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Changing treatments for overactive bladder

AUTHORS Elizabeth Waine, MRCS, ChB, MB, is urology specialist registrar; Mark Stott, FRCS, MD, is consultant urologist; both at Royal Devon and Exeter NHS Trust.

ABSTRACT Waine, E., Stott, M. (2008) Changing treatments for overactive bladder. Nursing Times; 104: 41, 45-48.
Overactive bladder is a common urological diagnosis which is often untreated as patients fail to seek help for this embarrassing problem. Elizabeth Waine and Mark Stott summarise the symptoms and investigations for overactive bladder and provide an overview of the treatments available.

Overactive bladder (OAB) syndrome is a symptomatic diagnosis characterised by the presence of urgency, which is a sudden and compelling desire to pass urine which cannot be deferred, with or without urge urinary incontinence (UUI). UUI is the involuntary leakage of urine accompanied by or preceded immediately by urgency. The patient may also experience urinary frequency as well as nocturia, which is the desire to void which wakes the patient from sleep.

In order to make the diagnosis of OAB, the presence of urinary tract infection or other pathology must be excluded (Abrams et al, 2002). A large proportion of patients with symptoms will not seek help and therefore the true prevalence of this disorder is difficult to estimate.

A study carried out in six European countries estimated that 16.6% of the population aged 40 or above had symptoms of OAB, frequency being most commonly reported (85%), while urgency (54%), and urge incontinence (36%) were the next most commonly reported symptoms (Milsom et al, 2001). Sixty per cent had sought a medical consultation and 27% were receiving treatment.

OAB has a social and economical impact on people. The University of Michigan reported that OAB and more notably UUI occurred in 37% of women between 18 and 60 years of age within their study. Of those with severe symptoms, 88% reported a reduction in concentration, performance of physical activities, self-confidence or the ability to complete tasks without interruption (Fultz et al, 2005). The overall cost of OAB in the US in 2000 was estimated to be between $US9.1bn (Getsios et al, 2005) and $US12.6bn (Hu et al, 2004).

Cause of OAB

The true cause of OAB has not yet been established but several theories have been suggested, all of which imply an abnormality within the nervous control of bladder muscle (detrusor) contraction. This theory is supported by the action of the medical treatments given for overactive bladder, which work at the neuromuscular junction by blocking the release of the neurotransmitter acetylcholine and this prevents contraction of the detrusor muscle.

Assessment of a patient withsymptoms of OAB

It is important to take a thorough history and fully examine the patient. The impact that the patient's symptoms are having on their daily activities is extremely useful as this can help to monitor the effect of an intervention.

Excluding the presence of blood in the urine (haematuria) or pain on voiding may help eliminate other causes for the symptoms, for example bladder tumours or bladder stones.

A detailed past medical history, including any previous surgery, a comprehensive drug history, and, if the patient is female, a full obstetric and gynaecological history, should be taken.

Thorough questioning may highlight the presence of conditions such as untreated heart failure, which may aggravate symptoms, or irritable bowel syndrome which is associated with the symptoms of OAB (Cukier, 1997).

It is important to ask the patient about smoking and the possible exposure to carcinogens during their working life. For example, painters and hairdressers may have been exposed to carcinogenic dye.

Daily fluid intake should also be assessed. It may be possible to identify lifestyle changes that can be made to alleviate symptoms.

Physical examination includes abdominal examination to assess for the presence of a palpable bladder. Incomplete bladder emptying may mimic the symptoms of OAB but requires different treatment.

A full neurological examination should be carried out.

In men, a digital rectal examination assesses the presence of faecal loading or of an enlarged and/or abnormal prostate. In a women, a pelvic examination is carried out, and observation of simple disorders such as vaginal dryness or vaginal or uterine prolapse should be made. Gynaecological prolapse can alter the shape of the bladder and make complete emptying of the bladder difficult. Vaginal dryness can signify atrophic vaginitis which has an association with urethral narrowing.

