Overactive Bladder

Practice Essentials

Overactive bladder (OAB) is a syndrome characterized by a sudden and compelling need to urinate. OAB affects physical functioning, social functioning, vitality, and emotional roles^[1] (see the image below).

View Image

Overactive bladder (OAB) and quality of life (QoL). Short Form-36 (SF-36). Reprinted with permission from Blackwell.

Signs and symptoms

Clinical manifestations of overactive bladder OAB include the following:

• Urinary urgency (hallmark symptom)
• Urgency urinary incontinence (may or may not be present)
• Urinary frequency and nocturia (usually present)

See Presentation for more detail.

Diagnosis

Diagnosis of OAB requires exclusion of infection and other pathologic conditions. In complicated cases, demonstration of underlying detrusor overactivity (phasic increases in detrusor pressure) can be valuable.

Diagnostic guidelines

Guidelines for diagnosis of OAB by the American Urological Association (AUA)/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU) include the following^[2] :

• A thorough history, physical examination, and urinalysis should be done initially
• If necessary, a urine culture, or postvoid residual assessment, or both can be done, along with use of bladder diaries or symptom questionnaires
• Urodynamic study, cystoscopy, and diagnostic renal and bladder ultrasonography are not necessary in the initial workup of uncomplicated cases and should be reserved for refractory or otherwise complicated cases
• Urine cytology is not recommended in the absence of hematuria when the patient responds to therapy

Examination and testing

A comprehensive physical examination for OAB includes the following:

• Pulmonary and cardiovascular evaluation
• Abdominal examination
• Pelvic examination and rectal examination
• Neurologic examination

Office and laboratory tests for OAB include the following:

• Urinalysis
• Urine culture (if infection is suspected)
• Postvoid residual testing
• Cystometry
• Urodynamic study

See Workup for more detail.

Management

The three main treatment approaches are as follows:

• Behavioral therapy (eg, bladder training, biofeedback, pelvic floor muscle therapy, pelvic floor electrical stimulation)
• Pharmacologic therapy (eg, anticholinergic/antimuscarinic agents)
• Surgical therapy (eg, neuromodulation and augmentation cytoplasty [rarely necessary])

Treatment guidelines

Guidelines for the treatment of OAB by the AUA/SUFU include the following recommendations^[2] :

• First-line therapy: Behavioral therapies and education should be offered first; starting antimuscarinic agents at the same time as behavior therapies may prove clinically beneficial
• Second-line therapy: Antimuscarinics; extended-release preparations should be used instead of immediate-release preparations when possible; transdermal oxybutynin can also be used
• Third-line therapy: Sacral neuromodulation or peripheral tibial nerve stimulation (PTNS) for carefully selected patients with severe refractory OAB symptoms or those who are not candidates for second-line therapy and are willing to undergo a surgical procedure; intradetrusor injection of onabotulinumtoxinA is another option

Chronic incontinence

Recommendations for improving symptoms of chronic incontinence and reducing cost of care include the following:

• Scheduled toileting
• Prompted voiding
• Improved access to toilets
• Management of fluids and diet
• Use of disposable absorbent pads or garments

See Treatment and Medication for more detail.

• References

Background

The International Continence Society (ICS) defines overactive bladder (OAB) as a syndrome consisting of urinary urgency, with or without urgency urinary incontinence, usually with urinary frequency and nocturia, in the absence of causative infection or pathologic conditions and suggestive of underlying detrusor overactivity (phasic increases in detrusor pressure).

Urgency, the hallmark of OAB, is defined as the sudden compelling desire to urinate, a sensation that is difficult to defer. Urgency urinary incontinence (UUI) is urinary leakage associated with urgency. UUI is one of the most common types of urinary incontinence. Some women may have both stress urinary incontinence and UUI, and this is called mixed urinary incontinence.

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.^[3]

The term OAB has been adopted by the US Food and Drug Administration (FDA) to expand the number and types of patients eligible for clinical trials. As noted, OAB may include not only urgency urinary incontinence but also urgency, frequency, dysuria, and nocturia. Other terms used include detrusor overactivity, detrusor instability, detrusor hyperreflexia, and involuntary bladder contractions.

A preliminary diagnosis of OAB can be made on the basis of the history and physical examination (see Presentation), in conjunction with a few simple office and laboratory tests (see Workup).

Treatment of OAB is aimed at reducing the debilitating symptoms in order to improve the overall quality of life in affected patients (see Treatment). Anticholinergic agents that target the muscarinic receptors in the bladder (antimuscarinic agents) are the pharmacologic treatment of choice because they reduce the contractility of the detrusor muscle. However, the use of antimuscarinic drugs is limited by certain adverse effects, particularly dry mouth and constipation.

Behavioral therapy focusing on dietary and lifestyle modification, voiding regimens, and pelvic floor muscle exercises is also helpful in the management of OAB and may be used by itself or in conjunction with antimuscarinic therapy.

Various attempts have been made to improve the bladder selectivity of these drugs, and thereby overcome the systemic adverse effects, as well as to come up with different formulations to lower peak levels of agents and avoid first-pass liver metabolism, which is often associated with an increased risk of adverse effects in some of these agents. These include the development of new antimuscarinic agents with structural modifications and the use of innovative drug-delivery methods.

The advancement in the drug-delivery systems extends to the long-term therapeutic efficacy, with improved tolerability and patient compliance; however, future prospective therapies are aimed at novel targets with novel mechanisms of action, including beta3-adrenoceptor agonists, K+ channel openers, and 5-HT modulators.^[4] These prospective therapies are currently at different stages of clinical development.

Among other investigational therapies, neurokinin receptor antagonists, alpha-adrenoceptor antagonists, nerve growth factor inhibitors, gene therapy, and stem cell–based therapies are of considerable interest. The future development of new modalities in OAB treatment appears promising.

OAB affects children as well as adults. For more information, see Overactive Bladder in Children and Urinary Incontinence.

• References

Anatomy

A normal bladder functions through a complex coordination of musculoskeletal, neurologic, and psychological functions that allow it to fill and empty. The prime effector of continence is the synergic relaxation of detrusor muscles and contraction of bladder neck and pelvic floor muscles.

Various efferent and afferent neural pathways and neurotransmitters are involved. Central neurotransmitters (eg, 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.

