Effect of Antimuscarinic Drugs on Cognitive Functions in the Management of Overactive Bladder in Elderly
Background: overactive bladder (OAB) affects 17-41% older adults in community dwelled setting. For several years, antimuscarinics have been validated as the first-line medical treatment for OAB. Despite abundant data obtained from clinical trials provisions the use of antimuscarinics, investigation about the effect of this drug on cognitive function in elderly remains scarce. The objective of this study is to investigate the effect of antimuscarinics therapy on cognitive functions in OAB geriatric patients. Methods: this study design is a systematic review and meta-analysis. Studies were collected using several search engines; those were PubMed, Science Direct, Cochrane, and EBSCOhost using predetermined MeSH keywords with Boolean operators. Selection of studies was done by three reviewers. Studies which fulfilled the inclusion and exclusion criteria underwent full-text review. For every selected full text, we extracted the following data if available: patients demographics, types of antimuscarinics used, placebo, dose, follow-up period, and Mini-Mental State Examination (MMSE) total score. Results: a total of 8 studies from an initial 146 publications were selected. There were 8 antimuscarinic agents evaluated in the studies, including Oxybutynin, Darifenacin, Tolterodine, Trospium, Imidafenacin, Propiverine hydrochloride, Fesoterodine, and Solifenacin. Oxybutynin was shown to have largest effect towards the decline of MMSE score [Mean difference: -2.90; 95% CI: -4.07, -1.73]. Darifenacin and Tolterodine were also shown to be significant in the decline of total MMSE score, although still inferior to Oxybutynin. Conclusion: the use of most antimuscarinics medication has little to no effect towards the cognitive function in the management of overactive bladder in elderly patients. However, Oxybutynin, Darifenacin, and Tolterodine was shown to have significant decrease in cognitive functions, as shown in the decline of total MMSE score.
Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003;20:327-36.
Haylen BT, Freeman RM, Swift SE, et al. International Urogynecological Association; International Continence Society; Joint IUGA/ICS Working Group on Complications Terminology. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint terminology and classification of the complications related directly to the insertion of prostheses (meshes, implants, tapes) and grafts in female pelvic floor surgery. Neurourol Urodyn. 2011;308:2e12.
Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U. Standardisation sub-committee of the International Continence Society. The standardization of terminology of lower urinary tract function: Report from the Standardisation Sub-committee of the International Continence Society. Neurourology and Urodynamics. 2002;21:167-78.
Brown JS, Vittinghoff E, Wyman JF, Stone KL, Nevitt MC, Ensrud KE, Grady D. Urinary incontinence: Does it increase risk for falls and fractures? Study of Osteoporotic Fractures Research Group. J Am Geriatrics Soc. 2000;48:721-5.
Chapple CR, Khullar V, Gabriel Z, Muston D, Bitoun CE, Weinstein D. The effects of antimuscarinic treatments in overactive bladder: An update of a systematic review and meta-analysis. Eur Urol. 2008; 54:543-62.
Francis PT, Palmer AM, Snape M, Wilcock GK. The cholinergic hypothesis of Alzheimer’s disease: A review of progress. J Neurol Neurosurg Psychiatry. 1999;66:137-47.
Feinberg M. The problems of anticholinergic adverse effects in older patients. Drugs & Aging. 1993;3:335-48.
Esin E, Ergen A, Cankurtaran M, et al. Influence of antimuscarinic therapy on cognitive functions and quality of life in geriatric patients treated for overactive bladder. Aging & Mental Health. 2015;19(3):217-23. DOI: 10.1080/13607863.2014.922528.
Sakakibara R, Tateno F, Yano M, et al. Imidafenacin on bladder and cognitive function in neurologic OAB patients. Clin Auton Res. 2013;23:189–95. DOI 10.1007/s10286-013-0200-3.
Sakakibara R, Hamano H, Yagi H. Cognitive safety and overall tolerability of imidafenacin in clinical use: a long-term, open-label, post-marketing surveillance study. LUTS. 2014;6:138–144. DOI: 10.1111/luts.12068.
