From the Editor-in-Chief’s Desk: Improving the Health of Children with Greater Rigor in the Clinical Science of Psychopharmacology

TO Our READERS:

There are important opportunities and unmet needs to improve the transparency, replicability, and overall rigor of clinical trials to advance our child and adolescent psychopharmacology evidence base (Singh, 2025). Developmentally sensitive designs, biomarker-driven approaches, and modern statistical approaches continue to address these needs (Mills and Strawn, 2025). In this issue, Roy and colleagues focus on the heterogeneity of treatment response definitions across randomized controlled trials focused on pharmacological interventions for youth with attention-deficit/hyperactivity disorder (ADHD). This effort identified 88 trials with defined thresholds for response based on reductions in ADHD symptoms severity. The most common definition used in 39 studies was a ≥30% reduction in ADHD rating scale scores. Other studies used ≥25%, ≥40%, or ≥50%. Notably, 79 studies did not define a response threshold. These findings identify opportunities for harmonized definitions of outcome measures for clinical trials of ADHD (Roy et al., 2025).

This issue includes an article from the Sertraline Pediatric Registry for the Evaluation of Safety (SPRITES). The SPRITES study was a large (N = 941), 3-year, observational study examining outcomes in patients aged 6–16 years who were prescribed sertraline with or without psychotherapy compared to patients in treatment with psychotherapy. Ramaker and colleagues examined the safety outcomes in this cohort. The majority of patients (N = 696) received sertraline, and there were patients who received other antidepressants. The patient group receiving sertraline had higher rates of adverse and serious adverse events compared with the group not receiving pharmacologic treatments. The incidence of adverse events improved over time. A repeated measures marginal structural model did not show effects of sertraline on new or worsening suicidal ideation or behavior. These results provide long-term, real-world data on youth treated with sertraline and are consistent with prior acute studies (Ramaker et al., 2025).

Clozapine is a therapeutic option for youth with severe aggression in the context of intractable mood, psychotic, and symptoms related to neurodevelopmental disorders. There is limited prior systematic research to guide clozapine treatment in youth (Pimenta de Figueiredo et al., 2024). Harris and colleagues address this need with a piece examining retrospective experience in youth (N = 58) with autism spectrum disorder with or without an intellectual disability to treat severe aggression and irritability. Patients (n = 40) who had longer-term treatment with clozapine had statistically significant reductions in psychiatric hospitalizations, emergency medicine department visits, and clinical global impression-improvement ratings. Notably, there was no statistically significant increase in BMI Z-score. Albeit not without limitations, this study provides additional information to guide future practice (Harris et al., 2025).

Additional work in this issue focuses on increasing the validity of posttraumatic stress disorder (PTSD) assessments. The study examined endorsement of Criterion A (exposure) in youth and parents with PTSD checklists and enhanced PTSD checklists compared to assessments with the PTSD module of the Kiddie Schedule of Affective Disorders and Schizophrenia Present and Lifetime Version for School-Age Children. Children and parents endorsed 45 and 41 false positive events, respectively, and the enhanced PTSD checklist did not reduce false positive events. This study identifies important opportunities for further research and limitations in current assessment tools for PTSD. Future improvements in assessments of PTSD will enhance related epidemiological work and intervention development (Scheeringa, 2025).

Other contributions in this issue focus on neurodevelopmental disorders. Wilson and Wong provide observations and clinical symptoms associated with a sample of patients with SPTAN1 variants (Wilson and Wong, 2025) to inform practice and future translational research efforts (Thom et al., 2025). A brief report by Ferguson and colleagues suggests that baseline heart rate variability may be a biomarker to guide treatment with propranolol for gastrointestinal symptoms in patients with autism spectrum disorder (Ferguson et al., 2025). A letter to the editor describes the innovative use of applied behavioral analysis teams and telepsychiatry for the pharmacological management of catatonia (Chu and Ince, 2025).

We round out this issue with important commentary from Bloch and colleagues focused on the 2024 clearance of transcranial magnetic stimulation as an adjunctive treatment for major depressive disorder in patients aged 15–21. This thoughtful and balanced letter raises concerns with respect to marketing, confusion regarding regulatory pathways, ethical informed consent processes, and opportunities for peer review of FDA registration data (Kump et al., 2025). We appreciate this dialogue for our journal and encourage readers to submit collegial discussions to elevate our journal, field, and work focused on improving the lives of children.

We hope you enjoy this issue of Journal of Child and Adolescent Psychopharmacology.