Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief (FREEDOM): a 6-month, double-blind, placebo-controlled trial with pregabalin. A randomized, double-blind, placebo-controlled, phase III trial of pregabalin in the treatment of patients with fibromyalgia. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial. Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens. Pregabalin in patients with central neuropathic pain: a randomized, double-blind, placebo-controlled trial of a flexible-dose regimen. Pregabalin for relief of neuropathic pain associated with diabetic neuropathy: a randomized, double-blind study. Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial. A 14-week, randomized, double-blinded, placebo-controlled monotherapy trial of pregabalin in patients with fibromyalgia.
This was a multicenter, double-blind (DB), placebo-controlled, randomized discontinuation trial to evaluate the efficacy of pregabalin monotherapy for durability of effect on fibromyalgia (FM) pain. The trial included a 6-week open-label (OL) pregabalin-treatment period followed by 26-week DB treatment with placebo or pregabalin. Adults with FM and 40-mm score on 100-mm pain visual analog scale (VAS) were eligible. During OL weeks 1-3, patients received escalating dosages of pregabalin to determine their optimal dosages. During OL weeks 4-6, patients received their optimal fixed dosages (300, 450, 600mg/d). To be randomized, patients must have had 50% decrease in pain VAS and a self-rating of "much" or "very much" improved on Patient Global Impression of Change (PGIC) at the end of OL. Double-blind treatment was with placebo or the patient's optimal fixed dosage of pregabalin. Primary outcome was time to loss of therapeutic response (LTR), defined as <30% reduction in pain (from OL baseline) or worsening of FM. A total of 1051 patients entered OL; 287 were randomized to placebo, 279 to pregabalin. Time to LTR was longer for pregabalin versus placebo (P<.0001). Kaplan-Meier estimates of time-to-event showed half the placebo group had LTR by Day 19; half the pregabalin group still had not lost response by trial end. At the end of DB, 174 (61%) placebo patients met LTR criteria versus 90 (32%) pregabalin patients. Pregabalin was well tolerated, though 178 (17%) discontinued during OL for treatment-related adverse events (AE), and more pregabalin than placebo patients discontinued for AEs during DB. In those who respond, pregabalin demonstrated durability of effect for relieving FM pain. To evaluate the efficacy and safety of pregabalin for symptomatic relief of pain associated with fibromyalgia (FM) and for management of FM.
                This multicenter, double-blind, placebo-controlled trial randomly assigned 748 patients with FM to receive placebo or pregabalin 300, 450, or 600 mg/day (dosed twice daily) for 13 weeks. The primary outcome variable for study objective 1, symptomatic relief of pain associated with FM, was comparison of endpoint mean pain scores between each pregabalin group and placebo. The outcome variable for study objective 2, management of FM, included endpoint mean pain scores, Patient Global Impression of Change (PGIC), and Fibromyalgia Impact Questionnaire (FIQ)-Total Score. Secondary outcomes included assessments of sleep, fatigue, and mood disturbance.
                Patients in all pregabalin groups showed statistically significant improvement in endpoint mean pain score and in PGIC response compared with placebo. Improvements in FIQ-Total Score for the pregabalin groups were numerically but not significantly greater than those for the placebo group. Compared with placebo, all pregabalin treatment groups showed statistically significant improvement in assessments of sleep and in patients' impressions of their global improvement. Dizziness and somnolence were the most frequently reported adverse events.
                Pregabalin at 300, 450, and 600 mg/day was efficacious and safe for treatment of pain associated with FM. Pregabalin monotherapy provides clinically meaningful benefit to patients with FM. Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and lowered pain threshold. Other prominent symptoms include disordered sleep and fatigue. FMS affects an estimated 2% of the population, predominantly women. This trial was designed to evaluate the efficacy and safety of pregabalin, a novel alpha(2)-delta ligand, for treatment of symptoms associated with FMS.
                This multicenter, double-blind, 8-week, randomized clinical trial compared the effects of placebo with those of 150, 300, and 450 mg/day pregabalin on pain, sleep, fatigue, and health-related quality of life in 529 patients with FMS. The primary outcome variable was the comparison of end point mean pain scores, derived from daily diary ratings of pain intensity, between each of the pregabalin treatment groups and the placebo group.
                Pregabalin at 450 mg/day significantly reduced the average severity of pain in the primary analysis compared with placebo (-0.93 on a 0-10 scale) (P </= 0.001), and significantly more patients in this group had >/=50% improvement in pain at the end point (29%, versus 13% in the placebo group; P = 0.003). Pregabalin at 300 and 450 mg/day was associated with significant improvements in sleep quality, fatigue, and global measures of change. Pregabalin at 450 mg/day improved several domains of health-related quality of life. Dizziness and somnolence were the most frequent adverse events. Rates of discontinuation due to adverse events were similar across all 4 treatment groups.
