Caroline Helwick

NEW ORLEANS – In patients with hypercholesterolemia and high cardiovascular risk, the novel agent mipomersen administered as add-on therapy led to robust reductions in LDL cholesterol, based on the results of a double-blind, phase III study presented at the annual scientific sessions of the American College of Cardiology.

"In high-risk patients refractory to maximally tolerated statin therapy, the addition of mipomersen significantly reduced LDL-C and other atherogenic lipids and lipoproteins," said Dr. William C. Cromwell of the Presbyterian Cardiovascular Institute in Charlotte, N.C.

Mipomersen is the first of a new class of agents called apolipoprotein B (apoB) synthesis inhibitors. In the study, the drug was administered subcutaneously once a week. Among its side effects were injection site reactions, increases in alanine aminotransferase (ALT) levels, and steatosis.

The study included 158 patients at high risk for cardiovascular events who were unable to achieve target LDL-C levels with statins, bile-acid sequestrants, and niacin. At baseline, all patients were on maximally tolerated doses of a statin; 63 were on the maximal approved dose, and 25 were also receiving ezetimibe.

All subjects had LDL-C levels of at least 100 mg/dL and triglycerides below 200 mg/dL. They were randomized 2:1 to 200 mg subcutaneous mipomersen or placebo weekly for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28 or 2 weeks after the last dose if treatment was not completed.

LDL-C levels of less than 100 mg/dL were achieved by 77 (76%) mipomersen-treated patients, compared with 19 (38%) placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 51 (50%) and 4 (8%), respectively.

The percent reduction in LDL cholesterol from baseline to the primary efficacy time point was a 37% drop in the mipomersen arm and a 5% drop in the placebo arm, a significant difference.

"LDL-C levels decreased through the first 17 weeks of treatment and remained relatively low through week 28," Dr. Cromwell observed. "Mipomersen’s lipid-lowering effects were independent of baseline LDL-C or race, and were similar for patients with and without diabetes."

The effect of the drug in the diabetic subset was robust. In the diabetes cohort, the mean decline in LDL-C from baseline was 51% for the 56 patients on mipomersen and 32% for the 29 on placebo.

Dr. Cromwell noted that the drug had a more pronounced effect in females and in patients whose age was above the median. However, mipomersen’s effects in males and in younger persons were still statistically significant and clinically meaningful.

Mipomersen also was associated with significant reductions from baseline values in apoB (38%), total cholesterol (26%), non-HDL cholesterol (36%), and lipoprotein(a) (24%). HDL-C levels did not change significantly from baseline.

Sixty of the 105 mipomersen-treated patients (57%) and 44 of 52 placebo patients (85%) completed treatment. A total of 26 mipomersen-treated patients and 2 placebo-treated patients discontinued due to on-treatment adverse events. Of the mipomersen noncompleters, seven discontinued due to a liver enzyme-related adverse event, and seven stopped because of an injection site reaction.

Injection site reactions were the most common adverse event, occurring in 78% of the mipomersen group and 31% of the placebo group. Flu-like symptoms occurred in 34% and 21%, respectively.

"Injection site reaction is the biggest side effect with this drug. This ranges from induration to redness, and some patients have skin discoloration. It’s real, and it does have to be managed," Dr. Cromwell acknowledged.

ALT elevations at least 3 times the upper limit of normal were observed in 14% of patients on mipomersen, versus none receiving placebo, but this occurred without concomitant significant bilirubin elevations, he said. For 10% of patients, ALT elevations occurred on consecutive measurements at least 7 days apart. One patient had an ALT of at least 10 times the upper limit of normal.

"We don’t see this as a huge ALT signal," Dr. Cromwell pointed out. "This is against the backdrop of a statin, which is already sensitizing the liver. We think it’s reassuring."

Approximately one-third of patients had an increase in steatosis, defined as liver fat increasing by at least 5%; median percent change from baseline was 15%. "This does not represent a huge accumulation of fat. Instead, it is a signal that it’s there at 28 weeks, and it is not particularly worrying. In a series of patients with much longer exposures, there is a plateau in this increase."

Dr. Patrick Moriarty, a lipid specialist who is assistant professor of medicine at the University of Kansas, Kansas City, commented, "We treat many refractory patients, and I can tell you that a drug of this class is very much needed in this patient population. It will help get their lipid numbers down."

The fact that patients achieve good LDL-C reductions on top of statin therapy is very encouraging, he said, noting, "The drug is not for every patient, but it could fill the need for an effective treatment in a small subset."

In Dr. Moriarty’s opinion, the injectable delivery will not be a barrier to acceptance. "It could be a problem for some patients and physicians, but patients can do these injections themselves, just like diabetes patients do. In studies I’ve participated in, we offer patients the opportunity to have the nurse give them the injections but most patients learn to do [the injections] themselves."

The study was sponsored by Isis Pharmaceuticals and Genzyme Corporation. Dr. Cromwell has received consultant fees or honoraria from Isis. Dr. Moriarty has participated in clinical trials of mipomersen.

NEW ORLEANS – In patients with hypercholesterolemia and high cardiovascular risk, the novel agent mipomersen administered as add-on therapy led to robust reductions in LDL cholesterol, based on the results of a double-blind, phase III study presented at the annual scientific sessions of the American College of Cardiology.

"In high-risk patients refractory to maximally tolerated statin therapy, the addition of mipomersen significantly reduced LDL-C and other atherogenic lipids and lipoproteins," said Dr. William C. Cromwell of the Presbyterian Cardiovascular Institute in Charlotte, N.C.

Mipomersen is the first of a new class of agents called apolipoprotein B (apoB) synthesis inhibitors. In the study, the drug was administered subcutaneously once a week. Among its side effects were injection site reactions, increases in alanine aminotransferase (ALT) levels, and steatosis.

The study included 158 patients at high risk for cardiovascular events who were unable to achieve target LDL-C levels with statins, bile-acid sequestrants, and niacin. At baseline, all patients were on maximally tolerated doses of a statin; 63 were on the maximal approved dose, and 25 were also receiving ezetimibe.

All subjects had LDL-C levels of at least 100 mg/dL and triglycerides below 200 mg/dL. They were randomized 2:1 to 200 mg subcutaneous mipomersen or placebo weekly for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28 or 2 weeks after the last dose if treatment was not completed.

LDL-C levels of less than 100 mg/dL were achieved by 77 (76%) mipomersen-treated patients, compared with 19 (38%) placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 51 (50%) and 4 (8%), respectively.

The percent reduction in LDL cholesterol from baseline to the primary efficacy time point was a 37% drop in the mipomersen arm and a 5% drop in the placebo arm, a significant difference.

"LDL-C levels decreased through the first 17 weeks of treatment and remained relatively low through week 28," Dr. Cromwell observed. "Mipomersen’s lipid-lowering effects were independent of baseline LDL-C or race, and were similar for patients with and without diabetes."

The effect of the drug in the diabetic subset was robust. In the diabetes cohort, the mean decline in LDL-C from baseline was 51% for the 56 patients on mipomersen and 32% for the 29 on placebo.

Dr. Cromwell noted that the drug had a more pronounced effect in females and in patients whose age was above the median. However, mipomersen’s effects in males and in younger persons were still statistically significant and clinically meaningful.

Mipomersen also was associated with significant reductions from baseline values in apoB (38%), total cholesterol (26%), non-HDL cholesterol (36%), and lipoprotein(a) (24%). HDL-C levels did not change significantly from baseline.

Sixty of the 105 mipomersen-treated patients (57%) and 44 of 52 placebo patients (85%) completed treatment. A total of 26 mipomersen-treated patients and 2 placebo-treated patients discontinued due to on-treatment adverse events. Of the mipomersen noncompleters, seven discontinued due to a liver enzyme-related adverse event, and seven stopped because of an injection site reaction.

Injection site reactions were the most common adverse event, occurring in 78% of the mipomersen group and 31% of the placebo group. Flu-like symptoms occurred in 34% and 21%, respectively.

"Injection site reaction is the biggest side effect with this drug. This ranges from induration to redness, and some patients have skin discoloration. It’s real, and it does have to be managed," Dr. Cromwell acknowledged.

ALT elevations at least 3 times the upper limit of normal were observed in 14% of patients on mipomersen, versus none receiving placebo, but this occurred without concomitant significant bilirubin elevations, he said. For 10% of patients, ALT elevations occurred on consecutive measurements at least 7 days apart. One patient had an ALT of at least 10 times the upper limit of normal.

"We don’t see this as a huge ALT signal," Dr. Cromwell pointed out. "This is against the backdrop of a statin, which is already sensitizing the liver. We think it’s reassuring."

Approximately one-third of patients had an increase in steatosis, defined as liver fat increasing by at least 5%; median percent change from baseline was 15%. "This does not represent a huge accumulation of fat. Instead, it is a signal that it’s there at 28 weeks, and it is not particularly worrying. In a series of patients with much longer exposures, there is a plateau in this increase."

Dr. Patrick Moriarty, a lipid specialist who is assistant professor of medicine at the University of Kansas, Kansas City, commented, "We treat many refractory patients, and I can tell you that a drug of this class is very much needed in this patient population. It will help get their lipid numbers down."

The fact that patients achieve good LDL-C reductions on top of statin therapy is very encouraging, he said, noting, "The drug is not for every patient, but it could fill the need for an effective treatment in a small subset."

In Dr. Moriarty’s opinion, the injectable delivery will not be a barrier to acceptance. "It could be a problem for some patients and physicians, but patients can do these injections themselves, just like diabetes patients do. In studies I’ve participated in, we offer patients the opportunity to have the nurse give them the injections but most patients learn to do [the injections] themselves."

The study was sponsored by Isis Pharmaceuticals and Genzyme Corporation. Dr. Cromwell has received consultant fees or honoraria from Isis. Dr. Moriarty has participated in clinical trials of mipomersen.

NEW ORLEANS – In patients with hypercholesterolemia and high cardiovascular risk, the novel agent mipomersen administered as add-on therapy led to robust reductions in LDL cholesterol, based on the results of a double-blind, phase III study presented at the annual scientific sessions of the American College of Cardiology.

"In high-risk patients refractory to maximally tolerated statin therapy, the addition of mipomersen significantly reduced LDL-C and other atherogenic lipids and lipoproteins," said Dr. William C. Cromwell of the Presbyterian Cardiovascular Institute in Charlotte, N.C.

Mipomersen is the first of a new class of agents called apolipoprotein B (apoB) synthesis inhibitors. In the study, the drug was administered subcutaneously once a week. Among its side effects were injection site reactions, increases in alanine aminotransferase (ALT) levels, and steatosis.

The study included 158 patients at high risk for cardiovascular events who were unable to achieve target LDL-C levels with statins, bile-acid sequestrants, and niacin. At baseline, all patients were on maximally tolerated doses of a statin; 63 were on the maximal approved dose, and 25 were also receiving ezetimibe.

All subjects had LDL-C levels of at least 100 mg/dL and triglycerides below 200 mg/dL. They were randomized 2:1 to 200 mg subcutaneous mipomersen or placebo weekly for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28 or 2 weeks after the last dose if treatment was not completed.

LDL-C levels of less than 100 mg/dL were achieved by 77 (76%) mipomersen-treated patients, compared with 19 (38%) placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 51 (50%) and 4 (8%), respectively.

The percent reduction in LDL cholesterol from baseline to the primary efficacy time point was a 37% drop in the mipomersen arm and a 5% drop in the placebo arm, a significant difference.

"LDL-C levels decreased through the first 17 weeks of treatment and remained relatively low through week 28," Dr. Cromwell observed. "Mipomersen’s lipid-lowering effects were independent of baseline LDL-C or race, and were similar for patients with and without diabetes."

The effect of the drug in the diabetic subset was robust. In the diabetes cohort, the mean decline in LDL-C from baseline was 51% for the 56 patients on mipomersen and 32% for the 29 on placebo.

Dr. Cromwell noted that the drug had a more pronounced effect in females and in patients whose age was above the median. However, mipomersen’s effects in males and in younger persons were still statistically significant and clinically meaningful.

Mipomersen also was associated with significant reductions from baseline values in apoB (38%), total cholesterol (26%), non-HDL cholesterol (36%), and lipoprotein(a) (24%). HDL-C levels did not change significantly from baseline.

Sixty of the 105 mipomersen-treated patients (57%) and 44 of 52 placebo patients (85%) completed treatment. A total of 26 mipomersen-treated patients and 2 placebo-treated patients discontinued due to on-treatment adverse events. Of the mipomersen noncompleters, seven discontinued due to a liver enzyme-related adverse event, and seven stopped because of an injection site reaction.

Injection site reactions were the most common adverse event, occurring in 78% of the mipomersen group and 31% of the placebo group. Flu-like symptoms occurred in 34% and 21%, respectively.

"Injection site reaction is the biggest side effect with this drug. This ranges from induration to redness, and some patients have skin discoloration. It’s real, and it does have to be managed," Dr. Cromwell acknowledged.

ALT elevations at least 3 times the upper limit of normal were observed in 14% of patients on mipomersen, versus none receiving placebo, but this occurred without concomitant significant bilirubin elevations, he said. For 10% of patients, ALT elevations occurred on consecutive measurements at least 7 days apart. One patient had an ALT of at least 10 times the upper limit of normal.

