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Objective The aims of this study were to determine the medium term subjective outcome of treatment for women with a urodynamic diagnosis of detrusor instability and low bladder compliance.
Setting A tertiary referral Urogynaecology clinic.
Participants and methods One thousand one hundred and five women referred for the investigation of their urinary symptoms were entered into a prospective, long term, quality of life study. Of these, 348 had a videourodynamic diagnosis of detrusor instability or low bladder compliance and form the basis of this paper. Women were contacted by post at least six months following their urodynamic assessment and asked to complete a questionnaire detailing their treatment, its efficacy and side effects, and any residual urinary symptoms.
Results Two hundred and fifty-six women (73.6%) responded to follow up; only 5.5% were cured of their urinary symptoms. The majority (90.2%) had received anticholinergic medication, although only 18.2% continued with this treatment in excess of six months. Many women had residual urinary symptoms following their investigation and treatment.
Conclusion The medium term efficacy of the treatment of detrusor instability and low compliance is disappointing, and a large part of this failure may be attributable to poor treatment efficacy, side effects of medication, or inadequate follow up following the diagnosis and instigation of therapy.
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Detrusor instability is a common cause of urinary frequency, nocturia, urgency and urge incontinence. It is the second commonest cause of urinary incontinence among women, and the commonest cause among the elderly1. Quality of life studies have shown that it has a significant impact on the lifestyle of sufferers, with particular effects on their emotional wellbeing and interpersonal relationships2,3. Although the ability to diagnose detrusor instability may have recently improved by ambulatory urodynamic monitoring4, both its cause and natural history are incompletely understood. It is perhaps for this reason that many different treatments have been used with varying degrees of success, and that none has been conclusively proven to have a convincing long term benefit.
The treatment of detrusor instability is either conservative or surgical. Conservative measures include drug therapy5, bladder retraining6, biofeedback7, psychotherapy, hypnotherapy8, electrical stimulation9, TENS10 and acupuncture11. Various surgical procedures, including cystodistension12, selective bladder denervation13, phenol injection14 bladder transection15 and augmentation cystoplasty16, have also been described. Conservative therapy is the usual first line treatment, and recourse to surgery is typically reserved for women who have failed conservative management. The two most commonly used conservative treatments are bladder retraining and drugs which reduce bladder contractility. Frewen17 initially popularised behavioural therapy and achieved a promising cure rate of 80% following a three month course of treatment. However, Oldenderg and Millard18 have since shown that patient compliance limits its long term efficacy, and follow up studies demonstrating persistent long term benefits are lacking.
Most of the drugs used in the treatment of detrusor instability have anticholinergic effects, but these are not specific to the detrusor muscle, and therefore systemic antimuscarinic side effects (e.g. dry mouth, blurred vision, constipation and tachycardia) are a common complication of treatment. The most frequently prescribed drugs are oxybutynin, propantheline, imipramine and flavoxate. Oxybutynin, a quaternary amine with moderately potent antimuscarinic, muscu-lotropic, and local anaesthetic properties, is the usual drug of first choice. Clinical trials have shown a significant benefit of this drug compared with placebo19, although side effects are a major limiting factor restricting patient compliance and ultimately treatment efficacy.
In order to improve compliance a number of measures have been advocated including commencing treatment with a very low dose of drug and taking oxybutynin on a prn (as necessary) basis20. Although this latter method of prescription appears to be preferable to patients, there are no data to suggest that it improves treatment efficacy. Alternative methods of administration via intravesical instillation, suppositories, pessaries or slow release preparations have been suggested, but are not widely available or as universally applicable as oral administration.
Irrespective of the treatment used there is a considerable placebo effect in the treatment of women with detrusor instability which has been repeatedly demonstrated in clinical trials. In one study placebo was found to be superior to the active drugs and the preferred treatment of choice!21
There are few data regarding the long term follow up of women with detrusor instability and clinical trials of new drugs are usually small and of short duration. In 1989 Aitchison and Carter22 published the results of a five-year follow up of 50 women with detrusor instability only 12% of whom were cured at the time of follow up and who among them had accumulated 129 changes of drug therapy; 40% of the women were still under regular urological review, and of the remainder (although many remained symptomatic) only 20% accepted further treatment. It was suggested, but not proven by the authors, that women had either become disillusioned with their treatment or merely come to terms with their urinary symptoms.
The major reason for this poor treatment efficacy remains unclear. Whether it is the result of side effects and poor compliance, lack of follow up, limited efficacy of the drugs used, or a combination of all these factors remains to be assessed. In view of the large placebo response in the treatment of detrusor instability, it is possible that many women are not helped by treatments which appear useful only for as long as the placebo effect persists.
