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(703)
S26 (700) Is reduced dopamine availability the catalyst for grey matter changes in fibromyalgia syndrome? P. Wood; Louisiana State University Health Sciences Center – Shreveport, Shreveport, LA Society for Neuroscience abstract
Abstracts
C08 - Neuropathic Pain (702) A double-blind, randomized, placebo-controlled trial of pregabalin: Time to onset of meaningful pain relief in patients with postherpetic neuralgia (PHN) B Stacey, J Barrett, E Whalen, R Chambers, K Phillips; Oregon Health & Science University, Portland, OR Post hoc analyses of pregabalin RCTs suggest rapid onset of pain relief. This double-blind, randomized, placebo-controlled trial of pregabalin in patients with PHN prospectively evaluated time to onset of meaningful pain relief. Clinically meaningful pain relief was defined as ⱖ1-point improvement in daily pain score (using an 11-point NRS recorded in electronic daily diaries) followed by a decrease of ⱖ30% in weekly pain score at endpoint. Patients with PHN pain ⱖ3 months, pain VAS score ⱖ40 mm (100-mm scale), and who completed the daily pain NRS at least 4 times (average daily score ⱖ4) during the 7-day screening period were eligible. Patients were allowed to continue on stable (ⱖ30 days) treatment regimens for their pain. Ninety-one patients were randomized to flexible-dosage pregabalin (dosage optimized for efficacy/tolerability to 150, 300, or 600 mg/d, BID); 88 to 300-mg/d fixed-dosage pregabalin; and 90 to placebo for 4 weeks of treatment. Primary efficacy parameter was time to onset of clinically meaningful pain relief, summarized with Kaplan-Meier plots and tested for treatment differences using a Cox model controlling for study site and baseline pain score. Most patients (56%) were male; mean age⫽67.4 years (range, 40-86); mean PHN duration ⫽2.5 years; baseline mean pain score⫽6.3-6.7. Eighty-six flexibledosage patients (94.5%), 70 fixed-dosage patients (79.5%), and 75 placebo patients (83.3%) completed the trial. Median time to meaningful pain relief: flexible-dosage pregabalin, 3.5 days (P⬍.0001 vs placebo); fixed-dosage, 1.5 days (P⬍.0001). Less than half of placebo patients achieved ⱖ30% response, so median time to meaningful pain relief is at least greater than the study observation period. Pregabalin was generally well-tolerated. Most common treatment-related AEs: dizziness (flexible-dosage, 24%; fixed-dosage, 28%; placebo, 7%) and somnolence (11%, 18%, 2%). Pregabalin demonstrated rapid onset of clinically meaningful and sustained pain relief, with median time to onset of 1.5 days in the fixed-dosage group.
(701) Medication use by patients with fibromyalgia V Piguet, M Besson, A Allaz, M Escher, C Cedraschi, P Guerne, S Genevay, M Jung, P Dayer, J Desmeules; University Hospital of Geneva, Geneva, Switzerland As patients with fibromyalgia (FM) often state to have received a variety of medication providing partial or no relief, we studied their medication use. Among 1147 patients referred to our Pain Center for chronic pain (1998-2004) who answered a standardized self administered questionnaire, 95 suffered from FM. They were asked to indicate on a list of trade names which drugs they had tried. They were also required to specify the drug efficacy. According to this last criteria 3 groups were determined in FM patients: G1 (n⫽57) rating one or more drug as effective; G2 (n⫽25) rating none as effective; G3: (n⫽13) no answer on efficacy. Bivariate statistical procedures were used to evaluate between-group differences. The groups did not differ in demographic data, pain characteristics or duration, pain prognosis, and in the total number of drugs indicated (mean 15; min:1 max :49), the number of NSAIDs (mean 5; min:1 max:13; taken by 92% of the FM patients), antidepressants (mean 2.5; min:1 max:14; taken by 87%) and anticonvulsivants (mean 1; min:1 max: 4; taken by 58%). There was no difference in medication use between groups but patients who had tried at least one weak (81%) or/ and strong (20%) opioid received statistically more drugs of all classes than the other patients (p⫽0.05). The satisfaction with the medication taken was very low on a VAS (mean 3/10; SD 2) in the 2 groups who rated this criteria. Antidepressants were less often cited as effective than weak opioids although they are recommended in fibromyalgia. Medication use in FM patients is high and does not always correspond to recommendations. Many different drugs are tried by these patients who nevertheless do not rate them as effective.