In addition to the history and examination a number of simple tests can be carried out to help make the correct diagnosis (Box 1).

Box 1. Test for OAB

A midstream urine specimen should be tested and, if necessary, sent for microscopy, and culture. As well as ruling out infection, urine testing will detect the presence of haematuria, alerting the healthcare professional to the possibility of bladder stones or tumours

If a palpable bladder is present, renal failure as a result of a high pressure within the bladder causing back pressure on the kidneys must be excluded and the patient catheterised

Assessment tools such as a frequency volume chart or modules from the International Consultation Incontinence Questionnaires (Abrams et al, 2006) can assist the physician to assess a patient's symptoms and how they affect activities of daily living

Bladder diaries can be used to document times of micturition, voided volumes, episodes of urgency and incontinence, the number of incontinence pads used and how wet they are, as well as fluid intake. A three-day diary is as effective as a seven-day diary in assessing patients' symptoms (Dmochowski et al, 2005)

Management of OAB

A summary of how to manage OAB can be found in Box 2.

Box 2. Summary of management of OAB

  • Change fluid intake, for example eliminate drinks that contain caffeine

  • Bladder training

  • Pelvic floor exercises

  • Antimuscarinic drugs

  • Botulinum toxin can be used when patients fail to respond to antimuscarinic medication

Conservative measures

The initial management of OAB should concentrate on conservative measures. Educating the patient about lifestyle changes and diet, as well as the effects of drug therapy and the impact they have on symptoms, is important to gain compliance (Herschorn et al, 2004).

Fluid management is extremely important and many patients will be able to control symptoms by simple measures such as eliminating caffeine from their fluid intake and understanding the fluid component of their daily food- a diet high in fresh fruit and vegetables has a high water content. Stopping fluid intake after 6pm and ensuring that they void before bed are also simple measures to be tried by the patient. These measures may reduce or eradicate frequency and nocturia.

Bladder training and pelvic floor exercises are useful non-pharmacological measures to enable the patient to gain control of symptoms. Bladder training leads to a reduction in voiding frequency and increases voided volumes. The patient is taught to void each hour on the hour, then asked to increase the interval by 15 minutes each week until they are satisfied with their voiding frequency.

In addition to this, the patient is also taught pelvic floor exercises to be carried out when they experience a bladder contraction, or when they rise from lying or sitting as these situations have been identified as triggers for involuntary detrusor contractions (Burgio, 2002).

Continence advisers are invaluable in introducing these techniques to patients and improving compliance by reinforcing the importance of these self-help therapies.

Educating the patient about their symptoms and active bladder management therapies, such as pelvic floor exercises and bladder drill, have been shown to be as effective as drug therapy (Burgio, 2004).

Drug therapy

Pharmacological agents for OAB are numerous. First-line treatment should be the use of one of the many antimuscarinic preparations (Andersson, 2004). Antimuscarinic drugs prevent the binding of acetylcholine (ACh) at the muscarinic receptors at the neuromuscular junction of the detrusor muscle. These drugs aim to reduce the frequency of voiding and the number of incontinent episodes, but these drugs are not 'bladder specific', resulting in often quite distressing side-effects such as dry mouth, blurred vision, dizziness and constipation. They may also cause confusion in the elderly and this is often marked in patients with dementia.

However, by using the range of preparations available, with different dosing schedules and modes of delivery, it is usually possible to find an acceptable balance for symptom control and tolerability of side-effects. What suits one patient may give intolerable side-effects or no symptom relief to another. It should be noted that these drugs should be used with caution in patients who have bowel motility problems and are also contraindicated in patients with glaucoma.

