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Multicenter, randomized, placebo-controlled trial of amitriptyline in children with functional gastrointestinal
Miguel Saps1, Nader Youssef, Adrian Miranda
1Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60614, USA. msaps@childrensmemorial.org
Insights
Amitriptyline did not show significant efficacy over placebo for treating pain in children with functional gastrointestinal disorders. While both treatments improved symptoms, amitriptyline specifically reduced anxiety scores in pediatric patients.
Area of Science:
- Pediatric Gastroenterology
- Clinical Pharmacology
- Child Psychology
Background:
- Functional gastrointestinal disorders (FGIDs) are common in children.
- Pain is a predominant symptom in pediatric FGIDs.
- Lack of high-quality trials on pharmacologic treatments for pediatric FGIDs.
Purpose of the Study:
- To evaluate the efficacy of amitriptyline in treating pain-predominant FGIDs in children.
- To compare amitriptyline with placebo in a randomized, double-blind trial.
Main Methods:
- A multicenter, placebo-controlled trial involving 90 children with irritable bowel syndrome, functional abdominal pain, or functional dyspepsia.
- Participants received 4 weeks of either placebo or amitriptyline (10-20 mg/d based on weight).
- Outcomes included overall treatment response, pain relief, psychosocial traits, and daily functioning, assessed via diaries and questionnaires.
Main Results:
- No significant difference in overall treatment response between amitriptyline and placebo groups (63% vs 57.5% improved).
- Pain relief levels were similar between amitriptyline and placebo groups (P=.85).
- Amitriptyline significantly reduced anxiety scores (P < .0001), but baseline pain severity predicted worse outcomes in both groups.
Conclusions:
- Amitriptyline and placebo demonstrated comparable therapeutic responses in children with pain-predominant FGIDs after 4 weeks.
- Neither treatment showed a statistically significant advantage over the other for overall symptom improvement.
- Patients with mild to moderate pain intensity experienced better treatment outcomes regardless of the group.
Background & Aims:
There are no prospective, multicenter, double-blind, placebo-controlled, randomized pharmacologic trials for the treatment of pain-predominant functional gastrointestinal disorders in children. The aim of this study was to evaluate the efficacy of amitriptyline in children with pain-predominant functional gastrointestinal disorders.
Methods:
In this multicenter placebo-controlled trial, children with irritable bowel syndrome, functional abdominal pain, or functional dyspepsia were randomized to 4 weeks of placebo or amitriptyline (10 mg/d, weight <35 kg; 20 mg/d, weight >35 kg). Assessment of gastrointestinal symptoms, psychological traits, and daily activities occurred before and after intervention. Pain was assessed daily with self-report diaries. The primary outcome was overall response to treatment (child's assessment of pain relief and sense of improvement). Secondary outcomes were effect on psychosocial traits and daily functioning.
Results:
Ninety children were enrolled, and 83 completed the study (placebo, 40 children [30 girls]; drug, 43 children [35 girls]). A total of 63% of patients reported feeling better and 5% feeling worse in the amitriptyline arm compared with 57.5% feeling better and 2.5% feeling worse in the placebo arm (P = .63). Pain relief was excellent in 7% and good in 38% of children receiving placebo compared with excellent in 15% and good in 35% of children treated with amitriptyline (P = .85). Logistic regression analysis of those reporting excellent or good response versus fair, poor, or failed response showed no difference between amitriptyline and placebo (P = .83). Children who had more severe pain at baseline in both groups (P = .0065) had worse outcome. Amitriptyline reduced anxiety scores (P < .0001).
Conclusions:
Both amitriptyline and placebo were associated with excellent therapeutic response. There was no significant difference between amitriptyline and placebo after 4 weeks of treatment. Patients with mild to moderate intensity of pain responded better to treatment.
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