Intravesical therapy options for neurogenic detrusor overactivity

Abstract

Objectives: This review considers intravesical treatment options of neurogenic detrusor overactivity and discusses the underlying mechanism of action, clinical safety and efficacy, and the future trends. Methods: The available literature was reviewed using medline services. Results: Oral anticholinergic drugs are widely used to treat detrusor overactivity, but they are ineffective in some patients or cause systemic side effects such as blurred vision or dry mouth. As an alternative, topical therapy strategies have been suggested to achieve a profound inhibition of the overactive detrusor and to avoid high systemic drug levels. Currently available intravesical treatment options either act on the afferent arc of the reflex such as local anaesthetics or vanilloids or on the efferent cholinergic transmission to the detrusor muscle such as intravesical oxybutynin or botulinum toxin. Although an established and effective therapy, intravesical oxybutynin is not widely used. Evidence for clinical significance of intravesical atropine and local anaesthetic is missing. Intravesical capsaicin has been shown to improve clinical and urodynamic parameters, but cause pain in some patients. The intravesical instillation of resiniferatoxin and the injection of botulinum-A toxin into the detrusor muscle are promising new options; however, randomised placebo-controlled studies to prove their safety and efficacy are still missing. Conclusion: Intravesical treatment strategies in patients with neurogenic detrusor overactivity may provide alternatives to established therapies such as oral anticholinergics. The selectivity of the intravesical treatment and the reduction or even the absence of side effects are major advantages of this topical approach.

Delayed complications of discontinuation of intrathecal baclofen therapy: resurgence of dyssynergic voiding, which triggered off autonomic dysreflexia and hydronephrosis

“…7 We believe that intermittent catheterisation with oral or intravesical 8 pharmacotherapy to control detrusor hyperreflexia and detrusor-sphincter dyssynergia 9 is the first choice of bladder drainage for these patients. When our patient started taking modified release formulations of oxybutynin and alfuzosin, symptoms of autonomic dysreflexia subsided.…”

The paediatric neuropathic bladder

“…Counter-intuitively, the serum levels of oxybutynin after intravesical administration are as high as when taken orally. [1] However, since first-pass liver metabolism is circumvented with this approach, a reduced side-effect profile is observed. Sideeffects are predominantly thought to be mediated by the metabolite N-desethyl oxybutynin.…”

“…Continence was restored in all 17 children investigated. [1] A further study demonstrated a reduced requirement for oral medication and improved quality of life for children treated with botulinum toxin type A. [11] Urodynamic efficacy lasts for about 6 months, after which repeated injections are necessary.…”

“…In pathophysiological terms, a neurogenic bladder is caused by a spinal reflex arc that occurs when the bladder becomes autonomous from higher centres. [1] Paediatric neurogenic bladder dysfunction is most commonly caused by a congenital neural tube defect (NTD), such as myelomeningocele (MMC) or another form of tethered spinal cord. Alternatively, it can be the result of traumatic spinal cord injury, transverse myelitis or anorectal malformation.…”

Effect of the intravesical resiniferatoxin instillation evaluated by the ice provocative urodynamic study

“…3,4 However, some patients cannot be controlled by oral medications, despite maximal dosages, and some cannot tolerate the side effects, 5,6 such as a dry mouth, visual disturbance or constipation, at any dosage. Recently, to minimize the side effects of anticholinergics, intravesical instillations, such as oxybutynin 7,8 or vanilloids, 9 have been tried. Of these, vanilloids, unmyelinated C-fiber blockers (capsaicin or resiniferatoxin), have been tried, but the effects of the treatment are equivocal.…”