Ruoyong Yang

A randomized trial of pregabalin in patients with neuropathic pain due to spinal cord injury

Objective: To assess the efficacy and tolerability of pregabalin for the treatment of central neuropathic pain after spinal cord injury (SCI). Methods: Patients with chronic, below-level, neuropathic pain due to SCI were randomized to receive 150 to 600 mg/d pregabalin (n = 108) or matching placebo (n = 112) for 17 weeks. Pain was classified in relation to the neurologic level of injury, defined as the most caudal spinal cord segment with normal sensory and motor function, as above, at, or below level. The primary outcome measure was duration-adjusted average change in pain. Key secondary outcome measures included the change in mean pain score from baseline to end point, the percentage of patients with ≥30% reduction in mean pain score at end point, Patient Global Impression of Change scores at end point, and the change in mean pain-related sleep interference score from baseline to end point. Additional outcome measures included the Medical Outcomes Study–Sleep Scale and the Hospital Anxiety and Depression Scale. Results: Pregabalin treatment resulted in statistically significant improvements over placebo for all primary and key secondary outcome measures. Significant pain improvement was evident as early as week 1 and was sustained throughout the treatment period. Adverse events were consistent with the known safety profile of pregabalin and were mostly mild to moderate in severity. Somnolence and dizziness were most frequently reported. Conclusions: This study demonstrates that pregabalin is effective and well tolerated in patients with neuropathic pain due to SCI. Classification of evidence: This study provides Class I evidence that pregabalin, 150 to 600 mg/d, is effective in reducing duration-adjusted average change in pain compared with baseline in patients with SCI over a 16-week period (p = 0.003, 95% confidence interval = −0.98, −0.20).

Sertraline Treatment of Children and Adolescents With Posttraumatic Stress Disorder: A Double-Blind, Placebo-Controlled Trial

OBJECTIVE The aim of this study was to evaluate the safety and efficacy of sertraline in children and adolescents who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for posttraumatic stress disorder (PTSD). METHOD Children and adolescents (6-17 years old) meeting DSM-IV criteria for PTSD were randomized to 10 weeks of double-blind treatment with sertraline (50-200  mg/day) or placebo. The primary efficacy measure was the University of California, Los Angeles Post-Traumatic Stress Disorder Index for DSM-IV (UCLA PTSD-I). RESULTS A total of 131 patients met entry criteria and were randomized to sertraline (n = 67; female, 59.7%; mean age, 10.8; mean UCLA PTSD-I score, 43.8 ± 8.5) or placebo (n = 62; female, 61.3%; mean age, 11.2; mean UCLA PTSD-I score, 42.1 ± 8.8). There was no difference between sertraline and placebo in least squares (LS) mean change in the UCLA PTSD-I score, either on a completer analysis (-20.4 ± 2.1 vs. -22.8 ± 2.1; p = 0.373) or on an last observation carried forward (LOCF) end point analysis (-17.7 ± 1.9 vs. -20.8 ± 2.1; p = 0.201). Attrition was higher on sertraline (29.9%) compared to placebo (17.7%). Discontinuation due to adverse events occurred in a 7.5% treated with sertraline and 3.2% treated with placebo. CONCLUSIONS Sertraline was a generally safe treatment in children and adolescents with PTSD, but did not demonstrate efficacy when compared to placebo during 10 weeks of treatment. ClinicalTrials.gov Identifier: NCT00150306.

Pregabalin for the treatment of postoperative pain: results from three controlled trials using different surgical models

