Comparative efficacy and acceptability of amitriptyline, duloxetine and milnacipran in fibromyalgia syndrome: a systematic review with meta-analysis

Rheumatology (Oxford). 2011 Mar;50(3):532-43. doi: 10.1093/rheumatology/keq354. Epub 2010 Nov 14.


Objectives: To evaluate and compare the efficacy and acceptability of the antidepressants amitriptyline (AMT), duloxetine (DLX) and milnacipran (MLN) for FM syndrome (FMS).

Methods: Cochrane Library, MEDLINE, SCOPUS, and were searched for randomized pharmacological placebo-controlled trials until 30 May 2010. Outcomes of interest were symptom reduction [pain, fatigue, sleep disturbance and reduced health-related quality of life (HRQOL)] and acceptability (total drop-out rates). We performed a meta-analysis of each drug vs placebo using a random-effects model and adjusted indirect analyses of the three drugs. Methodological quality was assessed by the Cochrane risk of bias tool.

Results: Ten AMT studies (612 patients), four DLX studies (1411 patients) and five MLN studies (4129 patients) met the inclusion criteria. The reported methodological quality of most AMT trials was poor, that of DLX and MLN were high. The three drugs were superior to placebo except DLX for fatigue, MLN for sleep disturbance and AMT for HRQOL. The significant effects of AMT and DLX were small and those of MLN not substantial. In adjusted indirect comparisons, AMT was superior to DLX and MLN in reduction of pain, sleep disturbances, fatigue and limitations of HRQOL. DLX was superior to MLN in reducing pain, sleep disturbances and limitations of HRQOL. MLN was superior to DLX in reducing fatigue. There were no significant differences in acceptability of the three drugs.

Conclusions: AMT cannot be regarded as the gold standard of FMS therapy with antidepressants because of the methodological limitations of its trials.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Amitriptyline / therapeutic use*
  • Antidepressive Agents / therapeutic use*
  • Cyclopropanes / therapeutic use*
  • Duloxetine Hydrochloride
  • Fibromyalgia / drug therapy*
  • Humans
  • Milnacipran
  • Thiophenes / therapeutic use*
  • Treatment Outcome


  • Antidepressive Agents
  • Cyclopropanes
  • Thiophenes
  • Amitriptyline
  • Duloxetine Hydrochloride
  • Milnacipran