Treatment of detrusor hyperreflexia in multiple sclerosis: a double-blind, crossover clinical trial comparing methantheline bromide (Banthine), flavoxate chloride (Urispas) and meladrazine tartrate (Lisidonil). Intravesical atropine compared to oral oxybutynin for neurogenic detrusor overactivity: a double-blind, randomized crossover trial. Oxybutynin versus propantheline in patients with multiple sclerosis and detrusor hyperreflexia.
34 patients suffering from detrusor hyperreflexia due to multiple sclerosis entered the trial and 32 patients accomplished. The patients received each drug for a period of 14 days. The patients made records of relevant symptoms, urgency and urge incontinence and compared the treatment periods according to these symptoms. Registration of the number of micturitions was also made. Furthermore, the patients underwent cystometric studies. The following parameters were recorded and compared: residual urine, volume at the first bladder contraction, effective volume and amplitude of the first bladder contraction. The study showed that the patients preferred methantheline bromide. The entire cystometric pattern changed statistically significant with methantheline bromide, but only with concordance to the patients preferences in 60%. Decrease in number of micturitions and volume at the first bladder contraction were the only parameters showing accordance with the preferences. The drugs caused many various side effects. 12 treatment periods were discontinued due to side effects of meladrazine tartrate. The cystometric recordings seem to be of little use in evaluation of a drugs therapeutic effect, and it is difficult to find parameters which reflect the patients preference of the drugs. We tested the efficacy and side effect profiles of intravesical atropine compared to oxybutynin immediate release when used by individuals with multiple sclerosis.
                We performed a study to determine the most effective dose of atropine. Eight participants used increasing doses of intravesical atropine during a 12-day period. Bladder diary data showed that the instillation of 6 mg atropine 4 times daily was most effective for increasing bladder capacity (voided/catheter volumes). We then did a randomized, double-blind crossover trial. Participants received 14 days of treatment with oral oxybutynin or with intravesical atropine, followed by 14 days of alternative treatment. Participants recorded a bladder diary and rated side effects and quality of life. The primary outcome variable was bladder capacity.
                A total of 57 participants with multiple sclerosis completed the study. Average change in bladder capacity was higher in the atropine arm. The mean +/- SD oxybutynin change was 55.5 +/- 67.2 ml, the mean atropine change was 79.6 +/- 89.6 ml and the mean difference between arms was 24.1 ml (95% CI -0.4, 49.7; p = 0.053). Changes in incontinence events and voiding frequency were not statistically different between the arms. Changes in total side effect and dry mouth scores were significantly better in the atropine treatment arm.
                Intravesical atropine was as effective as oxybutynin immediate release for increasing bladder capacity and it was probably better with less antimuscarinic side effects. We recommend that intravesical atropine should be made available to patients with neurogenic detrusor overactivity and voiding problems requiring intermittent catheterization as an alternative to oral therapy, which often has troublesome side effects. Hyperreflexia is the most common urological finding in patients with multiple sclerosis. A prospective randomized study was done to compare the effectiveness of 2 commonly used drugs, oxybutynin and propantheline. Of the 34 patients entered into the trial 19 were treated with oxybutynin and 15 with propantheline. The urological symptoms (frequency, nocturia, hesitancy, urgency and urge incontinence) were graded according to severity from 0 to 3. Patients with urinary infection were excluded. Urodynamic examination, consisting of cystometrography and electromyography, was performed in all patients before treatment. Both groups of patients had comparable neurological, urological and urodynamic status before treatment. In 4 patients (21 per cent) treated with oxybutynin and in 4 (27 per cent) treated with propantheline side effects were so severe that the treatment had to be discontinued. Symptomatic response to oxybutynin was good in 10 patients (67 per cent), fair in 2 (13 per cent) and poor in 3 (20 per cent). Propantheline produced good symptomatic results in 4 patients (36 per cent), fair in 1 (9 per cent) and poor in 6 (55 per cent). The mean increase in maximum cystometric capacity on cystometrography was significantly larger in the oxybutynin group than in the propantheline group (144 +/- 115 versus 35 +/- 101). Our results indicate that oxybutynin is more effective than propantheline in the treatment of detrusor hyperreflexia in patients with multiple sclerosis.
From the available evidence we cannot advocate the use of anticholinergics in MS.