Key Considerations When Treating the Older Patient with Symptoms of Urinary Frequency and Urgency

Introduction

Overactive bladder (OAB) is a chronic and distressing medical condition experienced by many individuals as they grow older, and affecting both men and women equally. Overactive bladder is defined by the International Continence Society as urgency, with or without urge incontinence, usually with frequency and nocturia in the absence of proven infection or other obvious pathology.1 Although the pattern of symptoms varies among individuals, frequency is the most commonly reported symptom; urgency incontinence is less common but is often the most troublesome symptom.2 Age is not in itself a predictive factor for the occurrence of OAB: individuals of all ages are affected by this debilitating condition, and the symptoms should not be regarded as normal or acceptable at any age. However, it is now clear that the prevalence of OAB symptoms, like that of cardiovascular disease, does increase with advancing age.2,3 Therefore, it is important to consider the challenges faced by clinicians when managing mature (age 50 years or older) patients with OAB. Overactive bladder is thought to affect approximately 16% of the adult U.S. population3 and is, in fact, more prevalent than many of the medical conditions more commonly associated with aging, including osteoporosis, diabetes mellitus, and Alzheimer’s disease.4 Overactive bladder has far-reaching effects on quality of life. Unfortunately, many patients suffer in silence, too ashamed to discuss their symptoms. Often this is because patients believe that OAB is an inevitable part of aging; they are unaware that effective treatments for OAB are available2 and that the majority of individuals can be managed simply and effectively. As patients will rarely voluntarily report urinary symptoms, it is necessary for physicians—particularly primary care physicians—to be aware of and actively seek out the treatable symptoms of OAB.5 This review will focus on the impact of OAB in relation to other common medical conditions as well as the particular clinical and practical considerations when deciding on appropriate treatment for older patients with OAB.

Impact of OAB

Situational Adaptive Behaviors Because symptoms of OAB are unpredictable and can occur at any time, patients often modify their behavior and develop various strategies to reduce the impact of their symptoms.6 Limiting fluid intake can affect kidney function and lead to constipation, while limiting social and physical activities in an effort to avoid public embarrassment can be detrimental to both psychological and physical well-being. In older patients, the need to use the toilet frequently (during the day and at night) and the urgent need to void leading to patients rushing to the toilet have been shown to increase the risk of falls by as much as 26% and bone fracture by as much as 34%, particularly in those with comorbid osteoporosis.7,8 Falling, even without serious injury, is particularly distressing for older patients and may further impact on their self-confidence, leading to an even greater reluctance to maintain their mobility.8 It follows then that active intervention to minimize the symptoms of urge and frequency may slow or avoid the potentially detrimental effects of OAB on older patients’ psychological and physical well-being, and may reduce the incidence of falls and risk of fractures as well.8

Quality of Life

The emergence of even mild OAB symptoms leads to limitation of social and personal activities and increased psychological stress, with increased feelings of shame and loss of self-confidence.2,3,9-17 The psychological burden of OAB can be particularly severe, with patients suffering from depression, low self-esteem, apathy, guilt, denial, feeling they are a burden to their caregivers, and fear that they smell of urine.18 Studies have consistently shown the considerable and far-reaching impact of OAB symptoms across multiple domains of quality of life, with patients experiencing significant detrimental effects regardless of whether they have an incontinence component in addition to the core symptoms of OAB.9,13,14 Although cross-study comparisons should be viewed with caution, they do suggest that the impact of OAB across all domains of the Medical Outcomes Study Short-Form (36-item) Health Survey (SF-36) is at least as great, if not greater, than that of other common medical conditions, including diabetes, heart disease, and hypertension (Figure 1).10,13,19

Economic Consequences

Urinary incontinence, which is just one component of OAB, places a significant burden on society and has been estimated to account for approximately 2% of all health care costs in the United States.20 Studies have suggested that costs of caring for patients over age 65 years with urinary incontinence reached $26.3 billion in 1995,21 and such costs are likely to increase as the population continues to age. However, it appears that the bulk of costs relates to management of the symptoms and consequences of urinary incontinence rather than actual treatment (Figure 2).20,21 Of particular concern is the observation that the presence of urinary incontinence is often a precipitating factor in the decision to move from community-based care to institutionalized care, including nursing home facilities.5 It is possible, therefore, that many patients enter long-term care facilities primarily because of issues that could have been effectively managed in the community if their urinary symptoms had been identified. Effective diagnosis and intervention for OAB may lead to cost savings with, for example, a reduction in the requirement for treatment for urinary tract infections (UTIs) and skin infections.22

Practical Aspects of Diagnosing OAB in Older Patients

It is now regarded as sufficient to identify and assess the severity of the symptoms of OAB as defined by the International Continence Society described above and exclude other potential causes, such as infection or other obvious pathology, in order for a diagnosis of OAB to be made and appropriate treatment to be initiated. Figure 3 illustrates a simplified diagnostic algorithm. When faced with an older patient with symptoms of urgency, frequency, and/or incontinence, the first step is to determine whether there is a reversible underlying cause for the symptoms, such as a comorbid medical condition or concomitant medication.

