From the Editor-in-Chief’s Desk: Special Issue on the Psychopharmacology of Neurodevelopmental Disorders

To Our Readers:

Our patients, practice, and field struggle with knowledge gaps in treatment planning for patients with neurodevelopmental disorders. Three thought leaders in this area, Drs. Ellen Hoffman, Robyn Thom, and Jeremy Veenstra-VanderWeele recently led a call for articles and special issue focused on neurodevelopmental disorders for our journal. The response and quality of work were superb and as a result we present one full issue this month and a follow-up to this later in 2025.

In this issue, Dr. Sarah Kevelson presents an intriguing discussion on the potential promises and perils of therapeutic self-disclosure in the context of work with autistic patients. Therapeutic self-disclosure requires careful consideration and management to ensure patient comfort and benefit. This piece describes the additional considerations for patients with variable patterns of social interactions (Kevelson, 2025). This is followed by an exhaustive expert review of drug discovery for autism spectrum disorder and related neurogenetic syndromes. This article outlines a translational precision medicine blueprint for autism spectrum disorder emphasizing the importance of various model systems, biomarkers, and clinical trial design strategies, with trofinetide for Rett syndrome as a successful example (Thom et al., 2025).

Research studies in this special issue include a phase 3, randomized, double-blind, placebo-controlled trial and open-label extension of brexpiprazole for the treatment of irritability in children and adolescents with an autism spectrum disorder. The study found no significant difference in efficacy between brexpiprazole and placebo, with both groups showing similar reductions in irritability scores. The safety profile of brexpiprazole was consistent with previous findings in schizophrenia patients, with the most common treatment-emergent adverse events being somnolence and increased weight (Ward et al., 2025). Another article describes a study that aimed to identify predictors of placebo response in autistic youth participating in a randomized controlled trial of intranasal oxytocin. Higher baseline severity on social communication measures predicted greater placebo response, which contrasted with other findings for repetitive behavior treatments. Distinct factors may contribute to placebo response in various autism symptom domains (Verdes et al., 2025). Another study in this issue examined the effects of single oral doses of lovastatin, minocycline, and placebo on electrophysiological and behavioral measures in patients with Fragile X Syndrome. No significant overall treatment effects were found, but lovastatin improved spatial awareness in older participants and females. The study validates the feasibility of single-dose drug studies for detecting subtle drug-target engagement in patients with neurodevelopmental disorders (McKinney et al., 2024).

Also in this issue, Thom and colleagues present findings from a 16-week prospective, open-label trial to evaluate the effectiveness, safety, and tolerability of buspirone in 20 individuals with Williams syndrome (WS) aged 5–65 years. The primary measure was the Pediatric Anxiety Rating Scale. Results indicated that buspirone use reduced anxiety severity with a Cohen’s d estimate of −4.02 with the Pediatric Anxiety Rating Scale. All participants showed significant improvement, and there were no serious adverse events or discontinuations due to side effects (Thom et al., 2024). Another piece focused on interventional psychiatry in the context of a study of the effects of prefrontal transcranial magnetic stimulation in individuals with autism spectrum disorder and treatment-resistant depression. Participants underwent 30 sessions of accelerated theta burst stimulation, which led to a decrease in prefrontal cortical excitability and an increase in right temporoparietal excitability. This resulted in significant improvements in fluid cognition and depression symptoms. The findings suggest a potential link between reduced prefrontal excitability and cognitive flexibility improvements in autism spectrum disorder, warranting further research on autism spectrum disorder populations without major depressive disorder (Elmaghraby et al., 2025).

Srinivasan and colleagues explored a strategy to improve processes for obtaining intravenous access in dysregulated patients with catatonia. Six autistic patients with hyperactive catatonia successfully received intramuscular ketamine to facilitate intravenous access to electroconvulsive therapy (ECT), with concurrent high-dose benzodiazepine treatment. The use of intramuscular ketamine allowed all patients to undergo ECT without serious adverse events (Srinivasan et al., 2025). Another brief report examined psychotropic medication use in children with Down syndrome (N = 670) and found that 19.1% were prescribed at least one psychotropic medication, with alpha-agonists being the most common. Older children had higher odds of being prescribed these medications, but no significant differences were found across sex, race, or household income. The study highlights the need for further research on medication efficacy and safe dosing practices for children with Down syndrome (Weas et al., 2024).

Lastly, this issue includes a letter describing a 17-year-old male with autism spectrum disorder and chronic catatonia who developed hyperkinetic movements after starting mirtazapine. Despite these movements, the patient continued mirtazapine due to its benefits, and the movements became less pronounced over time. These observations underscore the complexities of managing such side effects in patients with neurodevelopmental disorders on multiple psychotropic medications (Berman et al., 2024). Another letter reviews the literature and provides guidance on managing agitation with psychotropic medications in a pediatric patient with X chromosome-linked monoamine oxidase-A and monoamine oxidase-B deficiency, highlighting the increased risk of serotonin syndrome (Beser et al., 2024). The treatment of a boy with Norrie’s disease and monoamine oxidase deficiency is discussed, where clonidine was used successfully to manage agitation, emphasizing the need for further research on psychopharmacological challenges in this population. A final letter describes a boy with autism spectrum disorder who developed priapism after an increased dose of aripiprazole with concurrent risperidone treatment. Often youth with neurodevelopment disorders do need alternative treatment plans, but this letter highlights the importance of caution with complex medication regimens (Durak and Işık, 2024).

Please join me in thanking and congratulating our authors and Drs. Ellen Hoffman, Robyn Thom, and Jeremy Veenstra-Vander Weele for these important contributions to our journal and field. We hope you enjoy this issue of Journal of Child and Adolescent Psychopharmacology.