Aims of Study:
Antimuscarinic agents are known to reduce urge incontinence in patients with overactive bladder, but less attention has been paid to the effect on perception of urgency. Tolterodine is a muscarinic receptor antagonist with selectivity for the bladder over other body tissues. The aim of this study was to examine the effect on urgency of a new, once-daily (OD) formulation of tolterodine.

Methods:
A total of 1015 overactive bladder patients (81% female), diagnosed exclusively based on symptoms and average volume voided, were randomised into a double-blind, parallel-group, placebo-controlled, multinational, multicentre study comparing tolterodine 4 mg OD (n=507) and placebo (n=508). Patients were treated for 12 weeks after a 7-day washout (for patients currently on other treatments) and a 7 day run-in period (to collect baseline micturition diary information). Efficacy was assessed primarily with micturition diaries but also with patient perception evaluations. Tolerability profiles were determined through adverse event reports.

Results:
Overall, 39% of patients treated with tolterodine 4 mg OD reported improvement in their urgency symptoms, and 58% reported improvement in their bladder condition. Both of these results were statistically significant compared to placebo. As expected, treatment with tolterodine 4 mg OD produced a statistically significant decrease in urge incontinence episodes compared to placebo. Other micturition diary variables were also significantly improved compared to placebo (see Table).

Percent change from baseline in micturition variables after 12 week's treatment

Treatment with tolterodine 4 mg OD was well tolerated. More patients on placebo withdrew from treatment due to adverse events than tolterodine-treated patients (6.5% vs 5.3%). Dry mouth was reported by a total of 23% (2% severe) of tolterodine recipients, compared to 8% of placebo-treated patients. The next most common adverse events were headache (6% tolterodine; 5% placebo) and constipation (6% tolterodine; 4% placebo). No safety concerns were noted during the study.

Conclusions:
The new OD formulation of tolterodine is highly effective, safe and well tolerated in the treatment of overactive bladder. The effect on urgency and other patient perceptions is interesting and merits further study. This study was supported by Pharmacia & Upjohn