Management of urinary incontinence in older people Shashi Gadgil BSc, MRCP and Adrian Wagg FRCP

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1 Management of urinary incontinence in older people Shashi Gadgil BSc, MRCP and Adrian Wagg FRCP Prevalence (%) Our series Prescribing in older people gives practical advice for successful management of the special problems experienced by this patient group. Here, the authors describes the drug management of urinary incontinence Age group (years) severe moderate slight unknown Figure 1. Prevalence of urinary incontinence in women by age and severity, showing an increase in severe incontinence in older patients 1 Urinary incontinence is extremely common among older people, affecting an estimated 3.9 million people in the UK (see Figure 1). This is associated with an increased utilisation of health and social care, likelihood of institutionalisation and considerable co-morbidity such as skin infection, depression, urinary tract infection and an increased risk of falls and fractures in those with urgency incontinence. Early identification and intervention can greatly improve the health and quality of life in many of these patients. Incontinence can, in the majority of cases, be divided into stress, urge and mixed incontinence. Older people may also suffer from nocturia or nocturnal enuresis. Overactive bladder/ urgency incontinence Overactive bladder syndrome is the most common cause of urinary incontinence in the older population, yet for the vast majority of cases the cause is unknown. The patient suffers involuntary bladder contractions regardless of whether the bladder is full. This leads to symptoms of urgency, frequency and urge incontinence. The underlying urodynamic diagnosis, detrusor overactivity, is also associated with bladder outflow obstruction in men, pelvic surgery in women and neurological injury or disease. Stress urinary incontinence Stress incontinence is the involuntary leakage of urine during exertion or activities that increase intraabdominal pressure. For women, the risk of stress incontinence increases following pregnancy and vaginal delivery, and prevalence is higher at the age of menopause. Obesity and smoking are also risk factors. Nocturnal frequency and polyuria In later life, changes in renal physiology result in the kidneys working harder at night to produce greater quantities of more dilute urine. This can lead to increased nocturnal frequency. Nocturnal polyuria is defined as producing more than 35 per cent of total daily urine output at night. Other causes Older patients are subject to the same bladder problems as younger Prescriber 19 April

2 adults. However, factors such as concomitant dependency, disease and disability (see Table 1) and drug therapy (see Table 2) often compromise the older patient s coping ability and may render them incontinent. Diagnosis A three-day bladder diary and a thorough medical and drug history will establish the diagnosis and determine contributing factors for urinary incontinence (see Table 3). For the majority of patients presenting with urgency and frequency, referral for investigation is unnecessary, but these symptoms are not exclusive to overactive bladder and other lower urinary tract pathology should be excluded by examination (see Table 4). Indications for specialist referral are outlined in Table 5. Multichannel cystometry (urodynamics) is not recommended before starting conservative treatment, but should be reserved for those older women in whom the diagnosis is in doubt or for whom surgical management is contemplated. Management Conservative Ease of access to lavatory facilities needs to be considered, particularly in institutional settings. Maintaining mobility has a positive effect upon urinary incontinence. Use of incontinence pads should not be considered to be a treatment for incontinence and should only be used as long-term management after other options have been explored. A trial of supervised pelvic floor muscle training for at least three months should be offered as firstline treatment to women with stress or mixed urinary incontinence. Bladder retraining is recom- Diseases affecting mobility Nervous system disorders affecting cognition and neural control mechanisms Other medical conditions arthritis hip fracture contractures peripheral vascular disease stroke Parkinson s disease dementia stroke Parkinson s disease diabetes mellitus causing polyuria and autonomic neuropathy congestive heart failure leading to excess nocturnal urine production venous