Supplementary Material for: Intranasal Oxytocin as Add-On Treatment for Inpatients with Severe Mental Illness: A Randomized Clinical Trial

Introduction: In recent years, several studies were conducted to explore the potential augmenting effect of oxytocin for the treatment of individuals with severe mental illness. Nonetheless, studies exploring its effects in routine inpatient settings using high-quality randomized controlled trials are scarce. The current study assessed the effect of oxytocin administration on treatment process and outcome among psychiatric inpatients, while employing a rigorous experimental methodology. Methods: A double-blind, placebo-controlled, randomized trial was conducted at a public psychiatric hospital in Israel. Patients (N = 87, 71.3% female participants) were administered intranasal oxytocin/placebo twice daily for 4 weeks, as add-on to usual care. Patients were assessed for severity of anxiety and depression symptoms and their working alliance with their therapist after each therapy session, and treatment outcome was assessed weekly. Multilevel modeling was performed to assess the linear change from pre- to post-treatment. Results: Patients receiving OT demonstrated significantly larger symptomatic improvements (B = −0.01, t [437] = −2.36, p = 0.01). Larger gains were also observed for depression (B = −0.14, p < 0.001 in the OT group, B = −0.06, p = 0.02 in the placebo group) and general distress (B = −0.57, p < 0.001 in the OT group, B = −0.29, p = 0.02 in the placebo group). No significant effect was observed for anxiety, the working alliance, or attachment. Discussion: Oxytocin has the potential to improve treatment outcome among inpatients. Nonetheless, additional controlled research is needed to further assess its effects on therapy process, as well as to account for therapeutic, pharmacological, and neuronal intervening factors.