Multicenter, Randomized, Placebo-Controlled Trial of Amitriptyline in Children With Functional Gastrointestinal Disorders

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60614, USA.
Gastroenterology (Impact Factor: 16.72). 07/2009; 137(4):1261-9. DOI: 10.1053/j.gastro.2009.06.060
Source: PubMed


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.
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.
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).
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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Available from: Samuel Nurko, Aug 15, 2014
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    • "Placebo research, defined as the investigation of the mechanisms underlying suggestive and conditioned healing processes [15], has been mostly done in adults, and it remains unclear how and to what extent children form placebo effects [10] [76]. On the one hand, there is evidence from clinical studies that placebo responses are present in a variety of pediatric conditions including attention-deficit/hyperactivity disorder [64], asthma [6], atopic dermatitis [66], seasonal allergic conjunctivitis [51], autism [38], depression [13], epilepsy [59], functional gastrointestinal conditions [65], chronic fatigue syndrome [61], hypertension [67], migraine [68], and syncope [63]. On the other hand, it is important to understand whether the placebo mechanisms that have been explored so far are uniquely important for adults as opposed to children. "
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