Amitriptyline for fibromyalgia: Off-label treatment, but non-inferior to approved medication.

Abstract

Fibromyalgia (FM) is a chronic and widespread musculoskeletal pain disorder. The prevalence of FM is 2.7% worldwide, especially in women and in patients over the age of 50.1 The main symptoms of FM are chronic pain, fatigue, depression, and insomnia. FM is also associated with a variety of diseases.2-4 Patients commonly experience chronic and widespread pain. The clinical presentation may have a negative impact on the quality of life. The prognosis for FM is generally poor. Most patients experience only partial relief of symptoms and there is a risk of recurrence and chronic pain. In severe cases, the patient may even become too disabled to carry out daily tasks. The management of FM is currently divided between pharmacological and non-pharmacological therapies. Patients often use a variety of strategies to manage their pain and comorbidities.5, 6 There are three drugs currently approved by the US Food and Drug Administration (FDA) for the treatment of FM, which are pregabalin, duloxetine, and milnacipran. Amitriptyline is a tricyclic antidepressant that is widely used off-label for the treatment of FM;7 some studies even suggest that low doses of amitriptyline are the first choice for the treatment of FM.8 However, off-label policy use makes the definition of true efficacy and acceptability unclear. The lack of comparisons with other drugs may overestimate the clinical efficacy of amitriptyline. Recently, Farag et al9 published a network meta-analysis (NMA) to evaluate the effectiveness and acceptability of amitriptyline compared with other FDA-approved therapeutic agents. A total of 36 randomized clinical trials (11 930 patients) were included. NMA enables comparisons that cannot be made in clinical studies or traditional meta-analyses. This NMA confirms the results associated with the treatment of FM with pregabalin, duloxetine, and milnacipran. It was also found that the use of amitriptyline was associated with improvements in sleep disturbances (standardized mean difference [SMD], −0.97; 95% CI, −1.10 to −0.83) and quality of life (SMD −0.80; 95% CI, −0.94 to −0.65), fatigue (SMD, −0.64; 95% CI, −0.75 to −0.53), and small improvements in pain (SMD, −0.27; 95% CI, −0.21 to −0.32) compared with placebo. The NMA shows that amitriptyline is no less effective than other drugs in the treatment of symptoms of FM. The results of the study are presented in Table 1. Fibromyalgia brings a large economic burden to the healthcare system and society, with drugs being the main source of total costs.10, 11 In the previous cost-effectiveness analysis, amitriptyline, pregabalin, and duloxetine are considered cost-effective medications for FM. Most notably, amitriptyline is the drug of preference and the most cost-effective.12 In conclusion, the proven efficacy and acceptability of amitriptyline in fibromyalgia is an encouragement to both medical professionals and patients. Clinicians can choose the appropriate medication through shared decision-making with fibromyalgia patients based on disease severity, co-morbidities, and tolerability. Dr. James Wei is an Editorial Board member of APL and a co-author of this article. To minimize bias, he was excluded from all editorial decision-making related to the acceptance of this article for publication.