(703) Evaluation of safety and efficacy of pregabalin for chronic central neuropathic pain following spinal cord injury (SCI): An open-label extension study T Murphy, T Griesing, E Whalen; Pfizer Global Pharmaceuticals, New York, NY Pregabalin— dosed flexibly 150-600 mg/d (BID)—was evaluated in a 13week, double-blind, randomized, placebo-controlled trial as treatment of central neuropathic pain associated with SCI. This open-label, 9-month extension study enrolled compliant patients with no serious treatment-associated adverse events (AEs). Open-label treatment was initiated with pregabalin 150 mg/d BID within 1 week of concluding double-blind. Dosage adjustments from 150-600 mg/d were allowed to optimize efficacy and tolerability. Quarterly drug holidays lasted 3-28 days; if patients relapsed (ie, pain worsened at least “moderately”), they returned to treatment. Patients who did not relapse during a drug holiday were withdrawn. Efficacy was assessed by the SF-MPQ and safety by AEs and clinical and laboratory assessments. Of 104 patients entering open-label, 1 was not treated, 60 completed the study’s 9 months, 43 discontinued. 51 had received double-blind pregabalin, 53 placebo. Mean weighted dosage of pregabalin was 388 mg/d (estimated average excluding drug holidays). At endpoint, patients showed improvements from baseline in mean sensory (-0.7, SD⫽5.8), affective (-0.3, SD⫽2.8), and total (-1.0, SD⫽8.1) SF-MPQ scores. Improvements were also evident on the pain VAS (-7.9, SD⫽25.2) and PPI (-0.3, SD⫽1.2) scales. Most patients (n⫽88) rated their pain during drug holidays as “very much” or “much” worse (70.5%); 3 patients were withdrawn because they did not relapse during a drug holiday. The most frequent treatment-associated AEs were somnolence (18.4%), dizziness (16.5%), asthenia (12.6%), nausea (11.7%), and constipation and insomnia (10.7% each). 3.9% of patients had serious treatment-associated AEs; 14.6% withdrew because of AEs. One patient died of nontreatment-related cancer. Changes in other safety measures were not clinically meaningful. Results of this long-term study of pregabalin as treatment for chronic central neuropathic pain after SCI demonstrated sustained analgesic effect for ⱖ1 year. The AE profile observed with long-term treatment was consistent with that described in reports of short-term trials.
Abstracts
C08 - Neuropathic Pain (702) A double-blind, randomized, placebo-controlled trial of pregabalin: Time to onset of meaningful pain relief in patients with postherpetic neuralgia (PHN) B Stacey, J Barrett, E Whalen, R Chambers, K Phillips; Oregon Health & Science University, Portland, OR Post hoc analyses of pregabalin RCTs suggest rapid onset of pain relief. This double-blind, randomized, placebo-controlled trial of pregabalin in patients with PHN prospectively evaluated time to onset of meaningful pain relief. Clinically meaningful pain relief was defined as ⱖ1-point improvement in daily pain score (using an 11-point NRS recorded in electronic daily diaries) followed by a decrease of ⱖ30% in weekly pain score at endpoint. Patients with PHN pain ⱖ3 months, pain VAS score ⱖ40 mm (100-mm scale), and who completed the daily pain NRS at least 4 times (average daily score ⱖ4) during the 7-day screening period were eligible. Patients were allowed to continue on stable (ⱖ30 days) treatment regimens for their pain. Ninety-one patients were randomized to flexible-dosage pregabalin (dosage optimized for efficacy/tolerability to 150, 300, or 600 mg/d, BID); 88 to 300-mg/d fixed-dosage pregabalin; and 90 to placebo for 4 weeks of treatment. Primary efficacy parameter was time to onset of clinically meaningful pain relief, summarized with Kaplan-Meier plots and tested for treatment differences using a Cox model controlling for study site and baseline pain score. Most patients (56%) were male; mean age⫽67.4 years (range, 40-86); mean PHN duration ⫽2.5 years; baseline mean pain score⫽6.3-6.7. Eighty-six flexibledosage patients (94.5%), 70 fixed-dosage patients (79.5%), and 75 placebo patients (83.3%) completed the trial. Median time to meaningful pain relief: flexible-dosage pregabalin, 3.5 days (P⬍.0001 vs placebo); fixed-dosage, 1.5 days (P⬍.0001). Less than half of placebo patients achieved ⱖ30% response, so median time to meaningful pain relief is at least greater than the study observation period. Pregabalin was generally well-tolerated. Most common treatment-related AEs: dizziness (flexible-dosage, 24%; fixed-dosage, 28%; placebo, 7%) and somnolence (11%, 18%, 2%). Pregabalin demonstrated rapid onset of clinically meaningful and sustained pain relief, with median time to onset of 1.5 days in the fixed-dosage group.
