Perspectives on the impact of painful diabetic peripheral neuropathy in a multicultural population.

BACKGROUND: Since few studies have characterized painful diabetic peripheral neuropathy (pDPN) symptoms in multicultural populations, this study fielded a survey to better understand pDPN and its impact in African-American, Caucasian, and Hispanic populations. METHODS: Kelton fielded a survey by phone or Internet, in English or Spanish, among adults with pDPN symptoms in the United States between August and October 2015; African-Americans and Hispanics were oversampled to achieve at least 500 subjects for each group. Patients were required to have been diagnosed with pDPN or score ≥ 3 on ID Pain validated screening tool. The survey elicited information on pDPN symptoms and interactions with healthcare providers (HCPs), and included the Brief Pain Inventory and pain-specific Work Productivity and Assessment Questionnaire (WPAI:SHP). RESULTS: Respondents included 823 Caucasians, 525 African-Americans, and 537 Hispanics; approximately half of African-Americans and Hispanics were <40 years of age, vs 12% of Caucasians. Pain was less likely to be rated moderate or severe by African-Americans (65%) and Hispanics (49%) relative to Caucasians (87%; p < 0.05). African-Americans and Hispanics were less likely than Caucasians to report experiencing specific pDPN sensory symptoms. Significantly fewer African-Americans and Hispanics reported receiving a pDPN diagnosis relative to Caucasians (p < 0.05), and higher proportions of African-Americans and Hispanics reported difficulty communicating with their HCP (p < 0.05). WPAI:SHP activity impairment was lower in Hispanics (43%) relative to African-Americans (53%) and Caucasian (56%; p < 0.05). CONCLUSIONS: Multicultural patients reported differences in pDPN symptoms and pain relative to Caucasians, and fewer received a pDPN diagnosis. While further evaluation is needed to understand these differences, these data suggest a need to broaden pDPN educational initiatives to improve patient-HCP dialogue and encourage discussion of pDPN symptoms and their impact in a multicultural setting.

Bapineuzumab for mild to moderate Alzheimer's disease in two global, randomized, phase 3 trials.

BACKGROUND: Our objective was to evaluate the efficacy (clinical and biomarker) and safety of intravenous bapineuzumab in patients with mild to moderate Alzheimer's disease (AD). METHODS: Two of four phase 3, multicenter, randomized, double-blind, placebo-controlled, 18-month trials were conducted globally: one in apolipoprotein E ε4 carriers and another in noncarriers. Patients received bapineuzumab 0.5 mg/kg (both trials) or 1.0 mg/kg (noncarrier trial) or placebo every 13 weeks. Coprimary endpoints were change from baseline to week 78 on the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale and the Disability Assessment for Dementia. RESULTS: A total of 683 and 329 patients completed the current carrier and noncarrier trials, respectively, which were terminated prematurely owing to lack of efficacy in the two other phase 3 trials of bapineuzumab in AD. The current trials showed no significant difference between bapineuzumab and placebo for the coprimary endpoints and no effect of bapineuzumab on amyloid load or cerebrospinal fluid phosphorylated tau. (Both measures were stable over time in the placebo group.) Amyloid-related imaging abnormalities with edema or effusion were confirmed as the most notable adverse event. CONCLUSIONS: These phase 3 global trials confirmed lack of efficacy of bapineuzumab at tested doses on clinical endpoints in patients with mild to moderate AD. Some differences in the biomarker results were seen compared with the other phase 3 bapineuzumab trials. No unexpected adverse events were observed. TRIAL REGISTRATION: Noncarriers (3000) ClinicalTrials.gov identifier NCT00667810 ; registered 24 Apr 2008. Carriers (3001) ClinicalTrials.gov identifier NCT00676143 ; registered 2 May 2008.

Burden of HIV-Related Neuropathic Pain in the United States.

