AUA: Overactive Bladder (2019): Difference between revisions

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**#'''<span style="color:#ff0000">Nocturia</span>'''
**#'''<span style="color:#ff0000">Nocturia</span>'''
**#*'''OAB symptoms (frequency, urgency and urgency incontinence) may occur only at night, causing a single symptom of nocturia.'''
**#*'''OAB symptoms (frequency, urgency and urgency incontinence) may occur only at night, causing a single symptom of nocturia.'''
**'''When urinary frequency (both daytime and night) and urgency, with or without urgency incontinence, in the absence of UTI or other obvious pathology are self-reported as bothersome, the patient may be diagnosed with OAB'''
**'''<span style="color:#ff0000">When urinary frequency (both daytime and night) and urgency, with or without urgency incontinence, in the absence of UTI or other obvious pathology are self-reported as bothersome, the patient may be diagnosed with OAB</span>'''


=== Recommended Investigations ===
=== Recommended Investigations ===
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# '''<span style="color:#ff0000">Symptom questionnaire</span>'''
# '''<span style="color:#ff0000">Symptom questionnaire</span>'''


==== Not recommended in the initial workup of the uncomplicated patient ====
=== Not recommended in the initial workup of the uncomplicated patient ===
#'''Urodynamics'''
#'''Urodynamics'''
#'''Cystoscopy'''
#'''Cystoscopy'''
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*'''For complicated or refractory patients, the choice of additional diagnostic tests depends on patient history, QoL and clinician judgment. Neurogenic OAB requires specific evaluation.'''
*'''For complicated or refractory patients, the choice of additional diagnostic tests depends on patient history, QoL and clinician judgment. Neurogenic OAB requires specific evaluation.'''
**
**
=== History and Physical Exam ===
=== Mandatory ===
==== History ====
==== History and Physical Exam ====
===== History =====
* '''<span style="color:#ff0000">Characterize lower urinary tract symptoms (storage and voiding/emptying), including duration of symptoms and baseline symptoms</span>'''
* '''<span style="color:#ff0000">Characterize lower urinary tract symptoms (storage and voiding/emptying), including duration of symptoms and baseline symptoms</span>'''
**Assess bladder storage symptoms associated with OAB (e.g., urgency, urgency incontinence, frequency, nocturia) and other bladder storage problems (e.g., stress incontinence episodes)  
**Assess bladder storage symptoms associated with OAB (e.g., urgency, urgency incontinence, frequency, nocturia) and other bladder storage problems (e.g., stress incontinence episodes)  
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**Excessive fluid intake can produce voiding patterns that mimic OAB symptoms.
**Excessive fluid intake can produce voiding patterns that mimic OAB symptoms.
**'''Patients who do not appear able to provide accurate intake and voiding information should fill out a fluid diary.'''  
**'''Patients who do not appear able to provide accurate intake and voiding information should fill out a fluid diary.'''  
* '''Current medications'''  
* '''<span style="color:#ff0000">Current medications</span>'''  
**Should be reviewed to ensure that symptoms are not related to medications.  
**Should be reviewed to ensure that symptoms are not related to medications.  
* '''Co-morbid conditions'''  
* '''<span style="color:#ff0000">Co-morbid conditions</span>'''  
**Neurologic diseases and other genitourinary conditions should be considered as they directly impact bladder function.
**'''Neurologic diseases and other genitourinary conditions''' should be considered as they directly impact bladder function.
**Complicated OAB patients
**'''Criteria for Complicated OAB'''
***Patients with OAB symptoms and co-morbid conditions including  
***'''Female patient with significant prolapse (i.e., prolapse beyond the introitus)'''
****Neurologic diseases (i.e., stroke, multiple sclerosis, spinal cord injury)
***'''Failed multiple anti-muscarinics to control OAB symptoms'''
****Mobility deficits
***'''Patients with OAB symptoms and co-morbid conditions including'''
****Medically complicated/uncontrolled diabetes
***#'''Neurologic diseases (i.e., stroke, multiple sclerosis, spinal cord injury)'''
****Fecal motility disorders (fecal incontinence/constipation)
***#'''Mobility deficits'''
****Chronic pelvic pain
***#'''Medically complicated/uncontrolled diabetes'''
****History of recurrent urinary tract infections (UTIs)
***#'''Fecal motility disorders (fecal incontinence/constipation)'''
****Gross hematuria
***#'''Chronic pelvic pain'''
****Prior pelvic/vaginal surgeries (incontinence/prolapse surgeries)
***#'''History of recurrent urinary tract infections (UTIs)'''
****Pelvic cancer (bladder, colon, cervix, uterus, prostate)
***#'''Gross hematuria'''
****Pelvic radiation.
***#'''Prior pelvic/vaginal surgeries (incontinence/prolapse surgeries)'''
***The female patient with significant prolapse (i.e., prolapse beyond the introitus)
***#'''Pelvic cancer (bladder, colon, cervix, uterus, prostate)'''
***A patient who has failed multiple anti-muscarinics to control OAB symptoms
***#'''Pelvic radiation'''
*'''<span style="color:#ff0000">Degree of bother</span>'''
*'''<span style="color:#ff0000">Degree of bother</span>'''
** If patient is not significantly bothered by his/her bladder symptoms, then there is a less compelling reason to treat the symptoms.
** If patient is not significantly bothered by his/her bladder symptoms, then there is a less compelling reason to treat the symptoms.


==== Physical exam (4) ====
===== Physical exam (4) =====
# '''Abdominal exam'''  
# '''<span style="color:#ff0000">Abdominal exam</span>'''  
#*To assess for scars, masses, hernias and areas of tenderness as well as for suprapubic distension that may indicate urinary retention
#*Assess for scars, masses, hernias and areas of tenderness as well as for suprapubic distension that may indicate urinary retention
# '''Rectal/genitourinary exam'''  
# '''<span style="color:#ff0000">Rectal/genitourinary exam</span>'''  
#*To rule out pelvic floor disorders (e.g., pelvic floor muscle spasticity, pain, pelvic organ prolapse) in females and prostatic pathology in males.
#*'''To rule out'''
#*In menopausal females, atrophic vaginitis should be assessed as a possible contributing factor to incontinence symptoms.  
#**'''Pelvic floor disorders (e.g., pelvic floor muscle spasticity, pain, pelvic organ prolapse) in females'''
#**'''Prostatic pathology in males'''
#*'''In menopausal females, atrophic vaginitis should be assessed''' as a possible contributing factor to incontinence symptoms.  
#*'''Assess for perineal skin for rash or breakdown.'''
#*'''Assess for perineal skin for rash or breakdown.'''
#*Assess perineal sensation, rectal sphincter tone and ability to contract the anal sphincter in order to evaluate pelvic floor tone and potential ability to perform pelvic floor exercises (e.g., the ability to contract the levator ani muscles) as well as to rule out impaction and constipation.
#*'''Assess perineal sensation, rectal sphincter tone and ability to contract the anal sphincter''' to
# '''Assessment of lower extremities for edema'''  
#**Evaluate pelvic floor tone and potential ability to perform pelvic floor exercises (e.g., the ability to contract the levator ani muscles)
#**Rule out impaction and constipation.
# '''<span style="color:#ff0000">Assessment of lower extremities for edema</span>'''  
#*To assess for the potential for fluid shifts during periods of postural changes
#*To assess for the potential for fluid shifts during periods of postural changes
#'''Patient’s attire and ability to dress independently''' (as a surrogate for cognitive function)
#'''<span style="color:#ff0000">Patient’s attire and ability to dress independently</span>''' (as a surrogate for cognitive function)
#*The ability of the patient to dress independently is informative of sufficient motor skills related to toileting habits. This can provide information on the cognitive function of the patient, which is important to evaluate when considering anticholinergics.
#*The ability of the patient to dress independently is informative of sufficient motor skills related to toileting habits. This can provide information on the cognitive function of the patient, which is important to evaluate when considering anticholinergics.
#*A Mini-Mental State Examination (MMSE) should be conducted on all patients who may be at risk for cognitive impairment to determine whether symptoms are aggravated by cognitive problems, to ensure that they will be able to follow directions for behavioral therapy and/or to determine the degree of risk for cognitive decline with anti-muscarinic therapy.
#*A Mini-Mental State Examination (MMSE) should be conducted on all patients who may be at risk for cognitive impairment to determine whether symptoms are aggravated by cognitive problems, to ensure that they will be able to follow directions for behavioral therapy and/or to determine the degree of risk for cognitive decline with anti-muscarinic therapy.


=== Urinalysis ===
==== Urinalysis ====
* To rule out UTI and and evaluate for presence of hematuria
* '''To rule out UTI and and evaluate for presence of hematuria'''
*If evidence of infection is detected, then a culture should be performed, the infection treated appropriately and the patient should be queried regarding symptoms once the infection has cleared.
*If evidence of infection is detected, then a culture should be performed, the infection treated appropriately and symptoms should be reassessed once the infection has cleared.


=== Urine culture ===
=== Optional ===
* Not necessary unless indication of infection (i.e., nitrites/leukocyte esterase on dipstick, pyuria/bacteriuria on microscopic exam) is found
==== Urine culture ====
**Urinalysis is unreliable for identification of bacterial counts below 100,000CFU/mL.
* Usually not necessary unless indication of infection (i.e., nitrites/leukocyte esterase on dipstick, pyuria/bacteriuria on microscopic exam) is found
**In some patients with irritative voiding symptoms but without overt signs of infection, a urine culture may be appropriate to completely exclude the presence of clinically significant bacteriuria.  
*'''In some patients with irritative voiding symptoms but without overt signs of infection, a urine culture may be appropriate to completely exclude the presence of clinically significant bacteriuria'''
**Urinalysis is unreliable for identification of bacterial counts <100,000CFU/mL.  


=== Post-void Residual ===
==== Post-void Residual ====
* Measured with an ultrasound bladder scanner immediately after the patient voids.  
* Measured with an ultrasound bladder scanner immediately after the patient voids.  
**If an ultrasound scanner is not available, then urethral catheterization may be used to assess PVR.
**If an ultrasound scanner is not available, then urethral catheterization may be used to assess PVR.
*'''Not necessary for patients who are receiving first-line behavioral interventions or for uncomplicated patients (i.e., patients without a history of or risk factors for urinary retention) receiving antimuscarinic medications.'''
*'''<span style="color:#ff0000">Not necessary for patients who are receiving first-line behavioral interventions or for uncomplicated patients (i.e., patients without a history of or risk factors for urinary retention) receiving antimuscarinic medications.</span>'''
* '''Indications to assess PVR (4)'''
* '''<span style="color:#ff0000">Indications to assess PVR (4)</span>'''
*#Presence of voiding/obstructive symptoms
*#'''<span style="color:#ff0000">Neurologic diagnoses</span>'''
*#'''<span style="color:#ff0000">History of incontinence surgery or prostatic surgery</span>'''
*#'''<span style="color:#ff0000">Presence of voiding/obstructive symptoms</span>'''
*#*As there is considerable overlap between storage and emptying voiding symptoms, baseline PVRs should be performed for males with symptoms prior to initiation of anti-muscarinic therapy.
*#*As there is considerable overlap between storage and emptying voiding symptoms, baseline PVRs should be performed for males with symptoms prior to initiation of anti-muscarinic therapy.
*#History of incontinence surgery or prostatic surgery
*#'''<span style="color:#ff0000">Clinician discretion</span>'''
*#Neurologic diagnoses
*'''<span style="color:#ff0000">Anti-muscarinics should be used with caution in patients with PVR 250–300 mL.</span>'''
*#Clinician discretion
*'''Anti-muscarinics should be used with caution in patients with PVR 250–300 mL.'''
*For any patient on anti-muscarinic therapy, the clinician should be prepared to monitor PVR during the course of treatment should obstructive voiding symptoms appear.
*For any patient on anti-muscarinic therapy, the clinician should be prepared to monitor PVR during the course of treatment should obstructive voiding symptoms appear.