                Pregabalin at 450 mg/day was efficacious for the treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo. Pregabalin was well tolerated and improved global measures and health-related quality of life. Pregabalin, an alpha2-delta ligand with analgesic, anxiolytic, and anticonvulsant activity, has been evaluated for treatment of neuropathic pain. The authors assessed the efficacy and tolerability of pregabalin (75, 300, 600 mg/day) vs placebo in patients with diabetic peripheral neuropathy (DPN).
                Patients with a 1- to 5-year history of DPN and average weekly pain score of > or =4 on an 11-point numeric pain-rating scale were enrolled in a 5-week, double-blind, multicenter, placebo-controlled study. Patients (n = 338) were randomized to receive one of three doses of pregabalin or placebo TID. Pregabalin 600 mg/day was titrated over 6 days; lower doses were initiated on day 1.
                Patients in the 300- and 600-mg/day pregabalin groups showed improvements in endpoint mean pain score (primary efficacy measure) vs placebo (p = 0.0001). Improvements were also seen in weekly pain score, sleep interference score, patient global impression of change, clinical global impression of change, SF-McGill Pain Questionnaire, and multiple domains of the SF-36 Health Survey. Improvements in pain and sleep were seen as early as week 1 and were sustained throughout the 5 weeks. Responders (patients with > or =50% reduction in pain compared to baseline) were 46% (300 mg/day), 48% (600 mg/day), and 18% (placebo). Pregabalin was well tolerated with a low discontinuation rate. The most common adverse events were dizziness and somnolence.
                In patients with diabetic peripheral neuropathy, pregabalin demonstrated early and sustained improvement in pain and a beneficial effect on sleep, which were confirmed by positive patient global impression. Pregabalin was well tolerated at all doses. Pregabalin binds with high affinity to the alpha2-delta subunit protein of voltage-gated calcium channels and, thereby, reduces release of excitatory neurotransmitters. This 12-week randomised, double-blind, multicentre, placebo-controlled, parallel-group study evaluated the efficacy and safety of pregabalin in patients with chronic postherpetic neuralgia (PHN) or painful diabetic peripheral neuropathy (DPN). Patients were randomised to placebo (n=65) or to one of two pregabalin regimens: a flexible schedule of 150, 300, 450, and 600 mg/day with weekly dose escalation based on patients' individual responses and tolerability (n=141) or a fixed schedule of 300 mg/day for 1 week followed by 600 mg/day for 11 weeks (n=132). Both flexible- and fixed-dose pregabalin significantly reduced endpoint mean pain score (primary outcome) versus placebo (P=0.002, P<0.001) and were significantly superior to placebo in improving pain-related sleep interference (P<0.001). The most common adverse events (AEs) for pregabalin-treated patients were dizziness, peripheral oedema, weight gain (not affecting diabetes control), and somnolence. These results are consistent with previous studies' demonstrating pregabalin's efficacy, tolerability, and safety for treatment of chronic neuropathic pain associated with DPN or PHN. Pregabalin dosing aimed at optimal balance of efficacy and tolerability provides significant pain relief and may reduce risks for AEs and therapy discontinuation. The effective treatment of patients suffering from central neuropathic pain remains a clinical challenge, despite a standard pharmacological approach in combination with anticonvulsants and antidepressants. A randomized, double-blinded, placebo-controlled trial evaluated the effects of pregabalin on pain relief, tolerability, health status, and quality of life in patients with central neuropathic pain caused by brain or spinal cord injuries. At baseline and 4 weeks after the start of treatment subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analog scale, health status (Pain Disability Index and EQ-5D) and quality of life (SF-36). Forty patients received escalating doses of either pregabalin (150, 300, and 600mg/day) or matching placebo capsules. In both groups, patients started with 1 capsule per day (either 150mg of pregabalin or placebo). If pain relief was insufficient, patients were titrated to a higher dose. There was a statistically significant decrease in mean pain score at endpoint for pregabalin treatment, compared with placebo (P=0.016). Follow-up observation showed no significant difference in Pain Disability Index scores between the two groups. The pregabalin group, however, showed a statistically significant improvement for the EQ-5D. Pregabalin treatment led to a significant improvement in the bodily pain domain of the SF36. In the other domains, more favorable scores were reported without reaching statistical significance. Pregabalin, in a flexible-dose regime, produced clinically significant reductions in pain, as well as improvements in health status in patients suffering from severe central neuropathic pain. Seven published, randomized, placebo-controlled clinical trials with pregabalin have shown robust efficacy for relief of neuropathic pain from DPN and PHN. An investigation of the efficacy and safety of twice daily pregabalin enrolled 395 adults with painful DPN for > or = 