A double-blind randomized controlled trial of oxytocin nasal spray and social cognition training for young people with early psychosis

Abstract

Social-cognitive deficits contribute to poor functional outcomes in early psychosis; however, no effective pharmacological treatments exist for these problems. This study was the first to investigate the efficacy of an extended treatment of oxytocin nasal spray combined with social cognition training (SCT) to improve social cognition, clinical symptoms, and social functioning in early psychosis. In a double-blind, randomized, placebo-controlled, between-subjects trial, 52 individuals (aged 16-35 years) diagnosed with an early psychosis schizophrenia-spectrum illness were recruited. Participants received oxytocin (24 International Units) or placebo nasal spray twice-daily for 6 weeks, combined with group SCT (2 × 1 hour weekly sessions for 6 weeks). An additional dose of oxytocin was administered before each weekly session. Assessments were conducted at baseline, post-treatment, and at 3-month follow-up. Primary outcomes included the Reading the Mind in the Eyes Test, the Scale for the Assessment of Positive and Negative Symptoms, and the Social Functioning Scale. Secondary outcomes included self-report and behavioral assessments of social cognition, symptom severity, and social functioning. Results showed that on all primary and secondary outcomes, there was no benefit of oxytocin nasal spray treatment in comparison to placebo. Exploratory post hoc analysis suggested that increased use of nasal spray was, however, associated with reductions in negative symptoms in the oxytocin condition only. This study represents the first evaluation of oxytocin treatment for early psychosis. Although results suggest no benefit of oxytocin treatment, results also highlight an urgent need to consider nasal spray delivery and dose-related variables for future clinical trials.

Keywords: emotion recognition; neuropeptides; schizophrenia; social behavior.

Fig. 1.

Consolidated Standards of Reporting Trials flow diagram. A total of 58 participants with early psychosis were assessed for eligibility to participate in the trial. A total of 52 participants underwent randomization, with 27 allocated to the active treatment, oxytocin, and 25 allocated to placebo. Both groups received social cognition training. On the day of allocation, 1 participant in the active group and 1 participant in the placebo group withdrew consent to participate due to a change of mind. One participant discontinued in the placebo intervention due to study commitments. Two participants in the active and 1 participant in the placebo group were lost to post assessment. The participant allocated placebo, died due to suicide shortly after completion of the 6-week intervention. Three participants in the active and 1 participant in the placebo group were lost to follow-up. Using an intention-to-treat approach, all participants were included in the final analysis.

Fig. 2.

Change from baseline on primary outcomes. (A) Positive symptoms assessed using the Scale for Assessment of Positive Symptoms (SAPS), change in total score; (B) Negative symptoms assessed using the Scale for Assessment of Negative Symptoms (SANS), change in total score; (C) RMET: Reading the Mind in the Eyes Test, change in percentage correct; (D) Social functioning assessed using the Social Functioning Scale (SFS), change in total score. All primary outcomes are scored so that positive numbers indicate improvement compared with baseline. Error bars depict standard error of the mean.

Fig. 3.

Associations between nasal spray compliance and change in negative symptoms; oxytocin r ² = .36, placebo r ² = .11. A positive change in negative symptoms indicates a reduction in symptoms compared with baseline. A similar pattern of correlations was also found when assessing percentage of spray used (oxytocin r = .53; placebo r = −.17). Participants indicated here are treatment completers with available compliance data; oxytocin n = 21, placebo n = 19.