Sex differences in response to intranasal oxytocin as an adjunctive therapy for patients with severe mental illness

Studies investigating the potential benefits of intranasal oxytocin (IN[sbnd]OT) as an add-on treatment for patients with severe mental illness (SMI) have yielded inconsistent results, potentially due to sex differences in response to IN[sbnd]OT. This study explored the differential effects of IN[sbnd]OT among male and female patients with SMI. A secondary analysis was conducted on a previously studied group of patients who participated in a double-blind, placebo-controlled trial evaluating the impact of IN[sbnd]OT as an add-on treatment for patients with SMI. Patients treated in inpatient settings (N = 87) received twice-daily IN[sbnd]OT (32IU) or placebo (PLC) for a period of four weeks. Sex moderated the effect of OT/PLC on the Hamilton Rating Scale for Depression (HRDS) (p < 0.001). A significant effect for sex was found in the Hopkins Symptom Checklist–short form (HSCL-11) (p = 0.04) and HRDS (p < 0.001), with females showing greater reductions in anxiety and depression symptoms and severity. This effect was not found for males. We conclude that the addition of IN[sbnd]OT to the treatment of patients with SMI in an inpatient setting was beneficial for female patients, particularly reducing depressive symptoms, but not for male patients. Future studies should aim to identify patients who are more likely to benefit from IN[sbnd]OT administration.