Immediate-release tapentadol or oxycodone for treatment of acute postoperative pain after elective arthroscopic shoulder surgery: a randomized, phase IIIb study.

OBJECTIVE: Arthroscopic shoulder surgery can result in substantial postoperative pain. This study evaluated the efficacy and safety of tapentadol immediate release (IR) or oxycodone IR in this setting for the treatment of acute pain. DESIGN: Subjects received tapentadol IR 50 or 100 mg or oxycodone IR 5 or 10 mg every 4-6 hours as needed for pain up to 7 days after arthroscopic shoulder surgery. Twice daily, subjects recorded pain intensity from 0 (no pain) to 10 (pain as bad as you can imagine) and pain relief from 0 (none) to 5 (complete). Final assessments included patient and clinician global impression of change and subject satisfaction with treatment. The primary efficacy endpoint was the sum of pain intensity differences (SPID) over 3 days. RESULTS: Of 378 subjects (192 tapentadol IR, 186 oxycodone IR) who took study medication, 312 (158 tapentadol IR, 154 oxycodone IR) had pain intensity ≥4 before the first dose and were evaluated for efficacy. Mean SPID scores over 3 days were 32.1 and 41.1 in the tapentadol IR and oxycodone IR groups, respectively (least-squares mean difference [95% confidence interval], 9.0 [-18.9, 36.9]; p = 0.527). Secondary analyses of pain intensity, pain relief, and subject satisfaction were similar between groups. Subjects and clinicians reported significantly better global impression of change for tapentadol IR. Adverse events were consistent with established safety profiles for IR opioids. CONCLUSIONS: Tapentadol IR and oxycodone IR had similar efficacy for pain after arthroscopic shoulder surgery, but subjects and clinicians reported greater overall improvement with tapentadol IR.

Tapentadol, oxycodone or placebo for acute pain of vertebral compression fractures: a randomized Phase IIIb study.

UNLABELLED: SUMMARY  AIM: Tapentadol is a centrally acting analgesic that combines µ-opioid receptor agonism with norepinephrine reuptake inhibition. This study evaluated the efficacy and safety of tapentadol immediate-release (IR), oxycodone IR or placebo in subjects with acute pain from vertebral compression fracture (VCF) associated with osteoporosis. PATIENTS & METHODS: Study patients were adults with new onset of pain or acute exacerbation of previous pain from VCF associated with osteoporosis, radiographic confirmation of VCF and back pain intensity of 5 or greater on an 11-point scale from 0 (no pain) to 10 (pain as bad as you can imagine). Patients were randomized to treatment with tapentadol IR (50 mg, then 50 or 75 mg), oxycodone IR (5 mg, then 5 or 10 mg) or placebo every 4-6 h as needed for pain, for up to 10 days. Twice daily, subjects recorded pain intensity on the 11-point scale (numeric rating scale), pain relief on a 5-point scale from 0 (none) to 4 (complete), sleep assessments (morning assessment only) and any episodes of vomiting (evening assessment only). RESULTS: The study was designed to include 625 subjects, but was stopped after 14 months due to slow enrollment (44 tapentadol IR, 43 oxycodone IR and 21 placebo subjects) and had insufficient statistical power for comparative efficacy analyses. Discontinuation rates in the tapentadol IR, oxycodone IR and placebo groups were 18.2, 27.9 and 9.5%, respectively, often due to adverse events (4.5, 18.6 and 4.8%, respectively). Treatment-emergent adverse-event rates were 63.6, 81.4 and 38.1%, respectively. CONCLUSION: In this prematurely terminated study in adults with painful VCF, trends suggested that tapentadol IR was tolerated better than oxycodone IR.

Communication about results of comparative effectiveness studies: a pharmaceutical industry view.

This article provides a perspective from the pharmaceutical industry on a hypothetical comparative effectiveness research case, highlighting tension between the reality of conducting comparative effectiveness research and the regulation of biopharmaceutical industry communication. Specifically, under current law and regulations, Aesculapion, the hypothetical maker of the fictional migraine headache drug Hemikrane, would have limited ability to communicate findings or to respond to inaccurate "what-if" scenario communications. Principles for communicating drug information could increase decision makers' access to information while making it easier for them to assess the quality and potential biases of different information sources. The article proposes two complementary approaches: formal Food and Drug Administration guidance clarifying how industry can participate meaningfully and proactively in the comparative effectiveness research discourse, possibly based on 1997 legislation governing communication of "health care economic information"; and stakeholder collaboration on development and adoption of voluntary "good communication principles."