(701) Medication use by patients with fibromyalgia V Piguet, M Besson, A Allaz, M Escher, C Cedraschi, P Guerne, S Genevay, M Jung, P Dayer, J Desmeules; University Hospital of Geneva, Geneva, Switzerland As patients with fibromyalgia (FM) often state to have received a variety of medication providing partial or no relief, we studied their medication use. Among 1147 patients referred to our Pain Center for chronic pain (1998-2004) who answered a standardized self administered questionnaire, 95 suffered from FM. They were asked to indicate on a list of trade names which drugs they had tried. They were also required to specify the drug efficacy. According to this last criteria 3 groups were determined in FM patients: G1 (n⫽57) rating one or more drug as effective; G2 (n⫽25) rating none as effective; G3: (n⫽13) no answer on efficacy. Bivariate statistical procedures were used to evaluate between-group differences. The groups did not differ in demographic data, pain characteristics or duration, pain prognosis, and in the total number of drugs indicated (mean 15; min:1 max :49), the number of NSAIDs (mean 5; min:1 max:13; taken by 92% of the FM patients), antidepressants (mean 2.5; min:1 max:14; taken by 87%) and anticonvulsivants (mean 1; min:1 max: 4; taken by 58%). There was no difference in medication use between groups but patients who had tried at least one weak (81%) or/ and strong (20%) opioid received statistically more drugs of all classes than the other patients (p⫽0.05). The satisfaction with the medication taken was very low on a VAS (mean 3/10; SD 2) in the 2 groups who rated this criteria. Antidepressants were less often cited as effective than weak opioids although they are recommended in fibromyalgia. Medication use in FM patients is high and does not always correspond to recommendations. Many different drugs are tried by these patients who nevertheless do not rate them as effective.
(703) Evaluation of safety and efficacy of pregabalin for chronic central neuropathic pain following spinal cord injury (SCI): An open-label extension study T Murphy, T Griesing, E Whalen; Pfizer Global Pharmaceuticals, New York, NY Pregabalin— dosed flexibly 150-600 mg/d (BID)—was evaluated in a 13week, double-blind, randomized, placebo-controlled trial as treatment of central neuropathic pain associated with SCI. This open-label, 9-month extension study enrolled compliant patients with no serious treatment-associated adverse events (AEs). Open-label treatment was initiated with pregabalin 150 mg/d BID within 1 week of concluding double-blind. Dosage adjustments from 150-600 mg/d were allowed to optimize efficacy and tolerability. Quarterly drug holidays lasted 3-28 days; if patients relapsed (ie, pain worsened at least “moderately”), they returned to treatment. Patients who did not relapse during a drug holiday were withdrawn. Efficacy was assessed by the SF-MPQ and safety by AEs and clinical and laboratory assessments. Of 104 patients entering open-label, 1 was not treated, 60 completed the study’s 9 months, 43 discontinued. 51 had received double-blind pregabalin, 53 placebo. Mean weighted dosage of pregabalin was 388 mg/d (estimated average excluding drug holidays). At endpoint, patients showed improvements from baseline in mean sensory (-0.7, SD⫽5.8), affective (-0.3, SD⫽2.8), and total (-1.0, SD⫽8.1) SF-MPQ scores. Improvements were also evident on the pain VAS (-7.9, SD⫽25.2) and PPI (-0.3, SD⫽1.2) scales. Most patients (n⫽88) rated their pain during drug holidays as “very much” or “much” worse (70.5%); 3 patients were withdrawn because they did not relapse during a drug holiday. The most frequent treatment-associated AEs were somnolence (18.4%), dizziness (16.5%), asthenia (12.6%), nausea (11.7%), and constipation and insomnia (10.7% each). 3.9% of patients had serious treatment-associated AEs; 14.6% withdrew because of AEs. One patient died of nontreatment-related cancer. Changes in other safety measures were not clinically meaningful. Results of this long-term study of pregabalin as treatment for chronic central neuropathic pain after SCI demonstrated sustained analgesic effect for ⱖ1 year. The AE profile observed with long-term treatment was consistent with that described in reports of short-term trials.