Combination therapy with an antimuscarinic agent (tolterodine extended release [ER]) and alpha₁-receptor antagonist (tamsulosin) provided symptomatic benefit in men with moderate-to-severe lower urinary tract symptoms and overactive bladder, according to a large-scale, randomized, double-blind, placebo-controlled study published in the Journal of the American Medical Association (JAMA).

Researchers enrolled 851 male patients from 95 US urology clinics. Patients were aged ≥40 years and had moderate-to-severe lower urinary tract symptoms, including symptoms of overactive bladder—defined as an International Prostate Symptom Score ≥12, an International Prostate Symptom Score Quality of Life item score ≥3, a self-rated bladder condition of at least "moderate bother," and a bladder diary documenting high micturition frequency and urgency, with or without urgency incontinence. Patients were randomly assigned to receive either placebo (n=215), tolterodine ER 4 mg (n=210), tamsulosin 0.4 mg (n=209), or tolterodine ER 4 mg plus tamsulosin 0.4 mg (n=217) once daily for 12 weeks. The study's primary end point was the proportion of patients reporting benefit from therapy as measured by the "Perception of Treatment Benefit" question.

After 12 weeks, 172 men (80%) receiving combination therapy reported treatment benefit compared with 132 men (62%) receiving placebo (P<.001), 146 (71%) receiving tamsulosin (P=.06 vs placebo), and 136 (65%) receiving tolterodine ER (P=.48 vs placebo). Patients receiving combination therapy also experienced statistically significant reductions in the number of urgency episodes with incontinence (–0.88 vs –0.31; P=.005), the number of urgency episodes without incontinence (–3.33 vs –2.54; P=.03), the number of micturitions per 24 hours (–2.54 vs –1.41; P<.001), and the number of nocturia episodes per night (0.59 vs 0.39; P=.02) compared with patients receiving placebo. Men receiving combination therapy also demonstrated statistically significant improvements on the International Prostate Symptom Score (–8.02 vs –6.19; P=.003) and the International Prostate Symptom Score Quality of Life item score (–1.61 vs –1.17; P=.003) compared with men receiving placebo.

In an accompanying editorial, Phil B. Fontanarosa, MD, MBA, and Helene M.Cole, MD, said: "The relatively short duration of the study (12 weeks) and the rather modest clinical benefits must be balanced against the potential for adverse effects that may occur with longer-term use of the drug combination."

SOURCES Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: A randomized controlled trial. JAMA. 2006;296:2319–2328.

Fontanarosa PB, Cole HM. Improving men's health: Evidence and opportunity[editorial]. JAMA. 2006;296:2373–2375.