What is the comparison of efficacy and side effect profiles of different alpha blockers (e.g. alfuzosin, doxazosin, terazosin, tamsulosin, silodosin) in the treatment of Benign Prostatic Hyperplasia (BPH) and Bladder Outlet Obstruction (BOO)?

Comparison of Alpha Blockers for BPH/BOO: Efficacy and Side Effects

Direct Answer

All alpha blockers (alfuzosin, doxazosin, terazosin, tamsulosin) demonstrate equivalent efficacy for BPH symptom relief (4-6 point improvement in AUA Symptom Index), but tamsulosin and alfuzosin are preferred due to superior tolerability with fewer cardiovascular side effects including fatigue, dizziness, and orthostatic hypotension. 1

Efficacy Comparison

Symptom Improvement

• All four alpha blockers produce clinically equivalent symptom relief, with mean improvements of 4-6 points on the AUA Symptom Index 1
• Tamsulosin 0.4 mg once daily achieved a mean IPSS reduction of -8.3 points versus -5.5 for placebo at 13 weeks 2
• Doxazosin 4-8 mg once daily produced IPSS improvements of 2.3 to 3.3 points in obstructive and irritative symptoms 3
• Alfuzosin 10 mg once daily reduced mean IPSS from 17.1 to 9.3 (P < 0.0001) over 12 months 4

Flow Rate Improvements

• Tamsulosin 0.4 mg increased peak flow rate by 1.75 mL/sec versus 0.52 mL/sec for placebo 2
• Doxazosin 4-8 mg improved maximum flow rate by 2.3 to 3.3 mL/sec compared to 0.1 mL/sec with placebo 3
• Alfuzosin 10 mg increased peak flow rate from 9.1 to 11.3 mL/sec (P < 0.0001) 4
• Efficacy differences between agents are clinically negligible; choice should be based on side effect profile 1

Onset of Action

• Alpha blockers provide rapid symptom relief within 1-2 weeks of initiation 5
• Doxazosin showed significant improvement as early as one week, with flow rate increases of 0.8 mL/sec versus -0.5 mL/sec for placebo 3
• Tamsulosin demonstrated rapid symptom score decrease starting at week 1 and maintained through 13 weeks 2

Side Effect Profile Comparison

Uroselective vs Non-Selective Agents

Critical distinction: Uroselective agents (tamsulosin, alfuzosin) have significantly better tolerability than non-selective agents (doxazosin, terazosin). 1

Cardiovascular Side Effects

Non-Selective Agents (Doxazosin, Terazosin)

• Higher incidence of orthostatic hypotension, dizziness, and fatigue 1
• Doxazosin requires dose titration to minimize first-dose hypotensive effects 3
• Critical safety concern: Doxazosin monotherapy associated with higher incidence of congestive heart failure in men with cardiac risk factors 1
• Terazosin has dose-dependent adverse effects, with higher doses correlating with more events 1

Uroselective Agents (Tamsulosin, Alfuzosin)

• Tamsulosin demonstrates lower probability of cardiovascular side effects including asthenia/fatigue 1
• Alfuzosin 10 mg once daily: only 4.4% reported alpha-blockade-related adverse events (mainly dizziness) 4
• Alfuzosin showed low incidence of asymptomatic orthostatic hypotension (2.8%) with no age effect 4
• Both can be initiated without dose titration, improving compliance 6

Sexual Side Effects

Major trade-off: Tamsulosin has the highest rate of ejaculatory dysfunction among alpha blockers. 1

• Tamsulosin: ejaculatory disorders occur more frequently than other alpha blockers 1
• Alfuzosin: ejaculation disorders infrequent (0.6%) 4
• In head-to-head comparison: sexual function adverse events occurred in 8% with tamsulosin versus 3% with alfuzosin 10 mg and 0% with placebo 6
• Doxazosin and terazosin have lower rates of ejaculatory dysfunction compared to tamsulosin 1

Other Common Side Effects

• Dizziness: alfuzosin 10 mg (6%), alfuzosin 15 mg (7%), tamsulosin (2%), placebo (4%) 6
• Nasal congestion occurs with all alpha blockers but is generally mild 1
• Tiredness (asthenia) is more common with non-selective agents 1

Clinical Algorithm for Agent Selection

First-Line Choice

Start with tamsulosin 0.4 mg once daily for most patients 1

• Equal efficacy to other agents 1
• No dose titration required 2
• Lowest cardiovascular side effect burden 1
• Caveat: Discuss ejaculatory dysfunction risk (higher than other agents) before initiating 1

When Ejaculatory Function is Priority

Switch to alfuzosin 10 mg once daily 1, 4

• Equivalent efficacy to tamsulosin 6
• Significantly lower ejaculatory dysfunction rate (0.6% vs 8%) 4, 6
• Excellent long-term safety profile maintained up to 12 months 4
• Well tolerated even in at-risk elderly populations 4

When Patient Has Concomitant Hypertension

Do NOT rely on alpha blockers for hypertension management 1

• Alpha blockers should not be assumed to constitute optimal hypertension management 1
• If using doxazosin or terazosin, ensure separate antihypertensive therapy is optimized 1
• Avoid doxazosin monotherapy in patients with cardiac risk factors due to heart failure risk 1

Managing Fatigue/Tiredness

If patient develops fatigue on doxazosin or terazosin: 1

• Switch to tamsulosin 0.4 mg once daily (preferred) 1
• Alternative: reduce to lowest effective dose of current agent 1
• If fatigue persists after switching to tamsulosin, consider non-alpha-blocker therapy (5-alpha reductase inhibitors for enlarged prostates) 1

Dosing Considerations

• Tamsulosin: Start 0.4 mg once daily; can titrate to 0.8 mg if needed, though side effects may increase slightly 1, 2
• Alfuzosin: 10 mg once daily (no titration needed); 15 mg dose offers no additional benefit with worse tolerability 6
• Doxazosin: Requires dose titration; efficacy is dose-dependent (4-8 mg range) 3
• Terazosin: Requires dose titration; efficacy is dose-dependent 1

Acute Urinary Retention Management

• Prescribe an oral alpha blocker prior to voiding trial for AUR related to BPH 7
• Both alfuzosin and tamsulosin demonstrate improvement in trial without catheter (TWOC) success rates 7
• Patients should complete at least 3 days of alpha blocker therapy before attempting TWOC 7
• Inform patients who pass TWOC that they remain at increased risk for recurrent retention 7

Long-Term Disease Progression

• Alfuzosin 10 mg once daily prevents overall clinical progression of BPH (defined by symptom deterioration ≥4 points and/or AUR and/or surgery) with 26% risk reduction over 2 years 8
• Alpha blockers do NOT reduce the primary occurrence of acute urinary retention 8
• Combination therapy with 5-alpha reductase inhibitors reduces clinical progression more effectively than monotherapy in patients with enlarged prostates 7