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Two multicenter, randomized, placebo-controlled, adaptive-design trials of desvenlafaxine for fibromyalgia syndrome (FMS) were conducted. In study 1, male and female patients were randomized to a 27-week treatment with placebo or desvenlafaxine 50, 100, 200, or 400 mg/d. In study 2, female patients were randomized to an 8-week treatment with placebo, desvenlafaxine 200 mg/d, or pregabalin 450 mg/d after a placebo run-in. The primary efficacy end point was change from baseline in numeric rating scale (NRS) pain score. Protocol-specified interim analyses were planned after 12 (study 1) and 8 (study 2) weeks of treatment. Safety data were collected. In all, 697 patients were randomly assigned to treatment in study 1. At the interim analysis (n = 346), none of the desvenlafaxine doses met the efficacy criteria (mean [SE] advantage over placebo, -0.21 [0.36] to 0.04 [0.35]), and the study was terminated. Study 2 was stopped for business reasons before the planned interim analysis. NRS scores in week 8 were -1.98 (0.37), -1.60 (0.37), and -1.70 (0.38) for placebo (n = 26), desvenlafaxine 250 mg/d (n = 24), and pregabalin 450 mg/d (n = 21), respectively; neither active treatment differed significantly from placebo. Desvenlafaxine was generally safe and well tolerated. Efficacy of desvenlafaxine for pain associated with FMS was not demonstrated.

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PURPOSE: To assess the safety and efficacy of the serotonin-norepinephrine reuptake inhibitor desvenlafaxine in adults with painful diabetic peripheral neuropathy (DPN). CLINICALTRIALSGOV IDENTIFIERS: NCT00283842, NCT01050218. PATIENTS AND METHODS: This was a 13-week, randomized, double-blind, placebo-controlled, fixed-dose study of desvenlafaxine in adults with painful DPN. The primary efficacy endpoint was change from baseline in numeric rating scale (NRS) score. Patients who completed the 13-week trial could continue in a 9-month open-label, flexible-dose extension study. RESULTS: A total of 412 patients were randomized to treatment with placebo or desvenlafaxine 50, 100, 200, or 400 mg/day. Of those, 240 patients continued in the extension study. After a planned interim analysis, conducted when the first 225 patients had completed 6 weeks of treatment in the short-term study, randomization to the 50 mg or 400 mg doses was stopped. At week 13, the mean change from baseline in NRS score was significantly greater compared with placebo in the desvenlafaxine 200 mg (difference [95% confidence interval {CI}]: 1.10 [0.50 to 1.70]; P<0.001) and 400 mg groups (0.91 [95% CI: 0.23 to 1.59]; P=0.027); differences from placebo were not statistically significant for the 50 mg (0.58 [95% CI: -0.08 to 1.25]) and 100 mg (0.59 [95% CI: -0.03 to 1.21]) groups. Nausea and dizziness were the most common treatment-emergent adverse events reported in the short-term study, and the most common adverse events leading to discontinuation in the short-term study and the extension. Adverse events rates were dose-dependent in the short-term studies. CONCLUSION: Desvenlafaxine was effective in relieving pain associated with DPN at doses of 200 and 400 mg/day, and improved activity impairment at all doses assessed. Desvenlafaxine was generally well-tolerated in the short-term and long-term studies.

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Oral aprepitant 125 mg, an antiemetic and a moderate inhibitor of the metabolism of oral midazolam, was assessed for interaction with intravenous midazolam in 12 subjects randomized to intravenous midazolam 2 mg +/- oral aprepitant 125 mg. The hypothesis was that midazolam AUC would not change by more than 2-fold (consistent with no more than weak inhibition) when midazolam + aprepitant was compared with midazolam alone. An AUC geometric mean ratio (midazolam + aprepitant/midazolam) with 90% confidence interval upper bound < or =2.0 (an increase in midazolam felt to be of modest clinical significance in the highly monitored perioperative period) was prespecified. Aprepitant increased intravenous midazolam AUC(0-infinity) 1.47-fold (90% confidence interval, 1.36-1.59), which fell within the prespecified criterion.

