The Overactive Bladder Raji Gill, D.O., M.Sc. Clinical Assistant Professor of Surgery Division of Urology Tulsa Regional Medical Center & Cancer Treatment Centers of America

2002 ICS Terminology: Overactive Bladder OAB defined based on symptoms Urgency, with or without urge incontinence, usually with frequency and nocturia In the absence of pathologic or metabolic conditions that might explain these symptoms At the ICS meeting in Seoul, Korea in September of 2001, a consensus definition of OAB was derived. The definition is “urgency, with or without urge incontinence, usually with frequency and nocturia, in the absence of pathologic or metabolic conditions that might explain these symptoms.” This definition focuses on the symptoms of OAB rather than on urodynamic parameters and is much more clinically useful for physicians, because most do not conduct urodynamic studies on patients with OAB. In addition, this definition improves communication between physicians and their patients, since it includes terms that are much more intuitive and less likely to confuse or even alarm the patient. Thus, the new definition encompasses all of the important clinical aspects of OAB, without using terminology that is only interpretable by a specialist in urology. ICS = International Continence Society (www.icsoffice.org)

OAB Symptoms OAB Frequency Urination at night Urgency 8 or more visits to the toilet per 24 hours Urination at night • 2 or more visits to toilet during sleeping hours Urgency Sudden, strong desire to urinate Urge Incontinence Sudden & involuntary loss of urine Among the symptoms of OAB, frequency is defined as eight or more visits to the toilet per 24-hour period, two or more of which may be during the night. Urgency is defined as a sudden, strong desire to urinate. Urge incontinence is defined as the sudden, involuntary loss of urine. OAB

Types of Urinary Incontinence Urge urine loss accompanied by urgency resulting from abnormal bladder contractions Mixed symptoms combination of stress and urge incontinence Stress urine loss resulting from sudden increased intra-abdominal pressure (eg, laugh, cough, sneeze) Urge urinary incontinence is caused by uncontrollable contractions of the detrusor muscle; there may be very little warning time, and the volume of leakage is usually large. Stress incontinence occurs when the pressure on the bladder is greater than the urethral pressure, resulting in a sudden loss of urine (usually a small volume). Stress incontinence is typically due to weakened or damaged pelvic floor muscles. Mixed incontinence occurs when the symptoms of OAB and stress incontinence are present in the same person. Individuals with mixed incontinence may experience leakage of urine due to a sudden uncontrollable urge to urinate and when coughing or sneezing. Detrol ® LA is not indicated for stress or mixed incontinence. Sudden increase in intra-abdominal pressure Uninhibited detrusor contractions Urethral pressure

Differential Diagnosis: OAB and Stress Incontinence Medical History and Physical Examination Symptom Assessment Symptoms Overactive Stress incontinence bladder Urgency (strong, sudden desire to Yes No void) Frequency with urgency Yes No (>8 times/24 h) Leaking during physical activity; No Yes eg, coughing, sneezing, lifting A simple symptom assessment can differentiate between OAB, stress incontinence, and mixed incontinence. OAB is associated with urgency (a strong, sudden desire to void); frequency (more than 8 times per 24 hours); and a large amount of urinary leakage in patients who have episodes of incontinence. Patients with OAB are often unable to reach the toilet in time after an urge to void and usually wake up to pass urine during the night. Urine leakage associated with physical activity is not a symptom of OAB. Detrol ® LA is not indicated for stress or mixed incontinence. Amount of urinary leakage with Large Small each episode of incontinence (if present) Ability to reach the toilet in time Often no Yes following an urge to void Waking to pass urine at night Usually Seldom Abrams P, Wein AJ. The Overactive Bladder: A Widespread and Treatable Condition. Erik Sparre Medical AB; 1998.