  • Oxybutynin has been available for over 25 years with a variety of preparations and doses, thus enabling it to be used with great effect. It is broken down in the liver to provide an active metabolite component that acts with the parent compound as an antispasmodic. This reduces the number of detrusor muscle contractions. The immediate-release formulation of the drug should work within 30 minutes of administration and have a peak effect at 3-6 hours. However, it is also associated with quite marked side-effects, including dry mouth, indigestion and blurred vision. In order to reduce side-effects and prevent the peaks and troughs of drug levels within the circulation, slow release preparations and also a transdermal patch preparation have been developed. The compliance with these drugs is improved as the frequency of administration is reduced to a once-daily and twice-weekly application respectively. Overall control of symptoms with transdermal patches are comparable to the slow release preparations of oxybutynin and newer medication tolterodine but with fewer severe side-effects demonstrated.

  • Tolterodine and its active metabolite are more selective agonists of the bladder muscarinic receptor than those found in the salivary glands, so a dry mouth is less of a problem. It is an oral preparation that can be given as an immediate release twice daily or as in extended release once daily formula. Tolterodine has been shown to be effective in relieving the symptoms of urinary frequency, urgency and urge incontinence associated with OAB (Appell, 1997).

  • Trospium chloride is a safe drug to use with older people and patients with cognitive impairment as it does not penetrate the central nervous system and cause confusion. The
    twice-daily drug should be taken on an empty stomach as the presence of food alters absorption of the drug. It should also be used with care in patients with impaired kidney function as the kidneys excrete it. It has been shown to control symptoms within a week and a dry mouth is less
    of a problem when compared with standard preparation of oxybutynin.

  • Propiverine hydrochloride has a dual action of preventing ACh from binding to the muscarinic receptors and blocking calcium influx to the muscle, which is required by the muscle fibre to contract (Madersbacher and Murtz, 2001). Propiverine is a twice-daily preparation with a better side-effect profile than oxybutynin, and its effect on increasing bladder capacity at the first desire to void and also the total bladder capacity is comparable with oxybutynin (Madersbacher, 1999). It has been compared with tolterodine 2mg twice-daily preparation and shown to have a comparable efficacy, tolerability and improvement in quality of life (Junemann et al, 2005).

  • Solifenacin succinate is a once daily antimuscarinic that selectively binds to the M3 receptor within the bladder. Solifenacin has been shown to be effective in the management of OAB in those who have no incontinence. It significantly cuts daily urgency episodes and urinary frequency and increased voided volumes when compared with a placebo (Abrams and Swift, 2005).

  • Darifenacin is a once daily treatment that has been shown to have a similar effect on incontinent episodes and urgency as oxybutynin immediate release. Darifenacin was also found to be safe with older people (65 years) with OAB. It produced significant improvements in all major symptoms of OAB, with the main adverse effects of dry mouth and constipation being reported as only mild or moderate when compared with placebo (Foote et al, 2005). It has also been shown to increase the duration of time that the patient is free from urgency (Zinner et al, 2006).

  • Fesoterodine fumarate is a new antimuscarinic that was launched in July. As yet the authors have no experience of this drug in the clinical setting.

Botulinum toxin

Botulinum toxin type A (BTX-A) is one of the neurotoxins released by the soil-dwelling bacterium Clostridium botulinum. It acts at the neuromuscular junction by breaking down the intracellular proteins that aid in the release of acetylcholine into the synaptic cleft (Dolly, 2003) (Fig 1). The result is the muscle fibre served by that synapse fail to contract.

BOTX-A has therapeutic indications throughout the field of medicine and has been extensively used by plastic surgeons in cosmetic surgery procedures. Over the last few years, it has become a widely used treatment modality for patients
with OAB, who have failed to respond to antimuscarinic medication.

Following urodynamic studies, the toxin is injected via a cystoscope into the bladder at 20-30 sites under a local anaesthetic. Dosing regimens vary from 200 to 1,000 units of BTX-A. When used in patients with idiopathic OAB who fail to respond to behavioural and medical therapy, it appears that a dose of 300 units provides an immediate improvement in urgency and frequency, it increases urine volume at the first desire to void, and increases bladder capacity (Rajkumar, et al, 2005). The patient should be informed before the injection of the risk of bleeding, urinary tract infection and urinary retention. The last complication may require the patient to carry out intermittent self-catheterisation and this should be taught to the patient before the injection.

