EFFICACY AND SAFETY OF TOLTERODINE IN PATIENTS WITH DETRUSOR INSTABILITY - A DOSE-RANGING STUDY

Objective To investigate the efficacy and safety of tolterodine, a new antimuscarinic agent, and define the optimum dosage in patients with symptoms of detrusor instability (urgency, increased frequency of mict urition and/or urge incontinence). Patients and methods A double-blind , placebo-controlled, multicentre study was carried out: after a 1-wee k run-in period to establish baseline values, 81 patients were randomi zed to receive placebo or tolterodine 0.5, 1, 2 or 4 mg twice daily fo r 2 weeks. Micturition (diary) variables, urodynamics and subjective u rinary symptoms were assessed after 2 weeks' treatment. Results A per- protocol analysis of efficacy in 64 patients showed dose-related impro vements in recorded micturition and urodynamic variables, e.g. at a do sage of 2 mg twice daily, the frequency micturition, episodes of incon tinence and pad use were reduced by 20%, 46% and 29%, respectively, wh ile the volume at first contraction increased by 89 mL. The 4 mg dosag e was associated with a large increase in residual urinary volume and an increased incidence of dry mouth, The incidence of adverse events ( mainly mild or moderate antimuscarinic effects) was comparable with pl acebo at tolterodine dosages of less than or equal to 2 mg. No serious adverse events were observed and tolterodine had no clinically signif icant impact on electrocardiographic or laboratory findings. Conclusio n The results indicate that tolterodine offers an effective treatment for the symptoms of detrusor instability. The optimum dosage appears t o be 1-2 mg twice daily.