Abstract: Our searches identified two new published studies with classic design, and one new published study with an enriched enrolment randomised withdrawal (EERW) design. We included eight studies. Five (3283 participants) had a classic design in which participants were randomised at the start of the study to pregabalin (150, 300, 450, or 600 mg daily) or placebo, with assessment after 8 to 13 weeks of stable treatment. No studies included active comparators. Studies had low risk of bias, except that the last observation carried forward (LOCF) imputation method used in analyses of the primary outcomes could overestimate treatment effect. Pregabalin increased the number of participants experiencing substantial benefit (at least 50% pain intensity reduction after 12 or 13 weeks' stable treatment (450 mg: RR 1.8, 95% CI 1.4 to 2.1, 1874 participants, 5 studies, high quality evidence)). Substantial benefit with pregabalin 300 to 600 mg was experienced by about 14% of participants with placebo, but about 9% more with pregabalin 300 to 600 mg (22% to 24%) (high quality evidence). Pregabalin increased the number of participants experiencing moderate benefit (at least 30% pain intensity reduction after 12 or 13 weeks' stable treatment) (450 mg: RR 1.5, 95% CI (1.3 to 1.7), 1874 participants, 5 studies, high quality evidence). Moderate benefit with pregabalin 300 to 600 mg was experienced by about 28% of participants with placebo, but about 11% more with pregabalin 300 to 600 mg (39% to 43%) (high quality evidence). A similar magnitude of effect was found using PGIC of 'very much improved' and 'much or very much improved'. NNTs for these outcomes ranged between 7 and 14 (high quality evidence). A small study (177 participants) compared nightly with twice-daily pregabalin, and concluded there was no difference in effect. Two studies (1492 participants began initial dose titration, 687 participants randomised) had an EERW design in which those with good pain relief after titration were randomised, double blind, to continuing the effective dose (300 to 600 mg pregabalin daily) or a short down-titration to placebo for 13 or 26 weeks. We calculated the outcome of maintained therapeutic response (MTR) without withdrawal, equivalent to a moderate benefit. Of those randomised, 40% had MTR with pregabalin and 20% with placebo (high quality evidence). The NNT was 5, but normalised to the starting population tested it was 12. About 10% of the initial population would have achieved the MTR outcome, similar to the result from studies of classic design. MTR had no imputation concerns. The majority (70% to 90%) of participants in all treatment groups experienced adverse events. Specific adverse events were more common with pregabalin than placebo, in particular dizziness, somnolence, weight gain, and peripheral oedema, with number needed to harm of 3.7, 7.4, 18, and 19 respectively for all doses combined (high quality evidence). Serious adverse events did not differ between active treatment groups and placebo (very low quality evidence). Withdrawals for any reason were more common with pregabalin than placebo only with the 600 mg dose in studies of classic design. Withdrawals due to adverse events were about 10% higher with pregabalin than placebo, but withdrawals due to lack of efficacy were about 6% lower (high quality evidence). Pregabalin 300 to 600 mg produces a major reduction in pain intensity over 12 to 26 weeks with tolerable adverse events for a small proportion of people (about 10% more than placebo) with moderate or severe pain due to fibromyalgia. The degree of pain relief is known to be accompanied by improvements in other symptoms, quality of life, and function. These results are similar to other effective medicines in fibromyalgia (milnacipran, duloxetine).

Plain-language summary: We searched scientific databases for studies that looked at the effects of pregabalin in adults with fibromyalgia who had moderate or severe pain. The treatment had to last at least eight weeks. The evidence is current to March 2016. Eight studies satisfied the inclusion criteria, including three new studies for this update. Five studies randomised 3283 participants to immediate treatment with pregabalin or placebo. Two studies identified 687 out of 1492 participants who had a good pain response and could take the medicine, and then randomised them to continued treatment with pregabalin or placebo. Study quality was good. One other had no useful data. High quality evidence showed that 1 in 10 people with moderate or severe fibromyalgia pain reported a large fall in pain by a third to a half over 12 to 26 weeks. This is an outcome that people with fibromyalgia consider to be useful. The dose of pregabalin was 300 to 600 mg daily. Side effects occurred in 8 or 9 people in 10, often while adjusting to the medicine. Particular side effects were dizziness (affecting 1 in 4 participants), drowsiness (1 in 7), weight gain (1 in 18), and peripheral oedema (1 in 19) (high quality evidence). Serious side effects were no more common with pregabalin than with placebo, affecting 1 or 2 in 100. About 1 in 10 more participants taking pregabalin withdrew from the study because of side effects, and 1 in 17 fewer withdrew because the medicine was not working. The evidence was mostly of high quality, which means we are very confident that the true effect lies close to that of the estimate of the effect in this review. Concern about how information was handled when people left the studies was offset by other information showing that results were not impacted by this to any important degree.