Completion Date

Spring 4-16-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Program or Discipline Name

Pharmaceutical Sciences

First Advisor

Erik Hefti

Abstract

Introduction: Irritable Bowel Syndrome (IBS) is a gastrointestinal (GI) disorder that affects 13-38% of children (4-17 years) worldwide. Early life stresses like trauma, family pressure, abuse, and parenting factors may alter the HPA axis leading to GI sensitivity. IBS symptoms can impact an individual’s quality of life, affect school attendance, and can be emotionally and financially stressful for the caregivers. To date, there is no known cure for IBS. While antidepressants have shown some efficacy in treating moderate to severe IBS in adults, prescribing a universal antidepressant drug, especially to the pediatric population is challenging due to the variability in IBS symptoms, lack of available clinical data on antidepressant efficacy in children, and fear of adverse drug reactions. Parents/ caregivers are often unaware of the IBS triggers and may question a doctor’s recommendation on the use of antidepressants for pediatric IBS. Moreover, due to the lack of any specific diagnostic tests for IBS, doctors may prescribe diverse lab and imaging tests to rule out any organic disease before concluding an IBS diagnosis. Currently, there may be a gap of knowledge in diagnosing and treating pediatric IBS between medical professionals and caregivers’ understanding. The study aims to highlight the current awareness of IBS among caregivers worldwide and bridge the gap between challenges faced by medical professionals and caregivers during a child’s IBS management. By understanding the overlooked part of IBS treatment, a targeted approach can be used to guarantee the effects of antidepressant use that would provide comfort to the caregivers to adhere to a long-term treatment plan.

Methodology: A cross-sectional, observational study via online surveys was conducted worldwide with 12 medical experts and 69 parents/caregivers of children between 4-17 years of age to determine current awareness of IBS, challenges with IBS management, and opinions on using pharmacogenomic testing in antidepressant prescriptions for IBS in children. 8

Results: Forty-seven caregivers of children aged 4-17 years (24 males, 23 females) completed the survey. Ten out of 47 respondents had a confirmed diagnosis for their child’s IBS. Out of the remaining 37 respondents who have never been diagnosed with IBS, 22% reported two or more GI-related symptoms along with frequent complaints of abdominal pain. Statistically significant differences were found for anxiety issues (p=0.0027) and bloating/changing bowel habits (p=0.001) between IBS-positive and IBS-negative pediatric groups. One in 5 caregivers denied the antidepressant use due to its inefficacy while 67% of caregivers who utilized antidepressant treatment for their child’s IBS did not see any improvement in abdominal pain with the use of a Selective Serotonin Reuptake Inhibitor (SSRI). Rejection of antidepressant use by the caregiver and non-adherence to a long-term treatment plan were the main challenges faced by medical providers in prescribing antidepressants for pediatric IBS. Lastly, >50% of parents and medical professionals were open to utilizing pharmacogenomic testing for a targeted therapy approach.

Discussion: Anxiety and changing bowel habits are present in IBS patients making the use of antidepressants as a part of the treatment regimen. However, due to a lack of awareness about the pathophysiology of IBS, caregivers are often reluctant to utilize this approach for their children. Moreover, there is not enough clinical evidence currently that can assure the caregiver about the safety and efficacy of the antidepressant for their child. Emotional stress and expectation of immediate relief by the caregiver during their child’s IBS episode may contribute to frequent doctor visits and non-adherence to a long-term treatment plan. Multiple doctor visits also engage the caregiver to invest in the treatment costs and time involved in the diagnosis of IBS. It is noted that antidepressants have worked differently for different individuals. Most parents caring for a child with IBS experienced either worsening symptoms or inefficacy of the drug. Drug metabolizing enzymes (DMEs) play a crucial role in drug efficacy and safety. SSRIs (Prozac®, 9 Zoloft™) are approved by the FDA for pediatric use but have shown no improvement in IBS flareups. However, off-label use of low-dose Tricyclic Antidepressants (TCA) in pediatrics is challenging due to their narrow therapeutic index. By checking for any polymorphisms in the respective DMEs, adequate choice and dosage of antidepressants can be predicted to minimize any adverse drug reactions thereby comforting caregivers and medical providers.

Conclusion: Thus, there is an urgent need to bring a pharmacogenomic intervention that can aid in accurate stress-induced IBS management, faster relief, and better adherence to the treatment regimen.

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