Multicenter, randomized, placebo-controlled trial of amitriptyline in children with functional gastrointestinal disorders.
OBJECTIVE
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.
Saps
Miguel
M
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60614, USA. msaps@childrensmemorial.org
Youssef
Nader
N
Miranda
Adrian
A
Nurko
Samuel
S
Hyman
Paul
P
Cocjin
Jose
J
Di Lorenzo
Carlo
C
D015746:Abdominal Pain / Q000517:prevention & control* / Q000523:psychology; D000203:Activities of Daily Living; D000293:Adolescent; D000639:Amitriptyline / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D001007:Anxiety / Q000209:etiology / Q000517:prevention & control; D002648:Child; D004415:Dyspepsia / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000523:psychology; D016015:Logistic Models; D008297:Male; D055118:Medication Adherence; D010147:Pain Measurement; D011446:Prospective Studies; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D018712:Analgesics, Non-Narcotic; D005765:Gastrointestinal Agents; D000639:Amitriptyline