Longitudinal study of the diagnosis of components of the metabolic syndrome in individuals with binge-eating disorder.

BACKGROUND: Binge-eating disorder may represent a risk factor for the metabolic syndrome. OBJECTIVE: The objective was to assess longitudinally the relation between binge-eating disorder and components of the metabolic syndrome. DESIGN: At 2.5 and 5 y of follow-up, 134 individuals with binge-eating disorder and 134 individuals with no history of eating disorders, who were frequency-matched for age, sex, and baseline body mass index (BMI), were interviewed during the follow-up interval regarding new diagnoses of 3 metabolic syndrome components: hypertension, dyslipidemia, and type 2 diabetes. RESULTS: A comparison of individuals with and without a binge-eating disorder in analyses adjusted for age, sex, baseline BMI, and interval BMI change had hazard ratios (95% CIs) for reporting new diagnoses of metabolic syndrome components of 2.2 (1.2, 4.2; P = 0.023) for dyslipidemia, 1.5 (0.76, 2.9; P = 0.33) for hypertension, 1.6 (0.77, 3.9; P = 0.29) for type 2 diabetes, 1.7 (1.1, 2.6; P = 0.023) for any component, and 2.4 (1.1, 5.7; P = 0.038) for > or =2 components. CONCLUSION: Binge-eating disorder may confer a risk of components of the metabolic syndrome over and above the risk attributable to obesity alone. This trial was registered at www.clinicaltrials.gov as NCT00777634.

Co-occurrence of binge eating disorder with psychiatric and medical disorders.

BACKGROUND: Prior studies suggest that certain psychiatric and medical disorders co-occur with binge eating disorder (BED). However, there has been no large, community-based study with diagnoses made by clinician interviewers. We used data from that type of study to assess the co-occurrence of various psychiatric and medical disorders with DSM-IV BED and with subthreshold BED. METHOD: From October 2002 to July 2004, we interviewed 150 probands with BED, 150 probands without BED, and 888 of their first-degree relatives (135 of whom had BED, and 54 of whom met specific partial criteria for BED that we defined as subthreshold BED). Study participants were interviewed using the Structured Clinical Interview for DSM-IV to assess BED and other psychiatric disorders and a supplemental structured interview to assess certain medical disorders; participants also completed a self-report questionnaire, the Bad Things Scale. For each psychiatric and medical disorder, we calculated the age- and sex-adjusted co-occurrence odds ratio: the odds of having that disorder in one's lifetime among individuals with (full or subthreshold) lifetime BED compared to individuals without lifetime BED. We also used subjects' responses to the Bad Things Scale to adjust for adversity over-reporting, a type of response bias that could result in spurious findings of co-occurrence. RESULTS: Full BED co-occurred significantly with bipolar disorder, major depressive disorder, bulimia nervosa but not anorexia nervosa, most anxiety disorders, substance use disorders, body dysmorphic disorder, kleptomania, irritable bowel syndrome, and fibromyalgia. These results changed little after correcting for adversity over-reporting. Subthreshold BED co-occurred significantly with many, but not all, of the significantly co-occurring disorders for full BED. CONCLUSION: BED and, to a lesser degree, subthreshold BED exhibit substantial lifetime co-occurrence with psychiatric and medical disorders.

