Transcript OAB

Overactive bladder:
clinical evaluation and medical treatment
Philip E.V. Van Kerrebroeck, MD, PhD, MMSc
Professor of Urology
Maastricht University Medical Centre
the Netherlands
Overactive bladder definitions
Urgency1,2
Sudden compelling desire to pass urine that is difficult to defer
Frequency1,2
Patient considers that he/she voids too often by day
Normal is < 8 times per 24 hours
Nocturia1,2
Waking to urinate during sleep hours
Considered a clinical problem if frequency is greater than twice a
night
Urgency urinary
incontinence
(UUI)1
Involuntary leakage accompanied by or immediately preceded by
urgency
OAB “wet”1,2
OAB with UUI
OAB “dry”2
OAB without UUI
Warning time3
Time from first sensation of urgency to voiding
1Abrams
P, et al. Neurourol Urodyn. 2002;21:167-178.
AJ, et al. J Urol. 2006;175(3 pt 2):S5-S10.
3Zinner N, et al. Int J Clin Pract. 2006;60:119-126.
2Wein
Overactive bladder syndrome (OAB)
 Urgency, with or without urgency incontinence, usually
with increased day time frequency and nocturia,
if there is no proven infection or other obvious pathology
OAB
Wet
Abrams et al, Neurourol Urodyn, 2002
Abrams et al, Neurourol Urodyn, 2009
OAB
Dry
Prevalence of OAB in Europe & the US
EU SIFO Study
US NOBLE Study
Milsom I et al. 2001
Stewart et al. 2001
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Prevalence (%)
45
40
Men
35
35
Women
30
30
Men
Women
25
25
20
20
15
15
10
10
5
5
0
0
40–44 45–49 50–54 55–59 60–64 65–69 70–74
Age (years)
75+
18-24
25-34
35-44
45-54
Age (years)
 17% of the adult population have symptoms of OAB
 Prevalence of OAB increases with age
 Similar prevalence among men and women
(women may present more)
55-64
65-74
75+
Prevalence of OAB by age and gender
25
22.9
20
Prevalence, %
20.6
16.0
15.9
15
13.3
10.5
10
9.4
10.7
10.9
10.0
8.6
5
8.2
8.1
7.5
5.1
0
Age, years
Irwin DE, Milsom I, Hunskaar S et al Eur Urol 2006; 50: 1306-15
Men
14.5
Women
10.3
8.6
9.5
15.4
Diagnosis: Initial Evaluation
 Diagnosis based on presenting symptomology and
does not require invasive tests:
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Examine potential risk factors
Thorough history
Nature of symptoms
Physical examination
Urinalysis
Bladder diary
Medications influencing bladder function
Differential diagnosis of OAB
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Diagnosis: General OAB Risk Factors
 Smoking
 Relationship exists between smoking and UI
 Partly due to nicotine’s possible effect on bladder
contractility
 Chronic/frequent coughing can lead to damaged
urethral and vaginal supports, as well as perineal
nerve damage
 Obesity
 Increased pressure on bladder
 Greater urethral mobility
 Possible impaired blood flow or bladder innervation
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Diagnosis: OAB Risk Factors for Women
Pregnancy and Childbirth
 Can flatten, stretch, and weaken many of the pelvic floor
muscles
 Evidence that # of vaginal births related to increased
OAB risk and incontinence later in life
Menopause
 Weakens urethra’s ability to maintain tight seal
 Lack of estrogen weakens detrusor, and can cause the
urethra to open unexpectedly during physical activity
Pelvic surgery
 Weakens and damage pelvic floor muscles
 Women undergone removal of uterus have 40%
increased risk of UI
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Diagnosis: OAB Risk Factors for Men
 Benign Prostatic Hyperplasia
 Frequent cause of UI
 Detrusor contracting strongly and frequently to
compensate for reduced urinary flow due to urethral
obstruction
 Prostate/Bladder Surgery
 2 to 3 times more likely to experience UI than those
without the surgery
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Diagnosis: Patient History
 How long? How old when started?
 How much (volume)? Degree of bother?
 Characteristics of leakage?
 Activity related?