Estimated Prevalence of OAB in Comparison With Other Selected Chronic Conditions: 1990s Data Millions of Americans Chronic Sinusitis 37 Arthritis 33 Heart Conditions* 21 OAB 17 Asthma 15 Osteoporosis 10 Diabetes OAB is a highly prevalent condition in the United States and is more common than many other chronic conditions. Reports in the 1990s indicated that the prevalence of OAB was higher than rates of asthma, osteoporosis, diabetes, or Alzheimer’s disease. 9 Alzheimer’s Disease 5 * Excludes hypertension Payne CK. Campbell’s Urology Updates. 1999;1:1-20. Evans DA et al. Milbank Q. 1990;68:267-289. Bureau of the Census, Population Estimate Data, 1995. National Institutes of Health. Osteoporosis and Related Bone Diseases National Resource Center. Osteoporosis Overview. National Center for Health Statistics. Vital Health Stat. 10(199):1998.

Prevalence of OAB in the US 5 10 15 20 25 30 35 40 18–24 25–34 35–44 45–54 55–64 65–74 75+ Prevalence (%) Men Women Overall, 16.6% had symptoms of OAB Prevalence of OAB increased with age The prevalence is similar in men, approximately 16%, and women, approximately 16.9%. Consistent with other epidemiologic studies, the data from this program indicate that the incidence of OAB increases with age in both men and women. Age (years) Adapted from Stewart W et al. WHO/ICI 2001. Poster.

Prevalence of OAB: Wet versus Dry 12.2 million (6.1% of the population) Wet (37% of OAB) OAB Dry (63% of OAB) Of the total number of cases of OAB in the United States, 63% are classified as “dry.” This figure translates into 21.2 million people, or 10.5% of the overall US population. The other 37% of cases of OAB are classified as “wet.” This translates into 12.2 million people, or 6.1% of the population. 21.2 million (10.5% of the population) Adapted from Stewart W et al. WHO/ICI 2001. Poster.

Diagnosis of OAB A presumptive diagnosis of OAB can be based on patient history, symptom assessment physical examination urinalysis Initiation of noninvasive treatment may not require an extensive further workup A presumptive diagnosis of OAB can be made on the basis of the patient’s history, an assessment of the symptoms, a physical examination, and urinalysis. The initiation of noninvasive treatment may not require a more extensive workup. Fantl JA et al. Urinary Incontinence in Adults: Acute and Chronic Management. Clinical Practice Guideline No. 2, 1996 Update. Rockville, MD: Agency for Health Care Policy and Research; March 1996. AHCPR publication 96-0682.

A Hidden Condition* Many patients self-manage by voiding frequently, reducing fluid intake, and wearing pads Nearly two-thirds of patients are symptomatic for 2 years before seeking treatment 30% of patients who seek treatment receive no assessment Nearly 80% are not examined A survey conducted by the Gallup Group in Europe found that many patients with OAB attempt to self-manage their problem by voiding frequently, reducing fluid intake, and wearing pads. Nearly two-thirds of patients experience symptoms for 2 years before seeking treatment. Notably, of those who do seek treatment, 30% do not receive an assessment of their symptoms. Equally alarming is the finding that nearly 80% of patients are not examined. * Survey conducted by Gallup Group (European Study).

Barriers to Treatment Patient misconceptions and fears: “Part of normal aging or everyday life” “Not severe or frequent enough to treat” “Too embarrassing to discuss” “Treatment won't help” There are several barriers to the treatment of OAB. Among the most important are patients’ misconceptions and fears. Individuals with OAB are often under the mistaken impression that bladder dysfunction is a normal part of aging or everyday life. Some may feel that their symptoms are not severe enough or frequent enough to warrant treatment. Embarrassment comes into play, as many individuals feel ashamed of their problem and are reluctant to discuss it with a healthcare professional. Another common misperception is that there is no effective treatment available for OAB.

Screening and Diagnosing OAB “Do you have bladder problems that are troublesome, or do you ever leak urine?” YES Healthcare professionals should routinely ask patients whether they have bladder problems that are troublesome or whether they ever leak urine. If the answer is yes, the clinician should proceed with an assessment of the patient’s history and symptoms, as well as tests such as urinalysis, to determine whether a diagnosis of OAB can be established. Assess history, symptoms, and test results Establish a diagnosis

OAB Screening Can Help Diagnose Other Causes of Bladder Symptoms Local pathology infection bladder stones bladder tumors interstitial cystitis outlet obstruction Metabolic factors diabetes polydipsia Medications diuretics antidepressants antihypertensives hypnotics & sedatives narcotics & analgesics Other factors pregnancy psychological issues Bladder symptoms may be caused by a wide variety of factors other than OAB. Screening for OAB can help uncover these disorders. Bladder symptoms may be due to local pathology, metabolic factors, the use of certain medications, or other medical or psychological factors. Fantl JA et al. Urinary Incontinence in Adults: Acute and Chronic Management. Clinical Practice Guideline No. 2, 1996 Update. Rockville, MD: Agency for Health Care Policy and Research; March 1996. AHCPR publication 96-0682.