BACKGROUND: HIV-related neuropathic pain (HIV-NeP) is common; however, the burden of HIV-NeP is not well-understood. METHODS: The cross-sectional study aimed to characterize the HIV-NeP burden. A total of 103 patients with HIV-NeP recruited during routine office visits completed a questionnaire to assess patient-reported outcomes, including pain severity, health status, sleep, mood, and lost productivity. Physicians completed a 6-month retrospective chart review. RESULTS: The sample was predominantly male and not employed for pay. A majority (75.7%) of patients experienced moderate or severe pain. Pain interference, general health, physical health, and depression were worse among patients with more severe pain (all Ps < .006). Most (87.4%) patients were prescribed at least 1 medication for NeP. HIV-related neuropathic pain was associated with 36.1% work impairment. Adjusted annualized costs increased with increasing pain severity (P < .0001). CONCLUSION: The impact of HIV-NeP on health status, physical function, and depression increases with severity, resulting in substantial clinical and economic burden.

Efficacy and Safety of Pregabalin in the Treatment of Patients With Painful Diabetic Peripheral Neuropathy and Pain on Walking.

OBJECTIVES: This randomized, double-blind, placebo-controlled, multicenter, 2-period crossover study (two 6-week treatment periods separated by a 2-week washout period) evaluated the efficacy and safety of pregabalin (150 to 300 mg/d) for treatment of pain and pain on walking in patients with painful diabetic peripheral neuropathy (DPN) who experienced pain while walking. METHODS: Co-primary efficacy endpoints were: (1) mean pain score (last 7 daily pain diary scores, 0 to 10 numeric rating scale at end of each treatment period) and (2) DPN pain on walking (0 to 10 numeric rating scale immediately after walking 50 feet [15.2 m] on flat surface). Secondary endpoints included other pain parameters, patient-reported sleep, health-related quality of life, and safety measures. RESULTS: Two hundred three patients were treated (pregabalin, n=198; placebo, n=186), with no statistically significant treatment difference for pregabalin versus placebo in the co-primary efficacy endpoints, mean DPN pain (P=0.0656) and mean DPN pain on walking (P=0.412). A carryover effect was observed. Analysis of co-primary endpoints for period 1 showed significant treatment difference for DPN pain (P=0.034) and DPN pain on walking (P=0.001). Treatment with pregabalin resulted in significant improvements versus placebo on prespecified patient global impression of change (end of period 1; P=0.002), and sleep interference rating scale (end of period 2; P=0.011). Adverse events were more frequent with pregabalin than with placebo and caused discontinuation in 13 (6.6%) pregabalin patients versus 5 (2.7%) placebo patients. DISCUSSION: Failure to meet the co-primary objectives may be related to carryover effect from period 1 to period 2, lower pregabalin dose (150 to 300 mg/d), and/or placebo response in painful DPN.

Pain severity and the economic burden of neuropathic pain in the United States: BEAT Neuropathic Pain Observational Study.

BACKGROUND: As with many chronic conditions, patients with neuropathic pain (NeP) are high consumers of health care resources. However, limited literature exists on the economic burden of NeP, including its impact on productivity. The aim of this study was to characterize health care resource utilization, productivity, and costs associated with NeP by pain severity level in US adults. METHODS: Subjects (n=624) with painful diabetic peripheral neuropathy, human immunodeficiency virus-related peripheral NeP, post-trauma/post-surgical NeP, spinal cord injury with NeP, chronic low back pain with NeP, and small fiber neuropathy were recruited during routine office visits to US community-based general practitioners and specialists. Clinicians captured clinical characteristics, NeP-related medications, and health care resource utilization based on 6-month retrospective medical chart review. Subjects completed questionnaires on demographics, pain/symptoms, costs, and productivity. Brief Pain Inventory pain severity scores were used to classify subjects by mild, moderate, or severe pain. Annualized NeP-related costs (adjusted for covariates) were estimated, and differences across pain severity groups were evaluated. RESULTS: In total, 624 subjects were recruited (mean age 55.5±13.7 years; 55.4% male), and 504/624 (80.8%) reported moderate or severe pain. Statistically significant differences were observed across pain severity levels for number of comorbidities, prescription medications, physician office visits, and lost productivity (all P≤0.0001). At all pain severity levels, indirect costs were the primary cost driver. After adjusting for demographic and clinical variables, total mean (95% confidence interval [CI]) annualized direct medical costs to payers, direct costs to subjects, and indirect costs per subject were US$6,016 (95% CI 5,316-6,716), US$2,219 (95% CI 1,919-2,519), and US$19,000 (95% CI 17,197-20,802), respectively, with significant differences across pain severity levels. CONCLUSION: Subjects with NeP, mainly those showing moderate or severe pain, had significant associations between pain severity and NeP-related health care resource utilization, productivity, and costs. The economic burden, particularly indirect costs, was highest among those with severe pain and higher than previously reported in studies of specific NeP conditions.

