Pharmacotherapy and bladder function in children: effects of medications for behavioural disorders, exploring new biomarkers and evaluating the role of alpha blockers in treating functional daytime incontinence

Introduction: Non-neurogenic bladder dysfunction in children is a prevalent condition with many treatments available. No treatment completely guarantees a cure and often underlying comorbidities such as behavioural disorders and concomitant behavioural pharmacology can influence the efficacy and choice of bladder treatment. Additionally, children may not respond to first or second line therapies so further assessment and interventions may be necessary. The studies in this thesis aim to provide further understanding of how pharmacological agents affect bladder functioning and its subsequent assessment and management in three main aspects as outlined below. Bladder dysfunction in children with behavioural disorders. Chapter 2 of this thesis is a narrative review of literature regarding pharmacotherapy interventions for behavioural disorders and effects on bladder functioning with a focus on the main classes of medications, stimulants, alpha-2 agonists, antidepressants and antipsychotics. The review also examines optimal treatment strategies for children with both behaviour and bladder dysfunction. The primary finding being that treating behavioural disorder prior to bladder dysfunction is key to managing the comorbid conditions. Chapter 3 furthers the theme of management of bladder dysfunction in children with behavioural disorders to examine the response to standard urotherapy and combined treatments in managing children with behavioural disorders and bladder dysfunction. Children who are appropriately treated for behavioural disorders respond well to bladder dysfunction treatment at a comparable rate to to the general paediatric population. This ethically approved prospective cohort (DABBED – Drugs And Bladder in Behavioural Disorders) study was published in June 2021 in Lower 11 Urinary Tract Symptoms (LUTS). Together, these studies will better inform the clinical management of comorbid behavioural disorders and bladder dysfunction in a more systematic and unified approach. Serum anticholinergic activity assay (SAA) as a serum biomarker for predicting bladder effects. Chapter 4 of this thesis reviews the literature regarding bladder dysfunction assessment and particularly focusing on bioassays and the possible role of SAA. There are many bladder dysfunction biomarkers with poor clinical translatability, with the role of SAA in bladder being an untested entity though it may have a role in other clinical areas. Chapter 5 is a pilot study (part of DABBED study) which was undertaken in our cohort of children on pharmacotherapy to assess if we could predict the bladder response to behavioural medications. Only exploratory commentary was possible due to the limitations of the study but the initial data suggests that children with behavioural disorders may have an inherent elevated baseline SAA level that may be affected by their medications. Alpha blockers for the management of functional daytime incontinence in children. Chapter 6 of this thesis is a Cochrane supported systematic review looking at the role of alpha blockers in managing functional daytime incontinence. The review finds that there are few poor quality studies which are unable to provide enough support for the use of this medication in treating this condition and further study is required.