Do we need oxytocin to treat schizophrenia? A randomized clinical trial

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Abstract

Background

Schizophrenia is a disabling complex mental disorder and despite all available treatment, many patients unfortunately remain partial- or non-responders. A large body of research has shown that oxytocin is an important prosocial peptide and there is initial evidence that the central oxytocin system is altered in several mental disorders. The aim of this study was to test the efficacy of oxytocin, as augmentation therapy, in a sample of patients with schizophrenia.

Methods

We conducted an 8-month randomized, double-blind, controlled trial with a crossover design. We wanted to test the hypothesis that intranasal oxytocin could reduce symptoms in 32 patients with schizophrenia aged 18–45 with short-medium illness duration (< 11 years). Patients were randomly assigned to either 40 International Units oxytocin once daily or a vehicle placebo group, in addition to their pre-study antipsychotic medication regimen. We subsequently conducted a multi-dimensional assessment including psychopathological, psychosocial and neuropsychological aspects.

Results

Positive and Negative Syndrome Scale scores showed no significant differences in treatment effects between the experimental group and controls. Furthermore, no treatment effects were shown in any of the rating scales used in this study. However, a statistically significant period effect was shown in most outcome measurements.

Conclusions

In our trial, oxytocin did not add any significant beneficial effects to anti-psychotic treatment in terms of clinical symptoms or psychosocial functioning. Further research should focus on different ways to administer oxytocin, or investigate predictors (such as past traumas, or biomarkers), which could identify subgroups of patients with different treatment responses to oxytocin.

ClinicalTrials.gov Identifier: NCT01699997.

ID number: RF-2010-2311148.

URL: https://clinicaltrials.gov/ct2/show/NCT01699997.

Section snippets

Background

Schizophrenia is a complex mental disorder and an important public health problem. Although both First Generation Antipsychotics (FGAs) and Second Generation Antipsychotics (SGAs) are effective in treating schizophrenia, many patients remain partial- or non-responders, as shown by over fifty years of follow-up studies (Hegarty et al., 1994). In particular, the negative symptom triad, namely social cognitive impairment, low motivation and blunted motivational affect, is particularly resistant to

Participants

Subjects with a DSM-IV diagnosis of schizophrenia for at least one year, confirmed by Structured Clinical Interview (SCID) for DSM-IV interview, were enrolled. Main inclusion criteria were: age range 18–45 years and short-medium duration of illness (< 11 years).

Other main inclusion criteria included: PANSS score of at least 55 and a Clinical Global Impressions—Severity (CGI-S) scale score of at least 4 (moderately ill) at randomization, with a trustworthy caregiver ensuring necessary support

Results

Overall, 32 subjects were included in the trial (16 patients for each group). One patient discontinued pharmacological treatment (usual and experimental) in the first period of the intervention and subsequently, at month 3, dropped out of the study (Fig. 1). Follow-up evaluations ended in April 2015, when the last patient completed the treatment period.

Table 1 shows the sample's main socio-demographic and clinical characteristics. Eighty one per cent of completers were male, with a mean age of

Discussion

Several meta-analyses and follow-up studies have shown that a substantial proportion of patients with schizophrenia do not respond at all, or show only a partial response to anti-psychotic (AP) treatment, in particular as far as negative symptoms are concerned (Fusar-Poli et al., 2015, Leucht et al., 2012). This situation has prompted researchers and clinicians to study possible additions to AP treatment in order to improve response rates for remissions and, if possible, recovery for a larger

Conflict of interest

All authors report no biomedical financial interests or potential conflicts of interest. This work was entirely supported by the Italian Ministry of Health (Ministero della Salute) grant RF2010-2311148.

Role of the funding source

The funding body (Italian Ministry of Health) funded the project in the framework of the annual call of applications for biomedical research. The funding source had no role in the design and in the conduct of the study, in data analyses, in the interpretation of results and in the writing of the study report.

Acknowledgements

This work was supported by the Italian Ministry of Health (Ministero della Salute) grant RF2010-2311148. Many thanks are due to Dr. Vincenzo Giordano (SIGMA-TAU) for his invaluable support in all stages of the project, who kindly provided the study drugs on a complimentary basis.

This paper is dedicated to the memory of Michele Tansella, who emphasized the importance of rigorous evaluation of any treatment methods in psychiatry during all his career.

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