Efficacy and safety of topiramate monotherapy in civilian posttraumatic stress disorder: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: This double-blind, placebo-controlled trial assessed efficacy and safety of topiramate monotherapy in civilian posttraumatic stress disorder (PTSD). METHOD: Outpatients (18-64 years) with DSM-IV non-combat-related PTSD and Clinician-Administered PTSD Scale (CAPS) scores >or= 50 were eligible. Topiramate was started at 25 mg/day and titrated by 25-50 mg/week to 400 mg/day or maximum tolerated dose. Data were collected between April 26, 2002, and February 4, 2004. Primary efficacy, change in total CAPS score, and secondary efficacy measures were assessed by analysis of covariance in the intent-to-treat (ITT) population with last observation carried forward. RESULTS: The ITT population comprised 38 patients with mean +/- SD baseline total CAPS scores of 88.3 +/- 13.8 (topiramate, N = 19) and 91.1 +/- 13.7 (placebo, N = 19). Although a decrease in total CAPS score was noted (topiramate, -52.7; placebo, -42.0), this difference was not statistically significant (p = .232). Topiramate-treated patients exhibited significant reductions in reexperiencing symptoms (CAPS cluster B: topiramate, 74.9%; placebo, 50.2%; p = .038) and Treatment Outcome PTSD scale (topiramate, 68.0%; placebo, 41.6%; p = .025). Reductions approaching statistical significance, based on a nominal p value, were noted in mean total Clinical Global Impressions-Improvement Scale scores (topiramate, 1.9 +/- 1.2; placebo, 2.6 +/- 1.1; p = .055). CONCLUSION: These preliminary results suggest that further, adequately powered studies of topiramate for the treatment of civilian PTSD are warranted.

Randomized study of tramadol/acetaminophen versus placebo in painful diabetic peripheral neuropathy.

OBJECTIVE: To examine the efficacy and safety of tramadol/acetaminophen (APAP) for the management of painful diabetic peripheral neuropathy (DPN). METHODS: Adults with painful DPN involving the lower extremities received 37.5 mg tramadol/325 mg APAP or placebo, up to 1-2 tablets four times daily, for 66 days. Subjects rated average daily pain and sleep interference from 0 ('none') to 10 ('pain as bad as you can imagine' or 'complete interference') every night. Baseline values were recorded for 7 days before starting study medication. The primary endpoint was change in mean of average daily pain scores from baseline to final week. Secondary efficacy outcomes included pain intensity, sleep interference, quality of life, mood, and global impression of change. Potential study limitations included permission to use serotonin reuptake inhibitors concomitantly (except venlafaxine or duloxetine) and the lack of a tramadol-alone or APAP-alone control group. RESULTS: A total of 160 subjects received tramadol/APAP and 153 received placebo. Tramadol/APAP reduced average daily pain significantly compared to placebo from baseline to the final week (-2.71 vs. -1.83, p = 0.001). Tramadol/APAP was associated with significantly greater improvement than placebo (p < or = 0.05) for all measures of pain intensity, sleep interference, and global impression, as well as several measures of quality of life and mood. The only adverse event reported by > 10% of subjects in either the tramadol/APAP or placebo group was nausea (11.9% and 3.3%, respectively). Adverse events resulted in early study discontinuation for 8.1% and 6.5% of subjects in the tramadol/APAP and placebo groups, respectively. CONCLUSION: Tramadol/APAP was more effective than placebo and was well tolerated in the management of painful DPN.

Topiramate for the treatment of binge eating disorder associated with obesity: a placebo-controlled study.

BACKGROUND: In a single-center, placebo-controlled study, topiramate reduced binge eating and weight in patients with binge eating disorder (BED) and obesity. The current investigation evaluated the safety and efficacy of topiramate in a multicenter, placebo-controlled trial. METHODS: Eligible patients between 18 and 65 years with >or= 3 binge eating days/week and a body mass index (BMI) between 30 and 50 kg/m2 were randomized. RESULTS: A total of 407 patients enrolled; 13 failed to meet inclusion criteria, resulting in 195 topiramate and 199 placebo patients. Topiramate reduced binge eating days/week (-3.5 +/- 1.9 vs. -2.5 +/- 2.1), binge episodes/week (-5.0 +/- 4.3 vs. -3.4 +/- 3.8), weight (-4.5 +/- 5.1 kg vs. .2 +/- 3.2 kg), and BMI (-1.6 +/- 1.8 kg/m2 vs. .1 +/- 1.2 kg/m2) compared with placebo (p < .001). Topiramate induced binge eating remission in 58% of patients (placebo, 29%; p < .001). Discontinuation rates were 30% in each group; adverse events (AEs) were the most common reason for topiramate discontinuation (16%; placebo, 8%). Paresthesia, upper respiratory tract infection, somnolence, and nausea were the most common AEs with topiramate. CONCLUSIONS: This multicenter study in patients with BED associated with obesity demonstrated that topiramate was well tolerated and efficacious in improving the features of BED and in reducing obesity.