Burden of illness associated with peripheral and central neuropathic pain among adults seeking treatment in the United States: a patient-centered evaluation.

OBJECTIVE: The aim of this study was to evaluate patient-reported burden associated with peripheral and central neuropathic pain (NeP) by pain severity and NeP condition. DESIGN: Six hundred twenty-four subjects with one of six NeP conditions were recruited during routine office visits. Subjects consented to retrospective chart review and completed a one-time questionnaire (including EuroQol-5 dimensions, 12-item Short-Form Health Survey, Brief Pain Inventory-Short Form, Medical Outcomes Study Sleep Scale, Hospital Anxiety and Depression Scale, and demographic and clinical characteristics). Pain severity scores were used to stratify subjects by mild, moderate, and severe pain. Summary statistics and frequency distributions were calculated. Differences by severity level were compared using Kruskal-Wallis (continuous variables) and chi-square or Fisher's exact test (categorical variables). Effect size was computed with Cohen's d (mild vs severe). RESULTS: Subjects' mean age was 55.5. The majority (80.8%) had moderate or severe pain. Patient-reported outcomes (health status, physical and mental health, pain interference with function, sleep, anxiety, and depression) were significantly worse among subjects with greater pain severity (all P < 0.0001). Severe pain subjects were negatively impacted by ≥30% in each outcome compared with mild pain subjects; standardized effect size was moderate for anxiety (0.59) and large (>0.95) for all others. The observed burden was most substantial among chronic low back pain-NeP, although the pattern of disease burden was similar across the six NeP conditions. CONCLUSIONS: Subjects across NeP conditions exhibited high pain levels, which were significantly associated with poor function, compromised health status and sleep, and increased anxiety and depression. Results indicate substantial patient burden across broad NeP, particularly among subjects with severe pain.

Health status, function, productivity, and costs among individuals with idiopathic painful peripheral neuropathy with small fiber involvement in the United States: results from a retrospective chart review and cross-sectional survey.

OBJECTIVE: To characterize the burden of idiopathic painful peripheral neuropathy with small fiber involvement (idiopathic SFN) by pain severity in the US. METHODS: One hundred previously diagnosed idiopathic SFN subjects were enrolled during routine office visits. Subjects completed a one-time questionnaire, and investigators reported clinical characteristics and healthcare resource use, based on 6 month retrospective chart review. Annualized direct and indirect costs were estimated. Results were stratified across pain severity groups. RESULTS: Mean age was 63.5 years; 53.0% were female; 76.0% had moderate or severe pain. Most common comorbidities were sleep disturbance/insomnia (37.0%), anxiety (34.0%), and depressive symptoms (33.0%). Overall mean health status (0.59; -0.11-1.00 scale), physical and mental health (31.7 and 45.6, respectively, 0-100 scale), sleep index (45.1; 0-100 scale), and pain interference with function (5.0; 0-10 scale) differed by pain severity, with worse outcomes among those with greater pain (all p < 0.002). 84.0% were prescribed ≥1 SFN medication. 16.0% were employed; mean overall work impairment was 36.9%. Annualized average adjusted direct and indirect costs per subject ($8055 and $13,733, respectively) differed by pain severity. CONCLUSIONS: Idiopathic SFN subjects with pain experience moderate or severe pain, which negatively impacts health status, function, and productivity, and leads to substantial direct and indirect costs.

