Damian McNamara

MIAMI — Anxiety in men may be a robust and independent predictor of the 10-year incidence of myocardial infarction, according to a study presented at the annual conference of the Anxiety Disorders Association of America.

“This is kind of exciting because most work has been done with psychosocial factors like depression and hostility,” Yael E. Avivi said in an interview during the meeting.

Depression and negative affect have been the focus of most of the literature addressing a possible association between psychosocial factors and heart disease. Other researchers have reported evidence suggesting that anxiety contributes to coronary heart disease (Ann. Behav. Med. 1998;20:47–58) and to an elevated risk of fatal coronary heart disease (Circulation 1994;90:2225–9). But these investigators used relatively short assessment scales to measure anxiety, noted Ms. Avivi, a doctoral student in the department of psychology at the University of Miami.

Her associates, including lead author Biing-Jiun Shen, Ph.D., analyzed data that included a more comprehensive assessment to look for a possible association between anxiety and subsequent MI. The study assessed follow-up data for 740 healthy men who entered the Veterans Administration Normative Aging Study in 1986. Initial assessments included the Minnesota Multiphasic Personality Inventory, a comprehensive physical examination, and a cardiovascular disease risk profile. The participants did not have diabetes or a history of MI. The mean age at study entry was 60 years.

The researchers calculated an overall anxiety factor for each participant based on a combined score from four anxiety scales used in the Minnesota Multiphasic Personality Inventory. Those included measures for psychasthenia and social introversion, as well as scores from the Wiggins phobia scale and the Taylor Manifest Anxiety Scale.

During the 10 years of follow-up, there were 60 new-onset myocardial infarctions, including two fatal heart attacks. The researchers used hierarchical logistic regression to predict the likelihood of an MI using the composite score and each of the four anxiety constructs.

“We looked at the odds ratios for predicting new MI incidence when controlling for age, education, marital status, weight, blood pressure, glucose, cholesterol, drinking, smoking, and caloric intake,” Ms. Avivi said. “We could control for those and still see a significant effect.”

The overall anxiety factor was an independent and significant predictor of subsequent MI in the sample population (odds ratio, 1.46). Also, each of the four anxiety components independently and significantly predicted MI: psychasthenia (odds ratio, 1.42), social inhibition (odds ratio, 1.36), phobia (odds ratio, 1.44), and Taylor Manifest Anxiety (odds ratio, 1.50). In addition, being single and having lower HDL cholesterol levels predicted onset of MI in a multivariate analysis.

“The next question we had was, can depression and other psychosocial factors explain this association?” she said. Interestingly, these other psychosocial factors could not explain the link between anxiety and the new cases of MI that emerged in this study. After controlling for depression, anger, hostility, type A personality, and perceived stress, anxiety remained an independent predictor of a subsequent MI.

The researchers divided participants into quartiles based on their anxiety scores. “We also saw a dose-response effect,” Ms. Avivi said. “People with the highest anxiety scores had the highest incidence of MI.”

The association between anxiety and acute myocardial infarction was not surprising to Dr. James J. Ferguson, chairman of the Research Committee at the Texas Heart Institute, Houston. Still, he commented, the results could have important implications for any physician treating patients with anxiety.

“Yes, these people are at risk, but what can we do about it?” he asked. He described the findings as an important first step, but added that “there is a long ways to go before we understand how changing anxiety or stress can affect outcomes” and noted that the study did not address that point.

Mechanisms that would explain the relationship between anxiety and subsequent MI remain unknown and require further study, Ms. Avivi said. Anxiety might adversely affect health behaviors, promote atherogenesis, or trigger fatal coronary events through arrythmia, plaque rupture, coronary vasospasm, or thrombosis (Ann. Behavior. Med. 1998;20;47–58).

General distress across a range of negative emotions might play an important role in the relationship between psychosocial factors and coronary heart disease, according to a recently published study that also was based on follow-up data from the Veterans Administration Normative Aging Study (Ann. Behavior. Med. 2006;31:21–9).

Those researchers also concluded that aspects of anxiety may independently increase the risk for coronary heart disease. However, they also assessed anger and depression in their cohort, and they urged future researchers to consider a shared component of these features as a possible explanation for the elevated coronary disease risk.

