title: Examining the Time to Therapeutic Effect of Pregabalin in Spinal Cord Injury Patients With Neuropathic Pain.
abstract: OBJECTIVE
  In 2 large-scale, placebo-controlled trials, pregabalin improved both pain and pain-related sleep interference in patients with neuropathic pain due to spinal cord injury (SCI). In both trials, pregabalin found statistically significant improvement compared with placebo after 1 week of treatment. However, the effects of pregabalin in the days immediately after initiation of treatment are unknown. The purpose of the present analysis was to determine timing of pregabalin's therapeutic effect in the days after initiation of treatment.
  
  
  METHODS
  Data were derived from 2 trials of pregabalin in patients with SCI-related neuropathic pain. Each day patients rated severity of pain and pain-related sleep interference over the past 24 hours on a scale from 0 to 10, with higher scores indicating greater severity. To quantify timing of therapeutic effect, we compared (pregabalin [vs] placebo) daily average pain and pain-related sleep interference scores over the first 14 days of treatment. Significant improvement was defined as the first day, of ≥2 consecutive days, that pregabalin significantly (P < 0.05) reduced mean scores compared with placebo. To further quantify timing of therapeutic effect, each treatment group was examined to determine the time required to achieve a ≥1-point improvement in pain and pain-related sleep interference score among patients with a clinically meaningful and sustained response (≥30% improvement from baseline to end point) by using a time-to-event analysis method. Kaplan-Meier analyses were used to estimate the median (or 25th quartile) time (in days) required to achieve a ≥1-point improvement, among these responders, in pain and pain-related sleep interference scores. Comparisons between pregabalin and placebo were made with a log-rank test.
  
  
  RESULTS
  In both trials, significant improvement of pain and pain-related sleep interference occurred within 2 days of initiating treatment with pregabalin. Among patients reporting a clinically meaningful and sustained response to treatment (patients with ≥30% improvement from baseline to end point), the time to a ≥1-point improvement of pain and pain-related sleep interference occurred significantly earlier among pregabalin-treated patients than among placebo-treated patients. Finally, the timing of pregabalin's effect on pain and pain-related sleep interference was unaffected by the use of concomitant medications that were allowed for treatment of neuropathic pain in both trials.
  
  
  CONCLUSIONS
  Treatment with pregabalin results in rapid time to significant improvement in both pain and pain-related sleep interference in patients with neuropathic pain due to SCI. These findings should only be used as a guide to physicians and patients as to when clinical response to pregabalin may be expected.
authors: Department of Physical Medicine & Rehabilitation, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida. Electronic address: dcardenas@med.miami.edu.
authors: Diana D
authors: DD
authors: Cardenas
authors: Pfizer Inc, New York, New York.
authors: Birol
authors: B
authors: Emir
authors: Pfizer Inc, New York, New York.
authors: Bruce
authors: B
authors: Parsons
mesh_terms: D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000379:methods; D000069583:Pregabalin / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012893:Sleep Wake Disorders / Q000188:drug therapy / Q000209:etiology; D013119:Spinal Cord Injuries / Q000150:complications*; D016896:Treatment Outcome
chemical_list: D018712:Analgesics, Non-Narcotic; D000069583:Pregabalin
keywords: neuropathic pain; pregabalin; sleep interference; spinal cord injury