What therapeutic options are available for treating overactive bladder aside from anti-cholinergic (anticholinergic) medications that may cause xerostomia (dry mouth)?

Therapeutic Options for Overactive Bladder Beyond Anticholinergics

For patients with overactive bladder who cannot tolerate anticholinergics due to xerostomia, β3-adrenergic agonists (mirabegron 25-50 mg daily or vibegron 75 mg daily) should be the preferred first-line pharmacologic option, as they avoid anticholinergic side effects including dry mouth while maintaining comparable efficacy. 1, 2

First-Line: Behavioral Therapies

Before or alongside any pharmacologic therapy, all patients should receive behavioral interventions, which have excellent safety profiles and no risk of xerostomia 1, 3:

• Bladder training has the strongest evidence base and should be emphasized 3
• Fluid management and caffeine reduction 3
• Pelvic floor muscle training and delayed voiding 1
• Weight loss and physical activity modifications 2

These can be combined with pharmacotherapy without requiring sequential failure 1

Second-Line: β3-Adrenergic Agonists (Preferred Over Antimuscarinics)

β3-agonists are typically preferred before antimuscarinic medications due to their favorable side effect profile, particularly the absence of xerostomia and lower dementia risk 3, 2:

Mirabegron (Myrbetriq)

• Dosing: Start at 25 mg daily, may increase to 50 mg daily 4
• Efficacy: Demonstrated significant reduction in incontinence episodes (-0.34 to -0.42 episodes/24h vs placebo) and micturition frequency (-0.42 to -0.61 episodes/24h vs placebo) at 12 weeks 4
• Onset: 25 mg effective within 8 weeks; 50 mg effective within 4 weeks 4
• Advantage: No anticholinergic side effects, particularly beneficial for elderly patients concerned about cognitive impairment 2

Vibegron (Gemtesa)

• Dosing: 75 mg once daily 2
• Mechanism: β3-adrenergic receptor agonist with favorable side effect profile 2
• Advantage: Avoids xerostomia and other anticholinergic effects entirely 2

Third-Line: Combination Therapy

If monotherapy with β3-agonists provides inadequate response, combination therapy with a β3-agonist plus an antimuscarinic may be considered 1:

• Solifenacin 5 mg + mirabegron 25-50 mg has the strongest evidence from SYNERGY I/II and BESIDE trials 1
• Combination therapy improves efficacy without significantly affecting safety profile compared to monotherapy 1
• This approach may allow lower antimuscarinic doses, potentially reducing xerostomia severity 1

Fourth-Line: Minimally Invasive Therapies

For patients with inadequate response to or intolerable side effects from pharmacotherapy, clinicians should offer sacral neuromodulation, tibial nerve stimulation, and/or intradetrusor botulinum toxin injection 1:

Sacral Neuromodulation (SNM)

• High success rates, durable efficacy, and excellent patient satisfaction 1
• Reduces voiding frequency, nocturia, urgency episodes, and incontinence episodes 1
• No xerostomia or systemic anticholinergic effects 1

Peripheral Tibial Nerve Stimulation (PTNS)

• Effective for reducing OAB symptoms 1
• Limitation: Requires repeated in-office treatments 1
• Transcutaneous tibial nerve stimulation available as alternative 1

Intradetrusor Botulinum Toxin (OnabotulinumtoxinA)

• High efficacy for refractory OAB 1
• Critical requirement: Measure post-void residual (PVR) before injection; caution if PVR >100-200 mL 1
• Patient must be willing to perform clean intermittent catheterization if urinary retention develops 1
• Follow-up at 2 weeks post-injection to assess response and rule out retention 1

Important Clinical Considerations

Direct Access to Minimally Invasive Therapies

Clinicians may offer minimally invasive therapies without requiring trials of behavioral or pharmacologic management in the context of shared decision-making 1:

• This represents a paradigm shift from traditional stepwise approaches 1
• Particularly appropriate for patients unable or unwilling to undergo behavioral/pharmacologic therapies 1
• Long-term compliance with behavioral and pharmacotherapy is poor, leading to high failure rates 1

Common Pitfalls to Avoid

• Do not skip behavioral therapies entirely - they should be offered to all patients given their excellent safety profile 3
• Do not default to antimuscarinics first - β3-agonists are now preferred due to lower risk of xerostomia and cognitive effects 3, 2
• Do not continue ineffective therapy - if inadequate response after appropriate duration, escalate to next line rather than prolonging ineffective treatment 1
• Do not perform botulinum toxin injection without measuring PVR and counseling about catheterization risk 1