MIAMI — Anxiety in men may be a robust and independent predictor of the 10-year incidence of myocardial infarction, according to a study presented at the annual conference of the Anxiety Disorders Association of America.

“This is kind of exciting because most work has been done with psychosocial factors like depression and hostility,” Yael E. Avivi said in an interview during the meeting.

Depression and negative affect have been the focus of most of the literature addressing a possible association between psychosocial factors and heart disease. Other researchers have reported evidence suggesting that anxiety contributes to coronary heart disease (Ann. Behav. Med. 1998;20:47–58) and to an elevated risk of fatal coronary heart disease (Circulation 1994;90:2225–9). But these investigators used relatively short assessment scales to measure anxiety, noted Ms. Avivi, a doctoral student in the department of psychology at the University of Miami.

Her associates, including lead author Biing-Jiun Shen, Ph.D., analyzed data that included a more comprehensive assessment to look for a possible association between anxiety and subsequent MI. The study assessed follow-up data for 740 healthy men who entered the Veterans Administration Normative Aging Study in 1986. Initial assessments included the Minnesota Multiphasic Personality Inventory, a comprehensive physical examination, and a cardiovascular disease risk profile. The participants did not have diabetes or a history of MI. The mean age at study entry was 60 years.

The researchers calculated an overall anxiety factor for each participant based on a combined score from four anxiety scales used in the Minnesota Multiphasic Personality Inventory. Those included measures for psychasthenia and social introversion, as well as scores from the Wiggins phobia scale and the Taylor Manifest Anxiety Scale.

During the 10 years of follow-up, there were 60 new-onset myocardial infarctions, including two fatal heart attacks. The researchers used hierarchical logistic regression to predict the likelihood of an MI using the composite score and each of the four anxiety constructs.

“We looked at the odds ratios for predicting new MI incidence when controlling for age, education, marital status, weight, blood pressure, glucose, cholesterol, drinking, smoking, and caloric intake,” Ms. Avivi said. “We could control for those and still see a significant effect.”

The overall anxiety factor was an independent and significant predictor of subsequent MI in the sample population (odds ratio, 1.46). Also, each of the four anxiety components independently and significantly predicted MI: psychasthenia (odds ratio, 1.42), social inhibition (odds ratio, 1.36), phobia (odds ratio, 1.44), and Taylor Manifest Anxiety (odds ratio, 1.50). In addition, being single and having lower HDL cholesterol levels predicted onset of MI in a multivariate analysis.

“The next question we had was, can depression and other psychosocial factors explain this association?” she said. Interestingly, these other psychosocial factors could not explain the link between anxiety and the new cases of MI that emerged in this study. After controlling for depression, anger, hostility, type A personality, and perceived stress, anxiety remained an independent predictor of a subsequent MI.

The researchers divided participants into quartiles based on their anxiety scores. “We also saw a dose-response effect,” Ms. Avivi said. “People with the highest anxiety scores had the highest incidence of MI.”

The association between anxiety and acute myocardial infarction was not surprising to Dr. James J. Ferguson, chairman of the Research Committee at the Texas Heart Institute, Houston. Still, he commented, the results could have important implications for any physician treating patients with anxiety.

“Yes, these people are at risk, but what can we do about it?” he asked. He described the findings as an important first step, but added that “there is a long ways to go before we understand how changing anxiety or stress can affect outcomes” and noted that the study did not address that point.

Mechanisms that would explain the relationship between anxiety and subsequent MI remain unknown and require further study, Ms. Avivi said. Anxiety might adversely affect health behaviors, promote atherogenesis, or trigger fatal coronary events through arrythmia, plaque rupture, coronary vasospasm, or thrombosis (Ann. Behavior. Med. 1998;20;47–58).

General distress across a range of negative emotions might play an important role in the relationship between psychosocial factors and coronary heart disease, according to a recently published study that also was based on follow-up data from the Veterans Administration Normative Aging Study (Ann. Behavior. Med. 2006;31:21–9).

Those researchers also concluded that aspects of anxiety may independently increase the risk for coronary heart disease. However, they also assessed anger and depression in their cohort, and they urged future researchers to consider a shared component of these features as a possible explanation for the elevated coronary disease risk.

