EULAR | DLX 8 systematic reviews including 2–6 trials, with 443 to 2249 participants Milnacipran 7 reviews, 1–5 trials, 125-4118 participants | Häuser, W. et al. 2011 [49] | Meta-analysis, ten AMT (n = 612), four DLX (n = 1411) and five MLN (n = 4129) studies, showed that 3 drugs were superior to placebo except DLX for fatigue, MLN for sleep and AMT for quality of life. AMT was superior to DLX and MLN for pain reduction, sleep disturbance and quality fif life improvement. DLX was superior to MLN in pain reduction, sleep disturbance and quality f life improvement. MLN was superior to DLX in reducing fatigue. | Milnacipran and Duloxetine weak for (100% agreement) Level of evidence 1A. |
Perrot, S. et al. 2014 [52] | Meta-analysis. DLX showed a statistically significant improvement in reducing pain, sleep disturbance, fatigue, affective symptoms, functional deficit and cognitive impairment. MLN improved pain but had no effect on sleep disturbance, fatigue, affective symptoms and functional deficit. |
Häuser, W. et al. 2010 [21] | Review study on DLX, MLN and PGB (17 studies, n = 7739). The three drugs were superior to placebo for all outcomes. DLX and PGB were superior to MLN in reduction of pain and sleep disturbance, DLX was superior in reducing depressed mood, MLN and PGB were superior in reducing fatigue. |
Choy, E. et al. 2011 [66] | A systematic review and mixed treatment comparison, confirmed the efficacy of PGB and SNRIs in treatments of FMS. |
Häuser, W. et al. 2013 [27] | Cochrane review (n = 6038). 5 studied on Duloxetine, 5 studies on MLN. Both drugs provide a small benefit over placebo with no improvement in fatigue and quality of life (QOL). |
Sultan, A. et al. 2008 [87] | Systematic review. DLX is equally effective for the treatment of peripheral diabetic neuropathy and FM. Doses higher than 60 mg do not provide additional pain relief, but cause slightly more withdrawal due adverse effects. |
Lunn, M.P. et al. 2014 [22] | Cochrane review (n = 2249). Duloxetine in short-term (12 weeks) and long-term (28 weeks) is more effective than placebo at reducing pain (RR >30% pain, RR 1.38, 95% CI 1.22 to 1.56). There was no significant effect at 20–30 mg/day and no difference between 60 mg and 120 mg /day. |
Ormseth, M.J. et al. 2010 [24] | Review article. MLN has a demonstrated efficacy in managing global FMS symptoms and pain at doses of 100 and 200 mg divided twice daily however it has numerous side effects. |
Lunn, M.P. et al. 2014 [22] | Cochrane review on MLN for neuropathic pain in adults concluded that it was effective for a minority in the treatment of pain due to FM. |
Derry, S. et al. 2012 [23] | Cochrane review on use of MLN for neuropathic pain (n = 4138) concluded that MLN is effective in a minority in treating pain in treating pain associated with FMS. |
AWMF | No systematic reviews. Duloxetine: 5 RCTs n = 1157 in the experimental group Milnacipran | Arnold, L.M. et al. 2004 [88] | Randomised double-blind, placebo controlled trial (n = 207). DLX (120 mg/day) is effective and safe in treating any symptoms of FM. 120 mg/day resulted in more than 50% pain reduction in 3 months. | Treatment with DLX (60 mg) can be considered for a limited time period in patients without comorbid depressive disorders or generalized anxiety disorders , if treatment with AMT is not possible. MLN should not be used. EL 1a, negative recommendation, consensus. |
Arnold, L.M. et al. 2005 [89] | Randomised double-blind placebo controlled trial. DLX 60 g, 90 mg and 120 mg were effective in treatment of fibromyalgia with or without depressive symptoms. |
Arnold , L.M. et al. 2010a [90] | Randomised double blind placebo controlled trial, treatment with DLX 60, 90, 120 mg/day was associated with pain reduction, better sleep and quality of life. |
Chappell, A.S. 2009 [91] | Randomised double blind placebo controlled trial. DLX 60/120 mg failed to develop significant improvement in the co-primary outcome measures (pain and patient global impression of improvement). |
Russell, I.J. et al. 2008 [92] | Randomised double blind, placebo controlled trial (n = 1025) on MLN(100 mg/day vs. Placebo). MLN improved pain, global status, fatigue and physical and mental function. |
Arnold, L.M. et al. (2010b) [93] | Randomised double blind placebo control trial. Milnacipran administered at a dosage of 100 mg/day improved pain, global status, fatigue, and physical and mental function in patients with fibromyalgia. |
Branco, J.C. 2010 [94] | Randomised double blind, placebo controlled, multicentre clinical trial (n = 884). MLN 200 mg was associated with significant improvement. |
Clauw, D.J. et al. 2008 [26] | A 15-week, multicentre, randomised, double-blind, placebo-controlled, multi-dose trial (n = 2270) of MLN 100 g, 200 mg and placebo showed significant improvement in both doses of MLN. |
Mease, P.J. et al. 2009 [25] | Randomised double blind placebo controlled trial, on the efficacy and safety of MLN favored use of MLN in FM (n = 888). |
Vitton, O. et al. 2004 [95] | Double blind placebo-controlled trial (n = 125). 75% of treated patients reported overall improvement compared to 38% in placebo group (p < 0.01). MLN may have the potential of relieving not only pain but several other symptoms in FM. |
Canadian | | Üceyler, N. et al. 2008 [50] | Systematic review, 2 studies on DLX and 1 on Milnacipran. DLX 60–120 mg and MLN 25–500 mg/day reduce pain and depressive symptoms and improve sleep and quality if life. | Level 1 , Grade A All categories of antidepressants may be used for treatment of pain and other symptoms in fibromyalgia. |
Hauser, W. et al. 2009 [65] | Meta-analysis, 3 studies on DLX, 1 on MLN. Strong evidence for the efficacy of Duloxetine and MLN in reducing pain (smd, −0.36; 95% CI, −0.46 to −0.25; p < 0.001) and sleep disturbance. Strong evidence for DLX in improving depressed mood and quality of life. |