Tramadol/acetaminophen or hydrocodone/acetaminophen for the treatment of ankle sprain: a randomized, placebo-controlled trial.

STUDY OBJECTIVE: This randomized, multicenter study compares the analgesic efficacy and safety of tramadol/acetaminophen versus hydrocodone/acetaminophen versus placebo for the treatment of acute musculoskeletal pain caused by ankle sprain. METHODS: Adults were enrolled with ankle sprain with a diagnosis of partial ligament tear, pain visual analog scale score of 50 to 100 mm (0="no pain," 100="extreme pain"), and pain numeric rating scale score of 2 to 3 (0="none," 3="severe"). Patients reported pain intensity on these scales and pain relief (-1="pain worse," 4="complete relief") hourly for 4 hours after the first dose of tramadol/acetaminophen 75 mg/650 mg, hydrocodone/acetaminophen 7.5 mg/650 mg, or placebo, and daily for 5 days, with as-needed dosing. RESULTS: Tramadol/acetaminophen (n=192) and hydrocodone/acetaminophen (n=204) provided greater total pain relief than placebo (n=207; P<.001) during the first 4 hours (mean scores [95% confidence interval (CI)] 6.6 [95% CI 6.1 to 7.1], 6.8 [95% CI 6.3 to 7.3], and 5.4 [95% CI 4.9 to 5.9], respectively; possible range -4 to 16), decreased pain intensity during the first 4 hours, and increased average pain relief on days 1 to 5. No efficacy measure was significantly different between the tramadol/acetaminophen and hydrocodone/acetaminophen groups. Common adverse events included somnolence, nausea, dizziness, and vomiting. CONCLUSION: One or 2 capsules of 37.5 mg tramadol/325 mg acetaminophen and 1 capsule of 7.5 mg hydrocodone/650 mg acetaminophen were well tolerated, had comparable clinical utility, and were more effective than placebo in the management of acute musculoskeletal pain caused by ankle sprain.

Binge-eating disorder as a distinct familial phenotype in obese individuals.

CONTEXT: Binge-eating disorder (BED)-a syndrome that only recently has attracted scientific attention-is often seen in obese individuals, especially those with severe obesity. However, it remains unclear whether BED represents an etiologically distinct behavioral phenotype of obesity or simply a nonspecific eating pattern sometimes seen in obese individuals. OBJECTIVE: To test whether BED aggregates in families independently of obesity, and if so, whether familial factors for BED also independently increase the risk of obesity. DESIGN, PATIENTS, AND SETTING: Blinded family interview study of overweight or obese probands with (n = 150) and without (n = 150) BED, and their first-degree relatives (n = 888) in a community setting evaluated between October 2002 and July 2004. MAIN OUTCOME MEASURES: Lifetime diagnosis of BED; current and highest lifetime body mass index (calculated as the weight in kilograms divided by the square of the height in meters). RESULTS: Binge-eating disorder aggregated strongly in families independently of obesity (odds ratio, 2.2; 95% confidence interval, 1.4-3.6; P<.001). Furthermore, relatives of probands with BED displayed a markedly higher prevalence of severe obesity in adulthood (body mass index >/=40) than relatives of probands without BED even when controlling for proband body mass index (odds ratio, 2.5; 95% confidence interval, 1.4-4.4; P = .002). CONCLUSIONS: Binge-eating disorder is a familial disorder caused in part by factors distinct from other familial factors for obesity. Furthermore, these BED-specific familial factors may independently increase the risk of obesity, especially severe obesity. It follows that targeted interventions capable of preventing or treating traits influenced by these BED-specific familial factors could reduce the public health burden of obesity.

Adjunctive topiramate therapy in patients receiving a mood stabilizer for bipolar I disorder: a randomized, placebo-controlled trial.

