Evaluation of the Efficacy of Amitriptyline in Children with Abdominal Pain of Non-Organic Origin

Abstract

Purpose: Functional Abdominal pain (FAP) is common in children. Treatment is mostly empirical and not evidence based. Antidepressants are commonly used to treat FAP. To date there has been no prospective, multicenter double blind placebo (PL) controlled randomized trial in the treatment of FAP in children. Aim is to evaluate the effect of amitriptyline (AM) in children with FAP. Methods: Children from six tertiary care centers diagnosed with FAP (Rome II criteria) were randomized to 4 wks PL or low dose AM 10 mg/d in patients < 35 kg or 20 mg/d > 35 kg. Comprehensive evaluation of GI symptoms, psychological traits and ability to perform daily activities was conducted before and after intervention. Pain was assessed by daily diaries (visual analogue scale 1–100 mm). Primary outcome was overall response to treatment (child's assessment of pain relief and sense of improvement). Secondary outcomes included effect on psychosocial traits and ability to perform daily activity. Results: 90 children (mean 12.7, range 8–17 y) were enrolled, 83 completed the study (placebo: 40, 30 females; drug: 43, 35 females). 3 children (2 PL, 1 AM) discontinued for mild adverse events (fatigue, constipation, rash). Patients reported feeling better 63%, worse 5% in AM arm and feeling better 58%, worse 3% in PL arm (P= 0.85). Number needed to treat = 19. Absolute risk reduction = 5.3%. Pain relief was considered excellent (7%), good (39%) in children receiving AM and excellent (15%), good (35%) in PL (P= 0.85). Logistic regression analysis of patients reporting response to drug as excellent or good compared with those reporting fair, poor or failed showed no difference between AM and PL (P= 0.83). Correlation between overall assessment of pain at end of study and daily assessment of pain by daily diaries was moderate (r = 0.45, P < 0.0001). Worse outcome was associated with baseline: 1) pain > 60 mm in both groups (P= 0.0065), 2) higher depression scores (P < 0.0001). Age and gender had no effect on outcome. Conclusion: There was > 50% improvement in abdominal pain in children receiving AM. There was no significant difference compared to placebo after 4 weeks of treatment. Patients with mild to moderate intensity of pain responded better to therapy. Those who had higher depression scores at baseline correlated negatively with sense of improvement.Table