RCT of Methotrexate Added to Treatment As Usual in Schizophrenia

Inclusion Criteria: * Signed informed consent, indicating that the subject understood the purpose of and procedures required for the study, before the initiation of any study specific procedures * Aged 18 to 35 years * Diagnostic and Statistical Manual-IV (DSM-IV) diagnosed first episode psychosis, schizophrenia, schizoaffective disorder, psychosis not otherwise specified or schizophreniform disorder. * First episode (within first 5 years of diagnosis) * Competent and willing to give informed consent * Medication remained stable 4 weeks prior to baseline. * Able to take oral medication and likely to complete the required evaluations. * Female participants of child bearing capability must be willing to use adequate contraceptives for the duration of the study, and, willing to have a pregnancy test pre treatment and at ten weekly intervals while on study medication. 1. Adequate contraception is defined as use of contraceptive double barrier system (i.e. condom and spermicide) or contraceptive implant, oral contraceptive or injected depot contraceptive plus other form of contraceptive i.e. condom. Females will be considered incapable of child bearing if they are one year post-menopausal or irreversibly surgically sterilised. Exclusion Criteria: * Violation of any inclusion criteria * Failure to perform screening or baseline examinations * Relevant ICD 10 organic brain disease or neurological diagnoses * Patients with liver disease * Patients who will meet the criteria for a DSM-IV TR diagnosis of alcohol or substance abuse (other than for nicotine) within the last month or the criteria for DSM-IV TR alcohol or substance dependence (other than for nicotine) within the last 6 months * Any change of psychotropic medications within the previous 4 weeks * Recreational drugs or alcohol abuse * Pregnant or lactating women and those of reproductive age without adequate contraception * Relevant medical illness will be determined in the first instance by asking the patients mental health care team if the patient has any medical condition/problems. After consent has been obtained the research nurse/ research doctor will then have access to the patients' notes and will assess patient eligibility to take part in the clinical trial by scrutinising the patients' past medical history, most recent blood results, electrocardiograms, as well as any physical tests that have been performed on the patient.