OBJECTIVE: To investigate the efficacy and safety of topiramate versus placebo as adjunctive therapy for the outpatient management of bipolar I disorder. METHOD: In this 12-week, randomized, double-blind, placebo-controlled trial, adults with bipolar I disorder (DSM-IV criteria) experiencing a manic or mixed episode with a Young Mania Rating Scale (YMRS) score of >or= 18 while taking therapeutic levels of valproate or lithium received adjunctive topiramate or placebo. Topiramate was titrated from 25 to 400 mg/day over 8 weeks and was continued for 4 additional weeks. The study was conducted from October 2001 through October 2003. The primary outcome measure was the change in YMRS score from baseline to last study visit during the double-blind phase. RESULTS: The mean +/- SD change in YMRS score from baseline was -10.1 +/- 8.7 (-40.1%) in the topiramate group (N = 143) and -9.6 +/- 8.2 (-40.2%) in the placebo group (N = 144, p = .797). Greater than 50% reduction in YMRS was achieved by 39% of the topiramate group and 38% of the placebo group (p = .914). No significant treatment differences were observed for secondary efficacy measures. Compared with adjunctive placebo, adjunctive topiramate did not worsen mania or induce depression. Paresthesia, diarrhea, and anorexia were more common in the topiramate group. The topiramate group achieved greater reductions than the placebo group in body weight (-2.5 vs. 0.2 kg, p < .001) and body mass index (-0.84 vs. 0.07 kg/m(2), p < .001). CONCLUSION: In patients treated with lithium or valproate, there was no difference in the reduction of YMRS score in the topiramate and placebo groups. Both groups showed declines of 40%. Topiramate reduced body weight significantly relative to placebo without worsening depressive or manic symptoms.

Tramadol/acetaminophen for the treatment of acute migraine pain: findings of a randomized, placebo-controlled trial.

OBJECTIVE: To compare tramadol/acetaminophen (APAP) and placebo for the management of acute migraine pain. BACKGROUND: Tramadol/APAP tablets reduced moderate-to-moderately severe acute pain in controlled studies of other painful conditions. METHODS: This randomized, double-blind, placebo-controlled, parallel group study enrolled adults with migraine pain as per International Headache Society criteria. Subjects took tramadol/APAP (total dose, 75 mg/650 mg) or placebo for a typical migraine with moderate-to-severe pain. Severity of pain and migraine-related symptoms were recorded before study medication and at 0.5, 1, 2, 3, 4, 6, and 24 hours after study medication. RESULTS: Efficacy analyses included 305 subjects (154 tramadol/APAP and 151 placebo). Treatment response was higher for tramadol/APAP than a placebo at 2 hours after dosing (55.8% vs. 33.8%, P < .001) and at every other assessment from 30 minutes (12.3% vs. 6.6%) through 6 hours (64.9% vs. 37.7%) (all P< or = .022). Subjects in the tramadol/APAP group were more likely than those in the placebo group to be pain-free at 2 hours (22.1% vs. 9.3%), 6 hours (42.9% vs. 25.2%), and 24 hours (52.7% vs. 37.9%) (all P< or = .007). Two hours after dosing, moderate-to-severe symptoms that were less common for tramadol/APAP than placebo included photophobia (34.6% vs. 52.2%, P= .003) and phonophobia (34.3% vs. 44.9%, P = .008), but not migraine-related nausea (38.5% vs. 29.4%, P= .681). Treatment-related adverse events included nausea, dizziness, vomiting, and somnolence. CONCLUSIONS: Tramadol/APAP reduces the severity of pain, photophobia, and phonophobia associated with migraine headache, but does not reduce migraine-associated nausea. Tramadol/APAP might be an appropriate option for the management of moderate-to-severe migraine headache.

Safety and effectiveness of topiramate for the management of painful diabetic peripheral neuropathy in an open-label extension study.

