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

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.