Cochrane Summaries

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Serotonin and noradrenaline reuptake inhibitors for fibromyalgia

Häuser W, Urrútia G, Tort S, Üçeyler N, Walitt B
Published Online: 
30 April 2013

Researchers in the Cochrane Collaboration conducted a review of research about the effects of serotonin and noradrenaline reuptake inhibitors (SNRIs) on fibromyalgia syndrome (FMS). After searching for all relevant studies, they found 10 studies with up to 6038 people. Their findings are summarized below.

Adults with FMS, who took the SNRIs duloxetine or milnacipran rather than a fake medication (placebo), were likely to have :

- reduced pain,

- slightly improved quality of life and reduced fatigue,

- no improvement for sleep problems,

- more drug-induced side effects and a greater likelihood of stopping medication.

Serious side effects such as liver damage and suicidality were very rare. There was no difference between the SNRIs duloxetine or milnacipran and fake medication for these serious side effects.

What is fibromyalgia syndrome and what are serotonin and noradrenaline reuptake inhibitors?

People with FMS suffer from chronic widespread pain, sleep problems and fatigue. There is no cure for FMS at present, so the treatments aim to relieve the symptoms and to improve quality of life.

Serotonin and noradrenaline are chemicals which are produced by the human body, involved in the regulation of pain, sleep and mood. Low concentrations of serotonin have been reported in people with FMS. SNRIs are antidepressants that increase the concentration of serotonin and noradrenaline in the brain.

The SNRIs duloxetine and milnacipran had been approved by the US Food and Drug Administration but not by the European Medicines Agency for the management of FMS. The US and European Regulatory Authorities differed in their judgment of the efficacy and safety of both drugs. Therefore it is important to know for people with FMS and healthcare providers on the effects of SNRIs on FMS.

Best estimate of what happens to people with FMS when they take duloxetine or milnacipran after an average of 18 weeks


Pain was reduced by 50% in:

- 29 out of 100 people taking duloxetine or milnacipran

- 19 out of 100 people taking placebo.

- Therefore, 10 more people in every 100 benefited from duloxetine or milnacipran than benefited from placebo (10% absolute improvement).

Sleep problems and fatigue:

People taking duloxetine or milnacipran reported a slight reduction in fatigue and the same amount of sleep problems as people taking placebo.

Disease-related quality of life (QOL):

- People taking duloxetine or milnacipran scored their quality of life as 14 (on a scale of 0 to100),

- People taking placebo scored theirs as 10. 

- This means that people taking duloxetine or milnacipran rated their quality of life four points higher than people taking placebo.

Stopping treatment due to the side effects:

- 20 people out of 100 taking duloxetine or milnacipran stopped medication due to side effects.

- 11 people out of 100 taking fake medication stopped medication due to side effects.

- This means that 9 more people out of 100 stopped taking duloxetin or milnacipran than stopped taking fake medication because of side effects.

Serious adverse events:

There were no differences between duloxetine or milnacipran and fake medication in the number of serious adverse events.

We often do not have precise information about side effects and complications. This is particularly true for rare but serious side effects. Possible side effects may include nausea, dry mouth, headache, constipation and hyperhidrosis. Rare complications may include suicidality, liver damage, abnormal bleeding, elevated blood pressure and urinary hesitation.