The Definition of Overactive Bladder
Overactive bladder (OAB) is a symptom complex that is characterized by urinary urgency, with or without urgency-associated urinary incontinence. OAB is often associated with urinary frequency and nocturia in the absence of pathologic or metabolic conditions that may cause or mimic OAB, such as urinary tract infections, polyuria, transitional cell carcinoma of the bladder, and underlying neurologic abnormalities.
Urgency, the hallmark of OAB, is defined as the sudden compelling desire to urinate, a sensation that is difficult to defer. Urinary frequency is defined as voiding 8 or more times in a 24-hour period. Nocturia is defined as the need to wake 1 or more times per night to void. 
The Prevalence of Overactive Bladder
Two epidemiologic studies have assessed the prevalence of overactive bladder (OAB). The National Overactive Bladder Evaluation (NOBLE) program was initiated to assess the prevalence and burden of OAB in the United States.  Investigators in the NOBLE study used a computer-assisted telephone interview questionnaire to estimate the prevalence of OAB and its variation by sex, age, and other demographic factors. A sample of 5204 adults who closely represented the US population by sex, age, and geographic regions was evaluated.
Among the NOBLE study participants, 16.5% met the criteria for OAB. Of these, 6.1% met the criteria for OAB with urgency incontinence, and 10.4% met criteria for OAB without urgency incontinence. Among individuals with OAB with urgency incontinence, 45% had mixed incontinence symptoms (urgency incontinence plus stress incontinence).
The prevalence of OAB was similar in women and men, at 16.9% and 16%, respectively. However, the prevalence of incontinence associated with OAB differed. Among women, 9.3% reported having OAB with incontinence; 7.6% reported having OAB without incontinence. In contrast, more men reported having OAB without incontinence (13.4%) than with incontinence (2.6%). In women, the prevalence of OAB with urgency incontinence increased with increasing body mass index (BMI), whereas, in men, no difference was found. In both men and women, the prevalence of OAB increased with age.
Milsom et al (2001) collected data with a population-based survey (conducted by telephone or direct interview) of 16,776 men and women aged 40 years or older from the general population in Europe.  The main outcome measures included the prevalence of urinary frequency (>8 micturitions per day), urinary urgency, and urgency incontinence. The overall prevalence of OAB symptoms was 16.6%. Frequency was the most common symptom (85%), followed by urgency (54%) and urgency incontinence (36%). The prevalence of OAB increased with age, and rates in men and women were similar. Symptoms of urinary urgency and frequency were similar among both sexes, but urgency incontinence was more prevalent in women than in men.
Men tend to develop OAB slightly later in life than women do, and women are more likely to develop urgency incontinence. Thirty seven to 39% of OAB cases remit during a given year, but the majority of patients have symptoms for years. [4, 5]
Despite the high prevalence of OAB, a significant discrepancy is found between the number of affected individuals and those seeking treatment. A Finnish study sought to determine how the frequency of urinary urgency and urge urinary incontinence (UUI) affects symptom-related bother, health-related quality of life (HRQL), and, ultimately, clinically meaningful prevalence of OAB.  A questionnaire was mailed to 6000 subjects (age 18-79 y) randomly identified from the Finnish Population Register in 2003-2004, with 62.4% responding. Urgency was reported by more than 50% of respondents, whereas UUI was noted by 25.7% of females and 10.7% of males. However, only 1 in 7 of all respondents with urgency and less than 1 in 3 with UUI reported at least moderate symptom bother. The authors found that increased severity of urgency and UUI is associated with a statistically significant and clinically important decrease in HRQL.
Causes of Overactive Bladder
Overactive bladder (OAB) appears to be multifactorial in both etiology and pathophysiology. Urination involves the CNS and peripheral autonomic, somatic, and sensory afferent innervations of the lower urinary tract, bladder, and sphincter. Normal bladders store urine at low pressure until it is full. When normal urination begins, urethral pressure decreases, and detrusor contraction empties the bladder. Symptoms of OAB are usually associated with detrusor overactivity. Overactivity of the detrusor muscle—neurogenic, myogenic, or idiopathic in origin—may result in urinary urgency and urgency incontinence.
