A controlled study of nortriptyline in children and adolescents with attention deficit hyperactivity disorder

Objectives: To study the efficacy and tolerability of nortriptyline (NT) in the treatment of pediatric attention deficit hyperactivity disorder (ADHD) . Methodology: Subjects were outpatient children and adolescents with ADHD as certained from clinical referrals. Subjects were enrolled in a 6-week open study in which NT was titrated to 2 mg/kg/day as tolerated over 2 weeks. Us ing either a 30% reduction in the ADHD rating scale or a score of 1 or 2 on the Clinical Global Impression (CGI) scale for ADHD improvement, responder s to treatment were then randomized into a 3-week, controlled discontinuati on phase. During this phase, subjects either continued on their current dos e of NT or were tapered to placebo under double-blind conditions. Subjects were monitored for symptoms of ADHD, oppositionality, anxiety, and depressi on. Results: Of the 35 subjects enrolled in the study, 32 completed the open ph ase and 23 completed the discontinuation phase. The mean dose of NT was 80 mg (1.8 mg/kg/day), resulting in a serum level of 81 ng/ml. At the conclusi on of the open 6-week study, NT was related to a significant reduction in A DHD (p < 0.001) and oppositional symptoms (p < 0.001). At the conclusion of the discontinuation phase, the 12 subjects randomized to NT had significan tly lower scores on the DSM-IV ADHD symptom checklist than those 11 subject s randomized to placebo (31 versus 21; t = 2.2; p < 0.04). No significant a dverse events were observed, and children were noted to have weight gain du ring the trial. Conclusions: These data suggest that NT is effective in reducing symptoms n ot only of ADHD but also of oppositionality. This group of children and ado lescents tolerated robust dosing of NT well, with few clinical or cardiovas cular adverse events.