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Neuroleptic malignant syndrome: evaluation of drug safety data from the AMSP program during 1993–2015

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Abstract

Neuroleptic malignant syndrome (NMS) is a rare, but severe adverse drug reaction of drugs with anti-dopaminergic properties. The main symptoms are fever and rigor. In addition, other symptoms such as creatine kinase elevation, alteration of consciousness and various neurological symptoms may occur. A total of 52 NMS cases have been documented in the drug safety program ‘Arzneimittelsicherheit in der Psychiatrie’ from 1993 to 2015. We calculated incidences and analyzed imputed substances and additional risk factors to study the impact of changing therapy regimes. The overall incidence was 0.16‰. High-potency first-generation antipsychotics (FGAs) had the highest incidences, e.g. flupentixol with 0.61‰. Second-generation antipsychotics (SGAs) had lower incidences. Low-potency FGAs had very low incidences, comparable to SGAs, but in contrast to SGAs, had not been imputed alone in any case of NMS. Preexisting organic pathologies of the central nervous system, lithium treatment, infection/exsiccosis and the withdrawal of medication with anticholinergic properties or alcohol were found to be additional risk factors. With the increasing use of SGAs, one should always be aware of the risk of NMS. Better suited diagnostic criteria for ‘atypical NMS’ would lead to a better understanding and, therefore, to improved treatment possibilities.

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Acknowledgements

This study was supported by the AMSP Drug Safety Programme, Hannover, Germany. The analysis of the NMSdata and this publication were made possible by a grant from Immanuel Klinik Rüdersdorf.

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Author notes

  1. Michael Schneider and Johannes Regente shared first authorship.

Authors and Affiliations

  1. University Clinic for Psychiatry and Psychotherapy, Brandenburg Medical School, Immanuel Klinik Rüdersdorf, Seebad 82/83, 15562, Rüdersdorf bei Berlin, Germany

    Michael Schneider, Johannes Regente, Timo Greiner, Stephanie Lensky & Martin Heinze

  2. Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Johannes Regente

  3. Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany

    Stefan Bleich & Sermin Toto

  4. Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany

    Renate Grohmann

  5. Department of Psychiatry, Kbo-IAK, Academic Teaching Hospital of the Ludwig-Maximilians University, Haar, Munich, Germany

    Susanne Stübner

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  1. Michael Schneider
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Correspondence to Michael Schneider.

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Conflict of interest

T. Greiner, M. Schneider, S. Lensky, S. Stübner, J. Regente and M. Heinze declare no conflict of interests. The AMSP Drug Safety Program is based on non-profit associations in the German-speaking countries Germany, Austria and Switzerland. In recent years, financial support has been contributed by almost all the pharmaceutical companies involved in CNS research. Since 1993, educational and research grants have been awarded by the following pharmaceutical companies to the three national non-profit associations of the AMSP. Austrian companies: AstraZeneca Österreich GmbH, Boehringer Ingelheim Austria, Bristol–Myers Squibb GmbH, CSC Pharmaceuticals GmbH, Eli Lilly GmbH, Germania Pharma GmbH, GlaxoSmithKline Pharma GmbH, Janssen-Cilag Pharma GmbH, Lundbeck GmbH, Novartis Pharma GmbH, Pfizer Med Inform, Servier Pharma Austria, Wyeth Lederle Pharma GmbH. German companies: Abbott GmbH & Co. KG, AstraZeneca GmbH, Aventis Pharma Deutschland GmbH GE-O/R/N, Bayer Vital GmbH & Co. KG, Boehringer Mannheim GmbH, Bristol-Myers-Squibb, Ciba Geigy GmbH, Desitin Arzneimittel GmbH, Duphar Pharma GmbH & Co. KG, Eisai GmbH, esparma GmbH Arzneimittel, GlaxoSmithKline Pharma GmbH & Co. KG, Hoffmann-La Roche AG Medical Affairs, Janssen-Cilag GmbH, Janssen Research Foundation, Knoll Deutschland GmbH, Lilly Deutschland GmbH Niederlassung Bad Homburg, Lundbeck GmbH & Co. KG, Nordmark Arzneimittel GmbH, Novartis Pharma GmbH, Organon GmbH, Otsuka-Pharma Frankfurt, Pfizer GmbH, Pharmacia & Upjohn GmbH, Promonta Lundbeck Arzneimittel, Rhone-Poulenc Rohrer, Sanofi-Synthelabo GmbH, Sanofi-Aventis Deutschland, Schering AG, Servier Pharma, SmithKlineBeecham Pharma GmbH, Solvay Arzneimittel GmbH, Synthelabo Arzneimittel GmbH, Dr Wilmar Schwabe GmbH & Co., Thiemann Arzneimittel GmbH, Trommsdorff GmbH & Co. KG Arzneimittel, Troponwerke GmbH & Co. KG, Upjohn GmbH, Wander Pharma GmbH, Wyeth-Pharma GmbH. Swiss companies: AHP (Schweiz) AG, AstraZeneca AG, Bristol–Myers Squibb AG, Desitin Pharma GmbH, Eli Lilly (Suisse) S.A., Essex Chemie AG, GlaxoSmithKline AG, Janssen-Cilag AG, Lundbeck (Suisse) AG, Mepha Schweiz AG/Teva, MSD Merck Sharp & Dohme AG, Organon AG, Pfizer AG, Pharmacia, Sandoz Pharmaceuticals AG, Sanofi-Aventis (Suisse) S.A., Sanofi-Synthe´labo SA, Servier SA, SmithKlineBeecham AG, Solvay Pharma AG, Vifor SA, Wyeth AHP (Suisse) AG, Wyeth Pharmaceuticals AG. S. Bleich, R. Grohmann and S. Toto are project managers of the AMSP program. S. Toto has been a member of the advisory board for Otsouka and has received speaker’s honoria from Janssen-Cilag, Lundbeck, Otsouka and Servier.

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Schneider, M., Regente, J., Greiner, T. et al. Neuroleptic malignant syndrome: evaluation of drug safety data from the AMSP program during 1993–2015. Eur Arch Psychiatry Clin Neurosci 270, 23–33 (2020). https://doi.org/10.1007/s00406-018-0959-2

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