OBJECTIVE: The aim of this study was to further assess the long-term safety and effectiveness of open-label topiramate therapy in subjects with moderately to severely painful diabetic peripheral neuropathy (DPN). METHODS: Adults aged 18 to 75 years received open-label topiramate (25-600 mg/d for 26 weeks) in an extension of a previously published randomized, double-blind trial comparing topiramate with placebo. Safety analyses included adverse event (AE) reports and clinical laboratory tests. Metabolic end points included body weight and glycosylated hemoglobin (HbA(1c)). Effectiveness analyses included a 100-mm pain visual analog (PVA) scale, worst and current pain severity, and sleep disruption. RESULTS: Two hundred five subjects participated in this open-label extension study (118 formerly treated with topiramate and 87 who formerly received placebo). The groups did not differ in baseline demographics or disease characteristics. One hundred twenty-four (60.5%) subjects (68.6% of former topiramate recipients and 49.4% of former placebo recipients) completed the extension study; the most common reason for discontinuation was an AE (27.3% of subjects). AEs among subjects who received > or =1 dose of topiramate (n = 298) included upper respiratory tract infection (16.1%), anorexia (15.1%), diarrhea (12.8%), nausea (12.8%), paresthesia (10.7%), and headache (10.1%). Baseline pain scores were lower in those formerly treated with topiramate (n = 117) than in the former placebo group (n = 86) (PVA: 43.3 vs 52.5, P = 0.014; worst pain: 1.9 vs 2.5, P < 0.001; current pain: 1.6 vs 1.9, P = 0.026; sleep disruption: 3.6 vs 4.6, P = 0.021). At the final visit, PVA, current pain, and sleep disruption scores were not significantly different between the former topiramate and former placebo groups, but worst pain differed significantly (1.4 vs 1.8; P = 0.025). Mean weight loss from the start of topiramate therapy was 5.2 and 5.3 kg in the former topiramate and former placebo groups, respectively (P < 0.001 vs baseline). Mean HbA(1c) values before and after topiramate treatment were 7.7% and 7.4%, respectively, in the former topiramate group (P = 0.004 vs baseline), and 7.6% and 7.1%, respectively, in the former placebo group (P < 0.001 vs baseline). CONCLUSION: Although 39.5% of subjects discontinued, most often due to AEs, the results of this 26-week, open-label extension study with topiramate (up to 600 mg/d) in subjects with moderately to severely painful DPN suggest that pain relief was effective and durable.

Impact of fibromyalgia pain on health-related quality of life before and after treatment with tramadol/acetaminophen.

OBJECTIVE: To assess health-related quality of life (HRQOL) in patients with moderate-to-severe fibromyalgia pain compared with the general population, and to assess the relationship between pain severity and HRQOL before and after treatment with an analgesic. METHODS: Data were obtained from a randomized, double-blind study of patients with moderate-to-severe fibromyalgia pain. Patients received either tramadol/acetaminophen or placebo 4 times/day as needed for 91 days. HRQOL was measured with the Short Form 36 Health Survey (SF-36) and the Fibromyalgia Impact Questionnaire (FIQ). Baseline HRQOL scores were compared with a national sample of noninstitutionalized adults and a sample of patients with impaired HRQOL due to congestive heart failure. Patients with fibromyalgia were divided into tertiles by change in pain severity, and SF-36 scores were compared across the tertiles. Mean changes in SF-36 and FIQ scores were compared between treatment groups. RESULTS: Patients with fibromyalgia scored lower than the US norm on all SF-36 scales (P < 0.0001) and lower than patients with congestive heart failure on most scales. More severe pain was associated with greater impairment of HRQOL compared with less severe pain (P < 0.0001). Patients in the highest tertile for improved pain severity had greater improvement in HRQOL scores than patients in the lower tertiles. Compared with patients who received placebo (n = 157), patients treated with tramadol/acetaminophen (n = 156) showed greater improvement on SF-36 physical functioning, role physical, bodily pain, and physical summary scales, as well as FIQ scales for ability to do job, pain, and stiffness (P < 0.01). CONCLUSION: Moderate-to-severe fibromyalgia pain significantly impairs HRQOL, and effective pain relief in these patients significantly increases HRQOL.

A pilot controlled trial of topiramate for mania in children and adolescents with bipolar disorder.

OBJECTIVE: To assess the efficacy of topiramate monotherapy for acute mania in children and adolescents with bipolar disorder type I. METHOD: This double-blind, placebo-controlled study was discontinued early when adult mania trials with topiramate failed to show efficacy. Efficacy end points included the Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale for Children, Children's Depression Rating Scale, Children's Global Assessment Scale, and Clinical Global Impressions-Improvement. RESULTS: Fifty-six children and adolescents (6-17 years) with a diagnosis of bipolar disorder type I received topiramate (n=29, 52%) or placebo (n=27, 48%). The only statistically significant differences in efficacy measures between treatment groups were the difference between slopes of the linear mean profiles of the YMRS (p=.003) using a post hoc repeated measures regression and the change in Brief Psychiatric Rating Scale for Children at day 28 (-14.9 versus-5.9, p=.048) using observed data. Adverse events with topiramate included decreased appetite, nausea, diarrhea, and paresthesia. CONCLUSIONS: Topiramate was well tolerated; however, the results are inconclusive because of premature termination resulting in a limited sample size. Adequately powered controlled trials are necessary to determine whether topiramate has efficacy in reducing symptoms of acute mania in children and adolescents.