 Day and night, wet pads at night = instability
 Urgency?
 suppressible = probably SUI
 not suppressible (urgency incontinence) =
overactivity
 Other: fluid intake, UTI’s, pain, hematuria, LE swelling,
medications
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Diagnosis: Nature of OAB Symptoms
Questions to Consider
 Do you frequently limit your fluid intake or map out
restrooms when you are away from home?
 Do you urinate more than 8 times in a 24-hour period?
 Do you frequently get up 2 or more times at night to go
to the bathroom?
 Do you have uncontrollable urges to urinate, resulting
in wetting accidents?
 Do you use pads to protect your clothes?
 Are you bothered or concerned about bladder control?
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Diagnosis: Patient Physical Examination
 Abdomen
 Masses: palpable bladder, etc.
 Abdominal masses f.e. palpable bladder
 Pelvis/perineum
 External genitalia
• Prolapse (assoc. 50% of SUI patients)
• Malignancy, fistula
 Rectal
 tone, masses, teach Kegels during exam
 Prostate
 Neurological (reflexes, LE’s, sensory, motor)
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Diagnosis: Bladder Diary
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Diagnosis: Urinary Tract Infection
(= different from OAB!)
 UTI’s: Cystitis, Urethritis
 Timing of the onset of symptoms is usually very
different
 UTI being acute and OAB being chronic
 Pain with urination (dysuria), costovertebral angle
tenderness/pain and possibly elevated temperature are
features of UTI’s not usually associated with OAB
 UTIs may also occur in individuals with OAB
 usually present with an exacerbation of their OAB
symptoms and dysuria.
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Diagnosis: Bladder cancer
( = different from OAB !!)
 Haematuria, in the presence of bladder
symptoms, is the defining diagnostic feature of
bladder cancer
 haematuria in the presence of OAB
symptoms must be investigated further to
rule out pathology or malignancy.
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QoL: Physical Impact of OAB
 Increased risk of falls and fractures from rushing to the
toilet
 Higher rate with nocturia (night time visibility)
 Elderly population most susceptible
 Experience more urinary tract infections (UTIs) and skin
infections
 Sleep disturbances are reported by many patients with OAB
 correlated with poor health
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Diagnosis: Key Consideration
 Overactive Bladder diagnosed if there is no
proven infection, metabolic disorder, or other
obvious pathology
 OAB cannot be diagnosed without the
complaint of urgency, but can be without the
complaint of incontinence
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QoL: Emotional Impact of OAB
 Manage fear of incontinence and urgency episodes by
developing coping mechanisms
 mapping toilet locations, voiding frequently, use of
incontinence pads and limiting fluid intake
 Common daily activities (e.g., shopping, travel,
physical activity) and personal relationships are often
avoided due to fear of embarrassment
 Patients often express loss of self-esteem and
depression.
 depression associated with OAB is the same as other
chronic conditions: diabetes, rheumatoid arthritis,
and hypertension
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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”
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Which Patient - Which Treatment
 Diagnosis of the problem
 Understanding the major component
 SUI associated with exertion onset in reproductive years
 Urgency incontinence associated with urgency in post
menopausal women
 Mixed incontinence affects approximately 30%
 Having a clear picture of the patient’s goals from
treatment
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Non-invasive treatments for OAB
 Lifestyle modification
 Behavioural intervention
 Electrical stimulation
 Acupuncture
 Hypnotherapy
 Drugs
Lifestyle intervention fluid intake,
caffeine, tea, Coke, wt reduction
 Significant reduction in U, F, and N with 25% reduction in
fluid intake. Increasing fluid intake worsened F Hashim et al, 2008