"We don’t see this as a huge ALT signal," Dr. Cromwell pointed out. "This is against the backdrop of a statin, which is already sensitizing the liver. We think it’s reassuring."

Approximately one-third of patients had an increase in steatosis, defined as liver fat increasing by at least 5%; median percent change from baseline was 15%. "This does not represent a huge accumulation of fat. Instead, it is a signal that it’s there at 28 weeks, and it is not particularly worrying. In a series of patients with much longer exposures, there is a plateau in this increase."

Dr. Patrick Moriarty, a lipid specialist who is assistant professor of medicine at the University of Kansas, Kansas City, commented, "We treat many refractory patients, and I can tell you that a drug of this class is very much needed in this patient population. It will help get their lipid numbers down."

The fact that patients achieve good LDL-C reductions on top of statin therapy is very encouraging, he said, noting, "The drug is not for every patient, but it could fill the need for an effective treatment in a small subset."

In Dr. Moriarty’s opinion, the injectable delivery will not be a barrier to acceptance. "It could be a problem for some patients and physicians, but patients can do these injections themselves, just like diabetes patients do. In studies I’ve participated in, we offer patients the opportunity to have the nurse give them the injections but most patients learn to do [the injections] themselves."

The study was sponsored by Isis Pharmaceuticals and Genzyme Corporation. Dr. Cromwell has received consultant fees or honoraria from Isis. Dr. Moriarty has participated in clinical trials of mipomersen.

NEW ORLEANS - Carotid intima-media thickness was found to be increased in middle-aged men taking antidepressants in a study reported at the annual scientific sessions of the American College of Cardiology.

"There is a clear association between increased intima-media thickness [IMT] and taking an antidepressant of any kind, and this trend is even stronger when we look at people who are on these medications and are more depressed," said Dr. Amit Shah, a cardiology fellow at Emory University, Atlanta.

Dr. Janet Wright senior vice president of science and quality for the ACC, commented that the study should be viewed as "directional. ... It only tees things up for the next range of studies." Dr. Wright, a cardiologist in Chico, Calif., added that "it does suggest that perhaps a person who is depressed and on an antidepressant may need monitoring."

Carotid IMT and brachial flow-mediated dilation was assessed using B-mode ultrasound in 513 middle-aged male twins from the Vietnam Era Twin Registry. Traditional risk factors for ischemic heart disease were measured. Depression and posttraumatic stress disorder (PTSD) were assessed with the Structured Clinical Interview for the Diagnosis of Psychiatric Disorders, and depressive symptoms were measured via the Beck Depression Inventory. Medication regimens were verified by a clinician. Mixed effects regression models were used to analyze the overall association and to examine differences within twin pairs discordant for antidepressant intake.

Participants were a mean age of 55 years; 95% were white and 16% were taking antidepressants, mainly selective serotonin reuptake inhibitors (60%). In an analysis of the association by type of antidepressant, an increase in IMT was noted regardless of the class of antidepressants.

Antidepressant use was associated with an IMT increase of 37 microns, which represents about a 5% increase from the mean IMT value of 762 microns seen in the population, a significant difference compared with men not taking antidepressants.

The findings emerged from an adjusted analysis that controlled for conventional cardiovascular risk factors and for depressive symptoms, history of major depression and heart disease, alcohol and coffee consumption, statin use, physical activity, education, and employment status.

In an analysis of 59 twin pairs where one brother was taking an antidepressant and the other was not, the antidepressant user had an IMT that was 41 microns thicker (P = .01), he reported.

Each additional year of life is associated with a 10-micron increase in IMT, therefore, the brother on the antidepressant could be considered to be 4 years "older" in terms of atherosclerosis. In previous studies, each 10-micron increase in IMT has been linked to a 1.8% increase in risk, Dr. Shah noted.

Previous studies have linked the presence of depression with an increased risk of cardiovascular disease. In this study, neither depression nor posttraumatic stress disorder significantly predicted an increase in IMT. However, the study did show that subjects taking antidepressants who also reported clinical symptoms of depression had higher IMTs than those taking antidepressants who had fewer symptoms of depression.

"Because we didn’t see an association between depression itself and a thickening of the carotid artery, it strengthens the argument that this is more likely the antidepressants than the actual depression that is behind the association," Dr. Shah said.

History of a previous myocardial infarction, which was noted for 12% of the cohort, was not independently associated with increased IMT, nor was there a differential effect for identical and fraternal twins.

Speculating on the possible mechanism for the association, the investigators suggested that antidepressants may increase IMT through augmented release of vasoconstrictive neuropeptides. "The antidepressants may act synergistically with depressive symptoms to increase vascular disease," he said. "There is a potential interaction between the depressive symptoms, the neurohormonal effects of the depression itself, and the medication."

The findings suggest that the risk/benefit ratio of antidepressants should be considered, especially in patients with pre-existing cardiovascular disease, Dr. Shah said. "While not showing causality, it is important to take studies such as this into account in patient care, especially when the patient may not be deriving much benefit from the antidepressant."

Dr. Shah and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Carotid intima-media thickness was found to be increased in middle-aged men taking antidepressants in a study reported at the annual scientific sessions of the American College of Cardiology.

"There is a clear association between increased intima-media thickness [IMT] and taking an antidepressant of any kind, and this trend is even stronger when we look at people who are on these medications and are more depressed," said Dr. Amit Shah, a cardiology fellow at Emory University, Atlanta.

Dr. Janet Wright senior vice president of science and quality for the ACC, commented that the study should be viewed as "directional. ... It only tees things up for the next range of studies." Dr. Wright, a cardiologist in Chico, Calif., added that "it does suggest that perhaps a person who is depressed and on an antidepressant may need monitoring."

Carotid IMT and brachial flow-mediated dilation was assessed using B-mode ultrasound in 513 middle-aged male twins from the Vietnam Era Twin Registry. Traditional risk factors for ischemic heart disease were measured. Depression and posttraumatic stress disorder (PTSD) were assessed with the Structured Clinical Interview for the Diagnosis of Psychiatric Disorders, and depressive symptoms were measured via the Beck Depression Inventory. Medication regimens were verified by a clinician. Mixed effects regression models were used to analyze the overall association and to examine differences within twin pairs discordant for antidepressant intake.

Participants were a mean age of 55 years; 95% were white and 16% were taking antidepressants, mainly selective serotonin reuptake inhibitors (60%). In an analysis of the association by type of antidepressant, an increase in IMT was noted regardless of the class of antidepressants.

Antidepressant use was associated with an IMT increase of 37 microns, which represents about a 5% increase from the mean IMT value of 762 microns seen in the population, a significant difference compared with men not taking antidepressants.

The findings emerged from an adjusted analysis that controlled for conventional cardiovascular risk factors and for depressive symptoms, history of major depression and heart disease, alcohol and coffee consumption, statin use, physical activity, education, and employment status.

In an analysis of 59 twin pairs where one brother was taking an antidepressant and the other was not, the antidepressant user had an IMT that was 41 microns thicker (P = .01), he reported.

Each additional year of life is associated with a 10-micron increase in IMT, therefore, the brother on the antidepressant could be considered to be 4 years "older" in terms of atherosclerosis. In previous studies, each 10-micron increase in IMT has been linked to a 1.8% increase in risk, Dr. Shah noted.

Previous studies have linked the presence of depression with an increased risk of cardiovascular disease. In this study, neither depression nor posttraumatic stress disorder significantly predicted an increase in IMT. However, the study did show that subjects taking antidepressants who also reported clinical symptoms of depression had higher IMTs than those taking antidepressants who had fewer symptoms of depression.

"Because we didn’t see an association between depression itself and a thickening of the carotid artery, it strengthens the argument that this is more likely the antidepressants than the actual depression that is behind the association," Dr. Shah said.

History of a previous myocardial infarction, which was noted for 12% of the cohort, was not independently associated with increased IMT, nor was there a differential effect for identical and fraternal twins.

Speculating on the possible mechanism for the association, the investigators suggested that antidepressants may increase IMT through augmented release of vasoconstrictive neuropeptides. "The antidepressants may act synergistically with depressive symptoms to increase vascular disease," he said. "There is a potential interaction between the depressive symptoms, the neurohormonal effects of the depression itself, and the medication."

The findings suggest that the risk/benefit ratio of antidepressants should be considered, especially in patients with pre-existing cardiovascular disease, Dr. Shah said. "While not showing causality, it is important to take studies such as this into account in patient care, especially when the patient may not be deriving much benefit from the antidepressant."

Dr. Shah and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Carotid intima-media thickness was found to be increased in middle-aged men taking antidepressants in a study reported at the annual scientific sessions of the American College of Cardiology.

"There is a clear association between increased intima-media thickness [IMT] and taking an antidepressant of any kind, and this trend is even stronger when we look at people who are on these medications and are more depressed," said Dr. Amit Shah, a cardiology fellow at Emory University, Atlanta.

Dr. Janet Wright senior vice president of science and quality for the ACC, commented that the study should be viewed as "directional. ... It only tees things up for the next range of studies." Dr. Wright, a cardiologist in Chico, Calif., added that "it does suggest that perhaps a person who is depressed and on an antidepressant may need monitoring."

Carotid IMT and brachial flow-mediated dilation was assessed using B-mode ultrasound in 513 middle-aged male twins from the Vietnam Era Twin Registry. Traditional risk factors for ischemic heart disease were measured. Depression and posttraumatic stress disorder (PTSD) were assessed with the Structured Clinical Interview for the Diagnosis of Psychiatric Disorders, and depressive symptoms were measured via the Beck Depression Inventory. Medication regimens were verified by a clinician. Mixed effects regression models were used to analyze the overall association and to examine differences within twin pairs discordant for antidepressant intake.

Participants were a mean age of 55 years; 95% were white and 16% were taking antidepressants, mainly selective serotonin reuptake inhibitors (60%). In an analysis of the association by type of antidepressant, an increase in IMT was noted regardless of the class of antidepressants.

Antidepressant use was associated with an IMT increase of 37 microns, which represents about a 5% increase from the mean IMT value of 762 microns seen in the population, a significant difference compared with men not taking antidepressants.

The findings emerged from an adjusted analysis that controlled for conventional cardiovascular risk factors and for depressive symptoms, history of major depression and heart disease, alcohol and coffee consumption, statin use, physical activity, education, and employment status.

In an analysis of 59 twin pairs where one brother was taking an antidepressant and the other was not, the antidepressant user had an IMT that was 41 microns thicker (P = .01), he reported.

Each additional year of life is associated with a 10-micron increase in IMT, therefore, the brother on the antidepressant could be considered to be 4 years "older" in terms of atherosclerosis. In previous studies, each 10-micron increase in IMT has been linked to a 1.8% increase in risk, Dr. Shah noted.

Previous studies have linked the presence of depression with an increased risk of cardiovascular disease. In this study, neither depression nor posttraumatic stress disorder significantly predicted an increase in IMT. However, the study did show that subjects taking antidepressants who also reported clinical symptoms of depression had higher IMTs than those taking antidepressants who had fewer symptoms of depression.

"Because we didn’t see an association between depression itself and a thickening of the carotid artery, it strengthens the argument that this is more likely the antidepressants than the actual depression that is behind the association," Dr. Shah said.

History of a previous myocardial infarction, which was noted for 12% of the cohort, was not independently associated with increased IMT, nor was there a differential effect for identical and fraternal twins.

Speculating on the possible mechanism for the association, the investigators suggested that antidepressants may increase IMT through augmented release of vasoconstrictive neuropeptides. "The antidepressants may act synergistically with depressive symptoms to increase vascular disease," he said. "There is a potential interaction between the depressive symptoms, the neurohormonal effects of the depression itself, and the medication."

The findings suggest that the risk/benefit ratio of antidepressants should be considered, especially in patients with pre-existing cardiovascular disease, Dr. Shah said. "While not showing causality, it is important to take studies such as this into account in patient care, especially when the patient may not be deriving much benefit from the antidepressant."

Dr. Shah and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Carotid intima-media thickness was found to be increased in middle-aged men taking antidepressants in a study reported at the annual scientific sessions of the American College of Cardiology.

"There is a clear association between increased intima-media thickness [IMT] and taking an antidepressant of any kind, and this trend is even stronger when we look at people who are on these medications and are more depressed," said Dr. Amit Shah, a cardiology fellow at Emory University, Atlanta.

Dr. Janet Wright senior vice president of science and quality for the ACC, commented that the study should be viewed as "directional. ... It only tees things up for the next range of studies." Dr. Wright, a cardiologist in Chico, Calif., added that "it does suggest that perhaps a person who is depressed and on an antidepressant may need monitoring."

Carotid IMT and brachial flow-mediated dilation was assessed using B-mode ultrasound in 513 middle-aged male twins from the Vietnam Era Twin Registry. Traditional risk factors for ischemic heart disease were measured. Depression and posttraumatic stress disorder (PTSD) were assessed with the Structured Clinical Interview for the Diagnosis of Psychiatric Disorders, and depressive symptoms were measured via the Beck Depression Inventory. Medication regimens were verified by a clinician. Mixed effects regression models were used to analyze the overall association and to examine differences within twin pairs discordant for antidepressant intake.

