This site is intended for health professionals only

Urinary incontinence- recent therapeutic developments

Paul Bulmer
MRCOG
Urogynaecology Research Fellow

Paul Abrams
MD FRCS
Professor of Urology
Bristol Urological Institute
Southmead Hospital
Bristol

There are two main types of urinary incontinence - urge incontinence and stress incontinence. Urge urinary incontinence is usually caused by involuntary contractions of the bladder muscle (detrusor overactivity) during bladder filling. Stress incontinence occurs when a weak urethral sphincter mechanism is overcome by increases in bladder pressure that are secondary to physical activity.

Urge incontinence
Urge incontinence secondary to an overactive bladder (OAB) has traditionally been treated either by bladder retraining (behavioural therapy) or pharmacologically. OAB is a symptomatic diagnosis in patients with urgency or urge incontinence suggestive of detrusor overactivity, and various drugs are currently available that claim to successfully alleviate detrusor overactivity. The majority of these drugs have antimuscarinic activity and produce inevitable unwanted effects, which the practitioner must balance against any perceived benefit. These antimuscarinic effects typically produce dry mouth, difficulty in visual accommodation, constipation and somnolence. The drugs should therefore be avoided in patients with obstructive uropathy, bowel obstruction, ulcerative colitis, narrow-angle glaucoma, myasthenia gravis or severe cardiovascular disease.

Oxybutynin
Oxybutynin is still the most commonly prescribed treatment for OAB in the UK, and is given two or three times daily, titrating benefit with side-effects.

Tolterodine
Tolterodine is a new antimuscarinic agent that appears to offer equipotent effects in the bladder compared with oxybutynin, but has a lower affinity for muscarinic receptors in the salivary glands. Currently available data suggest that tolterodine is better tolerated and is associated with higher patient compliance than oxybutynin.(1)

Other treatments
No antimuscarinic so far developed is specific for the bladder only, and the search for a bladder-specific muscarinic receptor continues.
The year 2000 saw an extended-release oxybutynin preparation being licensed in the UK for the treatment of OAB. This modified preparation is intended to prevent the peak plasma levels seen after dosing with immediate- release oxybutynin and therefore has less side-effects. Initial trials seem encouraging.(2)
There has been recent evidence to suggest that the side-effects of oxybutynin may be related to high levels of its metabolite, N-desethyl-oxybutynin, which occur after hepatic degradation.(3) In 1998, Winkler and Sand offered oxybutynin suppositories to 25 women with an unstable detrusor who had not tolerated oral antimuscarinics.(4) A total of 48% responded to the suppositories, and 58% of these continued to use the suppositories for at least 90 days.
Theoretically, parenteral administration of oxybutynin should avoid first-pass metabolism in the liver and may therefore be associated with less side-effects. Trials are currently being held to investigate the use of oxybutynin skin patches as well as an intravesical, continuous-release drug delivery system.(5)

Stress incontinence
Stress incontinence is more common in women, whereas urge incontinence is more common in men. Initial treatment of stress incontinence normally comprises advice on weight reduction and smoking cessation, and pelvic floor exercises. This provides satisfactory improvement in 30% of women.
Women who fail to respond to such measures and who request further, non-surgical treatment can be considered for a variety of intravaginal or intraurethral devices. The Conveen Continence Guard(TM) (Coloplast Ltd) is an example of an intravaginal device (see Figure 1). The shape of the device is such that, when it is placed in the vagina, it supports the bladder neck and thus prevents or reduces leaking during physical activity. It is inserted into the vagina with the use of an applicator (see Figure 2) and can be used for up to 16 hours per day.

[[NIP02_fig1_84]]

[[NIP02_fig2_84]]

There is no pharmacological agent currently available that has been shown to be effective in the treatment of patients with genuine stress incontinence. However, randomised placebo-controlled trails are in progress that aim to assess the efficacy of an alpha-adrenergic agonist as well as a 5-HT reuptake inhibitor for the treatment of such patients.

Surgery
Surgery should be considered for patients who have failed conservative measures, and the type of repair should be chosen on the basis of presumed pathophysiology. Colposuspension is currently the most common surgical technique used in the UK. Two new techniques are being evaluated: laparoscopic colposuspension and a suburethral sling procedure, the transvaginal tape.
Urethral bulking therapy is a surgical option for the treatment of mild stress incontinence or for those not suited to more major surgery in which a bulking agent is injected to bulk the tissues around the bladder neck. The procedure is performed under a local or regional anaesthetic, and the most common bulking agent is glutaraldehyde crosslinked bovine collagen. However, some patients are allergic to bovine collagen and, in addition, collagen is expensive and biodegradable. However, new synthetic materials are being developed and tested. These will, it is hoped, have better long-term cure rates and be cheap, easy to use and non-allergenic.

Meeting patient demand
There is an increasing awareness among the patient population that there are effective therapies for the treatment of urinary incontinence. This has led to incontinence becoming a more common reason for referral to hospital departments.
It is essential that clinicians and pharmaceutical companies continue to develop treatments that are effective, have few side-effects and complications, and are acceptable to patients.

References

  1. Appell RA. Clinical efficacy and safety of tolterodine in the treatment of overactive bladder: a pooled analysis. Urology 1997;50:90-6.
  2. Anderson R, Mobley D, Blank B, et al. Once daily controlled versus immediate release oxybutynin chloride for urge urinary incontinence. J Urol 1999;161:1809-12.
  3. Buyse G, Waldeck K, Verpoorten C, et al. Intravesical oxybutynin for neurogenic bladder dysfunction: less systemic side effects due to reduced first pass metabolism. J Urol 1998;160:892-6.
  4. Winkler HA, Sand PK. Treatment of detrusor instability with oxybutynin rectal suppositories. Int Urogynecol J 1998;9:100-2.
  5. Bulmer P, Abrams P. The overactive bladder. Rev Contemp Pharmacother 2000;11:1-10.

Resources
Bristol Urological Institute
W:www.bui.ac.uk

European Association of Urology
W:www.uroweb.nl/eau

International Continence Society
W:www.icsoffice.org.uk