Various efferent and afferent neural pathways and neurotransmitters are involved in the storage of urine and emptying of the bladder (see image below). Central neurotransmitters, such as glutamate, serotonin, and dopamine, are thought to have a role in urination. Glutamate is an excitatory neurotransmitter in pathways that control the lower urinary tract. Serotonergic pathways facilitate urine storage. Dopaminergic pathways may have both inhibitory and excitatory effects on urination. Dopamine D1 receptors appear to have a role in suppressing bladder activity, whereas dopamine D2 receptors appear to facilitate voiding.
Acetylcholine, which is the predominant peripheral neurotransmitter responsible for detrusor contractions, is released from the parasympathetic nerve terminal and binds to muscarinic receptors on the detrusor muscle. Five muscarinic receptor subtypes are known. The M3 muscarinic receptor appears to be responsible for detrusor contractility in the normal bladder.  The role of the M2 receptor in the human bladder is not well-established. Data from small studies demonstrating up-regulation of the M2 receptor in certain pathologic states suggest that it may have a role in detrusor overactivity related to obstruction and spinal-cord injury.
Binding of acetylcholine to the M3 receptor activates phospholipase C via coupling with G proteins. This action causes the release of calcium from the sarcoplasmic reticulum and contraction of the bladder smooth muscle. Increased sensitivity to stimulation by muscarinic receptors may lead to OAB. Leakage of acetylcholine from the parasympathetic nerve terminal may lead to micromotion of the detrusor, which may activate sensory afferent fibers, leading to the sensation of urgency.
Sensory afferent nerves may also play a role in OAB (see image above). The activation of normally quiescent C sensory fibers may have a role in producing symptoms of OAB in individuals with neurologic and other disorders. Several types of receptors identified on sensory nerves may have a role in OAB symptoms. These include vanilloid, purinergic, neurokinin A, and nerve growth factor receptors. Substances such as nitric oxide, calcitonin gene-related protein, and brain-derived neurotropic factor may also have a role in modulating sensory afferent fibers in the human bladder. [7, 8]
Once thought to be biologically inert, the urothelium may also have a role in OAB (see image above). The urothelium communicates directly with suburothelial afferents acting as luminal sensors. Low pH, high potassium concentration, and increased osmolality in the urine can influence sensory nerves. Activation of suburothelial afferent fibers without changes in the smooth muscle may lead to urgency. Activation of the suburothelial afferents in the presence of enhanced smooth-muscle coupling may lead to urgency and unstable detrusor contractions. 
More recently, attention has focused on the role of the beta3-adrenoceptor in the human detrusor. The relaxant response of the human detrusor to catecholamines is primarily mediated by beta3-adrenoceptors. In addition, beta-adrenergic receptors, including beta-3, have been identified in the urothelium and suburothelium and may be involved with bladder afferent activity. 
Several risk factors are associated with OAB. White people, persons with insulin-dependent diabetes, and individuals with depression are 3 times as likely to develop OAB. Other individuals at increased risk include persons older than 75 years, persons with arthritis, individuals on oral hormone-replacement therapy, and those with an increased BMI. 
Methods of Diagnosis
The term overactive bladder (OAB) refers to a symptom complex. Therefore, the first part of the evaluation of OAB is to review the patient's lower urinary tract symptoms to ensure that the symptoms are consistent with OAB. The American Urologic Association (AUA) guidelines recommend assessing for comorbid conditions that may affect bladder function, such as neurologic disease, motility deficits, complicated diabetes mellitus, fecal motility disorders, chronic pelvic pain, history of recurrent urinary tract infections, gross hematuria, prior pelvic/vaginal surgeries, pelvic cancer, pelvic radiation, and pelvic organ prolapse in females. [12, 13]
A diagnosis of OAB depends on the presence of urgency, which differs from a simple urge to void. A typical urge to void is a normal sensation that progressively strengthens when deferred. In contrast, urgency is an abnormal condition characterized by a sudden onset of urgency and difficulty in deferring urination (see The Definition of Overactive Bladder).