A major breakthrough in improved compliance with anticholinergic drugs would be the design of drugs with specific anticholinergic effects on the bladder without unwanted systemic side effects. Recently a new class of drugs acting on the more specific M3 receptor have been described; at present two such agents tolterodine23 and darifenacin24 have entered phase 3 clinical trials. While this may in itself be a major breakthrough, whether it results in superior treatment of detrusor instability remains to be seen.
The aims of this study were to investigate the outcome of treatment for women with a videourodynamic diagnosis of detrusor instability or low compliance over a medium term follow up period using currently available treatment modalities.
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Over a two-year period 1105 women referred to a uro-gynaecology clinic were entered into a long term prospective quality of life study. All underwent videourodynamic investigations comprising uroflowmetry, subtracted medium fill fluid cystometry (100 mL/min) and videocystourethrography. Women entered into the study have since been contacted by means of a postal questionnaire. For the purpose of this paper data are presented from those women who had an initial urodynamic diagnosis of detrusor instability or low bladder compliance.
Detrusor instability was defined as the presence of unstable detrusor contractions associated with the symptom of urgency occuring either spontaneously or on provocation during the filling phase of cystometry while the patient was attempting to inhibit micturition. Low compliance is arbitrarily defined as an excessive linear increase in detrusor pressure during filling cystometry. A significant pressure rise was taken to be a pressure of > 15 cm water for an infused volume of 400 mL associated with the symptom of urgency. All other definitions used in this paper conform to the standards of the ICS standardisation committee25.
Three hundred and forty-eight women had a diagnosis of detrusor instability (n= 262) or low compliance (n= 86) without other concomitant urodynamic findings. None had been previously investigated for urinary symptoms, and none had other significant medical, surgical or gynaecological problems. The majority of women were referred to this department for the investigation of their urinary symptoms and subsequently returned to their referring consultant unit for treatment. Women were contacted by post six to twelve months following their urodynamic assessment and asked to complete and return a detailed subjective follow up questionnaire. Information sought included:
A detailed account of all treatments received, their duration, and side effects;
A standardised subjective assessment of the efficacy of treatment;
An analysis of residual urinary symptoms.
The questionnaire was specifically designed to collect data regarding the type and date of commencement of treatment as this was found to vary considerably among referring hospitals. Women were asked to assess the success of their treatment on a four-point scale: 1. cured completely; 2. significantly improved; 3. much the same; and 4. worse. All respondents were asked if they had residual incontinence, urinary symptoms, whether they used incontinence pads, and whether their residual urinary symptoms were still problematic. In addition women were asked if they would recommend investigation and treatment to their friends and relatives with symptoms similar to their own. If any problems were encountered in the completion of the questionnaire women were asked to telephone the department and discuss them with one of our members of staff. A reminder was sent to all women who failed to respond to the questionnaire within three months, following which no further reminders were sent.
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Where relevent the results for women with detrusor instability and low compliance will be described separately.
Two hundred and fifty-six women (73.6%; detrusor instability: n= 193 [73.7%]; low compliance: n= 63 [73.3%]) correctly completed and returned the questionnaire. The mean duration follow up was 6.2 months (range 5–12). The mean age of respondents was 50.7 years (range 21–84; detrusor instability: mean 50.1; low compliance: mean 52.5), and the mean duration of urinary symptoms was 4.2 years (range 0.5–9; detrusor instability: mean 4.1, low compliance: mean 4.5).
Of those women with detrusor instability who did not respond to follow up questioning, two had died; no reasons were given by the other nonresponders for not completing the questionnaire. There was no significant difference in the age or duration of symptoms for women with these two diagnoses responding or not responding to follow up questioning.
Fourteen women (5.5%) were completely cured of all their symptoms, 123 (48.0%) significantly improved, 104 (40.6%) were the same and 15 (5.9%) were worse than before their investigation and treatment (Table 1). There was no significant difference in the treatment outcome for women with detrusor instability or low compliance. A summary of the treatment received by women completing the follow up questionnaire is shown in Table 2.