MIAMI — Anxiety in men may be a robust and independent predictor of the 10-year incidence of myocardial infarction, according to a study presented at the annual conference of the Anxiety Disorders Association of America.

“This is kind of exciting because most work has been done with psychosocial factors like depression and hostility,” Yael E. Avivi said in an interview during the meeting.

Depression and negative affect have been the focus of most of the literature addressing a possible association between psychosocial factors and heart disease. Other researchers have reported evidence suggesting that anxiety contributes to coronary heart disease (Ann. Behav. Med. 1998;20:47–58) and to an elevated risk of fatal coronary heart disease (Circulation 1994;90:2225–9). But these investigators used relatively short assessment scales to measure anxiety, noted Ms. Avivi, a doctoral student in the department of psychology at the University of Miami.

Her associates, including lead author Biing-Jiun Shen, Ph.D., analyzed data that included a more comprehensive assessment to look for a possible association between anxiety and subsequent MI. The study assessed follow-up data for 740 healthy men who entered the Veterans Administration Normative Aging Study in 1986. Initial assessments included the Minnesota Multiphasic Personality Inventory, a comprehensive physical examination, and a cardiovascular disease risk profile. The participants did not have diabetes or a history of MI. The mean age at study entry was 60 years.

The researchers calculated an overall anxiety factor for each participant based on a combined score from four anxiety scales used in the Minnesota Multiphasic Personality Inventory. Those included measures for psychasthenia and social introversion, as well as scores from the Wiggins phobia scale and the Taylor Manifest Anxiety Scale.

During the 10 years of follow-up, there were 60 new-onset myocardial infarctions, including two fatal heart attacks. The researchers used hierarchical logistic regression to predict the likelihood of an MI using the composite score and each of the four anxiety constructs.

“We looked at the odds ratios for predicting new MI incidence when controlling for age, education, marital status, weight, blood pressure, glucose, cholesterol, drinking, smoking, and caloric intake,” Ms. Avivi said. “We could control for those and still see a significant effect.”

The overall anxiety factor was an independent and significant predictor of subsequent MI in the sample population (odds ratio, 1.46). Also, each of the four anxiety components independently and significantly predicted MI: psychasthenia (odds ratio, 1.42), social inhibition (odds ratio, 1.36), phobia (odds ratio, 1.44), and Taylor Manifest Anxiety (odds ratio, 1.50). In addition, being single and having lower HDL cholesterol levels predicted onset of MI in a multivariate analysis.

“The next question we had was, can depression and other psychosocial factors explain this association?” she said. Interestingly, these other psychosocial factors could not explain the link between anxiety and the new cases of MI that emerged in this study. After controlling for depression, anger, hostility, type A personality, and perceived stress, anxiety remained an independent predictor of a subsequent MI.

The researchers divided participants into quartiles based on their anxiety scores. “We also saw a dose-response effect,” Ms. Avivi said. “People with the highest anxiety scores had the highest incidence of MI.”

The association between anxiety and acute myocardial infarction was not surprising to Dr. James J. Ferguson, chairman of the Research Committee at the Texas Heart Institute, Houston. Still, he commented, the results could have important implications for any physician treating patients with anxiety.

“Yes, these people are at risk, but what can we do about it?” he asked. He described the findings as an important first step, but added that “there is a long ways to go before we understand how changing anxiety or stress can affect outcomes” and noted that the study did not address that point.

Mechanisms that would explain the relationship between anxiety and subsequent MI remain unknown and require further study, Ms. Avivi said. Anxiety might adversely affect health behaviors, promote atherogenesis, or trigger fatal coronary events through arrythmia, plaque rupture, coronary vasospasm, or thrombosis (Ann. Behavior. Med. 1998;20;47–58).

General distress across a range of negative emotions might play an important role in the relationship between psychosocial factors and coronary heart disease, according to a recently published study that also was based on follow-up data from the Veterans Administration Normative Aging Study (Ann. Behavior. Med. 2006;31:21–9).

Those researchers also concluded that aspects of anxiety may independently increase the risk for coronary heart disease. However, they also assessed anger and depression in their cohort, and they urged future researchers to consider a shared component of these features as a possible explanation for the elevated coronary disease risk.

MIAMI BEACH — A trial of labor should be considered an option for women with a history of prior cesarean delivery when preterm delivery is anticipated, Dr. Celeste P. Durnwald said at the annual meeting of the Society for Maternal-Fetal Medicine.

