A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis

Author(s):Show less -

Chaudhry, I. B. ^{[1, 2, 3]} ; Husain, M. O. ^{[4, 5, 6]} ; Khoso, A. B. ^[6] ; Husain, I, M. ; Buch, M. H. ^{[7, 8, 9]} ; Kiran, T. ^[6] ; Fu, B. ^[10] ; Bassett, P. ^[11] ; Qurashi, I ^[12] ; Rahman, R. ur ^[2] ; Baig, S. ^[13] ; Kazmi, A. ^[14] ; Corsi-Zuelli, F. ^[15] ; Haddad, P. M. ^[16] ; Deakin, B. ^[1] ; Husain, N. ^[12]

Affiliation:Show less -

^[1] Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Sch Biol Sci, Div Neurosci & Expt Psychol, Manchester M13 9PT, Lancs - England

^[2] Dow Univ Hlth Sci, Karachi - Pakistan

^[3] Ziauddin Univ Hosp, Karachi - Pakistan

^[4] I, Ctr Addict & Mental Hlth, Toronto, ON - Canada

^[5] I, Univ Toronto, Dept Psychiat, Toronto, ON - Canada

^[6] Pakistan Inst Living & Learning, Karachi - Pakistan

^[7] Leeds Teaching Hosp NHS Trust, Leeds Biomed Res Ctr, Natl Inst Hlth Res, Leeds, W Yorkshire - England

^[8] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear - England

^[9] Newcastle Tyne Hosp NHS Fdn, Newcastle Biomed Res Ctr, Natl Inst Hlth Res, Newcastle Upon Tyne, Tyne & Wear - England

^[10] Fundan Univ, Sch Data Sci, Shanghai - Peoples R China

^[11] Stats Consultancy, Amersham - England

^[12] Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Sch Biol Sci, Div Psychol & Mental Hlth, Manchester M13 9PT, Lancs - England

^[13] Baqai Univ, Karachi - Pakistan

^[14] Karwan e Hayat, Karachi - Pakistan

^[15] Univ Sao Paulo FMRP USP, Ribeirao Preto Med Sch, Dept Neurosci & Behav, Div Psychiat, BR-14048900 Sao Paulo, SP - Brazil

^[16] Hamad Med Corp, Doha - Qatar

• Document type: Journal article
• Source: TRANSLATIONAL PSYCHIATRY; v. 10, n. 1 DEC 30 2020.
• Web of Science Citations: 0

Abstract

NMDA autoantibody encephalitis presenting as schizophrenia suggests the possible role of adaptive cell-mediated immunity in idiopathic schizophrenia. However, to our knowledge there have been no trials of the immune-suppressant methotrexate in schizophrenia. We tested if low-dose methotrexate as used in the treatment of systemic autoimmune disorders would be tolerable and effective in people with schizophrenia in a feasibility study. Ninety-two participants within 5 years of schizophrenia diagnosis were recruited from inpatient and outpatient facilities in Karachi, Pakistan. They were randomised to receive once weekly 10-mg oral methotrexate (n = 45) or matching placebo (n = 47) both with daily 5-mg folic acid, in addition to treatment as usual for 12 weeks. There were eight dropouts per group. Side effects were non-significantly more common in those on methotrexate and were not severe. One person developed leukopenia. Positive symptom scores improved more in those receiving methotrexate than placebo (beta = -2.5; {[}95% CI -4.7 to -0.4]), whereas negative symptoms were unaffected by treatment (beta = -0.39; {[}95% CI -2.01 to 1.23]). There were no immune biomarkers but methotrexate did not affect group mean leucocyte counts or C-reactive protein. We conclude that further studies are feasible but should be focussed on subgroups identified by advances in neuroimmune profiling. Methotrexate is thought to work in autoimmune disorders by resetting systemic regulatory T-cell control of immune signalling; we show that a similar action in the CNS would account for otherwise puzzling features of the immuno-pathogenesis of schizophrenia. (AU)

• FAPESP's process: 19/13229-2 - Inflammatory profile in the general population: transdiagnostic dimensions in the context of the psychosis continuum
• Grantee: Fabiana Maria das Graças Corsi Zuelli
• Support Opportunities: Scholarships in Brazil - Doctorate