1 year in a 12-week, double-blind, placebo-controlled trial. Patients were randomized to placebo, 150, 300, or 600 mg/day pregabalin (n = 96, 99, 99, and 101). Primary efficacy measure was change from baseline in endpoint mean pain score from patients' daily pain diaries. Secondary efficacy measures included pain-related sleep-interference scores, Patient and Clinical Global Impressions of Change (PGIC, CGIC), and the EuroQOL Health Utilities Index (EQ-5D). Statistically significant reduction in pain was observed in patients receiving pregabalin 600 mg/day, and 46% of patients treated with 600 mg/day pregabalin reported > or = 50% improvement in mean pain scores from baseline (vs 30% of placebo patients, p = 0.036). Number needed to treat to achieve such response was 6.3. Pregabalin 600 mg/day was significantly superior to placebo in improving pain-related sleep-interference scores (p = 0.003), PGIC (p = 0.021), and CGIC (p = 0.009). (Neither pregabalin 150 nor 300 mg/day separated from placebo on these measures, largely because of an atypically large placebo response in one country representing 42% of patients.) All pregabalin dosages were superior to placebo in improving EQ-5D utility scores (all p > or = 0.0263 vs placebo). Pregabalin was well tolerated at all dosages; adverse events were generally mild to moderate. Number needed to harm (discontinuation because of adverse events) was 10.3 for pregabalin 600 mg/day. This was a 6-week, randomized, double-blind, multicenter study evaluating the efficacy of pregabalin in the treatment of painful diabetic neuropathy. Two hundred forty-six men and women with painful diabetic neuropathy received pregabalin (150 or 600 mg/day by mouth) or placebo. The primary efficacy variable was mean pain score at the end of treatment. Efficacy results indicate that pregabalin 600 mg/day significantly decreased mean pain score to 4.3 (vs 5.6 for placebo, P = .0002) and increased the proportion of patients who had a > or =50% decrease from baseline pain (39% vs 15% for placebo, P = .002). Pregabalin also significantly reduced sleep interference, past week and present pain intensity, sensory and affective pain scores, and bodily pain and decreased by > or =50% the number of patients describing their pain as gnawing, sickening, fearful, and punishing-cruel. More patients receiving pregabalin 600 mg/day than placebo showed improvement, as rated on the Clinical and Patient Global Impression of Change scales, 73% vs 45% and 85% vs 47%, respectively. Pregabalin 150 mg/day was essentially no different from placebo. Dizziness was the most common side effect. These study results show pregabalin 600 mg/day to be safe and effective in reducing the pain and other associated symptoms of painful diabetic neuropathy.
                Painful diabetic peripheral neuropathy is a challenging neuropathic pain syndrome. This randomized controlled trial demonstrates that pregabalin, a new drug that interacts with the alpha2-delta protein subunit of the voltage-gated calcium channel, is an efficacious and safe treatment for the pain of this condition. The purpose of the study was to assess the efficacy and safety of pregabalin monotherapy in patients with fibromyalgia in a randomized, double-blinded, placebo-controlled trial. After 1 week of single-blinded administration of placebo, 750 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to pregabalin (300 mg/d, 450 mg/d, 600 mg/d) or placebo, administered twice daily for 14 weeks. The primary outcome variable was comparison of end point mean pain scores, derived from daily diary ratings of pain intensity (0 to 10 scale), between each of the pregabalin groups and the placebo group. If positive, additional primary efficacy parameters included the Patient Global Impression of Change (PGIC) and the Fibromyalgia Impact Questionnaire (FIQ) total score. Compared with placebo-treated patients, mean changes in pain scores at the end point in pregabalin-treated patients were significantly greater (P < .001: 300 mg/d, -0.71; 450 mg/d, -0.98; 600 mg/d, -1.00). Compared with placebo, significantly more pregabalin-treated patients reported improvement on PGIC (P < .01 for all 3 pregabalin doses) and significant improvements in total FIQ score for the 450 mg/d (P = .004) and the 600 mg/d (P = .003) doses. Compared with placebo, all 3 doses of pregabalin were associated with significant improvement in sleep. The most commonly reported pregabalin-related adverse events were dizziness and somnolence, which tended to be dose-related.
                This randomized, placebo-controlled trial of 300, 450, and 600 mg/d of pregabalin monotherapy demonstrated that all 3 doses were efficacious for up to 14 weeks for the treatment of fibromyalgia and were well tolerated by most patients. These results provide evidence that pregabalin is an important treatment option for patients with fibromyalgia.
Pregabalin has proven efficacy in neuropathic pain conditions and fibromyalgia. A minority of patients will have substantial benefit with pregabalin, and more will have moderate benefit. Many will have no or trivial benefit, or will discontinue because of adverse events. Individualisation of treatment is needed to maximise pain relief and minimise adverse events. There is no evidence to support the use of pregabalin in acute pain scenarios.