Purpose To evaluate the efficacy and safety of pregabalin (150 or 300 mg/d) as an adjunctive therapy for the treatment of postoperative pain. Patients and methods This study reports findings from three separate, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive pregabalin for the treatment of postoperative pain. Patients underwent one of three categories of surgical procedures (one procedure per study): elective inguinal hernia repair (post-IHR); elective total knee arthroplasty (post-TKA); or total abdominal hysterectomy (posthysterectomy). The primary endpoint in each trial, mean worst pain over the past 24 hours, was assessed 24 hours post-IHR and posthysterectomy, and 48 hours post-TKA. Patients rated their pain on a scale from 0 to 10, with higher scores indicating greater pain severity. Results In total, 425 (post-IHR), 307 (post-TKA), and 501 (posthysterectomy) patients were randomized to treatment. There were no statistically significant differences between the pregabalin and placebo groups with respect to the primary endpoint in any of the three trials. The least squares mean difference in worst pain, between 300 mg/d pregabalin and placebo, was −0.7 (95% confidence interval [CI] =−1.4, −0.1; Hochberg adjusted P=0.067) post-IHR; −0.34 (95% CI =−1.07, 0.39; P=0.362) post-TKA; and −0.2 (95% CI =−0.66, 0.31; P=0.471) posthysterectomy. Conclusion There were no significant differences between pregabalin and placebo with respect to the primary pain intensity measure in each of the three clinical trials. These studies encompass a large dataset (1,233 patients in total), and their results should be considered when assessing pregabalin’s effectiveness in postoperative pain. Further studies are required to determine the potential pain-reducing benefit of pregabalin in the postoperative setting.

Efficacy and safety of pregabalin in patients with spinal cord injury: a pooled analysis.

Abstract Objective: To summarize the efficacy and examine the safety and tolerability of pregabalin in patients with central neuropathic pain due to spinal cord injury (SCI). Research design and methods: Data were pooled from two 12 to 16 week, placebo-controlled trials of pregabalin in patients with neuropathic pain due to SCI. Pain diaries were used to rate pain from 0 = no pain to 10 = worst possible pain. Efficacy measures included: mean change in pain from baseline to endpoint; duration adjusted average change (DAAC) in pain; the percentage of patients with ≥30% or ≥50% reductions in pain score from baseline to endpoint; and Patient Global Impression of Change (PGIC) score at endpoint. Adverse events (AEs) were also compared between treatment groups. Results: In total 174 patients received placebo and 182 received pregabalin. Mean change in pain from baseline to endpoint was improved in the pregabalin group compared with placebo (placebo-adjusted difference = −0.79; 95% CI = −1.15, −0.43; p < 0.001; baseline-observation-carried-forward). DAAC in pain was improved in patients receiving pregabalin compared with placebo (p < 0.001). The percentage of patients achieving ≥30% and ≥50% reductions in pain from baseline to endpoint was greater in the pregabalin arm compared with placebo (placebo: 30% = 22.5%, 50% = 11.6: pregabalin 30% = 35.6%, 50% = 22.4%) (all p < 0.01). PGIC scores at endpoint were significantly better in the pregabalin arm compared with placebo (p < 0.05). Treatment-related AEs, most commonly somnolence, dizziness, dry mouth, fatigue, edema, blurred vision, and constipation occurred more frequently in patients treated with pregabalin than placebo. The majority of AEs were mild to moderate in severity. Conclusions: Pregabalin reduced neuropathic pain due to SCI over a 12 to 16 week treatment period. Treatment-related AEs were mostly mild to moderate in severity and are consistent with the known safety profile of pregabalin. These findings should not be extrapolated to longer durations of treatment or other patient populations.

Pregabalin in Patients With Painful Diabetic Peripheral Neuropathy Using an NSAID for Other Pain Conditions: A Double-Blind Crossover Study.

Objectives:To evaluate pregabalin’s efficacy and safety versus placebo to reduce pain in patients with diabetic peripheral neuropathy (DPN) using a concomitant nonsteroidal anti-inflammatory drug. Materials and Methods:In a randomized, double-masked, 14-week, 2-period, crossover study, patients with painful DPN using a nonsteroidal anti-inflammatory drug for non–DPN-related pain received 150 to 300 mg/d pregabalin or placebo (period 1); 14-day washout; then, the opposite therapy (period 2). Endpoints included weekly change in DPN pain score, sleep interference, adverse events, and patient-reported outcomes. Results:Patients with similar baseline characteristics were randomized (period 1) to 1 of the 2 following possible sequences: pregabalin→placebo (n=154) or placebo→pregabalin (n=147). Results of the primary efficacy measure, mean weekly DPN pain at endpoint, showed no significant difference between pregabalin and placebo. However, 1 sensitivity analysis (mixed-model repeated measures) found greater pain score reductions with pregabalin than placebo at weeks 2 to 4 and overall (all P<0.05). One secondary endpoint analysis, mean treatment difference in DPN-related sleep interference, favored pregabalin over placebo (P=0.0009). Other sensitivity and secondary analyses were nonsignificant. Treatment-emergent adverse events were consistent with the known safety profile of pregabalin. Discussion:Pregabalin (vs. placebo) showed overall improvements in sleep, pain reduction in 1 sensitivity analysis, and was well tolerated. Potential factors that may have confounded the ability to detect a treatment difference in DPN pain reduction (high placebo response, carryover effect, short washout period, or pregabalin dose) are discussed in the context of future studies.