“There is little information reported to date on the efficacy of a [vaginal birth after cesarean] attempt in women undergoing preterm delivery,” said Dr. Durnwald, who presented a study on behalf of the National Institute of Child Health and Human Development maternal-fetal medicine units network.

One other research team has addressed the impact of preterm vaginal birth after cesarean (VBAC), said Dr. Durnwald of Ohio State University, Columbus. Investigators in that study reviewed medical records for 20,156 women with a singleton fetus and history of one cesarean delivery, including 12,463 (62%) who attempted a VBAC. They compared women who delivered preterm, at a mean of 34 weeks, with a group who delivered full term, at a mean of 39 weeks. VBAC was successful for 82% of the preterm group and 74% of the term group, a statistically significant difference. The study, however, was retrospective (Obstet. Gynecol. 2005;105:519–24).

Dr. Durnwald and her associates assessed 3,119 women with a preterm pregnancy. Of these, 2,338, or 75%, attempted a trial of labor. The researchers compared the success of VBAC and the rates of uterine rupture and maternal morbidities in these women with those in a control group of 15,331 women who attempted a trial of labor at term. The groups were similar, except women in the preterm group were more likely to be African American, government insured, and smokers.

VBAC was successful for 72.8% of the preterm group and 73.2% of the term group, Dr. Durnwald said. Rates of uterine rupture (0.34% vs. 0.74%, respectively) and dehiscence (0.26% vs. 0.73%) were lower in the preterm group.

Significantly more women in the preterm group had coagulopathy and/or a need for transfusion, according to a multivariate analysis.

MIAMI BEACH — A trial of labor should be considered an option for women with a history of prior cesarean delivery when preterm delivery is anticipated, Dr. Celeste P. Durnwald said at the annual meeting of the Society for Maternal-Fetal Medicine.

“There is little information reported to date on the efficacy of a [vaginal birth after cesarean] attempt in women undergoing preterm delivery,” said Dr. Durnwald, who presented a study on behalf of the National Institute of Child Health and Human Development maternal-fetal medicine units network.

One other research team has addressed the impact of preterm vaginal birth after cesarean (VBAC), said Dr. Durnwald of Ohio State University, Columbus. Investigators in that study reviewed medical records for 20,156 women with a singleton fetus and history of one cesarean delivery, including 12,463 (62%) who attempted a VBAC. They compared women who delivered preterm, at a mean of 34 weeks, with a group who delivered full term, at a mean of 39 weeks. VBAC was successful for 82% of the preterm group and 74% of the term group, a statistically significant difference. The study, however, was retrospective (Obstet. Gynecol. 2005;105:519–24).

Dr. Durnwald and her associates assessed 3,119 women with a preterm pregnancy. Of these, 2,338, or 75%, attempted a trial of labor. The researchers compared the success of VBAC and the rates of uterine rupture and maternal morbidities in these women with those in a control group of 15,331 women who attempted a trial of labor at term. The groups were similar, except women in the preterm group were more likely to be African American, government insured, and smokers.

VBAC was successful for 72.8% of the preterm group and 73.2% of the term group, Dr. Durnwald said. Rates of uterine rupture (0.34% vs. 0.74%, respectively) and dehiscence (0.26% vs. 0.73%) were lower in the preterm group.

Significantly more women in the preterm group had coagulopathy and/or a need for transfusion, according to a multivariate analysis.

MIAMI BEACH — A trial of labor should be considered an option for women with a history of prior cesarean delivery when preterm delivery is anticipated, Dr. Celeste P. Durnwald said at the annual meeting of the Society for Maternal-Fetal Medicine.

“There is little information reported to date on the efficacy of a [vaginal birth after cesarean] attempt in women undergoing preterm delivery,” said Dr. Durnwald, who presented a study on behalf of the National Institute of Child Health and Human Development maternal-fetal medicine units network.

One other research team has addressed the impact of preterm vaginal birth after cesarean (VBAC), said Dr. Durnwald of Ohio State University, Columbus. Investigators in that study reviewed medical records for 20,156 women with a singleton fetus and history of one cesarean delivery, including 12,463 (62%) who attempted a VBAC. They compared women who delivered preterm, at a mean of 34 weeks, with a group who delivered full term, at a mean of 39 weeks. VBAC was successful for 82% of the preterm group and 74% of the term group, a statistically significant difference. The study, however, was retrospective (Obstet. Gynecol. 2005;105:519–24).