Economic and humanistic burden of post-trauma and post-surgical neuropathic pain among adults in the United States.

BACKGROUND: Neuropathic pain (NeP) can be chronic, debilitating, and can interfere with sleep, functioning, and emotional well being. While there are multiple causes of NeP, few studies have examined the disease burden and treatment patterns associated with post-traumatic/post-surgical (PTPS) NeP. OBJECTIVE: To characterize pain, health status, function, health care resource utilization, lost productivity, and costs among subjects with PTPS NeP in the United States. METHODS: This observational study enrolled 100 PTPS NeP subjects recruited during routine visits from general practitioner and specialist sites. Subjects completed a one-time questionnaire with validated measures of pain severity and pain interference, health status, sleep, anxiety and depression, productivity, and study-specific items on demographics, employment status, and out-of-pocket expenses. Investigators completed a case report form based on a 6-month retrospective chart review, recording subjects' clinical characteristics as well as current and previous medications/treatments for NeP. Subjects were stratified into mild, moderate, and severe pain groups. RESULTS: Subjects' demographic characteristics were: mean age of 54.9 years, 53% female, and 22% employed for pay. Mean pain severity score was 5.6 (0-10 scale), with 48% and 35% classified as having moderate and severe pain, respectively. The mean number of comorbidities increased with greater pain severity (P = 0.0009). Patient-reported outcomes were worse among PTPS NeP subjects with more severe pain, including pain interference with function, health state utility, sleep, and depression (P < 0.0001). Eighty-two percent of subjects were prescribed two or more NeP medications. The total mean annualized adjusted direct and indirect costs per subject were $11,846 and $29,617, respectively. Across pain severity levels, differences in annualized adjusted direct and indirect costs were significant (P < 0.0001). CONCLUSION: PTPS NeP subjects reported high pain scores, which were associated with poor health utility, sleep, mood, and function, as well as high health care resource utilization and costs. The quality of life impact and costs attributable to PTPS NeP suggest an unmet need for effective and comprehensive management.

Burden of illness associated with painful diabetic peripheral neuropathy among adults seeking treatment in the US: results from a retrospective chart review and cross-sectional survey.

BACKGROUND: The purpose of this study was to characterize the burden of illness among adult subjects with painful diabetic peripheral neuropathy (pDPN) seeking treatment in the US. METHODS: This observational study recruited 112 subjects with pDPN during routine visits from general practitioner and specialist sites. Subjects completed a one-time questionnaire, which included demographics, symptom duration, health care resource use, out-of-pocket costs, employment status, and validated measures that assessed pain, functioning, sleep, anxiety and depression, health status, and productivity. Investigators completed a case report form based on a 6-month retrospective chart review to capture clinical information, pDPN-related treatments, and other pDPN-related health care resource use over the past 6 months. Annualized costs were extrapolated based on reported 6-month health care resource use. RESULTS: The mean age of the subjects was 61.1 years, 52.7% were female, and 17.9% were in paid employment. The most common comorbid conditions were sleep disturbance/insomnia (43.8%), depressive symptoms (41.1%), and anxiety (35.7%). The mean pain severity score was 5.2 (0-10 scale), and 79.5% reported moderate or severe pain. The mean pain interference with function score was 5.0 (0-10 scale) overall, with 2.0 among mild, 5.1 among moderate, and 7.0 among severe. The mean Medical Outcomes Study sleep problems index score was 48.5 (0-100 scale). The mean health state utility score was 0.61. Among subjects employed for pay, mean overall work impairment was 43.6%. Across all subjects, mean overall activity impairment was 52.3%. In total, 81.3% were prescribed at least one medication for their pDPN; 50.9% reported taking at least one nonprescription medication. Adjusted mean annualized total direct and indirect costs per subject were $4841 and $9730, respectively. Outcomes related to pain interference with function, sleep, health status, activity impairment, prescription medication use, and direct and indirect costs were significantly worse among subjects with more severe pain (P < 0.0020). CONCLUSION: Subjects with pDPN exhibited high pain levels, which were associated with poor sleep, function, and productivity. Health care resource utilization in pDPN was prevalent and costs increased with greater pain severity. The burden of pDPN was greater among subjects with greater pain severity.

