Antipsychotic drugs are associated with an almost one-third (32%) greater risk of venous thromboembolism, according to results of a nested case-control study of more than 100,000 primary care patients in the United Kingdom. The study was published online Sept. 21 in the British Medical Journal.
Previous research has suggested that these drugs – also commonly used for nausea, vomiting, and vertigo – might be linked with an increased risk of venous thromboembolism (VTE). However, the results have been inconsistent.
In the current study, the association was even greater for new users of antipsychotics. Those with any antipsychotic use in last 3 months had a 56% increased risk of VTE. Patients who started taking an antipsychotic in the past 3 months had a 97% increased risk. However, the absolute risks were low, with an excess of four extra cases of VTE per 10,000 patients treated over 1 year in patients of all ages and 10 for patients aged 65 years and older.
“Our study adds to the accumulating evidence of adverse health events associated with antipsychotic drugs,” the researchers wrote (BMJ 2010 Sept. 21[doi:10.1136/bmj.c4245]). “If other studies replicate these findings, antipsychotic drugs should be used more cautiously for nausea and agitation, etc., especially among patients at high risk of thromboembolism.”
The researchers used data from the QResearch database, which includes primary care clinical records for more than 11 million people registered in the past 16 years at more than 500 U.K. general practices. The study population was an open cohort of patients aged 16-100 years, who were registered with participating practices between January 1996 and July 2007. Case patients had a first-ever record of VTE – either deep vein thrombosis or pulmonary embolism – during the study period (including postmortem diagnoses).
Incidence density sampling was used to identify up to four control patients for each case patient. Control patients were matched by age, calendar time, sex, and practice. Control patients had no diagnoses of VTE prior to the date of the first recorded diagnosis of VTE in their matched case patient (index date).
Both case and control patients had to have at least 24 months of data before the index date. Control patients were excluded if they had any prescriptions for warfarin prior to the index date. Case patients with any use of warfarin earlier than 6 weeks prior to VTE diagnosis were also excluded, according to Chris Parker, a medical statistician at Hucknall Health Centre in Nottingham, England, and colleagues.
Each patient was classified for exposure to antipsychotics as a current user (one or more prescriptions within 3 months before the index date), a recent user (prescriptions within 4-12 months before the index date), a past user (prescriptions within 13-24 months before the index date), or not exposed within the previous 24 months.
Current users were subclassified as new users (a prescription for antipsychotic within 3 months of the index date, after at least 12 months with no prescription for that antipsychotic) or as continuing users. Exposure during the previous 24 months also was classified according by type (conventional, atypical, or both) and potency (high potency, low potency, or both). High potency was defined as equivalent dose of more than 100 mg chlorpromazine.
Patients with more than one mental health indication were categorized according to a hierarchy: schizophrenia, bipolar disorder without schizophrenia, and dementia without schizophrenia or bipolar disorder.
The analyses were adjusted for socioeconomic status, comorbidities (coronary heart disease, cardiac failure, stroke, cancer, inflammatory bowel disease, liver disease, varicose veins, gastrointestinal bleed, Parkinson’s disease, renal disease, asthma, diabetes, hypertension, hyperlipidemia), drug variables, and the number of complete months of data before the index date.
In addition, data were extracted for 6 months prior to the index date for several events that are associated with increased risk in the short term (hip surgery, hip or lower limb fractures, acute infections, pregnancy). The researchers also looked for whether there was any computer-recorded evidence of a hospital admission in the preceding 31-183 days.
In all, 25,532 eligible case patients – 15,975 with DVT and 9,557 with pulmonary embolism – and 89,491 control patients were included in the study. In terms of mental health disorders, the overall prevalence was 0.4% for schizophrenia, 0.3% for bipolar disorder, and 1.0% for dementia. Eight case patients and 31 control patients had more than one disorder. In all, 8.3% of case patients and 5.3% of control patients had received an antipsychotic in the previous 24 months.
Overall, antipsychotic users had a 32% greater risk of VTE than did nonusers. Among those on antipsychotics, 38% were current users and their increase in risk was 56% compared with 36% for recent users. The risk was not significantly increased for past users. Among current antipsychotic users, 15% had started a new drug within the 3 months prior to the index date. This group of new users showed a greater increase in risk (97%) than did continuing users (29%).