Can higher doses of oxybutynin improve efficacy in neurogenic bladder?

Purpose: We evaluated the efficacy and tolerability of higher dose oxybutynin chloride in patients with neurogenic bladder and multiple sclerosis, spinal cord injury or Parkinson's disease. Materials and Methods: The study design was a prospective, 12-week dose titration trial of controlled release oxybutynin (OXY-XL). A 7-day washout period was used before initiation of the starting dose of 10 mg OXY-XL. Doses of OXY-XL were increased by 5 mg at weekly intervals to a maximum dose of 30 mg per day guided by patient perception of efficacy versus side effect. Voiding diaries were completed at baseline, and weeks 6 and 12. Post-void residuals were recorded. Criteria for study admission included post-void residual less than 200 ml. Results: Of the 39 patients enrolled in the study 22 had multiple sclerosis, 10 had spinal cord injury and 7 had Parkinson's disease. There were 29 women (74%) and 10 men (26%). Within 1 week a decrease in the number of voids per day was seen in greater than 50% of the subjects. At the end of the study statistically significant decreases in the number of voids in 24 hours, episodes of nocturia and incontinence episodes were observed. Residual urine remained unchanged from 33.9+-7.6 ml at baseline to 51.3+-10.4 ml after 12 weeks at the final dose (p = 0.17). No patient experienced serious adverse events and none dropped out during the course of the 12-week study. At the end of the study 20.5% of subjects remained on 30 mg, 15.4% on 25 mg, 23.1% on 20 mg, 15.4% on 15 mg and 25.6% on 10 mg OXY-XL. Conclusions: Aggressive dosing of OXY-XL is safe and effective in patients with neurogenic bladder. Compared with nonneurogenic overactive bladder, higher doses of OXY-XL (15 mg daily or greater) were requested by 74.4% of the patients in our study. The onset of clinical efficacy can occur within 1 week, and doses up to 30 mg are well tolerated and effective in this population. The development of voiding dysfunction as a result of neurological diseases, including spinal cord injury (SCI), multiple sclerosis (MS) and Parkinson's disease (PD), presents a significant challenge for the health care professional. 1 Urological symptoms and type of injury are often poor predictors of long-term care needs, as symptoms do not accurately correlate with level of injury. 2 People who suffer from SCI may have injured a single level of the cord or multiple levels of the spine. Brain insult may also occur either occult to obvious. Neural injury, which can involve parasympathetic, sympathetic and somatic nerve fibers, results in a complex array of urinary signs and symptoms. 3,4 Urinary urgency, frequency and incontinence are common symptoms of those diagnosed with MS. Loss of normal bladder control significantly impacts daily activities, may enhance fatigue and negatively impacts quality of life. 5 It is estimated that 80% or more of people with MS will exhibit symptoms of urinary dysfunction during the course of the disease. 6 In cases of MS lesions resulting from demyelination in the brain or spinal cord interrupt the descending and ascending nerve pathways, especially the posterior and lateral columns of the cervical spine that control micturition. In a review of results of urodynamic patterns in MS detrusor hyperreflexia was the most common diagnosis. 7 Parkinson's disease is one of the most common neurological entities causing voiding dysfunction. Bladder overactivity and sphincter bradykinesia (impairment of relaxation of the striated muscle external urinated sphincter) are common voiding dysfunctions seen in patients with PD. Anticholinergic medications are the most effective agents available today to control overactive bladder symptoms. By blocking receptors of the detrusor muscle, frequency, urgency and incontinence are decreased. Recently, extended release oxybutynin has shown efficacy in the treatment of overactive bladder symptoms. 8 We assess the effectiveness of controlled release oxybutynin (OXY-XL) using diaries, residual urine ultrasound, urinalysis, culture and sensitivity testing as parameters of effectiveness. We also evaluate subjective efficacy, safety and tolerability of this medication during the 12-week treatment period.