Objective: The objectives of this pilot study were to explore the changes in symptom severity, tolerability, and the pharmacodynamics of venlafaxine treatment in youths with attention-deficit/hyperactivity disorder (ADHD).
Methods: This was a 2-week, open-label, outpatient trial of venlafaxine in children and adolescents, ages 5-17 years, with ADHD. Three dosing strata, 0.5, 1.0, and 2.0 mg/kg per day, were examined. ADHD symptom severity and improvement assessments included the ADHD Rating Scale (ARS-IV) and the Clinical Global Impressions Scale (CGI). During this study, venlafaxine, O-desmethylvenlafaxine (ODV), norepinephrine, and serotonin concentrations were obtained.
Results: Thirty-eight participants (33 males) were treated in this trial. Overall, parent-completed and teacher-completed ARS-IV total scores showed a statistically significant positive change at the end of the study when compared to baseline (p < 0.05). Significant increases in plasma venlafaxine concentrations were observed at day 15 when compared to day 8 (p = 0.04). In addition, plasma norepinephrine and serotonin concentrations were found to be significantly decreased from baseline at end of study (p < 0.05). Four patients ended participation in the study prematurely: lost to follow up (n = 2), withdrawal of consent (n = 1), and worsening of ADHD symptoms after 8 days of treatment (n = 1). There were no discontinuations due to other adverse events.
Conclusions: Venlafaxine appeared to offer some benefit and appears to be relatively safe for the short-term treatment of ADHD in this open-label trial. The pharmacodynamics of venlafaxine in youths are consistent with serotonergic and neuradrenergic modulation.