A double-edged hormone: The moderating role of personality and attachment on oxytocin's treatment facilitation effect

Background: Studies exploring the potential augmenting effect of oxytocin for patients with mental disorders have thus far reported mixed effects. However, oxytocin's effect may differ across patients with different interpersonal characteristics. This study aimed to examine the moderating role of attachment and personality traits on the effect of oxytocin administration on the therapeutic working alliance and symptomatic change, among hospitalized patients with severe mental illness. Methods: Patients (N = 87) were randomly assigned to receive oxytocin or placebo, as an add-on to psychotherapy for a period of four weeks, in two inpatient units. Therapeutic alliance and symptomatic change were measured weekly, and personality and attachment were assessed at pre- and post-intervention. Results: Oxytocin administration was significantly associated with improvement of depression (B=2.12, SE=0.82, t = 2.56, p = .012), and suicidal ideation (B=0.03, SE=0.01, t = 2.44, p = .016) for patients low in openness and extraversion, respectively. Nonetheless, oxytocin administration was also significantly associated with a deterioration in the working alliance for patients high in extraversion (B=−0.11, SE=0.04, t = −2.73, p = .007), low in neuroticism (B=0.08, SE=0.03, t = 2.01, p = .047) and low in agreeableness (B=0.11, SE=0.04, t = 2.76, p = .007). Conclusions: Oxytocin may act as a double-edged sword when it comes to its effect on treatment process and outcome. Future studies should focus on routes to characterize patients who might benefit the most from such augmentation. Clinical trial registration: Pre-registration in clinicaltrials.com: NCT03566069; Israel Ministry of Health: MOH_2017–12–05_002003.