Participants were a mean age of 55 years; 95% were white and 16% were taking antidepressants, mainly selective serotonin reuptake inhibitors (60%). In an analysis of the association by type of antidepressant, an increase in IMT was noted regardless of the class of antidepressants.

Antidepressant use was associated with an IMT increase of 37 microns, which represents about a 5% increase from the mean IMT value of 762 microns seen in the population, a significant difference compared with men not taking antidepressants.

The findings emerged from an adjusted analysis that controlled for conventional cardiovascular risk factors and for depressive symptoms, history of major depression and heart disease, alcohol and coffee consumption, statin use, physical activity, education, and employment status.

In an analysis of 59 twin pairs where one brother was taking an antidepressant and the other was not, the antidepressant user had an IMT that was 41 microns thicker (P = .01), he reported.

Each additional year of life is associated with a 10-micron increase in IMT, therefore, the brother on the antidepressant could be considered to be 4 years "older" in terms of atherosclerosis. In previous studies, each 10-micron increase in IMT has been linked to a 1.8% increase in risk, Dr. Shah noted.

Previous studies have linked the presence of depression with an increased risk of cardiovascular disease. In this study, neither depression nor posttraumatic stress disorder significantly predicted an increase in IMT. However, the study did show that subjects taking antidepressants who also reported clinical symptoms of depression had higher IMTs than those taking antidepressants who had fewer symptoms of depression.

"Because we didn’t see an association between depression itself and a thickening of the carotid artery, it strengthens the argument that this is more likely the antidepressants than the actual depression that is behind the association," Dr. Shah said.

History of a previous myocardial infarction, which was noted for 12% of the cohort, was not independently associated with increased IMT, nor was there a differential effect for identical and fraternal twins.

Speculating on the possible mechanism for the association, the investigators suggested that antidepressants may increase IMT through augmented release of vasoconstrictive neuropeptides. "The antidepressants may act synergistically with depressive symptoms to increase vascular disease," he said. "There is a potential interaction between the depressive symptoms, the neurohormonal effects of the depression itself, and the medication."

The findings suggest that the risk/benefit ratio of antidepressants should be considered, especially in patients with pre-existing cardiovascular disease, Dr. Shah said. "While not showing causality, it is important to take studies such as this into account in patient care, especially when the patient may not be deriving much benefit from the antidepressant."

Dr. Shah and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Carotid intima-media thickness was found to be increased in middle-aged men taking antidepressants in a study reported at the annual scientific sessions of the American College of Cardiology.

"There is a clear association between increased intima-media thickness [IMT] and taking an antidepressant of any kind, and this trend is even stronger when we look at people who are on these medications and are more depressed," said Dr. Amit Shah, a cardiology fellow at Emory University, Atlanta.

Dr. Janet Wright senior vice president of science and quality for the ACC, commented that the study should be viewed as "directional. ... It only tees things up for the next range of studies." Dr. Wright, a cardiologist in Chico, Calif., added that "it does suggest that perhaps a person who is depressed and on an antidepressant may need monitoring."

Carotid IMT and brachial flow-mediated dilation was assessed using B-mode ultrasound in 513 middle-aged male twins from the Vietnam Era Twin Registry. Traditional risk factors for ischemic heart disease were measured. Depression and posttraumatic stress disorder (PTSD) were assessed with the Structured Clinical Interview for the Diagnosis of Psychiatric Disorders, and depressive symptoms were measured via the Beck Depression Inventory. Medication regimens were verified by a clinician. Mixed effects regression models were used to analyze the overall association and to examine differences within twin pairs discordant for antidepressant intake.

Participants were a mean age of 55 years; 95% were white and 16% were taking antidepressants, mainly selective serotonin reuptake inhibitors (60%). In an analysis of the association by type of antidepressant, an increase in IMT was noted regardless of the class of antidepressants.

Antidepressant use was associated with an IMT increase of 37 microns, which represents about a 5% increase from the mean IMT value of 762 microns seen in the population, a significant difference compared with men not taking antidepressants.

The findings emerged from an adjusted analysis that controlled for conventional cardiovascular risk factors and for depressive symptoms, history of major depression and heart disease, alcohol and coffee consumption, statin use, physical activity, education, and employment status.

In an analysis of 59 twin pairs where one brother was taking an antidepressant and the other was not, the antidepressant user had an IMT that was 41 microns thicker (P = .01), he reported.

Each additional year of life is associated with a 10-micron increase in IMT, therefore, the brother on the antidepressant could be considered to be 4 years "older" in terms of atherosclerosis. In previous studies, each 10-micron increase in IMT has been linked to a 1.8% increase in risk, Dr. Shah noted.

Previous studies have linked the presence of depression with an increased risk of cardiovascular disease. In this study, neither depression nor posttraumatic stress disorder significantly predicted an increase in IMT. However, the study did show that subjects taking antidepressants who also reported clinical symptoms of depression had higher IMTs than those taking antidepressants who had fewer symptoms of depression.

"Because we didn’t see an association between depression itself and a thickening of the carotid artery, it strengthens the argument that this is more likely the antidepressants than the actual depression that is behind the association," Dr. Shah said.

History of a previous myocardial infarction, which was noted for 12% of the cohort, was not independently associated with increased IMT, nor was there a differential effect for identical and fraternal twins.

Speculating on the possible mechanism for the association, the investigators suggested that antidepressants may increase IMT through augmented release of vasoconstrictive neuropeptides. "The antidepressants may act synergistically with depressive symptoms to increase vascular disease," he said. "There is a potential interaction between the depressive symptoms, the neurohormonal effects of the depression itself, and the medication."

The findings suggest that the risk/benefit ratio of antidepressants should be considered, especially in patients with pre-existing cardiovascular disease, Dr. Shah said. "While not showing causality, it is important to take studies such as this into account in patient care, especially when the patient may not be deriving much benefit from the antidepressant."

Dr. Shah and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Carotid intima-media thickness was found to be increased in middle-aged men taking antidepressants in a study reported at the annual scientific sessions of the American College of Cardiology.

"There is a clear association between increased intima-media thickness [IMT] and taking an antidepressant of any kind, and this trend is even stronger when we look at people who are on these medications and are more depressed," said Dr. Amit Shah, a cardiology fellow at Emory University, Atlanta.

Dr. Janet Wright senior vice president of science and quality for the ACC, commented that the study should be viewed as "directional. ... It only tees things up for the next range of studies." Dr. Wright, a cardiologist in Chico, Calif., added that "it does suggest that perhaps a person who is depressed and on an antidepressant may need monitoring."

Carotid IMT and brachial flow-mediated dilation was assessed using B-mode ultrasound in 513 middle-aged male twins from the Vietnam Era Twin Registry. Traditional risk factors for ischemic heart disease were measured. Depression and posttraumatic stress disorder (PTSD) were assessed with the Structured Clinical Interview for the Diagnosis of Psychiatric Disorders, and depressive symptoms were measured via the Beck Depression Inventory. Medication regimens were verified by a clinician. Mixed effects regression models were used to analyze the overall association and to examine differences within twin pairs discordant for antidepressant intake.

Participants were a mean age of 55 years; 95% were white and 16% were taking antidepressants, mainly selective serotonin reuptake inhibitors (60%). In an analysis of the association by type of antidepressant, an increase in IMT was noted regardless of the class of antidepressants.

Antidepressant use was associated with an IMT increase of 37 microns, which represents about a 5% increase from the mean IMT value of 762 microns seen in the population, a significant difference compared with men not taking antidepressants.

The findings emerged from an adjusted analysis that controlled for conventional cardiovascular risk factors and for depressive symptoms, history of major depression and heart disease, alcohol and coffee consumption, statin use, physical activity, education, and employment status.

In an analysis of 59 twin pairs where one brother was taking an antidepressant and the other was not, the antidepressant user had an IMT that was 41 microns thicker (P = .01), he reported.

Each additional year of life is associated with a 10-micron increase in IMT, therefore, the brother on the antidepressant could be considered to be 4 years "older" in terms of atherosclerosis. In previous studies, each 10-micron increase in IMT has been linked to a 1.8% increase in risk, Dr. Shah noted.

Previous studies have linked the presence of depression with an increased risk of cardiovascular disease. In this study, neither depression nor posttraumatic stress disorder significantly predicted an increase in IMT. However, the study did show that subjects taking antidepressants who also reported clinical symptoms of depression had higher IMTs than those taking antidepressants who had fewer symptoms of depression.

"Because we didn’t see an association between depression itself and a thickening of the carotid artery, it strengthens the argument that this is more likely the antidepressants than the actual depression that is behind the association," Dr. Shah said.

History of a previous myocardial infarction, which was noted for 12% of the cohort, was not independently associated with increased IMT, nor was there a differential effect for identical and fraternal twins.

Speculating on the possible mechanism for the association, the investigators suggested that antidepressants may increase IMT through augmented release of vasoconstrictive neuropeptides. "The antidepressants may act synergistically with depressive symptoms to increase vascular disease," he said. "There is a potential interaction between the depressive symptoms, the neurohormonal effects of the depression itself, and the medication."

The findings suggest that the risk/benefit ratio of antidepressants should be considered, especially in patients with pre-existing cardiovascular disease, Dr. Shah said. "While not showing causality, it is important to take studies such as this into account in patient care, especially when the patient may not be deriving much benefit from the antidepressant."

Dr. Shah and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Carotid intima-media thickness was found to be increased in middle-aged men taking antidepressants in a study reported at the annual scientific sessions of the American College of Cardiology.

"There is a clear association between increased intima-media thickness [IMT] and taking an antidepressant of any kind, and this trend is even stronger when we look at people who are on these medications and are more depressed," said Dr. Amit Shah, a cardiology fellow at Emory University, Atlanta.

Dr. Janet Wright senior vice president of science and quality for the ACC, commented that the study should be viewed as "directional. ... It only tees things up for the next range of studies." Dr. Wright, a cardiologist in Chico, Calif., added that "it does suggest that perhaps a person who is depressed and on an antidepressant may need monitoring."

Carotid IMT and brachial flow-mediated dilation was assessed using B-mode ultrasound in 513 middle-aged male twins from the Vietnam Era Twin Registry. Traditional risk factors for ischemic heart disease were measured. Depression and posttraumatic stress disorder (PTSD) were assessed with the Structured Clinical Interview for the Diagnosis of Psychiatric Disorders, and depressive symptoms were measured via the Beck Depression Inventory. Medication regimens were verified by a clinician. Mixed effects regression models were used to analyze the overall association and to examine differences within twin pairs discordant for antidepressant intake.

Participants were a mean age of 55 years; 95% were white and 16% were taking antidepressants, mainly selective serotonin reuptake inhibitors (60%). In an analysis of the association by type of antidepressant, an increase in IMT was noted regardless of the class of antidepressants.

Antidepressant use was associated with an IMT increase of 37 microns, which represents about a 5% increase from the mean IMT value of 762 microns seen in the population, a significant difference compared with men not taking antidepressants.

The findings emerged from an adjusted analysis that controlled for conventional cardiovascular risk factors and for depressive symptoms, history of major depression and heart disease, alcohol and coffee consumption, statin use, physical activity, education, and employment status.

In an analysis of 59 twin pairs where one brother was taking an antidepressant and the other was not, the antidepressant user had an IMT that was 41 microns thicker (P = .01), he reported.

Each additional year of life is associated with a 10-micron increase in IMT, therefore, the brother on the antidepressant could be considered to be 4 years "older" in terms of atherosclerosis. In previous studies, each 10-micron increase in IMT has been linked to a 1.8% increase in risk, Dr. Shah noted.

Previous studies have linked the presence of depression with an increased risk of cardiovascular disease. In this study, neither depression nor posttraumatic stress disorder significantly predicted an increase in IMT. However, the study did show that subjects taking antidepressants who also reported clinical symptoms of depression had higher IMTs than those taking antidepressants who had fewer symptoms of depression.

"Because we didn’t see an association between depression itself and a thickening of the carotid artery, it strengthens the argument that this is more likely the antidepressants than the actual depression that is behind the association," Dr. Shah said.

History of a previous myocardial infarction, which was noted for 12% of the cohort, was not independently associated with increased IMT, nor was there a differential effect for identical and fraternal twins.

Speculating on the possible mechanism for the association, the investigators suggested that antidepressants may increase IMT through augmented release of vasoconstrictive neuropeptides. "The antidepressants may act synergistically with depressive symptoms to increase vascular disease," he said. "There is a potential interaction between the depressive symptoms, the neurohormonal effects of the depression itself, and the medication."

The findings suggest that the risk/benefit ratio of antidepressants should be considered, especially in patients with pre-existing cardiovascular disease, Dr. Shah said. "While not showing causality, it is important to take studies such as this into account in patient care, especially when the patient may not be deriving much benefit from the antidepressant."

Dr. Shah and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Carotid intima-media thickness was found to be increased in middle-aged men taking antidepressants in a study reported at the annual scientific sessions of the American College of Cardiology.