Tramadol/acetaminophen tablets in the treatment of postsurgical orthopedic pain.

Tramadol/acetaminophen (APAP) combination tablets were shown effective and safe for postsurgical orthopedic pain in a 6-day, multicenter, randomized, double-blind, active- and placebo-controlled study. Of 305 intent-to-treat (ITT) postsurgical patients, 153 patients undergoing arthroscopy who had at least moderate pain were randomized to receive either tramadol 37.5 mg/APAP 325 mg (mean, 4.3 tablets), or codeine 30 mg/APAP 300 mg (mean, 4.6 tablets), or placebo. Tramadol/APAP was superior to placebo for the following outcome variables: total pain relief (TOTPAR, P = .013), sum of pain intensity differences (SPID, P = .049), sum of total pain relief and sum of pain intensity differences (SPRID, P = .018), and average daily pain relief (P = .031). Similar incidence of adverse events for tramadol/APAP and codeine/APAP was found, except for constipation (0% vs 10.9%) and vomiting (8.2% vs 16.4%).

Topiramate in the long-term treatment of binge-eating disorder associated with obesity.

BACKGROUND: This study assessed the long-term effectiveness and tolerability of topiramate in binge-eating disorder (BED) with obesity. METHOD: Sixty-one patients with BED (DSM-IV-TR criteria) and obesity enrolled in a 14-week, single-center, randomized, double-blind, placebo-controlled study. Completers (N = 35) were offered participation in a 42-week, open-label extension trial of topiramate. Fifteen patients who received topiramate and 16 patients who received placebo in the double-blind study entered the open-label trial. Topiramate was titrated from 25 mg/day to a maximum of 600 mg/day. The primary endpoint was change from baseline to final visit in weekly binge frequency using the last observation carried forward for all patients who received topiramate. Baseline for patients receiving double-blind topiramate was the beginning of the controlled study; for patients receiving placebo, baseline was the beginning of the open-label trial. Open-label data were gathered from December 1998 to November 2000. RESULTS: Forty-four patients (31 who received topiramate in the open-label trial plus 13 who received topiramate in the double-blind study only) received at least 1 dose of topiramate; 43 patients provided outcome measures at a median final dose of 250 mg/day. Mean weekly binge frequency declined significantly from baseline to final visit for all 43 patients (-3.2; p < .001), for the 15 patients who received topiramate during the controlled and open-label studies (-4.0; p < .001), and for the 15 patients who received topiramate only during the open-label trial (-2.5; p = .044). Patients also exhibited statistically significant reduction in body weight. The most common reasons for topiramate discontinuation were protocol nonadherence (N = 17) and adverse events (N = 14). CONCLUSION: Topiramate treatment was associated with enduring improvement in some patients with BED and obesity but was also associated with a high discontinuation rate.

A double-blind placebo-controlled comparison of tramadol/acetaminophen and tramadol in patients with postoperative dental pain.

The objective of this study was to compare the analgesic efficacy of tramadol/acetaminophen (APAP) (total dose 75 mg/650 mg) and tramadol (total dose 100 mg) for the control of pain after oral surgery. A total of 456 patients with moderate-to-severe pain within 5 h after extraction of two or more third molars were randomized to receive two identical encapsulated tablets containing tramadol/APAP 37.5 mg/325 mg, tramadol 50 mg, or placebo. Tramadol/APAP was superior to tramadol (P < 0.001) or placebo (P < 0.001) on all efficacy measures: total pain relief (PAR) over 6 h (7.4, 2.5, and 1.5, respectively, on a scale of 0-24); sum of pain intensity differences (PIDs) (3.1, 0.6, and 0.1, respectively, on a scale of -6 to 18); and sum of PAR and PID (10.5, 3.1, and 1.6, respectively, on a scale of -6 to 42). Median times to onset of perceptible and meaningful PAR were 37.6 and 126.5 min, respectively, for the tramadol/APAP group (P < 0.001) for each, compared with tramadol and placebo arms). The most common adverse events with active treatment were nausea, dizziness, and vomiting; these events occurred more frequently in the tramadol group than in the tramadol/APAP group. This study established the superiority of tramadol/APAP 75 mg/650 mg over tramadol 100 mg in the treatment of acute pain following oral surgery.

