Randomized, controlled trial of amitriptyline versus placebo for adolescents with 'treatment-resistant' major depression

Objective: To assess the response to a serotonergic/noradrenergic tricyclic antidepressant, amitriptyline (AMI), in a group of adolescents with treatment-resistant major depressive disorder (MDD). Method: Twenty-seven depressed adolescents admitted to a state hospital underwent a 10-week randomized, controlled trial with a flexible dose of AMI or placebo. Results: 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. Conclusions: 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 or 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.