{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:51:44Z","timestamp":1791413504878,"version":"4.3.3"},"reference-count":72,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Attention-Deficit\/Hyperactivity Disorder (ADHD) in adults is frequently accompanied by psychiatric comorbidities that worsen outcomes and complicate treatment. Pharmacological management is central in care, yet its impact on co-occurring disorders remains uncertain. This systematic review evaluated the effectiveness of commonly prescribed medications for adult ADHD (methylphenidate, atomoxetine, bupropion, and lisdexamfetamine) on comorbid mood, anxiety, personality, and substance use disorders. Tricyclic antidepressants were also included in the search strategy; however, no eligible adult studies assessing imipramine or desipramine in patients with ADHD and psychiatric comorbidity were identified. Methods: A systematic search of the literature was conducted to identify studies examining these medications in adults with ADHD and at least one psychiatric comorbidity. Eligible studies reported clinical outcomes for both ADHD symptoms and the co-occurring disorder. Data were extracted and narratively synthesized, with particular attention paid to treatment effects and sources of heterogeneity. Results: Across the included studies, pharmacological treatments consistently improved core ADHD symptomatology. Their effects on psychiatric comorbidity were more variable. Some evidence suggested beneficial outcomes for selected anxiety disorder subtypes and for features of Cluster B personality disorders, possibly related to reductions in emotional dysregulation and impulsivity. Findings regarding substance use disorders were mixed: several studies reported reduced craving or substance use, but long-term stabilization was inconsistent. Marked heterogeneity in study design, populations, and outcome measures limited comparability. Conclusions: Current pharmacological treatments for adult ADHD show reliable efficacy for core symptoms but inconsistent benefits across comorbid psychiatric conditions. While targeted improvements may occur in specific domains, the evidence base is insufficient to define optimal long-term strategies for adults with ADHD and complex comorbidity. Rigorous, longitudinal studies are needed to clarify medication effects on distinct comorbid profiles and to inform integrated treatment planning.<\/jats:p>","DOI":"10.3390\/jcm14248848","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T09:57:24Z","timestamp":1765879044000},"page":"8848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effectiveness of Pharmacological Treatments for Adult ADHD on Psychiatric Comorbidity: A Systematic Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2184-5240","authenticated-orcid":false,"given":"Beniamino","family":"Tripodi","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, Division of Psychiatry, University of Insubria, Viale Luigi Borri 57, 21100 Varese, VA, Italy"},{"name":"Department of Clinical and Experimental Medicine, Division of Psychiatry, University of Pisa, Via Roma 57, 56100 Pisa, PI, Italy"},{"name":"Department of Mental Health and Addictions, Division of Psychiatry, ASST Crema, Via Largo Ugo Dossena 2, 26013 Crema, CR, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7457-6008","authenticated-orcid":false,"given":"Manuel Glauco","family":"Carbone","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Division of Psychiatry, University of Insubria, Viale Luigi Borri 57, 21100 Varese, VA, Italy"},{"name":"Department of Clinical and Experimental Medicine, Division of Psychiatry, University of Pisa, Via Roma 57, 56100 Pisa, PI, Italy"},{"name":"VP Dole Research Group, G. De Lisio Institute of Behavioural Sciences, Via di Pratale, 3, 56121 Pisa, PI, Italy"},{"name":"Departmental Faculty of Medicine, Saint Camillus International University of Health and Medical Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, RM, Italy"},{"name":"Addiction Research Methods Institute, World Federation for the Treatment of Opioid Dependence, 225 Varick Street, Suite 402, New York, NY 10014, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Matarese","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Molecular and Critical Area Pathology, Clinical and Health Psychology, University of Pisa, Via Roma 57, 56100 Pisa, PI, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Rizzato","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Division of Psychiatry, University of Insubria, Viale Luigi Borri 57, 21100 Varese, VA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7935-3524","authenticated-orcid":false,"given":"Filippo","family":"Della Rocca","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Division of Psychiatry, University of Pisa, Via Roma 57, 56100 Pisa, PI, Italy"},{"name":"VP Dole Research Group, G. De Lisio Institute of Behavioural Sciences, Via di Pratale, 3, 56121 Pisa, PI, Italy"},{"name":"Departmental Faculty of Medicine, Saint Camillus International University of Health and Medical Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, RM, Italy"},{"name":"Addiction Research Methods Institute, World Federation for the Treatment of Opioid Dependence, 225 Varick Street, Suite 402, New York, NY 10014, USA"},{"name":"Addiction Unit, Department of Mental Health and Addictions, ASL5 Liguria NHS, Via Dalmazia 1, 19124 La Spezia, SP, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"De Dominicis","sequence":"additional","affiliation":[{"name":"Department of Mental Health, Division of Psychiatry, U.S.L. Umbria 2, Via San Carlo 3, 06049 Spoleto, PG, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0624-9988","authenticated-orcid":false,"given":"Camilla","family":"Callegari","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Division of Psychiatry, University of Insubria, Viale Luigi Borri 57, 21100 Varese, VA, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,14]]},"reference":[{"key":"ref_1","unstructured":"(2013). Diagnostic and Statistical Manual of Mental Disorders: DSM-5\u2122, American Psychiatric Publishing, Inc.. [5th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Cristofani, C., Sesso, G., Cristofani, P., Fantozzi, P., Inguaggiato, E., Muratori, P., Narzisi, A., Pfanner, C., Pisano, S., and Polidori, L. (2020). 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