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Psychiatric management of anti-NMDAR encephalitis: a cohort analysis

Published online by Cambridge University Press:  19 November 2019

Nicola Warren Open the ORCID record for Nicola Warren [Opens in a new window] ,
Cullen O'Gorman ,
Gemma McKeon ,
Andrew Swayne ,
Stefan Blum  and
Dan Siskind
Nicola Warren*
Affiliation:
Metro South Addiction and Mental Health, Brisbane, Australia University of Queensland, Brisbane, Australia
Cullen O'Gorman
Affiliation:
University of Queensland, Brisbane, Australia Department of Neurology, Princess Alexandra Hospital, Brisbane, Australia Mater Centre for Neurosciences, Mater Hospital, Brisbane, Australia
Gemma McKeon
Affiliation:
Metro South Addiction and Mental Health, Brisbane, Australia University of Queensland, Brisbane, Australia
Andrew Swayne
Affiliation:
University of Queensland, Brisbane, Australia Department of Neurology, Princess Alexandra Hospital, Brisbane, Australia Mater Centre for Neurosciences, Mater Hospital, Brisbane, Australia
Stefan Blum
Affiliation:
University of Queensland, Brisbane, Australia Department of Neurology, Princess Alexandra Hospital, Brisbane, Australia Mater Centre for Neurosciences, Mater Hospital, Brisbane, Australia
Dan Siskind
Affiliation:
Metro South Addiction and Mental Health, Brisbane, Australia University of Queensland, Brisbane, Australia
*
Author for correspondence: Nicola Warren, E-mail: n.warren@uq.edu.au
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Abstract

Background

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disorder which requires multi-disciplinary treatment including immunomodulation therapy. First presentation is most commonly to psychiatric services and continuing psychiatric care is required to treat disabling symptoms, such as behaviour disturbance, psychosis and catatonia. There is minimal available evidence to guide symptomatic treatment and concern for increased sensitivity to antipsychotics complicates traditional approaches.

Methods

All cases of cerebrospinal fluid positive anti-NMDAR encephalitis tested in Queensland, Australia were identified. Demographic, clinical and therapeutic data were collected and reviewed by two independent clinicians. Pre-specified variables reflecting possible treatment side effects were compared.

Results

The majority of the 30 cases (83%) had early psychiatric symptoms and were treated with antipsychotics (67%), average daily olanzapine equivalence dose of 11.5 mg, prior to immunomodulation therapy. Although there was an 88% reduction in cases with aggression, there was little improvement in psychosis, affective symptoms or catatonia with antipsychotics alone. In the cases with psychiatric symptoms, there was no significant difference in the rate of occurrence of neurological and autonomic symptoms between cases prescribed and not prescribed antipsychotics.

Conclusions

Psychiatric input is imperative for both acute and longer-term management of anti-NMDAR encephalitis. Primary symptomatic treatment should remain immunotherapy and surgery. Antipsychotic medications have particular value in managing agitation and aggression. Potential side effects from antipsychotic treatment are difficult to differentiate from progression of anti-NMDAR encephalitis but there was no evidence in this cohort of increased antipsychotic sensitivity. Treatment with psychotropic medication should be individualised and adjusted during the course of the illness.

Keywords

AntipsychoticsautoimmuneencephalitisNMDApsychosis
Type
Original Articles
Information
Psychological Medicine , Volume 51 , Issue 3 , February 2021 , pp. 435 - 440
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Copyright
Copyright © Cambridge University Press 2019

