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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%).
Patients who were prescribed atypical antipsychotic drugs had a greater risk of VTE than did those who were prescribed conventional antipsychotics – 73% compared with 28%. Patients who had received only one prescription in the previous 12 months had a significantly greater risk (32%) than did those receiving none. In addition, those who were prescribed two or more different antipsychotics had a greater risk (99%) than did those who received only one (29%).
The most commonly prescribed drug was prochlorperazine – a high-potency phenothiazine – which also is commonly prescribed for nausea, vomiting, and vertigo. Prochlorperazine was prescribed for 75% of the total number of those on antipsychotics. The other most commonly prescribed drugs were (in order) risperidone, haloperidol, olanzapine, chlorpromazine, trifluoperazine, and quetiapine. Separate odds ratios were estimated for exposure to these drugs, with highest risks for those patients who were prescribed quetiapine, chlorpromazine, and haloperidol, with adjusted odds ratios of 2.81, 1.77, and 2.17, respectively.
Individuals with a diagnosis of dementia were at higher risk than were those with diagnoses of schizophrenia, bipolar disorder, or none of these conditions. There was a more than threefold increase associated with cancer and a roughly 13-fold increase associated with recent surgery or fractures. “Individuals prescribed statins or aspirin in the past 24 months had a lower risk of venous thromboembolism, and those prescribed NSAIDs, oral contraceptives, hormone replacement therapy, tamoxifen, or antimanics had a higher risk,” the authors noted.
The number needed for harm for any antipsychotic use in the past 24 months for patients aged 65 years and older was 1,044; for new users in the past 3 months this number was 344; and for continuing users it was 1,152. The corresponding numbers of excess cases of VTE per 10,000 treated patients were 10, 29, and 9, respectively.
The study authors reported that they have no relevant financial relationships.
The validity of the findings is strengthened by the large sample size and the low potential for exposure and outcome misclassification because of the detailed source of data and adjustment for a large number of confounders, according to Dr. Rosa Liperoti and Dr. Giovanni Gambassi.
It’s been demonstrated that “patients with schizophrenia have an increased risk of venous thromboembolism (VTE), and this might be associated with the use of antipsychotics, especially low-potency drugs such as chlorpromazine and thioridazine. So far, however, the possibility that the underlying psychiatric disorders themselves – and not the antipsychotics – are associated with VTE has never been excluded. This could occur, for example, by the increased concentrations of adrenaline seen during psychotic excitation increasing blood coagulation,” they noted.
In this study, in almost all cases the reason for prescription of antipsychotics could not be ascertained. Most of the antipsychotics used were conventional agents, with prochlorperazine – probably given for nausea and vomiting – accounting for almost 80% of all prescriptions, they wrote. “These findings indicate that VTE is directly linked to the use of an antipsychotic, and that the risk of VTE increases early after starting the drug.”
The implications are potentially far reaching. “Despite their association with serious risks and few data to support their efficacy, antipsychotics are widely used, and in 2008 they became the top selling drug class in the United States. Despite efforts to improve non–drug based interventions, antipsychotics are often used, especially for the treatment of agitation in people with dementia,” they wrote.
The findings suggest that physicians “need to be able to identify the best candidates for antipsychotic treatment, such as those people with the lowest vascular risk profile who may respond to short-term and low-dose treatment with antipsychotics because of individual pharmacogenetic characteristics, and those who may be more susceptible to developing side effects as a result of individual vascular risk factors possibly interacting with antipsychotics.”
Dr. Rosa Liperoti is a specialist in geriatrics and Dr. Giovanni Gambassi is a professor of geriatrics at Universit? Cattolica del Sacro Cuore in Rome. Both Dr. Liperoti and Dr. Gambassi reported that they have no relevant financial relationships. These comments were taken from a commentary that accompanied the study (BMJ 2010 Sept. 21[doi: 10.1136/bmj.c4216]).
