What is the first‑line medication for an adult with overactive bladder (urgency, frequency, with or without urge incontinence) considering anticholinergic side‑effect risks?

First-Line Medication for Overactive Bladder

For adults with overactive bladder, behavioral therapies (bladder training, pelvic floor muscle training, fluid management) should be initiated first, followed by pharmacologic treatment with either a beta-3 adrenergic agonist (mirabegron or vibegron) or an antimuscarinic agent as second-line therapy, with beta-3 agonists increasingly preferred due to their superior tolerability profile and lower risk of cognitive impairment, particularly in elderly patients. 1

Treatment Algorithm

Step 1: First-Line Behavioral Interventions (Required for All Patients)

• All patients must begin with behavioral therapies before or concurrent with pharmacologic management. 2, 1
• Bladder training and bladder control strategies reduce urgency and frequency with high-quality evidence supporting effectiveness equal to antimuscarinic medications. 1
• Pelvic floor muscle training provides symptom reduction comparable to pharmacotherapy. 1
• Fluid management with reduction in fluid intake can reduce frequency and urgency. 1
• Weight loss in obese patients can reduce incontinence episodes by up to 47%. 1
• Behavioral therapies may be combined with pharmacologic management to optimize outcomes. 2

Step 2: Second-Line Pharmacologic Treatment Selection

When behavioral therapies alone are insufficient, add pharmacotherapy with either a beta-3 agonist or antimuscarinic agent. 2, 1

Preferred Option: Beta-3 Adrenergic Agonists

• Mirabegron is typically preferred before antimuscarinic medications due to cognitive risk concerns, especially in elderly patients. 1
• Mirabegron 25 mg once daily is the starting dose, particularly effective and safe in older patients (≥65 years) with multiple comorbidities. 3
• Mirabegron 50 mg demonstrates efficacy within 4 weeks and has a superior tolerability profile with lower incidence of dry mouth and constipation compared to antimuscarinics. 1, 4, 5
• Mirabegron is as efficacious as most antimuscarinics (including tolterodine ER 4 mg) with similar adverse event rates to placebo. 6, 5

Alternative Option: Antimuscarinic Agents

• Darifenacin (selective M3 receptor antagonist) has a lower risk of cognitive effects. 1
• Fesoterodine (non-selective muscarinic receptor antagonist) is effective for overactive bladder. 1
• Tolterodine extended-release (4 mg daily) demonstrates better tolerability than immediate-release formulations. 1
• Solifenacin (5 mg) is effective, particularly if combination therapy becomes necessary later. 1
• Oxybutynin has the highest risk of discontinuation due to adverse effects and should generally be avoided. 1

Critical Safety Considerations

Antimuscarinic Contraindications and Cautions

• Use extreme caution in patients with narrow-angle glaucoma, impaired gastric emptying, or history of urinary retention. 1
• There is a potential cumulative and dose-dependent risk for developing dementia and cognitive impairment with antimuscarinic medications. 1
• Assess post-void residual (PVR) before starting antimuscarinics in patients with obstructive symptoms, history of urinary retention, or neurologic diagnoses; use caution if PVR is 250-300 mL. 1

Special Population: Frail Patients

• Use caution in prescribing antimuscarinics or beta-3 agonists in frail patients (those with mobility deficits, unexplained weight loss, weakness, or cognitive deficits) due to lower therapeutic index and higher adverse event profile. 2, 1

Mirabegron-Specific Monitoring

• Periodically monitor blood pressure, especially in hypertensive patients, as mirabegron can cause dose-dependent blood pressure increases. 3
• Common adverse events (>2%): hypertension, urinary tract infection, and headache. 3
• Renal impairment dosing: for eGFR 30-89 mL/min/1.73 m², start 25 mg, max 50 mg daily. 3

Step 3: If First Medication Fails

• If inadequate symptom control or unacceptable adverse events occur with one antimuscarinic, try dose modification or switch to a different antimuscarinic or beta-3 agonist. 2
• Do not abandon antimuscarinic therapy after failure of one medication without trying another agent or switching to a beta-3 agonist. 2, 1
• Patients often experience better symptom control or tolerability with different agents. 2

Step 4: Combination Therapy (For Refractory Cases)

• For patients remaining symptomatic on monotherapy, combination therapy with solifenacin 5 mg and mirabegron 25-50 mg once daily provides superior efficacy compared to either drug alone. 3, 7
• Combination therapy demonstrates statistically superior efficacy for reducing incontinence episodes, urgency episodes, and nocturia. 1, 3, 7
• Adverse events (dry mouth, constipation, dyspepsia) are slightly increased with combination versus monotherapy. 1, 3
• Do not use combination therapy as first-line treatment; reserve for patients refractory to monotherapy. 3

Common Pitfalls to Avoid

• Failing to optimize behavioral therapies before or concurrent with starting medications. 1
• Not considering cognitive risks when prescribing antimuscarinics, especially in elderly patients. 1
• Abandoning antimuscarinic therapy after failure of one medication instead of trying another agent or beta-3 agonist. 1
• Using antimuscarinics in patients with contraindications (narrow-angle glaucoma, impaired gastric emptying, urinary retention history). 1
• Starting with combination therapy instead of monotherapy. 3