Based on the recent finding that Tramadol ( Generic Ultram ) (TRAM) produces conditioned place preference (CPP) and dopamine release in the nucleus accumbens, it was suggested that the abuse liability of TRAM may be greater than hitherto assumed. We re-evaluated the effects of TRAM in CPP and behavioral sensitization, in comparison with morphine (MOR) and meptazinol (MEPT), an opioid drug with minimal abuse potential. While MOR produced CPP and very strong locomotor sensitization, TRAM and MEPT produced only CPP. It has been suggested that sensitization plays an important role in the development of addiction, hence our results suggest that the abuse potential of TRAM might resemble more that of MEPT than that of MOR, and they are consistent with the clinical picture, in that although TRAM is not completely devoid of positively reinforcing effects, reports on abuse are rare. The low propensity to induce addiction may be related to the lack of changes in the brain circuitry mediating reward and motivation, as evidenced by the lack of sensitization. Copyright 2002 Elsevier Science Ireland Ltd.

Efficacy and tolerability of sustained-release Tramadol ( Generic Ultram ) in the treatment of symptomatic osteoarthritis of the hip or knee: a multicenter, randomized, double-blind, placebo-controlled study.Malonne H, Coffiner M, Sonet B, Sereno A, Vanderbist F.Laboratoire de Physiologie et de Phannacologie, CP206-3, Institut de Pharmacie, Universite Libre de Bruxelles,1050 Bruxelles, Belgium. BACKGROUND: Opioid analgesics may be a useful alternative in patients with osteoarthritis who have not responded to first-line treatment with acetaminophen and in whom nonsteroidal anti-inflammatory drugs are contraindicated, ineffective, or poorly tolerated. OBJECTIVE: This study compared the efficacy and tolerability of Tramadol ( Generic Ultram ) LP 200 mg, a new once-daily,sustained-release formulation, with those of placebo in patients with osteoarthritis of the hip or knee. METHODS: In this multicenter, double-blind, placebo-controlled, parallel-group study, patients with osteoarthritis of the hip or knee (European League Against Rheumatism criteria) were randomized to receive either Tramadol ( Generic Ultram ) LP 200 mg once daily or placebo for 14 days. The primary efficacy end point was the change from baseline to the end of the study in scores on the Huskisson visual analog scale for pain. Secondary end points were change in the Lequesne functional discomfort index, global efficacy assessed by the patient and the investigator, time to improvement, and use of acetaminophen as rescue analgesic medication. Global tolerability was assessed by both patients and investigators at the end of the study The number and severity of adverse events occurring during the study and for 2 weeks thereafter were also recorded. RESULTS: Two hundred thirty patients (167 women, 63 men) were evaluable for efficacy and safety Demographic data for the Tramadol ( Generic Ultram ) and placebo groups were as follows: mean (SD) age, 67.1 (7.1) and 66.4 (92) years, respectively; female sex, 72.1% and 73.1%; and mean body weight, 74.7 (13.6) and 74.6 (14.8) kg. All patients were white. The completer analysis included 197 patients (85 Tramadol ( Generic Ultram ), 112 placebo). Pain was significantly reduced in the Tramadol ( Generic Ultram ) LP group compared with the placebo group on day 7 (P = 0.002) and day 14 (P = 0.010). In the patient's assessment of global efficacy, 77.6% (66) of the Tramadol ( Generic Ultram ) LP group reported improvement by day 14, compared with 59.8% (67) of the placebo group; in the investigator's assessment, the efficacy of Tramadol ( Generic Ultram ) LP was rated very good or good for 612% (52) of patients, compared with 30.4% (34) for placebo. Improvement was reported before day 7 in 882% (75) of patients in the Tramadol ( Generic Ultram ) LP group, compared with 65.2% (73) in the placebo group (P = 0.021); the mean time from the initiation of treatment to reported improvement was 3 days for Tramadol ( Generic Ultram ) LP and 6 days for placebo (P < 0.001). Rates of response (defined as > or =30% pain reduction between days 0 and 14) were 64.7% (55) for Tramadol ( Generic Ultram ) LP and 50.0% (56) for placebo (P = 0.039); no rescue medication was used by 60.0% (51) of the Tramadol ( Generic Ultram ) LP group and 36.6% (41) of the placebo group (P - 0.001). One or more adverse event was reported by 45.0% (50) of the Tramadol ( Generic Ultram ) LP group, compared with 193% (23) of the placebo group (P < 0.001). As would be expected with an opiate agonist such as Tramadol ( Generic Ultram ), the most common adverse events with this agent involved the gastrointestinal system (nausea, 22.5% [25] of patients; vomiting, 17.1% [19]) and the central nervous system (somnolence, 11.7% [13]). CONCLUSIONS: In this study, Tramadol ( Generic Ultram ) LP 200 mg was significantly more effective than placebo in alleviating pain in patients with osteoarthritis of the hip or knee. It appeared to be relatively well tolerated for an opioid compound.

Patient reporting of potential adverse drug reactions: a methodological study.