Other causes of urinary frequency, urgency, and urinary incontinence must be excluded. Incontinence has several subtypes: stress incontinence, mixed urinary incontinence, overflow incontinence, and transient incontinence. Transient incontinence may be related to delirium, infection, atrophy, pharmaceuticals, psychologic factors, excess urine output, restricted mobility, or stool impaction (DIAPPERS).
The patient's history should include information about the following:
Onset, nature, duration, severity, and bother of lower urinary tract symptoms
Medical and surgical history
Obstetric and gynecologic history
Prescription and over-the-counter medications: Medications that can affect bladder function include anticholinergics or antimuscarinics, antidepressants, antipsychotics, sedatives or hypnotics, diuretics, caffeine, alcohol, narcotics, alpha-adrenergic blockers, alpha-adrenergic agonists, beta-adrenergic agonists, and calcium channel blockers.
Review of systems, including genitourinary, obstetric and gynecologic, and neurologic findings
Social history, including smoking, alcohol consumption, fluid intake, and number of children (in women)
Bladder diary: This is used to record the times of micturitions and voided volumes, incontinence episodes, pad usage, and other information (eg, fluid intake, degree of urgency, degree of incontinence). A 3-day diary is ideal.
Physical examination should include the following:
Gynecologic examination to evaluate the strength of the muscles of the pelvic floor and to assess for prolapse of pelvic organ, urethral mobility, and stress urinary incontinence
Rectal examination to assess rectal tone and the prostate (in men)
Focused neurologic examination to examine pelvic reflexes, innervation of the feet, and the patient's mental status
Urinalysis to exclude microhematuria, pyuria, urinary tract infection, and glucosuria
Postvoid residual test: The AUA guidelines indicate that the measurement of postvoid residual (PVR) is not necessary for patients who are receiving first-line behavioral interventions or for uncomplicated patients receiving antimuscarinic medications. 
Urodynamic study: This is not indicated as part of the first-line evaluation of patients with OAB unless a neurologic etiology is suspected. Urodynamic study is most commonly performed in individuals in whom first-line therapies for OAB fail.
The Impact of Overactive Bladder
The impact of overactive bladder (OAB) extends far beyond its devastating effects on quality of life (QOL). Urinary incontinence remains one of the most common indications for admission to nursing homes. In addition, OAB and urinary incontinence are associated with other medical comorbidities, such as urinary tract infections, skin infections and irritations, and, in the elderly, an increased risk of falls and fractures. The economic impact of OAB is also considerable.
Quality of life
OAB significantly affects QOL. The symptoms of OAB the coping strategies used to manage or hide those symptoms commonly affect interactions with friends, colleagues, and families. Notable psychological effects of OAB and urinary incontinence include fear, shame, and guilt. In elderly people, OAB and incontinence may place an additional burden on family members if they need assistance with toileting, shopping for protective undergarments, and laundry. Worries and concerns regarding odor, uncleanliness, and leakage during sexual activity may lead individuals to refrain from intimacy. Frequent urination and the need to interrupt activities may affect the person's work and ability to travel. Studies of the impact of OAB and urinary incontinence demonstrate decreased levels of social and personal activities, increased psychological distress, and an overall decrease in QOL. 
The impact of OAB on QOL is independent of whether the symptoms are associated with urinary incontinence. Studies with the Short Form-36 (SF-36), a generic QOL questionnaire, demonstrated that OAB affects physical functioning, social functioning, vitality, and emotional roles (see image below). A shortened form of the SF-36, the Short Form-20 (SF-20) is another reliable and valid instrument to measure health-related QOL.  Instruments to assess disease-specific QOL, such as the Incontinence Impact Questionnaire (IIQ), the Kings Health Questionnaire, and the OAB-q, have been developed to determine the impact of OAB and urinary incontinence on QOL. These have all demonstrated the substantial impact of OAB and urinary incontinence.
