A Cochrane review [Abstract] 1 included 25 studies with a total of 7 652 subjects. Five studies (n= 3 323) examined the effects of pregabalin in fibromyalgia. Study duration was mainly between 8 and 14 weeks, and pregabalin was compared with placebo in all studies. One study used complete enriched enrolment randomised withdrawal (EERW) design which is very different from classic randomised design so its results are discussed separately.
Table 1 T1 shows results for efficacy outcomes with different doses of pregabalin (classic trial design only). There tended to be a greater response with a higher dose of up to 450 mg; 600 mg seemed to produce no better results than 450 mg for any outcome. A daily dose of 150 mg pregabalin was not significantly different from placebo on any measure.
The EERW trial used a 6-week open titration; participants who obtained a substantial benefit and had tolerable adverse events (54%) then entered a randomised, double blind, 26-week withdrawal phase in which either the established dose or placebo was used. For pregabalin, 32% experienced loss of therapeutic response over 26 weeks, compared with 61% with placebo. The NNT to prevent one patient experiencing a loss of treatment response for fibromyalgia was 3.5 (95% CI 2.8 to 4.9).
| Outcome | Daily dose | Number of patients (studies) | Per cent with outcome | Relative effect RR (95% CI) | NNT (95% CI) | ||
|---|---|---|---|---|---|---|---|
| Placebo | Pregabalin | ||||||
| At least 30% pain relief | 150 mg | 263 (1) | 27 | 31 | 1.1 (0.8 to 1.7) | - | |
| 300 mg | 1374 (4) | 28 | 39 | 1.4 (1.2 to 1.6) | 9 (6 to 17) | ||
| 450 mg | 1376 (4) | 28 | 43 | 1.5 (1.3 to 1.8) | 7 (5 to 10) | ||
| 600 mg | 1122 (3) | 28 | 39 | 1.4 (1.2 to 1.6) | 9 (6 to 18) | ||
| At least 50% pain relief | 150 mg | 263 (1) | 13 | 13 | 1.0 (0.5 to 1.9) | - | |
| 300 mg | 1374 (4) | 14 | 21 | 1.5 (1.2 to 1.9) | 14 (9 to 33) | ||
| 450 mg | 1376 (4) | 14 | 25 | 1.7 (1.4 to 2.1) | 10 (7 to 16) | ||
| 600 mg | 1122 (3) | 15 | 24 | 1.6 (1.3 to 2.1) | 11 (7 to 21) | ||
| Patient Global Impression of Change (PGIC) much or very much improved | 150 mg | 263 (1) | 27 | 32 | 1.2 (0.8 to 1.8) | - | |
| 300 mg | 1374 (4) | 28 | 36 | 1.5 (1.2 to 1.9) | 11 (7 to 26) | ||
| 450 mg | 1376 (4) | 28 | 42 | 1.5 (1.3 to 1.8) | 7 (5 to 10) | ||
| 600 mg | 1122 (3) | 28 | 41 | 1.5 (1.2 to 1.7) | 8 (5 to 13) | ||
| PGIC very much improved | 150 mg | no data | |||||
| 300 mg | 1352 (4) | 11 | 17 | 1.7 (1.2 to 2.9) | 16 (10 to 37) | ||
| 450 mg | 1354 (4) | 11 | 19 | 1.8 (1.4 to 2.4) | 11 (8 to 20) | ||
| 600 mg | 1095 (3) | 7 | 12 | 1.7 (1.1 to 2.4) | 21 (12 to 83) | ||
| Lack of efficacy discontinuation | 150 mg | 263 (1) | 14 | 9 | 0.7 (0.3 to 1.3) | - | |
| 300 mg | 1374 (4) | 10 | 4 | 0.4 (0.3 to 0.7) | 18 (12 to 34) | ||
| 450 mg | 1376 (4) | 10 | 3 | 0.3 (0.2 to 0.5) | 15 (11 to 25) | ||
| 600 mg | 1122 (3) | 9 | 2 | 0.3 (0.2 to 0.5) | 15 (11 to 26) | ||
Results for adverse events are shown in Table 2 T2. Higher doses produced higher adverse event rates with pregabalin. In the EERW study, 82% of participants entering the open label phase experienced at least one adverse event. The most common adverse events during this phase were dizziness and somnolence. 19% withdrew during the open label phase because of adverse events. Of the participants entering the double blind phase, 45% of participants in the placebo group, 59% of participants taking 300 mg, 63% taking 450 mg, and 62% taking 600 mg pregabalin experienced an adverse event. During the open label phase, serious adverse events occurred in 8/1051 participants (0.8%).
| Outcome | Daily dose | Number of patients (studies) | Per cent with outcome | Relative effect RR (95% CI) | NNH (95% CI) | |
|---|---|---|---|---|---|---|
| Placebo | Pregabalin | |||||
| Somnolence | 150 mg | 263 (1) | 5 | 16 | 3.5 (1.5 to 8.3) | 9 (5 to 24) |
| 300 mg | 1374 (4) | 5 | 20 | 4.0 (2.8 to 5.8) | 7 (6 to 9) | |
| 450 mg | 1376 (4) | 5 | 21 | 4.2 (2.9 to 6.0) | 6 (5 to 8) | |
| 600 mg | 1122 (3) | 5 | 23 | 4.5 (3.1 to 6.7) | 6 (5 to 7) | |
| Dizziness | 150 mg | 527 (3) | 10 | 13 | 1.3 (0.8 to 2.1) | - |
| 300 mg | 1374 (4) | 10 | 32 | 3.1 (2.4 to 3.9) | 5 (4 to 6) | |
| 450 mg | 1376 (4) | 10 | 43 | 4.1 (3.2 to 5.2) | 3 (3 to 4) | |
| 600 mg | 1122 (3) | 10 | 46 | 4.4 (3.4 to 5.8) | 3 (2.5 to 3.2) | |
| Adverse event discontinuation | 150 mg | 263 (1) | 8 | 8 | 1.1 (0.5 to 2.5) | - |
| 300 mg | 1374 (4) | 10 | 16 | 1.6 (1.2 to 2.1) | 17 (11 to 43) | |
| 450 mg | 1377 (4) | 10 | 20 | 1.9 (1.5 to 2.5) | 11 (8 to 18) | |
| 600 mg | 1122 (3) | 11 | 28 | 2.5 (1.9 to 3.3) | 6 (5 to 8) | |
Some patients will not have a useful benefit with pregabalin, and for those individuals another therapeutic intervention should be tried.
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