Fibromyalgia is a clinically well-defined chronic condition with a biopsychosocial aetiology. Fibromyalgia is characterized by chronic widespread musculoskeletal pain, sleep problems, cognitive dysfunction, and fatigue. Patients often report high disability levels and poor quality of life. Since there is no specific treatment that alters the pathogenesis of fibromyalgia, drug therapy focuses on pain reduction and improvement of other aversive symptoms.

The objective was to assess the benefits and harms of selective serotonin reuptake inhibitors (SSRIs) in the treatment of fibromyalgia.

We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 5), MEDLINE (1966 to June 2014), EMBASE (1946 to June 2014), and the reference lists of reviewed articles.

We selected all randomized, double-blind trials of SSRIs used for the treatment of fibromyalgia symptoms in adult participants. We considered the following SSRIs in this review: citalopram, fluoxetine, escitalopram, fluvoxamine, paroxetine, and sertraline.

Three authors extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion.

The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. We included seven placebo-controlled studies, two with citalopram, three with fluoxetine and two with paroxetine, with a median study duration of eight weeks (4 to 16 weeks) and 383 participants, who were pooled together.

All studies had one or more sources of potential major bias. There was a small (10%) difference in patients who reported a 30% pain reduction between SSRIs (56/172 (32.6%)) and placebo (39/171 (22.8%)) risk difference (RD) 0.10, 95% confidence interval (CI) 0.01 to 0.20; number needed to treat for an additional beneficial outcome (NNTB) 10, 95% CI 5 to 100; and in global improvement (proportion of patients who reported to be much or very much improved: 50/168 (29.8%) of patients with SSRIs and 26/162 (16.0%) of patients with placebo) RD 0.14, 95% CI 0.06 to 0.23; NNTB 7, 95% CI 4 to 17.

SSRIs did not statistically, or clinically, significantly reduce fatigue: standard mean difference (SMD) -0.26, 95% CI -0.55 to 0.03; 7.0% absolute improvement on a 0 to 10 scale, 95% CI 14.6% relative improvement to 0.8% relative deterioration; nor sleep problems: SMD 0.03, 95 % CI -0.26 to 0.31; 0.8 % absolute deterioration on a 0 to 100 scale, 95% CI 8.3% relative deterioration to 6.9% relative improvement.

SSRIs were superior to placebo in the reduction of depression: SMD -0.39, 95% CI -0.65 to -0.14; 7.6% absolute improvement on a 0 to 10 scale, 95% CI 2.7% to 13.8% relative improvement; NNTB 13, 95% CI 7 to 37. The dropout rate due to adverse events was not higher with SSRI use than with placebo use (23/146 (15.8%) of patients with SSRIs and 14/138 (10.1%) of patients with placebo) RD 0.04, 95% CI -0.06 to 0.14. There was no statistically or clinically significant difference in serious adverse events with SSRI use and placebo use (3/84 (3.6%) in patients with SSRIs and 4/84 (4.8%) and patients with placebo) RD -0.01, 95% CI -0.07 to 0.05.

There is no unbiased evidence that SSRIs are superior to placebo in treating the key symptoms of fibromyalgia, namely pain, fatigue and sleep problems. SSRIs might be considered for treating depression in people with fibromyalgia. The black box warning for increased suicidal tendency in young adults aged 18 to 24, with major depressive disorder, who have taken SSRIs, should be considered when appropriate.

Researchers of the Cochrane Collaboration conducted a review of research about the effects of antidepressants classified as serotonin reuptake inhibitors (SSRIs) on fibromyalgia. After searching for all relevant studies up to June 2014, they found seven studies that compared SSRIs with a fake medication. These studies included a total of 383 people. Most participants were middle-aged women. The SSRIs that they studied were citalopram, fluoxetine and paroxetine. Five studies were each funded by pharmaceutical companies, and two studies were funded by public institutions.

Key results
We are uncertain of the evidence of the outcomes of reduction of pain, sleep problems, fatigue, depression, global improvement (proportion of patients who reported to be much or very much improved), tolerability (dropout rates due to adverse events), and safety (serious adverse events).

Possible side effects of SSRIs may include dry mouth, nausea/vomiting, and sexual dysfunction. Rare complications may include allergies, diseases of the immune system, liver damage, and impairment of a person’s ability to drive or operate machinery; serious side effects, such as suicidal thoughts and liver failure, are very rare.

What is fibromyalgia and what are serotonin reuptake inhibitors?
People with fibromyalgia suffer from chronic widespread pain, sleep problems, and fatigue. There is no cure for fibromyalgia at present. Treatments aim at relieving the symptoms and improving health-related quality of life.

Serotonin is a chemical which is produced by the human body and is involved in the experiences of pain, sleep, and mood. Decreased concentrations of serotonin have been reported in people with fibromyalgia. SSRIs are antidepressants that increase the concentration of serotonin in the brain. SSRIs are not approved for use as fibromyalgia treatment, but are approved for depression and anxiety disorder.

Quality of the evidence
The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. Therefore we are uncertain whether taking SSRIs for an average of eight weeks improves fibromyalgia symptoms (number of people who reported that their pain was reduced by at least 30%, and number of people reporting a clinically important global improvement in pain intensity, fatigue, sleep problems, and depression).

This is the Abstract and Plain Language Summary of a Cochrane Review, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2011 Issue X, Copyright © 2011 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).

This record should be cited as: Walitt B, Urrútia G, Nishishinya MB, Riera Lizardo RJ, Cantrell SE, Häuser W. Selective serotonin reuptake inhibitors for fibromyalgia syndrome. Cochrane Database of Systematic Reviews