Letter: Improving Outcomes in Level 3 Autism after Treating Co-Occurring ADHD

To the Editor:

Children and adolescents with autism spectrum disorder (ASD) often present with co-occurring psychiatric conditions, including attention-deficit/hyperactivity disorder (ADHD). Identification of ADHD in the context of ASD can be clinically challenging due to symptom overlap; however, the appropriate diagnosis and treatment of ADHD can improve a wide range of target behaviors and, in many, cases alleviate the need for antipsychotic medications (Manter et al., 2025).

Level 3 ASD, defined by DSM-5 as requiring very substantial support, typically characterizes individuals presenting with profound challenges in emotional control and behavioral self-regulation (American Psychiatric Association, 2013). Among this group, co-occurring psychiatric conditions are prevalent yet often undiagnosed, with ADHD estimates as high as 30%–80% (Genovese and Butler, 2023). Diagnostic overshadowing of ADHD by autism-related behaviors is common, particularly in patients with severe ASD symptomatology, intellectual disability, or minimal verbal abilities (Young et al., 2020).

Pharmacologic management in this population often defaults to antipsychotics, especially when severe irritability, aggression, and self-injury are present. While risperidone and aripiprazole remain the only two FDA-approved medications for irritability associated with autism, the long-term use of antipsychotics can lead to significant side effects. Less frequently considered—but potentially more targeted treatments—are ADHD medications, which may alleviate the underlying executive dysfunction and emotional dysregulation driving many externalizing behaviors, and with a reduced side effect burden.

This case series was derived from retrospective chart review and clinical assessments conducted over a 2-year period at a tertiary child and adolescent psychiatry clinic. The original sample included 32 patients with level 3 ASD taking antipsychotic medication for irritability who were subsequently diagnosed and treated for ADHD. After establishing an effective ADHD treatment regimen, 12 patients (37.5% of cases, average age 15; range 10–21 years) were able to discontinue antipsychotic medications, with resolution of antipsychotic-related side effects, including weight gain, extrapyramidal symptoms, gynecomastia, priapism, and metabolic abnormalities (Table 1). At the end of year one, the average CGI-I score was 1.75 (range 1–2) defined as “much improved” or “very much improved.”

Two-year follow-up data demonstrated that all 12 were still taking ADHD medications as either monotherapy or in combination (stimulant with alpha 2 agonist, for example), with most demonstrating additional reductions in target behaviors compared to the previous year. Half of patients demonstrated additional improvement in CGI-S scores, with a reduction in severity ratings from an average of 6 (severely ill) to 4.9 (markedly ill) with none of the 12 rated as worse. Only one resumed an antipsychotic for treatment of re-emergent irritability and aggression.

This case series provides clinical evidence supporting the benefit of targeted ADHD treatment in children and adolescents with level 3 ASD. These patients often present with overlapping symptoms of ADHD; however, these behaviors are often misattributed to autistic traits. Our review of 12 identified cases suggests that when ADHD is recognized and treated, even within the context of severe ASD symptomatology, meaningful reductions in target symptoms can be achieved, and in many cases the need for antipsychotics can be alleviated.