Oxytocin as Adjunctive Therapy for Schizophrenia

The project has two main aims:

• Aims of the cross-over study To assess the efficacy of intranasal OXT in reducing negative symptoms in patients with SZ (as evaluated with PANSS), in association with standard Second Generation Antipsychotics (SGA)treatment; recruited patients will be aged 18-45 years and will have a disorder duration of no longer than 10 years.
• Aims of the neuropsychological assessment To use an Emotional Priming Paradigm (EPP) task to assess pre- and post-treatment change in the patients general cognitive and emotional status.

The investigators aim at treating a large sample size of patients with schizophrenia, consisting exclusively of patients with a limited disorder duration and rather young age, for a sufficiently long period of time. Our rationale for employing a longer treatment period than used in previous and on-going trials is to ascertain the possibility of a positive OXT dose-response relationship, which would be observable, however, with longer treatment exposure. Moreover, only patients with a disorder onset of 10 years or less will be enrolled.

They will then be standardized in terms of AP treatment and randomized to OXT or placebo for 8 months.

OXT is a hormone that is naturally present in the human body, and recent studies have suggested that patients with SZ show low levels of this neuropeptide. It is therefore hypothesized that the treatment proposed in this project might balance apparently lower OXT levels in these patients.

Finally, another innovative aspect of this project is the attention at ameliorating patients adherence to treatment by supporting them with a reminder program (automatic SMS will be sent every morning to remind patients the daily OXT self-administration) and involving a trustworthy caregiver who will be trained in OXT administration and will be asked to monitor the patient compliance by recording each self-administration on a written form.

Inclusion criteria

• Patients with a diagnosis of SZ, according to DSM-IV criteria, for at least one year, evaluated with SCID/P
• A minimum PANSS total score of 55 (indicating moderate severity, due to ongoing AP treatment) .
• A minimum CGI-S score of 4
• Age between 18 and 45 years
• A disorder duration of no longer than 10 years
• Women of childbearing age must test negative for pregnancy at the time of enrolment.

All patients must:

• be on a therapeutic dose of a SGA (or a maximum 2 SGAs) with no major dose changes for at least 4 weeks.
• have the ability to provide informed consent
• be able to use a nasal spray
• reside in the service catchment area
• show evidence of no alcohol or substance dependence in the last year

Exclusion criteria

• Diagnosis of mental retardation
• Diagnosis of organic mental disorder
• History of no response to treatment with clozapine
• History of hypersensitivity to OXT or vehicle
• Alcohol or substance dependence in the last year
• Presence of, or history of clinically significant allergic rhinitis as assessed by the treating clinician
• Being pregnant or breastfeeding
• Having given birth in the past 6 months or breast-feeding in the past 3 months
• Low literacy as indicated by an inability to read and understand the consent form