Amitriptyline and FDA Treatments for Fibromyalgia Save

Both old and newer pharmacological treatments for fibromyalgia (FM) are often promoted; but a recent systematic review and network meta-analysis showed that duloxetine had higher efficacy in pain and depression, while amitriptyline had higher efficacy in treating sleep, fatigue, and quality of life outcomes.

Albeit unapproved, and off-label, amitriptyline is frequently used as is an established FM medication.  Newer agents, such as pregabalin, duloxetine, and milnacipran are approved by the US Food and Drug Administration (FDA) for use in FM.  Using data from 36 studies published between 2018 and 2020, RCT data was extracted and analyzed and subjected to a random-effects bayesian network meta-analysis (NMA).

Study drugs and doses included 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).

Data from 11 930 patients were included, with a mean age of 48 years, and 94% being women.  

Key Findings:

• Amitriptyline - 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); compared to placebo.
• 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 higher that acceptable dropout rates (vs PBO), except amitriptyline (OR, 0.78; 95% CrI, 0.31 to 1.66).

Overall, duloxetine 120 mg was associated with higher efficacy for treating pain and depression, while amitriptyline was associated with higher efficacy for improving sleep, fatigue, and overall quality of life.

Not all FM approved therapies are equally effective and amitripyline has utility in sleep, fatigue and QOL, despite it's off-label status.