Table 1. The subjective treatment outcome of women with detrusor instability (DI) and low compliance (LC) (n= 256). Values are given as n (%).
|DI||11 (5.7)||96 (49.7)||75 (38.9)||11 (5.7)|
|LC||3 (4.8)||27 (42.9)||29 (46.0)||4 (6.3)|
|TOTAL||14 (5.5)||123 (48.0)||104 (40.6)||15 (5.9)|
Table 2. The treatment received by women with detrusor instability or low compliance completing the follow up phase of the questionnaire. In certain cases women received a combination of one or more different treatments. Values are shown as n (%) of women receiving each treatment. Key as for Table 1.
|Drug treatment||176 (91.2)||55 (87.3)|
|Bladder drill||46 (23.8)||16 (25.4)|
|Pelvic floor exercises||28 (14.5)||3 (4.8)|
|No treatment||6 (3.1)||2 (3.2)|
|Total abdominal hysterectomy||—||3 (4.8)|
|TOTAL||193 (100)||63 (100)|
Two hundred and thirty-one women (90.2%) had received drug treatment with anticholinergic medication, of whom 193 (83.5%) stated that they had been treated with oxybutynin. Sixty-two women (24.2%) had been formally instructed in some form of bladder drill, of whom nine (14.5%) had been admitted to hospital for inpatient bladder drill. Thirty-one women (12.1%) had been taught pelvic floor exercises.
Of the women with either diagnosis treated with anti-cholinergics, nine (3.9%) had continued with drug treatment for less than two weeks, 63 (27.3%) for two weeks to one month, 71 (30.7%) for one to three months, and 88 (38.1%) for greater than three months. Of the latter, 46 (19.9%) had continued treatment for less than six months (Fig. 1). Therefore, of the women commencing anticholinergic therapy, only 42 (18.2%) were still taking it on a regular basis six months following initial prescription. Ninety-two women (39.8%) had stopped treatment because of anticholinergic side effects, and 66 (28.6%) because they ran out of tablets! Of these 16 (24.2%) had run out of tablets within a month of the initial prescription.
Figure 1. The number and percentage of women with either detrusor instability or low compliance continuing with anticholinergic medication at the times specified on the graph. Numbers above the bars represent the number of women and the bars represent the percentage of the total (n= 231).
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Of the women treated with anticholinergic medication (n= 231), 121 (52.4%) felt that they were cured or improved, and 110 (47.6%) were the same or worse after treatment. However, 108 women (46.8%) still complained of frequency, 138 (59.7%) of nocturia, and 120 (51.9%) of urgency. In addition, 82 (35.5%) were still incontinent, of whom 74 (90.2%) found it troublesome (Fig. 2).
Figure 2. Residual urinary symptoms among the 231 women treated with anticholinergic medication for detrusor instability or low compliance. Numbers above the bars represent the actual number of women with each symptom, and the bars represent the percentage value.
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Sixty-six women (28.6%) still used protective pads either frequently or occasionally, and 126 (54.5%) felt that their lives were still affected by their urinary symptoms to some degree, although 214 (92.6%) felt that they would tell their friends to have investigation and treatment of urinary symptoms similar to their own. Overall 166 women (71.9%) felt that drug treatment was effective while they were able to tolerate it, and 31 (13.4%) felt that their treatment was worse than their urinary symptoms.
Of the women discontinuing treatment due to side effects (n= 92), 48 (52.2%) felt that it had been effective while they were able to take it. Fifty-two women (56.5%) in this group complained of residual urinary incontinence, 54 (58.7%) of urgency, and 47 (51.1%) occasionally or frequently wore protective pads or needed to change underclothes. Forty-eight women (52.2%) complained of frequency, 62 (67.4%) of nocturia, and 58 (63.0%) felt that their lives were still affected by their urinary symptoms. Only 14 women (15.2%) felt that their treatment had been worse than their urinary symptoms despite the high noncompliance rate.
Of the 92 women who discontinued treatment due to anticholinergic side effects, seven (7.6%) took medication for less than two weeks, 35 (38.0%) for two weeks to one month, and 33 (35.9%) for one to three months. Seventeen women (18.5%) continued with treatment for greater than three months.
Despite these figures, 81 women (88.0%) indicated that they wished they had been investigated sooner, and 79 (85.9%) felt that they would advise friends with similar symptoms to be investigated and treated. Women were not asked if they used medication intermittently, and failure to comply with treatment meant that they no longer took medication on a regular basis.
Of the women who had not received anticholinergic medication (n= 23), eight had received no treatment at all (detrusor instability: n= 6, low compliance: n=2), three women underwent total abdominal hysterectomy for low compliance attributable to uterine fibroids, and 12 had received bladder drill instruction alone.
Of the eight receiving no treatment, three were worse than before investigation and five were improved, (although two women who felt they were worse had never returned to their referring doctor for treatment following urodynamics). It is possible that these women may have been instructed regarding simple conservative measures (e.g. fluid restriction) and/or bladder drill at the time of their investigation, or that their urinary symptoms were not of major concern at the outset. All the women who underwent hysterectomy improved following surgery.
