The search terms run through these databases included ‘urinary incontinence’, ‘urinary incontinence elderly’, ‘treatment for urinary incontinence’, ‘Oxybutynin’ and ‘Tolterodine’.
The searches were conducted to include all relevant scientific information between the dates of 1942 to 2004.
Recruiting Papers
The use of a criteria helps to recruit studies that are matched in important categories such as relevance of sample, reliability and validity of methods and clarity of report so that accurate inferences can be drawn. A good criterion will reject studies with unreliable data and accept studies that can be reproduced.
Types of studies
All randomised-controlled trials of anticholinergic drugs for the treatment of urinary incontinence. Studies must be double-blinded.
Types of participants
All adult men and women with urinary urge incontinence (symptomatic or urodynamic diagnosis). The condition must not be related to any other underlying known medical condition.
Types of intervention
At least one arm of the study will use an anticholinergic drug and at least one other arm will use a different anticholinergic. Different formulation or route of administration may be included.
Types of outcome measures
Both subjective and objective outcome measures will be included in this review.
Primary outcomes of interest are:
A. Patient's observations e.g. symptom scores, perception of cure/improvement, satisfaction with outcome.
B. Quantification of symptoms e.g. number of leakage episodes, frequency and volume (urinary diary).
Data Extraction & Outcome Measures
The data from each paper that met the inclusion criteria was extracted and tabulated. The outcome measure of support for either drug was taken to be the actual conclusion inferred by the author’s of each individual study. Tolerability (adverse effects and patient compliance) for the drugs studied was also noted.
Results
Initial Search Results
The search term applied to achieve these results was ‘urinary incontinence AND elderly’.
Studies Recruited
Initially, six studies were recruited to the study, but one was excluded on the grounds of the outcome measures being tolerability and not efficacy of the drugs examined.
The final five studies recruited were:
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Dmochowski et al (2003)
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Leung et al (1998)
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Lee et al (2002)
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Abrams et al (1998)
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Homma et al (2003)
The data extracted from these studies are tabulated overleaf:
Tolerability Outcome Measures
Dmochowski et al (2003)
No scale of measurement was in place to determine whether adverse effects were present or whether these had a direct relationship to patient compliance. However, 8.3% of ‘Oxy-group’ experienced erythema (vs 1.7% of placebo-group) and 14.0% experienced pruritus (vs 4.3% of placebo-group). Anticholinergic side-effects only occurred in the ‘Tol-group’, dry-mouth accounted for 7.3% (vs 1.7% placebo-group) and constipation occurred in 5.7%. Thus, the study relied upon the assumption that all patients would report side-effects. 92% of patients in the oxy-group complied with treatment, with no comparable result recorded for tol- or placebo-group. Majority of withdrawals were due to side-effects.
Leung et al (1998)
The Xerostomia Questionnaire (XQ) was employed to specifically measure the salivation effect of the two drugs. XQ is designed to measure effect of dry mouth on the sensation of oral dryness, oral discomfort and on the ability to speak, chew, swallow and wear dentures, with each domain being assessed by 100-point visual analogue scale (VAS). Other side-effects were also recorded. Drug compliance was determined by counting returned tablets at the end of the trial: 87.5% for oxy-group (49.1% side-effects) and 75% for tol-group (60.4% side-effects). Although there was no significant difference between the two groups, patients withdrawing from the oxy-group were more likely to have a co-existing medical condition. Majority of withdrawals were unrelated to side-effects of the medication.
Lee et al (2002)
A three-point scale (mild/moderate/severe) categorised side-effects by intensity that were either spontaneously reported or directly observed. Of 101 side-effects reported by 65% of the tol-group and 152 side-effects reported by 82% of the oxy-group, dry mouth was the most commonly reported with a significantly higher incidence in the oxy-group. There was also a higher frequency of moderate-to-severe dry mouth among Oxybutynin recipients.
Compliance was determined by counting returned tablets at the end of the trial; patients were deemed compliant if 75% of medication had been taken. Majority of withdrawals were due to dry-mouth.
