NCT02637895.

Methods	Vortioxetine for posttraumatic stress disorder Study type: Interventional Study phase: Phase 4 Allocation: Randomised Intervention model: Parallel assignment Masking: quadruple (participant, care provider, investigator, outcomes assessor) Primary purpose: Treatment
Participants	Inclusion: Men and women between the ages of 18 and 65; Fulfill Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM‐5) criteria for primary diagnosis of PTSD; Able to give consent; Willingness to sign the treatment contract; a negative urine toxicology; for women of reproductive age, use of an effective birth control method* for the duration of the study or abstinence; Duration of illness of PTSD for at least 3 months; An initial score at screening, and visit 3 (randomisation) of ≥ 50 on the CAPS for PTSD Studies Exclusion: Lifetime or current diagnosis of schizophrenia or other psychotic disorder, dementia, bipolar disorder; person is currently participating in another clinical trial in which s/he is or will be exposed to an investigational or non‐investigational drug or device, or has done so within the preceding month; current evidence or history of significant unstable medical illness or organic brain impairment, including stroke, Central Nervous System (CNS) tumour, demyelinating disease, cardiac, pulmonary, gastrointestinal, renal or hepatic impairment that would likely interfere with the action, absorption, distribution, metabolism, or excretion of Vortioxetine. History of moderate or more severe Traumatic Brain Injury (TBHI) will also be exclusionary; People who in the investigator's judgment pose a current suicidal or homicidal risk; DSM‐5 substance abuse or dependence within the past 90 days. Person has a positive urine toxicology test for illegal substances; diagnosis of anorexia nervosa, bulimia, or Obsessive Compulsive Disorder (OCD) in the past year; person has a documented history of hepato‐biliary disease including a history of, or positive laboratory results for hepatitis (hepatitis B surface antigen and/or hepatitis C antibody), and clinically significant hepatic enzyme elevation, including any one of the following enzymes greater than 3 times the upper limit of normal (ULN) value (ALT, AST, ALP), or total or direct bil > 1.5 x ULN, unless consistent with presumed or diagnosed Gilbert's disease; person has taken systemic corticosteroids within 2 weeks of the randomisation visit; treatment with any other psychoactive medication within 2 weeks of visit 1, including all antidepressants, psychoactive herbal or nutritional treatments (St Johns Wort, SAM‐e), lithium, other mood stabilisers, oral antipsychotics, depot antipsychotics within 12 weeks, beta blockers, thioridazine, pimozide, opiates, anxiolytics, and sedatives (with the exception of zolpidem, eszopiclone, and zaleplon). Also any treatment with any medication that the PI judges not acceptable for this study; Pregnancy or lactation*; people who, in the opinion of the investigator, would be noncompliant with the visit schedule or study procedures (e.g. illiteracy, planned vacations, or planned hospitalisations during the study); any laboratory abnormality that in the investigator's judgement is considered to be clinically significant; People who are receiving exposure‐based psychotherapy that targets PTSD symptoms; Current or planned litigation or other actions related to secondary gain regarding the traumatic event; person has clinical evidence of, or ElectroCardiogram (ECG) results indicating any of the following at either screen or randomisation visit unless repeat ECG shows that the parameter had returned to within normal range by the randomisation visit: QTc > 450 msec for men, or > 475 msec for women;any cardiac condition or ECG evidence that the investigator feels may pose a potential safety concern
Interventions	Placebo comparator: Placebo; placebo pill once daily for 12 weeks of active treatment Intervention: drug: placebo Active comparator: Vortioxetine Vortioxetine pill 10 mg once daily up to 4 weeks followed by 20 mg once daily if tolerated for the rest of the study. Patients unable to tolerate the 20 mg/day dose may be reduced to 10 mg/day between weeks 4 and 8. The dose of study medication should remain stable for weeks 8 ‐ 12 Intervention: Drug: Vortioxetine
Outcomes	Primary outcome measures: An improved PTSD scale score (Time frame: from baseline to week 12). Mean changes in the Clinician‐Administered PTSD Scale (CAPS) Secondary outcome measures: A 50% improved overall response rate on a PTSD scaled score. (Time frame: from baseline to week 12). 50% improvement from baseline in the Clinically‐Administered PTSD Scale (CAPS) Reduction in depressive symptoms in PTSD (Time frame: from baseline to week 12). Determined by mean changes by the Montgomery‐Asberg Depression Rating Scale (MADRS) 50% improvement in CGI‐Score (Time frame: from baseline to week 12). 50% improvement in Clinical Global Impression of Improvement (CGI‐I) score of 1 or 2
Notes	Starting date: December 2016 Contact information: Principal investigator: Philip Harvey, PhD., University of Miami Responsible parties: University of Miami, Takeda, Emory University Estimated primary completion date: May 2019 Estimated study completion date: July 2019