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Encephalitis With Antibodies to GluN2B During Administration of Clozapine

Gon, Junji MD; Takehisa, Yasushi MD, PhD; Yada, Yuji MD; Kishi, Yoshiki MD; Oshima, Etsuko MD, PhD; Takahashi, Yukitoshi MD, PhD; Takaki, Manabu MD, PhD

doi: 10.1097/WNF.0000000000000181
Case Reports

Clozapine's immunomodulatory properties may contribute to its effect on schizophrenia as well as various adverse effects. However, a possible relationship between N-methyl-D-aspartate-type glutamate receptor antibodies, refractory schizophrenia, and clozapine has not been reported. We experienced a patient who developed refractory schizophrenia that mimicked an exacerbation of encephalitis with antibodies to N-methyl-D-aspartate–type glutamate receptor (GluN2B) after administration of clozapine for 26 days. We performed plasma exchange 5 times and subsequent steroid pulse therapy. The level of consciousness improved within a few weeks, but involuntary movement as well as psychotic symptoms remained. The production of anti-GluN2B antibodies may have contributed to the patient's resistance to the antipsychotic effects of clozapine in addition to mediating the encephalitis. When we administer clozapine to patients with refractory schizophrenia, we should be careful to differentiate between a diagnosis of refractory schizophrenia and encephalitis with antibodies to GluN2B.

*Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences; †Department of Neuropsychiatry, Zikei Hospital; ‡Department of Neurology, Okayama Red Cross Hospital; §Department of Neuropsychiatry, Okayama Psychiatric Medical Center, Okayama; and ∥Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.

Address correspondence and reprint requests to Manabu Takaki, MD, PhD, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan; E-mail:

The authors have no conflicts of interest to declare.

This study was funded in part by grants-in-aid for Scientific Research I No. 21591342, 23591238, and 24591537; Health and Labour Sciences Research Grants for Comprehensive Research on Disability Health and Welfare (H24-002); Research on rare and intractable diseases; and grants from the Japan Epilepsy Research Foundation (Y. Takahashi). This study was partly supported by a grant from Zikei Institute of Psychiatry.

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