Differential Diagnosis: Physical Examination Perform general, abdominal (including bladder palpation), and neurologic exams Perform pelvic and/or rectal exam in females and rectal exam in males Observe for urine loss with vigorous cough Fantl JA et al. Managing Acute and Chronic Urinary Incontinence. Clinical Practice Guideline. Quick Reference Guide for Clinicians, No. 2, 1996 Update. Rockville, MD: Agency for Health Care Policy and Research; January 1996. AHCPR publication 96-0686.

Differential Diagnosis: Laboratory Tests Urinalysis to rule out hematuria, pyuria, bacteriuria, glucosuria, proteinuria Blood work if compromised renal function is suspected or if polyuria (in the absence of diuretics) is present The differential diagnosis of OAB should include urinalysis to rule out hematuria, pyuria, bacteriuria, glucosuria, and proteinuria. Additional blood work (such as measures of glucose, BUN, creatinine, and calcium) should be performed, as appropriate. Fantl JA et al. Managing Acute and Chronic Urinary Incontinence. Clinical Practice Guideline. Quick Reference Guide for Clinicians, No. 2, 1996 Update. Rockville, MD: Agency for Health Care Policy and Research; January 1996. AHCPR publication 96-0686.

Consider referral to specialist Care Pathway Working diagnosis? Yes OAB? Yes No Treat if: Frequency and urgency, with or without urge incontinence, and normal urinalysis Consider referral to specialist >8 weeks tx Failed Abrams P. Wein AJ. The Overactive Bladder – A Widespread and Treatable Condition. 1998.

Suggested Reasons for Referral Symptoms do not respond to initial treatment within 2 to 3 months Hematuria without infection on urinalysis Recurrent symptomatic UTI Symptoms suggestive of poor bladder emptying Pelvic bladder, vaginal, or urethral pain Evidence of complicated neurologic or metabolic disease Failed previous incontinence surgery Elevated PVR volume Radical pelvic surgery Symptomatic prolapse Prostate problems Surgery planned (2nd opinion) Abrams P. Wein AJ. The Overactive Bladder – A Widespread and Treatable Condition. 1998.

Treatment Options Behavioral therapy Medication Combined therapy: behavioral and pharmacologic therapy Minimally invasive therapies Botulinum A-toxin Neuromodulation Surgery

So when the Drug Rep. visits, which drug do I use?

Pharmacotherapy Anticholinergic Agents Oxybutynin (Ditropan) Oxybutynin transdermal (Oxytrol) Tolterodine (Detrol) Solifenacin (Vesicare) Trospium chloride (Sanctura) Darifenacin (Enablex)

Oxybutynin (Ditropan) Immediate and long acting form Immediate – TID dosing Long acting XL – once a day, 5 or 10 mg. Side effects – dry mouth, constipation, headache Approved for pediatric use (age 6 or older)

Oxybutynin Transdermal (Oxytrol) 3.9 mg patch, twice weekly Similar in effects to po Side effects – less dry mouth but erythema/pruitis

Tolterodine (Detrol) Immediate 2 mg. and long acting LA 4 mg dosing Side effects profile similar to oxybutynin

Solifenacin (Vesicare) 5 – 10 mg daily dose Side effects – dry mouth, constipation

Trospium Chloride (Sanctura) Quaternary amine as opposed to tertiary amine 20 mg BID dose Theoretically harder to pass through blood/brain barrier with less side effects Not metabolized by liver 60% excreted in the urine unchanged

Darifenacin (Enablex) M3 selective anticholinergic 7.5 mg or 15 mg once a day Side effects – constipation and dry mouth