In bladder filling, sympathetic nerve fibers that originate from the T11 to L2 segments of the spinal cord, which innervate smooth-muscle fibers around the bladder neck and proximal urethra, cause these fibers to contract, allowing the bladder to fill. As the bladder fills, sensory stretch receptors in the bladder wall trigger a central nervous system (CNS) response. During bladder filling, the intravesical pressure remains low as a result of the viscoelastic properties of the bladder and antagonism of the parasympathetic nervous system (PNS).

The PNS causes contraction of the detrusor, while the muscles of the pelvic floor and external sphincter relax. The PNS fibers, as well as those responsible for somatic (voluntary) control of micturition (urination), originate from the S2 to S4 segments of the spinal cord in the sacral plexus. The somatic fibers innervate the external sphincter and are responsible for the voluntary control of continence in the face of a pressing desire to void.

The normal adult bladder accommodates 300-600 mL of urine; a CNS response is usually triggered when the volume reaches 400 mL However, urination can be prevented by cortical suppression of the PNS or by voluntary contraction of the external sphincter.

• References

Pathophysiology

OAB appears to be multifactorial in both etiology and pathophysiology. Symptoms of OAB are suggestive of underlying detrusor overactivity. Overactivity of the detrusor muscle—neurogenic, myogenic, or idiopathic in origin—may result in urinary urgency and urgency incontinence.^[5]

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. Activation of normally quiescent C sensory fibers may help produce 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.^{[6, 7]}

Once thought to be biologically inert, the urothelium may also have a role in OAB (see the image below). 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.^{[8, 9]}

View Image

Communication between urothelium and suburothelium. ACh—acetylcholine; ATP—adenosine triphosphate; M2—muscarinic receptor subtype 2; M3—muscarinic rec....

• References

Etiology

OAB is primarily a neuromuscular problem in which the detrusor muscle contracts inappropriately during bladder filling (ie, storage phase). These contractions often occur regardless of the amount of urine in the bladder. OAB may result from a number of different causes, both neurogenic and nonneurogenic.

Neurologic injuries that may cause OAB include the following:

• Spinal cord injury
• Stroke

Neurologic diseases that may cause OAB include the following:

• Multiple sclerosis
• Dementia
• Parkinson disease
• Medullary lesions
• Diabetic neuropathy

Detrusor overactivity can also occur in the absence of a neurogenic etiology. Contractions can be spontaneous or induced by rapid filling of the bladder, postural changes, or even walking or coughing. Because these causes are nonneurogenic, the pressing need to urinate can be contained for a few minutes after it is first sensed.

Idiopathic OAB is OAB in the absence of any underlying neurologic, metabolic, or other causes of OAB, or conditions that may mimic OAB, such as urinary tract infection, bladder cancer, bladder stones, bladder inflammation, or bladder outlet obstruction.

Certain medications may lead to symptoms of OAB. Diuretics can cause urge incontinence because of increased bladder filling, stimulating the detrusor. Bethanechol can also cause urge incontinence through its stimulation of bladder smooth-muscle contraction.

Heart failure or peripheral venous and vascular disease can also contribute to symptoms of OAB. During the day, such individuals have excess fluid collect in dependent positions (feet and ankles). When they recline to go to sleep, much of this fluid becomes mobilized and increases renal output, thereby increasing urine output. Many of these patients describe increased nocturia that manifests as OAB.

Only in rare cases does it prove impossible to identify a specific cause (idiopathic OAB).

Risk factors

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 risk factors include the following^[10] :

• Age >75 years
• Arthritis
• Use of oral hormone replacement therapy
• High body mass index (BMI)

The physiologic changes associated with aging, such as decreased bladder capacity and changes in muscle tone, favor the development of OAB when precipitating factors intervene.^{[11, 12, 13, 14, 15]} In postmenopausal women, many of these changes are related to estrogen deficiency. Estrogen deprivation therapy in younger women with breast cancer has also been associated with increased risk for OAB.^[16] Perhaps the most important age-related change in bladder function that leads to incontinence is the increased number of involuntary bladder contractions (detrusor instability).

Any disruption in the integration of musculoskeletal and neurologic responses can lead to loss of control of normal bladder function and to urge incontinence.

• References

Epidemiology

United States statistics

In the National Overactive Bladder Evaluation (NOBLE) study, which evaluated 5204 adults 18 years of age and older who were representative of the US population by sex, age, and geographical region, 16.5% of the study participants 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). Data in the study were gathered with the use of a computer-assisted telephone interview questionnaire.^[17]

International statistics

OAB affects millions of people worldwide, regardless of race. The frequency data on OAB found in Europe are similar to that found in the United States.

Age-related differences in incidence

The prevalence of OAB increases with age. However, OAB should not be considered a normal part of aging. Twenty percent of the population aged 70 years or older report symptoms of OAB; 30% of those aged 75 years or older report symptoms. Men tend to develop OAB slightly later in life than women do.

Sexual differences in incidence

In the NOBLE study, the prevalence of OAB was similar in women and men (16.9% and 16%, respectively).^[17] 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 urinary incontinence increased with increasing body mass index (BMI), whereas in men, no difference was found.

Milsom et al, in 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, found the overall prevalence of OAB symptoms to be 16.6%.^[18] The main outcome measures included the prevalence of urinary frequency (>8 micturitions per day), urinary urgency, and urgency incontinence.

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 between both sexes, but urgency incontinence was more prevalent in women than in men.

OAB in men is often related to obstruction; therefore, it may be important to differentiate between obstruction and irritative symptoms before the initiation of treatment.

• References

Prognosis

Behavioral therapy combined with pharmacologic therapy offers good results in OAB patients, with up to 80% of cases improved and excellent long-term results.

OAB can have devastating effects on quality of life (QoL),^{[19, 20]} but its impact is not limited to this (as is often mistakenly assumed). 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 infection (UTI), skin infection and irritation, and, in elderly persons, an increased risk of falls and fractures (see Presentation). The economic impact of OAB is also considerable.^[21]

Impact on quality of life

OAB significantly impairs QoL, increases depression scores, and reduces quality of sleep. OAB that involves urgency incontinence is associated with the most severe impairment. Persons with OAB who have poor sleep quality report chronic fatigue and difficulty performing daily activities. An increased number of hip fractures due to falls in elderly persons have been attributed to OAB because of the nocturia component. Many such falls involve the individual tripping or losing balance while getting out of bed.

Individuals with OAB develop coping strategies to manage or hide their problems (eg, modifying fluid intake, toilet mapping, reduced physical or social activity). These coping strategies, along with the OAB symptoms themselves, commonly affect interactions with friends, colleagues, and families and thereby have an adverse impact on QoL.

