Title:
Anticholinergic drugs versus non-drug active therapies for non-neurogenic overactive bladder syndrome in adults.

Abstract:
Overactive bladder syndrome is defined as urgency with or without urgency incontinence, usually with frequency and nocturia. Pharmacotherapy with anticholinergic drugs is often the first line medical therapy, either alone or as an adjunct to various non-pharmacological therapies after conservative options such as reducing intake of caffeine drinks have been tried. Non-pharmacologic therapies consist of bladder training, pelvic floor muscle training with or without biofeedback, behavioural modification, electrical stimulation and surgical interventions.
To compare the effects of anticholinergic drugs with various non-pharmacologic therapies for non-neurogenic overactive bladder syndrome in adults.
We searched the Cochrane Incontinence Group Specialised Register (searched 4 September 2012), which includes searches of the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE, and the reference lists of relevant articles.
All randomised or quasi-randomised, controlled trials of treatment with anticholinergic drugs for overactive bladder syndrome or urgency urinary incontinence in adults in which at least one management arm involved a non-drug therapy. Trials amongst patients with neurogenic bladder dysfunction were excluded.
Two authors evaluated the trials for appropriateness for inclusion and risk of bias. Two authors were involved in the data extraction. Data extraction was based on predetermined criteria. Data analysis was based on standard statistical approaches used in Cochrane reviews.
Twenty three trials were included with a total of 3685 participants, one was a cross-over trial and the other 22 were parallel group trials. The duration of follow up varied from two to 52 weeks. The trials were generally small and of poor methodological quality. During treatment, symptomatic improvement was more common amongst those participants on anticholinergic drugs compared with bladder training in seven small trials (73/174, 42% versus 98/172, 57% not improved: risk ratio 0.74, 95% confidence interval 0.61 to 0.91). Augmentation of bladder training with anticholinergics was also associated with more improvements than bladder training alone in three small trials (23/85, 27% versus 37/79, 47% not improved: risk ratio 0.57, 95% confidence interval 0.38 to 0.88). However, it was less clear whether an anticholinergic combined with bladder training was better than the anticholinergic alone, in three trials (for example 74/296, 25% versus 95/306, 31% not improved: risk ratio 0.80, 95% confidence interval 0.62 to 1.04). The other information on whether combining behavioural modification strategies with an anticholinergic was better than the anticholinergic alone was scanty and inconclusive. Similarly, it was unclear whether these complex strategies alone were better than anticholinergics alone.In this review, seven small trials comparing an anticholinergic to various types of electrical stimulation modalities such as Intravaginal Electrical Stimulation (IES), transcutaneous electrical nerve stimulation (TENS), the Stoller Afferent Nerve Stimulation System (SANS) neuromodulation and percutaneous posterior tibial nerve stimulation (PTNS) were identified. Subjective improvement rates tended to favour the electrical stimulation group in three small trials (54% not improved with the anticholinergic versus 28/86, 33% with electrical stimulation: risk ratio 0.64, 95% confidence interval 1.15 to 2.34). However, this was statistically significant only for one type of stimulation, percutaneous posterior tibial nerve stimulation (risk ratio 2.21, 95% confidence interval 1.13 to 4.33), and was not supported by significant differences in improvement, urinary frequency, urgency, nocturia, incontinence episodes or quality of life.The most commonly reported adverse effect among anticholinergics was dry mouth, although this did not necessarily result in withdrawal from treatment. For all comparisons there were too few data to compare symptoms or side effects after treatment had ended. However, it is unlikely that the effects of anticholinergics persist after stopping treatment.
The use of anticholinergic drugs in the management of overactive bladder syndrome is well established when compared to placebo treatment. During initial treatment of overactive bladder syndrome there was more symptomatic improvement when (a) anticholinergics were compared with bladder training alone, and (b) anticholinergics combined with bladder training were compared with bladder training alone. Limited evidence from small trials might suggest electrical stimulation is a better option in patients who are refractory to anticholinergic therapy, but more evidence comparing individual types of electrostimulation to the most effective types of anticholinergics is required to establish this. These results should be viewed with caution in view of the different classes and varying doses of individual anticholinergics used in this review. Anticholinergics had well recognised side effects, such as dry mouth.