L. LaMoreaux

Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale

&NA; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale (PI‐NRS), where 0=no pain and 10=worst possible pain. However, it is difficult to interpret the clinical importance of changes from baseline on this scale (such as a 1‐ or 2‐point change). To date, there are no data driven estimates for clinically important differences in pain intensity scales used for chronic pain studies. We have estimated a clinically important difference on this scale by relating it to global assessments of change in multiple studies of chronic pain. Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy, postherpetic neuralgia, chronic low back pain, fibromyalgia, and osteoarthritis were used. The studies had similar designs and measurement instruments, including the PI‐NRS, collected in a daily diary, and the standard seven‐point patient global impression of change (PGIC), collected at the endpoint. The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject. Categories of ‘much improved’ and ‘very much improved’ were used as determinants of a clinically important difference and the relationship to the PI‐NRS was explored using graphs, box plots, and sensitivity/specificity analyses. A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study, disease type, age, sex, study result, or treatment group. On average, a reduction of approximately two points or a reduction of approximately 30% in the PI‐NRS represented a clinically important difference. The relationship between percent change and the PGIC was also consistent regardless of baseline pain, while higher baseline scores required larger raw changes to represent a clinically important difference. The application of these results to future studies may provide a standard definition of clinically important improvement in clinical trials of chronic pain therapies. Use of a standard outcome across chronic pain studies would greatly enhance the comparability, validity, and clinical applicability of these studies.

Pregabalin for the treatment of postherpetic neuralgia A randomized, placebo-controlled trial

Objective: To evaluate the efficacy and safety of pregabalin in the treatment of postherpetic neuralgia (PHN). Methods: The authors conducted a multicenter, parallel-group, double-blind, placebo-controlled, 8-week, randomized clinical trial in PHN, defined as pain for 3 or more months following herpes zoster rash healing. Patients (n = 173) were randomized to treatment with pregabalin or placebo. Patients randomized to pregabalin received either 600 mg/day (creatinine clearance > 60 mL/min) or 300 mg/day (creatinine clearance 30 to 60 mL/min). The primary efficacy measure was the mean of the last seven daily pain ratings. Secondary endpoints included additional pain ratings, sleep interference, quality of life, mood, and patient and clinician ratings of global improvement. Results: Pregabalin-treated patients had greater decreases in pain than patients treated with placebo (endpoint mean scores 3.60 vs 5.29, p = 0.0001). Pain was significantly reduced in the pregabalin-treated patients after the first full day of treatment and throughout the study, and significant improvement on the McGill Pain Questionnaire total, sensory, and affective pain scores was also found. The proportions of patients with ≥30% and ≥50% decreases in mean pain scores were greater in the pregabalin than in the placebo group (63% vs 25% and 50% vs 20%, p = 0.001). Sleep also improved in patients treated with pregabalin compared to placebo (p = 0.0001). Both patients and clinicians were more likely to report global improvement with pregabalin than placebo (p = 0.001). Given the maximal dosage studied, pregabalin had acceptable tolerability compared to placebo despite a greater incidence of side effects, which were generally mild to moderate in intensity. Conclusions: Treatment of PHN with pregabalin is safe, efficacious in relieving pain and sleep interference, and associated with greater global improvement than treatment with placebo.

Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial ☆

&NA; A randomized, double‐blind, placebo‐controlled, parallel‐group, multicenter, 8‐week trial (with subsequent open‐label phase) evaluated the effectiveness of pregabalin in alleviating pain associated with diabetic peripheral neuropathy (DPN). For enrollment, patients must have had at baseline: 1‐ to 5‐year history of DPN pain; pain score ≥40 mm (Short‐Form McGill Pain Questionnaire [SF‐MPQ] visual analogue scale); average daily pain score of ≥4 (11‐point numerical pain rating scale [0=no pain, 10=worst possible pain]). One hundred forty‐six (146) patients were randomized to receive placebo (n=70) or pregabalin 300 mg/day (n=76). Primary efficacy measure was endpoint mean pain score from daily patient diaries (11‐point numerical pain rating scale). Secondary measures included SF‐MPQ scores; sleep interference scores; Patient and Clinical Global Impression of Change (PGIC and CGIC); Short Form‐36 (SF‐36) Health Survey scores; and Profile of Mood States (POMS) scores. Safety assessment included incidence and intensity of adverse events, physical and neurological examinations, and laboratory evaluations. Pregabalin produced significant improvements versus placebo for mean pain scores (P<0.0001); mean sleep interference scores (P<0.0001); total SF‐MPQ score (P<0.01); SF‐36 Bodily Pain subscale (P<0.03); PGIC (P=0.001); and Total Mood Disturbance and Tension–Anxiety components of POMS (P<0.03). Pain relief and improved sleep began during week 1 and remained significant throughout the study (P<0.01). Pregabalin was well tolerated despite a greater incidence of dizziness and somnolence than placebo. Most adverse events were mild to moderate and did not result in withdrawal. Pregabalin was safe and effective in decreasing pain associated with DPN, and also improved mood, sleep disturbance, and quality of life.

Pregabalin relieves symptoms of painful diabetic neuropathy A randomized controlled trial

Objective: 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). Methods: Patients with a 1- to 5-year history of DPN and average weekly pain score of ≥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. Results: 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 ≥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. Conclusions: 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.

Gabapentin as add-on therapy in children with refractory partial seizures: a 24-week, multicentre, open-label study

The efficacy and safety of gabapentin as add-on therapy for refractory partial seizures in 237 children, aged 3 to 12 years were evaluated over a 6-month period. All children received gabapentin at 24 to 70 mg/kg/day. Efficacy variables included the percent change in seizure frequency and the responder rate (defined as those patients who showed >50% reduction in seizure frequency). For all partial seizures, the median percent change in seizure frequency was -34% and the overall responder rate was 34%. Simple partial seizures showed a median reduction of -53%; complex partial seizures, -38%; and secondarily generalized tonic-clonic seizures, -35%. Thirteen patients (5%) withdrew during the 6-month period because of adverse events. Concurrent antiepileptic medication remained unchanged in 185 patients (78%), was decreased in 27 (11%), and increased in 25 (11%) patients. This 6-month follow-up study has demonstrated that gabapentin was well tolerated and appeared to show a sustained efficacy in a large population of children with refractory partial and secondarily generalized tonic-clonic seizures.

290 EFFICACY AND SAFETY OF PREGABALIN AS TREATMENT OF PAINFUL DIABETIC PERIPHERAL NEUROPATHY (DPN): A 13‐WEEK RANDOMIZED CONTROLLED TRIAL AND 6‐MONTH SAFETY EXTENSION

amputation, reason and area of amputation, intensity and appeased factors of phantom pain, amount and kind of medication for relive phantom pain and severity of pain was determined and controlled with MC GILL visual Analogue scale before and after acupressure findings were statistically by using SPSS software. Results. Analyzing statistical tests, indicates that acupressure treatment can decrease intensity of phantom pain (p < 0.0001) and decrease amount of medications (p < 0.005) and both of hypothesis were accepted.