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

Boris Birmaher, G. Scott Waterman, Neal D. Ryan, James Perel, Joanne McNabb, Lisa Balach, Mary Beth Beaudry, Farida N. Nasr, Jagannath Karambelkar, Gertrude Elterich, Humberto Quintana, Douglas E. Williamson, Uma Rao

    Research output: Contribution to journalArticlepeer-review

    62 Scopus citations


    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.

    Original languageEnglish (US)
    Pages (from-to)527-535
    Number of pages9
    JournalJournal of the American Academy of Child and Adolescent Psychiatry
    Issue number5
    StatePublished - May 1998


    • Adolescents
    • Antidepressants
    • Major depressive disorder

    ASJC Scopus subject areas

    • Developmental and Educational Psychology
    • Psychiatry and Mental health


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