Tramadol/acetaminophen combination tablets for the treatment of pain associated with osteoarthritis flare in an elderly patient population.

OBJECTIVES: To evaluate the efficacy and safety of adding tramadol 37.5 mg/acetaminophen (APAP) 325 mg combination tablets (tramadol/APAP) to existing therapy for painful osteoarthritis (OA) flare in a subset of elderly patients. DESIGN: Randomized, double-blind, placebo-controlled, 10-day add-on study. SETTING: Thirty outpatient centers. PARTICIPANTS: Of 308 patients with painful OA flare, a subset of 113 patients aged 65 and older. MEASUREMENTS: Average daily pain intensity and pain relief scores for Days 1 through 5 and secondary quality-of-life measures and medication assessments. METHODS: Patients received one or two tramadol/APAP tablets or placebo four times per day for 10 days during ongoing nonselective or cyclooxygenase (COX)-2-selective nonsteroidal antiinflammatory drug (NSAID) therapy. RESULTS: Tramadol/APAP (n=69) was significantly superior to placebo (n=44) for average daily pain intensity (P=.034) and pain relief (P=.010) for Days 1 through 5 and Days 1 through 10 (P=.012 and P=.019, respectively). Tramadol/APAP had significantly better investigator (P<.001) and patient (P=.001) overall medication assessments and significantly better scores on three of four Western Ontario and McMaster Universities Osteoarthritis Index measures (P< or =.027). Most common adverse events with tramadol/APAP were nausea (18.8%), vomiting (13.0%), dizziness (11.6%), and constipation (4.3%), with an incidence similar to that of the overall study population. Mean daily dose of tramadol/APAP was 4.5 tablets (168 mg/1,458 mg). CONCLUSION: Tramadol/APAP add-on therapy effectively managed painful OA flare in this elderly subset and was generally well tolerated.

Treatment of bulimia nervosa with topiramate in a randomized, double-blind, placebo-controlled trial, part 1: improvement in binge and purge measures.

BACKGROUND: This randomized, double-blind, placebo-controlled trial was designed to assess the efficacy and safety of topiramate in bulimia nervosa. METHOD: Patients with DSM-IV bulimia nervosa were randomly assigned in equal proportions to receive topiramate (N = 35) or placebo (N = 34) for 10 weeks (between April 1999 and Dec. 2000). Topiramate treatment was started at 25 mg/day and titrated by 25 to 50 mg/week to a maximum of 400 mg/day. The primary efficacy measure was mean weekly number of binge and/or purge days. Related outcome measures included mean weekly number of binge days and binge frequency, as well as mean weekly number of purge days and purge frequency. RESULTS: Sixty-four outpatients (33 placebo, 31 topiramate) were included in the intent-to-treat analysis. The median topiramate dose was 100 mg/day (range, 25-400 mg/day). Mean +/- SD baseline number of weekly binge and/or purge days was 5.0 +/- 1.6 for topiramate patients and 5.1 +/- 1.5 for placebo patients. The primary efficacy measure, mean weekly number of binge and/or purge days, decreased 44.8% from baseline with topiramate versus 10.7% with placebo (p =.004). The mean weekly number of binge days decreased 48.2% with topiramate versus 17.7% with placebo (p =.015), and mean binge frequency decreased 49.2% with topiramate versus 28.0% with placebo (p =.071). The mean weekly number of purge days decreased 43.4% with topiramate versus 16.6% with placebo (p =.016), and mean purge frequency decreased 49.8% with topiramate versus 21.6% with placebo (p =.016). Three patients (2 placebo, 1 topiramate) discontinued from the trial due to adverse events. CONCLUSION: Topiramate was associated with significant improvements in both binge and purge symptoms in this study population and represents a potential treatment for bulimia nervosa.