Amitriptyline use tied to favorable efficacy in the treatment of fibromyalgia: JAMA

Amitriptyline is an established medication used off-label for the treatment of fibromyalgia. Still, pregabalin, duloxetine, and milnacipran are the only pharmacological agents approved by the US Food and Drug Administration (FDA) to treat fibromyalgia.

A study was conducted to investigate the comparative effectiveness and acceptability associated with pharmacological treatment options for fibromyalgia.

This study follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. Four independent reviewers extracted data using a standardized data extraction sheet and assessed the quality of RCTs. A random-effects Bayesian network meta-analysis (NMA) was conducted. Data were analyzed from August 2020 to January 2021.

Comparative effectiveness and acceptability (defined as discontinuation of treatment owing to adverse drug reactions) associated with amitriptyline (off-label), pregabalin, duloxetine, and milnacipran (on-label) in reducing fibromyalgia symptoms. The following doses were compared: 60-mg and 120-mg duloxetine; 150-mg, 300-mg, 450-mg, and 600-mg pregabalin; 100-mg and 200-mg milnacipran; and amitriptyline. Effect sizes are reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with 95% credible intervals (95% CrIs). Findings were considered statistically significant when the 95% CrI did not include the null value (0 for SMD and 1 for OR). Using the surface under the cumulative ranking curve (SUCRA), relative treatment ranking was also evaluated.

Results:

A total of 36 studies (11 930 patients) were included. The mean (SD) age of patients was 48.4 (10.4) years, and 11 261 patients (94.4%) were women. Compared with placebo, amitriptyline was associated with reduced sleep disturbances (SMD, −0.97; 95% CrI, −1.10 to −0.83), fatigue (SMD, −0.64; 95% CrI, −0.75 to −0.53), and improved quality of life (SMD, −0.80; 95% CrI, −0.94 to −0.65). Duloxetine 120 mg was associated with the highest improvement in pain (SMD, −0.33; 95% CrI, −0.36 to −0.30) and depression (SMD, −0.25; 95% CrI, −0.32 to −0.17) vs placebo. All treatments were associated with inferior acceptability (higher dropout rate) than placebo, except amitriptyline (OR, 0.78; 95% CrI, 0.31 to 1.66). According to the SUCRA-based relative ranking of treatments, duloxetine 120 mg was associated with higher efficacy for treating pain and depression. In comparison,favourable amitriptyline was associated with higher efficacy for improving sleep, fatigue, and overall quality of life.

These findings suggest that clinicians should consider how treatments could be tailored to individual symptoms, weighing the benefits and acceptability, when prescribing medications to patients with fibromyalgia.

Reference:

Comparison of Amitriptyline and US Food and Drug Administration–Approved Treatments for Fibromyalgia: A Systematic Review and Network Meta-analysis by Hussein M. Farag, et al. published in the JAMA Netw Open.

doi:10.1001/jamanetworkopen.2022.12939

Keywords:

Comparison, Amitriptyline, US, Food and Drug Administration, Approved, Treatments, Fibromyalgia, Systematic Review, Network Meta-analysis, Hussein M. Farag, Ismaeel Yunusa, Hardik Goswami, Ihtisham Sultan, Joanne A. Doucette, Tewodros Eguale, JAMA Netw Open