Comorbidities associated with overactive bladder and urinary incontinence
Individuals with OAB and urinary incontinence may have other medical comorbidities. For instance, urinary tract infections, skin infections and irritation, falls, and fractures are more likely in persons with OAB and urinary incontinence. In women with daily urge incontinence, the risk of falls and fractures is increased by 26% and 34%, respectively.  The ramifications of hip fractures in elderly persons go well beyond the initial event. In addition, depression is more common in individuals with OAB. However, whether the depression is due to OAB or whether the 2 conditions share similar underlying neurologic etiologies is unclear.
Fortunately, treatment of OAB decreases the incidence of urinary tract infections and skin irritation and infection.
Economic impact of overactive bladder
OAB is often mistakenly considered to affect only QOL. However, as noted above, OAB is related to additional comorbidities.
Incontinence is a common indication for admission to nursing homes. The prevalence of OAB increases with age, and as many as 50% of nursing-home residents have either OAB or urinary incontinence. The annual cost of managing OAB in long-term care facilities has been estimated to exceed $3 billion; this figure increases to an estimated $9 billion in the community setting.
In total, an estimated $12.6 billion per year is spent in OAB-related costs (see image below). Some of the costs are obvious, such as those related to physician visits, protective devices, management of urinary tract infections, and skin infection and irritation. However, some are not. For example, decreased productivity and lost wages due to OAB is estimated to cost $841 million per year. These estimates do not reflect the intangible OAB-related costs such as time spent by family members away from work to care for elderly patients with OAB to accompany them to physician visits, to shop for protective devices, and to help with toileting and laundry. Therefore, the cost figures underestimate the economic impact of OAB. 
Management of OAB can decrease the economic impact of OAB. Two studies have demonstrated a cost-savings related to medical management of OAB. In both of these studies, savings were achieved by reducing the comorbidities of urinary tract infections and skin infection and irritation. [15, 16]
In summary, OAB is a highly prevalent condition that is associated with considerable QOL, medical, and economic effects.
Nonpharmacologic and Nonsurgical Intervention for Overactive Bladder
Behavioral therapy, also called behavioral modification, is a treatment approach that aims to alter an individual's actions or environment to improve bladder control. Components of behavioral therapy include (1) education, (2) dietary and lifestyle modification, (3) bladder training, (4) pelvic floor muscle therapy (PFMT), and (5) self-monitoring with bladder or voiding diaries. [17, 18, 19, 20]
Regarding dietary and lifestyle modification, changes in the amount and type of fluid consumed (eg, decreasing consumption of caffeinated and carbonated beverages) may improve the symptoms of overactive bladder (OAB).
Bladder training involves a program of patient education and a scheduled voiding regimen, which is progressively increased. The goals of bladder training are to normalize urinary frequency, to improve control over bladder urgency, to increase bladder capacity, to decrease incontinence episodes, to prolong voiding intervals, and to improve the patient's confidence in bladder control. The mechanism by which bladder training works is not fully identified; however, theories include improved cortical inhibition over detrusor contractions, improved cortical facilitation of urethral closure during bladder filling, improved central modulation of sensory afferent impulses, changes in behavior due to improved awareness of lower urinary tract function, and increased reserve capacity of the lower urinary tract.
PFMT involves exercises designed to improve the function of the pelvic floor muscles. The rationale for use of PFMT in urgency urinary incontinence and OAB is that contraction of the muscles can reflexly or voluntarily inhibit contraction of the detrusor muscle. PFMT is defined as any program of repeated voluntary pelvic floor muscle contractions (VPFMC) taught by a healthcare professional. 
Biofeedback-assisted behavioral therapy uses biofeedback to teach patients how to control normal physiologic responses of the bladder and pelvic floor muscles that mediate incontinence. Early biofeedback for OAB consisted of bladder-pressure biofeedback. [22, 23] Feedback of pelvic floor’s muscular activity was subsequently added.  Bladder-pressure biofeedback was not widely adopted because of the need for catheterization during each training session. Biofeedback is most commonly used to teach individuals to identify and contract their pelvic floor muscles.