A multicenter, randomized, double-blind, controlled dose finding study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia.

UNLABELLED: Postherpetic neuralgia (PHN) is a painful complication of acute herpes zoster. This multicenter, double-blind, controlled study randomized 299 PHN patients to receive either NGX-4010, a high-concentration capsaicin (8%) patch, or a low-concentration capsaicin (0.04%) control patch for 30, 60, or 90 minutes. The mean percent reductions in NPRS score from baseline to weeks 2 through 8 were significantly greater in the total NGX-4010 group (26.5%, P = .0286) and the 90-minute NGX-4010 group (27.8%, P = .0438) compared to the pooled control group (17.3%). After review of the data suggested a difference between genders in reporting of pain scores and a higher proportion of males (61%) in the 60-minute NGX-4010 group, post hoc gender-stratified analyses were performed and showed that the 60-minute NGX-4010 group also had a significantly larger mean percent reduction in average pain scores (28.0%, P = .0331). Pain reduction in the 30-minute NGX-4010 group, although similar in magnitude to the other doses, was not significantly different from control in either of these analyses. Similar results were observed during weeks 2 through 12. Most treatment-emergent adverse events were application-site specific, transient and mostly mild to moderate in severity. PERSPECTIVE: This article reports the safety and efficacy of NGX-4010 applied for 3 different durations (30, 60, or 90 minutes) in patients with PHN. The results identified the 60-minute duration as the dose to be evaluated in subsequent studies and identified a gender effect on reported changes in pain.

Central sensitization and Ca(V)α2δ ligands in chronic pain syndromes: pathologic processes and pharmacologic effect.

UNLABELLED: Central sensitization is one form of long-term plasticity in the central nervous system. Sustained activation of primary sensory fibers supplying dorsal horn can induce long-lasting increases in the discharge amplitude of primary afferent synapses. This is similar to the long-term potentiation that occurs in many other CNS regions. Drugs that limit the short-duration wind-up component of central sensitization include sodium channel blockers, NMDA antagonists, fast-acting opioids and the calcium-channel ligands gabapentin and pregabalin (S-3-(aminomethyl)-5-methylhexanoic acid). Pregabalin, like gabapentin, binds selectively to the Ca(V)α2δ auxiliary subunit of presynaptic voltage-gated calcium channels. The conformational changes induced by this binding inhibit abnormally intense neuronal activity by reducing the synaptic release of glutamate and other neurotransmitters. Recent identification in animal models of increased Ca(V)α2δ protein expression in chronic pain, allodynia, and hyperalgesia have drawn additional interest to drugs that bind the Ca(V)α2δ site. Experimental studies with animal models and healthy human volunteers have shown that pregabalin reduces nociceptive responses, particularly in conditions involving central sensitization. Since these actions occur with relatively modest effects on physiological and cognitive functions, pregabalin may be an important consideration in the pharmacotherapy of otherwise difficult-to-treat pain syndromes. PERSPECTIVE: This focus article discusses how the central nervous system plasticity phenomenon, central sensitization, is established in the induction and maintenance of chronic pain, allodynia, and hyperalgesia. In addition, it explores the neurophysiologic actions of the calcium-channel ligands gabapentin and pregabalin in limiting pathological manifestations of central sensitization.