Dr. Durnwald and her associates assessed 3,119 women with a preterm pregnancy. Of these, 2,338, or 75%, attempted a trial of labor. The researchers compared the success of VBAC and the rates of uterine rupture and maternal morbidities in these women with those in a control group of 15,331 women who attempted a trial of labor at term. The groups were similar, except women in the preterm group were more likely to be African American, government insured, and smokers.

VBAC was successful for 72.8% of the preterm group and 73.2% of the term group, Dr. Durnwald said. Rates of uterine rupture (0.34% vs. 0.74%, respectively) and dehiscence (0.26% vs. 0.73%) were lower in the preterm group.

Significantly more women in the preterm group had coagulopathy and/or a need for transfusion, according to a multivariate analysis.

SAN JUAN, P.R. — Low heart rate variability is significantly associated with an increased risk of death in depressed versus nondepressed patients after an acute myocardial infarction, Robert M. Carney, Ph.D., said at the annual meeting of the American College of Psychiatrists.

Depression is common among patients with a recent, acute myocardial infarction (MI)—incidence of major depression ranges from 15% to 23% in the literature. Other researchers found that low 24-hour heart rate variability is a strong predictor of cardiac mortality in patients with a recent MI (Ann. Noninvasive Electrocardiol. 2005;10:88–101). Heart rate variability was as robust a predictor as ventricular dysfunction or the size of the infarction in this review article.

The aim of the current study was to determine whether 24-hour heart rate variability is lower in depressed patients, and if so, whether this finding explains why depression reduces cardiovascular mortality after an MI, said Dr. Carney, professor of psychiatry and director of the behavioral medicine center at Washington University, St. Louis.

The researchers assessed 305 depressed patients (135 with major depression and 170 with minor depression) with 24-hour ambulatory ECG readings 1–3 weeks post MI. Another group of 366 nondepressed, post-MI patients was included in the study for comparison.

The investigators measured frequency domain heart rate variability using very-low-frequency (VLF) power spectral analysis. “VLF reflects parasympathetic modulation and is one of the best predictors of post-MI mortality,” Dr. Carney said.

Dr. Carney and his associates found a difference in log of VLF power (LnVLF) measurements: 6.32 in the depressed group, compared with 6.59 in the nondepressed patients.

“This was statistically significant, but is it clinically significant?” Dr. Carney asked.

In the study, 16% of depressed patients and 7% of nondepressed controls had a VLF below 180 squared milliseconds. The estimated probability of survival over 30 months of follow-up was statistically lower among depressed patients.

“So low heart rate variability is a significant and important factor post MI,” Dr. Carney said.

After adjustment for other risk factors, including left ventricular ejection fraction, smoking, older age, and diabetes, the low heart rate variability hazard ratio “goes from 3.1 to 2.8—a tiny difference,” he commented.

“About 27% of the mortality risk in these patients can be accounted for by low heart rate variability,” Dr. Carney said. “So there are other things that are important here—including platelet function and inflammation.”

The literature is conflicting about whether treatment of depression provides a beneficial increase in heart rate variability. For example, 10 studies with tricyclic antidepressants yielded mixed results, Dr. Carney said, “and the six SSRI studies are more confusing.” Three SSRI studies reported increased heart rate variability, and three reported no change. Studies with other antidepressants offer no clear answer, either. No change in heart rate variability was seen in a nefazodone study, while lower heart rate variability was observed in a bupropion study and a venlafaxine trial.

Dr. Carney assessed the effect of psychotherapy among depressed congestive heart disease (CHD) patients. After 12 sessions of cognitive-behavioral therapy, mean heart rate decreased 5 beats/min and root mean squared successive difference increased. There were no changes in other heart rate variability indices. “Whether any treatment can reduce risk in CHD patients is unclear,” he said.

Depression is associated with autonomic nervous system dysfunction, and heart rate variability is a noninvasive method for studying cardiac autonomic nervous system modification, Dr. Carney explained. Heart rate variability reflects the intrinsic firing rate of sinoatrial pacemaker cells, an action that the autonomic nervous system modulates.