Recommendations for behavioral therapy
In 1989, the Consensus Conference on urinary incontinence in adults recommended that the least invasive or dangerous procedure should be tried first.  In its guidelines for urinary incontinence in adults, the Agency for Health Care Policy and Research recommended behavioral therapy as a first-line therapy for incontinence.  Most recently, the Third International Consultation on Incontinence in June 2004 recommended behavioral therapy as a first-line therapy for incontinence.  The AUA guidelines recommend that behavioral therapies (ie, bladder training, bladder control strategies, pelvic floor muscle training, fluid management) should be offered as first-line therapy to all patients with OAB. 
Success rates of behavioral therapy
When behavioral therapy was compared with drug therapy in an outpatient geriatric medicine clinic, behavioral therapy yielded a mean 80.7% reduction in incontinence episodes. Behavioral therapy was significantly more effective than oxybutynin given at a dosage of 2.5 mg/day to 5 mg 3 times per day (mean 68.3% reduction in incontinence episodes; P = .04). Both therapies were better than placebo (mean 39.4% reduction; P < .001 and P = .009, respectively). In addition, patient-perceived improvement was also greatest among those treated with behavioral therapy.  In a randomized clinical trial of bladder training, Fantl et al (1991) observed that episodes of incontinence decreased by a mean of 57% in women aged 55 years and older who underwent bladder training compared with little improvement in a no-treatment control group. 
AUA guidelines note, "behavioral treatments are designated as first-line treatments because they are as effective in reducing symptom levels as are antimuscarinic medications, and they consist of many components that can be tailored to address the individual patient's needs and capacities.” 
The International Continence Society (ICS) recommends that PFMT be offered as a first-line therapy to all women with stress, urge, or mixed urinary incontinence. Different techniques of PFMT are described in the literature. They vary in the training schedule; the frequency, force, and duration of contractions of the pelvic floor muscle; and the use of adjuncts, such as biofeedback, electronic prompting devices, and intravaginal pressure-monitoring devices. Patients seem to benefit most from a PFMT program that provides intensive supervision. Most patients do not appear to have any posttreatment benefit from biofeedback-assisted PFMT.  However, for individuals who have trouble identifying and contracting the pelvic floor muscles, biofeedback may be useful. PFMT has been effective in women of all ages. 
Biofeedback-assisted behavioral training has been effective in treating urgency urinary incontinence with 76-86% mean reductions in episodes of urgency urinary incontinence. [24, 31, 32] However, biofeedback is not necessary for everyone. In a comparison of bladder training with and without biofeedback, Burgio et al (2002) evaluated biofeedback, verbal feedback based on vaginal palpation, and use of a self-help booklet about PFMT in a first-time behavioral therapy program in community-dwelling women aged 55-92 years.  All achieved similar reductions in episodes of urgency incontinence. However, the groups differed significantly regarding patient satisfaction: 75% complete satisfaction with treatment in the biofeedback group, 85.5% in the verbal feedback group, and 55.7% in the self-help booklet group (P = .001).
The combination of behavioral therapy and pharmacologic therapy
Burgio et al demonstrated an added benefit of combining drug and behavioral therapy in a stepped program. Individuals who were not completely continent or unsatisfied with monotherapy (behavioral therapy or oxybutynin) were offered combination therapy.  When behavioral or oxybutynin therapy was changed to a combined strategy, substantial improvements were noted (P = .032 and P = .001, respectively).
The limitations of behavioral therapy
Behavioral therapy relies on active participation of an involved and motivated patient. In addition, it requires a practitioner well-trained in behavioral therapy. Behavioral therapy does not cause any permanent changes in bladder function (eg, decreased detrusor overactivity as measured on urodynamic studies). Therefore, regular adherence and long-term compliance are needed.