Pharmacological treatment of urinary incontinence in the elderly

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Contributed by Dr. Adrian Wagg, MB, BS, FRCP, FRCP(E), FHEA (MD) Professor of Healthy Ageing Division Director, Geriatric Medicine University of Alberta

Case:

Phyllis, a 78-year-old woman with mild COPD comes to your office for a routine disease-monitoring visit. During the consultation, she tells you that she has been experiencing severe urinary urgency for many months and has had several accidents on the way to the washroom over the last few weeks.  She hadn’t mentioned this before as she was embarrassed and thought it normal for older women. Her close friend suggested she mention it to you.

The issue

Although extremely common1, lower urinary tract symptoms (LUTS) and urinary incontinence (UI) are often ignored, or are believed to be a normal consequence of aging by many older people. These beliefs contribute to a delay of sufferers seeking care, despite them being stigmatizing conditions2,3. Likewise, there appears to be a degree of therapeutic nihilism on the part of clinicians.  Evidence suggests older people receive a lower standard of care, when measured against national guidelines, than younger people4,5. The reasons for this are multifactorial, but seem to revolve around:

  • Disease and management-related education.
  • The priority of managing incontinence when weighed against other illnesses.
  • A scarcity of services for continence problems6.

The bottom line

Lower urinary tract symptoms and incontinence are common and profoundly affect quality of life.

The underlying cause of incontinence in older persons is usually multifactorial. Medication combinations and comorbid conditions may contribute to symptoms. Medication review and modifications to disease management where possible are necessary. Medication management is often needed in addition to lifestyle and behavioural techniques; one should actively consider rational, evidence-informed use.

Background

LUTS and UI are highly prevalent in the population and this prevalence increases in association with increasing age; in the eighth decade there is little difference in prevalence between men and women1. Frequency, urgency and nocturia, the most common LUTS, are components of overactive bladder syndrome (OAB) 7 and are extremely common in later life, with up to 50% of men and 60% of women aged over 70-years-old describing at least one LUTS1. LUTS and UI have a profound impact on quality of life8, are associated with falls9 and deconditioning10, social isolation, depression11 and an increased likelihood of institutionalization, particularly in the face of a dementia diagnosis12.  UI, particularly urgency UI, may be a marker of frailty in older persons13.  The majority of urinary incontinence can be accounted for by stress (exertional) incontinence, urgency incontinence, that resulting from severe urgency, or mixed incontinence symptoms (both).  In the elderly, an increasing prevalence of ineffective voiding needs to be taken into account.

Assessment

A history of storage and voiding symptoms; their duration, severity and impact; the impact of comorbid conditions; and toileting and fluid intake habits is required. This should supplement the usual medical, surgical and medication history. One should also make an assessment of potential environmental factors. Examination should exclude fecal loading, severe urogenital atrophy, prolapse beyond the introitus. It should assess pelvic muscle contraction strength and look for exertional incontinence in women. In men, examination of the external genitalia and an estimation of prostatic size should be made. A bedside urinalysis should be performed to exclude acute urinary tract infection and assess for hematuria. Postvoid residual should be evaluated only in patients with voiding symptoms, neurological diagnoses and history of either prostatic or incontinence surgery. In these patients, postvoid residual volume (PVR) should be measured prior to starting antimuscarinic treatment.  No other investigations are required as part of the initial assessment leading to a symptomatic diagnosis. This is supported by national and international guidelines14-16.

Management

·      Lifestyle and behavioural

Initial management for all patients should consist of fluid management; normalization of fluid intake results in a beneficial effect on symptoms (1.5-2L / day – reduce slowly for those with a large excess). This includes a trial of caffeine reduction and alcohol intake review. Weight reduction has benefits more for stress UI than urgency UI.  Pelvic floor muscle therapy is beneficial for both stress and urgency UI in women; in the latter condition as part of urgency suppression, where women can contract their pelvic floor17.  There are few data in men. Bladder retraining, the progressive prolongation of voiding interval by urgency suppression is recommended as first line treatment for overactive bladder and urgency UI18.  Depending on cognition and functional ability, varying toileting programmes, ranging from prompted voiding to scheduled voiding may be employed.  All are successful but require active caregiver participation for maximal benefit. International guidelines on management for frail older people contain algorithms for management19.

·      Pharmacological

Stress Incontinence

Where behavioural and lifestyle management provides suboptimal results, pharmacological therapy is available.  For stress UI in women, duloxetine has evidence of efficacy, but the balance of benefits and harms do not favour use20.  For post prostatectomy incontinence in men, current evidence does not support use21.

