The Lowest Effective Plasma Concentration Of Atomoxetine In Pediatric Patients With Attention Deficit/Hyperactivity Disorder A Non-Randomized Prospective Interventional Study

Background: Atomoxetine (ATX) is used as a first-line, non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD), although no studies have systematically examined the relationship between plasma concentration and clinical efficacy. We conducted this non-randomized prospective interventional study to examine the relationship between plasma concentration of ATX and clinical efficacy. Methods: Forty-three ADHD pediatric patients received ATX, and the steady-state through plasma concentration of the last daily dose that was maintained for at least 4 weeks were determined by high-performance liquid chromatography. Results: The receiver operating characteristic curve suggested that when plasma concentration exceeded 64.60 ng/mL, scores on the ADHD-Rating Scale improved by 50% or more (P = .14). Although 6 of the 8 final responders were unresponsive at the initial dose (.72 +/- .04 mg/kg [mean +/- standard deviation]), they responded after increasing the ATX dose to the final dose (1.52 +/- .31 mg/kg). Excluding 7 outlier participants, the concentration was 83.3 +/- 32.3 ng/mL in 7 responders and was significantly higher than 29.5 +/- 23.9 ng/mL (P < .01) for the 29 non-responders. Conclusions: These results suggest that a minimum effective plasma concentration of ATX is required to achieve sufficient clinical efficacy. We hypothesized a mechanism that results in the realization of a clinical effect when the plasma concentration exceeds a certain threshold in the potential response group, whereas will not improve even if the plasma concentration is increased in the unqualified non-responder group.