What are the appropriate first‑line medications and dosing for overactive bladder, considering the patient’s age (adult versus elderly) and comorbidities such as cognitive impairment, narrow‑angle glaucoma, urinary retention, uncontrolled hypertension, and renal or hepatic impairment?

Medication for Overactive Bladder

Mandatory First-Line: Behavioral Therapy Before Any Medication

All patients with overactive bladder must begin with behavioral interventions—including bladder training, pelvic floor muscle training, and fluid management—for 8–12 weeks before or alongside any pharmacologic therapy, as these non-drug approaches achieve efficacy equal to antimuscarinic medications with minimal adverse effects. 1

• Weight loss in obese patients reduces urgency incontinence episodes by up to 47%, making it a critical component of initial management. 1
• Behavioral therapies alone provide symptom reduction comparable to pharmacotherapy and should never be skipped. 1

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Second-Line: Pharmacologic Therapy Selection

Preferred Initial Medication: Mirabegron (Beta-3 Agonist)

When behavioral therapy alone is insufficient, mirabegron should be the preferred first-line pharmacologic agent due to its superior tolerability profile, lack of cognitive impairment risk, and absence of anticholinergic burden—particularly critical in elderly patients and those with cognitive concerns. 1, 2

Standard Dosing:

• Start mirabegron 25 mg once daily in elderly patients (≥65 years), those with multiple comorbidities, men with benign prostatic hyperplasia, patients with low detrusor contractility, or those with central nervous system lesions. 2, 3
• Increase to 50 mg once daily after 4–8 weeks if symptom control remains inadequate. 2, 3
• In younger, healthier adults without comorbidities, starting at 50 mg once daily is appropriate. 4

Key Advantages of Mirabegron:

• Dry mouth occurs with six-fold lower incidence compared to tolterodine extended-release in patients ≥65 years. 5
• Does not contribute to anticholinergic burden or cognitive impairment risk, unlike antimuscarinics. 1, 5
• Safe in patients with narrow-angle glaucoma, history of urinary retention, and impaired gastric emptying—all contraindications to antimuscarinics. 1
• Demonstrates maintained efficacy and safety in patients ≥75 years with multiple comorbidities. 2

Monitoring Requirements:

• Monitor blood pressure regularly during initial treatment, especially in patients with pre-existing hypertension; mirabegron is contraindicated in severe uncontrolled hypertension. 2, 4
• Assess post-void residual volume in men with lower urinary tract symptoms before and during therapy. 2
• Discontinue if worsening voiding symptoms or urinary stream deterioration occurs. 2

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Alternative: Antimuscarinic Agents

If mirabegron is contraindicated (e.g., severe uncontrolled hypertension) or not tolerated, select an antimuscarinic agent based on the following hierarchy, avoiding oxybutynin as first-line due to highest cognitive impairment risk and discontinuation rates. 1, 6

Recommended Antimuscarinic Options (in order of preference):

1. Fesoterodine: Superior efficacy to tolterodine in patients ≥80 years, with number-needed-to-benefit of 18 for achieving continence. 1

2. Tolterodine extended-release 4 mg once daily: Comparable efficacy to immediate-release formulations with better tolerability and fewer anticholinergic side effects (number-needed-to-benefit of 12 for continence). 1, 6

3. Solifenacin 5 mg once daily: High-quality evidence for achieving continence with number-needed-to-benefit of 9; particularly useful if combination therapy becomes necessary later. 1, 6

4. Darifenacin: Selective M3 receptor antagonist with lower risk of cognitive effects compared to non-selective agents. 1

Critical Contraindications for Antimuscarinics:

• Absolute contraindications: Narrow-angle glaucoma (unless cleared by ophthalmologist), impaired gastric emptying, history of urinary retention. 1
• Relative contraindications: Existing cognitive impairment, dementia risk, frailty (mobility deficits, unexplained weight loss, weakness). 1
• Assess post-void residual before initiating; use extreme caution if PVR ≥250–300 mL. 1

Common Antimuscarinic Adverse Effects:

• Dry mouth (most frequent complaint, varies by agent). 1
• Constipation (requires proactive monitoring and management). 1
• Potential cumulative, dose-dependent risk of cognitive impairment and dementia. 1

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Special Population Considerations

Elderly and Frail Patients:

• Beta-3 agonists (mirabegron) are strongly preferred over antimuscarinics due to cognitive safety concerns, even though both drug classes have narrower therapeutic windows in frail patients. 1, 6
• Frail patients (those with mobility limitations, unintended weight loss, weakness, or cognitive deficits) experience higher adverse event rates with all OAB medications; reinforce behavioral strategies if medications are not tolerated. 1, 6

Renal or Hepatic Impairment:

• Dose adjustments are required per FDA labeling; consult prescribing information for specific recommendations. 4

Men with Bladder Outlet Obstruction:

• If post-void residual ≥250 mL or maximum flow rate <10 mL/s, initiate alpha-blocker therapy first rather than antimuscarinic or beta-3 agonist monotherapy. 1

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Management of Inadequate Response or Intolerable Side Effects

Do not abandon a drug class after failure of a single agent; switching to another agent within the same class or to a different class often provides better symptom control or tolerability. 1

Stepwise Algorithm:

1. Trial each medication for 4–8 weeks before judging effectiveness or safety. 1

2. If first antimuscarinic fails or causes intolerable side effects:

   • Switch to a different antimuscarinic agent, OR
   • Switch to mirabegron (beta-3 agonist). 1

3. If mirabegron monotherapy (50 mg) provides inadequate response:

   • Switch to an antimuscarinic agent, OR
   • Add solifenacin 5 mg to mirabegron (combination therapy). 1, 2, 3

4. Combination therapy (mirabegron + solifenacin):

   • Solifenacin 5 mg + mirabegron 25 mg once daily OR solifenacin 5 mg + mirabegron 50 mg once daily are validated regimens. 1, 2
   • SYNERGY I/II and BESIDE trials provide strongest evidence for this combination, demonstrating superior efficacy to monotherapy with only slightly increased adverse events (dry mouth, constipation, dyspepsia). 1, 2

5. If combination therapy fails:

   • Consider third-line options: intradetrusor onabotulinumtoxinA injections, sacral neuromodulation, or peripheral tibial nerve stimulation. 1

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Common Pitfalls to Avoid

• Never start medications without first implementing behavioral therapies—this is the most common error in OAB management. 1, 6
• Do not use oxybutynin as first-line therapy in elderly patients despite lower cost; it has the highest risk of cognitive impairment and discontinuation due to adverse effects. 1, 6
• Do not discontinue antimuscarinic therapy after one agent fails without trying another antimuscarinic or switching to mirabegron; many patients achieve better outcomes with class switching. 1
• Do not prescribe antimuscarinics to patients with narrow-angle glaucoma, impaired gastric emptying, or history of urinary retention without addressing contraindications. 1
• Do not neglect blood pressure monitoring when prescribing mirabegron, especially in patients with pre-existing hypertension. 2