This study was designed to collect data on efficacy, safety and tolerability of darifenacin administered alone or in conjunction with BMP. As the addition of BMP to darifenacin did not provide any significant additional improvement on OAB symptoms, these data suggest that darifenacin alone may provide a degree of improvement that cannot be further enhanced by behavioural therapy. Although both behavioural and drug therapies are known to be effective treatments for OAB independently, there are relatively few trials assessing the value of combining these two modes of treatment. Whether behavioural therapy might have an additive benefit with drug treatment remains to be confirmed, with inconsistent findings reported to date (13
Two studies reported no increase with combined anticholinergic and bladder training, compared with bladder retraining without anticholinergic therapy (13
). In contrast, two studies found that the combination of drugs and behavioural training can produce more benefit than either therapy alone (15
). In one study, community-dwelling women with urodynamic evidence of bladder dysfunction, were randomised to behavioural treatment, oxybutynin or placebo and offered the opportunity to crossover into combined therapy if not satisfied after 8 weeks (15
). Twenty-seven subjects (41.5%) from drug therapy alone and eight subjects from behavioural treatment alone crossed to combined treatment, with both groups achieving an additional improvement in the reduction of incontinence. However, these results cannot be considered definitive based on the small sample size. The second (multicentre, single-blind) study compared tolterodine treatment with and without the addition of written information about bladder training (16
). In this study, the effect on voiding frequency and volume voided was enhanced by the combination, but there was no further improvement in urgency or incontinence episodes. Recently, a Cochrane review evaluated randomised or quasi-randomised controlled trials of treatment with anticholinergic drugs for OAB syndrome or UUI in adults, in which at least one management treatment group involved a non-drug new therapy, including BMPs (17
). The results regarding bladder training favoured a combination of anticholinergics with bladder training compared with anticholinergics during treatment even if the difference was not statistically significant.
In the present study, the addition of BMP to darifenacin produced no greater reduction in micturition frequency or UUI than was seen with darifenacin alone. One possible explanation for this is that the mechanisms underlying the two treatment effects, although different, may have a common single outcome of decreasing detrusor contraction, or increasing detrusor stability. Comparing the specific nature of the selective M3
receptor blockade provided by darifenacin, with the more general behavioural (both physiological and psychological) approach with BMP, this would seem unlikely. Indeed, both treatments are likely to do more than simply reduce detrusor activity. For example, it has been suggested that additional direct effects of antimuscarinic agents play a role in their overall therapeutic effects, and that the reduction of sensory symptoms such as urgency, may be mostly independent of their effect upon voiding contractions (18
Another possibility for the lack of additional benefit of BMP was inadequate compliance with the BMP, although this was not formally assessed in our study. In a previous retrospective study of 123 women with UUI, 55% of the women either never started the bladder retraining programme or discontinued it before study completion illustrating the difficulties with compliance faced by clinical trials (20
Interestingly, Burgio et al. (15
) performed a study in older women (mean age = 69.3 years) and demonstrated some benefit of combining drug and behavioural therapy. The patient population was entirely female, older than in the present study and employed biofeedback techniques as part of the training regimen (15
). In comparison, the present study population was mostly female (approximately 90%), and the analysis of older patients (≥ 65 years) did not yield any significant findings to suggest an additional benefit of BMP in older patients, although of note, the study was not powered to detect an effect in the older patient subgroup.
An additional consideration may be that the effectiveness of BMP may differ between different types of BMP. For example, the completion of patient diaries may themselves confer (albeit to a small extent) a degree of behavioural training. In this study, such an effect would have occurred for both patient groups, thereby reducing the potential for further benefit by addition of BMP. For formal BMP programmes, effectiveness would be expected to increase with intensity of training (with personal tuition expected to yield better results than paper/video instructions alone), and with subsequent monitoring and reinforcement of training by the caregiver. In the present study, training occurred only at baseline and week 2, and there are no data to confirm consistent application of the behavioural recommendations. This approach is expected to be consistent with that used in ‘real-life’ clinical settings.
Finally, it may be that behavioural modification training is more successful in patients with more pronounced incontinence problems. In our trial population the baseline mean number of UUI episodes per day was 2.8 in the darifenacin group, and 3.0 in the darifenacin + BMP group. Thus, there was limited scope for improvement in either group, and this is also demonstrated by the finding that near-normalisation of micturition frequency was already achieved by week 2. This relatively ‘dry’ profile of patients may therefore have further contributed to the non-significance of adding BMP to darifenacin treatment in this study.
In summary, the findings of the present study support the use of darifenacin as an effective agent for reducing the symptoms of OAB and improving HRQoL. However, the data do not support the hypothesis that behavioural modification of the type used in this study, adds any significant benefit over that achieved with darifenacin alone for treatment of the clinical symptoms of OAB, at least in our study population. Further studies are necessary to define the combination of patient populations, drugs and behavioural modification regimen that provide optimal reduction of OAB symptoms.