A randomised double-blind placebo-controlled 12- week feasibility trial of methotrexate added to treatment as usual in early schizophrenia: study protocol for a randomised controlled trial
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- 作者：Imran B Chaudhry (10)
Nusrat Husain (10)
Raza ur Rahman (11)
Mohammed Omair Husain (12)
Mohammed M Hamirani (13)
Ajmal Kazmi (14)
Shakeel Baig (15)
Peter M Haddad (16)
Maya H Buch (17)
Inti Qureshi (18)
Nasir Mehmood (14)
Tayyeba Kiran (14)
Bo Fu (19)
Salahuddin Afsar (11)
Bill Deakin (19)
10. University of Manchester & Lancashire Care Early Intervention Service ; Manchester ; UK
11. Dow University of Health Sciences ; Karachi ; Pakistan
12. Southwest London and St George’s NHS Trust ; London ; UK
13. Abbassi Shaheed Hospital ; Karachi ; Pakistan
14. Pakistan Institute of Leaning and Living ; Karachi ; Pakistan
15. Baqai University ; Karachi ; Pakistan
16. University of Manchester & Greater Manchester West Mental Health NHS Foundation Trust ; Manchester ; UK
17. University of Leeds ; Leeds ; UK
18. Mersey Care NHS Trust ; Liverpool ; UK
19. University of Manchester ; Manchester ; UK - 刊名：Trials
- 出版年：2015
- 出版时间：December 2015
- 年：2015
- 卷：16
- 期：1
- 全文大小：68 KB
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- 出版者：BioMed Central
- ISSN：1745-6215
文摘
Background Methotrexate is a commonly used anti-inflammatory and immunosuppressive drug. There is growing evidence that inflammatory processes are involved in the pathogenesis of schizophrenia. In our recent randomised double-blind placebo-controlled clinical trial in Pakistan and Brazil, the addition of minocycline (antibiotic and anti-inflammatory drug) for 1?year to treatment as usual reduced negative symptoms and improved some cognitive measures. A meta-analysis of cytokine changes in the peripheral blood has identified IL-2, IFN-gamma, TNF-alpha and soluble IL-2 receptor as trait markers of schizophrenia because their levels were elevated during acute exacerbations and reduced in remission. This suggests immune activation and an inflammatory syndrome in schizophrenia. Based on the evidence of the strong anti-inflammatory properties of methotrexate, we propose that low-dose methotrexate may be an effective therapy in early schizophrenia. Methods/Design This is a double-blind placebo-controlled study of methotrexate added to treatment as usual for patients suffering from schizophrenia, schizoaffective disorder, psychosis not otherwise specified or schizophreniform disorder. This will be with 72 patients, 36 in each arm over 3?months. There will be screening, randomisation and follow-up visits. Full clinical assessments will be carried out at baseline, 2, 4, 8 and 12?weeks. Social and cognitive assessments will be carried out at baseline and 12?weeks. Methotrexate will be given at a dose of 10 mgs orally once a week for a 3-month period. Discussion Evidence suggests inflammatory processes are involved in the pathogenesis of schizophrenia and anti-inflammatory treatments have shown to have some beneficial effects. Methotrexate is a known immunosuppressant and anti-inflammatory drug. The aim of this study is to establish the degree of improvement in positive and negative symptoms, as well as cognitive functioning with the addition of methotrexate to treatment as usual. ClinicalTrials.gov identifier: NCT02074319 (24 February 2014).