Efficacy and safety of pregabalin for painful diabetic peripheral neuropathy in a population of Chinese patients: A randomized placebo‐controlled trial

Limited information exists regarding the efficacy of pregabalin in Chinese patients with painful diabetic peripheral neuropathy (pDPN).

Efficacy and Safety of Once-Daily Controlled-Release Pregabalin for the Treatment of Patients with Postherpetic Neuralgia: A Double-blind, Randomized Withdrawal, Placebo-Controlled Trial.

Objectives: To assess efficacy and safety of once-daily controlled-release (CR) formulation of pregabalin in patients with postherpetic neuralgia. Methods: An enriched enrollment, randomized withdrawal trial, with 6-week single-blind pregabalin treatment phase and 13-week double-blind phase, where patients with ≥50% decrease in mean pain score at single-blind end point from baseline were randomized (1:1) to pregabalin CR (82.5 to 660 mg/d) or placebo. Primary efficacy outcome was time to loss of therapeutic response (LTR) (<30% decrease in weekly mean pain score from single-blind baseline or discontinuation due to adverse event or lack of efficacy). Secondary efficacy outcomes included change in weekly mean pain score (1-wk recall period) at double-blind end point. Results: In total, 801 patients were randomized and treated in the single-blind phase, and 413 in the double-blind phase (208, pregabalin CR; 205, placebo). Pregabalin CR significantly increased time to LTR versus placebo (Kaplan-Meier analysis) with significantly fewer LTR events with pregabalin CR than with placebo (29 [13.9%] vs. 63 [30.7%]; P<0.0001). Median time to LTR was not estimable. Pregabalin CR significantly improved weekly mean pain score versus placebo: LS mean difference (95% CI) of −1.11 (−1.47, −0.75) and −1.00 (−1.34, −0.65) (P<0.0001) from single-blind baseline and double-blind baseline, respectively. Most commonly reported adverse events in the single-blind phase were dizziness, somnolence, and peripheral edema. Pregabalin CR was well tolerated. Discussion: Time to LTR was significantly longer with pregabalin CR than with placebo. Safety profile of pregabalin CR was comparable to that reported for the immediate-release formulation in patients with postherpetic neuralgia.

Efficacy and Safety of Pregabalin in Patients with Neuropathic Pain Due to Spinal Cord Injury: A Pooled Analysis

were assumed to be experienced as they had completed 11 months of training, performed procedures with distant supervision, and their completion of the fellowship program was imminent. Results or Clinical Course: Data from 50 procedures was collected. After linear regression analysis, ICESI fluoroscopy times for T2 reached equivalency for T1 after 22.9 injection experiences. Prior to reaching equivalency, T1 required on average 11.7 seconds FT to perform ICESI in contrast to T2 which required 16.5 seconds FT with a p value <.05. After reaching equivalency, T1 required on average 11 seconds FT while T2 required 11.7 seconds FT to perform ICESI with a p value >.05. Conclusions: It is important to determine what constitutes competency for fellowship trainees when performing ICESI. The results of this study suggest that fluoroscopy procedure times may be used as an objective measure to aid in determination of level of competency amongst trainees in a pain fellowship program and to determine the minimum number of injections required for this achievement. Determination of competency also requires multiple matrices including patient satisfaction, length of therapeutic effect, adverse outcomes, supervisor approval, and repetitive exposure to procedures. Therefore these factors must also be considered when determining overall competency and approval for independent injection technique for graduation.