January 15, 2009 — Evidence from a meta-analysis of 18 trials of antidepressants in the treatment of fibromyalgia syndrome (FMS) shows that these drugs can improve FMS-associated symptoms of pain, sleep disturbance, depressed mood, and health-related quality of life (HRQOL). However, effect sizes vary significantly between classes of antidepressants.

Overall, there was strong evidence for a reduction of FMS symptoms with antidepressant use. However, effect sizes on pain with different classes of antidepressants varied, with small effect sizes associated with use of selective serotonin-reuptake inhibitors (SSRIs) and serotonin- and noradrenalin-reuptake inhibitors (SNRIs), medium effect sizes with use of monoamine oxidase inhibitors (MAOIs), and large effect sizes associated with tricyclic and tetracyclic antidepressants (TCAs).

The study is published January 14 in the Journal of the American Medical Association.

Analgesic Effect of Antidepressants

Fibromyalgia, which is estimated to affect 0.5% to 5.8% of people in North America and Europe, is characterized by widespread pain and tenderness as well as fatigue and nonrestorative sleep, the researchers write.

Antidepressants are the drugs most often studied for treatment of FMS, and some antidepressants (TCAs and SNRIs) have an analgesic effect independent of their effect on depressed mood; that is, patients may experience a reduction in pain even if they are not depressed, lead researcher Winfried Häuser, MD, from Klinikum Saarbrücken, in Germany, told Medscape Psychiatry.

The most recent meta-analysis of clinical trials of antidepressants for FMS was done in 2000. However, it did not include recent trials of duloxetine and milnacipran.

To evaluate the effect of antidepressants on symptoms of FMS in clinical trials up to 2008, the researchers performed a meta-analysis of 18 randomized, controlled clinical trials conducted mainly in the United States, Canada, and Western Europe.

Participants included 1427 outpatients, almost all women, with a mean age of 47 years, who had no severe somatic disease or severe mental disorders. Duration of the studies ranged from 4 to 28 weeks and investigated 4 classes of antidepressants:

  • TCAs: amitriptyline (7 studies), nortriptyline (1 study).
  • SSRIs: fluoxetine (3 studies), citalopram (2 studies), and paroxetine (1 study).
  • SNRIs: duloxetine (3 studies) and milnacipran (1 study).
  • MAOIs: moclobemide (2 studies) and pirlindole (1 study).

Consider Potential Adverse Effects

The researchers found that amitriptyline had a large effect on reducing pain, fatigue, and sleep disturbances, a small effect on HRQOL, and no significant effect on mood.

In addition, they found that the SSRIs fluoxetine and paroxetine had a small effect on reducing pain and improving HRQOL but had no effect on fatigue or sleep.

SNRIs duloxetine and milnacipran had a small effect on reducing pain and sleep disturbances, and duloxetine had a small effect on improving mood and HRQOL, but no effect on fatigue.

The MAOIs moclobemide and pirlindole had a small effect on pain reduction. Moclobemide had no effect on sleep or fatigue, and pirlindole did not affect depressed mood.

Reported rates of adverse effects were similar in subjects treated with antidepressants (75.5%) and those treated with placebo (62.5%), as were dropout rates due to adverse effects.

“Short-term use of amitriptyline and duloxetine can be considered for the treatment of pain and sleep disturbances in FMS,” said Dr. Häuser.

However, before treatment is initiated, potential adverse effects from the drug should be considered, and alternate treatments such as psychotherapy or balneotherapy (treatment with baths) should be discussed, he added.

Realistic Expectations

Since there is still no evidence for long-term benefits from antidepressant therapy in FMS, patients need to be monitored regularly to ensure that a drug’s benefits outweigh any adverse effects, he cautioned.

“We hope patients and clinicians will develop realistic expectations about antidepressant therapy in FMS, since these agents may reduce symptoms but don’t provide a cure,” said Dr. Häuser.

According to the authors, there is a need for longer clinical trials with broader patient populations to identify patient characteristics associated with positive and negative therapeutic outcomes.

The study was supported by funding from the German Rheumatology League, the German Fibromyalgia Association, the German Ministry of Education and Research, the German Research Network on Neuropathic Pain, and the University of Würzburg. Dr. Häuser discloses that he has received honoraria for educational talks from Lilly, Mundipharma, Pfizer, and Janssen-Cilag. He received travel grants for scientific conferences from Lilly and Pfizer. He will receive consulting honoraria from Lilly and Pfizer. The financial disclosures of the other authors are listed in the paper.

JAMA. 2009; 301:198-209. Abstract

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Marlene Busko is a staff journalist for Medscape Psychiatry. She can be contacted at mbusko@medscape.net.

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