Abrams et al (1998)
All side-effects were recorded and categorised as in Lee et al (2002). Proportion of patients reporting at least one side-effect was significantly higher in the oxy-group in comparison to Tolterodine or placebo. Dry mouth was the most commonly reported side-effect with significantly higher frequency in both oxy- and tol-groups in comparison to placebo and significantly higher in oxy-group than in tol-group. Intensity of dry mouth was also higher in oxy-group than tol-group. Patient compliance was not measured.
Homma et al (2003)
Directly observed or spontaneously reported side-effects were categorised as in Lee et al (2002). A significantly higher percentage of patients withdrew from the oxy-group than placebo or tol-group due to side-effects. Other frequencies of withdrawal were similar across the groups. Dry mouth was the most common side-effect occurring in over half of the oxy-group, a third of the tol-group and only 10% of the placebo-group. Severity of dry mouth was also greater in the oxy-group than the others. Patient compliance was not measured.
Discussion
According to this study, Tolterodine is more effective than Oxybutynin in terms of efficacy. Of the five studies examined, four showed support for Tolterodine and only one supported Oxybutynin (Dmochowski et al, 2003). However, it should be noted Dmochowiski’s study supported Oxybutynin when administered through the trans-dermal route as opposed to the traditional oral route.
How reliable are these results? This study may be criticised on it’s method of literature search, since the only articles that could be included were those that were free full-text articles with the University of Exeter subscription. This constraint would have eliminated all abstracts or pay-per-view articles that may have been valuable to this investigation. As such, the literature search cannot be said to be entirely comprehensive.
In addition to this, the selection criterion may have been subject to experimenter expectancy bias, since there was no systematic way of adding or relaxing criteria. Other studies have sought to eliminate this by using a scoring system for assessing the quality of a study. One such scoring method was developed by Jadad et al (1996) and assesses randomisation, double-blinding and reports of dropouts and withdrawals. Studies are awarded zero for absence of the category and 1 for presence. A score of 3 or more (with a maximum of 5) is required for the study to be included.
These limitations imply that, although each study had large samples (total n=1555), not enough papers were recruited to ensure a representative sample of studies examining the efficacy of these drugs.
This study employed no formal statistical testing to assign significance of it’s conclusion. Instead of assessing the data recorded by individual studies, the assumption was made that each individual conclusion was statistically significant. Therefore, one cannot be mathematically confident that the conclusion drawn here is completely accurate.
Assessing efficacy of a drug does not take into account the tolerability or the patient’s experience of the drug. This is important since it has great implications in a patient’s adherence to treatment. Fortunately, all the studies examined the side-effects in some form, whether this information was obtained by a formal method or by spontaneous reporting. It does appear that systematic reporting of side-effects (as accomplished in Lee et al, 2002; Abrams et al, 1998 & Homma et al, 2003) is more comprehensive rather than relying on spontaneous reporting. However, not all the studies assessed patient compliance, which is important in determining whether the condition of the group was fulfilled completely.
One solution, to gain understanding of side-effects as experienced with anticholinergic drugs such as Oxybutynin and Tolterodine, would be to develop an in-depth case study of several patients currently taking either drug.
Tolerability appears to be greater for Tolterodine than Oxybutynin, with the most commonly reported side-effect for both drugs being dry mouth. Interestingly enough, Abrams et al found that reducing the dosage of either drug to half of the initial amount reduced symptoms significantly enough without noticeably reducing efficacy. Although, clinical drug trials have long assessed the safe amount of the drug to be administered, it may be that lowering this dose might provide better tolerability and thus better patient compliance.
It also appears that different routes of administration may be the key to increasing tolerability and subsequent patient compliance as demonstrated by Dmochowski et al. The fact that he increased tolerability in Oxybutynin that is usually not well tolerated against Tolterodine which is usually better tolerated, implies that traditional drug taking is not always the best option. Given the fact that Tolterodine is usually better tolerated, a trans-dermal formulation might produce even better tolerability than the Oxybutynin which does not show as much selectivity for the bladder. Clearly, further research is needed in this area that eventually might significantly reduce, if not eliminate, anticholinergic side-effects.
