Functional brain changes after alternative pharmacological interventions in posttraumatic 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 alternative pharmacological agents to treat PTSD, but their associated neural correlates remain unclear. The present systematic review aims to summarize the changes in brain function associated with the use of these alternative pharmacological agents in PTSD. Methods: Clinical trials using functional magnetic resonance imaging, either at rest or during the performance of tasks, were included if they compared the effects of alternative pharmacological agents between PTSD patients and either trauma-exposed controls or never-exposed healthy controls. Results: Sixteen studies were included, of which 11 used intranasal oxytocin, 2 used hydrocortisone, and 3 used delta-9-tetrahydrocannabinol (THC). Oxytocin administration was associated with the normalization 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), and reward (e.g., putamen). Hydrocortisone did not influence brain function at rest or during the performance of an autobiographical memory task, whereas THC was associated with the reduction of the amygdala and increased medial prefrontal cortex activation. Conclusions: This systematic review identified preliminary evidence for normalizing brain function after the use of alternative pharmacological agents. Importantly, sex-specific differences were noted, in particular when using oxytocin, that will require further investigation.