Systematic Review of Combination Drug Therapy for Non-neurogenic Lower Urinary Tract Symptoms

Context: Several drugs are approved and available for the treatment of lower urinary tract symptoms (LUTS) in men and women. However, the vast majority of available data, upon which the approval and recommendation in guidelines are based, considered only the role of the monotherapies and did not evaluate possible combination therapies. Objective: This systematic review analyzes the efficacy and adverse events of combination therapies for male and female LUTS. Evidence acquisition: A systematic literature search in the PubMed/Medline, Web of Science, and Cochrane databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement to identify clinical trials, randomized controlled trials, meta-analyses, and guidelines on male and female LUTS combination therapy published from March 2012 to December 2017 for men (in order to update a previous men-focused work) and from January 1988 to December 2017 for women. A total of 58 papers were identified. Evidence synthesis: The most studied combination therapy for the treatment of male LUTS is the α1-adrenoceptor antagonist/5α-reductase inhibitor combination. This combination seems to be more efficacious in terms of several outcome variables, in particular in men who have moderate-to-severe LUTS and are at risk of disease progression. Also in terms of nocturia improvements, this combination is significantly more effective than the monotherapy. The other often studied combination treatment, in both male and female patients with LUTS, was the combination of antimuscarinics (in particular solifenacin) and mirabegron. This combination seems to be more effective in comparison with the monotherapies with respect to urinary incontinence and urgency urinary incontinence episodes and several other objective and subjective parameters, without relevant increase of adverse events. The combination of hormone therapy and antimuscarinics in women with LUTS does not seem to be useful. Conclusions: For the treatment of LUTS in men and women, combination therapy appears to be a promising option to optimize the efficacy of the available drugs for those who do not experience sufficient benefit with monotherapy. This add-on scenario offers the possibility to have a more tailored approach to the management of LUTS, always seeking the optimal balance between efficacy and tolerability for a given patient. Patient summary: Some combination of drugs may offer advantages over monotherapies for the treatment of voiding and storage complaints in men and women. For the treatment of lower urinary tract symptoms (LUTS) in men and women, combination therapy appears to be a promising option to optimize the efficacy of the available drugs. This add-on scenario offers the possibility to have a more tailored approach to the management of LUTS