Although there is a large body of research into the efficacy of Oxybutynin and Tolterodine, tolerability still remains a problem. This study has shown that the ‘holes’ in research lie in improving tolerability with different dosing schedules or different administration routes.
References
Abrams P, Freeman R, Anderstrom C, Mattiasson A (1998) Tolterodine, A New Antimuscarinic Agent: As Effective But Better Tolerated Than Oxybutynin in Patients With An Overactive Bladder. British Journal of Urology Vol 81:801-10pp
Connor EL, Lind L (2001) Urinary Incontinence in Nursing Homes: Epidemiology and Management Guidelines. Primary Care Update Obs/Gyn Vol 8:248-52pp
Coppola L, Caserta F, Grassia A, Mastrolorenzo L, Altrui L, Tondi G, Verde S, Coppola A (2002) Urinary Incontinence In The Elderly: Relation to Cognitive and Motor Function. Archives of Gerontology and Geriatrics Vol 35:27-34pp
Dmochowski RR, Sand PK, Zinner NR, Gittelman MC, Davila GW, Sanders SW (2003) Comparative Efficacy and Safety of Transdermal Oxybutynin and Oral Tolterodine Versus Placebo in Previously Treated Patients With Urge and Mixed Urinary Incontinence. Adult Urology Vol 62:237-42pp
Freeman R, Hill S, Millard R, Slack M, Sutherst J (2003) Reduced Perception of Urgency in Treatment of Overactive Bladder With Extended-Release Tolterodine. Obstetrics & Gynaecology Vol 102:605-11pp
Griffiths D (1998) Clinical Studies of Cerebral and Urinary Tract Function in Elderly People with Urinary Incontinence. Behavioural Brain Research Vol 92:151:5pp
Homma Y, Paick JS, Lee JG, Kawabe K (2003) Clinical Efficacy and Tolerability of Extended-Release Tolterodine and Immediate-Release Oxybutynin in Japanese and Korean Patients With An Overactive Bladder: A Randomised, Placebo-Controlled Trial. BJU International Vol 92:741-47pp
Jadad A, Moore A, Carrol D (1996) Assessing the Quality of Reports of Randomised Clinical Trials; Is blinding necessary? Control Clin Trials Vol 17:1-12p
Lee JG, Hong JY, Myung-Soo C, Hun YK, Do YC, Kyu SL, Ji YL, Tack L (2002) Tolterodine: As Effective But Better Tolerated Than Oxybutynin in Asian Patients With Symptoms of Overactive Bladder. International Journal of Urology Vol 9:247-252pp
Leung HY, Yip SK, Cheon C, Liu YS, Lau J, Wong HK, Chung KH (2002) A Randomised Controlled Trial of Tolterodine and Oxybutynin on Tolerability and Clinical Efficacy for Treating Chinese Women With Overactive Bladder. BJU International Vol 90:375-80pp
Miller KL (2003) Urinary Incontinence in Elderly Women. Primary Care Update Ob/Gyn Vol 10:242-6pp
Resnick NM (1988) Voiding Dysfunction in the Elderly. In: Yalla SV, McGuire EJ, Elbadawi A, Blaivas JG eds. Neurology and Urodynamics: Principles and Practice. New York: Macmillan:303-30pp
Sathyan G, Chancellor MB, Gupta SK (2001) Effect of OROS® Controlled-Released Delivery on the Pharmocokinetics and Pharmacodynamics of Oxybutynin Chloride. British Journal of Clinical Pharmacology Vol 52:409-17pp
Thüroff JW, Chartier-Kastler E, Corcus J, Humke J, Jonas U, Palmtag H, Tanagho EA (1998) Medical Treatment and Medical Side Effects in Urinary Incontinence in the Elderly. World Journal of Urology Vol 16:48-61pp
SSU 3: Urinary Incontinence in Elderly Page