AIMS: To develop a systematic generic method of enabling patients to report symptoms which they believe to be due to a particular prescribed drug. METHODS: A piloted body system-based questionnaire was distributed to patients registered with 79 medical practices in Grampian prescribed one of nine recently marketed 'black triangle' drugs. These comprised four antidepressants, three antiepileptics and two analgesics. This requested respondents to identify any symptoms experienced over the previous year which they thought could be due to the 'black triangle' drug they had used. A sample of medical records was examined to compare symptoms recorded with those reported by patients. A classification system was developed for the study to enable the assessment of symptoms reported for their potential relationship to patients' drug therapy. All symptoms reported were classified, taking into account information provided by patients on their concomitant drugs and diseases. A specialist pharmacist independently re-classified a sample of the symptoms to validate the process. RESULTS: A 36.3% response rate was obtained (837/2307) with 742 respondents (88.6%) reporting at least one symptom. The median per patient was 6.0 (range 0--71), with almost half (406, 48.5%) reporting fewer than five symptoms. Most symptoms (71.0%) were classified as being probably or possibly related to the drugs studied. Agreement between researcher and specialist on the classification of 75.3% of 716 symptoms was obtained (Kappa=0.563). Responses from patients prescribed antidepressant drugs were more likely to include symptoms potentially caused by these drugs (74.5% of all symptoms reported) than those from patients prescribed analgesics (67.4%) or antiepileptics (65.1%, chi2 = 23.858, d.f. = 2, P < 0.001). Patients reporting large numbers of symptoms were more likely to report some which were classed as unlikely to be an ADR or unattributable (chi2 = 80.587, d.f. = 3, P < 0.001). Of the 742 reporting symptoms in questionnaires, 402 (54.2%) claimed to have reported some or all of these to their doctor. Only 162 (22.6%) of 716 patient-reported symptoms were documented in the primary care medical records of 103 patients prescribed Tramadol ( Generic Ultram ) or venlafaxine. CONCLUSIONS: Respondents were clearly willing to report symptoms, the majority of which were classed as possibly/probably related to the drugs studied. The results suggest that patients do not report all symptoms they suspect to be ADRs to their GP and that GPs do not record all symptoms which may be reported to them. The method could help to identify problems which patients perceive as being related to their drug therapy and contribute to increased ADR reporting.

The pupillary effects of intravenous morphine, codeine, and Tramadol ( Generic Ultram ) in volunteers.Knaggs RD, Crighton IM, Cobby TF, Fletcher AJ, Hobbs GJ.University Department of Anaesthesia, Queen's Medical Centre, University Hospital, Nottingham, UK.Opioid analgesics have pharmacological effects in many organ systems, including the eye. Because the metabolites of morphine and codeine contribute to their overall pharmacological effect pupil diameter measurements were made over a 6-h period. We studied the pupillary effects of IV morphine (0.125 mg/kg), codeine (1 mg/kg), Tramadol ( Generic Ultram ) (1.25 mg/kg), or placebo (10 mL 0.9% w/v sodium chloride) in 10 healthy volunteers. Pupil diameter was measured every 30 min using a pupil densitometer. Comparisons of the change in pupil diameter for each drug were made using analysis of variance with repeated measures. No significant change in pupil diameter was observed after placebo. After IV morphine and codeine administration there was a 26% decrease in pupil diameter (P < 0.001). Over the course of the study period, pupil diameter gradually returned to baseline values. After administration of Tramadol ( Generic Ultram ) there were no significant changes in pupil diameter until 150 min after administration, after which there was a significant reduction for the remainder of the study period (P < 0.01). The changes in pupil diameter may be explained in part by the pharmacokinetic profiles of the opioids studied. Measurement of pupil diameter may have a place in monitoring the central effect of opioids.

Double-blind clinical trial of Tramadol ( Generic Ultram ) capsules. First communication: Comparison with pentazocine and placebo (author's transl)

A new administration form of Tramadol ( Generic Ultram ) (50 mg) was compared in a multicenter double-blind trial with pentazocine (50 mg) and with placebo in patients with acute pains. Each patient received a test preparation once. The preparations were available in identical capsules. During the five-hour observation period the effect on the intensity of pain was recorded with reference to a scale and the undesirable side effects noted. Tramadol ( Generic Ultram ) was shown to have an analgesic effect about equal to that of the comparative preparation. Both analgesics were superior in effect to the placebo, as was expected. The incidence of side effects from Tramadol ( Generic Ultram ) was less than that with the comparative substance, even if both analgesics had a higher incidence of side effects than the placebo. The results confirm earlier experience obtained with parenteral application of Tramadol ( Generic Ultram ).

Tramadol ( Generic Ultram ) (zydol, Searle).

The account of Tramadol ( Generic Ultram ) (Zydol) in this month's issue is the first in a new series of articles reviewing new drugs and drugs which have recently become established in intensive and critical care nursing practice. It is intended through these articles to consider drugs from a nursing perspective and, in doing so, the key role of the nurse in evaluating the appropriateness, efficacy and safety of drug therapy is readily acknowledged. The format provides a brief description of dosage and available dosage forms together with pharmaceutical aspects including preparation, administration and storage. The actions and clinical uses of drugs are also discussed and summarised in a brief therapeutic comment. The Editor is anxious that 'Drug Therapy Review' serves a useful and practical function within the nursing process and the comments of our readers, including suggestions on topics for future review, will be gratefully received.