Of the remaining twelve women receiving bladder drill, eight were improved and four the same or worse following treatment. It is unclear whether anticholinergic therapy was withheld due to medical contraindications, or whether bladder drill was the treatment preferred by their referring doctor. Due to the method of data collection, it is also possible that these women did in fact receive other forms of treatment, but this was not recorded.
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It is hoped that an accurate urodynamic diagnosis will result in successful long term treatment of women's urinary symptoms; although there is insufficient available evidence to support this expectation. In this study it was disappointing that despite an accurate diagnosis only 53.9% of respondents were cured or improved by subsequent management. This figure is similar to the placebo response achieved in many short term clinical trials of the treatment of detrusor instability.
Many women were treated with anticholinergic medication, and it is not surprising in view of the significant antimuscarinic side effects associated with this treatment that 92 women discontinued treatment for this reason. It is unclear whether a lower starting dose or less strict regimen of therapy would have made a significant difference to the results. A further study is underway to determine whether a lower starting dose and more explicit instructions will improve compliance. However, 54.4% of these women persevered with treatment in excess of one month, and of all the women prescribed anticholinergic therapy (n= 231) only 18.2% took it for longer than three months. Overall 52.3% of women prescribed anticholinergic medication felt that they were cured or improved by treatment, which is almost identical to the 52.2% efficacy described by women who discontinued treatment due to side effects whist they were able to tolerate it. This would offer strong support to the need for different drugs, different routes of administration, or different prescribing protocols to limit systemic side effects.
Many of the patients described in this study were merely investigated in our unit and subsequently sent back to their referring consultant for treatment and, as a consequence, we have no way of knowing whether compliance with treatment could have been affected by these factors. In addition, it is also possible that women for whom treatment was unsuccessful were more likely to respond to the follow up questionnaire than those for whom their urinary symptoms were improved.
Admittedly, retrospective patient-assessed data collection may have inaccuracies, particularly when the treatment has failed. This is especially relevant for the management of detrusor instability and may result in a considerably harsher assessment of treatment efficacy than if women had undergone repeat objective assessment and the response rate to follow up questioning had been better.
The aim of this study was to determine primarily if as a result of accurate urodynamic asessment and therefore clinical diagnosis of the cause of their urinary symptoms, women were subjectively improved following a reasonable duration of treatment. It is not usual practice to perform repeat cystometry once a diagnosis of detrusor instability has been made, and the objective measurement of improved cystometric parameters may have little relevance when the women themselves feel no better. It would have been interesting to compare subjective and objective data at follow up, although this would have necessitated women undergoing repeat cystometry and was not the primary purpose of this study.
It is of great concern in view of the many other reasons for poor treatment efficacy that 66 women stopped their medication because they ran out of tablets and that 16 of these ran out within a month of initial prescription. Although in some cases this may be an excuse, and side effects or poor treatment efficacy may have encouraged women not to renew their prescriptions, it would certainly indicate that we need to monitor the treatment of detrusor instability much more closely in order to improve our methods of treatment and justify our investigation and diagnosis of this condition.
It was interesting to find that considerably more women with detrusor instability were pleased to have been investigated and treated than were actually cured or improved thereafter. This would indicate that for many women a diagnosis is important, even if a cure is more difficult to achieve. Certainly this would emphasise the importance of ambulatory urodynamics which are reported to have a greater sensitivity for the investigation and diagnosis of the cause of irritative bladder symptoms than conventional cystometry.
Although the numbers were small (n= 3), women with low compliance attributable to compression of the bladder by fibroids were completely cured by hysterectomy. There are however many other reasons why this treatment would be advocated and in all cases urodynamics were performed not to diagnose low compliance, but to exclude severe genuine stress incontinence and the need for continence surgery at the time of hysterectomy.
Twelve women were treated with bladder drill alone, of whom eight were cured or improved. This result was better than that of anticholinergic therapy which may be attributable to the lack of side effects, or the presence of less severe urinary symptoms at the outset. There was no medical reason in six cases why anticholinergic therapy was not prescribed, and therefore this choice of treatment must have been made by the referring doctor or the patients.
The subjective assessment of the efficacy of treatment of detrusor instability and low compliance in this study is disappointing. Side effects restricted treatment compliance but a cure or improvement rate of only 52.3% is poor and could possibly be similarly achieved without performing urodynamics at all. It is clear that in order to improve compliance with anticholinergic medication, which does appear to be efficacious, closer monitoring of treatment compliance and efficacy are required. In addition it is hoped that the more selective action of the new M3 antimuscarinic agents will make these drugs more acceptable and therefore better tolerated in the long term.