Could intranasal oxytocin enhance the effects of psychotherapy in individuals with mental disorders? A systematic review and meta-analysis

Interest in the therapeutic potential of oxytocin for the treatment of mental health disorders, especially those involving social dysfunction, has increased considerably in recent years. To date, most studies have only evaluated oxytocin as monotherapy, with highly inconsistent results. A new line of research is exploring the effects of combining oxytocin with psychotherapy. The aim of the present review was to evaluate the therapeutic effects of intranasal oxytocin combined with psychotherapy in individuals with psychiatric disorders. Only randomized clinical trial design was eligible for inclusion. A search of relevant databases yielded 2480 articles published through April 30, 2024. Of these, 13 trials (518 participants) were included in this review and 4 of them in a meta-analysis. The trials evaluated a range of different psychotherapeutic interventions, oxytocin doses, and mental disorders. Overall, the trials suggested that combined treatment reduced negative mental representations, decreased stress, and increased therapeutic alliance. Meta-analysis showed that combined treatment significantly reduced depressive symptoms (d= −1.58, 95 % CI: −3.15 to −0.01). However, the treatment with oxytocin had no significant effects on psychiatric symptoms (d= 0.00, 95 % CI: −0.56–0.57) or social functioning (d = 0.21, 95 % CI: −0.07–0.49). Limitations included the heterogeneity and limited sample sizes of the trials. The findings suggest that the combination of intranasal oxytocin and psychotherapy may be an effective therapeutic approach to reduce depressive symptoms in individuals with mental disorders and may improve retention and therapeutic alliance.