TY - JOUR
T1 - Pregabalin for Postherpetic Neuralgia
T2 - Placebo-Controlled Trial of Fixed and Flexible Dosing Regimens on Allodynia and Time to Onset of Pain Relief
AU - Stacey, Brett R.
AU - Barrett, Jeannette A.
AU - Whalen, Ed
AU - Phillips, Kem F.
AU - Rowbotham, Michael C.
N1 - Funding Information:
The authors thank C. J. Asakiewicz and Marie Ortiz of Pfizer Inc for their contributions to the conduct and management of this trial. Writing assistance was provided by Elizabeth Miller of EAM Associates and was funded by Pfizer Inc. Additional editorial assistance was provided by Gregory Bezkorovainy, Adelphi Inc., and was funded by Pfizer.
PY - 2008/11
Y1 - 2008/11
N2 - Time to onset of pain relief and improvement in allodynia in 269 patients with postherpetic neuralgia was examined in a 4-week randomized trial comparing flexibly dosed pregabalin (150-600 mg/d), fixed-dose pregabalin (300 mg/d), and placebo. For each patient with clinically meaningful pain reduction (≥30%) at end point, onset of pain relief was defined as the first study day on which a patient reported ≥1-point reduction in pain relative to baseline. Average dose achieved was 396 mg/d in the flexible-dose group compared with 295 mg/d in the fixed-dose group. Median pain relief onset times were 3.5 days (flexible-dose), 1.5 days (fixed-dose), and >4 weeks (placebo). Compared with placebo, significantly more patients in both pregabalin treatment groups achieved ≥30% and ≥50% pain reduction at end point. Almost 95% of patients had brush-evoked allodynia, with 68% having moderate to severe allodynia (≥40/100 mm). At baseline, pain and allodynia were highly correlated. Independent of treatment assignment, improvement in pain and improvement in allodynia were significantly correlated. Allodynia could serve as a useful surrogate outcome measure in future studies. Pregabalin was significantly better than placebo in alleviating allodynia (flexible-dose reduction, 26 mm; fixed-dose, 21 mm; placebo, 12 mm). Discontinuation rates due to adverse events were more frequent in the fixed-dose group. Perspective: A flexible-dose regimen reduces discontinuations, facilitates higher final doses, and results in a slightly greater pain relief. Allodynia (touch-evoked pain) can be of disabling severity and is present in nearly all patients with postherpetic neuralgia. Allodynia severity is correlated with pain severity and improvement in allodynia is correlated with clinical response.
AB - Time to onset of pain relief and improvement in allodynia in 269 patients with postherpetic neuralgia was examined in a 4-week randomized trial comparing flexibly dosed pregabalin (150-600 mg/d), fixed-dose pregabalin (300 mg/d), and placebo. For each patient with clinically meaningful pain reduction (≥30%) at end point, onset of pain relief was defined as the first study day on which a patient reported ≥1-point reduction in pain relative to baseline. Average dose achieved was 396 mg/d in the flexible-dose group compared with 295 mg/d in the fixed-dose group. Median pain relief onset times were 3.5 days (flexible-dose), 1.5 days (fixed-dose), and >4 weeks (placebo). Compared with placebo, significantly more patients in both pregabalin treatment groups achieved ≥30% and ≥50% pain reduction at end point. Almost 95% of patients had brush-evoked allodynia, with 68% having moderate to severe allodynia (≥40/100 mm). At baseline, pain and allodynia were highly correlated. Independent of treatment assignment, improvement in pain and improvement in allodynia were significantly correlated. Allodynia could serve as a useful surrogate outcome measure in future studies. Pregabalin was significantly better than placebo in alleviating allodynia (flexible-dose reduction, 26 mm; fixed-dose, 21 mm; placebo, 12 mm). Discontinuation rates due to adverse events were more frequent in the fixed-dose group. Perspective: A flexible-dose regimen reduces discontinuations, facilitates higher final doses, and results in a slightly greater pain relief. Allodynia (touch-evoked pain) can be of disabling severity and is present in nearly all patients with postherpetic neuralgia. Allodynia severity is correlated with pain severity and improvement in allodynia is correlated with clinical response.
KW - PHN
KW - Postherpetic neuralgia
KW - allodynia
KW - pain
KW - pregabalin
KW - time to onset
UR - http://www.scopus.com/inward/record.url?scp=54449100216&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=54449100216&partnerID=8YFLogxK
U2 - 10.1016/j.jpain.2008.05.014
DO - 10.1016/j.jpain.2008.05.014
M3 - Article
C2 - 18640074
AN - SCOPUS:54449100216
SN - 1526-5900
VL - 9
SP - 1006
EP - 1017
JO - Journal of Pain
JF - Journal of Pain
IS - 11
ER -