Background

Overactive bladder (OAB) refers to the common and bothersome group of storage lower urinary tract symptoms (LUTS). The International Continence Society (ICS) defines OAB syndrome as urgency with or without urgency urinary incontinence (UUI), usually with frequency and nocturia [1]. Prevalence rates for OAB are estimated to range between 12% and 17% in the United States and Europe. Both men and women are equally affected by OAB, and the incidence rate increases with age [2–4]. This condition has a serious impact on both individuals and society [5,6]. OAB can be managed with bladder and behavioral training, biofeedback, electrical stimulation, pharmacological treatments or a combination of therapies [7]. Antimuscarinic agents are the first-line pharmacotherapy for OAB treatment [8]. This systematic review of the tolerability, safety, and efficacy of licensed antimuscarinic treatments in OAB, which is based on a recent article published in European Urology, provides an up-to-date summary of the efficacy, tolerability, and safety of licensed antimuscarinic treatments in OAB, and describes the effects of treatment on health-related quality of life (HRQL).

Overactive bladder (symptomatic diagnosis) is often assumed to be caused by detrusor overactivity (DO), even if this does not always seem to be the case [9–12]. DO/OAB can occur as a result of sensitization of afferent nerve terminals in the bladder or outlet region, changes of the bladder smooth muscle secondary to denervation, or consequent upon damage to the central nervous system (CNS) inhibitory pathways, as can be seen in various neurological disorders, such as multiple sclerosis, cerebrovascular disease, Parkinson’s disease, brain tumors, and spinal cord injury.

Normal bladder contraction in humans is mediated mainly through stimulation of muscarinic receptors in the detrusor muscle. The neurotransmitter acetylcholine (ACh) acts on two classes of receptors: the nicotinic and the muscarinic. While the former play a role in the signal transduction between neurons or between neurons and skeletal muscle (e.g. in the distal urethra), the signal transduction between parasympathetic nerves and smooth muscle of the detrusor involves muscarinic receptors [13]. Importantly, the endogenous muscarinic receptor agonist ACh is not necessarily derived only from parasympathetic nerves in the urinary bladder, but can also be formed and released non-neuronally by the urothelium [14–16]. Five subtypes of muscarinic receptors have been cloned in humans and other mammalian species, which are designated M1-5 [17]. Based upon structural criteria and shared preferred signal transduction pathways, the subtypes can be grouped into M1, M3 and M5 on the one hand and M2 and M4 on the other. However, most muscarinic receptors in the urinary bladder are located on smooth muscle and urothelial cells.

While the detrusor expresses far more M2 than M3 receptors, it appears that detrusor contraction under physiological conditions is largely if not exclusively mediated by the M3 receptor [18–23]. Previous reviews have demonstrated moderate efficacy for muscarinic receptor antagonists relative to placebo in controlled clinical studies [24–28].

Literature search

Findings of this analysis are summarized in Table 19.1. A greater proportion of patients treated with antimuscarinics than with placebo returned to continence. The pooled relative risk (RR) varied between 1.3 and 3.5 across treatments. There were no statistically significant differences between treatments in meta-analyses of active-controlled trials for this outcome. Active treatments were more effective than placebo in terms of the mean change in the number of incontinence episodes per day. Pooled differences in mean change ranged from 0.4 to 1.1 incontinence episodes per day. Active treatments were more effective than placebo in terms of the mean change in the number of micturitions per day. Pooled differences in mean changes ranged from 0.5 to 1.3 episodes per day. Fesoterodine, propiverine, solifenacin, and tolterodine were statistically significantly more effective than placebo in terms of the mean change in the number of urgency episodes per day, where reported. Pooled differences in mean changes varied between 0.64 and 1.56 episodes per day. Active treatments were all statistically significantly more effective than placebo in terms of the mean change in the volume voided per micturition (mL) where reported for each licensed drug other than trospium chloride, for which this outcome was not reported. Differences in pooled mean changes were 13 to 40 mL.

Table 19.1 Efficacy of antimuscarinics compared to placebo: results from meta–analyses*

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