title: Intranasal oxytocin as an adjunct to risperidone in patients with schizophrenia : an 8-week, randomized, double-blind, placebo-controlled study.
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.
  
  
  METHODS
  This was an 8-week, randomized, double-blind, placebo-controlled study.
  
  
  METHODS
  Inpatients of two large referral psychiatric hospitals in Iran were recruited for the study.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, South Kargar Street, Tehran, 13337, Iran.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Modabbernia
authors.forename: Farzin
authors.initials: F
authors.lastname: Rezaei
authors.forename: Bahman
authors.initials: B
authors.lastname: Salehi
authors.forename: Morteza
authors.initials: M
authors.lastname: Jafarinia
authors.forename: Mandana
authors.initials: M
authors.lastname: Ashrafi
authors.forename: Mina
authors.initials: M
authors.lastname: Tabrizi
authors.forename: Seyed M R
authors.initials: SM
authors.lastname: Hosseini
authors.forename: Masih
authors.initials: M
authors.lastname: Tajdini
authors.forename: Ali
authors.initials: A
authors.lastname: Ghaleiha
authors.forename: Shahin
authors.initials: S
authors.lastname: Akhondzadeh
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D010121:Oxytocin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D010121:Oxytocin; D018967:Risperidone