University of Sussex
Relationship Between Serum NMDA Receptor Antibodies and Response to Antipsychotic Treatment in First-Episode Psychosis.pdf (176.14 kB)

Relationship between serum NMDA receptor antibodies and response to antipsychotic treatment in first-episode psychosis

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journal contribution
posted on 2023-06-10, 04:57 authored by Thomas A Pollak, Anegla Vincent, Conrad Iyegbe, Ester Coutinho, Leslie Jacobson, Dan Rujescu, James StoneJames Stone, Julie Jezequel, Veronique Rogemond, Stephane Jamain, Laurent Groc, Anthony David, Alice Egerton, Rene S Kahn, Jerome Honnorat, Paola Dazzan, Marion Leboyer, Philip McGuire
Background When psychosis develops in NMDA receptor (NMDAR) antibody encephalitis, it usually has an acute or subacute onset, and antipsychotic treatment may be ineffective and associated with adverse effects. Serum NMDAR antibodies have been reported in a minority of patients with first-episode psychosis (FEP), but their role in psychosis onset and response to antipsychotic treatment is unclear. Methods Sera from 387 patients with FEP (duration of psychosis <2 years, minimally or never treated with antipsychotics) undergoing initial treatment with amisulpride as part of the OPTiMiSE (Optimization of Treatment and Management of Schizophrenia in Europe) trial ( number NCT01248195) were tested for NMDAR IgG antibodies using a live cell–based assay. Symptom severity was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions Scale at baseline and again after 4 weeks of treatment with amisulpride. Results At baseline, 15 patients were seropositive for NMDAR antibodies and 372 were seronegative. The seropositive patients had similar symptom profiles and demographic features to seronegative patients but a shorter duration of psychosis (median 1.5 vs. 4.0 months; p = .031). Eleven seropositive and 284 seronegative patients completed 4 weeks of amisulpride treatment: after treatment, there was no between-groups difference in improvement in Positive and Negative Syndrome Scale scores or in the frequency of adverse medication effects. Conclusions These data suggest that in FEP, NMDAR antibody seropositivity alone is not an indication for using immunotherapy instead of antipsychotic medications. Further studies are required to establish what proportion of patients with FEP who are NMDAR antibody seropositive have coexisting cerebrospinal fluid inflammatory changes or other paraclinical evidence suggestive of a likely benefit from immunotherapy.


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  • Published

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  • Published version


Biological Psychiatry




Elsevier BV





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United States

Department affiliated with

  • BSMS Neuroscience Publications

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  • Yes

Peer reviewed?

  • Yes

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