Evaluation of Alpha 1 Adrenoceptor Antagonist Dose Increase Therapy: An Essential Strategy for Patients with Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia

Introduction: There have been a number of reports on dose increase therapy (DI-T) with the alpha 1 adrenoceptor antagonists (α1-blockers) naftopidil and tamsulosin for lower urinary tract symptoms associated with benign prostatic hyperplasia. Methods and Results: The reports on DI-T (naftopidil 75 mg/d, tamsulosin 0.4 mg/d) in non-responders to low-dose initial therapy (LI-T, naftopidil 50 mg/d, tamsulosin 0.2 mg/d) were summarized. In each study, a non-responder was defined as a patient without sufficient improvements on the International Prostate Symptom Score (IPSS), IPSS Quality of Life, maximum flow rate of urine, or treatment satisfaction. These reports showed that 22.4-76.1% of patients were non-responders to LI-T, indicating that a novel treatment strategy for such patients is important. Moreover, 22.5-90.0% of non-responders to LI-T showed a response to DI-T, which achieved the same level of efficacy as low-dose maintenance therapy. Specifically, the improvements of the IPSS voiding symptom sub-score and maximum flow rate of urine were superior. The predictive factors for non-response to α1-blockers LI-T were insufficient improvement of subjective symptoms and objective findings during LI-T. These patients require high-dose initial therapy or DI-T at an early stage, since adverse events associated with naftopidil and tamsulosin do not show a dose-response relationship. Conclusions: DI-T with α1-blockers has high potential as an essential treatment strategy for lower urinary tract symptoms associated with benign prostatic hyperplasia.