Editing AUA: Overactive Bladder (2019) (section)

== Management ==

=== General Principles ===
* '''Provide education to patients regarding''' 
**'''Normal lower urinary tract function''' 
**'''What is known about OAB''' 
**'''Benefits vs. risks/burdens of the available treatment alternatives''' 
*'''<span style="color:#ff0000">Counsel patients that OAB</span>''' 
**'''<span style="color:#ff0000">Has a variable and chronic course</span>'''  
**'''<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 ===
# '''<span style="color:#ff0000">Observation</span>'''
# '''<span style="color:#ff0000">Behavioral therapies (first-line)</span>'''
# '''<span style="color:#ff0000">Pharmacologic management (second-line)</span>'''
# '''<span style="color:#ff0000">Intradetrusor onabotulinumtoxinA or neuromodulation (PTNS, SNS) (third-line)</span>'''
#'''<span style="color:#ff0000">Augmentation cystoplasty, cystectomy (fourth-line)</span>'''
#'''<span style="color:#ff0000">Indwelling catheter (fifth-line, not recommended except as a last resort)</span>'''
*'''<span style="color:#ff0000">Every patient does not need to proceed through each line of therapy before considering the next</span>'''
**'''<span style="color:#ff0000">PTNS can be considered in drug-naïve patients who opt to forego pharmacotherapy.</span>'''

=== Observation ===

* '''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) ===

* A group of risk-free tailorable therapies, which improve individual symptoms by changing patient behavior or the patient’s environment.
*'''<span style="color:#ff0000">Approaches (2):</span>'''
*# '''<span style="color:#ff0000">Changing voiding habits</span>, such as with bladder training and delayed voiding'''
*# '''<span style="color:#ff0000">Behavioral training</span>''', 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
*'''<span style="color:#ff0000">Should be offered to all patients</span>'''
**'''First-line treatments because they are''' 
**#'''Relatively non-invasive'''
**#'''Associated with virtually no adverse events'''
**#'''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 ===

==== Options ====

* '''<span style="color:#ff0000">Recommended</span>'''
** '''<span style="color:#ff0000">Oral anti-cholinergic</span>'''
** '''<span style="color:#ff0000">Oral β3-adrenoceptor agonists</span>'''
* '''<span style="color:#ff0000">May be offered</span>'''
** '''<span style="color:#ff0000">Transdermal oxybutynin (patch or gel)</span>'''
*'''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 ====

===== Options =====
# '''<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">Solifenacin</span>'''
## '''<span style="color:#ff0000">Trospium</span>'''
#'''<span style="color:#ff0000">Transdermal oxybutynin (patch or gel)</span>'''

===== Efficacy =====
*'''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 =====
#'''<span style="color:#ff0000">Narrow angle glaucoma</span>''' (unless approved by the treating ophthalmologist)
#'''<span style="color:#ff0000">Dementia</span>'''
#*Anti-cholinergics may be contraindicated entirely depending on the level of cognitive impairment.
#'''<span style="color:#ff0000">Impaired gastric emptying</span>'''
#*Prior to initiation of anti-cholinergics, a patient at risk for gastric emptying problems should receive clearance from a gastroenterologist
#'''<span style="color:#ff0000">Use of solid oral forms of potassium chloride</span>'''
#*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.
#'''<span style="color:#ff0000">History of urinary retention</span>'''
##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.
#'''<span style="color:#ff0000">Use caution in prescribing anti-cholinergics in patients who are already using''' '''other medications with anti-cholinergic properties.</span>'''
#* '''<span style="color:#ff0000">Medications with anti-cholinergic properties include (3)</span>'''
#*#'''<span style="color:#ff0000">Tricyclic antidepressants</span>'''
#*#'''<span style="color:#ff0000">Medications for Parkinsonism, other extra-pyramidal diseases and Alzheimer’s disease</span>''' (benzotropine, biperiden HCl, galantamine, rivastigmine and trihexyphenidyl HCl)
#*#'''<span style="color:#ff0000">Acetylcholinesterase inhibitors (donepezil)</span>'''
#*'''Certain anti-nausea medications and those with atropine-like properties may also potentiate adverse events.'''
#**Examples include trimethaphan, methscopolamine bromide and ipratropium
#'''<span style="color:#ff0000">Use caution in prescribing anti-cholinergics or β3-adrenoceptor agonists in the frail OAB patient.</span>'''
#* '''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) =====
#'''<span style="color:#ff0000">Dry mouth (20-40%)</span>'''
#'''<span style="color:#ff0000">Constipation (7-9%)</span>'''
#'''<span style="color:#ff0000">Dry or itchy eyes</span>'''
#'''<span style="color:#ff0000">Blurred vision</span>'''
#'''<span style="color:#ff0000">Dyspepsia</span>'''
#'''<span style="color:#ff0000">UTI</span>'''
#'''<span style="color:#ff0000">Urinary retention</span>'''
#'''<span style="color:#ff0000">Impaired cognitive function</span>'''
#'''<span style="color:#ff0000">Arrhythmias (rare)</span>'''
*'''<span style="color:#ff0000">Dry mouth</span>'''
**<span style="color:#ff0000">'''Dry mouth rates for oxybutynin (61%) significantly higher''' </span>than tolterodine (24%)
**'''<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>'''
*** 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
**<span style="color:#ff0000">'''Management'''</span>
***<span style="color:#ff0000">'''Can be mitigated with (4):'''</span>
***#<span style="color:#ff0000">'''Oral lubricants'''</span>
***#<span style="color:#ff0000">'''Small sips of water'''</span>
***#<span style="color:#ff0000">'''Sucking on sugar-free hard candies and chewing sugar-free gum'''</span>
***#<span style="color:#ff0000">'''Avoiding mouthwashes with alcohol'''</span>
***<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>
****<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
**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 ====
*<span style="color:#ff0000">'''Similar efficacy profile to the anti-muscarinics and a relatively lower adverse event profile.'''</span>
**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 =====
*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 =====