=== Bladder diaries ===
==== Bladder Diary ====
* '''Diaries that document intake and voiding behavior'''  
* '''See [https://www.urologyhealth.org/documents/Product-Store/English/Overactive-Bladder-OAB-Bladder-Diary.pdf Urology Care Foundation Link]'''
**Self-monitoring with a bladder diary for 3-7 days is a useful first step in initiating behavioral treatments for OAB.
*'''<span style="color:#ff0000">Documents (2)'''
***At a minimum, the patient documents the time of each void and incontinence episode and the circumstances or reasons for the incontinence episode.
*#'''<span style="color:#ff0000">Intake AND'''
***Rating the degree of urgency associated with each void and incontinence episode also can be useful. 
*#'''<span style="color:#ff0000">Voiding behavior'''
***Adding measures of voided volumes can provide a practical estimate of the patient's functional bladder capacity in daily life and estimate the amount of overall fluid intake. Recording voided volumes also can be useful to differentiate between polyuria (characterized by normal or large volume voids) from OAB (characterized by frequent small voids).
*##'''At a minimum, the patient documents (2):'''
***It is more burdensome, however, and is usually completed for only 24 to 48 hours.
*###'''Time of each void''' 
*May be useful, particularly for patient education and to document baseline symptoms and treatment efficacy                
*###'''Incontinence episode and the circumstances or reasons for the incontinence episode.'''
*##'''Other useful measures'''
*##*'''Voided volumes'''
*##**Provide a practical estimate of the patient's functional bladder capacity in daily life and estimate the amount of overall fluid intake.
*##**Useful to differentiate between polyuria (characterized by normal or large volume voids) from OAB (characterized by frequent small voids).
*##*Rating the degree of urgency associated with each void and incontinence episode
*'''May be useful, particularly for patient education and to document baseline symptoms and treatment efficacy'''              
**'''Self-monitoring with a bladder diary for 3-7 days is a useful first step in initiating behavioral treatments for OAB.'''
***Usually completed for only 24 to 48 hours due to burden of monitoring


=== Symptoms questionnaire ===
==== Symptoms questionnaire ====
* Useful in the quantification of bladder symptoms and bother changes with OAB treatment.
* '''Useful in the quantification of bladder symptoms and bother changes with OAB treatment'''
*Options (4)
*Options (4)
*#Urogenital Distress Inventory (UDI)
*#Urogenital Distress Inventory (UDI)
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== Differential Diagnosis ==
== Differential Diagnosis ==


# '''Nocturia'''
# '''<span style="color:#ff0000">Polydipsia and polyuria</span>'''
# '''Polydipsia and polyuria'''
#'''<span style="color:#ff0000">Nocturia</span>'''
# '''Interstitial cystitis/bladder pain syndrome'''
# '''<span style="color:#ff0000">Interstitial cystitis/bladder pain syndrome</span>'''
#'''Atrophic vaginitis'''
#'''<span style="color:#ff0000">Atrophic vaginitis</span>'''
 
=== Polydipsia and polyuria ===
* Frequency that is the result of polydipsia and resulting polyuria may mimic OAB
*'''Diagnosis and Evaluation'''
**'''Can only be distinguished from OAB with the use of frequency-volume charts.'''
***'''In OAB, urinary frequency is associated with many small volume voids.'''
***'''In polydipsia, urinary frequency is associated with normal or large volume voids and the intake is volume matched.''' In this case, the frequency is appropriate because of the intake volume and the patient does not have OAB
***'''Diabetes insipidus''' also is associated with frequent, large volume voids and should be distinguished from OAB.
*Management
**If polydipsia-related frequency is physiologically self-induced: education and consideration of fluid management
**If diabetes insipidus: desmopressin


=== Nocturia ===
=== Nocturia ===


* '''Often due to factors unrelated to OAB, including excessive nighttime urine production (i.e. nocturnal polyuria) and sleep apnea.'''
* '''Often due to factors unrelated to OAB, including excessive nighttime urine production (i.e. nocturnal polyuria) and sleep apnea.'''
**OAB symptoms (frequency, urgency and urgency incontinence) may occur only at night, causing a single symptom of nocturia.
* '''Differential of nocturia includes nocturnal polyuria, low nocturnal bladder capacity or both.'''
* The differential of nocturia includes nocturnal polyuria, low nocturnal bladder capacity or both.  
**'''Nocturnal polyuria'''
**Nocturnal polyuria
***Definition: the production of greater than 20 to 33% of total 24 hour urine output during the period of sleep, which is age-dependent with 20% for younger individuals and 33% for elderly individuals.
***Definition: the production of greater than 20 to 33% of total 24 hour urine output during the period of sleep, which is age-dependent with 20% for younger individuals and 33% for elderly individuals.  
***Often associated with sleep disturbances, vascular and/or cardiac disease and other medical conditions
***Nocturnal voids are frequently normal or large volume as opposed to the small volume voids commonly observed in nocturia associated with OAB.
***'''Nocturnal voids are frequently normal or large volume as opposed to the small volume voids commonly observed in nocturia associated with OAB.'''
***Sleep disturbances, vascular and/or cardiac disease and other medical conditions are often associated with nocturnal polyuria.
 
=== Polydipsia and polyuria ===
 
* Frequency that is the result of polydipsia and resulting polyuria may mimic OAB; the two can only be distinguished with the use of frequency-volume charts.
**In OAB, urinary frequency is associated with many small volume voids
**In polydipsia, urinary frequency occurs with normal or large volume voids and the intake is volume matched. In this case, the frequency is appropriate because of the intake volume and the patient does not have OAB
*Polydipsia-related frequency is physiologically self-induced and should be managed with education and consideration of fluid management.
*Diabetes insipidus also is associated with frequent, large volume voids and should be distinguished from OAB.


=== Interstitial cystitis/bladder pain syndrome ===
=== Interstitial cystitis/bladder pain syndrome ===


* Clinical presentation of interstitial cystitis/bladder pain syndrome shares the OAB symptoms of urinary frequency and urgency, with or without urgency incontinence
* Clinical presentation of interstitial cystitis/bladder pain syndrome shares the OAB symptoms of urinary frequency and urgency, with or without urgency incontinence
*'''Bladder and/or pelvic pain, including dyspareunia, is a crucial component of its presentation in contradistinction to OAB.'''
*'''<span style="color:#ff0000">Bladder and/or pelvic pain, including dyspareunia, is a crucial component of its presentation in contradistinction to OAB.</span>'''


=== Atrophic vaginitis ===
=== Atrophic vaginitis ===


* In the menopausal female patient, atrophic vaginitis can be a contributing factor to incontinence symptoms.  
* '''In the menopausal female patient, atrophic vaginitis can be a contributing factor to incontinence symptoms.'''
* Use of vaginal (but not systemic) estrogen may improve symptoms.
* '''Use of vaginal (but not systemic) estrogen may improve symptoms.'''


== Management ==
== Management ==


* OAB may compromise QoL but generally does not affect survival. A treatment plan, therefore, should carefully weigh the patient’s potential benefit of a particular treatment against that treatment’s risk for, severity and reversibility of AEs.
=== General Principles ===
* '''Provide education to patients regarding normal lower urinary tract function, what is known about OAB, the benefits vs. risks/burdens of the available treatment alternatives and the fact that acceptable symptom control may require trials of multiple therapeutic options before it is achieved.'''
* '''Provide education to patients regarding'''
** Counsel patients that OAB has a variable and chronic course likely requiring multiple management strategies over time with no single ideal treatment and understands that treatments vary in invasiveness, risk of AEs and reversibility.  
**'''Normal lower urinary tract function'''
** Most OAB treatments improve patient symptoms but are unlikely to eliminate all symptoms
**'''What is known about OAB'''
** Treatment failure occurs when the patient with reasonable expectations does not have the anticipated symptom improvement or is unable to tolerate the treatment due to AEs; lack of efficacy and the presence of intolerable AEs reduce compliance  
**'''Benefits vs. risks/burdens of the available treatment alternatives'''  
*Practitioners and patients should persist with new treatments (4 to 8 weeks for medications and 8 to 12 weeks for behavioral therapies) for a sufficient duration to achieve clarity regarding efficacy and adverse events for a particular therapy before abandoning the therapy prematurely or before adding a second therapy.  
*'''<span style="color:#ff0000">Counsel patients that OAB</span>'''
*If a comprehensive evaluation has demonstrated that the patient has signs and symptoms consistent with the OAB diagnosis and a particular therapy is not efficacious after a reasonable trial, then an alternative therapy should be tried
**'''<span style="color:#ff0000">Has a variable and chronic course</span>''' 
*Combination therapeutic approaches should be assembled methodically, beginning with the establishment of confidence in the partial efficacy of one therapy, continuing with an adequate trial of any additional therapies one at a time until the patient experiences adequate symptom control in the context of tolerable adverse events. If a patient does not achieve adequate symptom control with this approach, then referral to a specialist should be considered.  
**'''<span style="color:#ff0000">Most OAB treatments improve patient symptoms but are unlikely to eliminate all symptoms</span>'''
**'''<span style="color:#ff0000">Acceptable symptom control may require trials of multiple therapeutic options before it is achieved, with no single ideal treatment, and treatments vary in invasiveness, risk of AEs and reversibility.'''
*** OAB may compromise QoL but generally does not affect survival. A treatment plan, therefore, should carefully weigh the patient’s potential benefit of a particular treatment against that treatment’s risk for, severity and reversibility of AEs.
***Treatment failure occurs when the patient with reasonable expectations does not have the anticipated symptom improvement or is unable to tolerate the treatment due to AEs; lack of efficacy and the presence of intolerable AEs reduce compliance
*'''<span style="color:#ff0000">New treatments should persist for a sufficient duration to achieve (4 to 8 weeks for medications and 8 to 12 weeks for behavioral therapies) clarity regarding efficacy and adverse events for a particular therapy</span> before abandoning the therapy prematurely or before adding a second therapy.'''
**If a comprehensive evaluation has demonstrated that the patient has signs and symptoms consistent with the OAB diagnosis and a particular therapy is not efficacious after a reasonable trial, then an alternative therapy should be tried.