Oral zolmitriptan in the short-term prevention of menstrual migraine: a randomized, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and tolerability of oral zolmitriptan as a short-term preventative therapy for menstrual migraine. METHODS: This was a randomized, double-blind, parallel group, placebo-controlled, multicentre, two-phase study. The results of the second phase are reported here (the first phase evaluated zolmitriptan in the acute treatment of menstrual migraine and is reported elsewhere). Women who successfully completed phase I (with either a positive or negative outcome, and who still fulfilled the inclusion criteria) were randomized to zolmitriptan 2.5 mg oral tablet three times daily, zolmitriptan 2.5 mg twice daily or placebo three times daily. Patients were treated for three consecutive menstrual cycles, starting 2 days prior to the expected onset of menses, for 7 days in total. RESULTS: Two hundred and fifty-three patients completed phase I and were eligible for phase II. The intention-to-treat population comprised 244 patients (zolmitriptan three times daily [n = 83]; zolmitriptan twice daily [n = 80]; placebo [n = 81]). Both zolmitriptan regimens demonstrated superior efficacy versus placebo, as measured by the proportion of patients with a >or=50% reduction in the frequency of menstrual migraine attacks (zolmitriptan three times daily [58.6%], p = 0.0007 vs placebo; zolmitriptan twice daily [54.7%], p = 0.002 vs placebo; placebo three times daily [37.8%]). The mean frequency of breakthrough migraine attacks per menstrual cycle was reduced accordingly. Fewer breakthrough attacks were treated with escape medication in the zolmitriptan three times daily (61.6% of attacks; p = 0.0004 vs placebo) and twice daily (60.7%; p = 0.0055 vs placebo) treatment groups than in the placebo group (74.4%). Short-term preventative therapy with zolmitriptan was well tolerated. CONCLUSION: Zolmitriptan 2.5 mg oral tablet is effective and well tolerated as a short-term preventative therapy for menstrual migraine attacks.

Lamotrigine for treatment of pain associated with diabetic neuropathy: results of two randomized, double-blind, placebo-controlled studies.

To assess the efficacy and tolerability of lamotrigine in pain associated with diabetic neuropathy, two replicate randomized, double-blind, placebo-controlled studies were conducted. Patients (n=360 per study) with painful diabetic neuropathy were randomized to receive lamotrigine 200, 300, or 400 mg daily or placebo during the 19-week treatment phase, including a 7-week dose-escalation phase and a 12-week, fixed-dose maintenance phase. The mean reduction in pain-intensity score from baseline to week 19 (primary endpoint) was greater (p < or = 0.05) in patients receiving lamotrigine 400 mg than placebo in Study 2 (observed scores, -2.7 versus -1.6 on a 0- to 10-point scale). This finding was not replicated in Study 1. Lamotrigine 200 and 300 mg did not significantly differ from placebo at week 19 in either study. Lamotrigine 300 and 400 mg were only occasionally more effective than placebo for secondary efficacy endpoints. The 200-mg dose did not separate from placebo. In a post hoc analysis of pooled data including only patients who reached their target dose, lamotrigine 400 mg conferred greater (p0.05) mean reduction in pain-intensity score from baseline to week 19 than placebo (-2.5 for 300 mg and -2.7 for 400mg versus -2.0 for placebo). Adverse events were reported in 71-82% of lamotrigine-treated patients compared with 63-70% of placebo-treated patients. The most common adverse events with lamotrigine were headache and rash. Compared with placebo, lamotrigine (300 and 400 mg daily) was inconsistently effective for pain associated with diabetic neuropathy but was generally safe and well tolerated.

Efficacy and tolerability of zolmitriptan oral tablet in the acute treatment of menstrual migraine.