Notable psychological effects of OAB and urinary incontinence include fear, shame, and guilt. In elderly people with OAB and incontinence, the need for assistance with toileting, shopping for protective undergarments, and laundry may place an additional burden on family members.

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.^[17]

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 the image below). A shortened form of the SF-36, the Short Form-20 (SF-20), is another reliable and valid instrument for measuring health-related QoL.^[22]

View Image

Overactive bladder (OAB) and quality of life (QoL). Short Form-36 (SF-36). Reprinted with permission from Blackwell.

Validated instruments that 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.

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. 

Jayadevappa et al documented an increased risk of falls and fractures in elderly patients with OAB. In a review of Medicare data from 2006 to 2010 that included 33,631 enrollees with OAB (mean age, 77.8 years), the proportion of patients who had falls was higher in those with OAB than in those without OAB (11% vs 7%, respectively; P < 0.001). Treatment for OAB was associated with lower likelihood of falls (odds ratio [OR ] 0.88; 95% confidence interval [CI] 0.80–0.98).^[104]

In total, an estimated $12.6 billion per year is spent in OAB-related costs in the United States (see the image below). Some of these costs (eg, those related to physician visits, protective devices, management of UTIs, and skin infection and irritation) are obvious. Others are not. For example, decreased productivity and lost wages due to OAB is estimated to cost $841 million per year.

View Image

Total community and institutional costs of overactive bladder (OAB) (in millions of dollars). UTI—urinary tract infection (UTI). Reprinted with permis....

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.^[23]

Management of OAB can decrease the economic impact of OAB. Two studies have demonstrated cost savings related to medical management of OAB. In both of these studies, savings were achieved by reducing the comorbidities of UTI and skin infection and irritation.^{[24, 23]}

• References

History

The clinician should ask 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 - Relevant medications 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 and neurologic findings
• Social history, including smoking, alcohol consumption, fluid intake

Key screening questions should be asked, focusing on urgency, nocturia (>3 times per night), urinary frequency (>8 times per day), and urinary incontinence. Sample questions can include the following:

• Do you ever leak urine when you have a strong urge on the way to the bathroom? How often?
• How frequently do you empty your bladder during the day?
• How many times do you get up to urinate after going to sleep? Is it the urge to urinate that wakes you?
• How many pads a day do you wear for protection?
• Does this problem inhibit any activity or prevent you from doing things you like to do?

Patient who answer affirmatively to the screening questions should be given a bladder diary to complete for review at a subsequent visit. The bladder diary 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.

• References

Physical

A comprehensive physical examination can help to determine the nature, severity, and impact of the symptoms in patients with overactive bladder (OAB).

Pulmonary and cardiovascular evaluation may be indicated to assess control of cough or the need for medications such as diuretics.

An abdominal examination is performed to rule out diastasis recti, masses, ascites, and organomegaly, which can influence intra-abdominal pressure and urinary tract function. A palpable bladder may imply overflow incontinence or an obstructive problem.

A pelvic examination is used to evaluate for inflammation, infection, atrophy, and pelvic organ prolapse. Such conditions can increase afferent sensation, leading to urinary urgency, frequency, dysuria, and OAB. Because the urethra and trigone are estrogen-dependent tissues, estrogen deficiency can contribute to urinary incontinence and urinary dysfunction. The most common signs of inadequate estrogen levels include the following:

• Thinning and paleness of the vaginal epithelium
• Loss of rugae
• Disappearance of the labia minora
• Presence of a urethral caruncle

In females, the levator ani muscle function can be evaluated by asking the patient to tighten her vaginal muscles and to hold the contraction as long as possible. Normally, a woman can hold such a contraction for 5-10 seconds. Voluntary levator ani muscle contractions that are very weak or absent are an indication that biofeedback training sessions with a pelvic floor physical therapist may be necessary (see Treatment).

The bimanual examination should also include a rectal examination to check anal sphincter tone and, for fecal impaction, the presence of occult blood or rectal lesions. In males, the rectal examination should also be focused on the prostate to rule out benign prostatic hyperplasia (BPH) or prostate cancer.

A neurologic examination is important. This involves assessment of the lumbosacral nerve roots and should include evaluation of the deep-tendon reflexes, lower-extremity strength, sharp/dull sensation, and the bulbocavernosus and clitoral sacral reflexes. Abnormal findings (eg, deep tendon hyperreflexia or an absent bulbocavernosus reflex) should alert the physician to possible underlying neurologic lesions contributing to urinary incontinence.

• References

Comorbidities

Individuals with OAB and urinary incontinence may have other medical comorbidities. For instance, urinary tract infections (UTIs), skin infections and irritation, falls, and fractures are more likely in persons with OAB and urinary incontinence. In older women with daily urge incontinence, the risk of falls is increased by 26% and the risk of fractures, by 34%.^[24] 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, it is unclear whether the depression is due to OAB or whether the two conditions share similar underlying neurologic etiologies.

Fortunately, treatment of OAB decreases the incidence of UTI and skin irritation and infection.

• References

Approach Considerations

A few simple office and laboratory tests, in conjunction with the history and physical examination, usually suffice for a diagnosis of overactive bladder (OAB). A urinalysis and culture (if urinary tract infection [UTI] is suspected) is indicated in patients being evaluated for OAB. In select individuals, further testing such as an assessment of postvoid residual may be indicated.

Guidelines for diagnosis of OAB by the American Urological Association (AUA) and the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU) include the following^[2] :

• A thorough history, physical examination, and urinalysis should be done initially.
• If necessary, a urine culture, or postvoid residual assessment, or both, can be done, along with use of bladder diaries or symptom questionnaires.
• Urodynamic study, cystoscopy, and diagnostic renal and bladder ultrasonography are not necessary in the initial workup of uncomplicated cases and should be reserved for refractory or otherwise complicated cases. For more information, see Cystoscopy and Urethroscopy in the Assessment of Urinary Incontinence.
• Urine cytology is not recommended in the absence of hematuria when the patient responds to therapy.

• References

Urine Studies

Urinalysis is used to exclude microhematuria, pyuria, urinary tract infection, and glucosuria. In those individuals with microhematuria, further evaluation including a urine cytology is recommended. In individuals at risk for bladder cancer, a cytology study  even in the absence of microhematuria may be indicated.

• References

Postvoid Residual Testing

Postvoid residual testing is not indicated in all patients. It is helpful in men with both obstructive and OAB symptoms and in women who have undergone prior pelvic surgery (eg, prior incontinence surgery) and those with significant pelvic organ prolapse.