=== Options ===
=== Options ===
# '''Observation'''
# '''<span style="color:#ff0000">Observation</span>'''
# '''Behavioral therapies (first-line)'''
# '''<span style="color:#ff0000">Behavioral therapies (first-line)</span>'''
# '''Pharmacologic management (second-line)'''
# '''<span style="color:#ff0000">Pharmacologic management (second-line)</span>'''
# '''Intradetrusor onabotulinumtoxinA or neuromodulation (PTNS, SNS) (third-line)'''
# '''<span style="color:#ff0000">Intradetrusor onabotulinumtoxinA or neuromodulation (PTNS, SNS) (third-line)</span>'''
#'''Augmentation cystoplasty, cystectomy (fourth-line)'''
#'''<span style="color:#ff0000">Augmentation cystoplasty, cystectomy (fourth-line)</span>'''
#'''Indwelling catheter (fifth-line, not recommended except as a last resort)'''
#'''<span style="color:#ff0000">Indwelling catheter (fifth-line, not recommended except as a last resort)</span>'''
*'''Every patient does not need to proceed through each line of therapy before considering the next'''
*'''<span style="color:#ff0000">Every patient does not need to proceed through each line of therapy before considering the next</span>'''
**'''PTNS can be considered in drug-naïve patients who opt to forego pharmacotherapy.'''
**'''<span style="color:#ff0000">PTNS can be considered in drug-naïve patients who opt to forego pharmacotherapy.</span>'''


=== Observation ===
=== Observation ===


* '''OAB is not a disease; it is a symptom complex that generally is not a life-threatening condition.'''
* '''After assessment has been performed to exclude conditions requiring treatment and counseling, no treatment is an acceptable choice made by some patients and caregivers.'''
*'''Initiating treatment for OAB generally presumes that the patient can perceive an improvement in his or her QOL.'''  
**OAB is not a disease; it is a symptom complex that generally is not a life-threatening condition.
**In patients who cannot perceive symptom improvements, treatment may not be appropriate, may be potentially unsafe or may be futile (e.g., in the very elderly or demented patient) except in patients for whom OAB symptoms present a significant health risk (e.g., risk for skin breakdown).
**'''Initiating treatment for OAB generally presumes that the patient can perceive an improvement in his or her QOL.'''  
***In certain patients for whom hygiene and skin breakdown are major concerns, treatment may be considered regardless of the patient's perceptions when it is in the patient's best interests.  
***In patients who cannot perceive symptom improvements (e.g., in the very elderly or demented patient), treatment may not be appropriate, may be potentially unsafe or may be futile  
****In these patients, behavioral strategies that include prompted voiding and fluid management may be helpful.  
***In certain patients for whom hygiene and risk for skin breakdown are major concerns for a significant health risk, treatment may be considered regardless of the patient's perceptions when it is in the patient's best interests.  
****In these patients, behavioral strategies that include prompted voiding and fluid management may be helpful.
****Pharmacologic treatments and invasive treatments, however, are generally not appropriate for these individuals.
****Pharmacologic treatments and invasive treatments, however, are generally not appropriate for these individuals.
* '''After assessment has been performed to exclude conditions requiring treatment and counseling, no treatment is an acceptable choice made by some patients and caregivers.'''


=== Behavioral Therapies (first-line) ===
=== Behavioral Therapies (first-line) ===
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**'''First-line treatments because they are'''  
**'''First-line treatments because they are'''  
**#'''Relatively non-invasive'''
**#'''Relatively non-invasive'''
**#'''Associated with virtually no adverse events, in contrast to medications'''
**#'''Associated with virtually no adverse events'''
**#'''As effective in reducing symptom levels as are antimuscarinic medications.'''
**#'''As effective in reducing symptom levels as are antimuscarinic medications.'''
**#*Randomized trials indicates that behavioral treatments are generally either equivalent to or superior to medications in terms of reducing incontinence episodes, improving frequency and nocturia and improving QoL.
**#*Randomized trials indicates that behavioral treatments are generally either equivalent to or superior to medications in terms of reducing incontinence episodes, improving frequency and nocturia and improving QoL.
**Behavioral therapies require an investment of time and effort by the patient to achieve maximum benefits and may require sustained and regular contact with the clinician to maintain regimen adherence and consequent efficacy.
**While most patients do not experience complete symptom relief, most patients experience significant reductions in symptoms and improvements in QoL.
**While most patients do not experience complete symptom relief, most patients experience significant reductions in symptoms and improvements in QoL.
** '''May be combined with pharmacologic management.'''
*'''May be combined with pharmacologic management.'''
*Behavioral therapies require an investment of time and effort by the patient to achieve maximum benefits and may require sustained and regular contact with the clinician to maintain regimen adherence and consequent efficacy.
*In patients who are unwilling or unable to comply with behavioral therapy regimens and instructions, it is appropriate to move to second-line pharmacologic therapies.
*In patients who are unwilling or unable to comply with behavioral therapy regimens and instructions, it is appropriate to move to second-line pharmacologic therapies.


=== Pharmacologic management (second-line) ===
=== Second-line: Pharmacologic Management ===


==== Options ====
==== Options ====


* '''Recommended'''
* '''<span style="color:#ff0000">Recommended</span>'''
** '''Oral anti-cholinergic'''
** '''<span style="color:#ff0000">Oral anti-cholinergic</span>'''
** '''Oral β3-adrenoceptor agonists'''
** '''<span style="color:#ff0000">Oral β3-adrenoceptor agonists</span>'''
* '''May be offered'''
* '''<span style="color:#ff0000">May be offered</span>'''
** '''Transdermal oxybutynin (patch or gel)'''
** '''<span style="color:#ff0000">Transdermal oxybutynin (patch or gel)</span>'''
*Failure and/or the experience of adverse events with one medication should usually be addressed by trying at least one other medication before third-line therapies are considered.
*'''Consider beginning with the lowest possible dose and titrate slowly while carefully assessing for the balance between symptom control and AEs.'''
**In older patients who may metabolize drugs differently, it is advisable to start with a minimal dose and titrate as tolerated.
**Optimizing medication tolerability is critical to obtaining patient compliance in the treatment of this chronic condition.
*Compliance with a once daily dosing is greater than with medications taken more than once a day.


==== Anti-cholinergics ====
==== Anti-cholinergics ====
Line 254: Line 278:
===== Options =====
===== Options =====
# '''<span style="color:#ff0000">Oral</span>'''
# '''<span style="color:#ff0000">Oral</span>'''
##'''<span style="color:#ff0000">Oxybutynin</span>'''
##'''<span style="color:#ff0000">Tolterodine</span>'''
##'''<span style="color:#ff0000">Fesoterodine</span>'''
##'''<span style="color:#ff0000">Darifenacin</span>'''
##'''<span style="color:#ff0000">Darifenacin</span>'''
## '''<span style="color:#ff0000">Fesoterodine</span>'''
## '''<span style="color:#ff0000">Oxybutynin</span>'''
## '''<span style="color:#ff0000">Solifenacin</span>'''
## '''<span style="color:#ff0000">Solifenacin</span>'''
## '''<span style="color:#ff0000">Tolterodine</span>'''
## '''<span style="color:#ff0000">Trospium</span>'''
## '''<span style="color:#ff0000">Trospium</span>'''
#'''<span style="color:#ff0000">Transdermal oxybutynin (patch or gel)</span>'''
#'''<span style="color:#ff0000">Transdermal oxybutynin (patch or gel)</span>'''


===== Efficacy =====
===== Efficacy =====
*'''No compelling evidence for differential efficacy across oral medications'''
*'''Similar efficacy observed for all oral anti-cholinergic medications'''
**Since similar efficacy observed for all oral anti-cholinergic medications, the choice of medication is patient dependent; however, AE profiles for dry mouth and constipation vary with medications
**Choice of medication is patient dependent
**'''Adverse event profiles for dry mouth and constipation vary with medications'''
* Patients with more severe symptoms, on average, experience greater symptom reductions.  
* Patients with more severe symptoms, on average, experience greater symptom reductions.  
**Only patients with relatively low baseline symptom levels are likely to experience complete symptom relief
**Only patients with relatively low baseline symptom levels are likely to experience complete symptom relief


===== Contraindications =====
===== Contraindications =====
*'''Narrow angle glaucoma''' (unless approved by the treating ophthalmologist)
#'''<span style="color:#ff0000">Narrow angle glaucoma</span>''' (unless approved by the treating ophthalmologist)
*'''Impaired gastric emptying or a history of urinary retention'''
#'''<span style="color:#ff0000">Dementia</span>'''
**Prior to initiation of anti-cholinergics, a patient at risk for gastric emptying problems or for urinary retention should receive clearance from a gastroenterologist or urologist, respectively.
#*Anti-cholinergics may be contraindicated entirely depending on the level of cognitive impairment.
***A PVR may be useful in any patient suspected of a higher risk of urinary retention.
#'''<span style="color:#ff0000">Impaired gastric emptying</span>'''
*'''Use of solid oral forms of potassium chloride'''
#*Prior to initiation of anti-cholinergics, a patient at risk for gastric emptying problems should receive clearance from a gastroenterologist
**Reduced gastric emptying potentially caused by the anti-cholinergics may increase the potassium absorption of these agents.
#'''<span style="color:#ff0000">Use of solid oral forms of potassium chloride</span>'''
**Anti-cholinergic therapy may be used with caution with alternative forms of potassium chloride.
#*Reduced gastric emptying potentially caused by the anti-cholinergics may increase the potassium absorption of these agents.
* '''Dementia'''
#*Anti-cholinergic therapy may be used with caution with alternative forms of potassium chloride.
**Anti-cholinergics may be contraindicated entirely depending on the level of cognitive impairment.
#'''<span style="color:#ff0000">History of urinary retention</span>'''
*'''Use caution in prescribing''' '''anti-cholinergics or β3-adrenoceptor agonists in the frail OAB patient.'''
##Prior to initiation of anti-cholinergics, a patient with history of urinary retention should receive clearance from a urologist.
** Frail patients are defined as patients with mobility deficits (i.e., require support to walk, have slow gait speed, have difficulty rising from sitting to standing without assistance), weight loss and weakness without medical cause and who may have cognitive deficits
##*A PVR may be useful in any patient suspected of a higher risk of urinary retention.
**OAB medication trials generally are not conducted in the frail elderly, resulting in a lack of efficacy and AE data in this group.  
#'''<span style="color:#ff0000">Use caution in prescribing anti-cholinergics in patients who are already using''' '''other medications with anti-cholinergic properties.</span>'''
***Additional AEs are reported in this group, including impaired thermoregulation with dangerous core temperature elevation.
#* '''<span style="color:#ff0000">Medications with anti-cholinergic properties include (3)</span>'''
** Polypharmacy is common in frail community-dwelling patients, placing them at higher risk for AEs, including impaired cognition.
#*#'''<span style="color:#ff0000">Tricyclic antidepressants</span>'''
*'''Use caution in prescribing''' '''anti-cholinergics in patients who are already using''' '''other medications with anti-cholinergic properties.'''
#*#'''<span style="color:#ff0000">Medications for Parkinsonism, other extra-pyramidal diseases and Alzheimer’s disease</span>''' (benzotropine, biperiden HCl, galantamine, rivastigmine and trihexyphenidyl HCl)
** '''Medications with anti-cholinergic properties include (3)'''
#*#'''<span style="color:#ff0000">Acetylcholinesterase inhibitors (donepezil)</span>'''
**#'''Tricyclic antidepressants'''
#*'''Certain anti-nausea medications and those with atropine-like properties may also potentiate adverse events.'''
**#'''Acetylcholinesterase inhibitors'''
#**Examples include trimethaphan, methscopolamine bromide and ipratropium
**#'''Medications for Parkinsonism, other extra-pyramidal diseases and Alzheimer’s disease.'''
#'''<span style="color:#ff0000">Use caution in prescribing anti-cholinergics or β3-adrenoceptor agonists in the frail OAB patient.</span>'''
** '''Certain anti-nausea medications and those with atropine-like properties may also potentiate AEs.'''
#* '''Frail patients are defined as patients with mobility deficits (i.e., require support to walk, have slow gait speed, have difficulty rising from sitting to standing without assistance), weight loss and weakness without medical cause and who may have cognitive deficits'''
**These medications include tricyclic antidepressants, those used in the treatment of Parkinsonism and other extra-pyramidal diseases and of Alzheimer's disease, and include benzotropine, biperiden HCl, galantamine, rivastigmine and trihexyphenidyl HCl. Certain anti-nausea medications and those with atropine-like properties, such as trimethaphan, methscopolamine bromide and ipratropium, may also potentiate these side effects. Providers also should exercise caution in patients who are prescribed acetycholinesterase inhibitors such as donepezil.  
#*'''OAB medication trials generally are not conducted in the frail elderly''', resulting in a lack of efficacy and AE data in this group.  
#**Additional AEs are reported in this group, including impaired thermoregulation with dangerous core temperature elevation.
#* Polypharmacy is common in frail community-dwelling patients, placing them at higher risk for AEs, including impaired cognition.


