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

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Thomas Pollak, Angela Vincent, Conrad Iyegbe, Maria Ester Freitas Barbosa Pereira Coutinho, Leslie W Jacobson, D Rujescu, James Stone, Julie Jezequel, Véronique Rogemond, Stéphane Jamain, Laurent Groc, Anthony David, Alice Egerton, R S Kahn, Jérôme Honnorat, Paola Dazzan, M Leboyer, Philip McGuire

Original languageEnglish
JournalBiological psychiatry
Accepted/In press17 Nov 2020

King's Authors


Background When psychosis develops in 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 trial ( number NCT01248195) were tested for NMDAR IgG antibodies using a live cell-based assay (CBA). Symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS) and the clinical global impression (CGI) 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. Seropositive patients had similar symptom profiles and demographic features to seronegative patients but a shorter duration of psychosis (median 1.5 versus 4.0 months; p=0.031). 11 seropositive and 284 seronegative patients completed 4 weeks of amisulpride treatment: following treatment, there was no between-groups difference in improvement in PANSS scores, nor 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 NMDAR antibody seropositive FEP patients have coexisting CSF inflammatory changes or other paraclinical evidence suggestive of likely benefit from immunotherapy.

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