Chughtai et al that transdermal oxybutynin does not undergo ﬁrst-pass metabolism in the liver, much lower concentrations of N-desethyloxybutynin, the active metabolite of oxybutynin, are noted. For this reason, in various clinical trials, transder- mal oxybutynin has been shown to have a relatively low risk of side effects; most frequent was application-site reactions (Schaefer 2007). Even these may be reduced by the use of topical corticosteroid or antihistamine to the site. Similar to oxybutynin, tolterodine is available in both short-acting and long-acting formulations. Both formula- tions have shown good efﬁcacy for the symptoms of OAB in large studies (Choo et al 2008). The extended-release form is better-tolerated and more effective than the immediate- release formulation (Choo et al 2008). In one randomized controlled study of extended-release tolterodine 4 mg/day in patients with urge incontinence and urinary frequency, no differences were found for efﬁcacy, tolerability, or safety between older and younger patients (Wefer et al 2001). In another trial, there was a small but statistically signiﬁcant decrease in the efﬁcacy of tolterodine with age (Michel et al 2002). In another study, The Overactive Bladder: Perfor- mance of Extended-Release Agents trial, oxybutynin-ER and extended-release tolterodine (tolterodine-ER) were compared. Reduction in the frequency of incontinence epi- sodes was similar in the oxybutynin-ER and tolterodine-ER groups (Diokno et al 2003). Micturition frequency was more reduced in the oxybutynin-ER group than in the tolterodine- ER group. More importantly, a greater number of partients in the oxybutynin-ER group achieved complete continence (Diokno et al 2003). In a follow-up study using the same data set, central nervous system side effect proﬁles of oxy- butynin-ER and tolterodine-ER were compared (Kay et al 2006). Adverse events occurred in 9.0% in the oxybutynin- ER group and 8.3% in the tolterodine-ER treatment groups (p 0.8) (Kay et al 2006). Certain risk proﬁles apply to all members of the anti- cholinergic class. All anticholinergic agents should be used with caution and specialty consultation in patients with narrow-angle glaucoma, decreased gastrointestinal motility, or clinically signiﬁcant bladder outﬂow obstruction. Side effects of antimuscarinic agents can include changes in blood pressure, pulse rate or ECG when beginning treatment. Diz- ziness and blurred vision are occasionally reported as well. The most common side effect is dry mouth (Lam and Hilas 2007). Constipation and dyspepsia are also reported. Dizzi- ness and somnolence are common CNS side effects. On the whole, side effects are transient and tolerable – although constipation is one of the common side effects, the use 506 of laxatives and stool softeners is rarely necessary (Anon 2007). Adverse events or side effects infrequently lead to withdrawal of treatment. Trospium chloride, which is a quaternary ammonium compound, has recently been approved by the FDA for the treatment of OAB (Staskin et al 2007). It was initially provided as a single 20 mg dose for twice-daily use, and has more recently been approved in a 60 mg once-daily formu- lation. Trospium efﬁcacy has been shown to be equivalent to twice daily oxybutynin-IR with a lower incidence of dry mouth (Zinner et al 2004). Trospium also may have a lower risk of central nervous system side effects because of its low predilection to cross the blood–brain barrier (Guay 2003). It also has an added beneﬁt of being metabolized by the kidneys rather than the cytochrome P450 system, thereby having fewer interactions with other medications (Guay 2003). It may be beneﬁcial for patients who are elderly and/or receiving multiple medications. More recent additions for the treatment of OAB are dari- fenacin and solifenacin, both of which are available in once- daily formulations. Darifenacin is available in 7.5 mg/day and 15 mg/day formulations, with a recommended starting dose of 7.5 mg daily. Solifenacin is started at 5 mg once daily and dosing may be increased to 10 mg once daily. These are M3-selective receptor antagonists which potentially may be more bladder-speciﬁc with reduced tendency for anticholinergic side effects. Agents that are M3-selective are associated with relatively high rates of constipation. Reported rates of 9.1% and 14.4% have been demonstrated for both solifenacin 10 mg daily and darifenacin 7.5 mg daily respectively (Anon 2005). Solifenacin should be used with caution in patients with reduced hepatic or renal function, and darifenacin is not recommended for use in patients with severe hepatic impairment. Darfenacin in the 7.5 mg dose may be used with caution in patients with moderate hepatic impairment, and there are no dosing adjustments for patients with mild hepatic impairment. Darifenacin does not require dose adjustment for elderly patients, and both medications have been shown to have similar safety and efﬁcacy between older and younger patients (Wagg et al 2006; Chancellor and Miguel 2007). The literature is sparse on head to head trials of the newer agents. However, the STAR (solifenacin vs tolterodine mul- tinational trial) trial compared 4 mg of tolterodine to 5 mg then 10 mg of solfenacin (Chapple et al 2005a). At the 10 mg dose of solifenacin, there was a 10% greater reduction in the number of reported incontinence episodes compared with the tolerodine group. Criticism of the study stems from the Clinical Interventions in Aging 2008:3(3)