Pharmacologic treatment options
Anticholinergic/antimuscarinic agents, the standard therapy for patients with neurogenic detrusor overactivity,15 are often used in conjunction with CIC to allow for optimal storage and emptying. However, most are not registered for this indication, and data are limited. Medications with proven efficacy for NGB include oxybutynin, trospium, tolterodine, and propiverine.23
Adverse effects, such as dry mouth, often limit patient adherence. Constipation may be an issue, as many of these patients also have concomitant neurogenic bowel and may already be using laxatives, suppositories, and manual defecation.24-26
Combination therapy with two or three drugs may lead to significant urodynamic and clinical improvements for patients with NGB.27 A meta-analysis showed that longer-acting formulations were more effective and had a lower rate of adverse effects.28
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Imipramine
Tricyclic antidepressants suppress OAB via various mechanisms. Imipramine has improved incontinence in adults with NGB.29
Alpha-blockers/muscle relaxants
Alpha-blockers can treat DESD, lower bladder pressure during voiding, and reduce outlet resistance at the external sphincter.18 Muscle relaxants such as baclofen, benzodiazepines, and dantrolene have been used to treat outlet obstruction at the level of the striated sphincter due to DESD. Efficacy is not optimal in alleviating skeletal muscle spasticity, however, and adverse effects minimize their overall usefulness.30
Botulinum toxin injection: an emerging therapy
Botulinum toxin A (BoNTA) is an alternative for patients who fail or cannot tolerate the adverse effects of anticholinergic therapy. Detrusor injections of BoNTA are considered second-line treatment for neurogenic detrusor overactivity, and the US Food and Drug Administration (FDA) approved onabotulinumtoxinA (onaBoNTA; Botox®) for this indication in 2011.
Two other BoNTA preparations are available, abobotulinumtoxin A (Dysport®) and incobotulinumtoxin A (Xeomin®), and a botulinum toxin B (rimabotulinumtoxinB; Myobloc™).None have FDA approval for the treatment of neurogenic detrusor overactivity. These preparations cannot be used interchangeably.
BoNTA is usually administered in the office setting, with a local anesthetic. Patients should be closely monitored for autonomic dysreflexia.
The use of BoNTA to treat NDO was first published in 2000 by Schurch et al with 300 U of onaBoNTA injected into the detrusor muscle.31 The toxin inhibits acetylcholine release at the neuromuscular junction and prevents peripheral neurotransmitter release at presynaptic cholinergic nerve terminals. The neuromuscular contraction is then blocked and relaxes muscles that may be overactive or spastic.18,32
Many nonrandomized, single-dose studies have validated the use of 300 U of onaBoNTA in this patient population. Further investigation by Cruz et al was done in a multicenter, randomized controlled trial, including 275 patients with NGB.33 Patients with NGB secondary to MS or SCI were randomized to placebo and two doses of onaBoNTA (200 and 300 U).
Significant clinical and urodynamic improvements were seen in both onaBoNTA arms vs placebo, and the 300 U dose was not superior to 200 U. Baseline UI decreased by 21.8 episodes per week in the 200 U arm from a baseline of 33.5, and median time to request retreatment was 42.1 weeks. This study was one of two trials whose findings ultimately led to the FDA approving this drug for the indication of NDO at the dose of 200 U.
BoNTA appears to last 6 to 9 months in most patients. Reinjections do not appear to diminish efficacy34 or decrease bladder compliance and can improve quality of life.35 The most common adverse events are urinary retention and UTI.33 The risk for UTI may be decreased with BoNTA injection.35
More invasive procedures
An intraurethral stent may be an option for the long-term management of detrusor-sphincter dyssynergia in patients with SCIs.36 Potentially rever- sible, it can circumvent urethral obstruction while avoiding surgery.18
A transurethral resection of the external urinary sphincter converts the bladder into an open draining conduit.18 Considered irreversible, it reduces the intravesical voiding pressure me- diated by bladder contractions against a contracted external urethral sphincter from DESD.
Bladder augmentation uses an intestinal segment (usually ileum) to enlarge the bladder and increase bladder capacity. The aim is to restore continence and preserve upper urinary tracts by lowering intravesical storage pressures and minimizing the risk of reflux and hydronephrosis.18
Ileovesicostomy uses a section of ileum to create a channel leading from the urinary bladder upward to the abdominal wall. It provides for a low-pressure conduit for urinary drainage and decreases detrusor leak point pressures.37
Conclusion
NGB is common in patients with neurologic disorders and requires thorough assessment to select appropriate management. Diagnostics and treatment options are continually advancing, and clinicians need to remain up-to-date to accurately assess and optimally manage patients with this condition.
Part II of our series, coming in the July issue, will focus on evaluating treatment options for neurogenic bladder dysfunction.
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