To the Editor: Oxytocin (OT) is, first, a hormone synthesized in the hypothalamus and released by the neurohypophysis, but OT is also involved in the regulation of emotions, and OT receptors are distributed in various brain regions, including the limbic system and amygdala. There is much data suggesting a role for OT as an endogenous antidepressant/anxiolytic hormone and there is support for the idea that stimulation of OT receptors inhibits the hypothalamo-pituitary-adrenal (HPA) axis. The pathophysiology of stress-related diseases, such as depression or anxiety disorders, includes both endogenous/genetic predisposing factors and a dysregulated response to stress, and efficiency of antidepressants involves normalization of HPA-axis abnormalities.

RX is a 38-year-old man with a 15-year history of major depressive disorder without psychotic features. His depression severely worsened over a 5-year period despite various antidepressant treatments (tricyclics, serotonin reuptake inhibitors, and serotonin-noradrenaline reuptake inhibitors). He also received benzodiazepines and amisulpride without clinical success. His current treatment involves escitalopram 20 mg. After he gave full informed consent, intranasal synthetic OT (Syntocinon^®, 1 puff per nostril each with 4 U.I., twice daily; Novartis Pharmaceuticals Corporation, Switzerland) was added. Initial severity of depression was scored at 17 on the Hamilton Rating Scale for Depression (Ham-D), and anxiety reached 57 on the Spielberger State-Anxiety Inventory (STAI–A). One week after OT initiation, his Ham-D score decreased to 11, and the STAI–A score to 49. At this time, the patient bought a car after several months of hesitancy. He contracted a loan and explained that he was offered good buying conditions. One week later, the patient was very much improved; his HAM-D score dropped to 2, and his STAI–A to 37. Unfortunately, Syntocinon^® was stopped after 1 week because the patient missed the visit. After this period, the patient was much worse. Intranasal OT was then delivered at the dose of 36 UI per day in addition to escitalopram, 20 mg. His symptoms improved after 7 days (Ham-D: 5; STAI–A: 48). At the same time, he was very affected by the [bankruptcy] of his [step-]father, who raised him. One week later, he offered to install hardware [electronic equipment] in his parent's house. On The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), he scored at higher levels, going from 1 to 4 by the end of the study.

This is the first trial of OT as an adjunct to antidepressant in major depression. Our case report suggests that OT instillation significantly improves mood and anxiety. OT was already shown to reduce responses to social stress,¹ to increase trust,² and improve “mind-reading” in humans.³ It is possible that the efficacy of SSRIs in restoring interest in social interactions is due, in part, to their action on the reward circuit via the OT system.⁴ Further studies are needed to investigate the effects of OT or OT-receptor selective agonists in additional clinical models to promote the development of psychopharmacology targeting central OT receptors.