Medical Nitrous Oxide Combined With Personalized Traumatic Script Exposure for the Treatment of Post-Traumatic Stress Disorder

The goal of this double-blind randomized controlled superiority clinical trial is to evaluate whether medical nitrous oxide/oxygen premix (MEOPA), combined with exposure to a personalized traumatic script, can improve symptoms of posttraumatic stress disorder (PTSD) in adults with treatment-resistant PTSD related to interpersonal violence. The main questions it aims to answer are: 1. Does MEOPA combined with traumatic script exposure reduce PTSD symptom severity, as measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), compared with medical air combined with traumatic script exposure? 2. Does MEOPA improve associated symptoms and functioning, including depression, anxiety, dissociation, and functional impairment, while maintaining an acceptable safety profile? Researchers will compare participants receiving MEOPA plus traumatic script exposure with participants receiving medical air plus traumatic script exposure to determine whether MEOPA enhances the therapeutic effects of trauma-focused re-exposure. Participants will: * Attend a screening and baseline assessment visit. * Complete clinician-administered and self-reported questionnaires assessing PTSD symptoms, depression, anxiety, dissociation, suicidality, and functional impairment. * Write a personalized traumatic script based on their traumatic experience. * Be randomized to receive either MEOPA or medical air. * Undergo four weekly treatment sessions consisting of inhalation of the assigned gas combined with exposure to their personalized traumatic script. * Attend follow-up visits at 1, 3, 6, and 9 months after treatment for evaluation of efficacy and safety outcomes.

Inclusion Criteria: * Age 18 - 65 * Patient with PTSD who has failed to respond to at least one therapeutic approach, psychotherapy or treatment with an SSRI * Nature of the traumatic event: interpersonal violence, including sexual, physical and psychological abuse * PTSD as defined by the DSM-5, with symptoms present for more than 6 months * CAPS-5 score ≥35 * Participant who can receive MEOPA or medical oxygen through a face mask * French-speaking * Social security affiliation * Signed consent * A suitable method of contraception for women of childbearing age Exclusion Criteria: * Current substance use disorders or history of substance use disorder. * Psychotic, bipolar, dissociative identity, or eating disorders. \* suicidal risque with C-SSR score ≥4 * Pregnancy and/or breastfeeding. * Patients subject to legal guardianship and/or other circumstances rendering the patient unable to understand the nature, purpose or consequences of the study. * Contraindication to the use of MEOPA and any condition where air is trapped inside the body and where its expansion could be dangerous: pneumothorax, emphysema, intestinal obstruction, intracranial hypertension, known and untreated deficiency of vitamin B12 or B9 (based on a test result less than 1 month old), Patients requiring ventilation with pure oxygen; any impairment of consciousness preventing patient cooperation; head injury; Gas embolism; Diving accident; Abdominal gas distension; Patient who has recently received an ophthalmic gas (SF6, C3F8, C2F6) used in eye surgery (as long as a gas bubble persists inside the eye and for a minimum period of 3 months), neurological abnormalities of recent or non-recent onset. * Sub-physiological plasma concentration of vitamin B12 or B9 (below the lower limit of the laboratory's reference range). * Supraphysiological plasma concentration of homocysteine (above the upper limit of the laboratory's reference range).