Abstract
Objective: To describe the pharmacokinetics and safety of nefazodone (NFZ) in depressed children and adolescents. Method: Depressed youths aged 7 to 17 years were eligible to participate. Intensive sampling for pharmacokinetic analyses of NFZ and 3 of its active metabolites was performed after single and multiple dose administration. Treatment was continued for 6 more weeks and titrated to maximize clinical response. Results: Twenty-eight patients were enrolled. Systemic exposure to NFZ and 3 metabotites was generally higher in children than adolescents. NFZ and metabolite disposition profiles showed high intra- and interpatient variability. Compared to published data in adults, the half-life of NFZ and 2 of its metabolites appears shorter in children and adolescents. Meta-chlorphenylpiperazine pharmacokinetic parameters were different in 5 patients determined to be poor metabolizers of cytochrome P450 2D6 (CYP2D6). NFZ was well tolerated, and administration was associated with significant reductions (p angle .001) in depressive symptoms. Conclusions: The pharmacokinetics of NFZ in pediatric patients is highly variable. NFZ appears to be safe in this small, short-term study. Pediatric patients who are poor metabolizers of CYP2D6 do not appear to be at increased risk for NFZ-associated adverse events. Open-label treatment of NFZ is associated with reductions in depressive symptoms.
Original language | English (US) |
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Pages (from-to) | 1008-1016 |
Number of pages | 9 |
Journal | Journal of the American Academy of Child and Adolescent Psychiatry |
Volume | 39 |
Issue number | 8 |
DOIs | |
State | Published - 2000 |
Externally published | Yes |
Keywords
- Depression
- Nefazodone
- Pharmacokinetics
ASJC Scopus subject areas
- Developmental and Educational Psychology
- Psychiatry and Mental health