===== Adverse events (9) =====
===== Adverse events (9) =====
#'''Dry mouth (20-40%)'''
#'''<span style="color:#ff0000">Dry mouth (20-40%)</span>'''
#'''Constipation (7-9%)'''
#'''<span style="color:#ff0000">Constipation (7-9%)</span>'''
#'''Dry or itchy eyes'''
#'''<span style="color:#ff0000">Dry or itchy eyes</span>'''
#'''Blurred vision'''
#'''<span style="color:#ff0000">Blurred vision</span>'''
#'''Dyspepsia'''
#'''<span style="color:#ff0000">Dyspepsia</span>'''
#'''UTI'''
#'''<span style="color:#ff0000">UTI</span>'''
#'''Urinary retention'''
#'''<span style="color:#ff0000">Urinary retention</span>'''
#'''Impaired cognitive function'''
#'''<span style="color:#ff0000">Impaired cognitive function</span>'''
#'''Arrhythmias (rare)'''
#'''<span style="color:#ff0000">Arrhythmias (rare)</span>'''
*'''Dry mouth'''
*'''<span style="color:#ff0000">Dry mouth</span>'''
**Dry mouth rates for oxybutynin (61%) significantly higher than tolterodine (24%)
**<span style="color:#ff0000">'''Dry mouth rates for oxybutynin (61%) significantly higher''' </span>than tolterodine (24%)
**Can be mitigated with oral lubricants, small sips of water, sucking on sugar-free hard candies and chewing sugar-free gum, and avoiding mouthwashes with alcohol.
**'''<span style="color:#ff0000">If an immediate release (IR) and an extended release (ER) formulation are available, then ER formulations should preferentially be prescribed over IR formulations because of lower rates of dry mouth.</span>'''
**'''If an immediate release (IR) and an extended release (ER) formulation are available, then ER formulations should preferentially be prescribed over IR formulations because of lower rates of dry mouth.'''
*** ER formulations of oxybutynin and tolterodine result in significantly fewer patient reports of dry mouth than the IR formulations of either medication.
*** ER formulations of oxybutynin and tolterodine result in significantly fewer patient reports of dry mouth than the IR formulations of either medication.
***Compliance with a once-daily treatment has been shown to be greater than with medications that are taken more than once a day
***Compliance with a once-daily treatment has been shown to be greater than with medications that are taken more than once a day
**Transdermal preparations of oxybutynin may be offered instead of oral anti-muscarinics to patients who are at risk of or who have experienced dry mouth with oral agents
**<span style="color:#ff0000">'''Management'''</span>
***The use of transdermal anti-muscarinics should be monitored to ensure that the skin where the medication is applied remains intact.  
***<span style="color:#ff0000">'''Can be mitigated with (4):'''</span>
*'''Constipation'''
***#<span style="color:#ff0000">'''Oral lubricants'''</span>
**Can be mitigated with adequate dietary fiber and fluid, psyllium-based fiber supplements, regular exercise and normal bowel habits.
***#<span style="color:#ff0000">'''Small sips of water'''</span>
**Constipation rate significantly higher for darifenacin (17%) and oxybutynin (12%), compared to tolterodine (5%)
***#<span style="color:#ff0000">'''Sucking on sugar-free hard candies and chewing sugar-free gum'''</span>
*'''Constipation and dry mouth should be managed before abandoning effective anti-cholinergic therapy.'''
***#<span style="color:#ff0000">'''Avoiding mouthwashes with alcohol'''</span>
**'''Management may include bowel management, fluid management, dose modification or alternative anti-cholinergics.'''
***<span style="color:#ff0000">'''Transdermal preparations of oxybutynin may be offered instead of oral anti-muscarinics to patients who are at risk of or who have experienced dry mouth with oral agents'''</span>
*'''Cognitive impairment'''
****<span style="color:#ff0000">'''The use of transdermal anti-muscarinics should be monitored to ensure that the skin where the medication is applied remains intact.''' </span>
*'''<span style="color:#ff0000">Constipation</span>'''
**<span style="color:#ff0000">'''Can be mitigated with'''</span>
***<span style="color:#ff0000">'''Adequate dietary fiber and fluid'''</span>
***<span style="color:#ff0000">'''Psyllium-based fiber supplements'''</span>
***<span style="color:#ff0000">'''Regular exercise and normal bowel habits.'''</span>
**<span style="color:#ff0000">'''Constipation rate significantly higher for darifenacin (17%) and oxybutynin (12%)</span>''', compared to tolterodine (5%)
*'''<span style="color:#ff0000">Constipation and dry mouth should be managed before abandoning effective anti-cholinergic therapy.</span>'''
**'''<span style="color:#ff0000">Management may include bowel management, fluid management, dose modification or alternative anti-cholinergics.</span>'''
*'''<span style="color:#ff0000">Cognitive impairment</span>'''
**Patients may not recognize that memory deterioration has occurred, making it essential for the clinician, family members and caregivers to monitor for these effects
**Patients may not recognize that memory deterioration has occurred, making it essential for the clinician, family members and caregivers to monitor for these effects
**While newer agents (eg, darifenacin) are reported to be less likely to produce cognitive deficits in elderly patients, the literature is limited; the two-week drug administration period in these studies is not long enough to yield definitive conclusions.
**While newer agents (eg, darifenacin) are reported to be less likely to produce cognitive deficits in elderly patients, the literature is limited; the two-week drug administration period in these studies is not long enough to yield definitive conclusions.


==== β 3-adrenoceptor agonists: Mirabegron ====
==== β 3-adrenoceptor agonists: Mirabegron ====
*Similar efficacy profile to the anti-muscarinics and a relatively lower adverse event profile.
*<span style="color:#ff0000">'''Similar efficacy profile to the anti-muscarinics and a relatively lower adverse event profile.'''</span>
*most mirabegron doses produced statistically significant symptom reductions for voids per day and incontinence episodes per day compared to placebo. Improvements in UUI, urgency episodes, and QOL measures also occurred but were not as consistently statistically significant. Among studies with an active control group administered tolterodine ER 4 mg/daily, mirabegron generally performed similarly to tolterodine. Higher doses of mirabegron did not produce greater effects.
**Lower incidence of bothersome adverse events may inform the selection of medications for patients who already present with dry mouth (e.g., secondary to Sjogren's syndrome) and/or constipation or for patients who experience efficacy from the anti-muscarinics but cannot tolerate these adverse events.
*in general, mirabegron has similar efficacy to the anti-muscarinics
 
===== Efficacy =====
*Significant symptom reductions for voids per day and incontinence episodes per day
*Improvements in UUI, urgency episodes, and QOL measures also occur but were not as consistently statistically significant.  
*Among studies with an active control group administered tolterodine ER 4 mg/daily, mirabegron generally performed similarly to tolterodine. Higher doses of mirabegron did not produce greater effects.


===== Adverse events =====
===== Adverse events =====


*Increased heart rate
#<span style="color:#ff0000">'''Increased heart rate'''</span>
*Increased blood pressure
#<span style="color:#ff0000">'''Increased blood pressure'''</span>
**Changes in blood pressure and pulse rate are usually minor
#*Changes in blood pressure and pulse rate are usually minor
*Constipation
#<span style="color:#ff0000">'''Constipation'''</span>
**Similar to most anti-muscarinics in terms of risk of constipation except for solifenacin (5 mg and 10 mg), fesoterodine (8 mg) and trospium (60 mg), all of which had a higher risk of constipation.  
#*May produce lower/similar rates of constipation than some of the anti-muscarinics, except for solifenacin (5 mg and 10 mg), fesoterodine (8 mg) and trospium (60 mg), all of which had a higher risk of constipation.
*mirabegron appears to be similar in efficacy to the anti-muscarinics and has lower rates of dry mouth than any of these medications. Mirabegron may produce lower rates of constipation than some of the anti-muscarinics. This lower incidence of bothersome adverse events may inform the selection of medications for patients who already present with dry mouth (e.g., secondary to Sjogren's syndrome) and/or constipation or for patients who experience efficacy from the anti-muscarinics but cannot tolerate these adverse events.
*


