A randomized, controlled trial of amitriptyline in the acute treatment of adolescent major depression. Multicenter, randomized, placebo-controlled trial of amitriptyline in children with functional gastrointestinal disorders.
To determine amitriptyline's (AMI) efficacy in the acute treatment of adolescent major depressive disorder (MDD).
                Subjects aged 12 through 17 years meeting Research Diagnostic Criteria for MDD, diagnosed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), participated in a 2-week placebo-washout followed by an 8-week, randomized, double-blind, parallel-design, placebo-controlled trial of AMI, 5 mg/kg per day. The K-SADS nine-item scale, the Hamilton Depression Rating Scale, and the Clinical Global Impressions rating scale were used as outcome measures.
                Thirty-one subjects were randomized (18 AMI, 13 placebo). Twenty-two subjects were study completers (12 AMI, 10 placebo). AMI's efficacy was suggested by the Clinical Global Impressions but not the K-SADS-derived data. Perhaps the primary limitation of the current study is its small sample size.
                No definitive recommendation can be made regarding the efficacy of tricyclic antidepressants in the treatment of adolescent MDD. 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.
Clinicians must be aware that for the majority of antidepressant medications no evidence exists that supports their use for the treatment of abdominal pain-related FGIDs in children and adolescents. The existing randomised controlled evidence is limited to studies on amitriptyline and revealed no statistically significant differences between amitriptyline and placebo for most efficacy outcomes. Amitriptyline does not appear to provide any benefit for the treatment of FGIDs in children and adolescents. Studies in children with depressive disorders have shown that antidepressants can lead to substantial, sometimes life-threatening adverse effects. Until better evidence evolves, clinicians should weigh the potential benefits of antidepressant treatment against known risks of antidepressants in paediatric patients.