Hypothesis / aims of study
Overactive bladder (OAB) syndrome and irritable bowel syndrome (IBS) frequently coexist, yet treatment responses remain heterogeneous. We hypothesized that IBS subtype (diarrhea-predominant [IBS-D], constipation-predominant [IBS-C], or mixed-type [IBS-M]) predicts differential efficacy of OAB-targeted versus IBS-targeted monotherapy versus dual therapy and defines distinct mechanistic phenotypes (pelvic floor-driven, sensitization-driven, or synergistic) in OAB-IBS comorbidity.
Study design, materials and methods
This prospective observational per-protocol cohort study enrolled treatment-naïve adults with concomitant OAB (ICS criteria) and IBS (Rome IV criteria). Of 259 screened patients, 144 completed 8-week follow-up and were allocated to four non-randomized observational cohorts based on physician-determined primary treatment strategy (Figure 1): OAB-targeted monotherapy (OAB-TM), OAB-targeted dual therapy (OAB-TD), IBS-targeted monotherapy (IBS-TM), or IBS-targeted dual therapy (IBS-TD). All participants received standardized health education on fluid and dietary management. Primary outcomes were changes (Δ) in Overactive Bladder Symptom Score (OABSS) and IBS Severity Scoring System (IBS-SSS). Secondary outcomes included changes in PHQ-9, GAD-7, OAB-q, and IBS-QOL scores. Efficacy was compared using ANCOVA adjusted for baseline scores. Baseline uroflowmetry was performed and analyzed in blinded fashion; quantitative parameters (Qmax, Qavg, voiding time, voided volume, PVR) were recorded. Univariable logistic regression identified baseline predictors of cross-organ response. Post-hoc power analysis confirmed adequate power (1-β = 0.89).
Results
Dual therapy produced significantly greater improvements than monotherapy across all symptom, mood, and quality-of-life domains. Stratified analyses by IBS subtype (excluding IBS-U) revealed marked heterogeneity. In the IBS-targeted cohort, dual therapy was superior to monotherapy for OABSS improvement only in IBS-D patients (highly significant); no difference was observed in IBS-M or IBS-C subtypes. Objective uroflowmetry provided mechanistic support: IBS-D patients showed high-peak tower-shaped curves with higher Qmax and shorter voiding time (suggestive of detrusor overactivity), while IBS-C patients exhibited low-flow staccato patterns with lower flow rates, prolonged voiding time, and higher PVR (suggestive of pelvic floor dysfunction/dysfunctional voiding). Baseline anxiety (GAD-7) and depression (PHQ-9) scores significantly predicted OAB response in the IBS-TM cohort. Stronger gut-to-bladder crosstalk was confirmed in IBS-M and IBS-TM groups.
Interpretation of results
These findings establish that OAB-IBS comorbidity comprises three distinct clinical phenotypes: pelvic floor-driven (IBS-C), bladder-primary/sensitization-driven (IBS-D), and synergistic/central sensitization-driven (IBS-M). IBS subtype and baseline affective distress reliably predict treatment response and cross-organ improvement, while uroflowmetry patterns offer objective physiological correlates.