involuntary contractions of the bladder detrusor muscle, defined as detrusor overactivity, which occurs as the urinary bladder fills. The cause of this is unknown; ...
CLINICAL MEDICINE
JIACM 2006; 7(2): 109-12
Approach to Overactive Bladder JS Sandhu*, Anurag Gupta**, Varun Mohan**, A Markan**, P Sandhu***
Abstract Recent changes in terminology, diagnosis, and therapy have focussed attention on overactive bladder. This symptom syndrome is highly prevalent world-wide and significantly impairs the quality of life of those who suffer from it. The primary mode of therapy is the use of medications – currently antimuscarinic agents. Oxybutynin and tolterodine are the two most commonly used drugs with well-proven efficacy but with bothersome anticholinergic side effects. The perfect overactive bladder drug is not yet available. There is hope that future research will lead to a better understanding of this symptom complex; till then a combination of therapies is the best way to maximise outcomes.
Introduction
Prevalence
Overactive bladder (OAB), also known as Urge syndrome or urgency frequency syndrome, is a medical condition defined as urgency, with or without urge or reflex incontinence, usually accompanied with frequency, and in the absence of proven infection or other obvious pathology1. Incontinence is not a necessary condition for diagnosis, because approximately two-third of the patients with OAB do not have incontinence. OAB is suggestive of lower urinary tract dysfunction, detrusor overactivity.
Most previous studies concentrated on urinary incontinence and, until recently, little was known about the prevalence of OAB. The prevalence of OAB has been reported from six European countries to be 16.6% of the population aged more than 40 years5 and 16.5% of US population aged > 18 years6. The prevalence of OAB increases with age.
Urgency is defined as sudden compelling desire to pass urine, which is difficult to deter. Urge incontinence is defined as involuntary leakage accompanied by or preceded by urgency. Detrusor overactivity is urodynamically demonstrable involuntary detrusor contractions, during the filling phase of cystometry, which may be spontaneous or provoked2. Since OAB is a recently defined syndrome, its prevalence and natural history have not been well studied. Even though an overactive bladder is not a life threatening condition, it nevertheless decreases the quality of life. In contrast, “neurogenic bladder” results from detrusor hyperreflexia secondary to known neurologic disease. The symptoms of an overactive bladder and neurogenic bladder may be quite similar; however, the neurogenic bladder frequently results in compromised renal functions if an aggressive intervention is not undertaken3, 4.
Pathophysiology The symptoms of OAB are usually associated with involuntary contractions of the bladder detrusor muscle, defined as detrusor overactivity, which occurs as the urinary bladder fills. The cause of this is unknown; however, two theories of detrusor overactivity have been proposed. A. The myogenic theory7: suggests increased excitability of detrusor muscle cells producing involuntary pressure rise. B. The neurogenic theory8: suggests damage to the central inhibitory pathways, or sensitisation of peripheral afferent terminals in the bladder that can unmask primitive voiding reflexes that trigger detrusor overactivity.
Diagnostic evaluation An effective therapeutic treatment of OAB needs a targeted diagnostic evaluation9. History: A focussed relevant history in OAB includes –
* Professor of Nephrology, ** Resident in Nephrology, *** Associate Professor of Radiology, Departments of Nephrology and Radiology, Dayanand Medical College, Ludhiana - 141 001, Punjab.
Past history of genitourinary disorders and other conditions like stroke, dementia, parkinsonism, multiple sclerosis, diabetic neuropathy, etc.
to a combination of patient education, scheduled voiding and urge suppression techniques, and pelvic muscle exercises.
A symptom index of benign prostatic hypertrophy as recommended by American Urological Association10.
Lower urinary tract symptoms in females.
The patients are taught to void regularly on the hour, and then asked to increase the interval between voids by 15 minutes each week until they feel comfortable with their urinary frequency.
Examination: A focussed clinical examination should be carried out that includes –
Genitourinary examination
Pelvic examination
Rectal examination
Urine examination for haematuria and pyuria
Evaluation for residual urine (> 100 ml) in suspected patients. This may be estimated non-invasively with ultrasound examination that has > 90% accuracy, or invasively by catherisation.
Cystoscopic examination to exclude bladder malignancy or other intravesical pathology in those with haematuria. Prostate specific antigen (PSA) estimation in elderly men with suspicion of malignancy of prostate. The urodynamic testing in the evaluation of patients with symptoms of OAB is controversial11.