"There is a clear association between increased intima-media thickness [IMT] and taking an antidepressant of any kind, and this trend is even stronger when we look at people who are on these medications and are more depressed," said Dr. Amit Shah, a cardiology fellow at Emory University, Atlanta.

Dr. Janet Wright senior vice president of science and quality for the ACC, commented that the study should be viewed as "directional. ... It only tees things up for the next range of studies." Dr. Wright, a cardiologist in Chico, Calif., added that "it does suggest that perhaps a person who is depressed and on an antidepressant may need monitoring."

Carotid IMT and brachial flow-mediated dilation was assessed using B-mode ultrasound in 513 middle-aged male twins from the Vietnam Era Twin Registry. Traditional risk factors for ischemic heart disease were measured. Depression and posttraumatic stress disorder (PTSD) were assessed with the Structured Clinical Interview for the Diagnosis of Psychiatric Disorders, and depressive symptoms were measured via the Beck Depression Inventory. Medication regimens were verified by a clinician. Mixed effects regression models were used to analyze the overall association and to examine differences within twin pairs discordant for antidepressant intake.

Participants were a mean age of 55 years; 95% were white and 16% were taking antidepressants, mainly selective serotonin reuptake inhibitors (60%). In an analysis of the association by type of antidepressant, an increase in IMT was noted regardless of the class of antidepressants.

Antidepressant use was associated with an IMT increase of 37 microns, which represents about a 5% increase from the mean IMT value of 762 microns seen in the population, a significant difference compared with men not taking antidepressants.

The findings emerged from an adjusted analysis that controlled for conventional cardiovascular risk factors and for depressive symptoms, history of major depression and heart disease, alcohol and coffee consumption, statin use, physical activity, education, and employment status.

In an analysis of 59 twin pairs where one brother was taking an antidepressant and the other was not, the antidepressant user had an IMT that was 41 microns thicker (P = .01), he reported.

Each additional year of life is associated with a 10-micron increase in IMT, therefore, the brother on the antidepressant could be considered to be 4 years "older" in terms of atherosclerosis. In previous studies, each 10-micron increase in IMT has been linked to a 1.8% increase in risk, Dr. Shah noted.

Previous studies have linked the presence of depression with an increased risk of cardiovascular disease. In this study, neither depression nor posttraumatic stress disorder significantly predicted an increase in IMT. However, the study did show that subjects taking antidepressants who also reported clinical symptoms of depression had higher IMTs than those taking antidepressants who had fewer symptoms of depression.

"Because we didn’t see an association between depression itself and a thickening of the carotid artery, it strengthens the argument that this is more likely the antidepressants than the actual depression that is behind the association," Dr. Shah said.

History of a previous myocardial infarction, which was noted for 12% of the cohort, was not independently associated with increased IMT, nor was there a differential effect for identical and fraternal twins.

Speculating on the possible mechanism for the association, the investigators suggested that antidepressants may increase IMT through augmented release of vasoconstrictive neuropeptides. "The antidepressants may act synergistically with depressive symptoms to increase vascular disease," he said. "There is a potential interaction between the depressive symptoms, the neurohormonal effects of the depression itself, and the medication."

The findings suggest that the risk/benefit ratio of antidepressants should be considered, especially in patients with pre-existing cardiovascular disease, Dr. Shah said. "While not showing causality, it is important to take studies such as this into account in patient care, especially when the patient may not be deriving much benefit from the antidepressant."

Dr. Shah and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Carotid intima-media thickness was found to be increased in middle-aged men taking antidepressants in a study reported at the annual scientific sessions of the American College of Cardiology.

"There is a clear association between increased intima-media thickness [IMT] and taking an antidepressant of any kind, and this trend is even stronger when we look at people who are on these medications and are more depressed," said Dr. Amit Shah, a cardiology fellow at Emory University, Atlanta.

Dr. Janet Wright senior vice president of science and quality for the ACC, commented that the study should be viewed as "directional. ... It only tees things up for the next range of studies." Dr. Wright, a cardiologist in Chico, Calif., added that "it does suggest that perhaps a person who is depressed and on an antidepressant may need monitoring."

Carotid IMT and brachial flow-mediated dilation was assessed using B-mode ultrasound in 513 middle-aged male twins from the Vietnam Era Twin Registry. Traditional risk factors for ischemic heart disease were measured. Depression and posttraumatic stress disorder (PTSD) were assessed with the Structured Clinical Interview for the Diagnosis of Psychiatric Disorders, and depressive symptoms were measured via the Beck Depression Inventory. Medication regimens were verified by a clinician. Mixed effects regression models were used to analyze the overall association and to examine differences within twin pairs discordant for antidepressant intake.

Participants were a mean age of 55 years; 95% were white and 16% were taking antidepressants, mainly selective serotonin reuptake inhibitors (60%). In an analysis of the association by type of antidepressant, an increase in IMT was noted regardless of the class of antidepressants.

Antidepressant use was associated with an IMT increase of 37 microns, which represents about a 5% increase from the mean IMT value of 762 microns seen in the population, a significant difference compared with men not taking antidepressants.

The findings emerged from an adjusted analysis that controlled for conventional cardiovascular risk factors and for depressive symptoms, history of major depression and heart disease, alcohol and coffee consumption, statin use, physical activity, education, and employment status.

In an analysis of 59 twin pairs where one brother was taking an antidepressant and the other was not, the antidepressant user had an IMT that was 41 microns thicker (P = .01), he reported.

Each additional year of life is associated with a 10-micron increase in IMT, therefore, the brother on the antidepressant could be considered to be 4 years "older" in terms of atherosclerosis. In previous studies, each 10-micron increase in IMT has been linked to a 1.8% increase in risk, Dr. Shah noted.

Previous studies have linked the presence of depression with an increased risk of cardiovascular disease. In this study, neither depression nor posttraumatic stress disorder significantly predicted an increase in IMT. However, the study did show that subjects taking antidepressants who also reported clinical symptoms of depression had higher IMTs than those taking antidepressants who had fewer symptoms of depression.

"Because we didn’t see an association between depression itself and a thickening of the carotid artery, it strengthens the argument that this is more likely the antidepressants than the actual depression that is behind the association," Dr. Shah said.

History of a previous myocardial infarction, which was noted for 12% of the cohort, was not independently associated with increased IMT, nor was there a differential effect for identical and fraternal twins.

Speculating on the possible mechanism for the association, the investigators suggested that antidepressants may increase IMT through augmented release of vasoconstrictive neuropeptides. "The antidepressants may act synergistically with depressive symptoms to increase vascular disease," he said. "There is a potential interaction between the depressive symptoms, the neurohormonal effects of the depression itself, and the medication."

The findings suggest that the risk/benefit ratio of antidepressants should be considered, especially in patients with pre-existing cardiovascular disease, Dr. Shah said. "While not showing causality, it is important to take studies such as this into account in patient care, especially when the patient may not be deriving much benefit from the antidepressant."

Dr. Shah and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Carotid intima-media thickness was found to be increased in middle-aged men taking antidepressants in a study reported at the annual scientific sessions of the American College of Cardiology.

"There is a clear association between increased intima-media thickness [IMT] and taking an antidepressant of any kind, and this trend is even stronger when we look at people who are on these medications and are more depressed," said Dr. Amit Shah, a cardiology fellow at Emory University, Atlanta.

Dr. Janet Wright senior vice president of science and quality for the ACC, commented that the study should be viewed as "directional. ... It only tees things up for the next range of studies." Dr. Wright, a cardiologist in Chico, Calif., added that "it does suggest that perhaps a person who is depressed and on an antidepressant may need monitoring."

Carotid IMT and brachial flow-mediated dilation was assessed using B-mode ultrasound in 513 middle-aged male twins from the Vietnam Era Twin Registry. Traditional risk factors for ischemic heart disease were measured. Depression and posttraumatic stress disorder (PTSD) were assessed with the Structured Clinical Interview for the Diagnosis of Psychiatric Disorders, and depressive symptoms were measured via the Beck Depression Inventory. Medication regimens were verified by a clinician. Mixed effects regression models were used to analyze the overall association and to examine differences within twin pairs discordant for antidepressant intake.

Participants were a mean age of 55 years; 95% were white and 16% were taking antidepressants, mainly selective serotonin reuptake inhibitors (60%). In an analysis of the association by type of antidepressant, an increase in IMT was noted regardless of the class of antidepressants.

Antidepressant use was associated with an IMT increase of 37 microns, which represents about a 5% increase from the mean IMT value of 762 microns seen in the population, a significant difference compared with men not taking antidepressants.

The findings emerged from an adjusted analysis that controlled for conventional cardiovascular risk factors and for depressive symptoms, history of major depression and heart disease, alcohol and coffee consumption, statin use, physical activity, education, and employment status.

In an analysis of 59 twin pairs where one brother was taking an antidepressant and the other was not, the antidepressant user had an IMT that was 41 microns thicker (P = .01), he reported.

Each additional year of life is associated with a 10-micron increase in IMT, therefore, the brother on the antidepressant could be considered to be 4 years "older" in terms of atherosclerosis. In previous studies, each 10-micron increase in IMT has been linked to a 1.8% increase in risk, Dr. Shah noted.

Previous studies have linked the presence of depression with an increased risk of cardiovascular disease. In this study, neither depression nor posttraumatic stress disorder significantly predicted an increase in IMT. However, the study did show that subjects taking antidepressants who also reported clinical symptoms of depression had higher IMTs than those taking antidepressants who had fewer symptoms of depression.

"Because we didn’t see an association between depression itself and a thickening of the carotid artery, it strengthens the argument that this is more likely the antidepressants than the actual depression that is behind the association," Dr. Shah said.

History of a previous myocardial infarction, which was noted for 12% of the cohort, was not independently associated with increased IMT, nor was there a differential effect for identical and fraternal twins.

Speculating on the possible mechanism for the association, the investigators suggested that antidepressants may increase IMT through augmented release of vasoconstrictive neuropeptides. "The antidepressants may act synergistically with depressive symptoms to increase vascular disease," he said. "There is a potential interaction between the depressive symptoms, the neurohormonal effects of the depression itself, and the medication."

The findings suggest that the risk/benefit ratio of antidepressants should be considered, especially in patients with pre-existing cardiovascular disease, Dr. Shah said. "While not showing causality, it is important to take studies such as this into account in patient care, especially when the patient may not be deriving much benefit from the antidepressant."

Dr. Shah and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Carotid intima-media thickness was found to be increased in middle-aged men taking antidepressants in a study reported at the annual scientific sessions of the American College of Cardiology.

"There is a clear association between increased intima-media thickness [IMT] and taking an antidepressant of any kind, and this trend is even stronger when we look at people who are on these medications and are more depressed," said Dr. Amit Shah, a cardiology fellow at Emory University, Atlanta.

Dr. Janet Wright senior vice president of science and quality for the ACC, commented that the study should be viewed as "directional. ... It only tees things up for the next range of studies." Dr. Wright, a cardiologist in Chico, Calif., added that "it does suggest that perhaps a person who is depressed and on an antidepressant may need monitoring."

Carotid IMT and brachial flow-mediated dilation was assessed using B-mode ultrasound in 513 middle-aged male twins from the Vietnam Era Twin Registry. Traditional risk factors for ischemic heart disease were measured. Depression and posttraumatic stress disorder (PTSD) were assessed with the Structured Clinical Interview for the Diagnosis of Psychiatric Disorders, and depressive symptoms were measured via the Beck Depression Inventory. Medication regimens were verified by a clinician. Mixed effects regression models were used to analyze the overall association and to examine differences within twin pairs discordant for antidepressant intake.

Participants were a mean age of 55 years; 95% were white and 16% were taking antidepressants, mainly selective serotonin reuptake inhibitors (60%). In an analysis of the association by type of antidepressant, an increase in IMT was noted regardless of the class of antidepressants.

Antidepressant use was associated with an IMT increase of 37 microns, which represents about a 5% increase from the mean IMT value of 762 microns seen in the population, a significant difference compared with men not taking antidepressants.

The findings emerged from an adjusted analysis that controlled for conventional cardiovascular risk factors and for depressive symptoms, history of major depression and heart disease, alcohol and coffee consumption, statin use, physical activity, education, and employment status.

In an analysis of 59 twin pairs where one brother was taking an antidepressant and the other was not, the antidepressant user had an IMT that was 41 microns thicker (P = .01), he reported.

Each additional year of life is associated with a 10-micron increase in IMT, therefore, the brother on the antidepressant could be considered to be 4 years "older" in terms of atherosclerosis. In previous studies, each 10-micron increase in IMT has been linked to a 1.8% increase in risk, Dr. Shah noted.

Previous studies have linked the presence of depression with an increased risk of cardiovascular disease. In this study, neither depression nor posttraumatic stress disorder significantly predicted an increase in IMT. However, the study did show that subjects taking antidepressants who also reported clinical symptoms of depression had higher IMTs than those taking antidepressants who had fewer symptoms of depression.

"Because we didn’t see an association between depression itself and a thickening of the carotid artery, it strengthens the argument that this is more likely the antidepressants than the actual depression that is behind the association," Dr. Shah said.

History of a previous myocardial infarction, which was noted for 12% of the cohort, was not independently associated with increased IMT, nor was there a differential effect for identical and fraternal twins.

