Review: Pregabalin reduces fibromyalgia pain but increases adverse events

Question In patients with fibromyalgia pain, what are the efficacy and safety of pregabalin? Review scope Included studies compared pregabalin with placebo or an active comparator in adults 18 years of age who had pain due to fibromyalgia. Primary outcomes were patient-reported pain relief 30% and 50%, moderate pain relief on the Patient Global Impression of Change scale [PGIC] (much or very much improved), and substantial pain relief on the PGIC (very much improved). Secondary outcomes included adverse events and withdrawals due to adverse events or lack of efficacy. Review methods MEDLINE, EMBASE/Excerpta Medica, and Cochrane Central Register of Controlled Trials (all to Mar 2016), ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and reference lists were searched for double-blind, randomized, controlled trials (RCTs) with 20 patients per treatment group and duration 8 weeks. 8 RCTs (n =4147, mean age 47 to 50 y, 89% to 95% women) met the selection criteria. 5 trials compared pregabalin with placebo, 1 trial compared pregabalin dosing regimens, and 2 trials assessed withdrawal of pregabalin in patients who had been maintained on doses with maximum benefits and tolerable adverse events (withdrawal trials). 4 trials adequately described allocation concealment, and 5 trials described adequate blinding of patients and study personnel and of outcome assessors. Main results 1 RCT showed that pregabalin, 150 mg/d, did not increase the likelihood of achieving 30% pain relief, 50% pain relief, or moderate pain relief on the PGIC compared with placebo and did not affect adverse or serious adverse events or withdrawal due to adverse events or lack of efficacy. Meta-analyses of RCTs showed that pregabalin, 300 mg/d, 450 mg/d, and 600 mg/d, increased likelihood of 30% pain relief (Table), 50% pain relief (Table), and moderate and substantial pain relief on the PGIC compared with placebo. Pregabalin, 300 mg, 450 mg, and 600 mg, increased adverse events (relative risk [RR] 1.2 for all) and withdrawal due to adverse events (RR 1.6, 95% CI 1.2 to 2.1; RR 2.0, CI 1.6 to 2.6; RR 2.5, CI 1.9 to 3.3, respectively); reduced withdrawals due to lack of efficacy (RR 0.43, CI 0.28 to 0.65; RR 0.35, CI 0.24 to 0.52; RR 0.28, CI 0.15 to 0.50, respectively); and did not affect risk for serious adverse events. Conclusion In patients with fibromyalgia, pregabalin reduces pain but increases adverse events. Pregabalin vs placebo in patients with fibromyalgia pain* Outcomes (pain relief) (%) Pregabalin dose (mg/d) Number of trials (n) Weighted event rates RBI (95% CI) NNT (CI) Pregabalin Placebo 30 300 4 (1375) 39% 28% 40% (20 to 60) 10 (7 to 17) 50 4 (1375) 21% 14% 50% (20 to 90) 14 (9 to 32) 30 450 5 (1874) 44% 29% 50% (30 to 70) 8 (6 to 10) 50 5 (1874) 25% 14% 80% (40 to 110) 10 (8 to 15) 30 600 3 (1122) 39% 28% 40% (20 to 60) 10 (7 to 19) 50 3 (1122) 24% 15% 60% (30 to 110) 11 (8 to 21) *Abbreviations defined in Glossary. Weighted pregabalin event rates, RBI, and CI calculated from placebo event rates and risk ratios in article. Commentary The well-done review by Derry and colleagues provides a robust analysis of the efficacy and safety of pregabalin in fibromyalgia, one of the most difficult and disabling pain syndromes. The authors concluded that pregabalin, at daily doses of 300 to 600 mg, is more efficacious than placebo for moderate to substantial pain relief. However, as both the efficacy and the common side effects of somnolence, dizziness, weight gain, and peripheral edema are dose-related, the 450-mg dose seems to be the best compromise between efficacy and safety. Starting low and increasing slowly is a wise dosing strategy to minimize treatment dropouts. 1 trial included in the review (1) showed no difference in withdrawal rates between once-nightly and twice-daily administration of pregabalin, suggesting a strategy for minimizing daytime drowsiness from morning doses. The trial populations were generally typical of the spectrum of fibromyalgia patients seen in practicemostly women 50 to 60 years of agebut the applicability to patients with severe depression is uncertain because these patients were largely excluded. Derry and colleagues noted that the numbers needed to treat for pregabalin were similar to those for both milnacipran (2) and duloxetine (3, 4), and for all 3 medications, improvements in pain were paralleled by improvements in sleep, depression, functional and work ability, and quality of life. So, milnacipran and duloxetine offer alternatives when pregabalin is not tolerated. Recent evidence suggests that the combination of pregabalin and duloxetine is more effective than either drug alone (5).