Cochrane for Clinicians

Putting Evidence into Practice

Selective Serotonin Reuptake Inhibitors for Fibromyalgia


Am Fam Physician. 2016 Oct 1;94(7):548-549.

Author disclosure: No relevant financial affiliations.

Clinical Question

Would a selective serotonin reuptake inhibitor (SSRI) improve worsening fatigue, pain, and depression in a patient with fibromyalgia?

Evidence-Based Answer

SSRIs may have a small to moderate effect on pain (number needed to treat [NNT] = 10), global improvement (NNT = 7), and depression (NNT = 13) in patients with fibromyalgia, but the quality of evidence is very low because of bias and small studies. SSRIs do not reduce fatigue related to fibromyalgia.1 (Strength of Recommendation: B, based on very low–quality randomized controlled trials.)

Practice Pointers

Fibromyalgia is a poorly understood disorder characterized by chronic, widespread pain that is often complicated by severe fatigue, mood disturbance, and sleep difficulties.2 It affects 2% to 8% of the population, depending on the diagnostic criteria used.2,3 The widespread nature of the pain and confirmation of a biologic basis of the disorder via brain neuroimaging have led clinicians to believe that SSRIs may be helpful in managing the symptoms of the disorder.

This Cochrane meta-analysis reviewed eight double-blind randomized controlled trials that included 383 patients.1 The only SSRIs examined were citalopram (Celexa), fluoxetine (Prozac), and paroxetine (Paxil), and the studies lasted from four to 16 weeks. The overall quality of evidence from the studies was judged to be very low because of the small number of participants as well as concerns about bias, including pharmaceutical funding in a majority of the trials. The authors evaluated seven primary outcomes and four secondary outcomes for this review.

Six of the eight studies examined whether patients had at least 30% pain reduction. SSRIs were superior to placebo, but the confidence interval (CI) was wide (NNT = 10; 95% CI, 5 to 100). SSRIs were also superior to placebo in global improvement measures (NNT = 7; 95% CI, 4 to 17). Two of the eight studies compared SSRIs with other active drugs, including amitriptyline and melatonin, for the outcomes of 30% pain reduction and global improvement, and did not show a statistically significant difference.

SSRIs were found to be superior to placebo for depression symptoms in patients with fibromyalgia (NNT = 13; 95% CI, 7 to 37), although they were not significantly different compared with other active agents. There were no statistically significant differences in measures of fatigue or sleep problems. SSRIs were found to be as tolerable and safe as placebo.

SSRIs were also superior to placebo for improvements in pain intensity (standardized mean difference [SMD] = −0.37; 95% CI, −0.69 to −0.04) as well as disease-specific quality of life (SMD = −0.70; 95% CI, −1.12 to −0.28). No significant differences were noted between SSRIs and other active agents for these secondary outcomes. There were also no differences between SSRIs and placebo for physical functioning, anxiety, or tenderness.

Although a small, statistically significant benefit was detected for 30% pain reduction, global improvement, and depression with SSRIs vs. placebo in this meta-analysis, the quality of evidence was very low because of the limited numbers of patients and the potential for attrition and reporting bias. Five of the eight studies were sponsored by drug companies. Limitations of the analysis include different outcome assessment tools used in various studies, low number of studies because of strict exclusion criteria, and short study lengths (i.e., none longer than four months). Despite the limited evidence, the Department of Veterans Affairs/Department of Defense clinical practice guideline for chronic multisystem illness, which includes fibromyalgia, suggests considering SSRIs as an adjunctive treatment.4 The positive results in some studies and the limited therapies available for fibromyalgia suggest that more research is warranted.

The practice recommendations in this activity are available at

editor's note: The NNTs reported in this Cochrane for Clinicians were calculated by AFP medical editors from raw data provided in the original Cochrane review.

The views presented in this article are those of the authors and do not represent the views of the U.S. Army, the U.S. Air Force, the Department of Defense, or the U.S. government.

Author disclosure: No relevant financial affiliations.


show all references

1. Walitt B, Urrútia G, Nishishinya MB, Cantrell SE, Häuser W. Selective serotonin reuptake inhibitors for fibromyalgia syndrome. Cochrane Database Syst Rev. 2015;(6):CD011735....

2. Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014;311(15):1547–1555.

3. American College of Rheumatology. Fibromyalgia. Accessed January 2016.

4. Department of Veterans Affairs/Department of Defense. VA/DoD clinical practice guideline for the management of chronic multisymptom illness. Accessed March 2016.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, Assistant Medical Editor.

A collection of Cochrane for Clinicians published in AFP is available at



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