The quality of evidence is downgraded by study limitations (unclear allocation concealment and high loss to follow-up in relation to observed absolute effect).
A Cochrane review included 6 studies with a total of 4 238 subjects with fibromyalgia. The studies used titration to a target dose of 100 mg or 200 mg milnacipran. The vast majority of participants were women (92% to 97%) and the mean age was 47 to 50 years. Both doses of milnacipran provided moderate levels (≥ 30%) of pain relief (table ). Adverse events were common in both milnacipran and placebo groups, but serious adverse events (< 2%) did not differ between groups. Nausea, constipation and headache were the most common events showing the greatest difference between milnacipran and placebo (number needed to treat for an additional harmful outcome (NNH) of 5.7 for nausea, 13 for constipation, and 29 for headache). Withdrawals for any reason were more common with milnacipran than placebo, and more common with 200 mg than 100 mg (NNH of 23 and 9 respectively, compared with placebo). This was largely driven by adverse event withdrawals (table ).
| Outcome | Daily dose | Number of patients (studies) | Per cent with outcome | Relative effect RR (95% CI) | NNT (95% CI) | |
|---|---|---|---|---|---|---|
| Placebo | Milnacipran | |||||
| Substantial response: ≥ 50% reduction in pain | 100 mg | 1 250 (2) | 18% | 27% | 1.6 (1.3 to 2.0) | 10 (7.0 to 20) |
| 200 mg | 125 (1) | 14% | 28% | not calculated | not calculated | |
| Moderate response: ≥ 30% reduction in pain | 100 mg | 1 925 (3) | 30% | 41% | 1.4 (1.2 to 1.6) | 9 (6.5 to 15) |
| 200 mg | 1 798 (3) | 29% | 39% | 1.4 (1.2 to 1.5) | 10 (7.0 to 18) | |
| Adverse event withdrawals | 100 mg | 2 379 (4) | 12% | 19% | 1.6 (1.3 to 2.0) | 14 (10 to 24) |
| 200 mg | 2 470 (4) | 9.5% | 24% | 2.5 (2.0 to 3.1) | 7.0 (5.8 to 8.7) | |
| Serious adverse events | 100 mg | 2 378 (4) | 1.6% | 1.5% | 0.90 (0.47 to 1.7) | not calculated |
| 200 mg | 2 463 (4) | 2.1% | 1.9% | 0.91 (0.52 to 1.6) | not calculated | |
Another Cochrane review included 10 studies with a total of 6 038 subjects. Five studies (n=4 118) investigated milnacipran (100–200 mg daily) against placebo. Milnacipran had a small beneficial effect over placebo on pain, fatigue, and disease-related quality of life (table ). The dropout rate due to adverse events in the milnacipran group was higher than in placebo group. There was no statistically significant difference in serious adverse events.
| Outcome | Participants (studies) | Assumed risk–Placebo | Corresponding risk–Milnacipran (95% CI) | Effect size (95% CI) |
|---|---|---|---|---|
| 50% pain reduction | 4 110 (5) | 20% | 28% (25 to 32%) | RR 1.38 (1.25 to 1.51) |
| Pain | 4 087 (5) | SMD -0.20 (-0.26 to -0.13) | ||
| Fatigue | 4 088 (5) | SMD -0.14 (-0.21 to -0.08) | ||
| Sleep problems | 3 085 (4) | SMD 0.02 (-0.05 to 0.10) | ||
| Disease-related quality of life | 4 077 (5) | SMD -0.18 (-0.24 to -0.11) | ||
| Withdrawal due to adverse events | 4118 (5) | 10% | 20% (14 to 27%) | RR 2.00 (1.47 to 2.73) |
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