Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Tramadol in the treatment of neuropathic cancer pain: a double-blind, placebo-controlled study. Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy. Efficient assessment of neuropathic pain drugs in patients with small fiber sensory neuropathies.
The objective of this study was to evaluate the efficacy and safety of tramadol in treating the pain of diabetic neuropathy.
                The pain of diabetic neuropathy is a major cause of morbidity among these patients and treatment, as with other small-fiber neuropathies, is often unsatisfactory. Tramadol is a centrally acting analgesic for use in treating moderate to moderately severe pain.
                This multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group study consisted of a washout/screening phase, during which all analgesics were discontinued, and a 42-day double-blind treatment phase. A total of 131 patients with painful diabetic neuropathy were treated with tramadol (n=65) or placebo (n=66) tramadol, which were administered as identical capsules in divided doses four times daily. The primary efficacy analysis compared the mean pain intensity scores in the tramadol and placebo groups obtained at day 42 of the study or at the time of discontinuation. Secondary efficacy assessments were the pain relief rating scores and a quality of life evaluation based on daily activities and sleep characteristics.
                Tramadol, at an average dosage of 210 mg/day, was significantly (p < 0.001) more effective than placebo for treating the pain of diabetic neuropathy. Patients in the tramadol group scored significantly better in physical (p=0.02) and social functioning (p=0.04) ratings than patients in the placebo group. No statistically significant treatment effects on sleep were identified. The most frequently occurring adverse events with tramadol were nausea, constipation, headache, and somnolence.
                The results of this placebo-controlled trial showed that tramadol was effective and safe in treating the pain of diabetic neuropathy. To assess the efficacy, safety and impact on quality of life of tramadol in the treatment of neuropathic pain in patients with cancer.
                Patients with similar characteristics were grouped in pairs and randomised to receive either tramadol or placebo. The initial tramadol dosage was 1 mg/kg every 6 hours, increasing to 1.5 mg/kg every 6 hours if necessary to control pain.
                The study enrolled 36 patients (22 women, 14 men), with a mean age of 50 years. In the group receiving tramadol (n = 18), major improvements in pain intensity and Karnofsky scores occurred (p < 0.001), sleep quality improved by day 45 (p < 0.05) activities of daily living improved (p < 0.05), and use of analgesics that had been taken before the study was reduced (p < 0.05) compared with the placebo group. There was no difference between the groups with regard to changes in the Zung Depression Scale, Beck Anxiety Inventory scores and neurophysiological assessments. More patients in the tramadol group experienced adverse events (p < 0.05). The most common adverse events were nausea, vomiting and constipation.
                Tramadol is a therapeutic option for the control of neuropathic pain in patients with cancer, and appears to improve quality of life in these patients. The analgesic effect of tramadol is independent of changes in anxiety, depression and nervous system function. The objective of this study was to evaluate the efficacy and safety of tramadol in a 6-month open extension following a 6-week double-blind randomized trial.
                Patients with painful diabetic neuropathy who completed the double-blind study were eligible for enrollment in an open extension of up to 6 months. All patients received tramadol 50-400 mg/day. Self-administered pain intensity scores (scale 0-4; none to extreme pain) and pain relief scores (scale -1-4; worse to complete relief) were recorded the first day of the open extension (last day of the double-blind phase) and at 30, 90, and 180 days.
                A total of 117 patients (56 former tramadol and 61 former placebo) entered the study. On the first day of the study, patients formerly treated with placebo had a significantly higher mean pain intensity score (2. 2+/-1.02 vs. 1.4+/-0.93, P<0.001) and a lower pain relief score (0. 9+/-1.43 vs. 2.2+/-1.27, P<0.001) than former tramadol patients. By Day 90, both groups had mean pain intensity scores of 1.4, which were maintained throughout the study. Mean pain relief scores (2. 4+/-1.09 vs. 2.2+/-1.14) were similar after 30 days in the former placebo and former tramadol groups, respectively and were maintained for the duration of the study. Four patients discontinued therapy due to ineffective pain relief; 13 patients discontinued due to adverse events. The most common adverse events were constipation, nausea, and headache.
                Tramadol provides long-term relief of the pain of diabetic neuropathy. We sought to develop an enrichment crossover study design that would allow us to efficiently evaluate and compare promising candidate neuropathic pain drugs. We evaluated the efficacy of gabapentin or tramadol vs. active placebo (diphenhydramine) in subjects with biopsy-proven painful idiopathic small fiber neuropathy (SFN) who were self-reported gabapentin responders. Eligible subjects entered two single blind run-in phases. In the first phase (Period A), subjects were treated with single blinded gabapentin at their prestudy dose followed by a second run-in phase (Period B) in which they were treated with diphenhydramine active placebo. Subjects with >or=3 pain and a >or=30% increase in pain intensity in Period B compared to Period A were then randomized to a double-blind three period cross over trial of gabapentin at pre study dosage, tramadol 50mg QID and diphenhydramine 50mgqhs. Of the 59 subjects enrolled, 41 subjects were excluded: Twenty-three had an insufficient rise in pain intensity in Period B; eight had skin biopsies that did not confirm SFN. Eighteen subjects were randomized into the double-blind, crossover phase. There was a significant treatment effect of gabapentin vs. diphenhydramine (p=0.001) and tramadol vs. diphenhydramine (p=0.018) by the before-bed daily pain score averaged over the final 7 days of each treatment period. We conclude that gabapentin and tramadol were effective in the treatment of painful SFN and that this experimental enrichment paradigm is attractive to screen potential neuropathic pain compounds for efficacy in proof-of-concept studies.
Tramadol is an effective treatment for neuropathic pain.