Speculating on the possible mechanism for the association, the investigators suggested that antidepressants may increase IMT through augmented release of vasoconstrictive neuropeptides. "The antidepressants may act synergistically with depressive symptoms to increase vascular disease," he said. "There is a potential interaction between the depressive symptoms, the neurohormonal effects of the depression itself, and the medication."

The findings suggest that the risk/benefit ratio of antidepressants should be considered, especially in patients with pre-existing cardiovascular disease, Dr. Shah said. "While not showing causality, it is important to take studies such as this into account in patient care, especially when the patient may not be deriving much benefit from the antidepressant."

Dr. Shah and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Carotid intima-media thickness was found to be increased in middle-aged men taking antidepressants in a study reported at the annual scientific sessions of the American College of Cardiology.

"There is a clear association between increased intima-media thickness [IMT] and taking an antidepressant of any kind, and this trend is even stronger when we look at people who are on these medications and are more depressed," said Dr. Amit Shah, a cardiology fellow at Emory University, Atlanta.

Dr. Janet Wright senior vice president of science and quality for the ACC, commented that the study should be viewed as "directional. ... It only tees things up for the next range of studies." Dr. Wright, a cardiologist in Chico, Calif., added that "it does suggest that perhaps a person who is depressed and on an antidepressant may need monitoring."

Carotid IMT and brachial flow-mediated dilation was assessed using B-mode ultrasound in 513 middle-aged male twins from the Vietnam Era Twin Registry. Traditional risk factors for ischemic heart disease were measured. Depression and posttraumatic stress disorder (PTSD) were assessed with the Structured Clinical Interview for the Diagnosis of Psychiatric Disorders, and depressive symptoms were measured via the Beck Depression Inventory. Medication regimens were verified by a clinician. Mixed effects regression models were used to analyze the overall association and to examine differences within twin pairs discordant for antidepressant intake.

Participants were a mean age of 55 years; 95% were white and 16% were taking antidepressants, mainly selective serotonin reuptake inhibitors (60%). In an analysis of the association by type of antidepressant, an increase in IMT was noted regardless of the class of antidepressants.

Antidepressant use was associated with an IMT increase of 37 microns, which represents about a 5% increase from the mean IMT value of 762 microns seen in the population, a significant difference compared with men not taking antidepressants.

The findings emerged from an adjusted analysis that controlled for conventional cardiovascular risk factors and for depressive symptoms, history of major depression and heart disease, alcohol and coffee consumption, statin use, physical activity, education, and employment status.

In an analysis of 59 twin pairs where one brother was taking an antidepressant and the other was not, the antidepressant user had an IMT that was 41 microns thicker (P = .01), he reported.

Each additional year of life is associated with a 10-micron increase in IMT, therefore, the brother on the antidepressant could be considered to be 4 years "older" in terms of atherosclerosis. In previous studies, each 10-micron increase in IMT has been linked to a 1.8% increase in risk, Dr. Shah noted.

Previous studies have linked the presence of depression with an increased risk of cardiovascular disease. In this study, neither depression nor posttraumatic stress disorder significantly predicted an increase in IMT. However, the study did show that subjects taking antidepressants who also reported clinical symptoms of depression had higher IMTs than those taking antidepressants who had fewer symptoms of depression.

"Because we didn’t see an association between depression itself and a thickening of the carotid artery, it strengthens the argument that this is more likely the antidepressants than the actual depression that is behind the association," Dr. Shah said.

History of a previous myocardial infarction, which was noted for 12% of the cohort, was not independently associated with increased IMT, nor was there a differential effect for identical and fraternal twins.

Speculating on the possible mechanism for the association, the investigators suggested that antidepressants may increase IMT through augmented release of vasoconstrictive neuropeptides. "The antidepressants may act synergistically with depressive symptoms to increase vascular disease," he said. "There is a potential interaction between the depressive symptoms, the neurohormonal effects of the depression itself, and the medication."

The findings suggest that the risk/benefit ratio of antidepressants should be considered, especially in patients with pre-existing cardiovascular disease, Dr. Shah said. "While not showing causality, it is important to take studies such as this into account in patient care, especially when the patient may not be deriving much benefit from the antidepressant."

Dr. Shah and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Patients with suspected ST-elevation myocardial infarction who called an ambulance received lifesaving care in half the time as patients who got to the hospital by other means, according to a study conducted at two San Francisco hospitals.

"Patients who take an ambulance get a prehospital ECG," said lead investigator Dr. James M. McCabe of the University of California, San Francisco, at the annual scientific sessions of the American College of Cardiology. "These patients move through the emergency room and get to the cath lab much faster."

"We found that almost half of patients referred for a potential heart attack don’t take an ambulance but come in on their own, and it turns out they are doing themselves a great disservice," Dr. McCabe said.

The study analyzed 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in 2009. Of the 356 patients, 199 (56%) arrived by ambulance and 157 (44%) did not.

Variables affecting the time interval from the inciting ECG to STEMI pager activation, and door-to-balloon time, were analyzed in univariate and step-wise multivariate regression models.

All components of care were affected.

"The ultimate metric, door-to-balloon time, was reduced by 26% in patients taken by ambulance," Dr. McCabe reported. This highly significant finding is important because studies show mortality risks are higher when door-to-balloon times exceed 90 minutes, he added.

The investigators then broke down the door-to-balloon time into its various components and compared the groups. After adjusting for demographic factors, traditional cardiovascular risk factors, severity of illness and extent of ECG changes, merely not presenting by ambulance to the emergency department (ED), and therefore not receiving a prehospital ECG, significantly lengthened by 62% the total time in the ED before undergoing catheterization.

Among patients arriving by ambulance, "each interval that occurred within the emergency room was reduced by more than 50%," he reported.

The procedural time for revascularization, however, did not vary based on how the patient arrived at the hospital. This finding supports the conclusion that care was made more efficient prior to the catheterization itself, he said.

The one observable difference was that patients arriving by ambulance were more critically ill. They had more cardiac arrests, and required more cardiopulmonary resuscitation and intubation.

"That’s interesting, because while these patients are sicker and require more care in the ER, they are still getting through the ER faster, after adjusting for multiple risk factors and elements in the decision-making process," Dr. McCabe noted. "Taking the ambulance results in efficiency, and this translates into faster ER throughput and shorter door-to-balloon times."

Of some concern to the researchers was that calling 911 did not assure that patients with suspected STEMI arrived at the hospital with ECG results in hand. Among the 356 patients in the study, 68% did not receive an ECG, either because they did not travel by ambulance or because, in 43% of the cases, they were not given an ECG en route.

Dr. McCabe suspects that patients who did not receive an ECG in the ambulance may have had vague presenting symptoms when paramedics arrived. Of patients with symptoms more indicative of an MI, 78% got an ECG in the ambulance, he said.

"Our community is diverse, and we feel that barriers in communication with non-English speakers may also have played a role," he added.

He further noted that in San Francisco paramedics did not have the technology to forward the ECGs electronically to the receiving hospital. San Francisco will be implementing citywide remote transmission of ECGs soon, and the investigators plan to study whether this makes for even more efficient transfer of STEMI patients to the cath lab.

"These data suggest better triage systems may be necessary for patients with likely STEMIs, particularly for [more than] 40% of patients who do not arrive by ambulance," Dr. McCabe concluded.

Dr. Janet Wright, ACC senior vice president of science and quality, commented on the findings. "This is a safety message for patients: ‘Your local ER wants you to come by ambulance!’ And for physicians and health care systems, the message is that there are critical intervals within the overall pattern of care that need scrutiny," said Dr. Wright, a cardiologist in Chico, Calif.

"The person who arrives by private transportation may languish within those time intervals unnecessarily in a way that is unsafe," she said. "The message is to focus on every hand-off. They accumulate in precious minutes."

Dr. McCabe and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Patients with suspected ST-elevation myocardial infarction who called an ambulance received lifesaving care in half the time as patients who got to the hospital by other means, according to a study conducted at two San Francisco hospitals.

"Patients who take an ambulance get a prehospital ECG," said lead investigator Dr. James M. McCabe of the University of California, San Francisco, at the annual scientific sessions of the American College of Cardiology. "These patients move through the emergency room and get to the cath lab much faster."

"We found that almost half of patients referred for a potential heart attack don’t take an ambulance but come in on their own, and it turns out they are doing themselves a great disservice," Dr. McCabe said.

The study analyzed 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in 2009. Of the 356 patients, 199 (56%) arrived by ambulance and 157 (44%) did not.

Variables affecting the time interval from the inciting ECG to STEMI pager activation, and door-to-balloon time, were analyzed in univariate and step-wise multivariate regression models.

All components of care were affected.

"The ultimate metric, door-to-balloon time, was reduced by 26% in patients taken by ambulance," Dr. McCabe reported. This highly significant finding is important because studies show mortality risks are higher when door-to-balloon times exceed 90 minutes, he added.

The investigators then broke down the door-to-balloon time into its various components and compared the groups. After adjusting for demographic factors, traditional cardiovascular risk factors, severity of illness and extent of ECG changes, merely not presenting by ambulance to the emergency department (ED), and therefore not receiving a prehospital ECG, significantly lengthened by 62% the total time in the ED before undergoing catheterization.

Among patients arriving by ambulance, "each interval that occurred within the emergency room was reduced by more than 50%," he reported.

The procedural time for revascularization, however, did not vary based on how the patient arrived at the hospital. This finding supports the conclusion that care was made more efficient prior to the catheterization itself, he said.

The one observable difference was that patients arriving by ambulance were more critically ill. They had more cardiac arrests, and required more cardiopulmonary resuscitation and intubation.

"That’s interesting, because while these patients are sicker and require more care in the ER, they are still getting through the ER faster, after adjusting for multiple risk factors and elements in the decision-making process," Dr. McCabe noted. "Taking the ambulance results in efficiency, and this translates into faster ER throughput and shorter door-to-balloon times."

Of some concern to the researchers was that calling 911 did not assure that patients with suspected STEMI arrived at the hospital with ECG results in hand. Among the 356 patients in the study, 68% did not receive an ECG, either because they did not travel by ambulance or because, in 43% of the cases, they were not given an ECG en route.

Dr. McCabe suspects that patients who did not receive an ECG in the ambulance may have had vague presenting symptoms when paramedics arrived. Of patients with symptoms more indicative of an MI, 78% got an ECG in the ambulance, he said.

"Our community is diverse, and we feel that barriers in communication with non-English speakers may also have played a role," he added.

He further noted that in San Francisco paramedics did not have the technology to forward the ECGs electronically to the receiving hospital. San Francisco will be implementing citywide remote transmission of ECGs soon, and the investigators plan to study whether this makes for even more efficient transfer of STEMI patients to the cath lab.

"These data suggest better triage systems may be necessary for patients with likely STEMIs, particularly for [more than] 40% of patients who do not arrive by ambulance," Dr. McCabe concluded.

Dr. Janet Wright, ACC senior vice president of science and quality, commented on the findings. "This is a safety message for patients: ‘Your local ER wants you to come by ambulance!’ And for physicians and health care systems, the message is that there are critical intervals within the overall pattern of care that need scrutiny," said Dr. Wright, a cardiologist in Chico, Calif.

"The person who arrives by private transportation may languish within those time intervals unnecessarily in a way that is unsafe," she said. "The message is to focus on every hand-off. They accumulate in precious minutes."

Dr. McCabe and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Patients with suspected ST-elevation myocardial infarction who called an ambulance received lifesaving care in half the time as patients who got to the hospital by other means, according to a study conducted at two San Francisco hospitals.

"Patients who take an ambulance get a prehospital ECG," said lead investigator Dr. James M. McCabe of the University of California, San Francisco, at the annual scientific sessions of the American College of Cardiology. "These patients move through the emergency room and get to the cath lab much faster."

"We found that almost half of patients referred for a potential heart attack don’t take an ambulance but come in on their own, and it turns out they are doing themselves a great disservice," Dr. McCabe said.

The study analyzed 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in 2009. Of the 356 patients, 199 (56%) arrived by ambulance and 157 (44%) did not.

Variables affecting the time interval from the inciting ECG to STEMI pager activation, and door-to-balloon time, were analyzed in univariate and step-wise multivariate regression models.

All components of care were affected.

"The ultimate metric, door-to-balloon time, was reduced by 26% in patients taken by ambulance," Dr. McCabe reported. This highly significant finding is important because studies show mortality risks are higher when door-to-balloon times exceed 90 minutes, he added.

The investigators then broke down the door-to-balloon time into its various components and compared the groups. After adjusting for demographic factors, traditional cardiovascular risk factors, severity of illness and extent of ECG changes, merely not presenting by ambulance to the emergency department (ED), and therefore not receiving a prehospital ECG, significantly lengthened by 62% the total time in the ED before undergoing catheterization.

Among patients arriving by ambulance, "each interval that occurred within the emergency room was reduced by more than 50%," he reported.

The procedural time for revascularization, however, did not vary based on how the patient arrived at the hospital. This finding supports the conclusion that care was made more efficient prior to the catheterization itself, he said.

The one observable difference was that patients arriving by ambulance were more critically ill. They had more cardiac arrests, and required more cardiopulmonary resuscitation and intubation.

