Neurotoxin Treatments for Urinary Incontinence in Subjects With Spinal Cord Injury or Multiple Sclerosis: A Systematic Review of Effectiveness and Adverse Effects

Abstract Background/Objective: The objective was to evaluate the effectiveness of neurotoxin treatments of urinary incontinence (UI) in individuals with spinal cord injury (SCI) or multiple sclerosis (MS). Methods: Studies were included if published in English, presented randomized adults with SCI or MS, and reported UI outcomes. Results: Ten trials randomizing 288 subjects with SCI (43%), MS (52%), or other spinal conditions (5%) and UI refractory to oral antimuscarinics were included. The overall mean age was 41 years, and 46% were women. Study durations ranged from 1 to 18 months. Treatments included botulinum toxin-A (BTX-A, 2 trials) and 2 vanilloid compounds, capsaicin (6 trials) and resiniferatoxin (4 trials). BTX-A was superior to placebo and resiniferatoxin in reducing daily UI episodes, mainly in individuals with SCI, although significant reductions vs placebo were not evident throughout the study duration. There were 1.1 fewer daily UI episodes in the BTX-A 200 unit group vs 0.1 fewer for the placebo group at the final week 24 assessment. Capsaicin was generally superior to placebo. The weighted difference between capsaicin and placebo in a pooled analysis of 2 trials enrolling subjects with either paraplegia or tetraplegia (n = 32) was -3.8 daily UI episodes [95% Cl -4.7 to -2.9] after 30 days. Capsaicin was comparable to resiniferatoxin. Pelvic pain and facial flushing were associated with capsaicin. Conclusion: Neurotoxins may improve refractive UI in adults with SCI or MS, although trial results were inconsistent. Trials were small in size and relatively short in duration. Further studies are needed to determine the efficacy and tolerability of long-term application.

[1]  S. Chan,et al.  Botulinum toxin type A for refractory neurogenic detrusor overactivity in spinal cord injured patients in Singapore. , 2007, Annals of the Academy of Medicine, Singapore.

[2]  C. Chapple,et al.  Botulinum toxin injections for neurogenic and idiopathic detrusor overactivity: A critical analysis of results. , 2006, European urology.

[3]  M. Craggs,et al.  Botulinum toxin‐type A in the treatment of drug‐resistant neurogenic detrusor overactivity secondary to traumatic spinal cord injury , 2006, BJU international.

[4]  M. Ribeiro,et al.  Urodynamic effect of intravesical resiniferatoxin in patients with neurogenic detrusor overactivity of spinal origin: results of a double-blind randomized placebo-controlled trial. , 2005, European urology.

[5]  Z. Gabriel,et al.  The effects of antimuscarinic treatments in overactive bladder: a systematic review and meta-analysis. , 2005, European urology.

[6]  G. Kramer,et al.  Success of repeat detrusor injections of botulinum a toxin in patients with severe neurogenic detrusor overactivity and incontinence. , 2005, European urology.

[7]  V. Bini,et al.  Intravesical resiniferatoxin versus botulinum-A toxin injections for neurogenic detrusor overactivity: a prospective randomized study. , 2004, The Journal of urology.

[8]  Emmanuel Chartier-Kastler,et al.  European experience of 200 cases treated with botulinum-A toxin injections into the detrusor muscle for urinary incontinence due to neurogenic detrusor overactivity. , 2004, European urology.

[9]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[10]  B. Schurch,et al.  Botulinum toxin as a new therapy option for voiding disorders: current state of the art. , 2003, European urology.

[11]  M. Chancellor,et al.  Intravesical Resiniferatoxin For Refractory Detrusor Hyperreflexia: A Multicenter, Blinded, Randomized, Placebo-Controlled Trial , 2003, The journal of spinal cord medicine.

[12]  J. Wyndaele,et al.  Muscular weakness as side effect of botulinum toxin injection for neurogenic detrusor overactivity , 2002, Spinal Cord.

[13]  G. Scivoletto,et al.  Intravesical capsaicin versus resiniferatoxin in patients with detrusor hyperreflexia: a prospective randomized study. , 2002, The Journal of urology.

[14]  J. Ditunno,et al.  The Management of Neurogenic Bladder and Sexual Dysfunction After Spinal Cord Injury , 2001, Spine.

[15]  B. Schurch,et al.  Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. , 2000, The Journal of urology.

[16]  JS Fingerman,et al.  The overactive bladder in multiple sclerosis , 2000, The Journal of the American Osteopathic Association.

[17]  W. C. Groat,et al.  Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder. , 1999, The Journal of urology.

[18]  P. Joseph,et al.  The effects of capsaicin on the neurogenic hyperreflexic detrusor. A double blind placebo controlled study in patients with spinal cord disease. Preliminary results , 1998, Spinal Cord.

[19]  S. Jackson,et al.  The patient with an overactive bladder--symptoms and quality-of-life issues. , 1997, Urology.

[20]  M. Clarke,et al.  Identifying relevant studies for systematic reviews , 1995, BMJ.

[21]  R. J. Hayes,et al.  Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. , 1995, JAMA.

[22]  D. Sackett,et al.  Cochrane Collaboration , 1994, BMJ.

[23]  K. Dickersin,et al.  Systematic Reviews: Identifying relevant studies for systematic reviews , 1994 .

[24]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[25]  G. Serment,et al.  Intravesical glucidic capsaicin versus glucidic solvent in neurogenic detrusor overactivity: A double blind controlled randomized study , 2006, Neurourology and urodynamics.

[26]  P. Dasgupta,et al.  Botulinum toxin for the treatment of lower urinary tract symptoms: A review , 2005, Neurourology and urodynamics.

[27]  M. Brin,et al.  Botulinum toxin type a is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study. , 2005, The Journal of urology.

[28]  P. Joseph,et al.  Intravesical capsaicin versus resiniferatoxin for the treatment of detrusor hyperreflexia in spinal cord injured patients: a double-blind, randomized, controlled study. , 2004, The Journal of urology.

[29]  J. Nielsen,et al.  Intravesical capsaicin in patients with detrusor hyper-reflexia--a placebo-controlled cross-over study. , 1999, Scandinavian journal of urology and nephrology.

[30]  M. Spinelli,et al.  Intravesical resiniferatoxin for the treatment of detrusor hyperreflexia refractory to capsaicin in patients with chronic spinal cord diseases. , 1998, Scandinavian journal of urology and nephrology.

[31]  P. Joseph,et al.  Capsaicin and neurogenic detrusor hyperreflexia: A double‐blind placebo‐controlled study in 20 patients with spinal cord lesions , 1998, Neurourology and urodynamics.