Symptoms and Side Effects: Delicate Balance in the Management of Patients with Neurogenic Bladder

OXYBUTYNIN is routinely used in the pharmacological management of neuropathic bladder, and there is level one evidence on the efficacy of oxybutynin in the treatment of detrusor overactivity and urinary incontinence. In addition, oxybutynin is one of the few medications with the U.S. Food and Drug Administration and European Medicines Agency labeling for the treatment of pediatric neurogenic detrusor overactivity. In this issue of The Journal Veenboer et al (page 2228) address an important and sobering concern regarding the impact of longterm anticholinergics on the behavior of children with spinal dysraphism. 1 A significant concern with any anticholinergic therapy is the impact that it may have on the brain. This potential side effect is important because all 5 muscarinic subtypes are expressed in the brain. The M1 receptors are deemed particularly important in higher cognitive processes such as learning and memory. The first-pass hepatic metabolite of oral oxybutynin, n-desethyloxybutynin, has a strong affinityfortheM1muscarinicreceptorsinthebrainand is responsible for many of the central nervous system (CNS) related concerns. Although the intravesical and transdermal delivery systems minimize side effects by avoidance of the first-pass hepatic metabolite, they are not without CNS related sequelae. 2 The impact of anticholinergics on impaired cognition in healthy, older adults has been noted in a double-blind, placebo controlled crossover study 3 but a recent systematic review and metaanalysis has not shown similar findings. 4 Two pediatric case-control trials have examined the effects of oxybutynin on cognition and short-term memory in neurologically intact children. 5,6 Although one of these trials was randomized and double-blind, 6 neither study demonstrated any deleterious effect on cognition or short-term memory with oral oxybutynin. Veenboer et al address a different concern regarding the impact of anticholinergics on CNS function, that of the impact on psychological and psychiatric behaviors. 1 The association of psychological and psychiatric issues with urinary and/or fecal incontinence is well-known. 7,8 Nevertheless, no study has examined the impact of anticholinergics on psychological and psychiatric behaviors in children with spinal dysraphism with and without hydrocephalus. In this case-control trial there appears to be no difference in behavioral issues in children who have received long-term anticholinergic therapy compared to those who have not received anticholinergic therapy or 1 month or less treatment duration. The behavioral profiles were assessed by the Child Behavior Checklist, which is a widely used parental questionnaire by psychiatrists and psychologists that contains 113 empirically derived behavioral items and has been translated into many languages. The study is encouraging in that there is no difference in the incidence of behavioral issues with chronic anticholinergic therapy. The study has limitations that are recognized by the authors and notably include underpowering due to a small sample size. Further examination of the impact on behavior with chronic anticholinergic therapy in larger trials will expand these findings and add further insight to CNS related issues.