Stefania Chiappini ¹ Pietro Domenico Gramuglia ^1* Alessio Mosca ² Clara Cavallotto ² Andrea Miuli ² John Martin Corkery ³ Amira Guirguis ⁴ Fabrizio Schifano ³ Giovanni Martinotti ²

• ¹ Saint Camillus International University of Health and Medical Sciences, Rome, Italy
• ² Department of Neuroscience, Imaging and Clinical Sciences, University of Studies G. d'Annunzio Chieti and Pescara, Chieti, Italy
• ³ University of Hertfordshire, Hatfield, Herefordshire, United Kingdom
• ⁴ Swansea University, Swansea, Wales, United Kingdom

Methylphenidate (MPH), a central nervous system stimulant primarily prescribed for attention-deficit/hyperactivity disorder (ADHD), has seen increasing rates of misuse and abuse, particularly in patients with dual diagnosis (co-occurring psychiatric disorders and substance use disorders/SUDs). The heightened risk of dependence and adverse effects in these vulnerable populations warrants a systematic review to assess the prevalence and pattern of abuse/misuse of MPH among patients within this population and to understand risk factors, patterns of misuse, and outcomes, including the impact on psychiatric symptoms and mental health, the effects on SUD (e.g., exacerbation or mitigation of symptoms), and the incidence of adverse events and complications (e.g., cardiovascular issues, psychological effects).A systematic review was conducted in August-September 2024 using both PubMed and Scopus databases. The following search strategy was used: TITLE-ABS-KEY (methylphenidate OR Ritalin OR Concerta) AND TITLE-ABS-KEY (abuse OR misuse OR dependency OR addiction) AND TITLE-ABS-KEY (dual diagnosis OR comorbid psychiatric disorder OR psychiatric disorder AND substance use disorder). The systematic review was structured in accordance with the PRISMA guidelines and identified studies were assessed by title/abstract and full text screening against eligibility criteria. The research was registered on PROSPERO with ID: CRD42024576724.A total of 12 studies were selected for analysis after screening for relevance, quality, and adherence to inclusion criteria. Findings indicated that individuals with psychiatric disorders, particularly conduct disorder (N=593/1551 individuals), mood disorder (N=90/1551 individuals), anxiety disorder (N=66/ individuals), personality disorder (N=44/ individuals) and major depression disorder (N=40/ individuals), were more likely to misuse MPH. Co-occurring SUD, especially involving Alcohol Use Disorder (N=475), Cannabis Use Disorder (N=371/ individuals), Nicotine Use Disorder (N=343/ individuals), Cocaine Use Disorder (N=68/ individuals), significantly elevated the risk. Misuse often involved higher doses than prescribed (N=84/ individuals) or using non-oral routes of administration (N=20/ individuals; e.g., snorting). Adverse outcomes included heightened risk of gastrointestinal events (N=201/ individuals), cardiovascular events (N=108/ individuals), psychosis (N=69/ individuals), and exacerbation of psychiatric symptoms (N=1082).MPH misuse and abuse are significant concerns in patients with dual diagnosis. Risk factors include impulsivity, history of substance abuse, and access to prescription stimulants. Integrated therapeutic approaches and stricter prescription monitoring are recommended to mitigate misuse risks.