Double-blind placebo-controlled study of nortriptyline in depressed adolescents using a "fixed plasma level" design.

We performed a random assignment, double-blind, placebo-controlled study of nortriptyline (NT) in postpubertal 12- to 17-year-olds with Research Diagnostic Criteria (RDC) and DSM-III major depressive disorder. The protocol included a 2-week placebo washout phase and an 8-week double-blind, placebo-controlled phase with weekly plasma level monitoring. Active subjects had their plasma level placed at 80 +/- 20 ng/ml by using previously developed tables to determine the starting dose from a plasma level drawn 24 hours after a single dose administered at baseline. The study population was severely depressed and had a chronic, unremitting course prior to study; a high percentage of family histories with affective disorder, alcoholism, and suicidality; and a high rate of comorbidity. Of the 52 subjects enrolled, there were 17 placebo washout responders, 4 dropouts, and 31 completers (12 active and 19 placebo). Only one active subject responded; therefore, the study was terminated early. The mean NT plasma level was 91.1 (18.3 SD) ng/ml. The two treatment groups had similar postprotocol severity ratings. Subjects on active drug did not evidence the anticholinergic side effects reported in adult samples. The negative outcome in this study is similar to the findings in our previously reported NT study in prepubertal 6- to 12-year-olds.