Global developmental delay (GDD) is a complex disorder that requires multimodal treatment involving different developmental skills. The objective of this single-blind, randomized, controlled pilot study is to evaluate the feasibility and effectiveness of conventional rehabilitation programs integrated with the BTs-Nirvana virtual reality system. Patients with GDD aged 12 to 66 months were enrolled and treated for a 48-session cycle. Patients were randomized into two groups, (1) conventional treatment and (2) conventional treatment supplemented with the use of BTs-Nirvana, in a 1:1 ratio. Before and after treatments, areas of global development were tested with the Griffiths-III Mental Developmental Scale and the clinical indicator of global improvement were measured with the Clinical Global Impressions-Improvement (CGI-I). Feasibility was confirmed by the high retention rate. The experimental group presented a significantly improvement in General Quotient (GQ) after treatment (GQ, p = 0.02), and the effect of the two treatments was significantly different in both the GQ (t =2.44; p = 0.02) and the Foundations of Learning subscale (t =3.66; p < 0.01). The overall improvement was also confirmed by the CGI-I (p = 0.03). According to these preliminary data, virtual reality can be considered a useful complementary tool to boost the effectiveness of conventional therapy in children with GDD.

Background/Objectives: The co-occurrence of Attention-deficit/hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) is very common and worsens adaptive functioning. This systematic review evaluates both pharmacological and non-pharmacological interventions in this underserved population. Methods: Registered on PROSPERO (CRD42024526157), a systematic search was conducted on PubMed, Embase, and Web of Science until 5 April 2025. The review includes (a) pilot studies and RCTs, (b) participants aged <18 years, (c) diagnoses of ASD and ADHD based on DSM-IV/V or ICD-9/10, (d) at least one group receiving any intervention, and (e) publications in English, Italian, Spanish, or German. Newcastle Ottawa Scale tools for non-randomized studies and the Cochrane Risk of Bias Tools for randomized controlled trials were used to assess studies’ quality. Results: A total of 32 studies were included: 87.5% concerning pharmacological treatments. Specifically, methylphenidate (MPH, n = 11), atomoxetine (ATX, n = 11), guanfacina (n = 4), clonidine (n = 1), or atypical antipsychotics (n = 1) were examined. MPH and ATX were most frequently studied, with both showing positive effects in reducing ADHD core symptoms compared to placebo. ATX also reduces stereotyped behaviors and social withdrawal, although more withdrawals due to adverse events (AEs) were reported for ATX than MPH. Four studies (12.5%) examined non-pharmacological interventions, including treatment with virtual reality tools, digital platforms, educational animations, and biomedical protocols; improvements in emotion recognition, behavioral regulation, attention, and social functioning were found. Conclusions: While limited data prevent definitive conclusions, MPH and ATX appear to be relatively safe and effective on hyperactivity-impulsivity symptoms, even in individuals with ASD. Evidence on non-pharmacological treatments is limited, and further studies are needed to better establish their therapeutic potential.