Oxybutynin with bladder retraining for detrusor instability in elderly people: a randomized controlled trial

Age and Ageing, July, 1995 by George Szonyi, David M. Collas, Yew Y. Ding, James G. Malone-Lee

Introduction

Detrusor instability is a common cause of urinary incontinence in late life. Bladder retraining, which takes a variety of forms [1], is an important method of management [2], which can be supplemented with drug therapy. Several agents have been proposed, imipramine [3], propantheline [4], and oxybutynin [5-7]. The latter is the most widely used, and its efficacy in reducing symptoms has been demonstrated in women, both middle-aged (mean age 46) [7] and postmenopausal (mean age 61) [5]. By contrast it has been shown to be ineffective for chronically disabled elderly people in long-term institutions [6, 8], but has not hitherto been studied in frail elderly people living independently. A trial of terodiline with bladder retraining was reported from this centre and failed to show any benefit over placebo [9]. That drug has since been withdrawn because of serious adverse effects.

Oxybutynin is a tertiary amine with unselective antimuscarinic properties, although detrusor effects are mediated through M3 receptors. It is also a local anaesthetic and smooth muscle relaxant [10]. The aim of this study was to test the efficacy of oxybutynin in elderly ambulant patients with detrusor instability.

Methods

This was a randomized, double-blind, parallel-group study with dose titration. After a run-in period of 2 weeks, during which patients kept a diary chart of their frequencies of micturition and episodes of incontinence, patients were reviewed (day 15) and randomized to placebo tablets twice daily or oxybutynin 2.5mg twice daily. All patients were instructed in bladder retraining which was maintained throughout the treatment period. They were asked to delay micturition for as long as possible whenever they experienced the need to pass urine and to try by this means to reduce their frequency. The patients were reviewed on days 29 and 43 when their dose was adjusted in line with response and side-effects, and their symptoms and the contents of their diary charts noted: patients left the study on day 57.

Outpatients of either sex aged over 70 with symptoms of urinary frequency, urgency and urge incontinence were recruited. Patients had to be mobile, able to attend an outpatient department, able to keep a diary chart and willing to give consent. We excluded patients with urinary infections at the time of recruitment and patients with severe hepatic or renal disease, glaucoma, or uncontrolled diabetes. Patients on concomitant anticholinergic therapy with imipramine or propantheline were also excluded. The study was approved by the local ethics committee and all patients gave a witnessed written consent.

Before patients were included in the study they underwent a physical examination, with assessment of cognitive function by the Folstein Mini Mental State Evaluation (MMSE) and detrusor instability was diagnosed by water cystometry, filling at 1 ml/s, using the criteria of the International Continence Society [11]. Blood samples were taken for baseline haematology and biochemistry and a catheter specimen of urine was cultured. The randomization was achieved by allocating tablets in random permutations of blocks of four patients at a time.

Patients maintained a bladder chart throughout the study, recording with a tick, to the nearest hour, each micturition and each incontinence episode. At each review the charts were collected and the recordings summed over each period of a week. Their subjective response was assessed in two ways, firstly by asking `Has the treatment been of benefit to you (yes or no)?', and secondly by asking them to grade their improvement on a ranked ordinal scale; `No change', `Marginal improvement', `Significant improvement', `Cure'. Patients were also questioned about side-effects; specifically they were asked whether they had experienced dryness in the mouth, about its timing and severity, and whether it interfered with swallowing or speech, or prompted them to drink more. Other anticholinergic side-effects specifically asked after included hesitancy, constipation and blurred vision, With severity being graded on a five-point scale from nil (0) to unbearable (4). Their tablets were counted in order to check compliance. If there had been no objective or subjective improvement the dose of the drug was increased, in a stepwise manner, until either a response was obtained, side-effects became intolerable, or a dose of 5 mg three times daily had been reached. Blood samples were taken in order to check haemoglobin, blood cell counts, urea, electrolytes and hepatic function.

Statistical analysis. The sample numbers were estimated from an expected placebo response of 35% and an expected drug response of 75% [4, 6, 7]. With a probability of a type I error of 0.05 and probability of type II error of 0.10, a sample of 30 patients in each group was calculated as achieving sufficient power (85%-95%). The classification data were analysed for differences between groups using Fisher's. exact probability test. Comparisons of frequency data were achieved with the Mann-Whitney U test applied to the median changes in variables, quoting the test statistic W.