Neuro-urologyEffective Treatment of Neurogenic Detrusor Dysfunction by Combined High-Dosed Antimuscarinics without Increased Side-Effects
Introduction
The development of neurogenic bladder dysfunction is often one of the clinical symptoms that develop after a spinal cord injury (SCI). Patients suffering from multiple sclerosis or other spinal cord diseases such as neuroectodermal dysplasia (e.g., myelomeningoceles) frequently develop overactive bladder dysfunction. The patients’ primary problem is involuntary loss of urine triggered by sudden bladder contractions.
In SCI patients, detrusor-sphincter-dyssynergia starts after the period of bladder acontractility and can carry a high risk of complications; even life expectancy can be affected. In contrast, multiple sclerosis patients, for example, develop overactive spontaneous bladder contractions. It is primarily uncontrollable, recurring incontinence that causes the patients’ stressful situation, resulting in a distinct reduction in quality of life.
The goal of urological therapy of neurogenic bladder dysfunction is continence and normalised pressure in the lower urinary tract [1]. Continence, combined with frequent, clean intermittent catheterisation, helps to significantly reduce urological infections, disruptions of the upper urinary tract, and patient dissatisfaction [2], [3]. Most patients receive an oral antimuscarinic treatment [4]. Long-lasting experience and multiple clinical studies with antimuscarinic drugs have demonstrated their effectiveness in treating neurogenic bladder dysfunction. Tolterodine, oxybutynin, and trospium are typical antimuscarinic agents that are well tolerated, despite published side-effects such as dry mouth, blurred vision, dry skin, and constipation.
However, for some patients, these antimuscarinic drugs often fall short because of these side-effects or insufficient effect with continuing incontinence. Madersbacher et al [5] described that almost 30% of their treated patients suffered from persistent symptoms of detrusor overactivity. Madersbacher, along with van Kerrebroeck et al [6], [7] and Appell [8], have reported increased effectiveness with increased quantities of antimuscarinic drugs.
In light of these earlier studies, we previously reported an improved therapeutic strategy with dosage-doubling of these antimuscarinic drugs [9] in our clinic. Interestingly, we noted that the side-effects did not occur more often or more severely than at the recommended dosage. In fact, some patients treated with the increased levels of antimuscarinics still continued to suffer from incontinence caused by autonomous bladder contractions from DSD.
On the basis of the initial study results [9], we hypothesised that an additional antimuscarinic drug could be combined with the existing doubled medication to improve continence, bladder capacity, and intravesical pressure; the results of this treatment have not been published previously.
Section snippets
Patient enrollment and evaluation
Patients (n = 27) from the previous double-dosage antimuscarinic monotherapy whose initial symptoms did not resolve and who experienced mild or no side-effects were enrolled. The study was approved by the local ethics committee. The enrolled patients demonstrated (both in the initial study and present study) urodynamic-proven neurogenic bladder dysfunction with incontinence, reduced bladder capacity, and increased intravesical pressure, resulting from SCI in the chronic phase (n = 21 [15 with
Resultant medication
Group A (n = 8; mean age, 35.5 yr; SD ± 10.9) received 8 mg of tolterodine and oxybutynin dosages between 15 and 30 mg (Table 2). Group B (n = 11; mean age, 39.9 yr; SD ± 13.0) received 90 mg of trospium and tolterodine dosages between 4 and 8 mg. Group C (n = 8; mean age, 30.1 yr; SD ± 3.4) received 30 mg of oxybutynin and trospium dosages between 45 and 90 mg.
Reported side-effects
Seven patients reported side-effects under the combined therapy with two antimuscarinic drugs (Table 3). Five patients had only mild side-effects;
Antimuscarinics in the treatment of neurogenic bladder dysfunction
The use of antimuscarinic drugs as first-line therapy is well established, so normal bladder compliance can be achieved with the goal of protecting the upper urinary tract. The most important side-effect to address for the patient suffering from neurogenic bladder dysfunction is urine incontinence caused by involuntary urine leakage, which decreases the patient's quality of life. Side-effects such as dry mouth, blurred vision, and bowel constipation are extensively described by various authors
Conclusion
The results of this investigation demonstrate that the combination of antimuscarinic drugs in a higher-than-recommended dosage is an effective treatment option for incontinence in patients suffering from neurogenic bladder dysfunction, if the single-use antimuscarinic drug does not lead to satisfactory amelioration. Side-effects occurred equally in patients treated with only one antimuscarinic drug compared with the combined dosage. Further investigations are needed to collect data about
Conflicts of interest
The authors have nothing to disclose.
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