Pharmacokinetically designed double-blind placebo-controlled study of nortriptyline in 6- to 12-year-olds with major depressive disorder.
A random assignment, double-blind, placebo-controlled study of nortriptyline in 50 prepubertal 6- to 12-year-olds with Research Diagnostic Criteria and DSM-III major depressive disorder was performed. The protocol included a 2-week placebo wash-out phase and an 8-week double-blind, placebo-controlled phase with weekly plasma level monitoring. Active subjects had their plasma level pharmacokinetically placed at 80 +/- 20 ng/ml by using previously developed tables to determine the starting dose from a plasma level 24 hours after a single dose administered at baseline. The mean plasma level was 89.9 ng/ml. The study population was severely depressed, had a chronic, unremitting course of long duration before the study, had a high percentage of family histories with affective disorder, alcoholism and suicidality, and had a high rate of comorbidity. None of the subjects had ever received tricyclic antidepressants before this study. There was a poor rate of response in both treatment groups (30.8% active, 16.7% placebo). Active subjects did not evidence the anticholinergic side effects reported in adult samples. The implications of these findings for future pharmacotherapy studies of depressed children are discussed.
Geller
B
B
University of South Carolina School of Medicine, Columbia.
Cooper
T B
TB
Graham
D L
DL
Fetner
H H
HH
Marsteller
F A
FA
Wells
J M
JM
D002648:Child; D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009661:Nortriptyline / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010552:Personality Assessment
D009661:Nortriptyline