I recently saw a 77 year-old Latina woman with complaints of strong urinary urgency resulting in incontinence, frequency every 2 hours with nocturia x4. She described urgency as “pressure in my bladder.” She reported that her symptoms were “terrible.” Her symptoms were longstanding but appeared to be worsening. She had undergone lumbar spinal fusion 18 months ago, her third back surgery. This was about the time symptoms worsened.
Recent ultrasound was normal, post-void residual volume (PVR) was 20 mLs. In the past, I had diagnosed vaginal atrophy but the patient was non-compliant with transvaginal estrogen. Medical history included hypothyroidism, depression, osteoarthritis, hyperlipidemia, and controlled hypertension. She was taking 11 medications, including 3 anticholinergics. I had seen her 3 years ago and she had been following a bladder training program, but over time it was not as effective in suppressing urgency. She had seen some benefit from behavioral bladder training and had eliminated or decreased daily consumption of certain dietary bladder irritants (e.g. caffeine and spice foods). She has never tried overactive bladder (OAB) drug therapy.
You may be wondering why I decided to write a blog on OAB in a 77-year-old patient. My concern was the effects of medications for OAB that may have a negative effect on the patient’s cognition and you might be interested in my thought process for what I decided to recommend. There are two pharmacological classes for treatment of OAB, anti-muscarinic (targeting the M3 receptor) and β3-adrenoceptor agonists. Because of her age, I did not want to prescribe an antimuscarinic/anticholinergic drug. So I prescribed mirabegron, the alternative to antimuscarinics as it has a more favorable benefit-to-risk ratio in older patients.
My concern with prescribing an anti-muscarinic OAB drug is possible side effects, as the risk of anticholinergic adverse events (AEs) such as dry mouth and constipation increases with age. Particularly in older adults (>65 yo), exposure to medications with anticholinergic properties has also been linked to adverse cognitive effects. Older adults are particularly sensitive to anticholinergic effects as a result of age-related decrease in cholinergic neurons/receptors in the brain, reduction in hepatic and renal clearance of medications, and increase in blood-brain barrier permeability. In addition, the older patient population is likely to be receiving polypharmacy including other drugs with anticholinergic activity, potentially resulting in a problematic anticholinergic burden, with negative effects on cognitive performance. The 2019 updated Beers criteria list all antimuscarinic drugs used for the treatment of OAB as drugs with strong anticholinergic properties and potentially inappropriate for first-line treatment in those ≥65 year or older.2
Vouri and colleagues reported on randomized controlled trials (RCTs) along with sub-analyses and pooled analyses that compared antimuscarinics to placebo or another antimuscarinic, assessing AEs or treatment discontinuations in a population of adults 65 or older.9 They found anticholinergic AEs were more common in antimuscarinics compared to placebo. Incidence of dizziness, dyspepsia, and urinary retention with fesoterodine, headache with darifenacin, and urinary tract infections with solifenacin were significantly higher compared to placebo. Treatment discontinuation due to AEs and dry mouth were higher in the antimuscarinics when compared to placebo in older adults.
Antimuscarinics that have anticholinergic properties have also been linked to adverse cognitive effects. Welk conducted a population-based, retrospective, matched cohort study using linked administrative data (Ontario, Canada from 2010 to 2018) matching 47,324 new users of anticholinergic OAB medications (oxybutynin, tolterodine, solifenacin, darifenacin, fesoterodine, trospium) to 23,662 new users of a beta-3 agonist medication (mirabegron).11 The most common anticholinergics used were tolterodine (40%), oxybutynin (29%) and solifenacin (26%). The use of these medications among patients with OAB was associated with an increased risk of new-onset dementia compared to beta-3 agonist users. Interestingly, men, regardless of age, also tended to develop more dementia events.
Griebling published the results of a pre-planned analysis aimed to measure differences in cognitive function in subjects in the PILLAR phase 4 study which compared mirabegron vs placebo in patients ≥65 years with OAB and incontinence.6,10 This pre-planned analysis measured differences in cognitive function, using a rapid screening instrument for mild cognitive impairment: the Montreal Cognitive Assessment (MoCA). Treatment with mirabegron for 12 weeks had no adverse impact on cognitive function in patients aged ≥65 years, compared with those randomized to placebo. Mirabegron efficacy was demonstrated and it did not worsen cognition in older adults treated for OAB. The authors felt that mirabegron is a viable alternative for the treatment of older patients with OAB, especially for those on anticholinergic medications for other diseases.
So, my 77 yo patient started Mirabegron 25 mg daily. When she returned 4 weeks later, she noted she no longer gets up, as she doesn’t “have that pressure to urinate.”
“I could hold it until I get to the bathroom,” she said. A night, she reported only awakening two times to void instead of 3 to 4. And in the morning, she wakes up “dry, not wet." She thanked me for my care.
Written by: Diane Newman, DNP, CRNP, FAAN, BCB-PMD, Nurse Practitioner (NP), Co-Director, Penn Center for Continence and Pelvic Health Director, Clinical Trials, Division of Urology, Adjunct Professor of Urology in Surgery, Penn Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
- Ancelin ML, Artero S, Portet F, Dupuy A-M, Touchon J, Ritchie K. Nondegenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ. 2006;332:455.
- American Geriatrics Society 2019 Updated Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674-694. doi: 10.1111/jgs.15767
- Campbell N, Boustani M, Limbil T, Ott C, Fox C, Maidment I, et al. The cognitive impact of anticholinergics: A clinical review. Clin Interv Aging. 2009;4:225–33.
- Fortin M-P, Rouch I, Dauphinot V, Gédéon C, Genthon S, Bonnefoy M, et al. Effects of anticholinergic drugs on verbal episodic memory function in the elderly: a retrospective, cross-sectional study. Drugs Aging. 2011;28(3):195–204.
- Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175(3):401–7.
- Griebling, TL., Campbell, NL, Mangel J, Staskin D, Herschorn S, Elsouda D, Schermer CR. Effect of mirabegron on cognitive function in elderly patients with overactive bladder: MoCA results from a phase 4 randomized, placebo-controlled study (PILLAR). BMC Geriatrics 2020 20:109
- Mostafaei H, Shariat SF, Salehi-Pourmehr H, Janisch F, Mori K, Quhal F & Hajebrahimi S. (2020) The clinical pharmacology of the medical treatment for overactive bladder in adults, Expert Review of Clinical Pharmacology, DOI: 10.1080/17512433.2020.1779056
- Pratt, ST & Susskind, A. Management of Overactive Bladder in Older Women. Curr Urol Rep. 2018, Sep 10;19(11):92. doi: 10.1007/s11934-018-0845-5.
- Vouri SM, Kebodeaux CD, Stranges PM, Teshome BF. Adverse events and treatment discontinuations of antimuscarinics for the treatment of overactive bladder in older adults: A systematic review and meta-analysis. Arch Gerontol Geriatr. 2017 Mar-Apr;69:77-96. doi: 10.1016/j.archger.2016.11.006.
- Wagg A, Staskin D, Engel E, Herschorn S, Kristy RM, Schermer CR. Efficacy, safety, and tolerability of mirabegron in patients aged ≥65yr with overactive bladder wet: a phase IV, double-blind, randomised, placebo-controlled study (PILLAR). Eur Urol. 2020,77(2):211-220. doi: 10.1016/j.eururo.2019.10.002
- Welk B, McArthur E. Increased risk of dementia among patients with overactive bladder treated with an anticholinergic medication compared to a beta-3 agonist: a population-based cohort study. BJU Int. 2020 Jul;126(1):183-190. doi: 10.1111/bju.15040.