#<span style="color:#ff0000">'''Increased heart rate'''</span>
#<span style="color:#ff0000">'''Increased blood pressure'''</span>
#*Changes in blood pressure and pulse rate are usually minor
#<span style="color:#ff0000">'''Constipation'''</span>
#*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 ====
*'''<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>'''
**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.
*'''<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
**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 ===

==== 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

* 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 ====
* '''<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>'''
**'''<span style="color:#ff0000">Considered a treatment STANDARD in patients with moderate to severe OAB symptoms</span>'''
*'''<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/ §]'''
**'''<span style="color:#ff0000">Not FDA-approved in non-neurogenic OAB patients, 100U typically used</span>'''
*'''<span style="color:#ff0000">Adverse events</span>'''
*#'''<span style="color:#ff0000">Urinary retention</span>'''
*#*<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.'''
*#'''<span style="color:#ff0000">Gross hematuria</span>''' 
*#'''<span style="color:#ff0000">UTI</span>'''
*#'''<span style="color:#ff0000">Dry mouth</span>'''
*#'''<span style="color:#ff0000">Dysphagia</span>'''
*#'''<span style="color:#ff0000">Impaired vision</span>'''
*#'''<span style="color:#ff0000">Eyelid weakness</span>'''
*#'''<span style="color:#ff0000">Arm weakness</span>'''
*#'''<span style="color:#ff0000">Leg weakness</span>'''
*#'''<span style="color:#ff0000">Torso weakness</span>'''
*'''Technique'''
**'''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) ====

* See [https://test.urologyschool.com/index.php/Functional:_Neuromodulation#Posterior_Tibial_Nerve_Stimulation_(PTNS) Posterior Tibial Selective Nerve Stimulation Chapter Notes]
*'''<span style="color:#ff0000">Indications</span>'''
**'''<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>'''
***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'''
*<span style="color:#ff0000">'''Efficacy'''</span>
**<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>

==== Sacral Neuromodulation ====

* <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>
*'''<span style="color:#ff0000">Adverse events</span>'''
*#'''<span style="color:#ff0000">Pain at the stimulator site</span>'''
*#'''<span style="color:#ff0000">Pain at the lead site</span>'''
*#'''<span style="color:#ff0000">Lead migration</span>'''
*#'''<span style="color:#ff0000">Infection/irritation</span>'''
*#'''<span style="color:#ff0000">Electric shock</span>'''
*#'''<span style="color:#ff0000">Need for surgical revision</span>'''
*#*In most studies, the need for surgical revision occurred in greater than 30% of patients.
*#'''<span style="color:#ff0000">Difficulty passing through airport metal detectors</span>'''
*#'''<span style="color:#ff0000">Inability to undergo magnetic resonance imaging (MRI)</span>'''
*#<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
*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) ===

* 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 ===

* '''<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.
**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.