Ondansetron and simvastatin added to treatment as usual in patients with schizophrenia: study protocol for a randomized controlled trial
1 University of Manchester and Lancashire Care Early Intervention Service, The Mount Whalley Road, Accrington BB5 5DE, UK
2 St Georges University, Cranmer Terrace, London SW 17 ORE, UK
3 University of San Paulo, Rua da praca Relogio, 109 Sao Paulo, BR 05508-900, Brazil
4 KPT and Karwan e Hyat “Psychiatric Care and Rehabilitation Cent34 (PCRC)” Near KPT hospital, Keamari, Karachi, Pakistan
5 Dow University of Health Sciences, Baba-E-Urdu Road, Karachi 74200, Pakistan
6 Abbassi Shaheed Hospital, Block M, North Nazimabad, Karachi, Pakistan
7 Pakistan Institute of Learning & Living, D-9, Block I, Northnazimabad, Karachi 74700, Pakistan
8 Manchester Metropolitan University, All Saints Building, All Saints, Manchester M15 6BH, UK
Trials 2013, 14:101 doi:10.1186/1745-6215-14-101Published: 17 April 2013
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.
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.
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.