insufficiency a similar mechanism chronic lung disease exacerbation of stress incontinence Table 1. Concomitant diseases that may have an impact upon urinary continence mended as a first-line treatment for urgency incontinence. This requires motivation, will power and supervision to be effective. Where the patient is cognitively impaired or institutionalised, a progressive regular toileting regimen may be employed. Drug therapy For urgency and urge incontinence, the aim of drug therapy is to allow the patient to regain control of their bladder, reducing urgency, frequency and incontinence episodes and regaining quality of life. All of the currently available drugs have variable rates of similar side-effects, notably dry mouth, constipation, blurred vision and oesophageal reflux. Oxybutynin is a nonselective antimuscarinic agent with some local anaesthetic properties, and has a half-life of five hours in the older person. Studies of oxybutynin in older people using a dose lower than the licensed 5mg threetimes daily have shown efficacy, a reduction in adverse effects and increased tolerability. 2,3,4 A modified-release preparation of oxybutynin (Lyrinel XL) is effective and has fewer side-effects. Transdermal oxybutynin (Kentera) avoids the majority of antimuscarinic side-effects associated with the oral preparation, but its use is limited due to applicationsite reactions. Solifenacin (Vesicare) is a long-acting once-daily antimuscarinic agent that is effective in the treatment of overactive bladder. A metaanalysis of trial results from older subjects has shown the drug to be effective in reducing all objective disease variables with a restoration of continence in up to 49 per cent of people. 5 In a randomised controlled trial versus extended-release tolterodine (Detrusitol XL), solifenacin was shown to be noninferior in terms of reduction in micturition frequency and superior to tolterodine in a number of key indicators. 6 Tolterodine (Detrusitol) is a nonselective antimuscarinic agent that appears to have functional selectivity for bladder over salivary glands, perhaps accounting for 36 Prescriber 19 April 2008

3 Drug Diuretics Calcium-channel blockers Anticholinergics (including antihistamines, antipsychotics, antispasmodics, antiparkinsonian agents) Effect increase urinary frequency and may precipitate urge incontinence in predisposed individuals associated with polyuria, especially at night when fluid redistribution occurs constipation may precipitate confusion, especially in those with pre-existing cognitive impairment frequency of micturition day and night presence of urinary urgency how long can the patient voluntarily delay voiding? presence of urgency incontinence can the patient always get to the lavatory in time? presence of dysuria may suggest infection specific aggravating factors running water, putting key in door, etc? Table 3. Basic history for overactive bladder Alpha-blockers NSAIDs H 2 -antagonists ACE inhibitors SSRIs Cholinesterase inhibitors Lithium Benzodiazepines and antipsychotics may predispose to stress incontinence due to relaxant effect on the external urethral sphincter salt and water retention confusion chronic cough associated with new-onset urgency incontinence increase in urgency incontinence diabetes insipidus-type state any sedative medication with an appreciable hangover effect will exacerbate continence problems in predisposed older people Table 2. Drugs that may potentially aggravate or predispose to urinary incontinence the lower incidence of dry mouth 7 and the reduction in treatment withdrawals. Extended-release tolterodine offers improved tolerability and an enhanced efficacy compared with the immediaterelease compound. The drug begins to works within one week but the maximum effect is not attained until after five to eight weeks of treatment. Tolterodine does not significantly worsen postvoid residual volumes and has been effective in treating men with both over-active bladder and bladder outflow obstruction. 8,9 The drug is best tolerated when given as a nocturnal dose. Trospium chloride (Regurin) is a quaternary ammonium salt. Several randomised controlled trials, using urodynamic measures of diagnosis and extent of disease as well as clinical and quality of life outcomes, have shown trospium chloride to be effective in the treatment of detrusor overactivity Studies have included patients of up to 70 years of age, and there are no data to suggest that older age groups do less well. Trospium chloride has been found to be superior in effect to placebo and equivalent in efficacy to oxybutynin at doses of 5mg three times daily. Adverse effects occur less commonly than with oxybutynin. There are no significant drug interactions and trospium chloride does not cross the blood-brain barrier, therefore it is unlikely to have an adverse effect on cognition. Darifenacin (Emselex) is effective in terms of objective and subjective variables and quality of life. Pooled data demonstrate that efficacy for the over 65 year olds is similar to that observed in younger age groups. 