What are the first-line medications for treating overactive bladder (OAB)?

First-Line Medications for Overactive Bladder

Behavioral therapies—not medications—are the mandatory first-line treatment for all patients with overactive bladder, and pharmacologic therapy should only be initiated after an adequate 8-12 week trial of behavioral interventions. 1, 2

Treatment Algorithm

Step 1: Behavioral Interventions (Required First-Line)

All patients must begin with the following non-pharmacologic approaches before any medication is considered:

• Bladder training and delayed voiding techniques to increase bladder capacity and reduce urgency 1, 2
• Pelvic floor muscle training with urge suppression techniques 1, 2
• Fluid management: A 25% reduction in fluid intake can significantly reduce frequency and urgency 2
• Weight loss in obese patients: An 8% weight loss reduces urgency urinary incontinence episodes by 42-47% 1, 2
• Caffeine reduction to minimize bladder irritation 2

Behavioral therapies are as effective as antimuscarinic medications in reducing symptom levels, with high-quality evidence supporting this approach 1. The critical pitfall here is that practitioners commonly encounter patients seeking second- or third-line treatments who have never undergone an adequate first-line trial of behavioral therapy 3.

Step 2: Pharmacologic Therapy (Second-Line)

Only after 8-12 weeks of behavioral therapy should medications be added 3, 1. When behavioral approaches are insufficient, you have two main drug classes:

Beta-3 Adrenergic Agonist (Preferred First Medication)

• Mirabegron is the preferred initial pharmacologic agent due to better tolerability and lower cognitive risks compared to antimuscarinics 1
• Dosing: Start at 25 mg orally once daily, increase to 50 mg once daily after 4-8 weeks if needed 4
• Advantages: Lower incidence of dry mouth and constipation compared to antimuscarinics; no cognitive impairment risk 1
• Contraindications: Reduce dose to maximum 25 mg in moderate renal impairment (eGFR 15-29) or moderate hepatic impairment (Child-Pugh B); avoid in severe impairment 4

Antimuscarinic Medications (Alternative Second-Line)

If mirabegron is contraindicated or ineffective, antimuscarinics are appropriate:

• Darifenacin: Selective M3 receptor antagonist with lower risk of cognitive effects 1
• Fesoterodine: Non-selective muscarinic receptor antagonist 1
• Solifenacin: Effective as monotherapy or in combination 1, 2
• Tolterodine: Well-tolerated with less dry mouth than oxybutynin 2, 5
• Oxybutynin: Highest risk of discontinuation due to adverse effects; use as last resort 1
• Trospium: Another option in the antimuscarinic class 2

Critical safety considerations for antimuscarinics:

• Absolute contraindications: Narrow-angle glaucoma, impaired gastric emptying, history of urinary retention 1, 2
• Cognitive risks: Potential for dementia and cognitive impairment that may be cumulative and dose-dependent, particularly in elderly patients 1
• Common side effects: Dry mouth, constipation, dry eyes, blurred vision, dyspepsia, UTI, urinary retention 2

Beta-3 agonists are typically preferred before antimuscarinics due to cognitive risk concerns, especially in elderly patients 1.

Step 3: Adequate Trial Duration

• Medications require 4-8 weeks to determine efficacy and tolerability 3
• Do not abandon therapy prematurely or add a second therapy before establishing efficacy of the first 3
• If one antimuscarinic fails, try another agent or switch to beta-3 agonist before declaring pharmacologic failure 1

Step 4: Combination Therapy (If Monotherapy Fails)

• Solifenacin 5 mg plus mirabegron 50 mg is the evidence-based combination with strongest support from SYNERGY I/II and BESIDE trials 1
• Combination therapy is statistically superior to monotherapy for reducing incontinence episodes and micturitions 1
• Adverse events (dry mouth, constipation, dyspepsia) are slightly increased with combination versus monotherapy 1

Step 5: Third-Line Options (Specialist Referral)

If behavioral therapy plus pharmacologic therapy (including combination) fails after adequate trials:

• Intradetrusor onabotulinumtoxinA injections 1
• Sacral neuromodulation 1
• Peripheral tibial nerve stimulation 1

Common Pitfalls to Avoid

• Failing to optimize behavioral therapies before starting medications is the most common error 1
• Not considering cognitive risks when prescribing antimuscarinics in elderly patients 1
• Abandoning antimuscarinic therapy after failure of one medication instead of trying another agent or switching to beta-3 agonist 1
• Using antimuscarinics in patients with contraindications such as narrow-angle glaucoma, impaired gastric emptying, or urinary retention history 1
• Short medication trials or lack of dose modification before declaring treatment failure 3
• Adding multiple therapies simultaneously without establishing efficacy of individual treatments 3