Double anticholinergic therapy for refractory neurogenic and non-neurogenic detrusor overactivity in children: Long-term results of a prospective open-label study

Abstract

Introduction: In this study, we optimize pharmacotherapy in children who failed anticholinergic monotherapy by simultaneous administration of 2 anticholinergics (oxybutynin and/or tolterodine and/or solifenacin). Methods: This report is an update of our previously published study on double anticholinergic regimen in children with refractory incontinence due to neurogenic (NDO) and non-neurogenic (DO) detrusor overactivity. Patients with an insufficient response (clinically/urodynamically) to an optimized dose of a single anticholinergic (oxybutynin or tolterodine) received a second anticholinergic (tolterodine or solifenacin), in addition to the pre-existing medication. The primary end-point was efficacy (continence) and the secondary end-points were tolerability and safety. The Patient Perception of Bladder Condition (PPBC) scale was used to rate subjective improvement of patients. Results: In total, 56 patients with DO (n = 31) or NDO (n = 25) were enrolled at a mean age of 11.4 ± 3.5 years and were followed for a minimum of 3 months. The duration of double treatment was 36 ± 23 months. Our results found that 23 patients became dry, 18 improved significantly and 15 improved moderately. Urodynamic capacity improved from 158 ± 87 mL to 359 ± 148 mL and maximal pressure of contractions decreased from 76 ± 24 to 22 ± 22 cmH 2 O (p < 0.0001). The overall success rate was 82%, since 10 patients discontinued treatment for unsatisfactory clinical response or bothersome side effects. No side effects were reported by 28 patients, mild side effects by 20, moderate side effects by 8; 2 patients withdrew from the study due to their side effects. Of the 35 patients who voided spontaneously, 8 developed post-void residuals (>20%). Conclusions: With a larger cohort and prospective follow-up, we reiterated that double anticholinergic regimen in children with DO or NDO refractory to anticholinergic monotherapy is a feasible and efficient approach.

Overactive bladder in children

“…47 In a 36-month extension phase of this study including 56 patients, 41% of patients were dry and 32% were improved; 50% experienced mild or moderate side effects, with two patients requiring a different treatment regimen because of troublesome side effects. 48 Our group also recently reported on a prospective, open-label study to assess dual therapy with an antimuscarinic agent and mirabegron. Our results are promising, with improvement of continence in all 35 patients and mild side effects in only four patients.…”

Treatment Outcome of Overactive Bladder Patients Receiving Antimuscarinic Therapy for More than One Year

“…Combined antimuscarinic agents were used in some of our patients. It has been reported that combined antimuscarinic agents could provide good clinical and urodynamic effects for elderly, refractory, neurogenic or even child OAB patients . However, while a β3‐adrenoceptor agonist is available, a combination of antimuscarinics and mirabegron may be a good alternative for refractory OAB patients to avoid additive adverse effects of combined antimuscarinic agents …”

Neuropathic bladders: Investigation and treatment through their lifetime

“…Dr. Bolduc has pioneered increasing dosing and combining antimuscarinics to increase efficacy and minimize side effects. 23 Once adult dosing has been reached with a single medication, a second antimuscarinic is well-tolerated and may result in continence or safer bladder pressures. 23 In our patients who have persistent hydronephrosis despite maximal medical management, overnight catheter drainage can be attempted.…”

“…23 Once adult dosing has been reached with a single medication, a second antimuscarinic is well-tolerated and may result in continence or safer bladder pressures. 23 In our patients who have persistent hydronephrosis despite maximal medical management, overnight catheter drainage can be attempted. Since the highest bladder volumes, and therefore pressures, will likely occur overnight, continuous overnight drainage may decrease renal stress.…”

“…Many children's hospitals focus on transitioning the care to an appropriate adult provider and guidelines are beginning to emerge to facilitate this. 23,43 Several Canadian centres, including in Edmonton and Halifax, have independent adult spina bifida clinics, which closely resemble their pediatric model.…”