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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    • "According to previous pediatric studies about functional gastrointestinal disorders that included subjects with at least 8 years of age, we divided the study population into <8 and >8 years [16,17]. "
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    ABSTRACT: Gas-related symptoms represent very common complaints in children. The reduction of gas production can be considered as a valuable target in controlling symptoms. alpha-galactosidase has been shown to reduce gas production and related symptoms in adults.Aim: To evaluate the efficacy and tolerability of alpha-galactosidase in the treatment of gas-related symptoms in pediatric patients. Single center, randomized, double-blind, placebo-controlled, parallel group study performed in tertiary care setting. Fifty-two pediatric patients (32 female, age range 4--17) with chronic or recurrent gas-related symptoms were randomized to receive placebo (n = 25) or alpha-galactosidase (n = 27). Both treatments were given as drops or tablets, according to body weight for 2 weeks. The primary endpoint was the reduction in global distress measured by the Faces Pain Scale-Revised (FPS-R) at the end of treatment compared to baseline. Secondary endpoints were the reduction in severity and frequency of gas-related symptoms as recorded by parents and/or children. alpha-galactosidase significantly reduced global distress (p = 0.02) compared to placebo. The digestive enzyme decreased the number of days with moderate to severe bloating (p = 0.03) and the proportion of patients with flatulence (p = 0.02). No significant differences were found for abdominal spasms and abdominal distension. No adverse events were reported during treatment. Although larger and longer trials are needed to confirm this result, alpha-galactosidase seems to be a safe, well tolerated and effective treatment for gas-related symptoms in the pediatric population.Trial registration: - NCT01595932.
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    • "Significant benefits were observed in the amitriptyline groups [16]. On the other hand, a large multicenter study of amitriptyline in children with diverse FGIDs showed no benefit of the TCA over placebo [17]. "
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