Postvoid residual volume is assessed by means of urethral catheterization or ultrasonography. No definitive upper level of normal for postvoid residual has been established, but many would argue that postvoid residuals greater than 150-200 mL are indicative of incomplete bladder emptying and may warrant further evaluation.

• References

Cystometry

Cystometry is a simple method for testing the bladder’s storage function and provides information on bladder capacity, the extent of accommodation or compliance, the ability to sense bladder filling, and temperature. It can also help assess for detrusor overactivity during bladder filling.

• References

Urodynamic Study

Urodynamic study is not indicated as part of the first-line evaluation of patients with OAB unless a neurologic etiology is suspected. It is most commonly performed in individuals in whom first-line therapies for OAB fail and/or in whom a neurogenic etiology is suspected.

A urodynamic study consists of cystometrography (CMG) and uroflow/electromyelography. CMG assesses the storage phase of bladder function, which includes the following:

• Bladder capacity
• Bladder compliance
• Detrusor overactivity
• Sensation of filling

Uroflow/electromyelography assesses the voiding phase, which includes the following:

• Detrusor pressure during voiding
• Relaxation of the pelvic floor muscles during voiding
• The nature of the flow pattern (ie, bell-shaped curve, staccato)
• Presence or absence of Valsalva voiding

Intravesical pressure is a combination of intra-abdominal pressure and detrusor pressure. To determine the detrusor pressure, the intra-abdominal pressure is measured with a rectal catheter; this pressure is subtracted from the total intravesical pressure (measured with the bladder catheter). In males, a nomogram is available, the pressure/flow study, whereby detrusor pressure is plotted against flow rate, and this is used to assess for bladder outlet obstruction.

• References

Approach Considerations

If a specific cause of overactive bladder (OAB) symptoms is identified, it should be treated appropriately; for example, urinary tract infection (UTI) should be treated with antibiotics, while atrophic urethritis can be treated with topical application of estrogen vaginal cream. For idiopathic OAB, the three main treatment approaches are behavioral therapy, pharmacotherapy, and surgery.^{[26, 27, 28, 29, 30]}  The choice of a particular treatment depends on the severity of the symptoms and the extent that the symptoms interfere with the patient’s lifestyle.^[31]

Guidelines for the treatment of OAB by the American Urological Association (AUA) and the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU) include the following recommendations^[2] :

• First-line therapy: Behavioral therapies and education should be offered first; behavioral therapies may be combined with pharmacologic management.
• Second-line therapy: Antimuscarinics (extended-release preparations should be used instead of immediate-release preparations when possible) or beta-3 adrenoceptor agonists should be offered; transdermal oxybutynin may be offered. If an antimuscarinic provides inadequate symptom relief or produces unacceptable adverse effects, thendose modification, a different antimuscarinic medication, or a beta3-adrenoceptor agonist may be tried.
• Third-line therapy: Intradetrusor injection of onabotulinumtoxinA is an option for carefully selected and thoroughly counseled patients with severe refractory OAB symptoms or those who are not candidates for second-line therapy. Other third-line options are peripheral tibial nerve stimulation (PTNS), which may be offered to carefully selected patients, and sacral neuromodulation (SNS), which is an option for carefully selected patients who are not candidates for second-line therapy or who have severe refractory OAB symptoms despite such therapy, and who are willing to undergo a surgical procedure; .

A combined treatment approach using behavioral and pharmaceutical interventions is effective in most patients with OAB. Several drugs that have been proven safe and efficacious in clinical trials have been approved for the treatment of OAB. Behavioral interventions, such as the following, should be part of every treatment plan:

• Limiting bladder irritants (eg, caffeine, alcohol)
• Bladder training
• Urgency suppression techniques, including pelvic floor muscle exercises (consultation with a pelvic floor physical therapist may be helpful)

Surgery is rarely used to treat OAB and is reserved for patients in whom pharmacologic and behavioral therapy fail. Various surgical options are available, including sacral nerve neuromodulation and, rarely, bladder augmentation. Percutaneous tibial nerve stimulation is a minimally invasive option for patients in whom pharmacologic therapy fails or is contraindicated.

• References

Pharmacologic Therapy

Anticholinergics

Anticholinergic agents are currently the first-line pharmacologic therapy for OAB.^{[32, 33, 34, 35]} These agents are thought to act primarily by inhibiting involuntary detrusor muscle contractions (at the level of the efferent pathway), but identification of muscarinic receptors in the urothelium/suburothelium suggests that they may also affect the afferent sensory pathway. The goals of therapy with anticholinergic agents are to prevent inappropriate detrusor contractions and to maintain normal bladder function, while minimizing adverse effects.

A meta-analysis of 50 randomized controlled trials involving more than 27,000 women with OAB found only modest improvement in symptoms with anticholinergic treatment. Daily treatment reduced urge incontinence by 1.73 episodes per day and voids by 2.06 per day, while placebo reduced urge incontinence episodes by 1.06 and voids by 1.2 per day. No individual agent was shown to be superior to the others.^[36]  

The duration of treatment is controversial, although many physicians would argue that OAB is a chronic condition with symptom severity that may vary over time. In a prospective randomized, open-label, multicenter trial of symptom change and retreatment rate after discontinuation of the antimuscarinic tolterodine (extended-release, 4 mg) in known responders, 65% of patients requested retreatment and 62% experienced symptom relapse.^[37]

Symptom duration and baseline health-related quality of life (HRQol) were risk factors for retreatment according to univariate analysis. However, HRQol was the only independent risk factor. This article serves to highlight both the importance of patient education when managing those with OAB and the significant potential need for long-term anticholinergic therapy.^[37]

Oxybutynin and tolterodine are the more commonly used anticholinergics in OAB treatment. Oxybutynin (Ditropan) was among the first anticholinergic agents to be used to treat detrusor overactivity; its efficacy in treating OAB is well documented.^[38] However, the effects of oxybutynin are not tissue-specific, and studies have shown that oxybutynin has a greater inhibitory effect on salivation than on bladder contraction, resulting in a high incidence of dry mouth.

