107 JOURNAL OF PSYCHOPATHOLOGY 2020;26:107-118; doi: 10.36148/2284-0249-370 Received: December 20, 2019 Accepted: January 15, 2020 Correspondence Giorgio Di Lorenzo Department of Systems Medicine, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome E-mail: di.lorenzo@med.uniroma2.it Confict of interest The Authors declare no conflict of interest How to cite this article: Di Lorenzo G, Longo L, Jannini TB, et al. Oxytocin in the prevention and the treatment of post- traumatic stress disorder: a systematic review of randomized controlled trials. Journal of Psychopathology 2020;26:107-18. https:// doi.org/10.36148/2284-0249-370 © Copyright by Pacini Editore Srl OPEN ACCESS This is an open access Journal distributed in accord- ance with the Creative Commons Attribution Non Com- mercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non- commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http:// creativecommons.org/licenses/by-nc/4.0/ Review Giorgio Di Lorenzo 1,2 , Lucia Longo 1,2 , Tommaso B. Jannini 1,2 , Cinzia Niolu 1,2 , Rodolfo Rossi 1 , Alberto Siracusano 1,2 1 Chair of Psychiatry, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; 2 Psychiatry and Clinical Psychology Unit, Fondazione Policlinico Tor Vergata, Rome, Italy Oxytocin in the prevention and the treatment of post-traumatic stress disorder: a systematic review of randomized controlled trials SUMMARY Recent evidences are revealing the role of oxytocin in the pathophysiology of post-traumatic stress disorder (PTSD) and its possible application in prevention and the treatment of PTSD. Aim of the present article is to provide a systematic review of randomized controlled trials (RCT) of clinical effects of oxytocin in PTSD and trauma-related disorders was conducted. Only six articles were selected after applying the inclusion and exclusion criteria. We compared acute and long clinical effects of oxytocin administration on acute trauma symptomatology and PTSD. The acute clinical effects of oxytocin remain unclear, despite some studies show a reduction of global or single cluster of PTSD and of others clinical symptomatology. The long clinical effects of oxytocin administration show a non-statistically reduction of PTSD, although effect of oxytocin seem to be correlated to the severity on acute PTSD symptom. In fact, the presence of high acute PTSD symptoms showed significantly lower PTSD symptom severity across follow-up, indicating a long-term protective effect of oxytocin administration. Future clinical studies, with accurate psychopathological assessments and a structured clinical follow-up, are mandatory to understand the clinical efficacy of oxytocin administration in patients with PTSD or in patients with acute distress and an increasing risk in developing PTSD. Key words: oxytocin, post-traumatic stress disorder, trauma-related disorder, psychopharmacology, treatment Introduction Post-traumatic stress disorder (PTSD) is an invalidating psychiatric illness caused by psychological trauma, with aberrantly consolidated and persistent traumatic memories, and failing in fear extinction  1 . Despite psychological traumatic experiences are common in the general population, the prevalence of trauma-related disorders, including PTSD, is relatively low, around to 2 to 6%, expect for veteran population where the percentage reaches 30%  2 . The clinical picture in PTSD is heterogeneous, mainly characterized by re- experiencing phenomena of traumatic experience, avoidance thoughts and behaviours, hyperarousal symptoms, emotional mumbling, cognitive impairment and, sometimes, severe dissociative symptoms, self-harm and suicidality  3-7 . The psychotherapeutic approaches are relevant in alleviating of psychopathology of trauma-related disorders and PTSD  2,8 . However, psychopharmacological treatment has a relevant role in managing the PTSD symptoms  9 . Several neurobiological mechanisms are implicated in the PTSD pharmacological strategies  10 . Recent evidences are revealing the role of oxytocin (OXT) in the pathophysiology of PTSD and its possible application in prevention and