Sep 2, 2022
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The Brown University Psychopharmacology Update
Abstract
Phase 3 studies of centanafadine in adult ADHD show efficacy Stimulant medications have been effective in the treatment of attention-deficit hyperactivity disorder (ADHD) in adults, while nonstimulants such as atomoxetine have generally been less effective. Centanafadine, an inhibitor of norepinephrine, dopamine, and serotonin reuptake transporters, is considered a stimulant with nonstimulant characteristics and has shown effectiveness in Phase 2 trials. Two Phase 3 studies were conducted to compare the effectiveness of centanafadine and placebo in adult patients with ADHD. Each of the randomized, double-blind, placebo-controlled trials was conducted between January 2019 and May 2020 and consisted of a screening and washout period of up to 28 days, a 1-week single-blind placebo run-in, 6 weeks of double-blind treatment with centanafadine or placebo, and a 10-day follow-up. Eligible for inclusion were adults aged 18 to 55 who met DSM-5 criteria for ADHD. Participants received centanafadine 200 or 400 mg/ day or placebo, with the 400-mg group receiving 200 mg/day in the first 7 days of treatment. The primary efficacy measure was change from baseline to 6 weeks in total score on the Adult ADHD Investigator Symptom Rating Scale (AISRS), and the key secondary measure was change from baseline on the Clinical Global Impression-Severity (CGI-S) scale. Safety assessments included measures of adverse events, laboratory results, and suicidality. The studies included 446 and 430 participants in the double-blind phase, with mean ages of 35.6 and 35 years, respectively. The studies found that both doses of centanafadine resulted in significant improvement over placebo on the AISRS and the CGI-S. The most commonly reported adverse events reported by participants receiving centanafadine were headache and decreased appetite. Treatment discontinuation due to adverse events occurred in 4.8% of the centanafadine 200 mg/ day group, 6.2% of the centanafadine 400 mg/day group, and 1.4% of the placebo group. “Statistically significant reductions in ADHD symptoms observed in the first week of study 2 are similar to those seen in the Phase 2 centanafadine studies, suggesting that centanafadine provides a relatively rapid clinical effect,” the study’s authors wrote. [Adler L. et al. J Clin Psychopharmacol 2022; published online Jun 2; doi: 10.1097/JCP.0000000000001575]