Treatment The principles of treatment include increasing voided volume, decreasing urgency, and reducing urine urge incontinence episodes. Various treatment modalities include –
Non-pharmacological interventions
Pharmacotherapy
Surgery
A. Non-pharmacological interventions Life style interventions: include patient and attendant in education about OAB, stopping caffeine and alcohol, avoiding fluids after 6.00 PM, and voiding before going to bed in case of history of nocturia12. Bladder training and pelvic floor exercises: generally refer
110
Pelvic floor exercises include teaching the patient to tighten the pelvic floor when sitting-up from lying down and when standing-up from a sitting position. Biofeedback and/or electrical stimulation do not seem to add to efficacy as compared to bladder training alone; however, these methods can be used as an adjunct to bladder training in selected patients13, 14. B. Drug therapy Many classes of drugs have been studied or proposed for the medical treatment of overactive bladder.
Drugs with predominantly anticholinergic or antimuscarinic effects. Muscarinic receptors have an important role in overactive bladder, since the drugs can abolish or reduce both detrusor overactivity and the symptoms of overactive bladder. M3 receptors (and probably M2 receptors) are involved in the pathogenesis of detrusor overactivity; the role of the other subtypes is uncertain15. The recommended first line medical treatment of OAB is the use of anticholinergic drugs which, although effective, may be poorly tolerated in view of bothersome side effects of dryness of mouth, constipation, gastroesophageal reflux, blurred vision, and urinary retention. Among the anticholinergic agents, only oxybutynin, propiverine, tolterodine, and trospium have the highest level of clinical recommendations and evidence of efficacy. Oxybutynin and tolterodine have been studied extensively11, 16. Oxybutynin: is a non-selective antimuscarinic agent that relaxes the bladder muscles and has local anaesthetic activity. It is available as immediate release (5 mg TID),
Journal, Indian Academy of Clinical Medicine
Vol. 7, No. 2
April-June, 2006
extended release form (5 or 10 mg OD), and as transdermal patches (39 cm2 patch in a dose of 36 mg per patch) with a release of 3.9 mg of oxybutynin per day over 3 - 4 days.
selective M 3-receptor-antagonist action and, consequently, fewer systemic anticholinergic side effects22, 23. Capsaicin and resiniferatoxin are two promising intravesical agents used to treat detrusor hyperreflexia of the neurogenic bladder24.
The extended release formulation of oxybutynin appears to have the same benefits as immediate release form, with fewer side effects. There is decrease in episodes of urge incontinence by approximately 70%, as depicted in various studies17, 18. Tolterodine: is a muscarinic antagonist that is available in short- acting (twice daily) and long-acting (once a day) preparation. Various clinical trials have shown 2 mg or 4 mg per day of tolterodine to be as effective as 5 mg or 10 mg per day of oxybutynin. The decision to choose one drug over the other is very difficult and depends upon the local factors of availability and cost19, 20.
New treatments under research include calcium channel antagonists and potassium-channel openers, and selective serotonin and nor-epinephrine re-uptake inhibitors11, 25. C. Surgery In case the first line treatment of OAB fails, urologist should be consulted. Urodynamic study may be performed to confirm detrusor overactivity in the patients with symptomatic diagnosis of OAB. Surgical techniques, including sacral neuromodulation techniques, cystoscopic injection of botulinum toxin, and augmentation enterocystoplasty, are reserved for severe problems recalcitrant to pharmacological and behavioural therapeutic endeavours26, 27.
Propiverine and trospium: have been shown to be effective in OAB in randomised, controlled trials, and have fewer side effects compared to short-acting oxybutynin. Both drugs however are not currently available in the market11, 21.
Oestrogens (for women)
Conclusion
Local vaginal preparations are more effective than oral oestrogen, but definitive data on effectiveness are lacking12.
Overactive bladder is a common medical symptom complex that affects people of all ages with a serious impact on the quality of life and economic burden. The clinical approach to OAB includes a focussed history and a targeted physical examination followed by appropriate investigations. There is no cure for OAB at the moment and the treatment aims at minimising the symptoms. The first line treatment includes life style interventions, bladder training, pelvic exercises, and pharmacotherapy. The mainstay of drug therapy is an antimuscarinic agent. The two best-studied agents are oxybutynin and tolterodine, and both have well-proven efficacy. Promising future therapies include the development of more specific antimuscarinic agents and new drug delivery systems.
Alpha-adrenergic antagonists (for men) These agents are useful in men with benign prostate enlargement. Postural hypotension can be a serious side effect. Doses must be increased gradually to facilitate tolerance12.
Other drugs Imipramine-a tricyclic antidepressant with both anticholinergic and alpha-adrenergic effects and, possibly, a central effect on voiding reflexes, have been recommended for mixed urge-stress incontinence. However, it should be used carefully in view of its side effects of postural hypotension and cardiac conduction abnormalities11, 12.
References 1.
