Can alpha-blockers like alfluzosin or tamsulosin cause fatigue?

Alpha-Blockers and Fatigue: Clinical Evidence and Recommendations

Yes, both alfuzosin and tamsulosin can cause fatigue, with dizziness and asthenia (tiredness) being among the most common adverse events reported with tamsulosin, while alfuzosin has fatigue rates comparable to placebo. 1, 2

Mechanism and Prevalence

Alpha-blockers can cause fatigue through several mechanisms:

• Central nervous system (CNS) depression
• Orthostatic hypotension leading to reduced cerebral perfusion
• Peripheral vasodilation causing lethargy

The prevalence of fatigue-related side effects varies between different alpha-blockers:

• Tamsulosin: Dizziness and asthenia (tiredness) are among the most common adverse events, with asthenia reported in 1-2% of patients taking the standard 0.4 mg dose 2
• Alfuzosin: The incidence of asthenia and fatigue is comparable to placebo in clinical trials, making it potentially preferable for patients concerned about fatigue 3

Comparative Side Effect Profiles

Alpha-blockers differ in their side effect profiles based on their selectivity:

Alpha-Blocker	Selectivity	Fatigue/Asthenia Risk	Orthostatic Hypotension Risk
Tamsulosin	α1A/α1D-selective	Higher (1-2%)	Lower
Alfuzosin	Non-selective	Lower (similar to placebo)	Lower
Doxazosin	Non-selective	Moderate	Higher
Terazosin	Non-selective	Moderate	Higher

Clinical Recommendations

When prescribing alpha-blockers for LUTS:

1. For patients concerned about fatigue: Consider alfuzosin as first-line therapy due to its lower incidence of fatigue and asthenia compared to tamsulosin 3

2. For patients already experiencing fatigue on tamsulosin:

   • Consider switching to alfuzosin
   • Administer the medication at bedtime to minimize daytime drowsiness 1
   • Evaluate for other causes of fatigue (anemia, sleep disorders, depression)

3. Medication adjustments:

   • Before attributing fatigue to alpha-blockers, review other medications that may cause fatigue 1, 4
   • Consider dose reduction if clinically appropriate

Important Considerations

• Fatigue may improve over time as the body adjusts to the medication
• The American Urological Association recognizes that while alpha-blockers have equal clinical effectiveness, they differ in their adverse event profiles 1
• For patients with metabolic syndrome, tamsulosin may actually improve fatigue and sleep quality despite its potential side effects 5
• Elderly patients may be more susceptible to fatigue and other side effects of alpha-blockers

Monitoring and Follow-up

• Assess for fatigue at follow-up visits using direct questioning
• Document the severity and impact on quality of life
• Consider alternative treatments if fatigue significantly affects daily functioning
• Evaluate for orthostatic hypotension, which may contribute to fatigue symptoms

Remember that while fatigue is a potential side effect, the benefits of treating LUTS often outweigh this risk for many patients. Selection of the appropriate alpha-blocker should consider the individual's symptom profile and tolerance for specific side effects.