title: Ondansetron and simvastatin added to treatment as usual in patients with schizophrenia: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Negative symptoms and cognitive deficits are two partially-related features of schizophrenia which have a major negative impact on social function and objective quality of life. Standard drug treatments have little impact on either. There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Statins are cholesterol-lowering agents that have been found to be anti-inflammatory agents and are also known to decrease C-reactive protein (CRP). Ondansetron is a serotonin (5-HT3) receptor antagonist widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. Small studies have suggested that ondansetron is effective as an adjunct drug in improving the symptoms of schizophrenia.
  
  
  METHODS
  This is a two center, six-month, double-blind placebo controlled, factorial design study of ondansetron and/or simvastatin added to treatment as usual for patients suffering from schizophrenia, schizoaffective disorder, psychosis not otherwise specified or schizophreniform disorder. This will be a 2 × 2 design, with 54 patients in each cell, giving a total of 216 patients over three years. There will be a screening, a randomization and seven follow-up visits. Full clinical and neurocognitive assessments will be carried out at baseline (randomization), 14 weeks and at 26 weeks, while the positive and negative syndrome scale (PANSS), pill count and side effects checklist will be carried out at every visit. Simvastatin will be started at 20 mg once daily (OD), this will be increased to 40 mg after four weeks. Ondansetron will be administered in an 8 mg dose.
  
  
  CONCLUSIONS
  Anti-inflammatory treatments have been shown to have some beneficial effects in schizophrenia. Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared to treatment as usual. The aim of this study is to establish the degree of improvement in negative symptoms with the addition of ondansetron and/or simvastatin to treatment as usual.
  
  
  BACKGROUND
  [corrected] ClinicalTrials.gov NCT01602029.
authors.affiliation: University of Manchester and Lancashire Care Early Intervention Service, The Mount Whalley Road, Accrington BB5 5DE, UK. imran.chaudhry@manchester.ac.uk
authors.forename: Imran B
authors.initials: IB
authors.lastname: Chaudhry
authors.forename: Nusrat
authors.initials: N
authors.lastname: Husain
authors.forename: Mohammad O
authors.initials: MO
authors.lastname: Husain
authors.forename: Jamie
authors.initials: J
authors.lastname: Hallak
authors.forename: Richard
authors.initials: R
authors.lastname: Drake
authors.forename: Ajmal
authors.initials: A
authors.lastname: Kazmi
authors.forename: Raza ur
authors.initials: Ru
authors.lastname: Rahman
authors.forename: Mohammad M
authors.initials: MM
authors.lastname: Hamirani
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Kiran
authors.forename: Nasir
authors.initials: N
authors.lastname: Mehmood
authors.forename: John
authors.initials: J
authors.lastname: Stirling
authors.forename: Graham
authors.initials: G
authors.lastname: Dunn
authors.forename: Bill
authors.initials: B
authors.lastname: Deakin
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001938:Brazil; D057189:Checklist; D002985:Clinical Protocols; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D017294:Ondansetron / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010154:Pakistan; D011569:Psychiatric Status Rating Scales; D012107:Research Design; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D014150:Antipsychotic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012702:Serotonin Antagonists; D017294:Ondansetron; D019821:Simvastatin