Tolterodine (Detrol, Detrol LA) is the first major drug to address the problems of treatment tolerability.^[39] Unlike oxybutynin, tolterodine has a greater inhibitory effect on bladder contraction than on salivation. Therefore, it has fewer side effects (eg, dryness of mouth), but with comparable efficacy.^{[40, 41]}

A long-acting, extended-release formulation of oxybutynin (Ditropan XL), which is associated with fewer adverse effects than its immediate-release predecessor, and efficacy that is comparable to the agents above, is also currently available.^{[42, 43, 44]}

A study of 148 men aged 42-88 years with persistent OAB symptoms while receiving alpha-blocker therapy for bladder outlet obstruction found that behavioral and antimuscarinic therapy are effective in reducing these symptoms when added to alpha-blocker treatment. The study concluded that behavioral therapy is at least as effective as antimuscarinic therapy.^[45]

Other anticholinergic agents used to treat OAB include the following:

• Trospium chloride (Sanctura)^{[46, 47]}
• Propiverine hydrochloride (approved in Europe, not in the United States)
• Solifenacin (Vesicare)^{[48, 49, 50, 51]}
• Darifenacin (Enablex),^[52]
• Oxybutynin patch (Oxytrol)
• Fesoterodine (Toviaz)

The first over-the-counter (OTC) treatment for OAB in women aged 18 or older, Oxytrol for Women, was approved by the US Food and Drug Administration (FDA) in January 2013. The drug is available only by prescription for men.^[53]

No head-to-head trials of these agents have assessed efficacy and side effects. The available literature suggests that these agents are clinically similar and that none appears to offer a major distinct advantage over the others. However, slight differences in these agents may be clinically useful in drug selection.

In two placebo-controlled studies that compared tolterodine (Detrol LA) 4 mg and fesoterodine 8 mg, a statistically significant greater reduction in urge urinary incontinence episodes was found with fesoterodine 8 mg.^[54]

In a 16-week randomized, double-blind, placebo-controlled study, increasing the solifenacin dose from 5 to 10 mg in OAB patients with more severe symptoms improved outcomes.^[55] Patients who had their dose increased experienced greater reductions in the mean number of severe urgency episodes from week 8 through the end of the study and significant reductions in mean total urgency score, mean maximum Patient Perception of Intensity of Urgency Scale urgency rating, and mean micturition frequency.

Darifenacin has the most selective M₃ activity and has shown the greatest degree of safety with respect to lack of impact on cognitive function, which suggests that it may offer a slight advantage in elderly patients. It is available in 2 formulations.

Trospium is a large-molecule quaternary amine with minimal central nervous system (CNS) penetration. It has a unique liver metabolic pathway, making it the most suitable for patients receiving multiple drugs with cytochrome P-450 (CYP-450) utilization.

The patch version of oxybutynin has minimal dry mouth or constipation adverse effects but is available in only a single, relatively small dosage and may irritate the skin. A gel formulation of oxybutynin is available that delivers 5 mg of oxybutynin and is not associated with the skin irritation of the patch.

Fesoterodine is the newest anticholinergic available for OAB. It shares the same active metabolite as tolterodine, 5-HMT; however, fesoterodine is efficiently and extensively metabolized to 5-HMT via ubiquitous esterases and thus does not have the pharmacokinetic variability associated with tolterodine. Furthermore, head-to-head studies have demonstrated superiority of the 8-mg dose of fesoterodine compared with tolterodine (Detrol LA) 4 mg in the reduction of UUI episodes.

Although efficacious, anticholinergic agents cause frequent adverse effects such as dry mouth, constipation, blurred vision, and drowsiness. These effects are dose-related and can severely limit tolerability, especially in elderly patients. Anticholinergics may also produce confusion, especially in elderly patients with pre-existing dementia.

A meta-analysis of antimuscarinic therapy for OAB in adults aged 65 years and older found higher rates of treatment discontinuation due to adverse events and dry mouth, compared with placebo. Adverse events that occurred at rates significantly higher than with placebo were dizziness, dyspepsia, and urinary retention with fesoterodine; headache with darifenacin; and urinary tract infections with solifenacin.^[56]  

Anticholinergics are contraindicated in patients with urinary retention, gastric retention, and untreated narrow-angle glaucoma. They should be used with caution in patients with clinically significant bladder outlet obstruction, decreased gastrointestinal motility, treated narrow angle glaucoma, and myasthenia gravis. Cases of angioedema of the face, lips, tongue and/or pharynx have been reported with several of these agents, and patients should be counseled to seek care immediately if they experience swelling.

Various attempts have been made to improve the organ selectivity of these drugs to overcome their adverse effects. These include the development of new antimuscarinic agents with structural modifications^{[57, 58]} and the use of innovative drug-delivery methods. The benefits of improved drug-delivery systems extends to the long-term therapeutic efficacy, with improved tolerability and patient compliance.

Prospective therapies aimed at novel targets with novel mechanisms of action are currently at different stages of clinical development. These include beta3-adrenoceptor agonists, K⁺ channel openers, and 5-HT modulators.^{[4, 59]}

Beta3-receptor agonists

In June 2012, the FDA approved the first beta3-receptor agonist, mirabegron (Myrbetriq), for symptoms of urge urinary incontinence, urgency, and urinary frequency associated with OAB.^[60]

Beta3-receptor agonists act directly to inhibit afferent nerve firing independent of the relaxing effects on the bladder smooth muscle. In one trial, mirabegron was shown to be safe and efficacious over a 1-year period.^[61]  In another multicenter, randomized, double-blind, parallel-group placebo- and tolterodine-controlled phase 3 trial, mirabegron significantly improved the number of incontinence episodes and the number of micturitions per 24 hours compared with placebo and was well tolerated.^[62]  Benefits of mirabegron have been demonstrated in men, the elderly, and  Asian patients.^[63]

Combination therapy

Clinical studies that demonstrated benfit from combination therapy with an anticholinergic agent plus a beta3-adrenoceptor agonist. Based on data from these clinical trials, the FDA has approved mirabegron in combination with solifenacin for the treatment of OAB with symptoms of urinary incontinence, urgency, and urinary frequency.^{[64, 65]}

A dose-ranging study by Abrams et al that explored six doses of combination therapy with solifenacin plus mirabegron, five doses of monotherapy with either agent, or placebo, concluded that mirabegron 25/50 mg plus solifenacin 5/10 mg improves objective and subjective efficacy outcomes compared with placebo or solifenacin 5 mg. Micturition frequency normalization was approximately twofold greater with solifenacin 10 mg plus mirabegron 25 mg and solifenacin 5 mg plus mirabegron 50 mg versus solifenacin 5 mg.^[64]

