A recent multicenter, randomized controlled trial of antidepressants in patients with functional dyspepsia showed that amitriptyline may improve symptoms in some patients, while etanercept did not. The relevant study, published in Gastroenterology, was compiled by Medical Pulse as follows: To determine the efficacy of antidepressants on functional dyspepsia (FD) symptoms, gastric emptying, and satiety due to eating, researchers enrolled 292 patients with FD (70% dyskinetic FD; 30% ulcerative FD) from eight centers in North America after a 2- to 4-week washout period ( mean age 44 ± 15 years; 75% female; 86% white) were randomly assigned to receive either the placebo group, the 50 mg amitriptyline group, or the 10 mg etaprepitant group for 10 weeks. Adequate relief of dyspeptic symptoms and quality of life was evaluated by weekly questionnaires, gastric emptying by scintigraphy at baseline and at the end of treatment, and eating leading to satiety by nutritional beverage testing. Patients were followed up monthly for 6 months. Overall, adequate remission was reported in the 40% placebo group compared to 53% in the amitriptyline group, 38% in the etaprepitant group (p=0.05). Patients treated with amitriptyline had a significant response compared with the placebo group (OR=1.1; 95% CI, 0.6-2.1). Patients with ulcerative FD reported three times more adequate symptom relief than those receiving the placebo group (OR=3.1; 95% CI, 1.1-9). No antidepressant tests affected gastric emptying or eating leading to satiety after 10 weeks, but improved overall quality of life compared with placebo (P=0.02). Patients with delayed gastric emptying at baseline were less likely to report adequate symptom relief compared with patients with normal gastric emptying (OR=0.4; 95% CI, 0.2-0.8). Among responders who completed the 6-month follow-up, 73% relapsed on treatment. Reported side effects were 21% in the placebo group, 30% in the amitriptyline group, and 29% in the etanercept group (P > 0.05), with no serious side effects reported. The researchers concluded, “Amitriptyline is beneficial in FD, especially in patients with ulcerative FD. Although side effects were common, there were no overall differences among the three groups (except for neurological symptoms, which occurred most frequently in the etaprepitant group) suggesting that tricyclic antidepressants are generally well tolerated at low doses by providing counseling and support. The results do not support the use of etaprepitant in FD.” In an accompanying editorial, William L. Hasler (from Michigan Health System) and Kenneth L. Koch (from Wake Forest University) describe these findings as “the most comprehensive characterization of the response to antidepressant therapy for FD to date. .” The study showed “appropriate efficacy of tricyclics, but not a selective serotonin reuptake inhibitor, in reducing FD symptoms, primarily in a small subgroup of patients with ulcer-type pain,” they added. ”The lack of efficacy in patients with dyspepsia with delayed gastric emptying suggests the possibility of using a scintillation test to select patients with normal gastric emptying, rather than abnormal emptying, for amitriptyline treatment. Given the difficulty of conducting experiments with this drug family, this careful investigation may represent a definitive description of the use of tricyclic antidepressants for FD,” they conclude.