A Systematic Review and Meta-Analysis of Randomized Controlled Trials with Antimuscarinic Drugs for Overactive Bladder

Context: Anticholinergic drugs are commonly used in patients with overactive bladder (OAB) who do not achieve symptom relief and quality of life improvement with conservative management. Several drugs, with different doses, formulations, and routes of administration are currently available, making the choice quite difficult. Objective: To evaluate efficacy and safety of different doses, formulations, and route of administration of the available anticholinergic drugs. Evidence acquisition: A systematic review of the literature was performed in August 2007 using Medline, Embase, and Web of Science. Efficacy (micturitions per 24 h, volume voided per micturition, urgency urinary incontinence episodes per 24 h, incontinence episodes per 24 h) and safety (mainly, adverse events and withdrawal rates) end points were evaluated in the randomized control trials (RCTs) assessing the role of anticholinergic drugs in non-neurogenic OAB. Meta-analysis of RCTs was conducted using the Review Manager software 4.2 (Cochrane Collaboration). Evidence synthesis: our systematic search identified 50 RCTs and three pooled analyses. Tolterodine immediate release (IR) had a more favorable profile of adverse events than oxybutynin IR. Regarding different dosages of IR formulations, dose escalation might yield some limited improvements in the efficacy but at the cost of significant increase in the rate of adverse events. In the comparisons between IR and extended-release (ER) formulations, the latter showed some advantages, both in terms of efficacy and safety. With regard to the route of administration, use if a transdermal route of administration does not provide significant advantage over an oral one. Conclusion: Many of the available RCTs have good methodological quality. ER formulations should be preferred to the IR ones. With regard to IR formulations, dose escalation might yield some improvements in the efficacy with significant increase in the AE. More clinical studies are needed to indicate which of the drugs should be used as first-, second-, or third-line treatment. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.