In a 12-week study by Drake et al of patients who remained incontinent despite treatment with solifenacin at a dose of 5 mg, the addition of mirabegron (50 mg) significantly improved incontinence and frequent urination, and was superior to monotherapy with solifenacin at a dose of 10 mg. Combination therapy was well tolerated.^[65]

In a prospective study in 26 elderly Japanese men with OAB who had been taking tamsulosin, the addition of mirabegron significantly improved OAB symptoms and significantly increased voided volume without impairing bladder contractility during voiding.^[66]  In a multinational phase II 12-week trial, the combination of mirabegron (25/50 mg) with solifenacin (5/10 mg) resulted in improved objective and subjective efficacy outcomes compared with placebo or solifenacin (5 mg) alone.^[67]

Botulinum toxins

Detrusor injections of onabotulinumtoxinA are approved by the FDA for the treatment of adults with OAB who cannot use, or do not adequately respond to, anticholinergic medication. Most of the effects of botulinum toxin are thought to be the result of inhibition of the release of acetylcholine from the presynaptic nerve terminal, which prevents stimulation of the detrusor muscle. Review of the clinical data shows a profound effect of botulinum toxin on involuntary detrusor contractions and elevated detrusor pressures. Botulinum neurotoxin type A may also affect other neurotransmitters, such as sensory/afferent neurotransmitters.^[68]

Approval was based on safety and efficacy data from two double-blind, randomized, multi-center, placebo-controlled 24-week clinical studies. By week 12 in both clinical trials, patients treated with onabotulinumtoxinA had a reduction of at least 50% in frequency of daily urinary incontinence episodes from baseline compared to placebo. Duration for efficacy with onabotulinumtoxinA at reducing urinary leakage and other symptoms of OAB was 135-168 days compared to 88-92 days with placebo.^[69]

OnabotulinumtoxinA is also FDA approved for treatment of urinary incontinence due to detrusor overactivity associated with a neurologic condition (eg, spinal cord injury, multiple sclerosis) in adults who have an inadequate response to or are intolerant of an anticholinergic medication.

The benefits of repeated detrusor injections of botulinum neurotoxin type A were demonstrated in a prospective study by Khan et al in 137 patients with multiple sclerosis–neurogenic OAB. Before treatment, 83% of the patients were incontinent; 4 weeks after the first treatment, 76% were completely dry. The efficacy was sustained with repeat injections. The median interval between retreatments remained constant at 12-13 months. Furthermore, considerable improvement was noted in the mean urogenital distress inventory and incontinence impact questionnaire 7 scores initially and after subsequent treatments.^[68]

A network meta-analysis concluded that after 12 weeks, onabotulinumtoxinA 100 U provides greater relief of OAB symptoms than mirabegron or anticholinergics in adults with idiopathic OAB.^[70] However, a long-term follow-up study of 128 women who received intravesical onabotulinumtoxinA for idiopathic OAB found that 70% had discontinued treatment—27% because of insufficient effect and 43% of intolerance. Most patients discontinued treatment after the first (79%) and second (19%) injections. Only 2% of patients had discontinued treatment after more than two injections.^[71]

Tricyclic antidepressants

Tricyclic antidepressants such as imipramine and doxepin have also been used to treat OAB. These block the reuptake of noradrenaline and serotonin. However, whether this mechanism mediates the beneficial effects on bladder hyperactivity is unclear. These agents have been associated with cardiac dysrhythmias and mental status changes and thus should be used with caution in elderly patients. Tricyclic antidepressants are not recognized as first-line therapy for the treatment of OAB.

• References

Behavioral Therapy

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 the following^[72] :

• Education
• Dietary and lifestyle modification (see Dietary Measures)
• Bladder training
• Pelvic floor muscle therapy (PFMT)
• Self-monitoring with bladder or voiding diaries

Bladder training

Bladder training involves a program of patient education and a scheduled voiding regimen. 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 progressively prolong voiding intervals, and to improve the patient’s confidence in bladder control. Occasionally, it is used in conjunction with electrical stimulation and biofeedback therapy (see below).

How bladder training works is not fully identified; but proposed mechanisms include the following:

• 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
• Increased reserve capacity of the lower urinary tract

A program of bladder retraining involves becoming aware of patterns of incontinence episodes and relearning skills necessary for storage and proper emptying of the bladder. Bladder retraining alone is successful in 75% of patients treated for urge incontinence.

Bladder retraining involves developing a schedule of when the patient should try to urinate; the patient should then try to consciously delay urination between these times. One method is to urinate at definite intervals (eg, 30 min); then, as the patient becomes skilled at waiting, the time intervals are gradually increased by one half hour until the individual is urinating every 3-4 hours.

Because the desired level of bladder control may take months to achieve, the patient needs to be highly motivated. Furthermore, bladder training may be effective in the short term, but, because of the extensive effort required, its efficacy may decline over the long term.

Pelvic floor muscle therapy (PFMT)

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 reflexively or voluntarily inhibit contraction of the detrusor muscle. PFMT is defined as any program of repeated voluntary pelvic floor muscle contractions taught by a healthcare professional.^[73]

Regular daily exercising of pelvic muscles can improve, and even prevent, urinary incontinence. This is particularly helpful in younger women. PFM exercises should be performed 30-80 times daily for at least 8 weeks. The principle behind PFM exercises is to strengthen the muscles of the pelvic floor, thereby improving function of the urethral sphincter. The success of PFM exercises depends on proper technique and adherence to a regular exercise program. These exercises have limited value in elderly patients and in patients with poor mobility.

Another approach is to use vaginal cones to strengthen the muscles of the pelvic floor. A vaginal cone is a weighted device that is inserted into the vagina. The woman contracts the pelvic floor muscles in an effort to hold the device in place. The contraction should be held for up to 15 minutes and should be performed twice daily. Within 4-6 weeks, symptoms improve in about 70% of women who try this method.

Biofeedback-assisted therapy

Biofeedback is a method of positive reinforcement in which electrodes are placed on patient’s abdomen and the anal area. 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. Used in conjunction with PFM exercises, biofeedback helps patients gain awareness and control of the pelvic muscles.

Early biofeedback for OAB consisted of bladder-pressure biofeedback.^{[74, 75]} Feedback of pelvic floor muscular activity was subsequently added.^[76] 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.

Some therapists place a sensor in the vagina (in women) or in the anus (in men) to assess contraction of the pelvic floor muscles. A monitor displays a graph that shows which muscles are contracting and which are at rest. The therapist can help the patient identify the correct muscles for performing Kegel exercises. About 75% of people who use biofeedback to enhance performance of Kegel exercises report symptom improvement, with 15% considered cured.