*
==== Failure of medical therapy ====
*
*'''<span style="color:#ff0000">If a patient experiences inadequate symptom control and/or unacceptable adverse drug events with one anti-muscarinic medication, then a dose modification or a different anti-muscarinic medication or a β3-adrenoceptor agonist may be tried.</span>'''
*'''Begin with the lowest possible dose and titrate slowly while carefully assessing for the balance between symptom control and AEs.'''
**In older patients who may metabolize drugs differently, it is advisable to start with a minimal dose and titrate as tolerated.
* Optimizing medication tolerability is critical to obtaining patient compliance in the treatment of this chronic condition.
**Compliance with a once daily dosing is greater than with medications taken more than once a day.
'''Failure of medical therapy'''
*'''If a patient experiences inadequate symptom control and/or unacceptable adverse drug events with one anti-muscarinic medication, then a dose modification or a different anti-muscarinic medication or a β3-adrenoceptor agonist may be tried.'''
**Patients who had prior unsatisfactory symptom control and/or unacceptable adverse events with older medications (tolterodine or oxybutynin) reported better efficacy and/or more acceptable adverse event profiles with new medications (fesoterodine, solifenacin or darifenacin).
**Patients who had prior unsatisfactory symptom control and/or unacceptable adverse events with older medications (tolterodine or oxybutynin) reported better efficacy and/or more acceptable adverse event profiles with new medications (fesoterodine, solifenacin or darifenacin).
**Non-responders to anti-muscarinics should be tried on at least one other anti-muscarinic or mirabegron and/or dose modification attempted to determine if a better balance between efficacy and adverse events occurs. If adverse events are severe enough to compromise patient QOL, then strategies to manage specific adverse events, such as ameliorating constipation with appropriate bowel management, should be implemented before abandoning anti-muscarinic treatment.
**Non-responders to anti-muscarinics should be tried on at least one other anti-muscarinic or mirabegron and/or dose modification attempted to determine if a better balance between efficacy and adverse events occurs.  
*'''Clinicians may consider combination therapy with an anti-muscarinic and β3-adrenoceptor agonist for patients refractory to monotherapy with either anti-muscarinics or β3-adrenoceptor agonists.'''
***Failure and/or the experience of adverse events with one medication should usually be addressed by trying at least one other medication before third-line therapies are considered.
**If adverse events are severe enough to compromise patient QOL, then strategies to manage specific adverse events, such as ameliorating constipation with appropriate bowel management, should be implemented before abandoning anti-muscarinic treatment.
*'''<span style="color:#ff0000">Clinicians may consider combination therapy with an anti-muscarinic and β3-adrenoceptor agonist for patients refractory to monotherapy with either anti-muscarinics or β3-adrenoceptor agonists.</span>'''
**Studies have demonstrated improved efficacy with combination therapy without any significant effect on the safety profile when compared to monotherapy
**Studies have demonstrated improved efficacy with combination therapy without any significant effect on the safety profile when compared to monotherapy
**Combination therapeutic approaches should be assembled methodically, beginning with the establishment of confidence in the partial efficacy of one therapy, continuing with an adequate trial of any additional therapies one at a time until the patient experiences adequate symptom control in the context of tolerable adverse events.
*'''Patients who are refractory to behavioral''' '''and medical therapy should be evaluated''' '''by an appropriate specialist if they desire additional'''
*'''Patients who are refractory to behavioral''' '''and medical therapy should be evaluated''' '''by an appropriate specialist if they desire additional'''
**the refractory patient as the patient who has failed a trial of symptom-appropriate behavioral therapy of sufficient length to evaluate potential efficacy and who has failed a trial of at least one anti-muscarinic medication administered for 4 to 8 weeks. Failure of an anti-muscarinic medication may include lack of efficacy and/or inability to tolerate adverse drug effects.
**The refractory patient as the patient who has failed a trial of symptom-appropriate behavioral therapy of sufficient length to evaluate potential efficacy and who has failed a trial of at least one anti-muscarinic medication administered for 4 to 8 weeks. Failure of an anti-muscarinic medication may include lack of efficacy and/or inability to tolerate adverse drug effects.


=== Intradetrusor onabotulinumtoxinA, PTNS and Neuromodulation (third-line) ===
=== Third-line ===


==== Options (3): ====
# '''<span style="color:#ff0000">Intradetrusor onabotulinumtoxinA'''
# '''<span style="color:#ff0000">Peripheral tibial nerve stimulation (PTNS)'''
# '''<span style="color:#ff0000">Sacral neuromodulation'''
* Before a patient is exposed to third-line therapies with increased risk compared to behavioral or medical therapy, the patient’s realistic desire for further treatment should be ascertained, and a comprehensive evaluation should be conducted to confirm the diagnosis of OAB and not another disease process
* Before a patient is exposed to third-line therapies with increased risk compared to behavioral or medical therapy, the patient’s realistic desire for further treatment should be ascertained, and a comprehensive evaluation should be conducted to confirm the diagnosis of OAB and not another disease process


Line 356: Line 395:


==== OnabotulinumtoxinA ====
==== OnabotulinumtoxinA ====
* may offer intradetrusor onabotulinumtoxinA (100U) as third-line treatment in the carefully-selected and thoroughly-counseled patient who has been refractory to first- and second-line OAB treatments. The patient must be able and willing to return for frequent post-void residual evaluation and able and willing to perform self-catheterization if necessary.
* '''<span style="color:#ff0000">Intradetrusor onabotulinumtoxinA (100U) may be offered as third-line treatment in the carefully-selected and thoroughly-counseled patient who has been refractory to first- and second-line OAB treatments.</span>'''
*Considered a treatment STANDARD in patients with moderate to severe OAB symptoms
**'''<span style="color:#ff0000">Considered a treatment STANDARD in patients with moderate to severe OAB symptoms</span>'''
*Dosing: FDA-approved dose of 100U for neurogenic OAB
*'''<span style="color:#ff0000">Dosing: FDA-approved dose of 200U for neurogenic OAB</span>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649594/ §][https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739988/ §]'''
**'''Not FDA-approved in non-neurogenic OAB patients'''
**'''<span style="color:#ff0000">Not FDA-approved in non-neurogenic OAB patients, 100U typically used</span>'''
*'''Adverse events'''
*'''<span style="color:#ff0000">Adverse events</span>'''
**'''Urinary retention'''
*#'''<span style="color:#ff0000">Urinary retention</span>'''
**'''Gross hematuria'''  
*#*<span style="color:#ff0000">'''The patient must be able and willing to return for frequent post-void residual evaluation and able and willing to perform self-catheterization if necessary.'''
**'''UTI'''
*#'''<span style="color:#ff0000">Gross hematuria</span>'''  
**Dry mouth
*#'''<span style="color:#ff0000">UTI</span>'''
**Dysphagia
*#'''<span style="color:#ff0000">Dry mouth</span>'''
**Impaired vision
*#'''<span style="color:#ff0000">Dysphagia</span>'''
**Eyelid weakness
*#'''<span style="color:#ff0000">Impaired vision</span>'''
**Arm weakness
*#'''<span style="color:#ff0000">Eyelid weakness</span>'''
**Leg weakness
*#'''<span style="color:#ff0000">Arm weakness</span>'''
**Torso weakness
*#'''<span style="color:#ff0000">Leg weakness</span>'''
*Technique
*#'''<span style="color:#ff0000">Torso weakness</span>'''
**A randomized trial comparing trigone-including  versus trigone-sparing injections of abobotulinumtoxinA found greater symptom improvement in the trigone-including injected group
*'''Technique'''
*Effects diminish over time for most patients; therefore, patients also should be informed that repeat injections are likely to be necessary to maintain symptom reduction
**'''A randomized trial comparing trigone-including  versus trigone-sparing injections of abobotulinumtoxinA found greater symptom improvement in the trigone-including injected group'''
*'''<span style="color:#ff0000">Effects diminish over time for most patients; therefore, patients also should be informed that repeat injections are likely to be necessary to maintain symptom reduction</span>'''


==== Peripheral tibial nerve stimulation (PTNS) ====
==== Peripheral tibial nerve stimulation (PTNS) ====


* '''May offer peripheral tibial nerve stimulation (PTNS) as third-line treatment in a carefully selected patient population, characterized by moderately severe baseline incontinence and frequency and willingness to comply with the PTNS protocol.'''
* See [https://test.urologyschool.com/index.php/Functional:_Neuromodulation#Posterior_Tibial_Nerve_Stimulation_(PTNS) Posterior Tibial Selective Nerve Stimulation Chapter Notes]
**Patients must also have the resources to make frequent office visits both during the initial treatment phase and to obtain maintenance treatments in order to achieve and maintain treatment effects.  
*'''<span style="color:#ff0000">Indications</span>'''
*Improves OAB symptoms with magnitude to anti-muscarinics, but PTNS has a better adverse event profile.
**'''<span style="color:#ff0000">May offer peripheral tibial nerve stimulation (PTNS) as third-line treatment in a carefully selected patient population, characterized by moderately severe baseline incontinence and frequency and willingness to comply with the PTNS protocol.</span>'''
*Adverse events
***Patients must also have the resources to make frequent office visits both during the initial treatment phase and to obtain maintenance treatments in order to achieve and maintain treatment effects.
**Painful sensation during stimulation that did not interfere with treatment
**'''FDA-approved for OAB treatment'''
**Minor bleeding at the insertion site
*<span style="color:#ff0000">'''Efficacy'''</span>
* '''FDA-approved for OAB treatment'''
**<span style="color:#ff0000">'''Improves OAB symptoms with magnitude to anti-muscarinics, but PTNS has a better adverse event profile.'''</span>
*<span style="color:#ff0000">'''Adverse events (2):'''</span>
*#<span style="color:#ff0000">'''Painful sensation during stimulation'''</span>''' that did not interfere with treatment
*#<span style="color:#ff0000">'''Minor bleeding at the insertion site'''</span>


==== Neuromodulation ====
==== Sacral Neuromodulation ====


* May offer sacral neuromodulation (SNS) as third-line treatment in a carefully selected patient population characterized by severe refractory OAB symptoms or patients who are not candidates for second-line therapy and are willing to undergo a surgical procedure.
* <span style="color:#ff0000">'''May offer sacral neuromodulation (SNS) as third-line treatment in a carefully selected patient population characterized by severe refractory OAB symptoms or patients who are not candidates for second-line therapy and are willing to undergo a surgical procedure.'''</span>
*'''Adverse events'''
*'''<span style="color:#ff0000">Adverse events</span>'''
**'''Pain at the stimulator site'''
*#'''<span style="color:#ff0000">Pain at the stimulator site</span>'''
**'''Pain at the lead site'''
*#'''<span style="color:#ff0000">Pain at the lead site</span>'''
**'''Lead migration'''
*#'''<span style="color:#ff0000">Lead migration</span>'''
**'''Infection/irritation'''
*#'''<span style="color:#ff0000">Infection/irritation</span>'''
**'''Electric shock'''
*#'''<span style="color:#ff0000">Electric shock</span>'''
**'''Need for surgical revision'''
*#'''<span style="color:#ff0000">Need for surgical revision</span>'''
***In most studies, the need for surgical revision occurred in greater than 30% of patients.  
*#*In most studies, the need for surgical revision occurred in greater than 30% of patients.
**'''Difficulty passing through airport metal detectors'''
*#'''<span style="color:#ff0000">Difficulty passing through airport metal detectors</span>'''
**'''Inability to undergo magnetic resonance imaging (MRI)'''
*#'''<span style="color:#ff0000">Inability to undergo magnetic resonance imaging (MRI)</span>'''
**Adverse events more frequent than PTNS
*#<span style="color:#ff0000">'''Adverse events more frequent than PTNS'''</span>
***There is some evidence that newer, less invasive surgical procedures and tined devices may be associated with fewer adverse events
*#*There is some evidence that newer, less invasive surgical procedures and tined devices may be associated with fewer adverse events
*Patients should be counseled that the device requires periodic replacement in a planned surgical procedure and that the length of time between replacements depends on device settings. Patients also must be willing to comply with the treatment protocol because treatment effects typically are only maintained as long as the therapy is maintained and have the cognitive capacity to use the remote control to optimize device function.  
*Patients should be counseled that the device requires periodic replacement in a planned surgical procedure and that the length of time between replacements depends on device settings. Patients also must be willing to comply with the treatment protocol because treatment effects typically are only maintained as long as the therapy is maintained and have the cognitive capacity to use the remote control to optimize device function.  
*
*
=== Augmentation cystoplasty and urinary diversion (fourth-line) ===
=== Augmentation cystoplasty and urinary diversion (fourth-line) ===


