Editorial: Why JAACAP Published an "Inconclusive" Trial: Optimize, Optimize, Optimize Psychostimulant Treatment.

In this issue of the Journal, Blader et al.1 report the results of a double-blind randomized controlled trial (RCT) aimed at assessing the comparative efficacy and tolerability of adjunctive risperidone (RISP), valproex sodium (DVPX), or placebo for aggressive behaviors in children (aged 6-12 years) with attention-deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder (ODD) or conduct disorder (CD), as well as a prior history of psychostimulant treatment. Participants with aggressive symptoms persisting after an open-label optimization of psychostimulant medication entered the 8-week randomized phase. Weekly sessions of family-based behavioral treatment were offered during both the optimization and the randomized phases. Among the 151 participants who completed the optimization phase (175 were initially enrolled), an unexpected 63.6% met the study criteria for remission, that is, 3 consecutive weeks with subthreshold scores on the Retrospective-Modified Overt Aggression Scale (R-MOAS). Therefore, only 45 participants were eligible for randomization, and 40 (RISP: n = 17; DVPX: n = 14; placebo: n = 9) were included in the primary analysis. Why did JAACAP publish an inconclusive trial? Because, in our view, the lessons that can be learned from this RCT (in particular, from its optimization phase) are highly relevant for both clinicians and trialists in the field. We are confident that the Blader et al. study will contribute to make clinicians in the field more "optimizers" and trialists more "transparent."