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. Double-blind, placebo-controlled trial of famotidine in children with abdominal pain and dyspepsia: global and quantitative assessment. Randomized, controlled trial of amitriptyline versus placebo for adolescents with "treatment-resistant" major depression. A double-blind comparison of Org 3770, amitriptyline, and placebo in major depression. Symptom relief with amitriptyline in the irritable bowel syndrome. Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients. Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. A double-blind comparative trial with mianserin and amitriptyline in outpatients with major depressive 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. To determine the benefit of using an H2-receptor antagonist in children with abdominal pain and dyspepsia, 25 such children were enrolled in a double-blind, placebo-controlled trial of famotidine. Global and quantitative pain assessments were done before and after each treatment period. The quantitative assessment was calculated based on the abdominal pain score that was the sum of three components. Based on the global evaluation, there was a clear benefit of famotidine over placebo (68% vs 12%). Using the quantitative assessment, however, the mean improvement of the score using famotidine versus placebo was not statistically significant (3.37+/-3.53 vs 1.66+/-2.7). There was a significant improvement in this score during the first treatment period regardless of medication used (period effect: P = 0.05). A subset of patients with peptic symptoms demonstrated a significant drug effect that outweighed the period effect (drug effect: P = 0.01; period effect: P = 0.02). We conclude that famotidine subjectively improves the symptoms of children with recurrent abdominal pain but not objectively using the derived score. However, famotidine is significantly more effective than placebo among children with peptic symptoms. The use of this simple scoring scale may facilitate selecting those children who will benefit from H2-receptor antagonist therapy. To assess the response to a serotonergic/noradrenergic tricyclic antidepressant, amitriptyline (AMI), in a group of adolescents with treatment-resistant major depressive disorder (MDD).
                Twenty-seven depressed adolescents admitted to a state hospital underwent a 10-week randomized, controlled trial with a flexible dose of AMI or placebo.
                There were no differences between patients taking AMI (n = 13) and placebo (n = 14). Both treatment groups showed approximately 70% to 80% improvement on the clinical outcome measurements, and 65% to 70% showed functional improvement. At the end of the protocol, 30% of patients still fulfilled criteria for MDD and had impaired functioning. Patients taking AMI experienced significantly more dry mouth and tachycardia. The final AMI dose was 173.1 mg/day +/- 56.3 mg/day; blood levels were 226.2 ng/mL +/- 80.8 ng/mL.
                No significant differences were found between AMI and placebo, in part because of the high placebo response rate. Although both treatment groups showed substantial response, at the end of treatment a substantial proportion of patients still had MDD of subsyndromal symptoms of depression. This and other studies of tricyclic antidepressants question the use of this medication as first-line treatment for youths with MDD. A 6-week, double-blind, dose titration study was performed to evaluate efficacy and safety of the new antidepressant Org 3770 in comparison with amitriptyline and placebo.
                One hundred fifty outpatients of both sexes, 18 years and older, with a DSM-III diagnosis of major depressive episode, were randomly assigned to 6 weeks of treatment with Org 3770, amitriptyline, or placebo.
                At baseline, mean 17-item Hamilton Rating Scale for Depression (HAM-D) scores of all treatment groups were higher than 25, thus indicating that a large proportion of severely depressed patients entered the study. The overall mean daily doses were 22 mg/day for Org 3770, 133 mg/day for amitriptyline, and 4.9 capsules/day for placebo. The majority of times assessments were made, both active drugs produced significantly greater improvements than placebo on all efficacy variables (17-item HAM-D, Montgomery-Asberg Depression Rating Scale, Clinical Global Impressions, and Zung Self-Rating Depression Scale). After 6 weeks of treatment, significantly greater (p < or = .05) proportions of patients in both active treatment groups (70% in the Org 3770- and 58% in the amitriptyline-treatment groups) than in the placebo-treatment group (33%) were HAM-D responders. Org 3770 was well tolerated in this study; dry mouth and somnolence were the only adverse experiences that occurred significantly more frequently with Org 3770- than with placebo-treated patients. By contrast, treatment with amitriptyline was related to significantly higher rates of dry mouth, constipation, and dyspepsia as compared with both Org 3770 and placebo, and significantly higher rates of somnolence as compared with placebo.
