Placebo--the drug of choice in female motor urge incontinence? An objective comparison of the effects of parenterally administered drugs in patients suffering from detrusor instability. [Intravesical instillation of trospium chloride, oxybutynin and verapamil for relaxation of the bladder detrusor muscle. A placebo controlled, randomized clinical test]. Prospective study comparing hyoscyamine, doxazosin, and combination therapy for the treatment of urgency and frequency in women. [Comparative studies of the effect of mictonorm (propiverin hydrochloride) and Spasuret (flavoxate hydrochloride) on the bladder detrusor muscle].
In a randomised double-blind cross-over trial of 19 females with motor urge incontinence but without bladder suspension defect, the effects of 14 days' treatment with emepronium bromide 200 mg qid, flavoxate chloride 200 mg qid or placebo qid were compared by means of micturition charts, the patients' drug preferences and evaluation of side effects. Placebo was the only drug giving rise to a statistically significant decrease in the frequency of voidings, incontinence and nocturia. Forty-seven per cent of the patients preferred placebo and side effects were less frequent during treatment with this medication. No differences could be demonstrated between the effects of emepronium bromide and flavoxate chloride. Perhaps detrusor instability is not always the main reason for the voiding dysfunction in these patients, in whom the effect of placebo was equal or superior to the effect of "active drugs" and superior to no treatment at all. Cystometric changes produced by 3 parenterally administered drugs, flavoxate hydrochloride, emepronium bromide and imipramine hydrochloride, have been evaluated in 15 female patients with detrusor instability. Each patient was given 2 of the 3 drugs and cystometric recordings were done 10 and 30 minutes after the administration of each drug. Emepronium bromide was found to be the only drug to cause a significant improvement in bladder capacity and reduction in detrusor pressure. Therapy of detrusor hyperactivity with anticholinergic agents often is followed by adverse drug reactions. Intravesical application may be an interesting alternative. A randomised, single-blind, placebo-controlled, mono-centre clinical trial was carried out in 84 patients with urgency or urge incontinence. Due to intravesical administration of oxybutynin (CAS 5633-20-5) (n = 21) and trospium chloride (CAS 10405-02-4) (n = 21), respectively, a significant increase in maximum bladder capacity and decrease of detrusor pressure accompanied by an increase of residual urine were found in comparison to placebo in urodynamical investigations. Improvement of uninhibited bladder contractions occurred leading to higher filling volume. Under verapamil (CAS 152-11-4) (n = 21) no marked changes in the efficacy variables were found compared with placebo. All patients completed the study and were assessed with regard to efficacy and safety. No adverse events or marked changes in the vital signs were reported. The immediate onset of effect and the lack of adverse drug reactions suggest that treatment with topical oxybutynin or trospium chloride is an effective alternative in patients with intolerable side effects when orally treated. In addition, intravesical administration may be indicated in patients with bladder spasms due to indwelling catheter or in order to increase bladder capacity before percutaneous cystostomy. Anticholinergics are commonly used for the treatment of frequency, urgency, and urge incontinence in women. Alpha-blockers have been shown to have a modulating effect on bladder smooth muscle but are not commonly used clinically for this indication. To evaluate the clinical effectiveness of each treatment as well as the combination therapy, we performed an open prospective study comparing these agents. Between September 1994 and October 1995, 34 women aged 28-91 (mean age, 62) received either 0.375 mg of sustained-release hyoscyamine twice a day or 2 mg doxazosin QHS prior to being crossed over to the other drug and/or the combination. Symptoms were assessed using an expanded American Urological Association (AUA) symptoms score, which included questions regarding incontinence at completion of each therapeutic phase. Evaluation included 6-channel urodynamics. All three therapies were noted to be effective in reducing AUA symptom scores. By urodynamic evaluation, a greater percentage of patients with increased voiding pressures or decreased compliance responded to doxazosin than hyoscyamine. Side effects were noted to be less prevalent with doxazosin than with the other therapies. There appears to be a significant role for alpha-blockers in the treatment of voiding symptoms in women. 46 patients suffering from urgency/urge incontinency were treated with Mictonorm and Spasuret in a crossing-over study. In consideration of the placebo effect in this disease both agents were tested versus a non-verum. The application period was 4 weeks and the dosage was 45 mg/d Mictonorm and 300 mg/d Spasuret, respectively. Both with Mictonorm and with Spasuret a significant reduction of micturition frequency and an increase of the compliance could be observed, whereas the placebo was ineffective. A markedly growth of the maximal bladder capacity (16.9%) was obtained only by Mictonorm. Both agents keep likewise to an improvement of the symptoms or urgency/urge incontinency. Side effects could observed in a small size without a breaking-off of the treatment.
Many of the drugs considered in trials in this review are no longer used in clinical practice (and this includes the most commonly tested - flavoxate). There is inadequate evidence as to determine whether any of the available druge are better or worse than anticholinergic medications. Larger randomised controlled trials in clinical settings are required to further establish the role of these medications in the management of overactive bladder syndrome.