13,14 Darifenacin does not adversely affect cognition and CNS tolerability appears to be similar to placebo. 15 The major side-effects are constipation, which affected a maximum of 23.6 per cent of subjects at a dose of 15mg (10 per cent required treatment and 2.7 per cent stopped the medication), and dry mouth. Propiverine (Detrunorm) has combined antimuscarinic and calcium channel-blocking actions. Comparative trials against flavoxate (Urispas) and placebo and against oxybutynin and placebo have 38 Prescriber 19 April 2008

4 neurological examination of legs rectal and abdominal examination exclude presence of postvoiding residual volume (bladder ultrasound) exclude presence of urinary tract infection (dipstick testing or MSU) Table 4. Basic focussed physical examination haematuria in the absence of infection recurrent infections symptomatic prolapse at or below the introitus (entrance of the vagina) pelvic mass previous pelvic surgery suspected neurological disease pelvic pain Table 5. Indications for referral or investigation demonstrated that propiverine has a similar efficacy to oxybutynin 5mg three-times daily, but with a milder, less common incidence of dry month. Although there are no specific data from studies aimed at testing efficacy in older people, they were not specifically excluded from any study. Up to 20 per cent of patients experience mainly anticholinergic adverse effects. 16,17 Imipramine (licensed for nocturnal enuresis in children) is a nonselective antimuscarinic and alpha-adrenergic agent with a centrally active antidiuretic property. It has a strong inhibitory effect on detrusor muscle. In the treatment of 10 older patients with detrusor instability, continence was gained in six of the patients with a dose of mg. The incidence of sideeffects, particularly severe dry mouth, makes it difficult to titrate to an effective dose. 18 Duloxetine (Yentreve) is used in the management of stress incontinence and is thought to work by preventing the reuptake of serotonin and noradrenaline, increasing the activity of the pudendal nerve that supplies and controls the tone of the urethral rhabdosphincter. Women receiving duloxetine showed significant improvement in incontinence episodes and meaningful gains in quality of life. 19,20 The main limiting side-effect associated with duloxetine is nausea. Age does not appear to alter the safety profile. NICE 2006 guidelines recommend the use of nonproprietary oxybutynin as first-line treatment if bladder retraining fails. If this is not tolerated, any of the other agents may be used. Imipramine is not recommended and propiverine should be used for those with troublesome frequency as there are no continence data. DDAVP (desmopressin) There is evidence for the use of DDAVP (synthetic ADH with no effect on blood pressure) 21 in the management of nocturnal polyuria. The usefulness of DDAVP is limited to those with true nocturnal polyuria and it should be used with caution in patients on drugs predisposing to hyponatraemia. Serum sodium should Key points be monitored at three days following the start of therapy. There is also a role for this agent in the social control of daytime urinary frequency. Surgery Surgery is most applicable for those with detrusor overactivity associated with other conditions such as outflow tract obstruction; in this case the overactivity resolves in two-thirds of patients. For those with intractable disease uncontrollable by other means, then clam ileocystoplasty or detrusor myomectomy (bladder autoaugmentation) is used. Both of these techniques aim to create a high-capacity, low-pressure, stable reservoir. The operation is effective, with abolition of the underlying overactivity in 50 per cent of patients, in addition to an increase in bladder compliance and the functional capacity of the bladder. For per cent of patients the operation is associated with inefficient voiding that requires self-catheterisation to achieve complete bladder emptying. Further reading Good, better and