Heart rate variability may be improved through medication, exercise, and cardiac risk factor modification, Dr. Carney emphasized. “Regardless, depression in cardiac patients should be treated to improve quality of life, because we know we can do that.”

SAN JUAN, P.R. — Low heart rate variability is significantly associated with an increased risk of death in depressed versus nondepressed patients after an acute myocardial infarction, Robert M. Carney, Ph.D., said at the annual meeting of the American College of Psychiatrists.

Depression is common among patients with a recent, acute myocardial infarction (MI)—incidence of major depression ranges from 15% to 23% in the literature. Other researchers found that low 24-hour heart rate variability is a strong predictor of cardiac mortality in patients with a recent MI (Ann. Noninvasive Electrocardiol. 2005;10:88–101). Heart rate variability was as robust a predictor as ventricular dysfunction or the size of the infarction in this review article.

The aim of the current study was to determine whether 24-hour heart rate variability is lower in depressed patients, and if so, whether this finding explains why depression reduces cardiovascular mortality after an MI, said Dr. Carney, professor of psychiatry and director of the behavioral medicine center at Washington University, St. Louis.

The researchers assessed 305 depressed patients (135 with major depression and 170 with minor depression) with 24-hour ambulatory ECG readings 1–3 weeks post MI. Another group of 366 nondepressed, post-MI patients was included in the study for comparison.

The investigators measured frequency domain heart rate variability using very-low-frequency (VLF) power spectral analysis. “VLF reflects parasympathetic modulation and is one of the best predictors of post-MI mortality,” Dr. Carney said.

Dr. Carney and his associates found a difference in log of VLF power (LnVLF) measurements: 6.32 in the depressed group, compared with 6.59 in the nondepressed patients.

“This was statistically significant, but is it clinically significant?” Dr. Carney asked.

In the study, 16% of depressed patients and 7% of nondepressed controls had a VLF below 180 squared milliseconds. The estimated probability of survival over 30 months of follow-up was statistically lower among depressed patients.

“So low heart rate variability is a significant and important factor post MI,” Dr. Carney said.

After adjustment for other risk factors, including left ventricular ejection fraction, smoking, older age, and diabetes, the low heart rate variability hazard ratio “goes from 3.1 to 2.8—a tiny difference,” he commented.

“About 27% of the mortality risk in these patients can be accounted for by low heart rate variability,” Dr. Carney said. “So there are other things that are important here—including platelet function and inflammation.”

The literature is conflicting about whether treatment of depression provides a beneficial increase in heart rate variability. For example, 10 studies with tricyclic antidepressants yielded mixed results, Dr. Carney said, “and the six SSRI studies are more confusing.” Three SSRI studies reported increased heart rate variability, and three reported no change. Studies with other antidepressants offer no clear answer, either. No change in heart rate variability was seen in a nefazodone study, while lower heart rate variability was observed in a bupropion study and a venlafaxine trial.

Dr. Carney assessed the effect of psychotherapy among depressed congestive heart disease (CHD) patients. After 12 sessions of cognitive-behavioral therapy, mean heart rate decreased 5 beats/min and root mean squared successive difference increased. There were no changes in other heart rate variability indices. “Whether any treatment can reduce risk in CHD patients is unclear,” he said.

Depression is associated with autonomic nervous system dysfunction, and heart rate variability is a noninvasive method for studying cardiac autonomic nervous system modification, Dr. Carney explained. Heart rate variability reflects the intrinsic firing rate of sinoatrial pacemaker cells, an action that the autonomic nervous system modulates.

Heart rate variability may be improved through medication, exercise, and cardiac risk factor modification, Dr. Carney emphasized. “Regardless, depression in cardiac patients should be treated to improve quality of life, because we know we can do that.”

SAN JUAN, P.R. — Low heart rate variability is significantly associated with an increased risk of death in depressed versus nondepressed patients after an acute myocardial infarction, Robert M. Carney, Ph.D., said at the annual meeting of the American College of Psychiatrists.