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=== Indwelling catheter ===
=== Indwelling catheter ===


* '''Indwelling catheters (including transurethral, suprapubic, etc.) are not recommended as a management strategy for OAB because of the adverse risk/benefit balance except as a last resort in selected patients.'''
* '''<span style="color:#ff0000">Indwelling catheters (including transurethral, suprapubic, etc.) are not recommended as a management strategy for OAB because of the adverse risk/benefit balance except as a last resort in selected patients.</span>'''
**Management with diapering and absorbent garments is always preferred to indwelling catheterization because of the high risk of indwelling catheter-associated UTIs, urethral erosion/destruction and urolithiasis.
**Management with diapering and absorbent garments is always preferred to indwelling catheterization because of the high risk of indwelling catheter-associated UTIs, urethral erosion/destruction and urolithiasis.
**Intermittent catheterization may be an option when concomitant incomplete bladder emptying is present leading to overflow incontinence; however, this approach generally requires either patient willingness and ability or significant caregiver support.  
**Intermittent catheterization may be an option when concomitant incomplete bladder emptying is present leading to overflow incontinence; however, this approach generally requires either patient willingness and ability or significant caregiver support.  
Line 416: Line 460:
== Follow-Up ==
== Follow-Up ==


* Assess compliance, efficacy, side effects and possible alternative treatments.
* '''Assess compliance, efficacy, side effects and possible alternative treatments.'''
**Bladder diaries and validated questionnaires can be helpful to quantify baseline symptom levels and treatment effects so that both the patient and the clinician can assess whether a particular treatment approach is alleviating symptoms and whether the balance between symptom control and adverse events is appropriate for a given patient.
**Bladder diaries and validated questionnaires can be helpful to quantify baseline symptom levels and treatment effects so that both the patient and the clinician can assess whether a particular treatment approach is alleviating symptoms and whether the balance between symptom control and adverse events is appropriate for a given patient.
*Patients who are using incontinence pads, regardless of whether or how they are being treated, should be followed for appropriate skin care and skin integrity.
*'''Patients who are using incontinence pads, regardless of whether or how they are being treated, should be followed for appropriate skin care and skin integrity.'''
 
== Questions ==
 
== Answers ==


== References ==
== References ==

Latest revision as of 14:16, 21 March 2024

See Original Guidelines

See Diagnosis and Treatment Algorithm from Guideline

See 2017 CUA OAB Guideline Notes

See Pharmacological Management of LUTS Chapter Notes

  • This guideline does not apply to patients with symptoms related to neurologic conditions

Definitions[edit | edit source]

  • Urgency: complaint of a sudden, compelling desire to pass urine which is difficult to defer
  • Urgency urinary incontinence: involuntary leakage of urine associated with a sudden compelling desire to void
  • Overactive bladder: Urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence, in the absence of a urinary tract infection (UTI) or other obvious pathology.
  • Nocturia: interruption of sleep one or more times because of the need to void

Epidemiology[edit | edit source]

  • Prevalence
    • Females: 9-43%
    • Males: 7-27%
    • Some studies report higher prevalence rates in females than males, while others found similar rates across genders.
      • Urge urinary incontinence is consistently more common in females than in males
  • OAB symptom prevalence and severity tend to increase with age.

Natural history[edit | edit source]

  • ≈40% of OAB cases remit during a given year, but the majority of patients have symptoms for years.
  • OAB can negatively impact quality of life
    • Carrying out the activities of daily life and engaging in social and occupational activities can be profoundly affected by lack of bladder control and incontinence.
    • Urinary incontinence in particular may have severe psychological and social consequences, resulting in restricted activities and unwillingness to be exposed to environments where access to a bathroom may be difficult.
    • Sexual function and marital satisfaction
  • It is common for patients to have suffered with their symptoms for an extended time before seeking medical advice.

Diagnosis and Evaluation[edit | edit source]

  • Clinical diagnosis
    • OAB symptoms consist of 4 components:
      1. Frequency
      2. Urgency
      3. Urgency incontinence
      4. Nocturia
        • OAB symptoms (frequency, urgency and urgency incontinence) may occur only at night, causing a single symptom of nocturia.
    • When urinary frequency (both daytime and night) and urgency, with or without urgency incontinence, in the absence of UTI or other obvious pathology are self-reported as bothersome, the patient may be diagnosed with OAB

Recommended Investigations[edit | edit source]

Mandatory (2)[edit | edit source]

  1. History and Physical Exam
  2. Urinalysis

Optional (4)[edit | edit source]

  1. Urine culture
  2. Post void residual
  3. Bladder diary
  4. Symptom questionnaire

Not recommended in the initial workup of the uncomplicated patient[edit | edit source]

  1. Urodynamics
  2. Cystoscopy
  3. Diagnostic renal and bladder ultrasound
  • For complicated or refractory patients, the choice of additional diagnostic tests depends on patient history, QoL and clinician judgment. Neurogenic OAB requires specific evaluation.

Mandatory[edit | edit source]

History and Physical Exam[edit | edit source]

History[edit | edit source]
  • Characterize lower urinary tract symptoms (storage and voiding/emptying), including duration of symptoms and baseline symptoms
    • Assess bladder storage symptoms associated with OAB (e.g., urgency, urgency incontinence, frequency, nocturia) and other bladder storage problems (e.g., stress incontinence episodes)
      • Urinary frequency
        • Varies across individuals.
          • In community-dwelling healthy adults, normal frequency consists of voiding every 3-4 hours with a median of approximately 6 voids a day.
          • Traditionally, up to 7 micturition episodes during waking hours has been considered normal, but this number is highly variable based upon hours of sleep, fluid intake, comorbid medical conditions and other factors.
        • Can be reliably measured with a bladder diary.
      • Incontinence
        • Can be measured reliably with a bladder diary and the quantity of urine leakage can be measured with pad tests.
    • Assess bladder emptying (e.g., hesitancy, straining to void, prior history of urinary retention, force of stream, intermittency of stream).
  • Amount and type of fluid intake (e.g., with or without caffeine).
    • Excessive fluid intake can produce voiding patterns that mimic OAB symptoms.
    • Patients who do not appear able to provide accurate intake and voiding information should fill out a fluid diary.
  • Current medications
    • Should be reviewed to ensure that symptoms are not related to medications.
  • Co-morbid conditions
    • Neurologic diseases and other genitourinary conditions should be considered as they directly impact bladder function.
    • Criteria for Complicated OAB
      • Female patient with significant prolapse (i.e., prolapse beyond the introitus)
      • Failed multiple anti-muscarinics to control OAB symptoms
      • Patients with OAB symptoms and co-morbid conditions including
        1. Neurologic diseases (i.e., stroke, multiple sclerosis, spinal cord injury)
        2. Mobility deficits
        3. Medically complicated/uncontrolled diabetes
        4. Fecal motility disorders (fecal incontinence/constipation)
        5. Chronic pelvic pain
        6. History of recurrent urinary tract infections (UTIs)
        7. Gross hematuria
        8. Prior pelvic/vaginal surgeries (incontinence/prolapse surgeries)
        9. Pelvic cancer (bladder, colon, cervix, uterus, prostate)
        10. Pelvic radiation
  • Degree of bother
    • If patient is not significantly bothered by his/her bladder symptoms, then there is a less compelling reason to treat the symptoms.
Physical exam (4)[edit | edit source]
  1. Abdominal exam
    • Assess for scars, masses, hernias and areas of tenderness as well as for suprapubic distension that may indicate urinary retention
  2. Rectal/genitourinary exam
    • To rule out
      • Pelvic floor disorders (e.g., pelvic floor muscle spasticity, pain, pelvic organ prolapse) in females
      • Prostatic pathology in males
    • In menopausal females, atrophic vaginitis should be assessed as a possible contributing factor to incontinence symptoms.
    • Assess for perineal skin for rash or breakdown.
    • Assess perineal sensation, rectal sphincter tone and ability to contract the anal sphincter to
      • Evaluate pelvic floor tone and potential ability to perform pelvic floor exercises (e.g., the ability to contract the levator ani muscles)
      • Rule out impaction and constipation.
  3. Assessment of lower extremities for edema
    • To assess for the potential for fluid shifts during periods of postural changes
  4. Patient’s attire and ability to dress independently (as a surrogate for cognitive function)
    • The ability of the patient to dress independently is informative of sufficient motor skills related to toileting habits. This can provide information on the cognitive function of the patient, which is important to evaluate when considering anticholinergics.
    • A Mini-Mental State Examination (MMSE) should be conducted on all patients who may be at risk for cognitive impairment to determine whether symptoms are aggravated by cognitive problems, to ensure that they will be able to follow directions for behavioral therapy and/or to determine the degree of risk for cognitive decline with anti-muscarinic therapy.

Urinalysis[edit | edit source]

  • To rule out UTI and and evaluate for presence of hematuria
  • If evidence of infection is detected, then a culture should be performed, the infection treated appropriately and symptoms should be reassessed once the infection has cleared.

Optional[edit | edit source]

Urine culture[edit | edit source]

  • Usually not necessary unless indication of infection (i.e., nitrites/leukocyte esterase on dipstick, pyuria/bacteriuria on microscopic exam) is found
  • In some patients with irritative voiding symptoms but without overt signs of infection, a urine culture may be appropriate to completely exclude the presence of clinically significant bacteriuria
    • Urinalysis is unreliable for identification of bacterial counts <100,000CFU/mL.

Post-void Residual[edit | edit source]

  • Measured with an ultrasound bladder scanner immediately after the patient voids.  
    • If an ultrasound scanner is not available, then urethral catheterization may be used to assess PVR.
  • Not necessary for patients who are receiving first-line behavioral interventions or for uncomplicated patients (i.e., patients without a history of or risk factors for urinary retention) receiving antimuscarinic medications.
  • Indications to assess PVR (4)
    1. Neurologic diagnoses
    2. History of incontinence surgery or prostatic surgery
    3. Presence of voiding/obstructive symptoms
      • As there is considerable overlap between storage and emptying voiding symptoms, baseline PVRs should be performed for males with symptoms prior to initiation of anti-muscarinic therapy.
    4. Clinician discretion
  • Anti-muscarinics should be used with caution in patients with PVR 250–300 mL.
  • For any patient on anti-muscarinic therapy, the clinician should be prepared to monitor PVR during the course of treatment should obstructive voiding symptoms appear.