 High caffeine intake is an independent risk factor for DO
The relationship may be dose dependent Myers et al, 2000
 Tea drinking (but not coffee) epidemiologically associated
with all forms of incontinence Hannested et al, 2003
 Diet Coke and caffeine-free Diet Coke cause greater U and F
than carbonated water or Classic Coke Cartwright , ICS 2007
 Weight loss decreases incontinence in moderately and
morbidly obese women 4th ICI 2008, Level 1
Pelvic floor muscle/bladder training
 PFMT is better than no treatment, placebo, drug or
inactive control treatment for women with SUI, UUI or
MUI Level 1
 Supervised PFMT should be offered as a first line
therapy in all patients with SUI, UUI or MUI Grade A
 Not clear whether BT is more effective than drug
therapy for women with DO or UUI Level 1
 In a choice between BT and anticholinergic drug for
women with DO or UUI, either may be effective Grade B
Behavioural intervention
 Improves central control
 Underlying psychological abnormality
 Learn / re-learn both conscious and
unconscious physiological processes
 Avoids side effects of drugs
Bladder drill
 Requires high motivation
 Good support
 Encouragement
 High relapse rate
Pharmacological treatment of OAB
 Antimuscarinics
 Drugs with mixed action
 Antidepressants
 Alpha-adrenoceptor antagonists
 Beta-adrenoceptor agonists
 Drugs acting on membrane channels
 Toxins
 Future drugs
Antimuscarinic agents
 After lifestyle changes, antimuscarinic agents are the
most common and currently the most widely used
therapy for OAB syndrome
Andersson, 2004
 Antimuscarinics
−
−
−
−
reduce intra-vesical pressure
increase compliance
raise volume threshold for micturition
reduce uninhibited contractions
Abrams et al, 2002
OAB: Antimuscarinics
 Oxybutynin Oral, Transdermal, Intra-vesical, gel
Ditropan 2.5mg BD - 5mg QDS, Lyrinel XL 5-20mg OD,
Kentera 3.9mgx2/wk, Oxybutynin in water 10mg TDS
 Tolterodine Oral
Detrusitol 2mg BD, Detrusitol XL 4mg OD
 Propiverine Oral
Detrunorm 15mg OD-TDS
 Solifenacin Oral
Vesicare 5 or 10mg OD
 Trospium Oral
Regurin 20mg BD, 60 mg OD
 Darifenacin Oral
Emselex Enablex 7.5 or 15mg OD
 Fesoterodine Oral
Toviaz 4 or 8mg OD
Antimuscarinic side effects
Tolerability and Compliance
 Questionnaire follow-up study of women with detrusor
overactivity
 5.5% were cured of their urinary symptoms
 18.2% women continued drug therapy for more than
six months
Kelleher et al, 1997
Why do patients stop taking
Antimuscarinics?
 Lack of efficacy is the major reason for failure of
first-line antimuscarinic therapy:
0%
10%
20%
30%
Female ≤55 Years of Age
50%
60%
70%
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Male
50
In Employment/Activity Working
50
Retired/Unemployment
50
OAB Dry
Pure UUI
Insufficient efficacy
90%
24
18
3
31
7
30
26
61
24
Dosing convenience
16
Intolerable side effects
9
14
4
58
100%
2 9
4 8
39
66
Mixed UI
80%
30
47
Female >55 Years of Age
Based on Market research
40%
2 10
3 10
2
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Other reasons
Antimuscarinic adverse effects:
Meta-analysis
Drug
Constipation
Blurred Vision
Dry Mouth
Darifenacin 7.5mg od
2.39
5.05
2.57
Darifenacin 15mg od
3.32
-
4.40
Fesoterodine 4mg od
1.47
0.20
3.01
Fesoterodine 8mg od
2.03
0.21
3.95
Tolterodine ER 4mg od
1.49
2.76
3.00
Solifenacin 5mg od
3.09
1.20
3.32
Solifenacin 10mg od
4.70
2.29
5.90
Oxybutynin IR 7.5-10mg
1.26
1.65
2.96
Oxybutynin 3.9mg TDS
0.26
1.18
1.41
Trospium Chloride 40mg
2.10
-
3.17
Propiverine ER 30mg
3.36
9.30
3.38
Chapple et al, 2008
83 trials: p=0.05; p=0.01 Vs placebo
What’s new?
Β3 -adrenoceptor agonist (mirabegron)
Efficacy and Tolerance
 Significant effect in 60% of patients, dry rate 42%
 Equal efficacy in naïve and AM-resistant patients
 Side effects at placebo level
Chapple et al, 2014.
Combination therapy (AM + Β3)
Efficacy and Tolerance
 Increased efficacy in naïve and non-naïve patients
 Reduced dosage of AM
 Acceptable side effects
Drake et al, 2016.
Surgical OAB Treatment Options
Surgical (Invasive) Treatments
 Botulinum toxin (Botox 100 units?)
 Neuromodulation (TENS, PTNS, SNS)
 Augmentation enterocystoplasty (???)
 Urinary diversion (continent, Bricker)
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THANKS ALL OF YOU