Comorbid Medical Conditions

Many older people with OAB have coexisting illnesses that can exacerbate or, in some situations, may be the primary reason for the development of the symptoms of urgency, frequency, or urge incontinence (Table I). Medical conditions, such as hypertension managed with diuretics or congestive heart failure (CHF), can have a significant effect on bladder symptoms. Recent estimates suggest that as many as 4.8 million individuals in the United States alone currently suffer from CHF, with the majority being over age 70 years. CHF leads to increased fluid volume and the standard treatment, diuretics, leads to increased urine production, which if not carefully managed, can result in the bothersome symptoms of frequency, urgency, and urge incontinence. Increased urine production is also associated with diabetes, hypercalcemia, and peripheral venous congestion, again possibly leading to the emergence of OAB-like symptoms.

Other conditions that may be responsible for the development of OAB symptoms include neurological diseases such as Parkinson’s disease and multiple sclerosis (MS). OAB symptoms may also develop in patients who have suffered a cerebrovascular event (CVA or stroke), particularly if the damage is centered in the second frontal gyrus. Patients with suprasacral spinal cord lesions, such as those caused by tumors, trauma, or MS, can also experience symptoms similar to those characteristic of OAB. In males, benign prostatic hyperplasia (BPH) is a common condition that can lead to symptoms of OAB, in addition to obstructive symptoms. Diagnosis and therapy to treat or manage these comorbid conditions may serve to relieve these symptoms. However, it is likely that these patients will still require treatment to specifically manage their OAB symptoms as well if therapy for BPH alone is inadequate. Some patients may even benefit from combined medical therapy aimed at both the bladder and the prostate. In women, hormonal changes, either due to menopause or hormonal therapy, can lead to urogenital atrophy and associated bladder symptoms. Review of the treatment regimen for such patients and initiation of palliative treatments, such as estrogen creams and lubricants, may relieve some of the more troublesome symptoms. Urinary tract infections and skin breakdown are common comorbid conditions associated with OAB, particularly in older patients.22 Indeed, UTIs are the most common cause of acute bacterial sepsis in those over age 65 years.23

The presence of repeated symptomatic UTIs may suggest an underlying bladder dysfunction problem, such as incomplete bladder emptying, which would warrant investigation of the urinary tract. Concomitant Medications Drugs are a major cause of urinary incontinence in the elderly. Many frequently prescribed medications can cause urinary symptoms including frequency and urge (Table II). Indeed, of the 20 most frequently prescribed drugs in the United States in 2001, the majority of which fall into the categories outlined in Table II, 11 are known to be associated with some level of bladder-related side effects.24 Often, the pharmacological agents used to manage the medical conditions outlined in Table I can themselves cause symptoms that exacerbate or mimic the symptoms of OAB. Anticholinergics, antipsychotics, opioids, antidepressants, and calcium channel blockers, all of which are commonly prescribed to older persons, can result in urinary retention and overflow incontinence, while diuretics and alcohol can cause polyuria. Many of these agents can also cause sedation and/or delirium leading to functional incontinence.

Age-Related Changes in Metabolic Processes

Comorbid medical conditions such as renal disease, often encountered in older patients, can also affect the metabolism of certain drugs and should thus be taken into consideration. Indeed, changes in kidney function can result in a decreased ability to concentrate urine, which could give rise to bladder symptoms by increasing the volume of urine produced irrespective of fluid intake. This is particularly bothersome during the night. These changes may be a result of decreased renal clearance, reduced organ reserve, loss of carrier proteins in serum, and an increase in body fat.25 These factors can all alter the action of medication leading to an increased therapeutic effect, a longer duration of effect due to either slower elimination or increased systemic exposure, and even toxicity problems. Various age-related changes can affect drug metabolism and can also increase the risk for drug–drug interactions. In practice, these changes rarely cause problems if patients are carefully monitored for the emergence of any adverse effects during the early stages of treatment. The metabolic changes associated with aging mean that starting doses can generally be lower than those for adult patients.

Practical Aspects of Treating OAB in Older Patients

Medication with or without behavioral therapy is the current standard of care for patients with OAB regardless of age (Table III; Figure 4). The realistic goal of the treatment of OAB may not be to “cure” the condition, but rather to manage symptoms so as to minimize their burden and impact. An individual’s overall physical condition and treatment goals will influence the best approach to take for the management of OAB. For otherwise fit and healthy older individuals, the aim may be to significantly relieve or completely remove their major symptoms so that they no longer have an impact on their physical activities or quality of life. For these patients, a combination of pharmacotherapy and bladder retraining may be most appropriate. For a frail older person who experiences repeated episodes of urge incontinence but is physically unable to undertake bladder retraining, the aim may be to minimize the number of incontinence episodes with a combination of medication and regular assisted toileting. There are a number of practical considerations that must be considered when deciding on the most appropriate management strategy for older OAB patients:

