Assessment of prolonged-release tramadol efficacy and safety in general medical practice: A prospective observational study

Introduction: Pain is one of the most frequent symptoms leading to targeted intervention by General Practitioners (GPs). Tramadol is a weak analgesic opioid, prescribed in moderate/severe pain treatment, as 2nd ladder, according to WHO guidelines. To our knowledge, few Italian data are available concerning tramadol use in pain treatment. Aim of the Study: To evaluate efficacy of tramadol prolonged release formulation (SR), to assess incidence and severity of adverse drug reactions (ADRs) induced by such opioid, and to identify possible ADR risk factors. Methods: Sixty-four GPs, homogeneously distributed over all of Italy, were enrolled into this study to record, during daily clinical practice, demographic/clinical information about patients affected by chronic pain, neoplastic or less, receiving prescriptions of SR tramadol (100–200mg), for a period of at least 28 days. Efficacy was subsequently assessed throughout validated tools (Brief Pain Inventory, Visual Analogic Scale). Also anxious-depressive component was evaluated by Zung scale. Tolerability was analysed by reviewing all data about recorded ADR. Results: Study sample included 361 patients (mean age: 65 years, females 67%), affected by non-cancer pain in 93% of cases. Among these, 60% showed concomitant diseases or pharmacological treatments. Pain relief resulted complete/satisfactory in 75% of cases and the shortest period of SR tramadol treatment, enough to obtain significant complaint improvements, was 15 days. Anxiety/depression level decreased significantly only in patients affected by non-cancer pain. Regarding safety data, 47 patients (13%) reported at least one adverse reaction, all ADRs being described in drug-label. The most frequent events were: dizziness (5.3% of total ADR), vomiting (4.7%), nausea (3.5%) and confusion (2.5%). ADR clinical severity resulted mild in 24.7% of cases, moderate in 48% and severe in 22.1%. Most patients with ADR required treatment discontinuation, followed by complete resolution of the event. Among ADR patients, tramadol therapy followed another analgesic treatment: NSAIDs (75% of cases), NSAIDs/opioids (23%), and opioids (2%). ADRs occurred more frequently in patients aged 65–74 years, leading to treatment discontinuation more commonly than other age groups. Apart from age, other ADR risk factors were not identified. Conclusion: SR tramadol use resulted effective, providing complete pain relief in 75% of cases. On the other hand, all the reported ADRs were not serious, expected, and completely reversible after treatment discontinuation, suggesting an overall good benefit-risk/ratio for SR tramadol. Such research emphasises also the GP’s role in performing drug safety evaluations, especially concerning chronic pharmacological treatment.