An open-label dosing study of paroxetine in depressed children and adolescents

Abstract

Background: Depression is a common disorder in children and adolescents. It is often associated with psychologic distress, academic dysfunction, intrafamilial conflict, and the risk for suicide. For these reasons, safe and effective treatments are needed for depression in pediatric patients. Objective: This study considered the effectiveness of initiating the antidepressant paroxetine at a low dose and explored clinical and biochemical factors associated with response in juvenile depression. Methods: In this 8-week, single-center, open-label trial, children and adolescents with major depression were assessed weekly. Patients were initially treated with paroxetine at a dosage of 10 mg/d for 4 weeks. If a priori criteria for improvement were not met, the dosage of paroxetine was increased to 20 mg/d. Standard psychometric outcome measures were used. Prior to treatment, patients' phenotypes for cytochrome P450 2D6 and catechol O-methyltransferase activity were determined. Platelet-rich plasma serotonin was measured before and after 4 weeks of therapy. Plasma paroxetine concentration was measured after 4 weeks of treatment. Results: Thirty children and adolescents (15 boys, 15 girls) aged 6 to 17 years were enrolled and 29 were treated. Of the 27 patients who received at least 4 weeks of paroxetine treatment, 18 (66.7%) met improvement criteria at week 4. Open-label paroxetine was generally well tolerated and was associated with significant symptom amelioration by week 8 for most patients. Age, other demographic characteristics, and biochemical variables did not differ between the patients who had their dose of paroxetine increased and those who did not. Conclusions: The results of this study suggest that paroxetine 10 mg/d is effective in the open-label treatment of most depressed children and adolescents. For those who do not respond to this dosage, an increase to 20 mg/d appears to be an empirically supported treatment strategy.