Bladder Diary[edit | edit source]

  • See Urology Care Foundation Link
  • Documents (2)
    1. Intake AND
    2. Voiding behavior
      1. At a minimum, the patient documents (2):
        1. Time of each void
        2. Incontinence episode and the circumstances or reasons for the incontinence episode.
      2. Other useful measures
        • Voided volumes
          • Provide a practical estimate of the patient's functional bladder capacity in daily life and estimate the amount of overall fluid intake.
          • Useful to differentiate between polyuria (characterized by normal or large volume voids) from OAB (characterized by frequent small voids).
        • Rating the degree of urgency associated with each void and incontinence episode
  • May be useful, particularly for patient education and to document baseline symptoms and treatment efficacy              
    • Self-monitoring with a bladder diary for 3-7 days is a useful first step in initiating behavioral treatments for OAB.
      • Usually completed for only 24 to 48 hours due to burden of monitoring

Symptoms questionnaire[edit | edit source]

  • Useful in the quantification of bladder symptoms and bother changes with OAB treatment
  • Options (4)
    1. Urogenital Distress Inventory (UDI)
    2. UDI-6 Short Form
    3. Incontinence Impact Questionnaire (II-Q)
    4. Overactive Bladder Questionnaire (OAB-q)

Differential Diagnosis[edit | edit source]

  1. Polydipsia and polyuria
  2. Nocturia
  3. Interstitial cystitis/bladder pain syndrome
  4. Atrophic vaginitis

Polydipsia and polyuria[edit | edit source]

  • Frequency that is the result of polydipsia and resulting polyuria may mimic OAB
  • Diagnosis and Evaluation
    • Can only be distinguished from OAB with the use of frequency-volume charts.
      • In OAB, urinary frequency is associated with many small volume voids.
      • In polydipsia, urinary frequency is associated with normal or large volume voids and the intake is volume matched. In this case, the frequency is appropriate because of the intake volume and the patient does not have OAB
      • Diabetes insipidus also is associated with frequent, large volume voids and should be distinguished from OAB.
  • Management
    • If polydipsia-related frequency is physiologically self-induced: education and consideration of fluid management
    • If diabetes insipidus: desmopressin

Nocturia[edit | edit source]

  • Often due to factors unrelated to OAB, including excessive nighttime urine production (i.e. nocturnal polyuria) and sleep apnea.
  • Differential of nocturia includes nocturnal polyuria, low nocturnal bladder capacity or both.
    • Nocturnal polyuria
      • Definition: the production of greater than 20 to 33% of total 24 hour urine output during the period of sleep, which is age-dependent with 20% for younger individuals and 33% for elderly individuals.
      • Often associated with sleep disturbances, vascular and/or cardiac disease and other medical conditions
      • Nocturnal voids are frequently normal or large volume as opposed to the small volume voids commonly observed in nocturia associated with OAB.

Interstitial cystitis/bladder pain syndrome[edit | edit source]

  • Clinical presentation of interstitial cystitis/bladder pain syndrome shares the OAB symptoms of urinary frequency and urgency, with or without urgency incontinence
  • Bladder and/or pelvic pain, including dyspareunia, is a crucial component of its presentation in contradistinction to OAB.

Atrophic vaginitis[edit | edit source]

  • In the menopausal female patient, atrophic vaginitis can be a contributing factor to incontinence symptoms.
  • Use of vaginal (but not systemic) estrogen may improve symptoms.

Management[edit | edit source]

General Principles[edit | edit source]

  • Provide education to patients regarding
    • Normal lower urinary tract function
    • What is known about OAB
    • Benefits vs. risks/burdens of the available treatment alternatives
  • Counsel patients that OAB
    • Has a variable and chronic course
    • Most OAB treatments improve patient symptoms but are unlikely to eliminate all symptoms
    • Acceptable symptom control may require trials of multiple therapeutic options before it is achieved, with no single ideal treatment, and treatments vary in invasiveness, risk of AEs and reversibility.
      • OAB may compromise QoL but generally does not affect survival. A treatment plan, therefore, should carefully weigh the patient’s potential benefit of a particular treatment against that treatment’s risk for, severity and reversibility of AEs.
      • Treatment failure occurs when the patient with reasonable expectations does not have the anticipated symptom improvement or is unable to tolerate the treatment due to AEs; lack of efficacy and the presence of intolerable AEs reduce compliance
  • New treatments should persist for a sufficient duration to achieve (4 to 8 weeks for medications and 8 to 12 weeks for behavioral therapies) clarity regarding efficacy and adverse events for a particular therapy before abandoning the therapy prematurely or before adding a second therapy.
    • If a comprehensive evaluation has demonstrated that the patient has signs and symptoms consistent with the OAB diagnosis and a particular therapy is not efficacious after a reasonable trial, then an alternative therapy should be tried.

Options[edit | edit source]

  1. Observation
  2. Behavioral therapies (first-line)
  3. Pharmacologic management (second-line)
  4. Intradetrusor onabotulinumtoxinA or neuromodulation (PTNS, SNS) (third-line)
  5. Augmentation cystoplasty, cystectomy (fourth-line)
  6. Indwelling catheter (fifth-line, not recommended except as a last resort)
  • Every patient does not need to proceed through each line of therapy before considering the next
    • PTNS can be considered in drug-naïve patients who opt to forego pharmacotherapy.

Observation[edit | edit source]

  • After assessment has been performed to exclude conditions requiring treatment and counseling, no treatment is an acceptable choice made by some patients and caregivers.
    • OAB is not a disease; it is a symptom complex that generally is not a life-threatening condition.
    • Initiating treatment for OAB generally presumes that the patient can perceive an improvement in his or her QOL.
      • In patients who cannot perceive symptom improvements (e.g., in the very elderly or demented patient), treatment may not be appropriate, may be potentially unsafe or may be futile
      • In certain patients for whom hygiene and risk for skin breakdown are major concerns for a significant health risk, treatment may be considered regardless of the patient's perceptions when it is in the patient's best interests.
        • In these patients, behavioral strategies that include prompted voiding and fluid management may be helpful.
        • Pharmacologic treatments and invasive treatments, however, are generally not appropriate for these individuals.

Behavioral Therapies (first-line)[edit | edit source]

  • A group of risk-free tailorable therapies, which improve individual symptoms by changing patient behavior or the patient’s environment.
  • Approaches (2):
    1. Changing voiding habits, such as with bladder training and delayed voiding
    2. Behavioral training, including self-monitoring (bladder diary), scheduled voiding, delayed voiding, double voiding, pelvic floor muscle training, and exercise (including pelvic floor relaxation), active use of pelvic floor muscles for urethral occlusion and urge suppression (urge strategies), urge control techniques (distraction, self-assertions), normal voiding techniques, biofeedback, electrical stimulation, fluid management, caffeine reduction, dietary changes (avoiding bladder irritants), weight loss and other life style changes
      • 25% reduction in fluid intake reduces frequency and urgency
      • Weight loss may improve incontinence specifically
      • Behavioral therapies are most often implemented by advance practice nurses (e.g., continence nurses) or physical therapists with training in pelvic floor therapy.
      • No single component of behavioral therapy appears to be essential to efficacy, and no single type of behavioral therapy appears to be superior in efficacy
  • Should be offered to all patients
    • First-line treatments because they are
      1. Relatively non-invasive
      2. Associated with virtually no adverse events
      3. As effective in reducing symptom levels as are antimuscarinic medications.
        • Randomized trials indicates that behavioral treatments are generally either equivalent to or superior to medications in terms of reducing incontinence episodes, improving frequency and nocturia and improving QoL.
    • Behavioral therapies require an investment of time and effort by the patient to achieve maximum benefits and may require sustained and regular contact with the clinician to maintain regimen adherence and consequent efficacy.
    • While most patients do not experience complete symptom relief, most patients experience significant reductions in symptoms and improvements in QoL.
  • May be combined with pharmacologic management.
  • In patients who are unwilling or unable to comply with behavioral therapy regimens and instructions, it is appropriate to move to second-line pharmacologic therapies.

Second-line: Pharmacologic Management[edit | edit source]

Options[edit | edit source]

  • Recommended
    • Oral anti-cholinergic
    • Oral β3-adrenoceptor agonists
  • May be offered
    • Transdermal oxybutynin (patch or gel)
  • Consider beginning with the lowest possible dose and titrate slowly while carefully assessing for the balance between symptom control and AEs.
    • In older patients who may metabolize drugs differently, it is advisable to start with a minimal dose and titrate as tolerated.
    • Optimizing medication tolerability is critical to obtaining patient compliance in the treatment of this chronic condition.
  • Compliance with a once daily dosing is greater than with medications taken more than once a day.

Anti-cholinergics[edit | edit source]

