Long-term prospective randomized study comparing two different regimens of oxybutynin as a treatment for detrusor overactivity

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Abstract

Objective:

Prospective randomized trial to compare two low starting doses of oxybutynin, using an incremental regimen to assess patient compliance and treatment efficacy in the long-term.

Study design:

Women with detrusor overactivity were included. Oxybutynin was randomly prescribed with a starting dose of either 2.5 mg bd or 5 mg nocte. Instructions were given to increase oxybutynin up to 5 mg tds over a period of 6 weeks fortnightly. After two years we re-contacted all the women, using a specific questionnaire to assess the efficacy, acceptability and compliance with these two different regimens. Twenty-two women in each group were calculated to show a 5% difference with a significance of 0.05 and a power of 0.9. The χ2-test was used to compare the two groups and a P-value < 0.05 was considered significant.

Results:

Ninety-six women were included; 66 (68.75%) (mean age 57.5 years) responded to our questionnaire. Twenty-seven had a starting dose of 2.5 mg oxybutynin twice a day and 39 of 5 mg nocte. 34.8% complained of side effects. Only 19 (43.2%) out of the 44, not on medication anymore abandoned oxybutynin for adverse reactions. Most of the patients stopped oxybutynin within 4 months. 53.0% reported improvement or cure. 39.4% denied any benefit and 7.6% (none still on oxybutynin) did not answer. The two groups did not differ for duration of treatment, improvement with oxybutynin, maximum dose they reached, the present dose, and the present urinary symptoms.

Conclusion:

This study did not show any advantage in efficacy or compliance with oxybutynin when two different regimens of low starting were used. Two-thirds of patients discontinued the therapy within 4–6 months. Therefore, patients on anticholinergics should be reassessed after 6 months in clinical practice.

Introduction

Irritative bladder symptoms are very distressing and greatly compromise quality of life [1]. A major urodynamic cause is detrusor overactivity (DO), which is defined as involuntary detrusor contractions during the filling phase ,which may be spontaneous or provoked [2].

DO is the urinary condition which mostly impairs quality of life in women with urinary tract disorders [3], and its prevalence increases with age, being the most common cause of urinary incontinence in the elderly [4].

For this condition the current available treatments are behavioral (fluid restriction and bladder retraining), electrical stimulation, acupuncture, pharmacological (tolterodine, trospium chloride, oxybutynin, imipramine, propantheline, flavoxate) and surgical (neuromodulation, clam ileo-cystoplasty, urinary diversion).

Although it is now quite clear that tolterodine and trospium chloride are better tolerated than oxybutynin [5], [6], [7], [8], [9], the last one is still largely prescribed in Italy for its economic cost, being the cheapest one on the national market and being drugs for incontinence not reimbursed by the Italian government. Oxybutynin is a tertiary amine with unselective antimuscarinic activity and because of that it can cause unpleasant systemic side effects such as dry mouth, blurred vision, constipation and drowsiness. The common occurrence of these side effects reduces patient acceptability and use of oxybutynin, although its efficacy on a long-term basis is not known.

In fact, there is a lack of long-term studies of patients treated with anticholinergics, regarding either subjective or quality of life assessment or possible predictive factors for the success or failure of the treatment or patient compliance.

In a recent study Kelleher et al. [10] reported a 6-month analysis of the subjective efficacy of 5 mg twice daily of oxybutynin for the treatment of detrusor overactivity and low bladder compliance. These authors reported a cure or improvement rate of 52.3% with only 18.2% of women still on treatment after 6 months. In this study 92 (47.7%) women out of the 193 treated with oxybutynin stopped it because of side effects.

On the basis of these results, we started a further study to determine whether a low starting dose of oxybutynin, an incremental dose regimen and more explicit instructions could improve compliance with the treatment without altering its efficacy in the long-term.

An incremental increase in dose allows the woman to titrate improvement in urinary symptoms against worsening side effects [11]; this is extremely important since drug levels are different according to age and the individual's metabolism [12], [13].

Section snippets

Methods

Over a period of 1 year women with urinary symptoms referred to the Urogynecology Department of the King's College Hospital in London were recruited into this study after approval of our Ethical Committee. We only included those who had a videourodynamic diagnosis of detrusor overactivity or low bladder compliance and who signed an informed consent.

Detrusor overactivity was diagnosed when one or more detrusor contractions occurred during cystometry associated with symptoms (urgency or urge

Results

Ninety-six women were originally entered into this study.

Sixty-six (68.75%) out of 96 women responded to our questionnaire: 34 (51.51%) by phone, 22 (33.33%) after the first postal questionnaire and 10 (15.15%) after the second one. The overall mean age was 57.5 years (range 32–80) and the two groups did not significantly differ for age (59.2 ± 12.6 S.D. versus 53.3 ± 14.4 S.D.).

Twenty-seven of the responding women had a starting dose of oxybutynin of 2.5 mg twice a day whereas 39 had an initial

Discussion

In the treatment of bladder instability anticholinergic drugs are used worldwide, in conjunction with bladder training [16], as the first line treatment. Although new antimuscarinics such as tolterodine and trospium chloride seem to be better tolerated [5], [6], [7], [8], [9], oxybutynin is still largely prescribed in Italy because it is the cheapest one on the market since this kind of therapy is not reimbursed by the government. The available data [10], [11], [12], [13], [14], [15], [16] and

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