Conclusion

Successful management of OAB requires careful assessment to diagnose the problem accurately. Regular reassessment is also required to ensure that the patient is receiving the most appropriate treatment with the minimum amount of side- effects. Ensuring the treatment is appropriate helps to improve concordance with therapy and ultimately improves the patient's quality of life.

References

Abrams, P. et al (2002) The standardisation of terminology of lower urinary tract function: report from the Standardisation
Sub-committee of the International Continence Society.
Neurourology and Urodynamics; 21: 2167-2178.

Abrams, P., Swift, S. (2005) Solifenacin is effective for the treatment of OAB dry patients: a pooled analysis. European Urology; 48: 3, 483-487.

Andersson, K.E. (2004) Antimuscarinics for treatment of overactive bladder. The Lancet Neurology; 3: 1, 46-53.

Appell, R.A. (1997) Clinical efficacy and safety of tolterodine in the treatment of overactive bladder: a pooled analysis. Urology; 50: 6A Suppl, 90-96.

Burgio, K.L. (2004) Current perspectives on management of urgency using bladder and behavioral training. Journal of the American Academy of Nurse Practitioners;16: 10 (suppl), 4-7.

Burgio, K.L. (2002) Influence of behavior modification on overactive bladder. Urology; 60: 5 Suppl 1, 72-76.

Cukier, J.M. et al (1997) A case-control study to examine any association between idiopathic detrusor instability and gastrointestinal tract disorder, and between irritable bowel syndrome and urinary tract disorder. British Journal of Urology; 79: 6, 865-878.

Dmochowski, R.R. et al (2005) Bladder-health diaries: an assessment of 3-day vs 7-day entries. British Journal of Urology International; 96: 7,1049-1054.

Dolly, O. (2003) Synaptic transmission: inhibition of neurotransmitter release by botulinum toxins. Headache; 43: Suppl 1, S16-S24.

Foote, J. et al (2005) Treatment of overactive bladder in the older patient: pooled analysis of three phase III studies of darifenacin, an M3 selective receptor antagonist. European Urology; 48: 3, 471-477.

Fultz, N. et al (2005) Prevalence, management and impact of urinary incontinence in the workplace. Occupational Medicine; 55: 7, 552-557.

Getsios, D. et al (2005) Pharmacological management of overactive bladder: a systematic and critical review of published economic evaluations. Pharmacoeconomics; 23: 10, 995-1006.

Herschorn, S. et al (2004) Impact of a health education intervention in overactive bladder patients. Canadian Journal of Urology; 11: 6, 2430-2437.

Hu, T.W. et al (2004) Costs of urinary incontinence and overactive bladder in the United States: a comparative study. Urology; 63: 3, 461-465.

Junemann, K.P. et al (2005) Propiverine versus tolterodine: efficacy and tolerability in patients with overactive bladder. European Urology; 48: 3, 478-482.

Madersbacher, H. et al (1999) A placebo-controlled, multicentre study comparing the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence. British Journal of Urology International ; 84: 6, 646-651.

Madersbacher, H., Murtz, G. (2001) Efficacy, tolerability and safety profile of propiverine in the treatment of the overactive bladder (non-neurogenic and neurogenic). World Journal of Urology; 19: 5, 324-35.

Milsom, I. et al (2001) How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. British Journal of Urology International; 87: 9, 760-766

Rajkumar, G.N. et al (2005) A prospective study to evaluate the safety, tolerability, efficacy and durability of response of intravesical injection of botulinum toxin type A into detrusor muscle in patients with refractory idiopathic detrusor overactivity. British Journal of Urology International; 96: 6, 848-852.

Zinner, N. et al (2006) Efficacy, tolerability and safety of darifenacin, an M(3) selective receptor antagonist: an investigation of warning time in patients with OAB. International Journal of Clinical Practice; 60: 1, 119-126.

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