The validity of the findings is strengthened by the large sample size and the low potential for exposure and outcome misclassification because of the detailed source of data and adjustment for a large number of confounders, according to Dr. Rosa Liperoti and Dr. Giovanni Gambassi.
It’s been demonstrated that “patients with schizophrenia have an increased risk of venous thromboembolism (VTE), and this might be associated with the use of antipsychotics, especially low-potency drugs such as chlorpromazine and thioridazine. So far, however, the possibility that the underlying psychiatric disorders themselves – and not the antipsychotics – are associated with VTE has never been excluded. This could occur, for example, by the increased concentrations of adrenaline seen during psychotic excitation increasing blood coagulation,” they noted.
In this study, in almost all cases the reason for prescription of antipsychotics could not be ascertained. Most of the antipsychotics used were conventional agents, with prochlorperazine – probably given for nausea and vomiting – accounting for almost 80% of all prescriptions, they wrote. “These findings indicate that VTE is directly linked to the use of an antipsychotic, and that the risk of VTE increases early after starting the drug.”
The implications are potentially far reaching. “Despite their association with serious risks and few data to support their efficacy, antipsychotics are widely used, and in 2008 they became the top selling drug class in the United States. Despite efforts to improve non–drug based interventions, antipsychotics are often used, especially for the treatment of agitation in people with dementia,” they wrote.
The findings suggest that physicians “need to be able to identify the best candidates for antipsychotic treatment, such as those people with the lowest vascular risk profile who may respond to short-term and low-dose treatment with antipsychotics because of individual pharmacogenetic characteristics, and those who may be more susceptible to developing side effects as a result of individual vascular risk factors possibly interacting with antipsychotics.”
Dr. Rosa Liperoti is a specialist in geriatrics and Dr. Giovanni Gambassi is a professor of geriatrics at Universit? Cattolica del Sacro Cuore in Rome. Both Dr. Liperoti and Dr. Gambassi reported that they have no relevant financial relationships. These comments were taken from a commentary that accompanied the study (BMJ 2010 Sept. 21[doi: 10.1136/bmj.c4216]).
The validity of the findings is strengthened by the large sample size and the low potential for exposure and outcome misclassification because of the detailed source of data and adjustment for a large number of confounders, according to Dr. Rosa Liperoti and Dr. Giovanni Gambassi.
It’s been demonstrated that “patients with schizophrenia have an increased risk of venous thromboembolism (VTE), and this might be associated with the use of antipsychotics, especially low-potency drugs such as chlorpromazine and thioridazine. So far, however, the possibility that the underlying psychiatric disorders themselves – and not the antipsychotics – are associated with VTE has never been excluded. This could occur, for example, by the increased concentrations of adrenaline seen during psychotic excitation increasing blood coagulation,” they noted.
In this study, in almost all cases the reason for prescription of antipsychotics could not be ascertained. Most of the antipsychotics used were conventional agents, with prochlorperazine – probably given for nausea and vomiting – accounting for almost 80% of all prescriptions, they wrote. “These findings indicate that VTE is directly linked to the use of an antipsychotic, and that the risk of VTE increases early after starting the drug.”
The implications are potentially far reaching. “Despite their association with serious risks and few data to support their efficacy, antipsychotics are widely used, and in 2008 they became the top selling drug class in the United States. Despite efforts to improve non–drug based interventions, antipsychotics are often used, especially for the treatment of agitation in people with dementia,” they wrote.
The findings suggest that physicians “need to be able to identify the best candidates for antipsychotic treatment, such as those people with the lowest vascular risk profile who may respond to short-term and low-dose treatment with antipsychotics because of individual pharmacogenetic characteristics, and those who may be more susceptible to developing side effects as a result of individual vascular risk factors possibly interacting with antipsychotics.”
Dr. Rosa Liperoti is a specialist in geriatrics and Dr. Giovanni Gambassi is a professor of geriatrics at Universit? Cattolica del Sacro Cuore in Rome. Both Dr. Liperoti and Dr. Gambassi reported that they have no relevant financial relationships. These comments were taken from a commentary that accompanied the study (BMJ 2010 Sept. 21[doi: 10.1136/bmj.c4216]).