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References

Ananth, J. V., & Jain, R. C. (1973). Benztropine psychosis. Canadian Psychiatric Association Journal, 18, 409–414.CrossRefGoogle ScholarPubMed
Baddeley, A., & Wilson, B. A. (1994). When implicit learning fails: Amnesia and the problem of error elimination. Neuropsychologia, 32, 53–68.CrossRefGoogle ScholarPubMed
Barry, H., Byrne, S., Barrett, E., Murphy, K. C., & Cotter, D. R. (2015). Anti-N-methyl-d-aspartate receptor encephalitis: Review of clinical presentation, diagnosis and treatment. British Journal of Psychiatry Bulletin, 39, 19–23.Google ScholarPubMed
Berman, B. D. (2011). Neuroleptic malignant syndrome: A review for neurohospitalists. The Neurohospitalist, 1, 41–47.CrossRefGoogle ScholarPubMed
Boettger, S., Jenewein, J., & Breitbart, W. (2015). Haloperidol, risperidone, olanzapine and aripiprazole in the management of delirium: A comparison of efficacy, safety, and side effects. Palliative and Supportive Care, 13, 1079–1085.CrossRefGoogle Scholar
Brodie, M. J., Besag, F., Ettinger, A. B., Mula, M., Gobbi, G., Comai, S., Steinhoff, B. J. (2016). Epilepsy, antiepileptic drugs, and aggression: An evidence-based review. Pharmacological Reviews, 68, 563–602.CrossRefGoogle Scholar
Chapman, M. R., & Vause, H. E. (2011). Anti-NMDA receptor encephalitis: Diagnosis, psychiatric presentation, and treatment. American Journal of Psychiatry, 168, 245–251.CrossRefGoogle ScholarPubMed
Cicerone, K. D., Langenbahn, D. M., Braden, C., Malec, J. F., Kalmar, K., Fraas, M., Ashman, T. (2011). Evidence-based cognitive rehabilitation: Updated review of the literature from 2003 through 2008. Archives of Physical Medicine and Rehabilitation, 92, 519–530.CrossRefGoogle ScholarPubMed
Clegg, A., & Young, J. B. (2010). Which medications to avoid in people at risk of delirium: A systematic review. Age and Ageing, 40, 23–29.CrossRefGoogle ScholarPubMed
Correll, C. U., Rubio, J. M., & Kane, J. M. (2018). What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? World Psychiatry, 17, 149–160.CrossRefGoogle ScholarPubMed
Dalmau, J. (2016). NMDA receptor encephalitis and other antibody-mediated disorders of the synapse: The 2016 Cotzias Lecture. Neurology, 87, 2471–2482.CrossRefGoogle ScholarPubMed
Dalmau, J., Armangué, T., Planagumà, J., Radosevic, M., Mannara, F., Leypoldt, F., Graus, F. (2019). An update on anti-NMDA receptor encephalitis for neurologists and psychiatrists: Mechanisms and models. The Lancet Neurology, 11, 1045–1057.CrossRefGoogle Scholar
Dalmau, J., Gleichman, A. J., Hughes, E. G., Rossi, J. E., Peng, X., Lai, M., Lynch, D. R. (2008). Anti-NMDA-receptor encephalitis: Case series and analysis of the effects of antibodies. The Lancet Neurology, 7, 1091–1098.10.1016/S1474-4422(08)70224-2CrossRefGoogle ScholarPubMed
Dalmau, J., Lancaster, E., Martinez-Hernandez, E., Rosenfeld, M. R., & Balice-Gordon, R. (2011). Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurology, 10, 63–74.10.1016/S1474-4422(10)70253-2CrossRefGoogle ScholarPubMed
Dayalu, P., & Chou, K. L. (2008). Antipsychotic-induced extrapyramidal symptoms and their management. Expert Opinion on Pharmacotherapy, 9, 1451–1462.CrossRefGoogle ScholarPubMed
De Bruijn, M. A. A. M., Aarsen, F. K., Van Oosterhout, M. P., Van Der Knoop, M. M., Catsman-Berrevoets, C. E., Schreurs, M. W. J., Titulaer, M. J. (2018). Long-term neuropsychological outcome following pediatric anti-NMDAR encephalitis. Neurology, 90, e1997–e2005.CrossRefGoogle ScholarPubMed
