Behavioral Therapy Noninferior to Solifenacin in Managing Overactive Bladder Symptoms of Parkinson Disease

Camille P. Vaughan, MD, MS

(Credit: Emory University)

In a newly published 12-week randomized noninferiority trial (NCT03149809), findings showed that behavioral therapy was noninferior to solifenacin (VESIcare; Astellas) in improving overactive bladder (OAB) symptoms among patients with Parkinson disease (PD). Published in JAMA Neurology, these results could inform clinical guidelines for urinary symptoms in PD and potentially support behavioral therapy as an initial treatment option for patients.¹

Among 77 patients with PD (men, n = 65; mean age, 71.3 [SD, 8.9] years; mean years with PD, 6.6 [SD, 5.8]) randomized to behavioral (n = 36) or solifenacin (n = 41), 73 participants completed the study. At 12 weeks post randomization, researchers reported that scores on the International Consultation on Incontinence Questionnaire OAB module (ICIQ-OAB) were significantly improved across both groups and were in the a priori noninferiority margin of 15% (mean score, solifenacin, 5.8 [SD, 2.4]; behavioral, 5.5 [SD, 2.0]; P = .02).

Additional results showed that reduction in symptom frequency was associated with reduction in bother (mean, solifenacin, 28.7 [SD, 6.6] to 17.0 [SD, 10.4]; behavioral, 27.8 [SD, 8.0] to 17.2 [SD, 11.6]; P = .02). Notably, researchers observed improvement in quality of life (QOL) related to OAB reported in both groups, with a significant test of noninferiority for all 3 comparisons between groups. Overall, this further suggested that behavioral therapy was noninferior to solifenacin therapy.

“This study builds on the emerging literature suggesting behavioral therapy may have utility as an initial therapy for the most common urinary symptoms affecting persons with PD. The study suggests clinically important treatment outcomes, including fewer OAB symptoms, reduced bother, and improved QOL, among those receiving behavioral therapy, with noninferiority compared with drug therapy,” lead author Camille P. Vaughan, MD, MS, professor and division director of the Division of Geriatrics and Gerontology in the Department of Medicine at Emory University, and colleagues wrote.¹ “Additionally, behavioral therapy is feasible among persons with PD, including those with evidence of cognitive impairment, and is associated with a high level of adherence compared with drug therapy.”

Conducted between 2018 and 2023 in 4 US Veterans Affairs health care systems, participants enrolled in the study were diagnosed with PD by a movement disorder neurologist and had an ICIQ-OAB symptom score of 7 or higher and Montreal Cognitive Assessment (MOCA) score of 18 or higher.^2,3 Patients were randomized 1:1 following stratification by sex, recruitment site, OAB severity, and PD motor symptom severity. Researchers performed analyses between October 2023 and April 2024. Baseline characteristics were balanced across groups, including on the MOCA score (mean, solifenacin, 23.9 [SD, 3.1]; behavioral, 24.8 [SD, 3.3]) and on the ICIQ-OAB score (mean, solifenacin, 9.1 [SD, 1.7]; behavioral, 8.5 [SD, 1.4]).

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Authors noted that behavioral therapy, which included pelvic floor muscle training and urge suppression strategies, was executed by a nurse practitioner. In the drug therapy group, administration of solifenacin started at 5-mg daily, with titration to 10-mg daily if needed. The primary outcome of the study was the ICIQ-OAB score across groups at 12 weeks in a 15% noninferiority margin. In terms of safety, investigators assessed adverse events every 2 weeks for 8 weeks and then again at 12 weeks.

All told, participants who received solifenacin were more likely to report experiencing adverse events like dry mouth, dry skin, or pain and/or burning with urination. During the study period, 1 patient in the solifenacin treatment group and 1 participant in the behavioral therapy group were diagnosed with a urinary tract infection. Researchers noted no difference observed in constipation by the participants. Notably, authors reported 6 falls in the drug therapy group and no falls in the behavioral therapy group by participants in the trial. Furthermore, 1 fall by a participant was associated with a hip fracture, but the patient remained in the study after rehabilitation.

Only 4 participants dropped out in the solifenacin group after randomization, with 1 dropout reported because of treatment-emergent AEs. Authors noted that only 8 patients (19.5%) requested to stop use of the drug therapy because of treatment-emergent AEs but remained in the trial for outcome assessments. Moreover, 9 participants who received the drug therapy (22%) at 6 weeks opted to increase the dose of solifenacin to 10 mg daily based on inadequate symptom control. In the exploratory analyses, results showed no statistical difference in the 12-week OAB symptom score based on the level of cognitive function measured by the MOCA.

The current study had some limitations, including a short follow-up period and a participant group that was predominantly made up of men, though the follow-up duration aligned with prior behavioral and drug trials for urinary symptoms. Although there was some differential dropout in the drug therapy group, missing data were limited, with only 4 participants who exited early. Researchers recommended that future research could focus on identifying baseline factors that affect treatment response and whether combining drug and behavioral therapies benefits patients who do not respond to a single approach.

“The findings of this randomized noninferiority trial indicate evidence of the effectiveness of [pelvic floor muscle exercise-based behavioral therapy] comparable to that of drug therapy as a treatment for common urinary symptoms in persons with PD,” Vaughan et al noted.^{1 “}The finding of increased falls in the solifenacin therapy group reinforces the need to carefully consider the risk-benefit ratio of medications for urinary symptoms, especially given the increased risk of falls among persons with PD. Given the potential adverse effects and burden of drug therapy, these results suggest behavioral therapy may be a suitable initial treatment approach, even among persons with PD and mild cognitive dysfunction.”

REFERENCES
1. Vaughan CP, Morley JF, Lehosit J, McGwin G, Muirhead L, Khakharia A, Johnson TM 2nd, Evatt ML, Sergent T, Burgio KL, Markland AD. Behavioral Compared With Drug Therapy for Overactive Bladder Symptoms in Parkinson Disease: A Randomized Noninferiority Trial. JAMA Neurol. 2025 Jul 14:e251904. doi: 10.1001/jamaneurol.2025.1904. Epub ahead of print. PMID: 40658410; PMCID: PMC12261112.
2. Jackson S, Donovan J, Brookes S, Eckford S, Swithinbank L, Abrams P. The Bristol Female Lower Urinary Tract Symptoms questionnaire: development and psychometric testing. Br J Urol. 1996 Jun;77(6):805-12. doi: 10.1046/j.1464-410x.1996.00186.x. PMID: 8705212.
3. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x. Erratum in: J Am Geriatr Soc. 2019 Sep;67(9):1991. doi: 10.1111/jgs.15925. PMID: 15817019.