Urge incontinence, also referred to as overactive bladder (OAB)-wet, is the involuntary loss of urine accompanied by or immediately preceded by a sensation of urgency. It has a reported overall prevalence of 16.0% in men and 16.9% in women.1 Currently, the mainstay of management for symptomatic urgency and OAB-wet is medical therapy.
In this article, we review the pathophysiology, evaluation, and different medical treatment options available for OAB-wet.
Various causes for OAB and OAB-wet have been proposed. A neurogenic theory for the pathophysiology of OAB-wet is based on increased excitability of detrusor smooth muscle in the bladder.2 This has been seen in several neurogenic disorders, including multiple sclerosis, stroke, spinal cord injury, transverse myelitis, and Parkinson disease. A myogenic theory attributes symptoms to alterations of the detrusor smooth muscle that lead to failure to store or failure to empty properly.3 The detrusor instability and overactivity lead to decreased compliance of the bladder secondary to structural and functional changes that may include infiltration of detrusor smooth muscle by elastin and collagen.4
Other proposed mechanisms for the pathophysiology of OAB-wet include inflammatory conditions and infection, or the condition may be idiopathic.5
A detailed evaluation is essential before proceeding to treatment of patients with OAB-wet. History and physical examination should include assessment of comorbidities and concurrent medical conditions—such as multiple sclerosis or diabetes and history of urinary tract infections, previous pelvic surgery, and use of medications—and any evidence of vaginal atrophy or pelvic prolapse.
Review of the patient's medications is useful, because certain drugs, such as bethanechol and cisapride, can potentiate OAB-wet. Other agents (ie, α-blockers, benzodiazepines, and neuroleptics) can increase incontinence episodes by decreasing urethral resistance.6
A voiding diary is often helpful in assessing the degree of incontinence.7 Diaries include accounts of frequency, nocturia, and incontinence episodes; timing and amount of fluid intake; voids; and number of pads used per day; this information helps differentiate between frequency alone and high urine production with resultant frequency.
Patients in whom urodynamic studies may also be useful include those who present with mixed symptoms or underlying neurologic conditions or those in whom empiric medical therapy has failed. Important urodynamic parameters include bladder capacity, compliance, presence of detrusor overactivity with associated incontinence, and postvoid residual volumes (Figure).
In addition, cystoscopy to rule out bladder tumors or carcinoma in situ may be appropriate for a select group of patients.
Medical therapy remains the standard for OAB and OAB-wet. Various nonsurgical modalities in addition to medications have been described, including behavioral modification, pelvic floor muscle training, and biofeedback with or without electrical stimulation. The latter options are often used in conjunction with medications to optimize outcomes.
Nonsurgical modalities. Behavioral modification is directed at improving voluntary control of bladder function to decrease urgency and may result in improvement rates in incontinence episodes in excess of 50%.8,9 Pelvic floor muscle training has also been reported to help improve symptoms associated with bladder overactivity.10 There are subjective reports of improvement in patients with OAB-wet treated with biofeedback, with or without electrical stimulation. One study produced subjective improvement in 51.4% of patients treated with electrical stimulation and in 50% of those using biofeedback-assisted pelvic floor muscle training.11,12
Medical therapy. Various medications have been used both exclusively and concomitantly with the aforementioned behavioral modifications. The foundation of medical therapy for OAB-wet remains the anticholinergic/antimuscarinic agents. Acetylcholine stimulates postganglionic muscarinic receptors in the bladder to initiate detrusor contraction and voiding. Five types of muscarinic receptors (M1-M5) mediate cognition, salivation, sympathetic output, ciliary muscle contraction in the eye, and GI motility. M2 and M3 receptors are the most pertinent receptors for bladder function. M2 receptors, which are most prevalent in the bladder, also mediate cardiac output; M3 receptors, which have the most selectivity for bladder contractions, are also present in the smooth muscle of the GI tract.13
Oxybutynin. The nonspecific muscarinic antagonists, or anticholinergics, act by antagonizing the muscarinic actions of acetylcholine on smooth muscle and by exerting a spasmolytic effect on the detrusor muscle.14 The most widely prescribed anticholinergic is oxybutynin, which is available in immediate-release, extended-release, and transdermal forms. In addition, off-label use has been described with intravesical oxybutynin.15
Oxybutynin is a nonselective tertiary amine ester that also provides local anesthetic properties. Cystometric studies have demonstrated that oxybutynin increases maximum bladder capacity and volume to first detrusor contraction.16 It also decreases urinary urgency and frequency of both incontinence episodes and voluntary urination.
Adverse effects associated with antimuscarinic agents are dose-related and include dry mouth, constipation, drowsiness, and blurred vision. The adverse effects associated with oxybutynin are thought to be related to the metabolite N-desethyloxybutynin, which is rendered via the cytochrome P-450 system.
The extended-release formulation of oxybutynin was developed to reduce the first-pass metabolism and rate of absorption.17 The decreased rate of absorption allows the medication to reach the colon, where cytochrome P-450-mediated oxidation is less extensive than in the small intestine. The incidence of dry mouth with extended-release oxybutynin was reduced by about 50% when compared with the immediate-release formulation, but the efficacy was comparable to immediate-release oxybutynin.14,18,19
The transdermal system delivers oxybutynin continuously over a 3- to 4-day interval. Oxybutynin is transported across intact skin into the systemic circulation by passive diffusion across the stratum corneum. The average daily dose of oxybutynin absorbed from the 39-cm2 transdermal oxybutynin system is 3.9 mg.20 The transdermal route also bypasses first-pass metabolism, reducing the formation of the N-desethyloxybutynin metabolite.21
Contraindications to use of all formulations of oxybutynin include narrow-angle glaucoma, urinary or gastric retention, myasthenia gravis, or ulcerative colitis or other obstructive GI tract disease.
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