Overactive bladder involves the symptom complex of urge incontinence, and urinary urgency and frequency. It is commonly treated with antimuscarinic agents to suppress involuntary bladder contractions, but anticholinergic effects like dry mouth, constipation and dizziness have decreased patient compliance with these agents. Appell and colleagues compared the efficacy and tolerability of two newer agents, extended-release oxybutynin chloride and tolterodine tartrate, in the OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study.
OBJECT was a prospective, randomized, double-blind, parallel-group study with 378 participants (315 women, 63 men; ages 21 to 87). The efficacy of the medications was evaluated using urinary diaries documenting frequency of micturition, episodes of urge incontinence and total incontinence episodes.
The two main inclusion criteria used to select participants were multiple episodes of urge incontinence (seven to 50) per week, and 10 or more voids per 24 hours. Patients with mixed stress and urge incontinence were included if most leakage episodes were related to urge incontinence. The list of exclusion criteria was much longer, consisting of incontinence with other etiologies (urinary tract infection, bladder tumor, etc.), recent childbirth or urogenital surgery, preexisting conditions that could worsen with the medications, and risk of developing complete urinary retention. Patients were recruited regardless of prior treatment with anticholinergic agents, but were asked to stop all such therapy during the screening process.
The participants were stratified into two groups, mild and moderate-to-severe, based on severity of urge incontinence, to ensure similar baseline symptoms in both treatment groups. Participants within each stratum were randomized to receive 10 mg daily of extended-release oxybutynin chloride or 2 mg twice daily of tolterodine tartrate for 12 weeks.
Adverse effects, although low overall, were the most frequent cause of discontinuation of therapy, with dry mouth the primary side effect (28.1 percent of patients taking extended-release oxybutynin and 33.2 percent of those taking tolterodine). Extended-release oxybutynin was found to be more effective than tolterodine in all of the main clinical outcome measures, including weekly micturition frequency (P .02), urge incontinence episodes per week (P .03) and total incontinence episodes per week (P .02).
The authors conclude that the tolerability profiles of both drugs are excellent and certainly better than the profile of immediate-release oxybutynin. As for efficacy, they conclude that extended-release oxybutynin chloride is superior to tolterodine, causing 28 percent fewer episodes of urge incontinence.
editor's note: The authors pointed out that all of the patients were referred from specialists rather than primary care physicians. Thus, the study was potentially biased toward patients with more severe urge incontinence. Of note, funding was provided by the Alza Corporation, the makers of an oxybutynin product.—s.m.