Options[edit | edit source]
  1. Oral
    1. Oxybutynin
    2. Tolterodine
    3. Fesoterodine
    4. Darifenacin
    5. Solifenacin
    6. Trospium
  2. Transdermal oxybutynin (patch or gel)
Efficacy[edit | edit source]
  • Similar efficacy observed for all oral anti-cholinergic medications
    • Choice of medication is patient dependent
    • Adverse event profiles for dry mouth and constipation vary with medications
  • Patients with more severe symptoms, on average, experience greater symptom reductions.
    • Only patients with relatively low baseline symptom levels are likely to experience complete symptom relief
Contraindications[edit | edit source]
  1. Narrow angle glaucoma (unless approved by the treating ophthalmologist)
  2. Dementia
    • Anti-cholinergics may be contraindicated entirely depending on the level of cognitive impairment.
  3. Impaired gastric emptying
    • Prior to initiation of anti-cholinergics, a patient at risk for gastric emptying problems should receive clearance from a gastroenterologist
  4. Use of solid oral forms of potassium chloride
    • Reduced gastric emptying potentially caused by the anti-cholinergics may increase the potassium absorption of these agents.
    • Anti-cholinergic therapy may be used with caution with alternative forms of potassium chloride.
  5. History of urinary retention
    1. Prior to initiation of anti-cholinergics, a patient with history of urinary retention should receive clearance from a urologist.
      • A PVR may be useful in any patient suspected of a higher risk of urinary retention.
  6. Use caution in prescribing anti-cholinergics in patients who are already using other medications with anti-cholinergic properties.
    • Medications with anti-cholinergic properties include (3)
      1. Tricyclic antidepressants
      2. Medications for Parkinsonism, other extra-pyramidal diseases and Alzheimer’s disease (benzotropine, biperiden HCl, galantamine, rivastigmine and trihexyphenidyl HCl)
      3. Acetylcholinesterase inhibitors (donepezil)
    • Certain anti-nausea medications and those with atropine-like properties may also potentiate adverse events.
      • Examples include trimethaphan, methscopolamine bromide and ipratropium
  7. Use caution in prescribing anti-cholinergics or β3-adrenoceptor agonists in the frail OAB patient.
    • Frail patients are defined as patients with mobility deficits (i.e., require support to walk, have slow gait speed, have difficulty rising from sitting to standing without assistance), weight loss and weakness without medical cause and who may have cognitive deficits
    • OAB medication trials generally are not conducted in the frail elderly, resulting in a lack of efficacy and AE data in this group.
      • Additional AEs are reported in this group, including impaired thermoregulation with dangerous core temperature elevation.
    • Polypharmacy is common in frail community-dwelling patients, placing them at higher risk for AEs, including impaired cognition.
Adverse events (9)[edit | edit source]
  1. Dry mouth (20-40%)
  2. Constipation (7-9%)
  3. Dry or itchy eyes
  4. Blurred vision
  5. Dyspepsia
  6. UTI
  7. Urinary retention
  8. Impaired cognitive function
  9. Arrhythmias (rare)
  • Dry mouth
    • Dry mouth rates for oxybutynin (61%) significantly higher than tolterodine (24%)
    • If an immediate release (IR) and an extended release (ER) formulation are available, then ER formulations should preferentially be prescribed over IR formulations because of lower rates of dry mouth.
      • ER formulations of oxybutynin and tolterodine result in significantly fewer patient reports of dry mouth than the IR formulations of either medication.
      • Compliance with a once-daily treatment has been shown to be greater than with medications that are taken more than once a day
    • Management
      • Can be mitigated with (4):
        1. Oral lubricants
        2. Small sips of water
        3. Sucking on sugar-free hard candies and chewing sugar-free gum
        4. Avoiding mouthwashes with alcohol
      • Transdermal preparations of oxybutynin may be offered instead of oral anti-muscarinics to patients who are at risk of or who have experienced dry mouth with oral agents
        • The use of transdermal anti-muscarinics should be monitored to ensure that the skin where the medication is applied remains intact.
  • Constipation
    • Can be mitigated with
      • Adequate dietary fiber and fluid
      • Psyllium-based fiber supplements
      • Regular exercise and normal bowel habits.
    • Constipation rate significantly higher for darifenacin (17%) and oxybutynin (12%), compared to tolterodine (5%)
  • Constipation and dry mouth should be managed before abandoning effective anti-cholinergic therapy.
    • Management may include bowel management, fluid management, dose modification or alternative anti-cholinergics.
  • Cognitive impairment
    • Patients may not recognize that memory deterioration has occurred, making it essential for the clinician, family members and caregivers to monitor for these effects
    • While newer agents (eg, darifenacin) are reported to be less likely to produce cognitive deficits in elderly patients, the literature is limited; the two-week drug administration period in these studies is not long enough to yield definitive conclusions.

β 3-adrenoceptor agonists: Mirabegron[edit | edit source]

  • Similar efficacy profile to the anti-muscarinics and a relatively lower adverse event profile.
    • Lower incidence of bothersome adverse events may inform the selection of medications for patients who already present with dry mouth (e.g., secondary to Sjogren's syndrome) and/or constipation or for patients who experience efficacy from the anti-muscarinics but cannot tolerate these adverse events.
Efficacy[edit | edit source]
  • Significant symptom reductions for voids per day and incontinence episodes per day
  • Improvements in UUI, urgency episodes, and QOL measures also occur but were not as consistently statistically significant.
  • Among studies with an active control group administered tolterodine ER 4 mg/daily, mirabegron generally performed similarly to tolterodine. Higher doses of mirabegron did not produce greater effects.
Adverse events[edit | edit source]
  1. Increased heart rate
  2. Increased blood pressure
    • Changes in blood pressure and pulse rate are usually minor
  3. Constipation
    • May produce lower/similar rates of constipation than some of the anti-muscarinics, except for solifenacin (5 mg and 10 mg), fesoterodine (8 mg) and trospium (60 mg), all of which had a higher risk of constipation.

Failure of medical therapy[edit | edit source]

  • If a patient experiences inadequate symptom control and/or unacceptable adverse drug events with one anti-muscarinic medication, then a dose modification or a different anti-muscarinic medication or a β3-adrenoceptor agonist may be tried.
    • Patients who had prior unsatisfactory symptom control and/or unacceptable adverse events with older medications (tolterodine or oxybutynin) reported better efficacy and/or more acceptable adverse event profiles with new medications (fesoterodine, solifenacin or darifenacin).
    • Non-responders to anti-muscarinics should be tried on at least one other anti-muscarinic or mirabegron and/or dose modification attempted to determine if a better balance between efficacy and adverse events occurs.
      • Failure and/or the experience of adverse events with one medication should usually be addressed by trying at least one other medication before third-line therapies are considered.
    • If adverse events are severe enough to compromise patient QOL, then strategies to manage specific adverse events, such as ameliorating constipation with appropriate bowel management, should be implemented before abandoning anti-muscarinic treatment.
  • Clinicians may consider combination therapy with an anti-muscarinic and β3-adrenoceptor agonist for patients refractory to monotherapy with either anti-muscarinics or β3-adrenoceptor agonists.
    • Studies have demonstrated improved efficacy with combination therapy without any significant effect on the safety profile when compared to monotherapy
    • Combination therapeutic approaches should be assembled methodically, beginning with the establishment of confidence in the partial efficacy of one therapy, continuing with an adequate trial of any additional therapies one at a time until the patient experiences adequate symptom control in the context of tolerable adverse events.
  • Patients who are refractory to behavioral and medical therapy should be evaluated by an appropriate specialist if they desire additional
    • The refractory patient as the patient who has failed a trial of symptom-appropriate behavioral therapy of sufficient length to evaluate potential efficacy and who has failed a trial of at least one anti-muscarinic medication administered for 4 to 8 weeks. Failure of an anti-muscarinic medication may include lack of efficacy and/or inability to tolerate adverse drug effects.

Third-line[edit | edit source]

Options (3):[edit | edit source]

  1. Intradetrusor onabotulinumtoxinA
  2. Peripheral tibial nerve stimulation (PTNS)
  3. Sacral neuromodulation
  • Before a patient is exposed to third-line therapies with increased risk compared to behavioral or medical therapy, the patient’s realistic desire for further treatment should be ascertained, and a comprehensive evaluation should be conducted to confirm the diagnosis of OAB and not another disease process
  • Neuromodulation or onabotulinumtoxinA therapy may be offered to the carefully selected patient who has failed behavioral and anti-muscarinic therapy or who is not a candidate for these therapies and continues to have bothersome symptoms after appropriate counseling.

OnabotulinumtoxinA[edit | edit source]

  • Intradetrusor onabotulinumtoxinA (100U) may be offered as third-line treatment in the carefully-selected and thoroughly-counseled patient who has been refractory to first- and second-line OAB treatments.
    • Considered a treatment STANDARD in patients with moderate to severe OAB symptoms
  • Dosing: FDA-approved dose of 200U for neurogenic OAB§§
    • Not FDA-approved in non-neurogenic OAB patients, 100U typically used
  • Adverse events
    1. Urinary retention
      • The patient must be able and willing to return for frequent post-void residual evaluation and able and willing to perform self-catheterization if necessary.
    2. Gross hematuria
    3. UTI
    4. Dry mouth
    5. Dysphagia
    6. Impaired vision
    7. Eyelid weakness
    8. Arm weakness
    9. Leg weakness
    10. Torso weakness
  • Technique
    • A randomized trial comparing trigone-including  versus trigone-sparing injections of abobotulinumtoxinA found greater symptom improvement in the trigone-including injected group
  • Effects diminish over time for most patients; therefore, patients also should be informed that repeat injections are likely to be necessary to maintain symptom reduction

Peripheral tibial nerve stimulation (PTNS)[edit | edit source]

  • See Posterior Tibial Selective Nerve Stimulation Chapter Notes
  • Indications
    • May offer peripheral tibial nerve stimulation (PTNS) as third-line treatment in a carefully selected patient population, characterized by moderately severe baseline incontinence and frequency and willingness to comply with the PTNS protocol.
      • Patients must also have the resources to make frequent office visits both during the initial treatment phase and to obtain maintenance treatments in order to achieve and maintain treatment effects.
    • FDA-approved for OAB treatment
  • Efficacy
    • Improves OAB symptoms with magnitude to anti-muscarinics, but PTNS has a better adverse event profile.
  • Adverse events (2):
    1. Painful sensation during stimulation that did not interfere with treatment
    2. Minor bleeding at the insertion site

Sacral Neuromodulation[edit | edit source]

  • May offer sacral neuromodulation (SNS) as third-line treatment in a carefully selected patient population characterized by severe refractory OAB symptoms or patients who are not candidates for second-line therapy and are willing to undergo a surgical procedure.
  • Adverse events
    1. Pain at the stimulator site
    2. Pain at the lead site
    3. Lead migration
    4. Infection/irritation
    5. Electric shock
    6. Need for surgical revision
      • In most studies, the need for surgical revision occurred in greater than 30% of patients.
    7. Difficulty passing through airport metal detectors
    8. Inability to undergo magnetic resonance imaging (MRI)
    9. Adverse events more frequent than PTNS
      • There is some evidence that newer, less invasive surgical procedures and tined devices may be associated with fewer adverse events
  • Patients should be counseled that the device requires periodic replacement in a planned surgical procedure and that the length of time between replacements depends on device settings. Patients also must be willing to comply with the treatment protocol because treatment effects typically are only maintained as long as the therapy is maintained and have the cognitive capacity to use the remote control to optimize device function.

Augmentation cystoplasty and urinary diversion (fourth-line)[edit | edit source]

  • In rare cases, augmentation cystoplasty or urinary diversion for severe, refractory, complicated OAB patients may be considered.
  • Substantial risks to these procedures including the likely need for long-term intermittent self-catheterization and the risk of malignancy

Indwelling catheter[edit | edit source]

  • Indwelling catheters (including transurethral, suprapubic, etc.) are not recommended as a management strategy for OAB because of the adverse risk/benefit balance except as a last resort in selected patients.
    • Management with diapering and absorbent garments is always preferred to indwelling catheterization because of the high risk of indwelling catheter-associated UTIs, urethral erosion/destruction and urolithiasis.
    • Intermittent catheterization may be an option when concomitant incomplete bladder emptying is present leading to overflow incontinence; however, this approach generally requires either patient willingness and ability or significant caregiver support.
    • As a last resort, an indwelling catheter may be considered when urinary incontinence has resulted in the development and progression of decubiti, during the management of those decubiti, or rarely, where urinary incontinence is the predominant disability affecting activities of daily living and therefore may result in institutionalization.

Follow-Up[edit | edit source]

  • Assess compliance, efficacy, side effects and possible alternative treatments.
    • Bladder diaries and validated questionnaires can be helpful to quantify baseline symptom levels and treatment effects so that both the patient and the clinician can assess whether a particular treatment approach is alleviating symptoms and whether the balance between symptom control and adverse events is appropriate for a given patient.
  • Patients who are using incontinence pads, regardless of whether or how they are being treated, should be followed for appropriate skin care and skin integrity.

Questions[edit | edit source]

Answers[edit | edit source]

References[edit | edit source]