"That’s interesting, because while these patients are sicker and require more care in the ER, they are still getting through the ER faster, after adjusting for multiple risk factors and elements in the decision-making process," Dr. McCabe noted. "Taking the ambulance results in efficiency, and this translates into faster ER throughput and shorter door-to-balloon times."

Of some concern to the researchers was that calling 911 did not assure that patients with suspected STEMI arrived at the hospital with ECG results in hand. Among the 356 patients in the study, 68% did not receive an ECG, either because they did not travel by ambulance or because, in 43% of the cases, they were not given an ECG en route.

Dr. McCabe suspects that patients who did not receive an ECG in the ambulance may have had vague presenting symptoms when paramedics arrived. Of patients with symptoms more indicative of an MI, 78% got an ECG in the ambulance, he said.

"Our community is diverse, and we feel that barriers in communication with non-English speakers may also have played a role," he added.

He further noted that in San Francisco paramedics did not have the technology to forward the ECGs electronically to the receiving hospital. San Francisco will be implementing citywide remote transmission of ECGs soon, and the investigators plan to study whether this makes for even more efficient transfer of STEMI patients to the cath lab.

"These data suggest better triage systems may be necessary for patients with likely STEMIs, particularly for [more than] 40% of patients who do not arrive by ambulance," Dr. McCabe concluded.

Dr. Janet Wright, ACC senior vice president of science and quality, commented on the findings. "This is a safety message for patients: ‘Your local ER wants you to come by ambulance!’ And for physicians and health care systems, the message is that there are critical intervals within the overall pattern of care that need scrutiny," said Dr. Wright, a cardiologist in Chico, Calif.

"The person who arrives by private transportation may languish within those time intervals unnecessarily in a way that is unsafe," she said. "The message is to focus on every hand-off. They accumulate in precious minutes."

Dr. McCabe and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Patients with suspected ST-elevation myocardial infarction who called an ambulance received lifesaving care in half the time as patients who got to the hospital by other means, according to a study conducted at two San Francisco hospitals.

"Patients who take an ambulance get a prehospital ECG," said lead investigator Dr. James M. McCabe of the University of California, San Francisco, at the annual scientific sessions of the American College of Cardiology. "These patients move through the emergency room and get to the cath lab much faster."

"We found that almost half of patients referred for a potential heart attack don’t take an ambulance but come in on their own, and it turns out they are doing themselves a great disservice," Dr. McCabe said.

The study analyzed 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in 2009. Of the 356 patients, 199 (56%) arrived by ambulance and 157 (44%) did not.

Variables affecting the time interval from the inciting ECG to STEMI pager activation, and door-to-balloon time, were analyzed in univariate and step-wise multivariate regression models.

All components of care were affected.

"The ultimate metric, door-to-balloon time, was reduced by 26% in patients taken by ambulance," Dr. McCabe reported. This highly significant finding is important because studies show mortality risks are higher when door-to-balloon times exceed 90 minutes, he added.

The investigators then broke down the door-to-balloon time into its various components and compared the groups. After adjusting for demographic factors, traditional cardiovascular risk factors, severity of illness and extent of ECG changes, merely not presenting by ambulance to the emergency department (ED), and therefore not receiving a prehospital ECG, significantly lengthened by 62% the total time in the ED before undergoing catheterization.

Among patients arriving by ambulance, "each interval that occurred within the emergency room was reduced by more than 50%," he reported.

The procedural time for revascularization, however, did not vary based on how the patient arrived at the hospital. This finding supports the conclusion that care was made more efficient prior to the catheterization itself, he said.

The one observable difference was that patients arriving by ambulance were more critically ill. They had more cardiac arrests, and required more cardiopulmonary resuscitation and intubation.

"That’s interesting, because while these patients are sicker and require more care in the ER, they are still getting through the ER faster, after adjusting for multiple risk factors and elements in the decision-making process," Dr. McCabe noted. "Taking the ambulance results in efficiency, and this translates into faster ER throughput and shorter door-to-balloon times."

Of some concern to the researchers was that calling 911 did not assure that patients with suspected STEMI arrived at the hospital with ECG results in hand. Among the 356 patients in the study, 68% did not receive an ECG, either because they did not travel by ambulance or because, in 43% of the cases, they were not given an ECG en route.

Dr. McCabe suspects that patients who did not receive an ECG in the ambulance may have had vague presenting symptoms when paramedics arrived. Of patients with symptoms more indicative of an MI, 78% got an ECG in the ambulance, he said.

"Our community is diverse, and we feel that barriers in communication with non-English speakers may also have played a role," he added.

He further noted that in San Francisco paramedics did not have the technology to forward the ECGs electronically to the receiving hospital. San Francisco will be implementing citywide remote transmission of ECGs soon, and the investigators plan to study whether this makes for even more efficient transfer of STEMI patients to the cath lab.

"These data suggest better triage systems may be necessary for patients with likely STEMIs, particularly for [more than] 40% of patients who do not arrive by ambulance," Dr. McCabe concluded.

Dr. Janet Wright, ACC senior vice president of science and quality, commented on the findings. "This is a safety message for patients: ‘Your local ER wants you to come by ambulance!’ And for physicians and health care systems, the message is that there are critical intervals within the overall pattern of care that need scrutiny," said Dr. Wright, a cardiologist in Chico, Calif.

"The person who arrives by private transportation may languish within those time intervals unnecessarily in a way that is unsafe," she said. "The message is to focus on every hand-off. They accumulate in precious minutes."

Dr. McCabe and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Patients with suspected ST-elevation myocardial infarction who called an ambulance received lifesaving care in half the time as patients who got to the hospital by other means, according to a study conducted at two San Francisco hospitals.

"Patients who take an ambulance get a prehospital ECG," said lead investigator Dr. James M. McCabe of the University of California, San Francisco, at the annual scientific sessions of the American College of Cardiology. "These patients move through the emergency room and get to the cath lab much faster."

"We found that almost half of patients referred for a potential heart attack don’t take an ambulance but come in on their own, and it turns out they are doing themselves a great disservice," Dr. McCabe said.

The study analyzed 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in 2009. Of the 356 patients, 199 (56%) arrived by ambulance and 157 (44%) did not.

Variables affecting the time interval from the inciting ECG to STEMI pager activation, and door-to-balloon time, were analyzed in univariate and step-wise multivariate regression models.

All components of care were affected.

"The ultimate metric, door-to-balloon time, was reduced by 26% in patients taken by ambulance," Dr. McCabe reported. This highly significant finding is important because studies show mortality risks are higher when door-to-balloon times exceed 90 minutes, he added.

The investigators then broke down the door-to-balloon time into its various components and compared the groups. After adjusting for demographic factors, traditional cardiovascular risk factors, severity of illness and extent of ECG changes, merely not presenting by ambulance to the emergency department (ED), and therefore not receiving a prehospital ECG, significantly lengthened by 62% the total time in the ED before undergoing catheterization.

Among patients arriving by ambulance, "each interval that occurred within the emergency room was reduced by more than 50%," he reported.

The procedural time for revascularization, however, did not vary based on how the patient arrived at the hospital. This finding supports the conclusion that care was made more efficient prior to the catheterization itself, he said.

The one observable difference was that patients arriving by ambulance were more critically ill. They had more cardiac arrests, and required more cardiopulmonary resuscitation and intubation.

"That’s interesting, because while these patients are sicker and require more care in the ER, they are still getting through the ER faster, after adjusting for multiple risk factors and elements in the decision-making process," Dr. McCabe noted. "Taking the ambulance results in efficiency, and this translates into faster ER throughput and shorter door-to-balloon times."

Of some concern to the researchers was that calling 911 did not assure that patients with suspected STEMI arrived at the hospital with ECG results in hand. Among the 356 patients in the study, 68% did not receive an ECG, either because they did not travel by ambulance or because, in 43% of the cases, they were not given an ECG en route.

Dr. McCabe suspects that patients who did not receive an ECG in the ambulance may have had vague presenting symptoms when paramedics arrived. Of patients with symptoms more indicative of an MI, 78% got an ECG in the ambulance, he said.

"Our community is diverse, and we feel that barriers in communication with non-English speakers may also have played a role," he added.

He further noted that in San Francisco paramedics did not have the technology to forward the ECGs electronically to the receiving hospital. San Francisco will be implementing citywide remote transmission of ECGs soon, and the investigators plan to study whether this makes for even more efficient transfer of STEMI patients to the cath lab.

"These data suggest better triage systems may be necessary for patients with likely STEMIs, particularly for [more than] 40% of patients who do not arrive by ambulance," Dr. McCabe concluded.

Dr. Janet Wright, ACC senior vice president of science and quality, commented on the findings. "This is a safety message for patients: ‘Your local ER wants you to come by ambulance!’ And for physicians and health care systems, the message is that there are critical intervals within the overall pattern of care that need scrutiny," said Dr. Wright, a cardiologist in Chico, Calif.

"The person who arrives by private transportation may languish within those time intervals unnecessarily in a way that is unsafe," she said. "The message is to focus on every hand-off. They accumulate in precious minutes."

Dr. McCabe and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Patients with suspected ST-elevation myocardial infarction who called an ambulance received lifesaving care in half the time as patients who got to the hospital by other means, according to a study conducted at two San Francisco hospitals.

"Patients who take an ambulance get a prehospital ECG," said lead investigator Dr. James M. McCabe of the University of California, San Francisco, at the annual scientific sessions of the American College of Cardiology. "These patients move through the emergency room and get to the cath lab much faster."

"We found that almost half of patients referred for a potential heart attack don’t take an ambulance but come in on their own, and it turns out they are doing themselves a great disservice," Dr. McCabe said.

The study analyzed 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in 2009. Of the 356 patients, 199 (56%) arrived by ambulance and 157 (44%) did not.

Variables affecting the time interval from the inciting ECG to STEMI pager activation, and door-to-balloon time, were analyzed in univariate and step-wise multivariate regression models.

All components of care were affected.

"The ultimate metric, door-to-balloon time, was reduced by 26% in patients taken by ambulance," Dr. McCabe reported. This highly significant finding is important because studies show mortality risks are higher when door-to-balloon times exceed 90 minutes, he added.

The investigators then broke down the door-to-balloon time into its various components and compared the groups. After adjusting for demographic factors, traditional cardiovascular risk factors, severity of illness and extent of ECG changes, merely not presenting by ambulance to the emergency department (ED), and therefore not receiving a prehospital ECG, significantly lengthened by 62% the total time in the ED before undergoing catheterization.

Among patients arriving by ambulance, "each interval that occurred within the emergency room was reduced by more than 50%," he reported.

The procedural time for revascularization, however, did not vary based on how the patient arrived at the hospital. This finding supports the conclusion that care was made more efficient prior to the catheterization itself, he said.

The one observable difference was that patients arriving by ambulance were more critically ill. They had more cardiac arrests, and required more cardiopulmonary resuscitation and intubation.

"That’s interesting, because while these patients are sicker and require more care in the ER, they are still getting through the ER faster, after adjusting for multiple risk factors and elements in the decision-making process," Dr. McCabe noted. "Taking the ambulance results in efficiency, and this translates into faster ER throughput and shorter door-to-balloon times."

Of some concern to the researchers was that calling 911 did not assure that patients with suspected STEMI arrived at the hospital with ECG results in hand. Among the 356 patients in the study, 68% did not receive an ECG, either because they did not travel by ambulance or because, in 43% of the cases, they were not given an ECG en route.

Dr. McCabe suspects that patients who did not receive an ECG in the ambulance may have had vague presenting symptoms when paramedics arrived. Of patients with symptoms more indicative of an MI, 78% got an ECG in the ambulance, he said.

"Our community is diverse, and we feel that barriers in communication with non-English speakers may also have played a role," he added.

He further noted that in San Francisco paramedics did not have the technology to forward the ECGs electronically to the receiving hospital. San Francisco will be implementing citywide remote transmission of ECGs soon, and the investigators plan to study whether this makes for even more efficient transfer of STEMI patients to the cath lab.

"These data suggest better triage systems may be necessary for patients with likely STEMIs, particularly for [more than] 40% of patients who do not arrive by ambulance," Dr. McCabe concluded.

Dr. Janet Wright, ACC senior vice president of science and quality, commented on the findings. "This is a safety message for patients: ‘Your local ER wants you to come by ambulance!’ And for physicians and health care systems, the message is that there are critical intervals within the overall pattern of care that need scrutiny," said Dr. Wright, a cardiologist in Chico, Calif.

"The person who arrives by private transportation may languish within those time intervals unnecessarily in a way that is unsafe," she said. "The message is to focus on every hand-off. They accumulate in precious minutes."

Dr. McCabe and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Patients with suspected ST-elevation myocardial infarction who called an ambulance received lifesaving care in half the time as patients who got to the hospital by other means, according to a study conducted at two San Francisco hospitals.

"Patients who take an ambulance get a prehospital ECG," said lead investigator Dr. James M. McCabe of the University of California, San Francisco, at the annual scientific sessions of the American College of Cardiology. "These patients move through the emergency room and get to the cath lab much faster."

"We found that almost half of patients referred for a potential heart attack don’t take an ambulance but come in on their own, and it turns out they are doing themselves a great disservice," Dr. McCabe said.

