{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T01:20:53Z","timestamp":1783473653028,"version":"3.55.0"},"reference-count":71,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aripiprazole as a long-acting injectable (LAI) is initiated in oral aripiprazole-stabilised patients and needs, after first injection, 14 days supplementation of oral aripiprazole (one-injection start, OIS). Recently, an alternative two-injection start (TIS) was advanced, involving two 400 mg injections with a single 20 mg oral supplementation of aripiprazole. We tested the two regimens in patients with schizophrenia (SCZ, n = 152, 90 men and 62 women) with (SUD+; n = 93) or without (SUD\u2013; n = 59) substance use disorders (SUDs), comparing OIS (n = 66) with TIS (n = 86) and SUD+ vs. SUD\u2013. For 26 patients, we measured weekly for one month, aripiprazole + dehydroaripiprazole (active moiety) levels. Patients were followed for three months after LAI with psychopathology and quality-of-life scales (BPRS, CGI-S, ACES, BIS-11, and WHOQOL). All groups improved in psychopathology with no differences between OSI and TIS and between SCZ\u2013SUD+ and SCZ\u2013SUD\u2013. The TIS group was associated with serum blood levels of the active moiety within the therapeutic window, while the OIS group showed peaks above the window, possibly exposing patients to toxicity. Treatments were well-tolerated. Here we showed no disadvantages for TIS vs. OIS and possibly increased safety. Shifting the initiation of aripiprazole LAIs to the TIS modality may be safe and pharmacokinetically advantageous.<\/jats:p>","DOI":"10.3390\/ijms26031394","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T04:00:28Z","timestamp":1738900828000},"page":"1394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Optimising Aripiprazole Long-Acting Injectable: A Comparative Study of One- and Two-Injection Start Regimens in Schizophrenia with and Without Substance Use Disorders and Relationship to Early Serum Levels"],"prefix":"10.3390","volume":"26","author":[{"given":"Giada","family":"Trovini","sequence":"first","affiliation":[{"name":"Clinica Villa von Siebenthal Neuropsychiatric Hospital, Via della Madonnina 1, 00040 Rome, Italy"},{"name":"Department of Molecular and Developmental Medicine, Division of Psychiatry, School of Medicine, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7039-1820","authenticated-orcid":false,"given":"Ginevra","family":"Lombardozzi","sequence":"additional","affiliation":[{"name":"Clinica Villa von Siebenthal Neuropsychiatric Hospital, Via della Madonnina 1, 00040 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios D.","family":"Kotzalidis","sequence":"additional","affiliation":[{"name":"Clinica Villa von Siebenthal Neuropsychiatric Hospital, Via della Madonnina 1, 00040 Rome, Italy"},{"name":"Department of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, LargoAgostino Gemelli 8, 00168 Rome, Italy"},{"name":"Department of Neuroscience, Section of Psychiatry, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana","family":"Lionetto","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry, Mass Spectrometry Section, Sant\u2019Andrea University Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2306-6830","authenticated-orcid":false,"given":"Felicia","family":"Russo","sequence":"additional","affiliation":[{"name":"SPDC DSM ASL BA (SPDC Ospedale Santa Maria Degli Angeli), P.za Padre Pio 21, 70017 Putignano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5553-648X","authenticated-orcid":false,"given":"Angela","family":"Sabatino","sequence":"additional","affiliation":[{"name":"DSM ASL Viterbo Distretto C (CSM Civita Castellana), via Francesco Petrarca snc, 01033 Civita Castellana, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elio","family":"Serra","sequence":"additional","affiliation":[{"name":"Azienda Sanitaria Locale Lecce, UOC CSM Nard\u00f2, Via XXV Luglio, 4, 73048 Nard\u00f2, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1204-3282","authenticated-orcid":false,"given":"Simone","family":"Castorina","sequence":"additional","affiliation":[{"name":"Clinica Villa von Siebenthal Neuropsychiatric Hospital, Via della Madonnina 1, 00040 Rome, Italy"},{"name":"Department of Mental, Neurological, Dental and Sensory Organ Wellbeing, Fondazione PTV\u2014Policlinico Tor Vergata, Tor Vergata University Hospital, Viale Oxford, 81, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Civita","sequence":"additional","affiliation":[{"name":"Clinica Villa von Siebenthal Neuropsychiatric Hospital, Via della Madonnina 1, 00040 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Frezza","sequence":"additional","affiliation":[{"name":"Clinica Villa von Siebenthal Neuropsychiatric Hospital, Via della Madonnina 1, 00040 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"De Bernardini","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry, Mass Spectrometry Section, Sant\u2019Andrea University Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Costanzi","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry, Mass Spectrometry Section, Sant\u2019Andrea University Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Alborghetti","sequence":"additional","affiliation":[{"name":"Clinica Villa von Siebenthal Neuropsychiatric Hospital, Via della Madonnina 1, 00040 Rome, Italy"},{"name":"Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, University of Rome \u201cLa Sapienza\u201d, Via di Grottarossa 1035-1039, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Simmaco","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry, Mass Spectrometry Section, Sant\u2019Andrea University Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy"},{"name":"Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, University of Rome \u201cLa Sapienza\u201d, Via di Grottarossa 1035-1039, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinando","family":"Nicoletti","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cVittorio Erspamer\u201d, Faculty of Medicine and Pharmacy, University of Rome \u201cLa Sapienza\u201d, Piazzale Aldo Moro 5, 00185 Rome, Italy"},{"name":"IRCCS Neuromed, Pozzilli, Via Atinense, 18, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"De Filippis","sequence":"additional","affiliation":[{"name":"Clinica Villa von Siebenthal Neuropsychiatric Hospital, Via della Madonnina 1, 00040 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5319","DOI":"10.1038\/s41380-023-02138-4","article-title":"Incidence, prevalence, and global burden of schizophrenia\u2014Data, with critical appraisal, from the Global Burden of Disease (GBD) 2019","volume":"28","author":"Solmi","year":"2023","journal-title":"Mol. 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