title: Intranasal oxytocin reduces provoked symptoms in female patients with posttraumatic stress disorder despite exerting sympathomimetic and positive chronotropic effects in a randomized controlled trial.
abstract: BACKGROUND
  Posttraumatic stress disorder (PTSD) is a severe psychiatric disease accompanied by neuroendocrine changes such as adrenergic overdrive and hence an elevated cardiovascular morbidity. Current pharmacotherapeutic options for PTSD are less than suboptimal, necessitating the development of PTSD-specific drugs. Although the neuropeptide oxytocin has been repeatedly suggested to be effective in PTSD treatment, there are, to our knowledge, only three studies that have assessed its efficacy on the intensity of PTSD symptoms in PTSD patients - among them one symptom provocation study in male veterans.
  
  
  METHODS
  To evaluate for the first time how oxytocin influences the intensity of provoked PTSD symptoms and, furthermore, cardiac control in female PTSD patients, we assessed their psychic and cardiac response to trauma-script exposure with and without oxytocin pretreatment in a double-blind randomized placebo-controlled study. We used a within-subject design to study 35 female PTSD patients who received oxytocin and placebo in a 2-week interval. Furthermore, we performed a small pilot study to get an idea of the relation of the stress-modulated endogenous oxytocin levels and heart rate - we correlated oxytocin serum levels with the heart rate of 10 healthy individuals before and after exposure to the Trier Social Stress Test (TSST).
  
  
  RESULTS
  Intranasal oxytocin treatment was followed by a reduction of provoked total PTSD symptoms, in particular of avoidance, and by an elevation in baseline and maximum heart rate together with a drop in the pre-ejection period, a marker for sympathetic cardiac control. Furthermore, we found a positive correlation between endogenous oxytocin levels and heart rate both before and after TSST challenge in healthy control subjects.
  
  
  CONCLUSIONS
  This study provides the first evidence that oxytocin treatment reduces the intensity of provoked PTSD symptoms in female PTSD patients. The small size of both samples and the heterogeneity of the patient sample restrict the generalizability of our findings. Future studies have to explore the gender dependency and the tolerability of the oxytocin-mediated increase in heart rate. This randomized controlled trial was retrospectively registered at the German Trials Register (DRKS00009399) on the 02 October 2015.
authors.affiliation: Technische Universität München, Klinikum rechts der Isar, Department of Psychosomatic Medicine and Psychotherapy, Langerstr. 3, 81675, München, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Sack
authors.affiliation: Technische Universität München, Klinikum rechts der Isar, Department of Psychosomatic Medicine and Psychotherapy, Langerstr. 3, 81675, München, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Spieler
authors.affiliation: Technische Universität München, Klinikum rechts der Isar, Department of Psychosomatic Medicine and Psychotherapy, Langerstr. 3, 81675, München, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Wizelman
authors.affiliation: Technische Universität München, Klinikum rechts der Isar, Department of Psychosomatic Medicine and Psychotherapy, Langerstr. 3, 81675, München, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Epple
authors.affiliation: Max Planck Institute of Psychiatry, Department of Clinical Research, RG Molecular Psychotraumatology & Trauma Outpatient Clinic, Kraepelinstrasse 10, 80804, München, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Stich
authors.affiliation: Max Planck Institute of Psychiatry, Department of Clinical Research, RG Molecular Psychotraumatology & Trauma Outpatient Clinic, Kraepelinstrasse 10, 80804, München, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zaba
authors.affiliation: Max Planck Institute of Psychiatry, Department of Clinical Research, RG Molecular Psychotraumatology & Trauma Outpatient Clinic, Kraepelinstrasse 10, 80804, München, Germany. uschmidt@psych.mpg.de.
authors.forename: U
authors.initials: U
authors.lastname: Schmidt
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010121:Oxytocin / Q000627:therapeutic use*; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy*; D013566:Sympathomimetics; D016896:Treatment Outcome
chemical_list: D013566:Sympathomimetics; D010121:Oxytocin
keywords: Intranasal pharmacotherapy; Oxytocin; PTSD; Psychophysiology; Randomized controlled trial (RCT); Script-driven trauma imagery; Symptom provocation study; Trier Social Stress Test (TSST)