title: Efficacy and safety of pregabalin 600 mg/d for treating painful diabetic peripheral neuropathy: a double-blind placebo-controlled trial.
abstract: BACKGROUND
  Recent consensus guidelines recommend pregabalin as a first-tier treatment for painful diabetic peripheral neuropathy (DPN). We evaluated the efficacy of pregabalin 600 mg/d (300 mg dosed BID) versus placebo for relieving DPN-associated neuropathic pain, and assessed its safety using objective measures of nerve conduction (NC).
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled trial, the primary efficacy measure was endpoint mean pain score (MPS) from daily pain diaries (11-point scale). NC velocity and sensory and motor amplitudes were assessed at baseline, endpoint, and end of follow-up (2 weeks post-treatment). At each timepoint, the median-motor, median-sensory, ulnar-sensory, and peroneal-motor nerves were evaluated. Secondary efficacy measures included weekly MPS and proportion of responders (patients achieving >or=50% reduction in MPS from baseline to endpoint). After 1-weeks' dosage escalation, pregabalin-treated patients received 300 mg BID for 12 weeks.
  
  
  RESULTS
  Eighty-two patients received pregabalin and 85 placebo. Mean durations were 10 years for diabetes and approximately 5 years for painful DPN. Pregabalin-treated patients had lower MPS than controls (mean difference, -1.28; p <.001). For all four nerves, 95% CIs for median differences in amplitude and velocity from baseline to endpoint and baseline to follow-up included 0 (ie, no significant difference vs. placebo). Significant pain improvement among pregabalin-treated patients was evident at week 1 and sustained at every weekly timepoint. More pregabalin-treated patients (49%) than controls (23%) were responders (p <.001).
  
  
  CONCLUSIONS
  Pregabalin 600 mg/d (300 mg BID) effectively reduced pain, was well tolerated, and had no statistically significant or clinically meaningful effect on NC in patients with painful DPN.
authors.affiliation: Albert Einstein College of Medicine, New York, NY, USA. Arezzo@aecom.yu.edu
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Arezzo
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.forename: Linda
authors.initials: L
authors.lastname: Lamoreaux
authors.forename: Lynne
authors.initials: L
authors.lastname: Pauer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000187:drug effects / Q000503:physiopathology; D008875:Middle Aged; D009431:Neural Conduction / Q000187:drug effects; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D010543:Peroneal Nerve / Q000187:drug effects / Q000503:physiopathology; D010919:Placebos; D000069583:Pregabalin; D016896:Treatment Outcome; D014459:Ulnar Nerve / Q000187:drug effects / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D010919:Placebos; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid
references.citation: Am J Med. 1999 Aug 30;107(2B):9S-16S
references.pmid: 10484040
references.citation: Muscle Nerve. 1998 Nov;21(11):1368-73
references.pmid: 9771658
references.citation: Eur J Neurol. 2006 Nov;13(11):1153-69
references.pmid: 17038030
references.citation: Diabetes Metab Rev. 1995 Oct;11(3):193-225
references.pmid: 8536541
references.citation: Eur J Pain. 2008 Feb;12(2):203-13
references.pmid: 17631400
references.citation: Pain. 1987 Aug;30(2):191-197
references.pmid: 3670870
references.citation: Mayo Clin Proc. 2006 Apr;81(4 Suppl):S12-25
references.pmid: 16608049
references.citation: Diabetes Care. 2005 Apr;28(4):956-62
references.pmid: 15793206
references.citation: Pain. 2004 Aug;110(3):628-638
references.pmid: 15288403
references.citation: Neurology. 2004 Dec 14;63(11):2104-10
references.pmid: 15596757
references.citation: J Pain Symptom Manage. 2005 Oct;30(4):374-85
references.pmid: 16256902
references.citation: Pain. 2005 Jun;115(3):254-263
references.pmid: 15911152
references.citation: Diabetes Care. 2005 Sep;28(9):2192-200
references.pmid: 16123489
references.citation: Clin J Pain. 2006 Oct;22(8):681-5
references.pmid: 16988563
references.citation: Drugs. 2004;64(24):2813-20; discussion 2821
references.pmid: 15563250
references.citation: Neurology. 1992 Sep;42(9):1823-5
references.pmid: 1513476
references.citation: Pain. 2004 May;109(1-2):26-35
references.pmid: 15082123
references.citation: Neurology. 2003 Apr 22;60(8):1274-83
references.pmid: 12707429
references.citation: Clin J Pain. 2002 Nov-Dec;18(6):350-4
references.pmid: 12441828
references.citation: Diabetes Care. 2004 Jun;27(6):1458-86
references.pmid: 15161806
references.citation: J Pain. 2005 Apr;6(4):253-60
references.pmid: 15820913
references.citation: Curr Med Res Opin. 2006 Feb;22(2):375-84
references.pmid: 16466610
references.citation: Neurology. 2004 Sep 28;63(6):959-65
references.pmid: 15452284
references.citation: Br Med J (Clin Res Ed). 1988 May 21;296(6634):1454-6
references.pmid: 3132290
references.citation: Diabetes Care. 1989 Oct;12(9):649-52
references.pmid: 2676432
references.citation: Int Rev Neurobiol. 2002;50:229-55
references.pmid: 12198812