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Clinical and Research NewsFull Access

Oxytocin Nasal Spray Fails to Improve Social Functioning in Psychosis Patients

Published Online:https://doi.org/10.1176/appi.pn.2014.8a6

Abstract

Improving cognition and cognitive skills related to social functioning is a vital research area, since these variables are seen as major obstacles to improved daily functioning for people with schizophrenia.

What appears to be the first randomized, controlled trial of oxytocin nasal spray for patients with early psychosis found no benefit over placebo with regard to social functioning—although a follow-up analysis looking at dosing suggested that increased use of oxytocin nasal spray was associated with reductions in negative symptoms.

The study findings were published online June 23 in Schizophrenia Bulletin.

Oxytocin is a hormone that has been associated with empathy and other factors critical to social functioning. Some preliminary studies have suggested that oxytocin might benefit patients with psychosis, especially with regard to the cognitive and social deficits experienced by schizophrenia patients.

Researchers at the Brain and Mind Institute at Australia’s University of Sydney conducted a double-blind, randomized, placebo-controlled trial in which 52 individuals aged 16 to 35 diagnosed with an early-onset schizophrenia-spectrum illness received oxytocin or a placebo nasal spray twice a day for six weeks, combined with group social-cognition training.

Assessments were conducted at baseline, after treatment, and three-month follow-up. Primary outcomes were scores on standardized tests measuring social cognition and social functioning. Secondary outcomes included self-report and behavioral assessments of social cognition, symptom severity, and social functioning.

The data analysis showed that on all primary and secondary outcomes, there was no benefit for oxytocin nasal spray treatment compared with placebo.

However, additional exploratory analysis looking at dosing suggested that increased use of the nasal spray was associated with reductions in negative symptoms.

“Although the 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,” the researchers said.

Photo: Stephen Marder, M.D.

Stephen Marder, M.D., says that the study results are useful for clarifying when and how oxytocin might be useful in the treatment of schizophrenia.

Stephen Marder, M.D.

Psychiatrist Stephen Marder, M.D., of the Semel Institute for Neuroscience at UCLA has conducted research using oxytocin to study its effects on empathy. Commenting on the Schizophrenia Bulletin study, Marder said that though the findings are disappointing, the results are important for clarifying when and how oxytocin might be useful. “All of the subjects in the trial received social-cognition training,” he said. “It’s possible that this was very effective, and oxytocin could add little to it.”

Efforts to improve cognition, and especially cognitive skills related to social functioning, have emerged as an important area of research, as these variables are often viewed as major obstacles to improved daily functioning for people with schizophrenia.

At the International Congress on Schizophrenia in Orlando, Fla., last year, Marder described studies at UCLA using oxytocin. One of those involved a single-dose pilot evaluation of the effects of oxytocin on social-cognition measures and found statistically significant effects on a composite score of higher-order social-cognition measures, such as the ability to detect lies and sarcasm.

Photo: William Carpenter, M.D.

While the results of the study were disappointing, William Carpenter, M.D., points out that a clinical trial with negative results “is critical in guiding future work.”

Vito Sesuknas

In a second study, oxytocin was administered just prior to social-cognition training to find out whether by increasing the salience of social information, oxytocin could facilitate learning for schizophrenia patients during such training.

The findings were intriguing: both the placebo and oxytocin groups improved on the social-cognition composite measure, but while the training demonstrated effectiveness on lower-level measures of cognition, oxytocin appeared to facilitate learning of higher-level social-cognition abilities, particularly empathic accuracy (Psychiatric News, May 17, 2013).

Regarding the Schizophrenia Bulletin study, Marder added that it could be that oxytocin loses some of its effectiveness when it is administered chronically, as in this study. “As the authors indicate, more work should be done to clarify the best dose of oxytocin and when it should be administered.”

William Carpenter, M.D., who was chair of APA’s DSM-5 Work Group on Psychotic Disorders, said oxytocin is the most compelling pharmacological lead for improving social-cognition impairment. “As an unmet therapeutic need in schizophrenia, hope is high for new discovery,” he told Psychiatric News. “In this circumstance, report of a carefully conducted clinical trial with negative results is critical in guiding future work.” ■

“A Double-Blind Randomized Controlled Trial of Oxytocin Nasal Spray and Social Cognition Training for Young People With Early Psychosis” can be accessed here.