Electrical stimulation

Pelvic floor electrical stimulation involves the use of mild electrical pulses to elicit contractions in a specific group of muscles. The current may be delivered using an anal or vaginal probe. Pelvic floor electrical stimulation should be performed in conjunction with PFM exercises. The electrical stimulation therapy may be performed at the clinic or at home. Treatment sessions usually last 20 minutes and may be performed every 1-4 days. Some clinical studies have shown promising results in treating urge incontinence with electrical stimulation.^{[77, 78]}

Urgent PC (Cogentix Medical, Minnetonka, MN) is an office-based method of neuromodulation that uses percutaneous tibial nerve stimulation (PTNS) via needle electrodes to deliver retrograde access to the sacral nerve. Typically, twelve 30-minute sessions are performed, followed by a maintenance regimen. Urgent PC is approved by the FDA for treatment of OAB symptoms such as urinary urgency, urinary frequency, and urge incontinence. The long-term efficacy of PTNS has been demonstrated in a 3-year trial.^[105]

Recommendations

In 1989, the Consensus Conference on urinary incontinence in adults recommended that the least invasive or dangerous procedure should be tried first.^[79] 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.^[80] More recently, the Third International Consultation on Incontinence in June 2004 recommended behavioral therapy as a first-line therapy for incontinence.^[73]

Success rates

In a study in an outpatient geriatric medicine clinic, behavioral therapy yielded a mean 80.7% reduction in incontinence episodes.^[81] Behavioral therapy was significantly more effective than oxybutynin given at a dosage of 2.5 mg/day to 5 mg three times per day (mean reduction in incontinence episodes. 68.3%). Both therapies were better than placebo (mean reduction, 39.4%). In addition, patient-perceived improvement was also greatest in those treated with behavioral therapy.^[81]

In a randomized clinical trial of bladder training, Fantl et al observed that episodes of incontinence decreased by a mean of 57% in women aged 55 years and older who underwent bladder training. Patients in a no-treatment control group showed little improvement.^[82]

Burgio et al demonstrated an added benefit of combining drug and behavioral therapy in a stepped program. Individuals who were not completely continent or were unsatisfied with behavioral therapy or oxybutynin alone were offered combination therapy.^[83] With the change to a combined strategy, substantial improvements were noted.

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.^[84]

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.^[85] 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.^[86]

Biofeedback-assisted behavioral training has been effective in treating urge urinary incontinence, with 76-86% mean reductions in episodes.^{[76, 87, 88]} However, biofeedback is not necessary for everyone.

Burgio et al 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.^[86] All groups achieved similar reductions in episodes of urge incontinence. However, the groups differed significantly regarding patient satisfaction: complete satisfaction with treatment was reported by 75% of the biofeedback group, 85.5% of the verbal feedback group, and 55.7% of the self-help booklet group.

Limitations

Behavioral therapy relies on the active participation of an involved and motivated patient. In addition, it requires a practitioner who is well trained in such therapy. Behavioral therapy does not produce any permanent changes in bladder function (eg, decreased detrusor overactivity as measured on urodynamic studies). Therefore, regular adherence and long-term compliance are needed.

• References

Surgical Therapy

Guidelines for the management of OAB by the American Urological Association (AUA) and the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU) suggest that surgical treatment may be offered as a third-line option for carefully selected patients. Procedures include neuromodulation and, rarely, augmentation cystopasty or urinary diversion.^[2]

Neuromodulation (sacral nerve stimulation; InterStim, Medtronic, Minneapolis, Minn) is a new technique that is FDA approved for the management of OAB and urge urinary incontinence. It requires the surgical implantation of a small device at the S3 level. Typically, an external stimulator is placed initially, and if the patient experiences a 50% or greater reduction in symptoms, a permanent internalized stimulator is placed.

A prospective study in 272 patients undergoing neuromodulation reported an adverse event rate of 30%. Most were minor, but 13% of patients required surgical intervention, typically revision or replacement.^[89] For more information, go to Sacral Nerve Stimulation.

Augmentation cystoplasty is rarely necessary in idiopathic OAB. However, it may be used in individuals with refractory neurogenic OAB, particularly in those with poor compliance. In this reconstructive procedure, a segment of the bowel is removed and used to replace a portion of the bladder. For more information, go to Augmentation Cystoplasty.

• References

Investigational Therapies

Six weeks of electro-acupuncture treatment significantly improved OAB symptom scores and King's Health Questionnaire scores in a study of 45 women with OAB. First sensation of bladder filling, first urge to void, and maximum cystometric capacity also significantly improved.^[95]

Prospects for new modalities in OAB treatment appear promising.^{[90, 91, 92, 93, 59]}  Investigational therapies of considerable interest include the following^[106] :

• Neurokinin receptor antagonists
• Alpha-adrenoceptor antagonists
• Nerve growth factor inhibitors
• Gene therapy^[94]
• Stem cell–based therapies
• Novel antimucarinic agents including imidafenacin and tarafenacin
• Combination therapies with beta3-adrenoceptor agonists or muscarinic agonists (eg, tolterodine/pilocarpine)
• A unique vaginal delivery formulation for oxybutynin
• Novel beta3-adrenoceptor agonists (eg, solabegron, ritobegron, aryloxpropanolamine, TRK-380, CL 316.243)

• References

Dietary Measures

Elimination of dietary caffeine (in those with urge incontinence) and consumption of adequate dietary fiber is advisable. Some have suggested that the avoidance of certain foods and beverages may improve the symptoms of OAB in some cases.^[96] These include the following:

• Alcohol
• Spicy foods
• Nuts
• Chocolate
• High-potassium foods
• Carbonated and caffeinated beverages

Consider providing the patient with such a list and advise the patient to try systematically eliminating one item at a time, to see whether that results in any improvement in symptoms.

Adequate fluid intake is important because many persons with OAB restrict fluids in hopes of voiding less. However, concentrated urine may act as a bladder irritant.

• References

Management of Chronic Incontinence

Although management approaches such as medical therapy, pelvic muscle exercises, and bladder training improve continence in most patients, some never achieve complete dryness. Treatment failures are sometimes due to concurrent use of necessary medications such as diuretics, which can cause incontinence, or to restricted mobility. Other patients may have dementia or other physical impairments that keep them from being able to perform pelvic muscle exercises or to retrain their bladders.