Dubovsky, A. N., Arvikar, S., Stern, T. A., & Axelrod, L. (2012). The neuropsychiatric complications of glucocorticoid use: Steroid psychosis revisited. Psychosomatics, 53, 103–115.CrossRefGoogle ScholarPubMed
Espinola-Nadurille, M., Flores-Rivera, J., Rivas-Alonso, V., Vargas-Cañas, S., Fricchione, G. L., Bayliss, L., Ramirez-Bermudez, J. (2019). Catatonia in patients with anti-NMDA receptor encephalitis. Psychiatry and Clinical Neurosciences, 9, 574–580.CrossRefGoogle Scholar
Finke, C., Kopp, U. A., Pruss, H., Dalmau, J., Wandinger, K. P., & Ploner, C. J. (2012). Cognitive deficits following anti-NMDA receptor encephalitis. Journal of Neurology, Neurosurgery and Psychiatry, 83, 195–198.CrossRefGoogle ScholarPubMed
Florance, N. R., Davis, R. L., Lam, C., Szperka, C., Zhou, L., Ahmad, S., Dalmau, J. (2009). Anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Annals of neurology, 66, 11–18.CrossRefGoogle ScholarPubMed
Gabilondo, I., Saiz, A., Galan, L., Gonzalez, V., Jadraque, R., Sabater, L., Graus, F. (2011). Analysis of relapses in anti-NMDAR encephalitis. Neurology, 77, 996–999.CrossRefGoogle ScholarPubMed
Goodwin, F. K. (1971). Psychiatric side effects of levodopa in man. The Journal of the American Medical Association, 218, 1915–1920.CrossRefGoogle ScholarPubMed
Graus, F., Titulaer, M. J., Balu, R., Benseler, S., Bien, C. G., Cellucci, T., Dalmau, J. (2016). A clinical approach to diagnosis of autoimmune encephalitis. The Lancet. Neurology, 15, 391–404.CrossRefGoogle ScholarPubMed
Hasan, A., Falkai, P., Wobrock, T., Lieberman, J., Glenthoj, B., Gattaz, W. F., Moller, H. J. (2017). World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia – a short version for primary care. International Journal of Psychiatry in Clinical Practice, 21, 82–90.CrossRefGoogle Scholar
Howes, O. D., & Kapur, S. (2009). The dopamine hypothesis of schizophrenia: Version III—the final common pathway. Schizophrenia Bulletin, 35, 549–562.10.1093/schbul/sbp006CrossRefGoogle ScholarPubMed
Huffman, J. C., & Stern, T. A. (2007). Neuropsychiatric consequences of cardiovascular medications. Dialogues in Clinical Neuroscience, 9, 29–45.Google ScholarPubMed
Juengst, S. B., Kumar, R. G., & Wagner, A. K. (2017). A narrative literature review of depression following traumatic brain injury: Prevalence, impact, and management challenges. Psychology Research and Behavior Management, 10, 175–186.CrossRefGoogle ScholarPubMed
Kayser, M. S., & Dalmau, J. (2011). Anti-NMDA receptor encephalitis in psychiatry. Current Psychiatry Reviews, 7, 189–193.CrossRefGoogle Scholar
Kayser, M. S., Titulaer, M. J., Gresa-Arribas, N., & Dalmau, J. (2013). Frequency and characteristics of isolated psychiatric episodes in anti–N-methyl-d-aspartate receptor encephalitis. The Journal of the American Medical Association – Neurology, 70, 1133–1139.Google ScholarPubMed
Kessels, R. P., & Haan, E. H. (2003). Implicit learning in memory rehabilitation: A meta-analysis on errorless learning and vanishing cues methods. Journal of Clinical and Experimental Neuropsychology, 25, 805–814.CrossRefGoogle ScholarPubMed
Kuppuswamy, P. S., Takala, C. R., & Sola, C. L. (2014). Management of psychiatric symptoms in anti-NMDAR encephalitis: A case series, literature review and future directions. General Hospital Psychiatry, 36, 388–391.CrossRefGoogle ScholarPubMed