Overactive bladder (OAB) and urgency incontinence

Antimuscarinics

For OAB and urgency UI, antimuscarinics have, until relatively recently, been the only class of medication available for treatment.  Immediate release oral oxybutynin which, unfortunately, we are compelled to use first-line, is associated with the greatest likelihood of harm and non-adherence in older people22,23. Despite evidence for efficacy in older people for the newer antimuscarinic agents (Table 1) – and in medically complex older people for fesoterodine24  – many practitioners tend to avoid these medications. However, there is evidence for the absence of an increased rate of falls in treated older people25, cognitive safety in older people26 and absence of treatment-associated delirium27.  Avoidance of these medications is often supported by the opinion of geriatricians but ignores the evidence in this area and cites genericized evidence concerning the effects of anticholinergic drugs to support the position28. With that in mind, there remains little evidence to guide management of frail older persons. A recent systematic review from Sweden29 concluded that anticholinergics have a small, but significant, effect on urinary leakage in older adults with UUI but that treatment with drugs for UUI in the frail elderly is not evidence-based.  The 5th International Consultation on Incontinence notes that treatment, which has evidence for efficacy in older people should not be denied to the frail elderly, but that due regard should be made of likely benefits and harms, remaining life expectancy and expectations of either the patient or, where appropriate, the caregiver19. Thus pharmacological treatment of older and medically complex older people needs to be a contextually appropriate decision.

Of note is the association of worsening OAB symptoms with the prescription of cholinesterase inhibitors for Alzheimer’s disease30,31. Where the cholinesterase inhibitor is effective and the patient or caregiver wishes to continue it and the LUTS are disabling and bothersome, there is evidence that pharmacological treatment of the incontinence with antimuscarinics is not the counterintuitive manoeuvre that the opposing mechanisms of action might dictate27,32.

Dosing should start at the lowest level to optimise tolerability and consideration should be made to the individual total anticholinergic load and the individual degree of cognitive risk.  Epidemiological data largely support an association between high anticholinergic drug exposure and cognitive impairment over a two-to-three year period33.

Beta-3-agonist: mirabegron

There is evidence of short-term efficacy and longer-term safety of mirabegron in the treatment of older adults with OAB in a pooled analysis of patients >65 years old from registration studies34.  Mirabegron, although associated with a similar frequency of adverse events in older people, does not cause dry mouth, the adverse effect commonly associated with withdrawal from treatment with antimuscarinics.  There has been some concern regarding the potential of adverse cardiovascular effects, but there appears to be no excess risk over placebo or when compared to the rates of hypertension or tachycardia associated with antimuscarinic treatments35.  There is no evidence for an effect on cognition, nor as yet any prospectively-gathered evidence for older patients or the medically complex elderly.  Results of this trial are expected in 2018.

Phosphodiesterase inhibitors

A recent meta-analysis of the drug tadalafil for LUTS and ED in men has concluded that, in men >75 years of age, the efficacy of tadalafil is reduced compared to that in younger men36.  This drug should therefore not be routinely used in older men for this indication.

Topical oestrogens

There are no specific data on the use of topical oestrogens for vaginal symptoms in the elderly. Data in younger women support their use for the symptoms associated with urogenital atrophy. Use can also ameliorate urinary urgency37. They have no role in the treatment of UI38.

Appropriate prescribing

A recent specific systematic review of oral pharmacological treatments for LUTS in older people has categorised drugs into categories of appropriateness based upon available evidence as part of the Fit foR The Aged (FORTA) system.  Consideration should be made to using the highest-rated drug where possible but the use of lower-rated drugs needs to consider the patient’s context.  For example, although rated “C- Caution”, tamsulosin has been widely used, although there are few published data on its use in older men39.

1. Irwin DE, Milsom I, Hunskaar S, et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol. 2006;50(6):1306-1314; discussion 1314-1305.

2. Horrocks S, Somerset M, Stoddart H, Peters TJ. What prevents older people from seeking treatment for urinary incontinence? A qualitative exploration of barriers to the use of community continence services. Fam Pract. 2004;21(6):689-696.

3. Elstad EA, Taubenberger SP, Botelho EM, Tennstedt SL. Beyond incontinence: the stigma of other urinary symptoms. J Adv Nurs. 2010;66(11):2460-2470.

4. Wagg A, Duckett J, McClurg D, Harari D, Lowe D. To what extent are national guidelines for the management of urinary incontinence in women adhered? Data from a national audit. BJOG : an international journal of obstetrics and gynaecology. 2011;118(13):1592-1600.

5. Gibson W, Harari D, Husk J, Lowe D, Wagg A. A national benchmark for the initial assessment of men with LUTS: data from the 2010 Royal College of Physicians National Audit of Continence Care. World J Urol. 2015.