The following recommendations can help keep persons with chronic incontinence improve symptoms and reduce their cost of care:

• Scheduled toileting - Take the patient to the toilet every 2-4 hours or according to his or her toilet habits.
• Prompted voiding - Check for dryness and encourage use of the toilet.
• Improved access to toilets - Use assistive devices such as canes, walkers, and wheelchairs, and clear a well-lit path to the toilet. Raising the seating level of the toilet can facilitate toileting. Bedside commodes and urinals may be appropriate.
• Managing fluids and diet - Eliminate dietary caffeine (for those with urge incontinence) and encourage adequate fiber in the diet. Modify fluid intake. Reduce volume overload (for nocturia).
• Disposable absorbent pads or garments - Use these to keep patients dry.

• References

Medication Summary

The goals of pharmacotherapy are to improve overactive bladder (OAB) symptoms, reduce morbidity, and prevent complications. Anticholinergics are the first-line agents used to treat OAB. Other treatments approved for use in OAB include the beta3-receptor agonist mirabegron (Myrbetriq) and detrusor injections of onabotulinumtoxinA. Individuals with genital atrophy may benefit from topical estrogen therapy. In select cases of refractory OAB, tricyclic antidepressants may be helpful.

• References

Tolterodine (Detrol, Detrol LA)

• Dosing, Interactions, etc.

Clinical Context:  Tolterodine is a nonspecific competitive muscarinic receptor antagonist for OAB. However, it differs from other anticholinergic types in that it has selectivity for urinary bladder over salivary glands. Tolterodine exhibits a high specificity for muscarinic receptors. It has minimal activity or affinity for other neurotransmitter receptors and other potential targets, such as calcium channels.

• References

Oxybutynin (Gelnique)

• Dosing, Interactions, etc.

Clinical Context:  Oxybutynin inhibits the action of acetylcholine on smooth muscle and has a direct antispasmodic effect on smooth muscles. This, in turn, increases bladder capacity and decreases uninhibited contractions. Oxybutynin is relatively M3, M1 specific. Indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.

• References

Trospium

• Dosing, Interactions, etc.

Clinical Context:  Trospium is a nonspecific quaternary ammonium compound that is excreted intact in the urine and thus is not dependent on the cytochrome P450 system for its metabolism. Being a quaternary amine, it is less likely to penetrate the blood-brain barrier. It antagonizes acetylcholine's effect on muscarinic receptors. Its parasympathetic effect reduces smooth-muscle tone in the bladder. Trospium is indicated to treat symptoms of OAB (eg, urinary incontinence, urgency, frequency). It is available as a single dose, and the extended release formulation should not be taken at night.

• References

Darifenacin (Enablex)

• Dosing, Interactions, etc.

Clinical Context:  Darifenacin is an extended-release product that elicits competitive muscarinic receptor antagonistic activity. It reduces bladder smooth-muscle contractions. It has high affinity for the M3 receptors and less affinity for other muscarinic receptors. Darifenacin is indicated for OAB with symptoms of urge incontinence, urgency and frequency. Swallow it whole; do not chew, divide, or crush it.

• References

Solifenacin (VESIcare)

• Dosing, Interactions, etc.

Clinical Context:  Solifenacin is a competitive muscarinic-receptor antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency Also, indicated in combination with mirabegron for the treatment of OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency.

• References

Fesoterodine (Toviaz)

• Dosing, Interactions, etc.

Clinical Context:  Fesoterodine is a competitive muscarinic receptor antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. After oral administration, fesoterodine is rapidly and extensively hydrolyzed by nonspecific esterases to its active metabolite, 5-hydroxymethyl tolterodine, which is responsible for the antimuscarinic activity of fesoterodine.

• References

Class Summary

Anticholinergics inhibit the binding of acetylcholine to the muscarinic receptors in the detrusor, thereby suppressing involuntary bladder contractions. This results in an increase in bladder volume voided and a decrease in micturition frequency, sensation of urgency, and number of urge incontinence episodes.

Angioedema of the face, lips, tongue, and/or pharynx has been noted in several of these agents in postmarketing surveillance, including solifenacin, darifenacin, trospium chloride, and fesoterodine. Warnings are noted in the prescribing information for these agents, and if patients experience such symptoms they should seek emergency care.

• References

Mirabegron (Myrbetriq)

• Dosing, Interactions, etc.

Clinical Context:  Mirabegron is a beta-3 adrenergic receptor agonist that causes relaxation of the detrusor smooth muscle of the urinary bladder and increases bladder capacity. It is indicated for overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Also, indicated in combination with the muscarinic antagonist solifenacin for the treatment of OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency.

• References

Class Summary

These agents elicit a direct inhibition of afferent nerve firing independent of the relaxing effects on bladder smooth muscle.

• References

OnabotulinumtoxinA (Botox)

• Dosing, Interactions, etc.

Clinical Context:  OnabotulinumtoxinA is a neurotoxin derived from Clostridium botulinum. It prevents ACh release from presynaptic membrane, resulting in a temporary calming effect of muscle contractions by blocking the transmission of nerve impulses. The procedure involves multiple injections of a small amount of botox into the muscle of the bladder. The effects are not permanent and thus periodic repeat injections are often needed to maintain response.  Urinary retention is a side effect of the injections and thus individuals must be willing to catheterize intermittently until the retention resolves.

• References

Class Summary

Detrusor injections of botulinum neurotoxin type A may be considered for adults with OAB who cannot use or do not adequately respond to anticholinergic medication.

• References

Imipramine (Tofranil)

• Dosing, Interactions, etc.

Clinical Context:  Imipramine is useful in facilitating urine storage. It decreases bladder contractility and increases outlet resistance.

• References

Doxepin

• Dosing, Interactions, etc.

Clinical Context:  Doxepin increases the concentration of serotonin and norepinephrine in the central nervous system (CNS) by inhibiting their reuptake by presynaptic neuronal membrane. These effects are associated with a decrease in symptoms of depression.

• References

Class Summary

Tricyclic antidepressants that have been used to treat OAB include imipramine and doxepin. Some agents of this type may decrease bladder contractility. They are not indicated for the first-line treatment of OAB.

• References

Estrogen (Premarin)

• Dosing, Interactions, etc.

Clinical Context:  Detrusor overactivity can be associated with atrophic urethritis; topical application of estrogen vaginal cream should be considered in women with symptomatic atrophic urethritis/vaginits.

• References

Class Summary

Hormones are used to treat OAB in association with atrophic urethritis and are not recommended as first-line therapies for OAB.

• References