Nocturia frequency unchanged by pharmacotherapy augmentation of behavioral modification

Adding pharmacotherapy to behavioral modification for treating lower urinary tract symptoms (LUTS) in men improves 24-hour voiding frequency compared with behavioral modification alone, but had no significant benefit for improving nocturia, according to the results of a recently published retrospective study.¹

“Several papers have questioned the efficacy of non-antidiuretic pharmacological treatment for improving nocturia in men with LUTS, but there is a paucity of real-world data on this issue,” said Connelly Miller, MPH, first author of the paper. “Individualized behavioral counseling targeting lifestyle modifications is recommended as first-line therapy for LUTS-related nocturia. Our study finds no evidence to support supplementing that approach with pharmacotherapy.”

Miller is a fourth year medical student at SUNY Downstate Health Sciences University, Brooklyn, New York who has been conducting retrospective analyses to understand features of nocturia using information from a prospectively kept database of men seen for LUTS at the outpatient clinic of the Veteran Affairs New York Harbor Healthcare System, Brooklyn. The database, which includes voiding diaries, quality of life questionnaires, and patient and visit-level data, was started and is overseen by Jeffrey Weiss, MD, PhD, senior author of the published article and professor and chairman of urology at SUNY Downstate Health Sciences University.

The study investigating the efficacy of non-antidiuretic pharmacotherapy for nocturia identified men aged 18 years or older who had at least 1 pair of nocturnal void entries with the second entry recorded between 2 and 365 days after the first (baseline) date. It excluded men who were prescribed an antidiuretic or had surgery in the interval between the baseline and follow-up entries.

Determination of whether the patient’s management involved behavioral modification alone or concomitant pharmacotherapy with a LUTS drug (alpha-1 adrenergic antagonist, antimuscarinic agent, 5-alpha-reductase inhibitor, beta-3 agonist, or phosphodiesterase inhibitor) was done through chart review. Patients who were on the same pharmacotherapy at the time of their baseline and follow-up entries were included in the behavioral modification-only group. Information on demographics, tobacco use, medical comorbidities, vital signs, laboratory results, and uroflowmetry results was also extracted for each patient.

The study included data from 93 patients who were seen at the outpatient clinic between 2008 and 2019. There were a total of 156 diary entry pairs from patients who received behavioral modification alone and 57 diary pairs from patients who started on pharmacotherapy after the baseline entry. Median time between baseline and follow-up diary entries was 107 days. The patients included in the study had a median age of about 70 years.

Comparisons between the behavioral modification alone and adjunctive pharmacotherapy groups showed that they were similar with respect to all clinical and voiding diary characteristics with the exception that peripheral edema was more prevalent in the behavioral modification group and median maximum voided volume (MVV) was significantly lower in the pharmacotherapy group.

Median nocturnal voids was 2 in both study groups at baseline and did not change significantly between the baseline and follow-up entries in either group. Nocturnal frequency improved by at least 1 void in 38% of diary entries for men treated by behavioral modification alone and in 42% of diary entries for those prescribed adjunctive medication. A crude logistic regression analysis showed that adjunctive pharmacotherapy did not significantly change the odds of improving nocturia severity (odds ratio 1.16 [95% confidence interval: 0.63-2.16]; P = .63). Further analysis adjusting for the baseline difference between groups in MVV also showed no significant benefit of pharmacotherapy for improving nocturia severity nor was any single class of LUTS drug associated with a significant benefit when added to behavioral modification. Analyses of multiple other nocturnal voiding diary parameters also showed no significant changes from baseline to follow-up in either study group.

Median number of 24-hour voids decreased significantly in the adjunctive pharmacotherapy group from 12 at baseline to 10 at follow-up (P < .001) and was unchanged in the behavioral modification group. In the crude logistic regression analysis, men receiving adjunctive pharmacotherapy had a twofold greater likelihood of achieving improvement in 24-hour urinary frequency compared with their counterparts receiving behavioral modification alone (P = .04). The significant benefit of pharmacotherapy persisted in an analysis adjusting for between group differences in MVV and comparing the pharmacotherapy group of patients prescribed an antimuscarinic agent to the group receiving behavioral modification alone.

Reference

1. Miller CD, Monaghan TF, Robins DJ, Weiss JP. Does traditional pharmacotherapy augment behavioral modification in the treatment of nocturia? Neurourol Urodyn. Published online May 11, 2021. doi:10.1002/nau.24692