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Pharmacokinetically designed double-blind placebo-controlled study of nortriptyline in 6- to 12-year-olds with major
B Geller1, T B Cooper, D L Graham
1University of South Carolina School of Medicine, Columbia.
Insights
Nortriptyline showed a poor response rate in treating major depressive disorder in children. This study found no significant difference compared to placebo, with fewer side effects than in adults.
Area of Science:
- Child and Adolescent Psychiatry
- Pharmacology
- Clinical Psychology
Background:
- Major depressive disorder (MDD) in prepubertal children is a significant concern.
- Limited research exists on the efficacy and safety of tricyclic antidepressants (TCAs) in this population.
- Previous studies on TCAs in children have yielded mixed results.
Purpose of the Study:
- To evaluate the efficacy and safety of nortriptyline in prepubertal children diagnosed with MDD.
- To compare nortriptyline's effectiveness against a placebo in a double-blind, randomized controlled trial.
- To assess side effect profiles in pediatric patients receiving nortriptyline.
Main Methods:
- A double-blind, placebo-controlled study involving 50 children aged 6-12 with MDD.
- Inclusion of a 2-week placebo washout and an 8-week treatment phase with plasma level monitoring.
- Pharmacokinetic dosing of nortriptyline to achieve target plasma levels (80 +/- 20 ng/ml).
Main Results:
- A low response rate was observed in both the nortriptyline group (30.8%) and the placebo group (16.7%).
- No significant difference in efficacy was found between nortriptyline and placebo.
- Children treated with nortriptyline did not exhibit the anticholinergic side effects commonly seen in adult samples.
Conclusions:
- Nortriptyline demonstrated limited efficacy in treating major depressive disorder in this cohort of prepubertal children.
- The findings suggest a need for further research into effective pharmacotherapeutic strategies for pediatric depression.
- The favorable side effect profile in children warrants consideration in future treatment development.
Abstract:
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.