Several studies have demonstrated the neuromodulating function of oxytocin (OT) in response to anxiogenic stimuli as well as its potential role in the pathogenesis of depression. Consequently, intranasal OT (IN-OT) has been proposed as a potential treatment of anxiety and depressive disorders. The present systematic review aimed to summarize the randomized controlled trials (RCTs) evaluating the effect of IN-OT on anxiety and depressive symptoms. Overall, 15 studies were included, involving patients with social anxiety disorders (7 studies), arachnophobia (1), major depression (3) or post-natal depression (4), and mainly evaluating single-dose administrations of IN-OT. Results showed no significant effects on core symptomatology. Five crossover studies included functional magnetic resonance imaging investigation: one trial showed reduced amygdala hyper-reactivity after IN-OT in subjects with anxiety, while another one showed enhanced connectivity between amygdala and bilateral insula and middle cingulate gyrus after IN-OT in patients but not in healthy controls. More studies are needed to confirm these results. In conclusion, up to date, evidence regarding the potential utility of IN-OT in treating anxiety and depression is still inconclusive. Further RCTs with larger samples and long-term administration of IN-OT are needed to better elucidate its potential efficacy alone or in association with standard care.
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