What medications are used to control storage and voiding symptoms of the bladder?

Medications for Bladder Storage and Voiding Symptoms

For storage symptoms (urgency, frequency, nocturia, urge incontinence), anticholinergics and beta-3 agonists are first-line pharmacotherapy, while for voiding symptoms associated with benign prostatic obstruction, alpha-blockers are the primary treatment. 1

Storage Symptoms Medications

First-Line Anticholinergics

Anticholinergic medications are the established first-line pharmacotherapy for overactive bladder and storage symptoms. 1, 2

Tolterodine

• Tolterodine 2 mg twice daily (immediate release) or 4 mg once daily (extended release) is effective for reducing urgency, frequency, and urge incontinence episodes 1
• Extended release formulation has lower risk of dry mouth compared to immediate release (23% reduction) 3
• Tolterodine demonstrates superior tolerability compared to oxybutynin with significantly less dry mouth (RR 0.65,95% CI 0.60-0.71) while maintaining equivalent efficacy 1, 4
• The 1 mg twice daily dose may be equally effective as 2 mg with reduced dry mouth risk 5

Oxybutynin

• FDA-approved for relief of bladder instability symptoms including urgency, frequency, urinary leakage, and urge incontinence 6
• Extended release preparations preferred over immediate release due to reduced dry mouth risk 1, 5
• Transdermal oxybutynin formulation available with less dry mouth than oral immediate release, though skin reactions at patch site may occur 1

Solifenacin

• Solifenacin 5 mg once daily demonstrates superior efficacy compared to immediate release tolterodine for quality of life (SMD -0.12), patient-reported improvement (RR 1.25), and leakage episodes (WMD -0.30) 1, 5
• Can be increased to 10 mg once daily for improved efficacy in frequency and urgency reduction, though with increased dry mouth risk 1, 5
• Lower dry mouth risk compared to immediate release tolterodine (RR 0.69,95% CI 0.51-0.94) 5

Fesoterodine

• Fesoterodine 4 mg once daily is the recommended starting dose, with superior efficacy compared to extended release tolterodine for quality of life (SMD -0.20), cure/improvement (RR 1.11), and symptom reduction 1, 5
• Can be increased to 8 mg once daily for better clinical efficacy, but carries higher risk of withdrawal due to adverse events (RR 1.45) and dry mouth (RR 1.80) 5

Propiverine

• Studied in combination with alpha-blockers for men with overactive bladder and benign prostatic obstruction 1

Beta-3 Adrenergic Agonists

Mirabegron

• Mirabegron 25 mg or 50 mg once daily is effective for overactive bladder symptoms, with efficacy demonstrated within 4-8 weeks 1, 7
• FDA-approved based on three 12-week trials showing significant reductions in incontinence episodes and micturition frequency compared to placebo 7
• May offer advantages over anticholinergics including lower risk of dry mouth, constipation, and cognitive effects 8
• Generally well-tolerated with low cardiovascular risk in clinical trials 1

Voiding Symptoms Medications

Alpha-Blockers

Alpha-blockers are the primary treatment for voiding symptoms associated with benign prostatic hyperplasia by relaxing smooth muscle in the prostate and bladder neck. 8

Tamsulosin

• Standard treatment for lower urinary tract symptoms in men with benign prostatic hyperplasia 1, 8
• Dose: 0.4 mg daily 8

Alfuzosin

• Alternative alpha-blocker for treating lower urinary tract symptoms 1

Doxazosin and Terazosin

• Non-selective alpha-blockers used for voiding symptoms 1

Phosphodiesterase-5 Inhibitors

Tadalafil

• Tadalafil 5 mg once daily improves lower urinary tract symptoms and can be used alone or in combination with alpha-blockers 1
• Meta-analyses demonstrate efficacy for benign prostatic hyperplasia-related symptoms 1

5-Alpha Reductase Inhibitors

Finasteride and Dutasteride

• Effective for treating lower urinary tract symptoms in men with benign prostatic obstruction and gland enlargement 1
• Work by reducing prostate size over time 1

Combination Therapy Approaches

For Persistent Storage Symptoms Despite Alpha-Blocker Therapy

The European Association of Urology recommends combination treatment of an alpha-blocker with a beta-3 agonist (mirabegron) in patients with persistent storage symptoms after alpha-blocker monotherapy. 8, 9

Alpha-Blocker Plus Beta-3 Agonist

• Mirabegron added to tamsulosin demonstrates superior efficacy compared to tamsulosin alone for reducing overactive bladder symptoms 1, 9
• Contraindicated in men with post-void residual volume >150 mL 8, 9
• Low risk of urinary retention with this combination 8

Alpha-Blocker Plus Anticholinergic

• Multiple randomized controlled trials support combining alpha-blockers with anticholinergics (tolterodine, solifenacin, oxybutynin, propiverine) for men with both voiding and storage symptoms 1
• The NEPTUNE trial demonstrated efficacy and safety of solifenacin plus tamsulosin combination 1
• Monitor post-void residual volume, especially in men with elevated baseline values or significant bladder outlet obstruction 8

Important Clinical Considerations

Anticholinergic Precautions

• Anticholinergics are contraindicated in narrow-angle glaucoma unless approved by ophthalmologist 2
• Use extreme caution in patients with impaired gastric emptying or history of urinary retention 2
• Listed in Beers Criteria as potentially inappropriate for older adults due to CNS impairment, vision impairment, urinary retention, constipation, and sedation risks 2
• Common side effects include dry mouth, constipation, dry eyes, blurred vision, dyspepsia, and impaired cognitive function 2

Treatment Algorithm for Men with Both Storage and Voiding Symptoms

1. Start with alpha-blocker monotherapy (tamsulosin 0.4 mg daily) and evaluate response after 4-8 weeks 8
2. If storage symptoms persist, measure post-void residual volume 8, 9
3. If post-void residual <150 mL, add beta-3 agonist (mirabegron) or anticholinergic 8, 9
4. If post-void residual >150 mL, combination therapy is not recommended 9

Extended Release Formulations

• Extended release preparations of oxybutynin and tolterodine are preferred over immediate release due to reduced dry mouth risk while maintaining equivalent efficacy 1, 5