Editing CUA: Overactive Bladder (2017) (section)

== Management of OAB ==

* '''First-line (3): lifestyle changes, behavioural therapies, patient education'''
*# '''Lifestyle changes'''
*#* '''Modifications of fluids/caffeine intake, weight control, dietary modifications, management of bowel regularity, smoking cessation, and optimization of other comorbidities (i.e., diabetes, CHF, OSA)'''
*#** Smoking cessation is a recommendation even though a Cochrane review described the effect of nicotine on OAB as uncertain
*#* '''Restricting fluid intake 2‒4 hours before bedtime, or after 6 pm decreases nocturia and nighttime incontinence'''
*# '''Behavioural therapies'''
*#* '''Bladder training''' includes the use of bladder diaries, bladder control strategies, timed voiding, prompted or scheduled voiding, or delayed voiding. These are all used to alter patient voiding patterns.
*#** Rapid short pelvic contractions (termed, "quick flicks") have been shown to decrease bladder overactivity and urinary urgency.
*#* '''Pelvic floor muscle therapy''' may also include urgency suppression, control strategies, and biofeedback
*# '''Patient education'''
*#* Education empowers patients to engage and participate in their treatment.

* '''Second-line (3): oral antimuscarinics, transdermal oxybutynin or oral beta-3 adrenoceptor agonist'''
** '''Antimuscarinics (AM)'''
*** '''See Table 2 from Original Guideline'''
*** '''Mechanism of action'''
**** Antagonistic action on muscarinic receptors throughout the body
***** In the bladder, '''blocks the M2 and M3 receptors in the bladder and urothelium. M2 receptors predominate, but M3 receptors mediate cholinergic contractions.'''
**** '''Reduces involuntary detrusor contraction and reduces sensory afferent signalling'''
*** '''Available agents'''
**** '''7 AM agents are available for OAB in Canada (daily dosing described):'''
****# '''Oxybutynin [Ditropan] (immediate release [IR], extended release [ER], transdermal)''' ER: 5 or 10 mg
****# '''Tolterodine (IR, ER) [Detrol, Detrol LA]''' ER 2mg or 4mg
****# '''Darifenacin [Enablex] 7.5 or 15mg'''
****# '''Trospium (IR) [Trosec]'''
****# '''Solifenacin [Vesicare] 5 or 10mg'''
****# '''Propiverine [Mictoryl]''' 30 or 45mg
****# '''Fesoterodine [Toviaz] 4 or 8mg'''
**** Tolterodine has similar efficacy vs. oxybutynin but with less adverse events. ER preparations of oxybutynin or tolterodine provided similar improvement, while having less risk of dry mouth compared to IR. '''Immediate release formulations of AMs should be avoided if other formulations are available.'''
**** Transdermal oxybutynin and tolterodine-ER had similar rates of dry mouth, but the transdermal patch was associated with a higher withdrawal rate due to skin reactions. Therefore, tolterodine [Detrol]-ER would be a first choice compared to other formulations of tolterodine and oxybutynin.
**** The highest of the two doses for both solifenacin and fesoterodine (10 mg and 8 mg, respectively) had better clinical efficacy, but with higher rates of dry mouth. Fesoterodine had favourable clinical outcomes compared to tolterodine-ER, but higher rates of withdrawal due to adverse events and risk of dry mouth.
**** '''The overall adverse event profile is comparable for darifenacin, fesoterodine, transdermal oxybutynin, propiverine, solifenacin, tolterodine, and trospium. However oral oxybutynin, in doses of or exceeding 10 mg/day was associated with the worst adverse event profile'''
*** '''Adverse events'''
**** '''The most commonly adverse events reported groups are gastrointestinal, followed by neurological, ocular, and renal/genitourinary'''
**** '''The most common adverse events are (4):'''
****# '''Dry mouth'''
****# '''Pruritis'''
****# '''Constipation'''
****# '''CNS effects'''
**** '''Combining different AMs has limited clinical improvement with much higher adverse events'''
**** '''Anticholinergic burden has been linked to cognitive dysfunction''' but also with increased mortality and cardiovascular risk
*** '''Contraindications'''
***# '''Uncontrolled narrow-angle glaucoma'''
***#* Can induce or precipitate acute angle-closure glaucoma due to their antagonistic actions on M3 and M5 receptors in the eye
***# '''Functional GI obstruction'''
***# '''Myasthenia gravis'''
*** '''All require dose adjustment in hepatic or renal impairment, except oxybutynin'''
*** '''Tolterodine, darifenacin, tropsium, and solifenacin require dose adjustment with concomitant CYP3A4 inhibitors'''
*** '''Tolterodine most likely associated with QT prolongation'''
*** '''The potential of AM agents to improve OAB symptoms may not be fully realized for a period of 12 weeks, whereas side effects may present earlier''' with varying degrees of severity
** '''Beta-3 adrenoreceptor agonist'''
*** '''Mechanism of action:'''
**** '''Activates beta-3 adrenoceptors'''
**** '''Increases bladder relaxation, improving bladder filling and storage of urine'''
*** '''Available agents'''
**** Mirabegron is the only approved beta-3 adrenoceptor agonist in Canada for the treatment of OAB
**** '''A starting dose of 25 mg and increasing to 50 mg, if needed, is recommended. The lowest dose is also recommended for renal and hepatic impairment'''
*** '''Efficacy'''
**** '''Similar efficacy in patients who were AM-naïve and those with prior use of AM'''
*** '''Adverse events:'''
**** '''The most common adverse events (3):'''
****# '''Hypertension'''
****# '''Nasopharyngitis'''
****# '''UTI'''
***** '''Headache and back pain also occurred in the one-year study.'''
*** '''Contraindications (2):'''
***# '''Pregnancy'''
***# '''Severe uncontrolled hypertension'''
*** '''Mirabegron vs. AMs'''
**** '''Mirabegron 50 mg had a similar efficacy in decreasing the number of frequency, UUI episodes, and overall incontinence episodes, compared to all AM except for solifenacin.'''
***** Only solifenacin 10 mg had a higher efficacy than mirabegron 50 mg in the improvement of frequency and UUI episodes.
***** Mirabegron 50 mg had a similar rate of dry mouth and constipation compared to placebo. For dry mouth, all other AMs had higher rates than mirabegron 50 mg; for constipation, darifenacin 15 mg, fesoterodine 8 mg, solifenacin 5 mg, solifenacin 10 mg, and trospium 60 mg had higher rates than mirabegron 50 mg.
**** Although there is no direct comparison, '''mirabegron appears to have similar clinical effectiveness compared to most AMs, but has a different side-effect profile'''
** '''Prescribing second-line treatment'''
*** The adverse event profile and possible contraindications should be considered when prescribing the drug of choice as second-line treatment.
*** '''The lowest recommended dose should first be prescribed''', '''followed by dose increases in order to obtain the best clinical improvement while monitoring for adverse events.'''
*** '''If the initial selected drug is not tolerated or does not provide adequate symptom relief, patients should be offered an alternative medication, preferably with a different mechanism of action.'''
*** '''Patients who remain incontinent after the initial treatment with an AM could be offered combination treatment with solifenacin and mirabegron'''
*** '''UrologySchool.com takeaway: start with 50mg mirabegron. If not effective, solifenacin 5mg then 10mg. If still ineffective, consider combination solifenacin and mirabegron'''