The study analyzed 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in 2009. Of the 356 patients, 199 (56%) arrived by ambulance and 157 (44%) did not.

Variables affecting the time interval from the inciting ECG to STEMI pager activation, and door-to-balloon time, were analyzed in univariate and step-wise multivariate regression models.

All components of care were affected.

"The ultimate metric, door-to-balloon time, was reduced by 26% in patients taken by ambulance," Dr. McCabe reported. This highly significant finding is important because studies show mortality risks are higher when door-to-balloon times exceed 90 minutes, he added.

The investigators then broke down the door-to-balloon time into its various components and compared the groups. After adjusting for demographic factors, traditional cardiovascular risk factors, severity of illness and extent of ECG changes, merely not presenting by ambulance to the emergency department (ED), and therefore not receiving a prehospital ECG, significantly lengthened by 62% the total time in the ED before undergoing catheterization.

Among patients arriving by ambulance, "each interval that occurred within the emergency room was reduced by more than 50%," he reported.

The procedural time for revascularization, however, did not vary based on how the patient arrived at the hospital. This finding supports the conclusion that care was made more efficient prior to the catheterization itself, he said.

The one observable difference was that patients arriving by ambulance were more critically ill. They had more cardiac arrests, and required more cardiopulmonary resuscitation and intubation.

"That’s interesting, because while these patients are sicker and require more care in the ER, they are still getting through the ER faster, after adjusting for multiple risk factors and elements in the decision-making process," Dr. McCabe noted. "Taking the ambulance results in efficiency, and this translates into faster ER throughput and shorter door-to-balloon times."

Of some concern to the researchers was that calling 911 did not assure that patients with suspected STEMI arrived at the hospital with ECG results in hand. Among the 356 patients in the study, 68% did not receive an ECG, either because they did not travel by ambulance or because, in 43% of the cases, they were not given an ECG en route.

Dr. McCabe suspects that patients who did not receive an ECG in the ambulance may have had vague presenting symptoms when paramedics arrived. Of patients with symptoms more indicative of an MI, 78% got an ECG in the ambulance, he said.

"Our community is diverse, and we feel that barriers in communication with non-English speakers may also have played a role," he added.

He further noted that in San Francisco paramedics did not have the technology to forward the ECGs electronically to the receiving hospital. San Francisco will be implementing citywide remote transmission of ECGs soon, and the investigators plan to study whether this makes for even more efficient transfer of STEMI patients to the cath lab.

"These data suggest better triage systems may be necessary for patients with likely STEMIs, particularly for [more than] 40% of patients who do not arrive by ambulance," Dr. McCabe concluded.

Dr. Janet Wright, ACC senior vice president of science and quality, commented on the findings. "This is a safety message for patients: ‘Your local ER wants you to come by ambulance!’ And for physicians and health care systems, the message is that there are critical intervals within the overall pattern of care that need scrutiny," said Dr. Wright, a cardiologist in Chico, Calif.

"The person who arrives by private transportation may languish within those time intervals unnecessarily in a way that is unsafe," she said. "The message is to focus on every hand-off. They accumulate in precious minutes."

Dr. McCabe and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Patients with suspected ST-elevation myocardial infarction who called an ambulance received lifesaving care in half the time as patients who got to the hospital by other means, according to a study conducted at two San Francisco hospitals.

"Patients who take an ambulance get a prehospital ECG," said lead investigator Dr. James M. McCabe of the University of California, San Francisco, at the annual scientific sessions of the American College of Cardiology. "These patients move through the emergency room and get to the cath lab much faster."

"We found that almost half of patients referred for a potential heart attack don’t take an ambulance but come in on their own, and it turns out they are doing themselves a great disservice," Dr. McCabe said.

The study analyzed 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in 2009. Of the 356 patients, 199 (56%) arrived by ambulance and 157 (44%) did not.

Variables affecting the time interval from the inciting ECG to STEMI pager activation, and door-to-balloon time, were analyzed in univariate and step-wise multivariate regression models.

All components of care were affected.

"The ultimate metric, door-to-balloon time, was reduced by 26% in patients taken by ambulance," Dr. McCabe reported. This highly significant finding is important because studies show mortality risks are higher when door-to-balloon times exceed 90 minutes, he added.

The investigators then broke down the door-to-balloon time into its various components and compared the groups. After adjusting for demographic factors, traditional cardiovascular risk factors, severity of illness and extent of ECG changes, merely not presenting by ambulance to the emergency department (ED), and therefore not receiving a prehospital ECG, significantly lengthened by 62% the total time in the ED before undergoing catheterization.

Among patients arriving by ambulance, "each interval that occurred within the emergency room was reduced by more than 50%," he reported.

The procedural time for revascularization, however, did not vary based on how the patient arrived at the hospital. This finding supports the conclusion that care was made more efficient prior to the catheterization itself, he said.

The one observable difference was that patients arriving by ambulance were more critically ill. They had more cardiac arrests, and required more cardiopulmonary resuscitation and intubation.

"That’s interesting, because while these patients are sicker and require more care in the ER, they are still getting through the ER faster, after adjusting for multiple risk factors and elements in the decision-making process," Dr. McCabe noted. "Taking the ambulance results in efficiency, and this translates into faster ER throughput and shorter door-to-balloon times."

Of some concern to the researchers was that calling 911 did not assure that patients with suspected STEMI arrived at the hospital with ECG results in hand. Among the 356 patients in the study, 68% did not receive an ECG, either because they did not travel by ambulance or because, in 43% of the cases, they were not given an ECG en route.

Dr. McCabe suspects that patients who did not receive an ECG in the ambulance may have had vague presenting symptoms when paramedics arrived. Of patients with symptoms more indicative of an MI, 78% got an ECG in the ambulance, he said.

"Our community is diverse, and we feel that barriers in communication with non-English speakers may also have played a role," he added.

He further noted that in San Francisco paramedics did not have the technology to forward the ECGs electronically to the receiving hospital. San Francisco will be implementing citywide remote transmission of ECGs soon, and the investigators plan to study whether this makes for even more efficient transfer of STEMI patients to the cath lab.

"These data suggest better triage systems may be necessary for patients with likely STEMIs, particularly for [more than] 40% of patients who do not arrive by ambulance," Dr. McCabe concluded.

Dr. Janet Wright, ACC senior vice president of science and quality, commented on the findings. "This is a safety message for patients: ‘Your local ER wants you to come by ambulance!’ And for physicians and health care systems, the message is that there are critical intervals within the overall pattern of care that need scrutiny," said Dr. Wright, a cardiologist in Chico, Calif.

"The person who arrives by private transportation may languish within those time intervals unnecessarily in a way that is unsafe," she said. "The message is to focus on every hand-off. They accumulate in precious minutes."

Dr. McCabe and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS - Patients with suspected ST-elevation myocardial infarction who called an ambulance received lifesaving care in half the time as patients who got to the hospital by other means, according to a study conducted at two San Francisco hospitals.

"Patients who take an ambulance get a prehospital ECG," said lead investigator Dr. James M. McCabe of the University of California, San Francisco, at the annual scientific sessions of the American College of Cardiology. "These patients move through the emergency room and get to the cath lab much faster."

"We found that almost half of patients referred for a potential heart attack don’t take an ambulance but come in on their own, and it turns out they are doing themselves a great disservice," Dr. McCabe said.

The study analyzed 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in 2009. Of the 356 patients, 199 (56%) arrived by ambulance and 157 (44%) did not.

Variables affecting the time interval from the inciting ECG to STEMI pager activation, and door-to-balloon time, were analyzed in univariate and step-wise multivariate regression models.

All components of care were affected.

"The ultimate metric, door-to-balloon time, was reduced by 26% in patients taken by ambulance," Dr. McCabe reported. This highly significant finding is important because studies show mortality risks are higher when door-to-balloon times exceed 90 minutes, he added.

The investigators then broke down the door-to-balloon time into its various components and compared the groups. After adjusting for demographic factors, traditional cardiovascular risk factors, severity of illness and extent of ECG changes, merely not presenting by ambulance to the emergency department (ED), and therefore not receiving a prehospital ECG, significantly lengthened by 62% the total time in the ED before undergoing catheterization.

Among patients arriving by ambulance, "each interval that occurred within the emergency room was reduced by more than 50%," he reported.

The procedural time for revascularization, however, did not vary based on how the patient arrived at the hospital. This finding supports the conclusion that care was made more efficient prior to the catheterization itself, he said.

The one observable difference was that patients arriving by ambulance were more critically ill. They had more cardiac arrests, and required more cardiopulmonary resuscitation and intubation.

"That’s interesting, because while these patients are sicker and require more care in the ER, they are still getting through the ER faster, after adjusting for multiple risk factors and elements in the decision-making process," Dr. McCabe noted. "Taking the ambulance results in efficiency, and this translates into faster ER throughput and shorter door-to-balloon times."

Of some concern to the researchers was that calling 911 did not assure that patients with suspected STEMI arrived at the hospital with ECG results in hand. Among the 356 patients in the study, 68% did not receive an ECG, either because they did not travel by ambulance or because, in 43% of the cases, they were not given an ECG en route.

Dr. McCabe suspects that patients who did not receive an ECG in the ambulance may have had vague presenting symptoms when paramedics arrived. Of patients with symptoms more indicative of an MI, 78% got an ECG in the ambulance, he said.

"Our community is diverse, and we feel that barriers in communication with non-English speakers may also have played a role," he added.

He further noted that in San Francisco paramedics did not have the technology to forward the ECGs electronically to the receiving hospital. San Francisco will be implementing citywide remote transmission of ECGs soon, and the investigators plan to study whether this makes for even more efficient transfer of STEMI patients to the cath lab.

"These data suggest better triage systems may be necessary for patients with likely STEMIs, particularly for [more than] 40% of patients who do not arrive by ambulance," Dr. McCabe concluded.

Dr. Janet Wright, ACC senior vice president of science and quality, commented on the findings. "This is a safety message for patients: ‘Your local ER wants you to come by ambulance!’ And for physicians and health care systems, the message is that there are critical intervals within the overall pattern of care that need scrutiny," said Dr. Wright, a cardiologist in Chico, Calif.

"The person who arrives by private transportation may languish within those time intervals unnecessarily in a way that is unsafe," she said. "The message is to focus on every hand-off. They accumulate in precious minutes."

Dr. McCabe and Dr. Wright reported no relevant conflicts of interest.

AMSTERDAM – A targeted cognitive-behavioral treatment program designed by German addiction specialists for cannabis use disorder promoted abstinence in 40% of subjects at 6 months, and significantly reduced global addiction severity and psychopathological symptoms.

The approach was described at the congress by Hans-Ulrich Wittchen, Ph.D., director of the Institute of Clinical Psychology and Psychotherapy at Technische Universität Dresden.

A good percentage of participants was abstinent 6 months after treatment, even when urine tests are done. “This is a remarkable finding that we did not expect at the beginning,” Dr. Wittchen said.

For many individuals, cannabis is the primary drug of abuse. Regular heavy use is associated with a substantial risk of a cannabis-dependence syndrome and when this is combined with other substance-abuse and internalizing disorders, the result is often psychosocial, cognitive, and mental health problems.

“Cannabis use is regularly associated with a wide range of psychological symptoms, and the largest group has anxiety and depression. Patients with primary CUD [cannabis-use disorder] have become the largest group in substance-abuse centers in many European countries. These individuals have different profiles and treatment needs that are not being met in the current health care system. No clear interventional strategies have been developed,” Dr. Wittchen said.

“The patients tell us they do not feel well placed, sitting next to heroin users. In fact, that's how impressionable young people learn how to use other drugs.”

CBT as the Foundation

Dr. Wittchen and his colleagues designed a treatment program (10 individual sessions of 90 minutes each) specifically related to CUD. Based on evidence that types of cognitive-behavioral therapy (CBT) can be effective (via motivational enhancement, cognitive restructuring, psychosocial problem solving), they used CBT as a foundation. Modular components include CBT, motivational enhancement, and psychosocial problem solving. Patients develop an individual change concept and set goals. There is “quit day” preparation and training in relapse prevention, cannabis refusal skills, and so forth.

A randomized, controlled trial was designed to assess the effect of the program, compared with a delayed-treatment group, which included individuals seeking help but who were asked to wait until there was availability within the program.

Two approaches were evaluated: a standardized approach and a variant tailored to the individual's specific needs that minimized components deemed unnecessary (such as less motivational work in patients who express high motivation at baseline).

Participants were aged 16-45 years with substantial current cannabis use and meeting criteria for DSM-IV CUD. They also had significant CUD-associated psychosocial problems and could have comorbid mental disorders (though no history of psychotic disorder, suicidal ideation, or phobias) as well as concomitant other drug use (though no other dependencies).

“Our entry criteria [were] meant to correspond to the most frequent and typical characteristics of this population,” he said. “And our general campaign message was for 'everyone who wants to stop, reduce, or think about his or her cannabis use.'”

The typical patient was a male who used cannabis more than 20 times per week. Seventy percent met criteria for cannabis dependence, 78% reported life-time use of other illicit drugs, and 38% had signs of dependency for those. Anxiety disorders were diagnosed in 40% and mood disorders in 38%. “We concluded that a severe chronic CUD sample of patients was included in the study,” he said.

