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Associations Between Venous Thromboembolism and Antipsychotics

A Study of the WHO Database of Adverse Drug Reactions

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Abstract

Background: Concern has been raised about the occurrence of venous thromboembolism (VTE) during treatment with antipsychotics. However, to date, clozapine is the only antipsychotic agent for which recurring evidence supports an association with VTE. Therefore, the aim of this study was to investigate the association between antipsychotic drugs, including clozapine and VTE.

Study design and methods: Data mining of the WHO database of adverse drug reactions (ADRs) using Bayesian statistics is in routine use for early alerting to possible ADRs. An information component measure was used to investigate the association between antipsychotic drugs and VTE reactions in the database.

Results: A total of 754 suspected cases of VTE related to treatment with antipsychotics had been reported. After excluding cases related to clozapine, 379 cases remained. A robust association was found for the second-generation antipsychotics group but not for the high-potency, first-generation antipsychotics group or the low-potency first-generation antipsychotics group. The individual compounds with statistically significant associations were olanzapine, sertindole and zuclopenthixol. A time-dependent analysis showed that the associations were positive for these drugs in 2002, 2001 and 2003, respectively. Case analyses were undertaken after excluding ten suspected duplicate reports. Of the remaining 369 cases, 91 cases were associated with olanzapine, 9 with zuclopenthixol and 6 with sertindole.

Conclusions: VTE was more often reported with the antipsychotic drugs olanzapine, sertindole and zuclopenthixol than with other drugs in the WHO database. Further studies are warranted to explain this disproportional reporting. Since the associations found were based on incomplete clinical data, the results should be considered as preliminary and interpreted cautiously.

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Acknowledgements

We thank the national centres that contribute data to the WHO international drug monitoring programme. The opinions and conclusions in this article are, however, not necessarily those of the various national centres or of the WHO. The research was funded by the Swedish Research Council and the WHO Collaborating Centre without other external funding. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. The authors have no conflicts of interest directly relevant to the content of this study.

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Authors and Affiliations

  1. Division of Clinical Pharmacology, Linköping University Hospital, S-581 85, Linköping, Sweden

    Staffan Hägg

  2. Division of Clinical Pharmacology, Sahlgrenska University Hospital, Göteborg, Sweden

    Staffan Hägg

  3. Uppsala Monitoring Centre, WHO Collaborating Centre for International Drug Monitoring, Uppsala, Sweden

    Andrew Bate & Malin Stahl

  4. Department of Clinical Pharmacology, St Olav University Hospital, Trondheim, Norway

    Olav Spigset

  5. Department of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology, Trondheim, Norway

    Olav Spigset

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  1. Staffan Hägg
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  2. Andrew Bate
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  4. Olav Spigset
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Correspondence to Staffan Hägg.

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Hägg, S., Bate, A., Stahl, M. et al. Associations Between Venous Thromboembolism and Antipsychotics. Drug-Safety 31, 685–694 (2008). https://doi.org/10.2165/00002018-200831080-00005

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