6. Nguyen K, Hunter KF, Wagg A. Knowledge and understanding of urinary incontinence: survey of family practitioners in northern Alberta. Can Fam Physician. 2013;59(7):e330-337.

7. Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourology and urodynamics. 2002;21(2):167-178.

8. Sexton CC, Coyne KS, Thompson C, Bavendam T, Chen CI, Markland A. Prevalence and effect on health-related quality of life of overactive bladder in older americans: results from the epidemiology of lower urinary tract symptoms study. Journal of the American Geriatrics Society. 2011;59(8):1465-1470.

9. Brown JS, Vittinghoff E, Wyman JF, et al. Urinary incontinence: does it increase risk for falls and fractures? Study of Osteoporotic Fractures Research Group. J Am Geriatr Soc. 2000;48(7):721-725.

10. McGrother CW, Donaldson MM, Hayward T, Matthews R, Dallosso HM, Hyde C. Urinary storage symptoms and comorbidities: a prospective population cohort study in middle-aged and older women. Age Ageing. 2006;35(1):16-24.

11. Zorn BH, Montgomery H, Pieper K, Gray M, Steers WD. Urinary incontinence and depression. J Urol. 1999;162(1):82-84.

12. Thomas P, Ingrand P, Lalloue F, et al. Reasons of informal caregivers for institutionalizing dementia patients previously living at home: the Pixel study. Int J Geriatr Psychiatry. 2004;19(2):127-135.

13. Tinetti ME, Inouye SK, Gill TM, Doucette JT. Shared risk factors for falls, incontinence, and functional dependence. Unifying the approach to geriatric syndromes. JAMA. 1995;273(17):1348-1353.

14. Lucas MG, Bedretdinova, D., Berghmans, L.C., Bosch, J.L.H.R., Burkhard, F.C., Cruz, F., Nambiar, A.K., Nilsson, C.G., Tubaro, A., Pickard, R.S. . Guidelines on urinary incontinence. web page 2015; 2015.

15. . Urinary Incontinence in Women: The Management of Urinary Incontinence in Women. London2013.

16. Bettez M, Tu, L. M., Carlson, K., Corcos, J., Gajewski, J., Jolivet, M., Bailly, G. Guidelines for Adult Urinary Incontinence Collaborative Consensus Document for the Canadian Urological Association. 2012.

17. Dumoulin C, Hay-Smith J. Pelvic floor muscle training versus no treatment, or inactive control treatments, for urinary incontinence in women. Cochrane Database Syst Rev. 2010(1):CD005654.

18. Qaseem A, Dallas P, Forciea MA, et al. Nonsurgical management of urinary incontinence in women: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014;161(6):429-440.

19. Wagg A, Gibson W, Ostaszkiewicz J, et al. Urinary incontinence in frail elderly persons: Report from the 5th International Consultation on Incontinence. Neurourol Urodyn. 2015;34(5):398-406.

20. Maund E, Schow Guski, L., Gøtzsche, P.C. Considering benefits and harms of duloxetine for treatment of stress urinary incontinence: a meta-analysis of clinical study reports Canadian Medical Association Journal. 2017;189(5).

21. Lovvik A, Muller S, Patel HR. Pharmacological Treatment of Post-Prostatectomy Incontinence: What is the Evidence? Drugs Aging. 2016;33(8):535-544.

22. Gibson W, Athanasopoulos A, Goldman H, et al. Are we shortchanging frail older people when it comes to the pharmacological treatment of urgency urinary incontinence? Int J Clin Pract. 2014;68(9):1165-1173.

23. Wagg A, , Diles, D. Four year persistence and drug treatment patterns in overactive bladder: data from Canadian datasets.; . Paper presented at: 68th Annual Meeting of the Canadian Urological Association 2013; Niagra Falls, ON,.

24. Dubeau CE, Kraus SR, Griebling TL, et al. Effect of Fesoterodine in Vulnerable Elderly Subjects with Urgency Incontinence: A Double-Blind, Placebo Controlled Trial. The Journal of urology. 2013.

25. Gomes T, Juurlink DN, Ho JM, Schneeweiss S, Mamdani MM. Risk of serious falls associated with oxybutynin and tolterodine: a population based study. The Journal of urology. 2011;186(4):1340-1344.

26. Wagg A, Verdejo C, Molander U. Review of cognitive impairment with antimuscarinic agents in elderly patients with overactive bladder. International journal of Clinical Practice. 2010;64(9):1279-1286.

27. Sink KM, Thomas J, 3rd, Xu H, Craig B, Kritchevsky S, Sands LP. Dual use of bladder anticholinergics and cholinesterase inhibitors: long-term functional and cognitive outcomes. Journal of the American Geriatrics Society. 2008;56(5):847-853.