Lejuste, F., Thomas, L., Picard, G., Desestret, V., Ducray, F., Rogemond, V., Honnorat, J. (2016). Neuroleptic intolerance in patients with anti-NMDAR encephalitis. Neurology(R) Neuroimmunology and Neuroinflammation, 3, e280–e280.CrossRefGoogle ScholarPubMed
Leucht, S., Samara, M., Heres, S., Patel, M. X., Furukawa, T., Cipriani, A., Davis, J. M. (2015). Dose equivalents for second-generation antipsychotic drugs: The classical mean dose method. Schizophrenia Bulletin, 41, 1397–1402.10.1093/schbul/sbv037CrossRefGoogle ScholarPubMed
Lindenmayer, J.-P., & Kotsaftis, A. (2000). Use of sodium valproate in violent and aggressive behaviors: A critical review. Journal of Clinical Psychiatry, 61, 123–128.CrossRefGoogle ScholarPubMed
Liu, X., Li, J., Guo, C., Wang, H., Sun, Y., Wang, H., Si, T. (2018). Olanzapine reverses MK-801-induced cognitive deficits and region-specific alterations of NMDA receptor subunits. Frontiers in Behavioral Neuroscience, 11, 260.CrossRefGoogle ScholarPubMed
Lonergan, E., Britton, A. M., & Luxenberg, J. (2007). Antipsychotics for delirium. Cochrane Database of Systematic Reviews, 2, 5–8.Google Scholar
Lonergan, E., Luxenberg, J., & Sastre, A. A. (2009). Benzodiazepines for delirium. Cochrane Database of Systematic Reviews, 4, p. 7.Google Scholar
Marsden, C., Mindham, R., & Mackay, A. (1982). Extrapyramidal movement disorders produced by antipsychotic drugs. In Bradley, PB and Hirsch, SL (eds), The Psychopharmacology and Drug Treatment of Schizophrenia, Oxford: Oxford University Press, 340–402.Google Scholar
Mckeon, G. L., Robinson, G. A., Ryan, A. E., Blum, S., Gillis, D., Finke, C., & Scott, J. G. (2018). Cognitive outcomes following anti-N-methyl-d-aspartate receptor encephalitis: A systematic review. Journal of Clinical and Experimental Neuropsychology, 40, 234–252.CrossRefGoogle ScholarPubMed
Mohammad, S. S., Jones, H., Hong, M., Nosadini, M., Sharpe, C., Pillai, S. C., Dale, R. C. (2016). Symptomatic treatment of children with anti-NMDAR encephalitis. Developmental Medicine and Child Neurology, 58, 376–384.CrossRefGoogle ScholarPubMed
Ozbolt, L. B., Paniagua, M. A., & Kaiser, R. M. (2008). Atypical antipsychotics for the treatment of delirious elders. Journal of the American Medical Directors Association, 9, 18–28.CrossRefGoogle ScholarPubMed
Scharko, A. M., Panzer, J., & Mcintyre, C. M. (2015). Treatment of delirium in the context of anti-N-methyl-D-aspartate receptor antibody encephalitis. Journal of the American Academy of Child and Adolescent Psychiatry, 54, 233–234.CrossRefGoogle ScholarPubMed
Titulaer, M. J., Mccracken, L., Gabilondo, I., Armangué, T., Glaser, C., Iizuka, T., Dalmau, J. (2013). Treatment and prognostic factors for long-term outcome in patients with anti-N-Methyl-d-Aspartate (NMDA) receptor encephalitis: A cohort study. Lancet Neurology, 12, 157–165.CrossRefGoogle Scholar
Warden, D. L., Gordon, B., Mcallister, T. W., Silver, J. M., Barth, J. T., Bruns, J., Katz, D. I. (2006). Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury. Journal of Neurotrauma, 23, 1468–1501.CrossRefGoogle ScholarPubMed
Warren, N., Grote, V., O'Gorman, C., & Siskind, D. (2019). Electroconvulsive therapy for anti-N-methyl-d-aspartate (NMDA) receptor encephalitis: A systematic review of cases. Brain Stimulation, 12, 329–334.CrossRefGoogle ScholarPubMed
Warren, N., Siskind, D., & O'Gorman, C. (2018). Refining the psychiatric syndrome of anti-N-methyl-d-aspartate receptor encephalitis. Acta Psychiatrica Scandinavica, 138, 401–408.CrossRefGoogle ScholarPubMed