fact that FDA dosing allowed for an escalated 10 mg dose of solifenacin, whereas tolterodine remained at 4 mg. In a more recently available subcut analysis of the data comparing tolterodine 4 mg ER with solfenacin 5 mg, the authors found that within 4 weeks of solifenacin 5 mg therapy, solifenacin 5 mg was signiﬁcantly better than tolterodine ER 4 mg in improving incontinence episodes and reducing incontinence pad use. At the endpoint of the trial, there was a reduction in the number of incontinence episodes from 1.1 in the toltero- dine arm and 1.6 in the solifenacin arm (p = 0.006) (Chapple et al 2005a, 2007a). Differences in efﬁcacy continued for the duration of the study after the dose increase of solifenacin was allowed. Clinical trials of darifenacin Darifenacin has been the subject of several randomized clini- cal trials. Pooled data analysis from 3 studies enrolled over a thousand patients (85% female; age range 19–88 years) with a minimum 6-month history of overactive bladder symptoms including urgency, frequency, and urge inconti- nence. All participants had a 2-week washout and a 2-week placebo run-in prior to the beginning of the trial. Patients were randomized to be given either 1) darifenacin 7.5 mg or matched placebo or 2) darifenacin 15 mg or matched placebo. Outcome data were collected by use of an electronic diary. Although there was a noted placebo response, both doses of darifenacin were superior to placebo in alleviat- ing symptoms associated with OAB (Chapple et al 2005b). Darifenacin has also been compared with oxybutynin as well as a matched placebo. Seventy-six patients (93% female) had detrusor overactivity veriﬁed with urodynamics with at least 4 urge incontinence episodes per week and a frequency of at least 8 micturitions per day. All patients underwent a 2-week run-in period prior to 2 weeks of treatment in each arm. A paper diary was used to assess outcomes. Results revealed a comparable efﬁcacy with oxybutynin, in comparison to the placebo arm with reduced a side effect proﬁle (Chapple and Abrams 2005). Another study looked at the onset of action of darifenacin. 561 patients (age range 19–88 years; 85% female) with OAB symptoms were enrolled for at least 6 months (Haab et al 2004). After a 2-week washout and a 2-week placebo trial, participants were randomized to 3.75 mg darifenacin, 7.5 mg darifenacin, 15 mg darifenacin or placebo. Onset of action was noted by 2 weeks, although increased beneﬁt was seen up to 12 weeks in this study (Haab et al 2004). Another parameter to measure the severity of urinary urgency includes warning time. This is the time between Clinical Interventions in Aging 2008:3(3) Darifenacin for overactive bladder ﬁrst sensation and time of micturition. This in theory rep- resents the time available for the patient to ﬁnd a toilet and could reduce social embarrassment. In a study by Chapple et al (2007b), 72 patients (51 female) with urinary urgency of more than 6 months duration and at least 4 urge episodes per day, received either darifenacin 30 mg or placebo. All patients again had a 2-week washout period and 2 weeks of treatment double blinded. Warning time was recorded before and after treatment using electronic event markers. The severity of the urgency was recorded on a Likert scale from 0 (no urgency) to 3 (severe urgency). After 2 weeks of treatment, the warning time increased in the patients taking darifenacin by 22.5% compared with a reduction of 18.9% in the placebo group (Chapple et al 2007b). This equated to a mean increase in warning time of 4.3 min in those taking darifenacin (Chapple et al 2007b). This may seem insigniﬁ- cantly small but especially in those at home or while in bed it provides time to ﬁnd a toilet and avoid a socially embar- rassing event of urge incontinence. Darifenacin’s symptom improvement is supported by improvement in quality of life scores, as assessed by the King’s Health Questionnaire (Nabi et al 2006). In light of selectivity of muscarinic M3 receptors, dari- fenacin minimizes the risk of blockade of other muscarinic subtypes, eg, M1-mediated cognitive impairment. This is of particular importance for older patients who may be more sus- ceptible to cognitive impairment and central nervous system effects. This patient population is at increased risk of cerebral exposure from increased permeability of the blood – brain barrier associated with advancing age, diabetes, Alzheimer’s disease, or multiple sclerosis. There is a low incidence of cognitive side effects, which is especially beneﬁcial for the elderly (Nabi et al 2006). In an analysis by Foote et al (2005), 317 patients aged 65 years or more were evaluated in one of three multicenter, randomized, double-blind, and placebo controlled studies. All patients had had symptoms of OAB for more than 6 months. If patients needed, they had a 2-week washout period and a 2-week drug-free/placebo run-in, prior to receiving once-daily darifenacin 7.5 mg versus placebo, or darifenacin 15 mg versus placebo. At 12 weeks, both doses of darifenacin were signiﬁcantly superior along all symptoms of OAB assessed (Foote et al 2005). This analysis conﬁrmed the efﬁcacy in the elderly population. An important ﬁnding in this trial was the low incidence of nervous system effects (eg, somnolence, dizziness) during darifenacin therapy, similar to that with placebo in the present analysis of older patients, and also similar to that previously reported for the wider patient population. 507