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First Line Therapies: Non-Med/Surg

Behavioral

• Options:Bladder training, delayed voids, scheduled voids, double voids, consider pelvic floor muscle training and biofeedback
• Fluid intake: balance with risk for dehydration
• Caffeine reduction: may reduce OAB symptoms but may not affect incontinence episodes
• Weight loss: 8% weight loss in obese women decreased incontinence by 47% (vs 28%)
• Bowel habits: avoid constipation, maintain fiber intake

No Treatment?

• Consider other management strategies in elderly or demented patients
• Consider managing functional incontinence

Second Line Therapies: Medications

Anticholinergics

• Mechanism: inhibit bladder contractions (stimulated by parasympathetic signals)
• Extended release and transdermal have lower side effect profiles
• Different medications have different side effect risks
• Contraindications: narrow angle glaucoma, impaired gastric emptying, urinary retention
• Manage side effects first with OTC therapies prior to stopping anticholinergic
• Synergistic effect: seen with other medications with anticholinergic effects, includes TCAs, Parkinson meds, Alzheimer meds
• Increased risk of side effects (including cognitive deficits) in elderly/frail patients

Beta-3 Agonists

• Mechanism: increases sympathetic signals causing bladder relaxation without impairing bladder sensation
• Does not prolong QT interval
• Similar efficacy to anticholinergics
• Synergy trial (Herschorn 2017): can combine B3 agonist and anticholinergics for improved effect

Anticholinergic dosing

Medication	Dosing	Side effects
Oxybutynin (Ditropan)	5-10mg BID/TID XL 5-15mg QD-BID transdermal patch QD	Dry mouth (20-60%) Constipation (7-17%) Dry eyes Blurred vision Dyspepsia UTI Retention Impaired cognition Arrhythmias (rare)
Solifenacin (Vesicare)	5-10mg QD
Darifenacin (Enablex)	7.5-15mg QD
Tolterodine (Detrol)	1-2mg BID XL 2-4mg QD
Fesoterodine (Toviaz)	4-8mg QD
Trospium (Sanctura)	20mg BID XL 60mg QD	Quaternary amine does not cross blood/brain barrier, less cognitive effects
Mirabegron (Myrbetriq)	25-50mg daily	Headache (3-4%) Nasopharyngitis (3-4%) Tachycardia (rare) Retention (rare) Hypertension (10% mirabegron, 2% vibegron)
Vibegron (Gemtesa)	75mg QD

Third Line Therapies: Interventions

Botox (intravesical botulinum toxin)

• Mechanism: inhibits ACh release at neuromuscular junction
• Dosing: inject 100U for non-NGB, 200U if NGB
• Effects: reduced frequency by 29%, urgency by 38%, incontinence episodes by 59%, with 25% reporting complete resolution of symptoms, overall 60-75% report > 50% improvement and 30-40% report complete symptom resolution
• Timing: injections are temporary and need to be repeated q6-12mo, cannot repeat more often than q3mo
• Side effects: UTI (4-55%), retention (0-43%), dysuria (9%)
• Contraindications: unwilling/unable to catheterize, UTI, pregnancy, breastfeeding, myasthenia gravis, ALS

Sacral Neuromodulation

• Mechanism: signal generator implanted with lead in S3 foramen, modulates signals causing improved symptoms
• Placement: S3 stimulates anal bellows and toe flexion
• Test phase: implant lead, assess bladder diary after testing to determine whether device can be permanently implanted, considered success if > 50% improvement in 1+ parameters
• Effects: 5yr success rate 70-80%, may improvement in sexual dysfunction and fecal incontinence
• Indications: FDA-approved for OAB with(out) incontinence, detrusor underactivity without obstruction, fecal incontinence, but not approved for bladder pain or neurogenic bladder
• Side effects: pain at simulator site (3-20%), pain at lead site (4.5-19%), lead migration (1-8.6%, infection/irritaton (2-14%), electric shock (5.5-10%), need for surgical revision (6-39.5%)
• MRI compatibility: depends on age of device, older models less likely to be safe
• Placement tips: getting a better response from the distal electrode (number 0) indicates better placement location next to S3

Percutaneous Tibial Nerve Stimulation

• Mechanism: alters efferent signals from sacral spinal cord to bladder
• Technique: apply 34g needle 3-4cm superior to medial malleolus between tibia and soleus muscle, grounding pad on same leg
• Needle positioning: correct stimulation should lead to great toe flexion (fanning) and tickling sensation of sole
• Timing: 30 minute treatments in clinic x12 weeks, then as individually needed
• Success: 71% improvement (>50% symptom reduction) vs 0% in placebo
• Side effects: overall minimal, main issue is frequent clinic visits
• Contraindications: pregnancy, pacemaker/defibrillator, high bleeding risk

Fourth-line therapies: surgical interventions

Augment

• Indications: refractory DO, reduced capacity, reduced compliance
• Technique: bladder opened, detubularized intestine patched onto open bladder, increases volume and lowers pressure
• Effects: 80% are improved/dry, but 10-40% require CIC to empty

Other options

• Autoaugment: incise/remove detrusor, allowing bladder epithelium to balloon outwards, need to have good capacity preoperatively
• Diversion: for severely refractory patients, options include conduit, chimney, neobladder, catheterizable conduit