Abstract
BackgroundPosttraumatic 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.MethodsTo 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).ResultsIntranasal 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.ConclusionsThis 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.
Highlights
Posttraumatic stress disorder (PTSD) is a severe psychiatric disease accompanied by neuroendocrine changes such as adrenergic overdrive and an elevated cardiovascular morbidity
Oxytocin acts through the oxytocin receptor (OTX) [4], which is expressed for instance in the amygdala and the anterior cingulate cortex [5], two brain regions known to be involved in the pathobiology of stress-related psychiatric diseases such as PTSD [3]
Besides the positive chronotropic effect of oxytocin treatment, we did not observe any other unintended effect or harm of treatment. This is the first study assessing the effects of oxytocin on the intensity of provoked PTSD symptoms in female PTSD patients and, to the best of our knowledge, the second symptom provocation study analyzing the efficacy of oxytocin in PTSD patients ever
Summary
Posttraumatic stress disorder (PTSD) is a severe psychiatric disease accompanied by neuroendocrine changes such as adrenergic overdrive and an elevated cardiovascular morbidity. There is an unmet need for the development of drugs tackling the core symptoms of this trauma spectrum disorder [6], which are hyperarousal, aversive re-experiencing, emotional numbing and avoidance anxiety, because 20–30% of PTSD patients do not respond at all to treatment with the current gold standard of PTSD drug therapy, the serotonin re-uptake inhibitors [7] Among other neuropeptides such as neuropeptide S (NPS) [8] and neuropeptide Y (NPY) [8, 9], oxytocin has been repeatedly suggested to be effective in PTSD treatment [3, 9]
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