The condition of Overactive bladder (OAB) is a symptom based condition and defined by the International Continence Society (ICS) standardization committee as urgency, with or without urgency incontinence, usually with frequency and nocturia, if there is no proven infection or other obvious pathology.
- Urgency with at least one other symptom is essential to diagnose OAB.
- Urgency is the central symptom, defined by the ICS as the complaint of a sudden compelling desire to void that is difficult to defer.
- The normal urge to void is terms the desire to void, by the ICS and is used to describe normal filling sensation.
- Urgency incontinence is defined as involuntary leakage of urine, accompanied or immediately preceded by urgency.
- The symptom of “increased daytime frequency” is the complaint by the patient who considers that they void too often throughout the day.
- Although the ICS has not defined normal daytime voiding frequency, many references and clinical trials have reported baselines of 8 - 10 daytime voids as normal. Variables include the intake of liquids and medications that may increase voiding frequency.
- The symptom of nocturia is the complaint that the individual is awakened from sleep at night one or more times to void.
- Urgency urinary incontinence (UUI) is disproportionately more common among women.
- The impact of OAB on health related quality of life is substantial.
Treatment of OAB:
The goals for treatment are directed towards improving the patients quality of life by decreasing symptom severity balanced with managing treatment sside effects.
Conservative treatment:
- Behavioral and lifestyle modifications, timed voiding, pelvic floor muscle therapy and biofeedback. These therapies require effort from the patient.
- Conservative therapies are effective, well tolerated, safe, and preferred by many patients.
- It is generally appropriate that the least invasive treatment that takes into account patient preferences and offers a reasonable chance for success be used first.
- Although it is important to rule out serious underlying or associated conditions, invasive testing is rarely required before initiating treatment with conservative measures.
Treatments - Behavioral Therapy
- Behavioral therapy describes a group of treatments founded on the prinicpal that the incontinent patient can be educated about his or her condition and develop strategies to minimize or eliminate UI.
- Education is the core of all the behavioral therapies.
- The behavioral techniques are implemented through patient education aiming at healthy bladder habits, while suppressing urgency to improve continence and decrease symptom severity.
- Pelvic Floor Muscle training - goal is improving muscle strength and control
- Bladder diary - The largest voided volume on a diary correlates with the cystometric capacity defined by urodynamic testing
- Urge Inhibition - goal is to break the cycle of rushing to the toilet in response to urgency
- Scheduled voiding - goal is to normalize frequency
- Fluid management
- The different treatment approaches are unified by education about normal urinary tract function.
- Pelvic floor muscle training is both a behavioral therapy (education about anatomy and function of the muscles, learning to use the muscles properly to control lower urinary tract function) and a physical therapy (strengthening the muscles to improve function).
- PFMT consists of repetitive contractions of the pelvic floor muscles; various techniques including quick flicks or rapid, intense muscle contractions and sustained pelvic contractions can be effective. The quick flicks are more effective at suppressing urgency and detrusor overativity while sustained contractions are more effective at improving occlusion of the sphincteric unit during increases in intra-abdominal pressure.
- The goal of therapy is to increase the strength and control of the pelvic floor muscles such that maximal force can be generated when needed to overcome urgency and leakage.
- Bladder training starts a patient voiding on a fixed time interval schedule with the intention that the patient will urinate before experiencing urgency and UI.
- It can be used with or without medical therapy.
- Most OAB patients can benefit from multimodality therapy including bladder training, PFMT, and medical therapy.
- After appropriate evaluation, sacral neuromodulation, botulinum toxin injections, and surgical reconstruction/diversion are options for refractory OAB.
Pharmacologic Management of OAB:
- Antimuscarinic agents are the first line pharmacologic treatment for OAB.
- Antimuscarinics produce symptomatic improvement by reducing urgency and therefore reducing UUI and frequency, decreasing detrusor overactivity or involuntary contractions of the bladder muscle, and increasing bladder capacity.
- Antimuscarinic agents have demonstrated in clinical trials that they improve continent days, mean voided volume, urgency episodes, and micturition frequency.
- They have for the most part demonstrated improvement in health related quality of life.
- Across large patient samples, all of the currently available antimuscarinics appear to have comparable efficacy but do show some measurable differences in tolerability.
Antimuscarinic agents commonly used in the management of OAB
- Oxybutynin IR 7.5-20 mg daily (2.5-5 mg PO tid-qid)
- Oxybutynin XL 5-30 mg daily (given once daily)
- Oxybutynin patch twice weekly
- Oxybutynin gel
- Tolterodine 2 mg twice daily
- Tolterodine LA 4 mg daily
- Darifenacin (7.5-15 mg qd)
- Solifenacin (5-10 mg qd)
- Trospium (20 mg daily to twice daily; XL qd)
- Fesoterodine
Consideration in treatment selection and adverse events:
- Regardless of which antimuscarinic is used, urinary retention may develop.
- Since the profiles of each drug and the dosing schedules differ, these things along with medical co-morbidities and concomitant medications should be considered when individualizing treatment for patients.
- The most common adverse effects include dry mouth, blurred vision, pruritis, tachycardia, somnolence, impaired cognition and headache.
- Recent large meta-analyses of the most widely used antimuscarinic drugs have clearly shown these drugs provide a significant clinical benefit.
- More research is needed to decide the best drugs for first-, second-, or third-line treatment.
- None of the commonly used antimuscarinic drugs (darifenacin, fesoterodine, oxybutynin, propiverine, solifenacin, tolterodine and trospium) is an ideal first-line treatment for all OAB/DO patients.
- Optimal treatment should be individualised, considering the patient’s co-morbidities, concomitant medications and the pharmacological profiles of the different drugs.
Additonal Treatments: β3-AR selective agonists
A number of β3-AR selective agonists are currently being evaluated as potential treatment for OAB including solabegron and mirabegron.
- Mirabegron is currently approved in Japan, USA, throughout several countries in Europe and around the globe.
Botulinum Toxin Botulinum toxin (Botox®; Allergan, Inc., Irvine, CA, USA) is a neurotoxin produced by Clostridium botulinum that acts as a potent presynaptic inhibitor of acetylcholine release at the neuromuscular junction.
- It was approved by the United States Food and Drug Administration in 2011 for the treatment of refractory neurogenic OAB for the treatment of refractory idiopathic OAB in patients who are refractory to conventional antimuscarinic therapy or who do not tolerate it due to systemic side effects.
Neuromodulation in the Treatment of OAB:
Percutaneous Tibial Nerve Stimulation (PTNS), a non-invasive way of modulating pelvic reflexes via projections from the posterior tibial nerve.
- Urgent® PC (Uroplasty, Inc., Minnetonka, MN, USA) is an office-based procedure approved by the US Food and Drug Administration that is used to deliver stimulation to the posterior tibial nerve using a 34-gauge needle electrode placed slightly cephalad to the medial malleolus.
- The recommended course of treatment is 12 weekly sessions of 30 minutes each.
- The Overactive Bladder Innovative Therapy (OrBIT) trial was a randomized, multicenter, control trial that compared PTNS with tolterodine ER; 79.5% of patients in the PTNS arm reported cure or improvement in symptoms compared with 54.8% of the tolterodine group as measured by the global response assessment (p = 0.01).
- Objective measures, including urinary frequency, urge UI episodes, urge severity, nighttime voids, and volume voided, showed similar improvement in the two groups.
- The authors concluded that PTNS was a clinically significant treatment alternative for OAB.
- 33 month data is recently avaiable that demonstrates no difference from the 12 week data.
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