Amitriptyline for the treatment of fibromyalgia: a comprehensive review

Abstract

Fibromyalgia is characterized by chronic generalized pain accompanied by a wide range of clinical manifestations. Most clinical practice guidelines recommend multidisciplinary treatment using a combination of pharmacological and non-pharmacological therapies. The tricyclic antidepressant amitriptyline has been most thoroughly studied in fibromyalgia. Amitriptyline has been evaluated in placebo-controlled studies, and it has served as an active comparator to other therapeutic interventions in the treatment of fibromyalgia. In addition, several systematic reviews and meta-analyses have evaluated its efficacy and safety for the treatment of fibromyalgia. Data from individual studies as well as from systematic reviews indicate that low doses (10–75 mg/day) of amitriptyline are effective for the treatment of fibromyalgia and, despite the limited quality of the data, they do not seem to be associated with relevant tolerability or safety issues. Consistent with some clinical guidelines, we believe amitriptyline in low doses should be considered a first-line drug for the treatment of fibromyalgia.

Keywords:

• amitriptyline
• antidepressants
• clinical practice guidelines
• fibromyalgia management
• randomized clinical trials
• review
• systematic reviews

Financial & competing interests disclosure

F Rico-Villademoros has served as a freelance consultant for Almirall, AstraZeneca, Eli Lilly, GSK, Lundbeck, Pfizer, Roche and Sanofi-Aventis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Fibromyalgia is a disabling and difficult to treat chronic painful condition.

• The management of fibromyalgia involves, in most patients, the combination of non-pharmacological and pharmacological interventions.

• Amitriptyline is an antidepressant with an unselective mechanism of action, responsible for its poor tolerability profile but also for its efficacy for the treatment of some chronic painful conditions.

• We reviewed 10 placebo-controlled pharmacological trials, 11 active-controlled trials or comparison with non-pharmacological interventions, seven systematic reviews, and four clinical practice guidelines involving the study of amitriptyline for the treatment of fibromyalgia.

• The quality of many of the randomized controlled trials with amitriptyline was low to moderate.

• Randomized clinical trials and systematic reviews indicate that, in patients with fibromyalgia, amitriptyline reduces pain and sleep disturbances to a clinically relevant extent.

• Despite the limited quality of data, they suggest that amitriptyline at low doses is not associated with major tolerability or safety issues.

• Overall, we think that amitriptyline at low doses (10–75 mg/day) should be considered a first-line option for the treatment of fibromyalgia.