                In this study, Org 3770 was as effective as amitriptyline in the treatment of major depression, with advantages regarding improvements of depressed mood (HAM-D Item 1), responder rates, and safety. Anti-depressants have been reported to be useful in the management of the Irritable Bowel syndrome. We studied the efficacy of amitriptyline for 12 weeks in a randomized double-blind placebo-controlled trial. Forty patients who met predefined criteria entered the trial. They received 25 mg amitriptyline for the first week, 50 mg for the second week and 75 mg nightly thereafter until the end of the 12th week. The drug and placebo groups were comparable in all major pretreatment variables. Amitriptyline was found to be significantly more effective than placebo in producing global improvement, increasing feelings of well-being, reducing abdominal pain and increasing satisfaction with bowel movements. Younger age and increasing extroversion predicted a better response to amitriptyline. Severity of depressive and anxiety symptoms and other personality variables did not influence outcome. Two hundred forty-one elderly depressed patients entered the 8-week, double-blind phase of this parallel-group, multicenter study; 161 patients were randomized to receive sertraline (50-200 mg/day) and 80 were randomized to receive amitriptyline (50-150 mg/day). Among evaluable patients, there were no statistically significant differences between treatments in any of the primary efficacy variables: change in total Hamilton Rating Scale for Depression (HAM-D) score (17 items), percentage change in HAM-D score, change in HAM-D Item 1, change in Clinical Global Impressions (CGI) Severity score, change in the Depression Factor of the 56-item Hopkins Symptom Checklist, and the CGI Improvement score at the last visit. Similar results were obtained using data from all patients (intention-to-treat analysis), except that amitriptyline was superior in HAM-D Total score (p = .044). The two drugs produced a similar degree of response: on the basis of the HAM-D criterion, 69.4% of sertraline patients and 62.5% of amitriptyline patients responded, and, on the basis of CGI criterion, 79.5% of sertraline and 73.4% of amitriptyline patients responded. Twenty-eight percent of the sertraline patients withdrew from the study because of a treatment-related side effect and 2.5% (4) because of a laboratory abnormality. In comparison, 35% of the amitriptyline patients withdrew because of treatment-related side effects. Sertraline was associated with a statistically lower frequency of somnolence, dry mouth, constipation, ataxia, and pain and a higher frequency of nausea, anorexia, diarrhea/loose stools, and insomnia; thus, anticholinergic effects were less common and gastrointestinal effects were more common with sertraline than with amitriptyline.(ABSTRACT TRUNCATED AT 250 WORDS) Patients (n = 150) were randomized to a 6-week, double-blind study to evaluate the relative efficacy and safety of mirtazapine, amitriptyline, and placebo in the treatment of major depressive disorder symptoms. Average daily modal doses were mirtazapine, 18 mg; amitriptyline, 111 mg; and placebo, 4.6 capsules. Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression (HAM-D) score reductions (weekly visits 1, 2, 4, and endpoint) compared to placebo. These findings were supported by the Montgomery-Asberg Depression Rating Scale (MADRS); the Zung Self-rating Depression Scale (SDS); and the Clinical Global Impressions (CGI) scales. Somnolence and weight gain were the only adverse clinical experiences (ACEs) reported substantially more often by mirtazapine-treated patients than by those in the placebo group. However, more amitriptyline-treated patients reported decreased visual accommodation, dry mouth, dyspepsia, constipation, tachycardia, hypertension, hypotension, discoordination, dizziness, and tremor than mirtazapine- or placebo-treated patients. Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients, and superior to amitriptyline in respect to anticholinergic and cardiovascular effects. 1 A double-blind trial with parallel treatment groups was conducted to compare the safety and efficacy of mianserin with amitriptyline. 2 This was a six week trial with weekly visits. Measurements at each visit included: 21 item Hamilton Depression (HAMD) Scale. Clinical Global Impression (CGI) Scale and Treatment Emergent Symptom Scale (TESS). 3 Mianserin and amitriptyline were comparable with respect to efficacy. 4 More adverse experiences were reported by amitriptyline patients. The predominant amitriptyline adverse experiences were of the anticholinergic type; the predominant mianserin adverse experience was drowsiness/fatigue. 5 The Efficacy Index (EI), a scale combining efficacy and adverse experiences, clearly demonstrated the superiority of mianserin over amitriptyline.
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.