −0.310; 95% CI, −0.457 to −0.163), and sleep disturbances (SMD, −0.199; 95% CI, −0.342 to −0.057). There was strong evidence for an association of the use of SSRIs and SNRIs with improved health-related quality of life (SMD, −0.304; 95% CI, −0.377 to −0.231).

CONCLUSIONS SSRI and SNRI medications are associated with improvements in pain, depression, fatigue, sleep disturbance, and HRQoL in patients with FMS. Off-label drugs (fluoxetine, paroxetine, and citalopram) have been shown to improve pain, sleep, depression, fatigue, and HRQoL. There is a need for large, rigorous trials to extend this body of evidence.