Scheife R, Takeda M. Central nervous system safety of anticholinergic drugs for the treatment of overactive bladder in the elderly. Clin Ther. 2005;27:144–53.
Anderson RU, Mobley BB, Saltzstein D, et al. Once daily controlled versus immediate release oxybutynin chloride for urge urinary incontinence. J Urol. 1999;161:1809–12.
Katz IR, Sands LP, Bilker W, DiFilippo S, Boyce A, D’Angelo K. Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride. J Am Geriatr Soc. 1998;46(1):8–13.
Kay G, Crook T, Rekeda L, et al. Differential effects of the antimuscarinic agents darifenacin and oxybutynin ER on memory in older subjects. Eur Urol. 2006;50(2):317–26.
Devineni D, Skerjanec A, Woodworth TG. Low central nervous system (CNS) penetration by darifenacin, a muscarinic M3 selective receptor antagonist, in rats. Proc Br Pharmacol Soc Summer 2005 (abstr092P) http://www.pa2online.org/abstracts/Vol3Issue2abst092P.pdf.
Skerjanec A, Devineni D. Affinity of darifenacin for the p-glycoprotein efflux pump: a mechanism contributing to the CNS sparing profile? Abstract presented at British Pharmacological Society Winter Meeting, 14-16 December, 2004, Newcastle, UK.
van Assema DM, Lubberink M, Boellaard R, et al. P-glycoprotein function at the blood-brain barrier: effects of age and gender. Mol Imaging Biol. 2012;14(6):771–6. doi:10.1007/s11307-012-0556-0.
Nilvebrant L. The mechanism of action of tolterodine. Rev Contemp Pharmacother. 2000;11:13-27.
Malhotra B. Lipophilicity of 5 Hydroxymethyl Tolterodine, the active metabolite of Fesoterodine. Uro Today Int J. 2008;1(15). DOI: 10.3834/uij.1939-4810.2008.06.35.
DuBeau CE, Kraus SR, Griebling TL, et al. Effect of fesoterodine in vulnerable elderly subjects with urgency incontinence: a double-blind, placebo-controlled trial. J Urol. 2014;191:395-404. DOI: 10.1016/j.juro.2013.08.027.
Wagg A, Khullar V, Marschall-Kehrel D, Michel MC, Oelke M, Darekar A. Flexible-dose Fesoterodine in elderly adults with overactive bladder: Results of the randomized, double-blind, placebo-controlled study of Fesoterodine in an aging population trial. JAGS. 2013; 61:185–93. DOI: 10.1111/jgs.12088.
Lee YS, Lee KS, Kim JC, et al. Persistence with solifenacin add-on therapy in men with benign prostate obstruction and residual symptoms of overactive bladder after tamsulosin monotherapy. Int J Clin Pract. 2014;68(12):1496-502. doi: 10.1111/ijcp.12483. Epub 2014 Oct 6.
Geller EJ, Dumond JB, Bowling JM, et al. Effect of trospium chloride on cognitive function in women aged 50 and older: a randomized trial. Female Pelvic Med Reconstr Surg. 2017;23: 118–23. DOI: 10.1097/SPV.0000000000000374.
Hampel C, Betz D, Burger M, Nowak C, Vogel M. Solifenacin in the elderly: Results of an observational study measuring efficacy, tolerability, and cognitive effects. Urol Int. DOI: 10.1159/000455257.
Kirill Kosilov, Irina Kuzina, Vladimir Kuznetsov, et al. Cognitive functions and health-related quality of life in men with benign prostatic hyperplasia and symptoms of overactive bladder when treated with a combination of tamsulosin and solifenacin in a higher dosage. Aging Male. 2017. DOI: 10.1080/13685538.2017.1398723.
Ouslander JG. Geriatric considerations in the diagnosis and management of overactive bladder. Urology. 2002; 60 (5):Supp 1. DOI: 10.1016/S0090-4295(02)01795-8.
- There are currently no refbacks.