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Intranasal Oxytocin as an Adjunct to Risperidone in Patients with Schizophrenia

An 8-Week, Randomized, Double-Blind, Placebo-Controlled Study

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Abstract

Background

Impairment of oxytocinergic function and/or oxytocin receptor genetic abnormalities has been demonstrated in patients with schizophrenia. Oxytocin reverses emotional recognition deficit and might restore sense of trust in patients with schizophrenia. Some short-term studies have shown efficacy and tolerability of oxytocin in patients with schizophrenia. However, there is a lack of evidence on the efficacy and tolerability of oxytocin in patients with schizophrenia beyond 3 weeks.

Objective

The objective of this study was to assess the efficacy and tolerability of oxytocin intranasal spray (given as an adjuvant to risperidone) in patients with schizophrenia.

Study Design

This was an 8-week, randomized, double-blind, placebo-controlled study.

Study Setting

Inpatients of two large referral psychiatric hospitals in Iran were recruited for the study.

Patients

Forty patients (male and female gender) aged 18–50 years with a diagnosis of schizophrenia (DSM-IV-TR) who were on a stable dose of risperidone for a minimum of 1 month and who were chronically partially responsive to antipsychotic monotherapy were included in the study.

Interventions

The patients were randomly assigned to oxytocin intranasal spray (Syntocinon®; Novartis, Basel, Switzerland) or placebo intranasal spray containing normal saline (ACER, Tehran, Iran) for 8 weeks. Oxytocin spray was administered as 20 IU (five sprays) twice a day for the first week followed by 40 IU (ten sprays) twice a day for the following 7 weeks. Placebo spray was administered at the same dose as the oxytocin spray. In addition, participants were on a stable dose of risperidone (5 or 6 mg/day).

Outcomes

The patients were assessed using Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 0, 2, 4, 6 and 8. Primary outcomes were the differences in the PANSS scores between the two groups at the end of the trial. Adverse effects were recorded using a checklist and the Extrapyramidal Symptom Rating Scale (ESRS) at baseline and at weeks 1, 2, 4, 6 and 8.

Results

All patients had at least one post-baseline measurement and 37 patients (19 in the oxytocin and 18 in the placebo group) completed the study. Repeated measure analysis of variance showed significant effect for time X treatment interaction on the PANSS total [F(2.291,87.065) = 22.124, p < 0.001], positive [F(1.285,48.825) = 11.655, p = 0.001], negative [F(2.754,104.649) = 11.818, p < 0.001] and general psychopathology [F(1.627,61.839) = 4.022, p = 0.03] subscale scores. By week 8, patients in the oxytocin group showed significantly greater improvement on the positive (Cohen’s d = 1.2, 20 % vs. 4 % reduction in score, p < 0.001), negative (Cohen’s d = 1.4, 7 % vs. 2 % reduction in score, p < 0.001) and general psychopathology (Cohen’s d = 0.8, 8 % vs. 2 % reduction in score, p = 0.021) subscales and total (Cohen’s d = 1.9, 11 % vs. 2 % reduction in score, p < 0.001) PANSS scores than the placebo group. Adverse effects including the sodium concentration change were similar between the two groups.

Conclusion

Oxytocin as an adjunct to risperidone tolerably and efficaciously improves positive symptoms of schizophrenia. In addition, effects on negative and total psychopathology scores were statistically significant, but likely to be clinically insignificant. The interesting findings from the present pilot study need further replication in a larger population of patients.

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Acknowledgements

The study was supported by a grant from the Tehran University of Medical Sciences to Professor Shahin Akhondzadeh (Grant number: 12949). The trial was registered in the Iranian registry of clinical trials (www.irct.ir, registration number: IRCT201202251556N35). The authors have declared that there are no conflicts of interest in relation to the subject of this study.

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Authors and Affiliations

  1. Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, South Kargar Street, Tehran, 13337, Iran

    Amirhossein Modabbernia, Morteza Jafarinia, Mandana Ashrafi, Seyed M. R. Hosseini, Masih Tajdini & Shahin Akhondzadeh

  2. Department of Psychiatry, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Farzin Rezaei

  3. Department of Psychiatry, Arak University of Medical Sciences, Arak, Iran

    Bahman Salehi

  4. Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mina Tabrizi

  5. Research Center for Behavioral Disorders and Substance Abuse, Hamadan University of Medical Sciences, Hamadan, Iran

    Ali Ghaleiha

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  1. Amirhossein Modabbernia
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Correspondence to Shahin Akhondzadeh.

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Modabbernia, A., Rezaei, F., Salehi, B. et al. Intranasal Oxytocin as an Adjunct to Risperidone in Patients with Schizophrenia. CNS Drugs 27, 57–65 (2013). https://doi.org/10.1007/s40263-012-0022-1

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