28. Panel. AGSBCUE. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatrics Society. 2015;63(11):2227-2246.

29. Samuelsson E, Odeberg J, Stenzelius K, et al. Effect of pharmacological treatment for urinary incontinence in the elderly and frail elderly: A systematic review. Geriatr Gerontol Int. 2015;15(5):521-534.

30. Starr JM. Cholinesterase inhibitor treatment and urinary incontinence in Alzheimer’s disease. J Am Geriatr Soc. 2007;55(5):800-801.
31. Gill SS, Mamdani M, Naglie G, et al. A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs. Archives of internal medicine. 2005;165(7):808-813.

32. Isik AT, Celik T, Bozoglu E, Doruk H. Trospium and cognition in patients with late onset Alzheimer disease. J Nutr Health Aging. 2009;13(8):672-676.
33. Wagg A. The cognitive burden of anticholinergics in the elderly- implications for the treatment of overactive bladder. European Urology Review. 2012;7( (1)):42-49.

34. Wagg A, Cardozo L, Nitti VW, et al. The efficacy and tolerability of the beta3-adrenoceptor agonist mirabegron for the treatment of symptoms of overactive bladder in older patients. Age Ageing. 2014;43(5):666-675.

35. Rosa GM, Ferrero S, Nitti VW, Wagg A, Saleem T, Chapple CR. Cardiovascular Safety of beta3-adrenoceptor Agonists for the Treatment of Patients with Overactive Bladder Syndrome. Eur Urol. 2016;69(2):311-323.

36. Oelke M, Wagg A, Takita Y, Buttner H, Viktrup L. Efficacy and safety of tadalafil 5 mg once daily in the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia in men aged >/=75 years: integrated analyses of pooled data from multinational, randomized, placebo-controlled clinical studies. BJU Int. 2016.

37. Weber MA, Kleijn MH, Langendam M, Limpens J, Heineman MJ, Roovers JP. Local Oestrogen for Pelvic Floor Disorders: A Systematic Review. PLoS One. 2015;10(9):e0136265.

38. Weber MA, Lim V, Oryszczyn J, et al. The Effect of Vaginal Oestriol Cream on Subjective and Objective Symptoms of Stress Urinary Incontinence and Vaginal Atrophy: An International Multi-Centre Pilot Study. Gynecol Obstet Invest. 2017;82(1):15-21.

39. Oelke M, Becher K, Castro-Diaz D, et al. Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014). Age Ageing. 2015;44(5):745-755.

40. Bemelmans BL, Kiemeney LA, Debruyne FM. Low-dose oxybutynin for the treatment of urge incontinence: good efficacy and few side effects. Eur Urol. 2000;37(6):709-713.

41. Szonyi G, Collas DM, Ding YY, Malone-Lee JG. Oxybutynin with bladder retraining for detrusor instability in elderly people: a randomized controlled trial. Age and Ageing. 1995;24(4):287-291.

42. Kay GG, Abou-Donia MB, Messer WS, Jr., Murphy DG, Tsao JW, Ouslander JG. Antimuscarinic drugs for overactive bladder and their potential effects on cognitive function in older patients. J Am Geriatr Soc. 2005;53(12):2195-2201.

43. Kay GG, Staskin DR, Macdiarmid S, McIlwain M, Dahl NV. Cognitive effects of oxybutynin chloride topical gel in older healthy subjects: a 1-week, randomized, double-blind, placebo- and active-controlled study. Clinical drug investigation. 2012;32(10):707-714.

44. Kay G, Kardiasmenos, K., Crook, T. Differential effects of the antimuscarinic agents tolterodine tartrate ER and oxybutynin chloride ER on recent memory in older subjects. Proceedings of the 36th meeting of the International Continence Society. 2006;25(6):P087.

45. Kay GG, Ebinger U. Preserving cognitive function for patients with overactive bladder: evidence for a differential effect with darifenacin. International journal of Clinical Practice. 2008;62(11):1792-1800.

46. Staskin D, Kay, G., Tannenbaum,C., Goldman, H.B., Bhashi, K., Ling, J., Oefelein, M.G. Trospium chloride has no effect on memory testing and is assay undetectable in the central nervous system of older patients with overactive bladder. International journal of Clinical Practice. 2010;64(9):1294 – 1300.

47. Wagg A, Dale, M., Compion, G., Stow, B. Tretter, R. Solifenacin and cognitive impairment in elderly people with mild cognitive impairment: the SENIOR study. 2012.

48. Kay GG, Maruff P, Scholfield D, et al. Evaluation of cognitive function in healthy older subjects treated with fesoterodine. Postgraduate medicine. 2012;124(3):7-15.

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