BARCELONA, Spain—The tricyclic antidepressant amitriptyline (Elavil) may not be effective for long-term treatment of fibromyalgia, according to a review article published online in Rheumatology,1 but questions have been raised about the quality of the trials included in the analysis.

“These trials are all fixed doses, which underestimates the benefits of the drug…these are very small trials. I think people should still be trying amytriptiline in fibromyalgia and this should not discourage them.”—Daniel J. Clauw, MD
“There is some evidence supporting the efficacy of amitriptyline 25 mg for the short-term treatment of fibromyalgia symptoms although better studies are needed to specify the magnitude of the effect and its clinical relevance,” conclude researchers who were led by Betina Nishishinya, MD, of the Universitat Autònoma de Barcelona in Spain. “There is no evidence supporting the use of higher doses of amitriptyline or using it for periods longer than 6 weeks.”

The new review analyzed 10 randomized, controlled trials comparing amitriptyline with placebo, which found that amitriptyline 25 mg/day improved pain, sleep, fatigue, and overall patient and researcher impression.

However, these benefits were generally seen at 6 to 8 weeks, with no effect noted at 12 weeks, the review concluded. There was no benefit seen for amitriptyline 50 mg/day, which was analyzed in four clinical trials. Neither the 25 mg nor the 50 mg dose had any effect on tender joint count.

The discrepancies in efficacy by dose were “not an anticipated finding,” the researchers write. Moreover, the study only looks at amitryptyline as monotherapy, “which gives little insight into its efficacy as part of a multidisciplinary treatment plan that couples combinations of pharmacological therapies with nonpharmacological cognitive and physical therapies that are currently recommended in clinical treatment,” they conclude.

(Not) translating research into practice

Daniel J. Clauw, MD, professor of medicine in the division of rheumatology and director of the chronic pain and fatigue research center at the University of Michigan, in Ann Arbor, cautioned that the new review should not influence clinicians’ use of amitryptyline for the treatment of fibromyalgia.

“The studies were done extremely poorly,” he told MSKreport.com. “We know you have to dose it…to find the right dose [and] these trials are all fixed doses, which underestimates the benefits of the drug…these are very small trials,” he said. “I think people should still be trying amytriptiline in fibromyalgia and this should not discourage them.”

Reference
1. Nishishinya B, Urrútia G, Walitt B, et al. Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy. [published online ahead of print August 12 2008]. Rheumatology. 2008. http://rheumatology.oxfordjournals.org/cgi/content/abstract/ken317.