There were 51 subjects in the standardized treatment group, 39 in the targeted standardized treatment group and 32 in the delayed-treatment group, which served as controls. Assessments were made after 3 and 6 months to test the stability of the effects. The primary outcome measure was abstinence as measured by self-report and negative urine screen, cannabis use, addiction severity total score and domains, and severity of psychopathological symptoms.

The tailored treatment was found not to be superior to the standardized treatment; therefore, these two groups were combined for the analysis.

Trial Showed Robust Effect

At the end of treatment, approximately 50% of participants reported complete abstinence for at least 7 days and this remained stable at 3 months, dropping to approximately 40% at 6 months.

At all time points, urine screens were negative for approximately 40% of participants. In contrast, abstinence was reported by approximately 10% of the control group at the end of treatment.

Similarly, mean number of cannabis-use episodes per week was substantially decreased, according to the last-observation-carried-forward analysis. Mean use (past 7 days) at baseline was 27 for the active-treatment group and 21 for the delayed-treatment group.

After the intervention, this dropped to 7.4 per week with treatment but rose to 25 per week for the control group. At 6 months' follow-up, mean weekly use was 12 in the treatment group and 20 in the control group.

Scores on the Addiction Severity Index were significantly improved in all domains except for “satisfaction,” which Dr. Wittchen attributed to the requirement that participants alter their social network, which in turn affected their quality of life.

Psychopathological symptoms also were significantly improved, but a reduction in alcohol use was not found.

All together, at 6 months, compared with baseline, stable continued abstinence was observed in 49%, and marked reduction or temporal abstinence was observed in 38%, while 11% had no change and 3% progressed to heavier use of cannabis.

More than 80% of participants reported that the therapy was “very helpful,” Dr. Wittchen said. “They particularly liked the character of the program.” For example, it was not a typical substance-abuse setting. Also, they appreciated the limited number of “dense” sessions and the short-term duration of treatment.

The researchers prepared a manual describing the program, which has procedural specifications of all elements, including diagnostic assessments. It is modular (to identify the core active components of the therapy) and highly structured (with scripts and verbatim descriptions of critical procedures). Specification and standardization are meant to enhance the ease of training, transfer, consistency of use, and reproducibility. The program also has just been evaluated in a 15-site translational study involving 450 persons, “with similarly impressive findings,” Dr. Wittchen added.

The campaign message was for 'everyone who wants to stop, reduce, or think about his or her cannabis use.'

Source DR. WITTCHEN

AMSTERDAM – A targeted cognitive-behavioral treatment program designed by German addiction specialists for cannabis use disorder promoted abstinence in 40% of subjects at 6 months, and significantly reduced global addiction severity and psychopathological symptoms.

The approach was described at the congress by Hans-Ulrich Wittchen, Ph.D., director of the Institute of Clinical Psychology and Psychotherapy at Technische Universität Dresden.

A good percentage of participants was abstinent 6 months after treatment, even when urine tests are done. “This is a remarkable finding that we did not expect at the beginning,” Dr. Wittchen said.

For many individuals, cannabis is the primary drug of abuse. Regular heavy use is associated with a substantial risk of a cannabis-dependence syndrome and when this is combined with other substance-abuse and internalizing disorders, the result is often psychosocial, cognitive, and mental health problems.

“Cannabis use is regularly associated with a wide range of psychological symptoms, and the largest group has anxiety and depression. Patients with primary CUD [cannabis-use disorder] have become the largest group in substance-abuse centers in many European countries. These individuals have different profiles and treatment needs that are not being met in the current health care system. No clear interventional strategies have been developed,” Dr. Wittchen said.

“The patients tell us they do not feel well placed, sitting next to heroin users. In fact, that's how impressionable young people learn how to use other drugs.”

CBT as the Foundation

Dr. Wittchen and his colleagues designed a treatment program (10 individual sessions of 90 minutes each) specifically related to CUD. Based on evidence that types of cognitive-behavioral therapy (CBT) can be effective (via motivational enhancement, cognitive restructuring, psychosocial problem solving), they used CBT as a foundation. Modular components include CBT, motivational enhancement, and psychosocial problem solving. Patients develop an individual change concept and set goals. There is “quit day” preparation and training in relapse prevention, cannabis refusal skills, and so forth.

A randomized, controlled trial was designed to assess the effect of the program, compared with a delayed-treatment group, which included individuals seeking help but who were asked to wait until there was availability within the program.

Two approaches were evaluated: a standardized approach and a variant tailored to the individual's specific needs that minimized components deemed unnecessary (such as less motivational work in patients who express high motivation at baseline).

Participants were aged 16-45 years with substantial current cannabis use and meeting criteria for DSM-IV CUD. They also had significant CUD-associated psychosocial problems and could have comorbid mental disorders (though no history of psychotic disorder, suicidal ideation, or phobias) as well as concomitant other drug use (though no other dependencies).

“Our entry criteria [were] meant to correspond to the most frequent and typical characteristics of this population,” he said. “And our general campaign message was for 'everyone who wants to stop, reduce, or think about his or her cannabis use.'”

The typical patient was a male who used cannabis more than 20 times per week. Seventy percent met criteria for cannabis dependence, 78% reported life-time use of other illicit drugs, and 38% had signs of dependency for those. Anxiety disorders were diagnosed in 40% and mood disorders in 38%. “We concluded that a severe chronic CUD sample of patients was included in the study,” he said.

There were 51 subjects in the standardized treatment group, 39 in the targeted standardized treatment group and 32 in the delayed-treatment group, which served as controls. Assessments were made after 3 and 6 months to test the stability of the effects. The primary outcome measure was abstinence as measured by self-report and negative urine screen, cannabis use, addiction severity total score and domains, and severity of psychopathological symptoms.

The tailored treatment was found not to be superior to the standardized treatment; therefore, these two groups were combined for the analysis.

Trial Showed Robust Effect

At the end of treatment, approximately 50% of participants reported complete abstinence for at least 7 days and this remained stable at 3 months, dropping to approximately 40% at 6 months.

At all time points, urine screens were negative for approximately 40% of participants. In contrast, abstinence was reported by approximately 10% of the control group at the end of treatment.

Similarly, mean number of cannabis-use episodes per week was substantially decreased, according to the last-observation-carried-forward analysis. Mean use (past 7 days) at baseline was 27 for the active-treatment group and 21 for the delayed-treatment group.

After the intervention, this dropped to 7.4 per week with treatment but rose to 25 per week for the control group. At 6 months' follow-up, mean weekly use was 12 in the treatment group and 20 in the control group.

Scores on the Addiction Severity Index were significantly improved in all domains except for “satisfaction,” which Dr. Wittchen attributed to the requirement that participants alter their social network, which in turn affected their quality of life.

Psychopathological symptoms also were significantly improved, but a reduction in alcohol use was not found.

All together, at 6 months, compared with baseline, stable continued abstinence was observed in 49%, and marked reduction or temporal abstinence was observed in 38%, while 11% had no change and 3% progressed to heavier use of cannabis.

More than 80% of participants reported that the therapy was “very helpful,” Dr. Wittchen said. “They particularly liked the character of the program.” For example, it was not a typical substance-abuse setting. Also, they appreciated the limited number of “dense” sessions and the short-term duration of treatment.

The researchers prepared a manual describing the program, which has procedural specifications of all elements, including diagnostic assessments. It is modular (to identify the core active components of the therapy) and highly structured (with scripts and verbatim descriptions of critical procedures). Specification and standardization are meant to enhance the ease of training, transfer, consistency of use, and reproducibility. The program also has just been evaluated in a 15-site translational study involving 450 persons, “with similarly impressive findings,” Dr. Wittchen added.

The campaign message was for 'everyone who wants to stop, reduce, or think about his or her cannabis use.'

Source DR. WITTCHEN

AMSTERDAM – A targeted cognitive-behavioral treatment program designed by German addiction specialists for cannabis use disorder promoted abstinence in 40% of subjects at 6 months, and significantly reduced global addiction severity and psychopathological symptoms.

The approach was described at the congress by Hans-Ulrich Wittchen, Ph.D., director of the Institute of Clinical Psychology and Psychotherapy at Technische Universität Dresden.

A good percentage of participants was abstinent 6 months after treatment, even when urine tests are done. “This is a remarkable finding that we did not expect at the beginning,” Dr. Wittchen said.

For many individuals, cannabis is the primary drug of abuse. Regular heavy use is associated with a substantial risk of a cannabis-dependence syndrome and when this is combined with other substance-abuse and internalizing disorders, the result is often psychosocial, cognitive, and mental health problems.

“Cannabis use is regularly associated with a wide range of psychological symptoms, and the largest group has anxiety and depression. Patients with primary CUD [cannabis-use disorder] have become the largest group in substance-abuse centers in many European countries. These individuals have different profiles and treatment needs that are not being met in the current health care system. No clear interventional strategies have been developed,” Dr. Wittchen said.

“The patients tell us they do not feel well placed, sitting next to heroin users. In fact, that's how impressionable young people learn how to use other drugs.”

CBT as the Foundation

Dr. Wittchen and his colleagues designed a treatment program (10 individual sessions of 90 minutes each) specifically related to CUD. Based on evidence that types of cognitive-behavioral therapy (CBT) can be effective (via motivational enhancement, cognitive restructuring, psychosocial problem solving), they used CBT as a foundation. Modular components include CBT, motivational enhancement, and psychosocial problem solving. Patients develop an individual change concept and set goals. There is “quit day” preparation and training in relapse prevention, cannabis refusal skills, and so forth.

A randomized, controlled trial was designed to assess the effect of the program, compared with a delayed-treatment group, which included individuals seeking help but who were asked to wait until there was availability within the program.

Two approaches were evaluated: a standardized approach and a variant tailored to the individual's specific needs that minimized components deemed unnecessary (such as less motivational work in patients who express high motivation at baseline).

Participants were aged 16-45 years with substantial current cannabis use and meeting criteria for DSM-IV CUD. They also had significant CUD-associated psychosocial problems and could have comorbid mental disorders (though no history of psychotic disorder, suicidal ideation, or phobias) as well as concomitant other drug use (though no other dependencies).

“Our entry criteria [were] meant to correspond to the most frequent and typical characteristics of this population,” he said. “And our general campaign message was for 'everyone who wants to stop, reduce, or think about his or her cannabis use.'”

The typical patient was a male who used cannabis more than 20 times per week. Seventy percent met criteria for cannabis dependence, 78% reported life-time use of other illicit drugs, and 38% had signs of dependency for those. Anxiety disorders were diagnosed in 40% and mood disorders in 38%. “We concluded that a severe chronic CUD sample of patients was included in the study,” he said.

There were 51 subjects in the standardized treatment group, 39 in the targeted standardized treatment group and 32 in the delayed-treatment group, which served as controls. Assessments were made after 3 and 6 months to test the stability of the effects. The primary outcome measure was abstinence as measured by self-report and negative urine screen, cannabis use, addiction severity total score and domains, and severity of psychopathological symptoms.

The tailored treatment was found not to be superior to the standardized treatment; therefore, these two groups were combined for the analysis.

Trial Showed Robust Effect

At the end of treatment, approximately 50% of participants reported complete abstinence for at least 7 days and this remained stable at 3 months, dropping to approximately 40% at 6 months.

At all time points, urine screens were negative for approximately 40% of participants. In contrast, abstinence was reported by approximately 10% of the control group at the end of treatment.

Similarly, mean number of cannabis-use episodes per week was substantially decreased, according to the last-observation-carried-forward analysis. Mean use (past 7 days) at baseline was 27 for the active-treatment group and 21 for the delayed-treatment group.

After the intervention, this dropped to 7.4 per week with treatment but rose to 25 per week for the control group. At 6 months' follow-up, mean weekly use was 12 in the treatment group and 20 in the control group.

Scores on the Addiction Severity Index were significantly improved in all domains except for “satisfaction,” which Dr. Wittchen attributed to the requirement that participants alter their social network, which in turn affected their quality of life.

Psychopathological symptoms also were significantly improved, but a reduction in alcohol use was not found.

All together, at 6 months, compared with baseline, stable continued abstinence was observed in 49%, and marked reduction or temporal abstinence was observed in 38%, while 11% had no change and 3% progressed to heavier use of cannabis.

More than 80% of participants reported that the therapy was “very helpful,” Dr. Wittchen said. “They particularly liked the character of the program.” For example, it was not a typical substance-abuse setting. Also, they appreciated the limited number of “dense” sessions and the short-term duration of treatment.

The researchers prepared a manual describing the program, which has procedural specifications of all elements, including diagnostic assessments. It is modular (to identify the core active components of the therapy) and highly structured (with scripts and verbatim descriptions of critical procedures). Specification and standardization are meant to enhance the ease of training, transfer, consistency of use, and reproducibility. The program also has just been evaluated in a 15-site translational study involving 450 persons, “with similarly impressive findings,” Dr. Wittchen added.

The campaign message was for 'everyone who wants to stop, reduce, or think about his or her cannabis use.'

Source DR. WITTCHEN