best practice. Continence Foundation. October urinary incontinence is extremely common in the older population; early recognition, investigation and treatment can improve symptoms and quality of life for many of these people a full history and examination is essential to make the diagnosis and exclude other treatable causes conservative measures should be considered before commencing treatment incontinence pads should not be considered to be a treatment but may be required in addition to other measures or if other measures fail NICE guidelines recommend oxybutynin as the first-line agent for urge incontinence stress incontinence is mainly treated by pelvic floor exercises but may also respond to duloxetine consider specialist referral for difficult or resistant cases 40 Prescriber 19 April 2008

5 org.uk/campaigns/goodbetterbest Practice.pdf Good practice in continence services. National Service Framework, statistics/publications/publications PolicyAndGuidance/DH_ Urinary incontinence: the management of urinary incontinence in women. National Institute for Health and Clinical Excellence. October References 1. National Institute for Health and Clinical Excellence. Urinary incontinence: the management of urinary incontinence in women. October www. nice.org.uk/cg 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): Szonyi G. Oxybutynin with bladder retraining for detrusor instability in elderly people: a randomized controlled trial. Age Ageing 1995;24: Malone-Lee JG, Lubel D, Szonyi G. Low dose oxybutynin for the unstable bladder. BMJ 1992;304: Wagg A, Wyndaele J-J, Sieber P. Efficacy and tolerability of solifenacin in elderly subjects with overactive bladder syndrome: a pooled analysis. Amer J Geriatr Pharmacotherapy 2006;4: Chapple CR, Martinez-Garcia R, Selvaggi L, et al. for the STAR study group. A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome: results of the STAR trial. Eur Urol 2005;48: Abrams P, Freeman R, Anderstrom C, et al. Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder. Br J Urol 1998; 81: Wagg AS, Malone-Lee JG. Changes in the pressure flow plot in response to tolterodine treatment of detrusor overactivity BJU Int 2003;92: Abrams P, Kaplan S, De Koning Gans HJ, et al. Safety and tolerability of tolterodine for the treatment of overactive bladder in men with bladder outlet obstruction. J Urol 2006;175(3 Pt 1): Cardozo L, Chapple CR, Toozs- Hobson P, et al. Efficacy of trospium chloride in patients with detrusor instability: a placebo-controlled, randomized, double-blind, multicentre clinical trial. BJU Int 2000;85: Zinner N, Gittelman M, Harris R, et al. for the trospium chloride study group. Trospium chloride improves overactive bladder symptoms: a multicentre phase III trial. J Urol 2004;171: Halaska M, Ralph G, Wiedemann A, et al. Controlled, double-blind, multicentre clinical trial to investigate longterm tolerability and efficacy of trospium chloride in patients with detrusor instability. World J Urol 2003;20 (6): Croom KF, Keating GM. Darifenacin: in the treatment of overactive bladder. Drugs Aging 2004;21(13): Foote J, Glavind K, Kralidis G, et al. Treatment of overactive bladder in the older patient: pooled analysis of three phase III studies of darifenacin, an M3 selective receptor antagonist. Eur Urol 2005;48: Lipton RB, Kolodner K, Wesne K. Assessment of cognitive function of the elderly population: effects of darifenacin. J Urol 2005;173: Madersbacher H, Halaska M, Voigt R, et al. A placebo-controlled, multicentre study comparing the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence. BJU Int 1999;84(6): Halaska M, Dorschner W, Frank M. Treatment of urgency and incontinence in elderly patients with propiverine hydrochloride. Neurourol Urodyn 1994;13: Castleden CM, Duffin HM, Gulati RS. Double blind study of imipramine and placebo for incontinence due to bladder instability. Age Ageing 1986;15: van Kerrebroeck P, Abrams P, Lange R, et al. Duloxetine versus placebo in the treatment of European and Canadian women with stress urinary incontinence. BJOG 2004;111: Millard RJ, Moore K, Rencken R, et al, for the Duloxetine UI Study Group. Duloxetine vs placebo in the treatment of stress urinary incontinence: a fourcontinent randomized clinical trial. BJU Int 2004;93: Hilton P, Stanton SL. The use of desmopressin (DDAVP) in nocturnal frequency in the female. Br J Urol 1982; 54: Dr Gadgil is a specialist registrar and Dr Wagg is consultant geriatrician in the Department of Geriatric Medicine, University College London 42 Prescriber 19 April 2008