Norman R. Rosenthal

Tramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study

PURPOSE To evaluate the efficacy and safety of a combination analgesic tablet (37.5 mg tramadol/325 mg acetaminophen) for the treatment of fibromyalgia pain. METHODS This 91-day, multicenter, double-blind, randomized, placebo-controlled study compared tramadol/acetaminophen combination tablets with placebo. The primary outcome variable was cumulative time to discontinuation (Kaplan-Meier analysis). Secondary measures at the end of the study included pain, pain relief, total tender points, myalgia, health status, and Fibromyalgia Impact Questionnaire scores. RESULTS Of the 315 subjects who were enrolled in the study, 313 (294 women [94%], mean [+/- SD] age, 50 +/- 10 years) completed at least one postrandomization efficacy assessment (tramadol/acetaminophen: n = 156; placebo: n = 157). Discontinuation of treatment for any reason was less common in those treated with tramadol/acetaminophen compared with placebo (48% vs. 62%, P = 0.004). Tramadol/acetaminophen-treated subjects also had significantly less pain at the end of the study (53 +/- 32 vs. 65 +/- 29 on a visual analog scale of 0 to 100, P <0.001), and better pain relief (1.7 +/- 1.4 vs. 0.8 +/- 1.3 on a scale of -1 to 4, P <0.001) and Fibromyalgia Impact Questionnaire scores (P = 0.008). Indexes of physical functioning, role-physical, body pain, health transition, and physical component summary all improved significantly in the tramadol/acetaminophen-treated subjects. Discontinuation due to adverse events occurred in 19% (n = 29) of tramadol/acetaminophen-treated subjects and 12% (n = 18) of placebo-treated subjects (P = 0.09). The mean dose of tramadol/acetaminophen was 4.0 +/- 1.8 tablets per day. CONCLUSION A tramadol/acetaminophen combination tablet was effective for the treatment of fibromyalgia pain without any serious adverse effects.

Topiramate vs placebo in painful diabetic neuropathy Analgesic and metabolic effects

Background: Using identical methods, three simultaneous placebo-controlled trials of topiramate for painful diabetic neuropathy (PDN) did not reach significance. This independent yet concurrent placebo-controlled trial used different methods to assess topiramate efficacy and tolerability in PDN. Methods: This 12-week, multicenter, randomized, double-blind trial included 323 subjects with PDN and pain visual analog (PVA) score of at least 40 on a scale from 0 (no pain) to 100 (worst possible pain). Topiramate (n = 214) or placebo (n = 109) was titrated to 400 mg daily or maximum tolerated dose. Short-acting rescue analgesics were permitted only during the first 6 weeks. Results: Baseline characteristics were comparable between groups except for mean body weight (topiramate, 101.4 kg; placebo, 95.7 kg; p = 0.028). Twelve weeks of topiramate treatment reduced PVA scale score (from 68.0 to 46.2 mm) more effectively than placebo (from 69.1 to 54.0 mm; p = 0.038). Fifty percent of topiramate-treated subjects and 34% of placebo-treated subjects responded to treatment, defined as >30% reduction in PVA scale score (p = 0.004). Topiramate monotherapy also reduced worst pain intensity (p = 0.003 vs placebo) and sleep disruption (p = 0.020 vs placebo). Diarrhea, loss of appetite, and somnolence were the most commonly reported adverse events in the topiramate group. Topiramate reduced body weight (−2.6 vs +0.2 kg for placebo; p < 0.001) without disrupting glycemic control. Conclusions: Topiramate monotherapy reduced pain and body weight more effectively than placebo in patients with painful diabetic neuropathy.

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 combination tablets for the treatment of chronic lower back pain: A multicenter, randomized, double-blind, placebo-controlled outpatient study☆

BACKGROUND Tramadol and acetaminophen (APAP) have both shown efficacy in the treatment of lower back pain. The combination of these 2 agents has demonstrated synergistic analgesic action in animal models at specific ratios. OBJECTIVE This study assessed the long-term (3-month) efficacy and safety of tramadol 37.5 mg/APAP 325 mg combination tablets in the treatment of chronic lower back pain. METHODS Patients with at least moderate lower back pain (pain visual analog [PVA] score >/=40 mm on a 100-mm scale) were randomized to receive up to 8 tablets of tramadol/APAP per day or placebo for 91 days. Medication was titrated from 1 to 4 tablets/d by day 10. The primary efficacy measure was PVA score at the final visit. Secondary measures included scores on the Pain Relief Rating Scale (PRRS), Short-Form McGill Pain Questionnaire (SF-MPQ), Roland Disability Questionnaire (RDQ), and 36-Item Short-Form Health Survey (SF-36); the incidence of discontinuation due to insufficient pain relief (Kaplan-Meier analysis); and overall assessments of medication by the patients and investigators. RESULTS Three hundred eighteen patients (161 tramadol/APAP, 157 placebo) were included in the intent-to-treat population, defined as all patients who took >/=1 dose of study medication and had >/=1 postrandomization efficacy measurement. The mean age of the study population was 53.9 years, 63.2% were female, 90.3% were white, and the mean baseline PVA score was 70.0 mm. There were no significant differences between groups at baseline. Tramadol/APAP significantly improved final PVA scores (P = 0.015) and final PRRS scores (P < 0.001) compared with placebo. Tramadol/APAP also significantly improved RDQ scores (P </= 0.027) and scores on many subcategories of the SF-MPQ, including total score (P = 0.021). The tramadol/APAP group had significant improvements on the role-physical (P = 0.005), bodily pain (P = 0.046), role-emotional (P = 0.001), mental health (P = 0.026), reported health transition (P = 0.038), and mental component summary (P = 0.008) subscales of the SF-36. The cumulative incidence of discontinuation due to insufficient pain relief was 22.1% for tramadol/APAP and 41.0% for placebo (P < 0.001). Treatment-emergent adverse events in the tramadol/APAP group included nausea (13.0%), somnolence (12.4%), and constipation (11.2%). CONCLUSIONS In this study, tramadol 37.5 mg/APAP 325 mg combination tablets were effective and had a favorable safety profile in the treatment of chronic lower back pain.

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.

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

ABSTRACT 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 ≤ 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.

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

&NA; 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.

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.

PULMONARY EMBOLISM: ITS INCIDENCE AT NECROPSY IN RELATION TO PERIPHERAL THROMBOSIS

Excerpt The most dangerous complication of venous thrombosis is pulmonary embolism, with its mortality of about 20 per cent.1Such embolism has been reported by Barnes3to be responsible for 34,000 d...