Future promising drugs for OAB include two antimuscarinic agents – darifanacin and solifenacin – with
Journal, Indian Academy of Clinical Medicine
Vol. 7, No. 2
Abrams P, Cardozo L, Fall M et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 2002; 21: 167-78.
April-June, 2006
111
2.
Staskin DR, Wein AJ, eds. New perspectives on the overactive bladder. Urology 2002; 60 (Suppl): 1-104.
3.
Elliott DE, Lightner DJ, Blute ML. Medical management of overactive bladder. Mayo Clin Proc 2001; 76: 353-5.
4.
Garnett S, Abrams P. The natural history of the overactive bladder and detrusor overactivity: a review of the evidence regarding the long-term outcome of the overactive bladder. J Urol 2003; 169: 843-8.
5.
Milson I, Abrams P, Cardozo L, Roberts RG, Thuroff J, Wein AJ. How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int 2001; 87: 760-6. (Erratum, BJU Int 2001; 88: 807).
6.
Stewart W, Herzog R, Wein A et al. Prevalence and impact of overactive bladder in the US: results for the NOBLE program. Neurourol Urodyn 2001; 20: 406, Abstract.
7.
Brading AF. A myogenic basis for the overactive bladder. Urology 1997; 50 (Suppl): 57-73.
8.
De Groat WC. A neurogenic basis for the overactive bladder. Urology 1997; 50 (Suppl): 36-52.
9.
Fantl JA, Newman DK, Colling J 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 no. 96-0682.)
10. Barry MJ, Fowler FJ Jr, O’Leary MP et al. The American Urological Association symptom index for benign prostatic hyperplasia. J Urol 1992; 148: 1549-57. 11. Ouslander JG. Management of overactive bladder. N Eng J Med 2004; 350: 786-99. 12. Hashim H, Abrams P. Drug treatment of overactive bladder, efficacy, cost and quality-of-life considerations. Drugs 2004; 64: 1643-56. 13. Cardozo LD. Biofeedback in overactive bladder. Urology 2000; 55 (Suppl.): 24-8. 14. Goode PS, Burgio KL, Locher JL et al. Effect of behavioural training with or without pelvic floor electrical stimulation on stress incontinence in women: a randomised controlled trial. JAMA 2003; 290: 345-52.
17. Herbison P, Hay-Smith J, Ellis G, Moore K. Effectiveness of anticholinergic drugs compared with placebo in the treatment of overactive bladder: systematic review. BMJ 2003; 326: 841-4. 18. Birns J, Lukkari E, Malone-Lee JG. A randomised controlled trial comparing the efficacy of controlled-release oxybutynin tablets (10 mg once daily) with conventional oxybutynin tablets (5 mg twice daily) in patients whose symptoms were stabilised on 5 mg twice daily of oxybutynin. BJU Int 2000; 85: 793-8. 19. Appell RA, Sand P, Dmochowski R et al. Prospective randomised controlled trial of extended-release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder: results of the OBJECT Study. Mayo Clin Proc 2001; 76: 358-63. 20. Diokno AC, Appell RA, Sand PK et al. Prospective, randomised, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial. Mayo Clin Proc 2003; 78: 687-95. 21. Madersbacher H, Murtz G. Efficacy, tolerability and safety profile in propiverine in the treatment of the overactive bladder (non-neurogenic and neurogenic). World J Urol 2001; 19: 324-35. 22. Chapple C, Rechberger T, Al-Shukri S et al. Randomised double-blind placebo and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder. BJU Int 2004; 93: 303-10. 23. Haab F, Stewart L, Dwyer P. Darifenacin, an M3 selective receptor antagonist, is an effective and well tolerated once-daily treatment for overactive bladder. Eur Urol 2004; 45: 420- 9. 24. Chancellor MB, de Groat WC. Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder. J Urol 1999; 162: 3-11. 25. Martin SW, Radley SC, Chess-Williams R et al. Relaxant effects of potassium-channel openers on normal and hyperreflexic detrusor muscle. Br J Urol 1997; 80: 405-13.
15. Chapple CR, YamanishiT, Chess-Willium R. Muscarinic receptor subtypes and management of overactive bladder. Urology 2002; 60 (Suppl.): 82-8
26. Schurch B, Stohrer M, Kramer G et al. Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol 2000; 164: 692-7.
16. Andersson KE. Antimuscarinic for treatment of overactive bladder. The Lancet Neurol 2004; 3: 46-53.
27. Gross M, Bonne TB, Appell RA. Surgical management of overactive bladder. Curr Urol Rep 2002; 3: 388-95.
112
Journal, Indian Academy of Clinical Medicine
Vol. 7, No. 2
April-June, 2006