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%).
Patients who were prescribed atypical antipsychotic drugs had a greater risk of VTE than did those who were prescribed conventional antipsychotics – 73% compared with 28%. Patients who had received only one prescription in the previous 12 months had a significantly greater risk (32%) than did those receiving none. In addition, those who were prescribed two or more different antipsychotics had a greater risk (99%) than did those who received only one (29%).
The most commonly prescribed drug was prochlorperazine – a high-potency phenothiazine – which also is commonly prescribed for nausea, vomiting, and vertigo. Prochlorperazine was prescribed for 75% of the total number of those on antipsychotics. The other most commonly prescribed drugs were (in order) risperidone, haloperidol, olanzapine, chlorpromazine, trifluoperazine, and quetiapine. Separate odds ratios were estimated for exposure to these drugs, with highest risks for those patients who were prescribed quetiapine, chlorpromazine, and haloperidol, with adjusted odds ratios of 2.81, 1.77, and 2.17, respectively.
Individuals with a diagnosis of dementia were at higher risk than were those with diagnoses of schizophrenia, bipolar disorder, or none of these conditions. There was a more than threefold increase associated with cancer and a roughly 13-fold increase associated with recent surgery or fractures. “Individuals prescribed statins or aspirin in the past 24 months had a lower risk of venous thromboembolism, and those prescribed NSAIDs, oral contraceptives, hormone replacement therapy, tamoxifen, or antimanics had a higher risk,” the authors noted.
The number needed for harm for any antipsychotic use in the past 24 months for patients aged 65 years and older was 1,044; for new users in the past 3 months this number was 344; and for continuing users it was 1,152. The corresponding numbers of excess cases of VTE per 10,000 treated patients were 10, 29, and 9, respectively.
The study authors reported that they have no relevant financial relationships.
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%).
Patients who were prescribed atypical antipsychotic drugs had a greater risk of VTE than did those who were prescribed conventional antipsychotics – 73% compared with 28%. Patients who had received only one prescription in the previous 12 months had a significantly greater risk (32%) than did those receiving none. In addition, those who were prescribed two or more different antipsychotics had a greater risk (99%) than did those who received only one (29%).
The most commonly prescribed drug was prochlorperazine – a high-potency phenothiazine – which also is commonly prescribed for nausea, vomiting, and vertigo. Prochlorperazine was prescribed for 75% of the total number of those on antipsychotics. The other most commonly prescribed drugs were (in order) risperidone, haloperidol, olanzapine, chlorpromazine, trifluoperazine, and quetiapine. Separate odds ratios were estimated for exposure to these drugs, with highest risks for those patients who were prescribed quetiapine, chlorpromazine, and haloperidol, with adjusted odds ratios of 2.81, 1.77, and 2.17, respectively.
Individuals with a diagnosis of dementia were at higher risk than were those with diagnoses of schizophrenia, bipolar disorder, or none of these conditions. There was a more than threefold increase associated with cancer and a roughly 13-fold increase associated with recent surgery or fractures. “Individuals prescribed statins or aspirin in the past 24 months had a lower risk of venous thromboembolism, and those prescribed NSAIDs, oral contraceptives, hormone replacement therapy, tamoxifen, or antimanics had a higher risk,” the authors noted.
The number needed for harm for any antipsychotic use in the past 24 months for patients aged 65 years and older was 1,044; for new users in the past 3 months this number was 344; and for continuing users it was 1,152. The corresponding numbers of excess cases of VTE per 10,000 treated patients were 10, 29, and 9, respectively.
The study authors reported that they have no relevant financial relationships.
FROM THE BRITISH MEDICAL JOURNAL
Major Finding: Patients taking antipsychotics had a 32% greater risk of venous thromboembolism, compared with those not on the drugs.
Data Source: A nested case-control study of 115,023 primary care patients in the United Kingdom.
Disclosures: The authors reported that they have no relevant financial relationships.