{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:44:24Z","timestamp":1788867864847,"version":"build-2803163510"},"reference-count":94,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health, Italy, Current Research Funds","award":["2025"],"award-info":[{"award-number":["2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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 &lt;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\u2019 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.<\/jats:p>","DOI":"10.3390\/jcm14114000","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T11:04:06Z","timestamp":1749121446000},"page":"4000","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Children and Adolescents with Co-Occurring Attention-Deficit\/Hyperactivity Disorder and Autism Spectrum Disorder: A Systematic Review of Multimodal Interventions"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8868-8485","authenticated-orcid":false,"given":"Carmela","family":"De Domenico","sequence":"first","affiliation":[{"name":"I.R.C.C.S. Centro Neurolesi Bonino Pulejo, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6609-579X","authenticated-orcid":false,"given":"Angelo","family":"Alito","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Dental Sciences and Morphological and Functional Images, University Hospital \u201cG. Martino\u201d, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9532-0220","authenticated-orcid":false,"given":"Giulia","family":"Leonardi","sequence":"additional","affiliation":[{"name":"Department of Physical and Rehabilitation Medicine, University Hospital \u201cG. Martino\u201d, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Pironti","sequence":"additional","affiliation":[{"name":"Woman-Child Department, Unit of Child Neurology and Psychiatry, Policlinico Riuniti Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4275-4340","authenticated-orcid":false,"given":"Marcella","family":"Di Cara","sequence":"additional","affiliation":[{"name":"I.R.C.C.S. Centro Neurolesi Bonino Pulejo, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Piccolo","sequence":"additional","affiliation":[{"name":"I.R.C.C.S. Centro Neurolesi Bonino Pulejo, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9643-349X","authenticated-orcid":false,"given":"Carmela","family":"Settimo","sequence":"additional","affiliation":[{"name":"I.R.C.C.S. Centro Neurolesi Bonino Pulejo, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Quartarone","sequence":"additional","affiliation":[{"name":"I.R.C.C.S. Centro Neurolesi Bonino Pulejo, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Child and Adolescent Neuropsychiatry, Department of Medicine and Surgery, \u201cKore\u201d University of Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8477-7826","authenticated-orcid":false,"given":"Francesca","family":"Cucinotta","sequence":"additional","affiliation":[{"name":"I.R.C.C.S. Centro Neurolesi Bonino Pulejo, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders., American Psychiatric Publishing. 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