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BACKGROUND: Patients and physicians consider rapid onset of pain relief and pain freedom among the most important attributes of migraine therapy. OBJECTIVE: This study compared the effectiveness of rizatriptan 10 mg and usual-care oral migraine medications in everyday clinical practice settings. METHODS: This was a multicenter, prospective, open-label study. Adult patients treated 2 sequential migraine attacks with rizatriptan 10 mg and a usual-care prescription migraine medication in a crossover manner. Patients chose which medication to take first. They recorded the treatment outcomes using a stopwatch and a treatment diary. End points included time to pain freedom (length of time from dosing to no pain) and time to onset of pain relief (mean time to onset of pain relief and proportion of patients reporting onset of pain relief at 30 minutes), satisfaction with treatment, and medication preference. Information on adverse events was collected through the normal post-marketing reporting mechanism. Comparisons were made using the paired t test and McNemar test for continuous and categorical variables, respectively. A mixed model, accounting for multiple observations per patient, was fitted for the time to pain freedom, controlling for age, sex, treatment period, medication, and headache severity. RESULTS: Of 2346 enrolled patients, 1489 treated 2 migraines in a crossover manner and were included in the analysis (86.8% women, 13.2% men; mean age, 41.7 years). A majority of patients (80.6%) treated both migraines with oral triptans. The most commonly used nontriptans were NSAIDs (5.4%), butalbital-containing combinations (4.3%), and isometheptene (3.4%). Over-the-counter medications were used by 22.3% of patients during rizatriptan-treated attacks and by 28.9% of patients during attacks treated with usual-care medications. The mean time to pain freedom was significantly shorter when an attack was treated with rizatriptan compared with usual-care medications (222 vs 298 minutes, respectively; P<0.001), and the onset of pain relief was significantly more rapid (85 vs 107 minutes; P=0.003), with significant differences noted as early as 15 minutes after dosing (P<0.001). The findings remained similar after adjustment for potential confounding factors. No significant sequence effect was detected. Significantly more patients reported being very satisfied or satisfied with rizatriptan compared with usual-care medications (65.4% vs 57.7%; P<0.001) and preferred rizatriptan (58.0% vs 42.0%; P<0.001). One female patient reported having hives and itchy skin the day after taking rizatriptan; the symptoms subsided after treatment with methylprednisolone. CONCLUSIONS: In this selected population, treatment of a migraine attack with rizatriptan 10 mg was associated with a faster time to pain freedom and onset of pain relief compared with treatment with usual-care oral migraine medications. Patients reported greater satisfaction with and preference for rizatriptan.

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OBJECTIVE: This study evaluated the accuracy of 2 administrative claims-based selection rules to identify patients with hypertension (HTN) using medical records as the gold standard. RESEARCH DESIGN: The claims database consisted of inpatient, outpatient, pharmacy, and eligibility claims for members of a single insurance company from January 2000 through March 2003. Medical records were abstracted for 258 matched patient pairs selected by Rule A (at least 1 HTN-related International Classification of Diseases, 9th Revision [ICD-9] claim) and 138 pairs selected by Rule B (at least 1 HTN-related ICD-9 and at least 1 HTN prescription claim) from 31 provider sites. Sensitivity and specificity of the 2 selection rules were computed using medical chart review as the gold standard for a diagnosis of HTN. SUBJECTS: Of patients selected by Rule A, chart review identified 281 patients with and 235 patients without HTN. Of patients selected by Rule B, chart review identified 172 patients with and 104 patients without HTN. RESULTS: The sensitivity and specificity was 70.8% and 74.9% for Rule A and 76.2% and 93.3% for Rule B. The kappa score was 0.45 for Rule A and 0.65 for Rule B. CONCLUSION: To identify patients with HTN, a selection rule using both a diagnosis and prescription claim has greater sensitivity and specificity than a rule using a diagnosis claim only.

