Efficacy of oxytocin administration early after psychotrauma in preventing the development of PTSD: study protocol of a randomized controlled trial

Abstract

BackgroundCurrently few evidence based interventions are available for the prevention of PTSD within the first weeks after trauma. Increased risk for PTSD development is associated with dysregulated fear and stress responses prior to and shortly after trauma, as well as with a lack of perceived social support early after trauma. Oxytocin is a potent regulator of these processes. Therefore, we propose that oxytocin may be important in reducing adverse consequences of trauma. The ‘BONDS’ study is conducted in order to assess the efficacy of an early intervention with intranasal oxytocin for the prevention of PTSD.Methods/DesignIn this multicenter double-blind randomized placebo-controlled trial we will recruit 220 Emergency Department patients at increased risk of PTSD. Trauma-exposed patients are screened for increased PTSD risk with questionnaires assessing peri-traumatic distress and acute PTSD symptoms within 7 days after trauma. Baseline PTSD symptom severity scores and neuroendocrine and psychophysiological measures will be collected within 10 days after trauma. Participants will be randomized to 7.5 days of intranasal oxytocin (40 IU) or placebo twice a day. Follow-up measurements at 1.5, 3 and 6 months post-trauma are collected to assess PTSD symptom severity (the primary outcome measure). Other measures of symptoms of psychopathology, and neuroendocrine and psychophysiological disorders are secondary outcome measures.DiscussionWe hypothesize that intranasal oxytocin administered early after trauma is an effective pharmacological strategy to prevent PTSD in individuals at increased risk, which is both safe and easily applicable. Interindividual and contextual factors that may influence the effects of oxytocin treatment will be considered in the analysis of the results.Trial registrationNetherlands Trial Registry: NTR3190.

Intranasal Oxytocin Affects Amygdala Functional Connectivity after Trauma Script-Driven Imagery in Distressed Recently Trauma-Exposed Individuals

“…Given that Paloyelis et al observed neural OT effects peaked between 39 and 51 min post administration and slowly attenuated onwards (Paloyelis et al, 2014), we explored correlations of duration between intranasal administration, scanning, and our observed neural effects in the OT group (see Supplementary Material). Participants who also enrolled in the randomized clinical trial on the efficacy of multiple OT intranasal doses for PTSD prevention (n = 23) (Frijling et al, 2014) were scanned after the first intranasal dose.…”

“…Acute distress was assessed using the Trauma Screening Questionnaire (TSQ; cutoff score ⩾ 5 (Mouthaan et al, 2014;Walters et al, 2007) and Peritraumatic Distress Inventory (PDI; cutoff score ⩾ 17 (Nishi et al, 2010) (see Frijling et al (2014) for details). Individuals with increased PTSD risk (ie, scoring above TSQ and/or PDI cutoff) were invited to participate.…”

“…Intranasal oxytocin (OT) administration has been proposed as a preventive intervention for PTSD (Frijling et al, 2014), based on animal studies suggesting that both endogenous OT release and central OT administration have anxiolytic effects by affecting amygdala functioning (Viviani and Stoop, 2008). OT's stimulatory effect on GABAergic interneurons in the lateral central amygdala inhibit medial central amygdala output to hypothalamic and brainstem nuclei, thereby modulating fear expression (Huber et al, 2005;Knobloch et al, 2012;Viviani et al, 2011).…”

Intranasal Drug Delivery in Neuropsychiatry: Focus on Intranasal Ketamine for Refractory Depression

“…29 Intranasal oxytocin is also being studied for the prevention of posttraumatic stress disorder in persons who experience trauma. 30 …”

Early interventions for the prevention of PTSD in adults: a systematic literature review

“…Possible investigation targets for future research include cannabinoid compounds, and especially cannabidiol (CBD), since this compound seems to play an important role in the blockade of the reconsolidation of aversive memories 41 . In addition, preclinical studies provide support for the test of oxytocin as a promising strategy in the prevention of PTSD-like manifestations 42 .…”