Functional brain changes after pharmacological interventions in post-traumatic stress disorder: A systematic review of clinical trials

Background Posttraumatic stress disorder (PTSD) is a complex and heterogeneous mental health condition that can develop after exposure to a traumatic event. Clinical trials have used new pharmacological agents to treat PTSD, but their associated neural correlates remain unclear. The present systematic review aims to summarise the changes in brain function associated with the use these pharmacological agents in PTSD. Methods Clinical trials using functional magnetic resonance imaging (fMRI), either at rest or during the performance of tasks, were included if they compared the effects of pharmacological agents in patients with PTSD to either trauma-exposed controls or never exposed to trauma healthy controls. Results Twelve studies were included, of which eight used intranasal oxytocin, two used hydrocortisone, and one used Tolcapone. Oxytocin administration was associated with normalisation of functional connectivity between the ventromedial prefrontal cortex and amygdala, as well as enhanced the function of brain regions specifically involved in emotion processing (e.g., amygdala), working memory (e.g., dorsolateral prefrontal cortex), reward (putamen). Hydrocortisone did not influence brain function at rest or during the performance of an autobiographical memory task, while tolcapone was associated with increased function in frontal, parietal and striatal regions during the performance of an emotional working memory task. Conclusions This systematic review identified preliminary evidence for normalizing brain function after use of alternative pharmacological agents to first-line pharmacological treatments.