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OBJECTIVE: To perform a meta-analysis comparing the efficacy and safety of recommended dosages of nonsteroidal antiinflammatory drugs (NSAIDs), including cyclooxygenase 2 inhibitors, versus acetaminophen in the treatment of symptomatic hip and knee osteoarthritis. METHODS: Medline and EMBASE searches were performed for original clinical trials directly comparing NSAIDs with acetaminophen. A standardized form was used to abstract all data, including outcome measures of pain at rest, walking pain, and dropouts due to adverse effects. Inverse-variance-weighted mean differences (WMDs) and 95% confidence intervals (95% CI) for pain measures were determined for treatment groups. Odds ratios (ORs) and 95% CIs were calculated for withdrawals due to adverse events. Results were compared using a random effects model. RESULTS: Seven articles met inclusion criteria with sufficient data for analysis. Participants had a mean age of 61.1 years and 71.1% were women. Test of heterogeneity was not significant for either rest (P = 0.73) or walking (P = 0.76) pain. The scores for overall pain at rest (WMD -6.33 mm on a 100-mm visual analog scale [VAS], 95% CI -9.24, -3.41) and walking pain (WMD -5.76 mm on a 100-mm VAS, 95% CI -8.99, -2.52) favored the NSAID-treated group. Although NSAIDs elevated the risk of withdrawals due to adverse events, the difference was not statistically significant (OR 1.45, 95% CI 0.93, 2.27). CONCLUSION: NSAIDs are statistically superior in reducing rest and walking pain compared with acetaminophen for symptomatic osteoarthritis. Safety, measured by discontinuation due to adverse events, was not statistically different between NSAID- and acetaminophen-treated groups.

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When anti-inflammatory/analgesic agents are not well tolerated, patients with arthritis may be prescribed a cyclooxygenase-2 (COX-2) inhibitor. Since these patients often require daily treatment and COX-2 inhibitors are more expensive than nonselective nonsteroidal anti-inflammatory agents, it is important to assess their patterns of use. In this retrospective study, rofecoxib and celecoxib were compared, in a managed care population with arthritis, in terms of average daily medication consumption and cost. Celecoxib was found to be significantly more costly than rofecoxib, and certain factors, such as the treating physician's specialty, correlated with prescribing patterns. Given the high prevalence of arthritic conditions, these results suggest that the selection of a COX-2 inhibitor may substantially affect health care costs.

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BACKGROUND: Identification and management of women to reduce fractures is often limited to T scores less than -2.5, although many fractures occur with higher T scores. We developed a classification algorithm that identifies women with osteopenia (T scores of -2.5 to -1.0) who are at increased risk of fracture within 12 months of peripheral bone density testing. METHODS: A total of 57 421 postmenopausal white women with baseline peripheral T scores of -2.5 to -1.0 and 1-year information on new fractures were included. Thirty-two risk factors for fracture were entered into a classification and regression tree analysis to build an algorithm that best predicted future fracture events. RESULTS: A total of 1130 women had new fractures in 1 year. Previous fracture, T score at a peripheral site of -1.8 or less, self-rated poor health status, and poor mobility were identified as the most important determinants of short-term fracture. Fifty-five percent of the women were identified as being at increased fracture risk. Women with previous fracture, regardless of T score, had a risk of 4.1%, followed by 2.2% in women with T scores of -1.8 or less or with poor health status, and 1.9% for women with poor mobility. The algorithm correctly classified 74% of the women who experienced a fracture. CONCLUSIONS: This classification tool accurately identified postmenopausal women with peripheral T scores of -2.5 to -1.0 who are at increased risk of fracture within 12 months. It can be used in clinical practice to guide assessment and treatment decisions.

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OBJECTIVE: Since the findings from the Women's Health Initiative became available in July 2002, millions of women have discontinued postmenopausal hormone therapy (HT). The objective of this study was to evaluate the association between HT cessation and hip fracture risk. METHODS: Women who participated in the National Osteoporosis Risk Assessment and completed the 12-month follow-up survey were studied. All participants were aged at least 50 years, were postmenopausal, and had no previous diagnosis of osteoporosis. Baseline and 12-month follow-up questionnaires assessed use of HT and incident fractures. Of the 140,584 women in this study, 269 reported an incident hip fracture. A logistic regression model was used to assess association between HT use and incident hip fracture, controlling for potential confounders. RESULTS: Consistent with the Women's Health Initiative, women in National Osteoporosis Risk Assessment who were currently on HT had a 40% lower incidence of hip fractures compared with those who never used HT. Women who stopped using HT more than 5 years earlier had similar hip fracture risk to never users, as expected. However, surprisingly, women who had discontinued HT within the previous 5 years had an increased hip fracture odds ratio of 1.65 (95% confidence interval 1.05, 2.59) relative to never users of HT. CONCLUSION: Postmenopausal women who have discontinued HT within the past 5 years have a risk for hip fracture that is at least as high as that in women who have never used HT. LEVEL OF EVIDENCE: II-2

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