Systematic review of combination drug therapy for non-neurogenic male lower urinary tract symptoms

Abstract

Background: Several drugs are approved for the treatment of lower urinary tract symptoms (LUTS) in men, but these are mostly used by clinicians as monotherapies. The combination of different compounds, each of which targets a different aspect of LUTS, seems appealing. However, only few clinical trials have evaluated the effects of combination therapies.

Objective: This systematic review analyzes the efficacy and adverse events of combination therapies for male LUTS.

Evidence acquisition: PubMed and Cochrane databases were used to identify clinical trials and meta-analyses on male LUTS combination therapy. The search was restricted to studies of level of evidence ≥ 1b. A total of 49 papers published between January 1988 and March 2012 were identified.

Evidence synthesis: The α1-adrenoceptor antagonist (α1-blocker)/5α-reductase inhibitor (5-ARI) combination provides the most data. This combination seems to be more efficacious in terms of several outcome variables in patients whose prostate volume is between 30 ml and 40 ml when treatment is maintained for >1 yr; when given for <1 yr, α1-blockers alone are just as effective. The combination of α1-blocker/5-ARI shows a slightly increased rate of adverse events. It remains unknown whether its safety and superiority over either drug as monotherapy are sustained after >6 yr. The α1-blocker/muscarinic receptor antagonist (antimuscarinic) combination was most frequently assessed as an add-on therapy to already existing α1-blocker therapy. Inconsistent data derive from heterogeneous study populations and different study designs. Currently, the α1-blocker/antimuscarinic combination appears to be a second-line add-on for patients with insufficient symptom relief after monotherapy. The combination seems to be safe in men with postvoid residual <200 ml. However, there are no trials >4 mo concerning safety and efficacy of this combination. The α1-blocker/phosphodiesterase type 5 inhibitor combination is a new treatment option with only preliminary reports. More studies are needed before definitive conclusions can be drawn.

Conclusions: An α1-blocker/5-ARI combination is beneficial for patients whose prostate volume is between 30 ml and 40 ml when medical treatment is intended for >1 yr. Based on short-term follow-up studies, add-on of antimuscarinics to α1-blockers is an option when postvoid residual is <200 ml.

Keywords: 5α-reductase inhibitors; Adrenergic α(1)-receptor antagonists; Lower urinary tract symptoms; Muscarinic antagonists; Prostatic hyperplasia.