Medication Choice

The medications of choice for OAB are antimuscarinic agents including tolterodine tartrate and oxybutynin chloride.26-29 These agents act to suppress muscarinic activation of bladder contraction during the filling phase, a major cause of the characteristic symptoms of OAB. Antimuscarinics are contraindicated in patients with urinary retention, gastric retention, and uncontrolled narrow angle glaucoma. Both tolterodine and oxybutynin are available as once-daily oral tablets,27,28 and the efficacy and tolerability of the extended-release formulations of both these agents has been confirmed in a large-scale prospective study.30 Tolterodine tartrate extended-release (TOL ER) can be initiated at a maintenance dose of 4 mg/day as a single once-daily tablet. A recent large-scale study found that TOL ER initiated at this dose is efficacious, safe, and well-tolerated in patients age 65 years and older.28 Oxybutynin chloride extended-release (OXY XL) should be initiated at a 5 mg/day dose with weekly 5-mg dose increments (up to a maximum of 30 mg/day to achieve a balance of efficacy and tolerability).

Oxybutynin chloride extended-release tablets are available in three strengths: 5 mg, 10 mg, and 15 mg. Oxybutynin is also available as a transdermal patch.31 Once treatment is initiated, many people begin to see improvement in their symptoms right away. Indeed, in a recent open-label study of TOL ER 4 mg once daily some patients experienced a marked reduction in the number of urgency episodes as early as the first week of treatment.29 Importantly, patients continued to improve as their therapy proceeded with further reductions in the number of urgency episodes recorded after 1 and 3 months. It is important, therefore, to set realistic short- and medium-term goals when treatment is initiated and to encourage patients to “stick with” their treatment. After 6 months of successful treatment, including behavioral modification, consideration can be given to lowering the dose of medication. Managing Potential Side Effects and Maximizing Compliance. While older patients can benefit from drug therapy for OAB, they are also more likely to experience side effects.25 Indeed the emergence of side effects is a common cause of treatment discontinuation.32 An awareness of the potential side effects of any medication, as well as strategies to manage and minimize their impact, is an important part of the overall management process for the older patient with OAB. Dry mouth is a common side effect of antimuscarinic therapy and can present particular problems in older patients, especially those with dentures. Dry mouth may prove less problematic for patients treated with tolterodine due to its high selectivity for bladder versus salivary gland muscarinic receptors.33 This has been supported by clinical trials that have shown that dry mouth (along with other adverse effects associated with the autonomic nervous system) occurs less frequently and is less severe with tolterodine treatment than with oxybutynin.26,30,34

Ensuring such patients maintain a normal fluid intake is important, especially as many OAB patients limit fluid intake in an attempt to manage their symptoms. Because cognitive disturbance is a potential side effect of anticholinergic therapy and can lead to a worsening of existing OAB symptoms, it is important to monitor older patients for any worsening in cognitive function on a regular basis. When prescribing any new agent for an older patient, a full review of existing medication is warranted as many older patients are already receiving treatment for concomitant disease. An important example of the need to monitor polypharmacy in elderly persons is the possibility for anticholinergic overload if patients are receiving several medications—all with anticholinergic effects—either through prescription from the physician or as over-the-counter medications. Behavioral Therapy Behavioral therapies, such as bladder retraining through a program of preemptive and timed voiding, while useful, can be less appropriate in older patients who may be less able to comply with a complex regimen. However, they may prove beneficial in combination with pharmacological therapy in motivated and mobile older patients.35-37

Pelvic floor (Kegel) exercises may also offer some benefit to the motivated older person. For such patients, it is important to emphasize the need for persistence with the exercises, which should become a part of the patient’s normal daily routine because the benefit will be lost if the exercises are stopped as the muscles will atrophy. For less mobile and perhaps cognitively challenged older patients, the caregivers should be recruited to ensure compliance with medication and assist with preemptive voiding. For a small number of patients, combined pharmacotherapy and bladder retraining may allow discontinuation of pharmacotherapy once maximal benefit has been achieved and maintained for several months, as long as the exercises are continued. However, for most patients there will need to be a commitment to life-long treatment for this condition.

Conclusions

Overactive bladder is a highly prevalent condition among older people, with the symptoms causing significant distress and disruption in their normal daily lives. While individuals of any age can develop the symptoms of OAB, managing older patients can present specific problems and issues that must be considered when diagnosing and treating them. Older patients with symptoms of OAB are in the offices of primary care physicians every day—waiting to be asked about their bladder function. Anyone who is receiving a diuretic is at risk, particularly if they have decreased mobility. Once OAB has been identified in individual patients, many can be treated successfully, regardless of age, by their primary care physician.

Dr. Josephson has reported that she is a consultant for and receives research support from Pfizer Inc. Dr. Ginsberg has reported that he is on the speaker’s bureau for Pfizer Inc, and Yamanouchi Pharmaceutical Co., Ltd., and is a consultant for Pfizer, Yamanouchi, Allergan Inc., and Indevus Pharmaceuticals, Inc.