OBJECTIVE: To determine the efficacy and tolerability of zolmitriptan 2.5 mg oral tablet as an acute treatment for menstrual migraine attacks. METHODS: This was a two-phase, multicentre, randomised, double-blind, placebo-controlled, parallel-group outpatient study (Phase I is reported here). The study was conducted at 27 sites in the USA. Eligible women were randomised (1 : 1) to receive either zolmitriptan 2.5 mg oral tablet or placebo, and instructed to acutely treat up to two menstrual migraine attacks per menstrual period for up to three menstrual cycles with a single dose of study medication. Menstrual migraine was operationally defined as an attack occurring within the time period of 2 days prior to the expected onset of menses to 5 days after the onset of menses. Participants were asked to treat migraine headaches of moderate or severe intensity only that occurred >24 hours after the end of the last migraine attack and that had not been acutely treated with other medications. Information regarding each migraine attack was recorded by patients in treatment diary cards. The primary efficacy variable was 2-hour headache response (defined as a 2-point drop on a 4-point scale) for all attacks treated. Secondary variables included 1- and 4-hour headache response rate; 1-, 2- and 4-hour headache response based on a 100 mm visual analogue scale (VAS); pain-free rate at 1, 2 and 4 hours; use of escape medication; the proportion of patients with recurrence within 24 hours of initial treatment; and tolerability. RESULTS: The intention-to-treat population comprised 334 patients (zolmitriptan [n = 174]; placebo [n = 160]). Patients treated 625 attacks with zolmitriptan and 529 attacks with placebo. Twice as many patients who took zolmitriptan achieved a 2-hour headache response compared with placebo recipients (65.7% vs 32.8%; p < 0.0001). Furthermore, a significantly higher headache response was observed with zolmitriptan than placebo at all timepoints assessed. Significantly more zolmitriptan recipients were pain-free 2 hours post-dose compared with placebo recipients (p < 0.0001). The use of escape medication was considerably lower in zolmitriptan recipients (42.6% vs 71.3%; p < 0.0001). Based on the reduction in VAS score of > or = 30 mm from baseline, significantly more zolmitriptan recipients achieved headache response compared with placebo recipients at 1, 2 and 4 hours post-dose (all p < 0.0001). Recurrence was reported in 29.1% of zolmitriptan-treated attacks versus 45.1% of placebo-treated attacks (p = 0.0009), with median time to recurrence of 8.5 and 4.0 hours, respectively. Zolmitriptan was well tolerated. CONCLUSION: Oral zolmitriptan is effective and well tolerated for the acute treatment of menstrual migraine attacks. The results are similar to those seen with zolmitriptan in studies of the general migraine population.

Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial.

A randomized, double-blind, placebo-controlled, parallel-group, multicenter, 8-week trial (with subsequent open-label phase) evaluated the effectiveness of pregabalin in alleviating pain associated with diabetic peripheral neuropathy (DPN). For enrollment, patients must have had at baseline: 1- to 5-year history of DPN pain; pain score > or =40 mm (Short-Form McGill Pain Questionnaire [SF-MPQ] visual analogue scale); average daily pain score of > or =4 (11-point numerical pain rating scale [0 = no pain, 10 = worst possible pain]). One hundred forty-six (146) patients were randomized to receive placebo (n = 70) or pregabalin 300 mg/day (n = 76). Primary efficacy measure was endpoint mean pain score from daily patient diaries (11-point numerical pain rating scale). Secondary measures included SF-MPQ scores; sleep interference scores; Patient and Clinical Global Impression of Change (PGIC and CGIC); Short Form-36 (SF-36) Health Survey scores; and Profile of Mood States (POMS) scores. Safety assessment included incidence and intensity of adverse events, physical and neurological examinations, and laboratory evaluations. Pregabalin produced significant improvements versus placebo for mean pain scores (P < 0.0001); mean sleep interference scores SF-36 Bodily Pain subscale (P < 0.0001); total SF-MPQ score (P < 0.01); SF-36 Bodily Pain subscale (P < 0.03); PGIC (P = 0.001); and Total Mood Disturbance and Tension-Anxiety components of POMS (P < 0.03). Pain relief and improved sleep began during week 1 and remained significant throughout the study (P < 0.01). Pregabalin was well tolerated despite a greater incidence of dizziness and somnolence than placebo. Most adverse events were mild to moderate and did not result in withdrawal. Pregabalin was safe and effective in decreasing pain associated with DPN, and also improved mood, sleep disturbance, and quality of life.