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Antipsychotic drugs and risk of venous thromboembolism: nested case-control study

BMJ 2010; 341 doi: (Published 22 September 2010) Cite this as: BMJ 2010;341:c4245

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  1. Chris Parker, medical statistician1,
  2. Carol Coupland, associate professor in medical statistics2,
  3. Julia Hippisley-Cox, professor of clinical epidemiology and general practice2
  1. 1Nottinghamshire County Teaching Primary Care Trust, Hucknall Health Centre, Hucknall, Nottingham NG15 7JE
  2. 2Division of Primary Care, University Park, Nottingham NG2 7RD
  1. Correspondence to: J Hippisley-Cox juliahippisleycox{at}
  • Accepted 22 June 2010


Objective To determine whether antipsychotic drugs are associated with an increased risk of venous thromboembolism, and to examine risks by type of antipsychotic, potency, and dose.

Design Population based nested case-control study.

Setting The UK QResearch primary care database.

Participants Patients (cases) with a first ever record of venous thromboembolism between 1 January 1996 and 1 July 2007; each was matched with up to four controls by age, calendar time, sex, and practice.

Main outcome measures Odds ratios for venous thromboembolism associated with antipsychotic drugs adjusted for comorbidity; concomitant drug exposure.

Results There were 25 532 eligible cases (15 975 with deep vein thrombosis and 9557 with pulmonary embolism) and 89 491 matched controls from a study population of 7 267 673. Individuals prescribed antipsychotic drugs in the previous 24 months had a 32% greater risk of venous thromboembolism than non-users, despite adjustment for potential risk factors (odds ratio 1.32, 95% confidence interval 1.23 to 1.42). Patients who had started a new drug in the previous three months had about twice the risk (1.97, 1.66 to 2.33). The risk was greater for individuals prescribed atypical rather than conventional drugs (adjusted odds ratio 1.73, 1.37 to 2.17, for atypical drugs; 1.28, 1.18 to 1.38, for conventional drugs). It also tended to be greater for patients prescribed low rather than high potency drugs (1.99, 1.52 to 2.62, for low potency; 1.28, 1.18 to 1.38, for high potency). The estimated number of extra cases of venous thromboembolism per 10 000 patients treated over one year was 4 (3 to 5) in patients of all ages and 10 (7 to 13) for patients aged 65 and over.

Conclusions There is an association between use of antipsychotic drugs and risk of venous thromboembolism in a large primary care population. The increased risk was more marked among new users and those prescribed atypical antipsychotic drugs.


  • We acknowledge the contribution of EMIS and EMIS practices contributing to the QResearch database.

  • Contributors: CP contributed to the design, reviewed the literature, undertook the primary analysis, contributed to the interpretation, and wrote the first and subsequent drafts of the paper. CC contributed to the development of the protocol, design and analysis, and interpretation and drafting of the paper. JH-C initiated the study, contributed to the design, obtained approvals, prepared the data, and checked and added to the analysis, interpretation, and drafting of the paper. All authors approved the final draft of the paper originally submitted to the BMJ. JH-C and CC approved the final draft of the paper revised after referees’ comments as CP had retired. JH-C is guarantor.

  • Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare no support from any organisation for the submitted work. JHC is codirector of QResearch, a not-for-profit organisation that is a joint partnership between the University of Nottingham and EMIS. EMIS is the leading supplier of IT for 60% of UK general practices. This work and any views expressed within it are solely those of the co-authors and not of any affiliated bodies or organisations.

  • Ethical approval: The proposal was approved by the Trent multicentre research ethics committee.

  • Data sharing: The patient level data from the QResearch are specifically licensed according to its governance framework. See for further details. The Read codes groups used are available from the authors on request.

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