Effects of Intranasal Oxytocin Across Various Depressive Disorders

Objective Depression is a prevalent psychiatric disorder posing significant global public health challenges. Although traditional antidepressants are widely used, their full therapeutic effects typically require prolonged administration, which may compromise patient outcomes. To enhance treatment efficacy and patient well-being, identifying rapidly acting and safe therapeutic agents is critical. Oxytocin, an endocrine polypeptide hormone, has shown therapeutic potential in depression by modulating physiological, cognitive, and social behaviors via central and peripheral mechanisms. Methods This review was conducted using the PubMed and Web of Science databases without time restrictions. It provides the first systematic synthesis of empirical evidence on the oxytocin’s therapeutic efficacy across depressive disorders, comprehensively describes its potential neurobiological targets, and rigorously evaluates its therapeutic mechanisms. Data from randomized controlled trials were analyzed to assess the clinical feasibility and scientific validity of oxytocin. Results Evidence from included studies suggested that oxytocin enhanced maternal perception of infants in females with postpartum depression, although its impact on maternal mood was inconsistent. Oxytocin demonstrated efficacy as an adjunctive therapy to psychotherapy or pharmacotherapy in major depressive disorder and treatment-resistant depression. Additionally, studies identified sex differences in oxytocin’s antidepressant effects. Conclusion The present study provides a comprehensive summary of oxytocin’s antidepressant effects, offers new insights into its use for treating diverse subtypes of depression, and presents useful guidance for developing evidence-based depression treatment protocols.