** '''Age-related changes in pharmacology'''
*** '''See Table 3 from Original Guideline'''
***The age-related changes in pharmacology suggest that '''some UI drugs may be effective at lower than standard doses in frail older persons with concomitant decreased adverse effects'''
*** '''Immediate-release oxybutynin may be associated with cognitive impairment'''

* AMs for treatment of OAB remain as potentially inappropriate medications for frail older people
* '''Cholinesterase inhibitors treatment is associated with either precipitation or worsening of OAB symptoms. Although intuitively illogical, given the opposing pharmacological actions, there seems to be no reason not to use bladder AMs for older people with dementia, ensuring that the cholinesterase inhibitors is warranted and effective, that the incontinence is sufficiently bothersome to warrant treatment, and that the patient (where possible) and the caregiver are fully informed.'''

* '''Third-line treatments (3): Botox, PTNS, SNM'''
** '''Onabotulinum toxin A'''
*** '''Mechanism of action'''
**** '''Inhibits acetylcholine (ACh) release at the presynaptic neuromuscular junction. Inhibited ACh release results in regionally decreased muscle contractility and atrophy at the injection site'''
*** '''Intradetrusor onabotulinum toxinA 100U''' is an effective, safe, and long-term treatment option for OAB with UUI refractory to second-line OAB pharmacotherapies
**** '''Doses of onabotulinumtoxinA should not exceed 360U every 12 weeks'''
**** '''200U is recommended in neurogenic overactivity'''
*** '''Efficacy'''
**** '''Clinical effects begin within 5-7 days of injection, with maximal effects reached within 4-6 weeks'''
**** '''Median duration of effect: 7.6 months'''
*** '''Adverse events'''
**** '''Most common adverse events'''
****# '''UTI'''
****# '''Dysuria''' (12%)
****# '''Bacteriuria''' (5%)
****# '''Urinary retention (5%)'''
****# '''Transient weakness'''
**** Rate of discontinuation due to lack of efficacy or adverse events was 5.7% and 5.1%, respectively.
*** Long-term treatment with onabotulinumtoxinA is well-tolerated, with no evidence of increasing occurrence of adverse events with repeat treatments.
*** '''Patients must be carefully counselled regarding the:'''
***# '''Need for close follow-up; patients must be followed closely after initial treatment, with assessment of PVR for the possibility of acute urinary retention and need for catheterization'''.
***# '''Possible need for catheterization (indwelling or CIC)'''
***# '''Likelihood of repeat injections to maintain symptom improvement'''
*** '''If deemed effective and safe, a repeat injection can be offered at 6 months and adjusted according to individual response'''
** '''Peripheral tibial nerve stimulation and sacral neuromodulation'''
*** '''Treatment effect of PTNS is similar compared to AMs, but with a more tolerable side effect profile'''
*** '''The treatment effects duration for SNM responders is similar to the pattern of PTNS in that maintenance of symptom improvement occurs only with continued use of the intervention'''.
*** Separating SNM from PTNS and onabotulinumtoxinA injections is the different adverse event profile, including the '''need for surgical re-intervention in up to 40% of patients''', with up to 1/3 of patients in the majority of studies requiring revision. SNM was also complicated by pain at the stimulator site (3.3‒19.8%), pain at the lead site (4.5‒19.1%), lead migration (2.2‒8.6%), electric shock (5.5‒7.9%), and infection/irritation

* '''Additional treatment options'''
** '''Indwelling catheterization, augmentation cystoplasty, or other urinary diversions are rare long-term management strategies for OAB and should only be considered after all other medical and surgical options have been exhausted and only after careful consideration of the likely benefits and risks.'''
*** Indwelling catheter
**** In the patient with contraindications to other treatment options, including intolerance to medications, allergy, severe debilitation or immobility, and cognitive deficit or expected cognitive decline, indwelling or intermittent catheterization may be tried.
**** However, this carries a high risk of catheter-associated UTIs, long-term issues of urethral erosion (indwelling urethral catheters), and development of bladder calculi, and comes at the requirement of patient compliance and/or caregiver support.