Depression is common among patients with a recent, acute myocardial infarction (MI)—incidence of major depression ranges from 15% to 23% in the literature. Other researchers found that low 24-hour heart rate variability is a strong predictor of cardiac mortality in patients with a recent MI (Ann. Noninvasive Electrocardiol. 2005;10:88–101). Heart rate variability was as robust a predictor as ventricular dysfunction or the size of the infarction in this review article.

The aim of the current study was to determine whether 24-hour heart rate variability is lower in depressed patients, and if so, whether this finding explains why depression reduces cardiovascular mortality after an MI, said Dr. Carney, professor of psychiatry and director of the behavioral medicine center at Washington University, St. Louis.

The researchers assessed 305 depressed patients (135 with major depression and 170 with minor depression) with 24-hour ambulatory ECG readings 1–3 weeks post MI. Another group of 366 nondepressed, post-MI patients was included in the study for comparison.

The investigators measured frequency domain heart rate variability using very-low-frequency (VLF) power spectral analysis. “VLF reflects parasympathetic modulation and is one of the best predictors of post-MI mortality,” Dr. Carney said.

Dr. Carney and his associates found a difference in log of VLF power (LnVLF) measurements: 6.32 in the depressed group, compared with 6.59 in the nondepressed patients.

“This was statistically significant, but is it clinically significant?” Dr. Carney asked.

In the study, 16% of depressed patients and 7% of nondepressed controls had a VLF below 180 squared milliseconds. The estimated probability of survival over 30 months of follow-up was statistically lower among depressed patients.

“So low heart rate variability is a significant and important factor post MI,” Dr. Carney said.

After adjustment for other risk factors, including left ventricular ejection fraction, smoking, older age, and diabetes, the low heart rate variability hazard ratio “goes from 3.1 to 2.8—a tiny difference,” he commented.

“About 27% of the mortality risk in these patients can be accounted for by low heart rate variability,” Dr. Carney said. “So there are other things that are important here—including platelet function and inflammation.”

The literature is conflicting about whether treatment of depression provides a beneficial increase in heart rate variability. For example, 10 studies with tricyclic antidepressants yielded mixed results, Dr. Carney said, “and the six SSRI studies are more confusing.” Three SSRI studies reported increased heart rate variability, and three reported no change. Studies with other antidepressants offer no clear answer, either. No change in heart rate variability was seen in a nefazodone study, while lower heart rate variability was observed in a bupropion study and a venlafaxine trial.

Dr. Carney assessed the effect of psychotherapy among depressed congestive heart disease (CHD) patients. After 12 sessions of cognitive-behavioral therapy, mean heart rate decreased 5 beats/min and root mean squared successive difference increased. There were no changes in other heart rate variability indices. “Whether any treatment can reduce risk in CHD patients is unclear,” he said.

Depression is associated with autonomic nervous system dysfunction, and heart rate variability is a noninvasive method for studying cardiac autonomic nervous system modification, Dr. Carney explained. Heart rate variability reflects the intrinsic firing rate of sinoatrial pacemaker cells, an action that the autonomic nervous system modulates.

Heart rate variability may be improved through medication, exercise, and cardiac risk factor modification, Dr. Carney emphasized. “Regardless, depression in cardiac patients should be treated to improve quality of life, because we know we can do that.”

SAN JUAN, P.R. — Growing evidence points to an association between inflammation and depression, according to a presentation at the annual meeting of the American College of Psychiatrists.

For example, depressed patients have elevated inflammatory markers—such as interleukin-6 and C-reactive protein. In fact, the levels of proinflammatory cytokines correlate with the severity of depressive symptoms in studies. In addition, administration of cytokine antagonists can effectively reverse depressive symptoms in patients, Dr. Andrew H. Miller said.

“We really stand at a point that is very exciting in terms of novel therapies and translation of research,” Dr. Miller said. “The notion quite simply is that stress or depression affects the HPA [hypothalamic-pituitary-adrenal] axis, [affects] the endocrine system, alters the immune system, and leaves patients open to diseases.”

Physicians from many specialties already recognize that inflammation plays a key role in cardiovascular disease, diabetes, metabolic syndrome, and cancer, said Dr. Miller, professor in the department of psychiatry and behavioral sciences at Emory University, Atlanta. “We did not want to be left out in terms of psychiatry,” said Dr. Miller, who also is director of the psychiatric oncology program at the Winship Cancer Institute at Emory.

There are multiple possible mechanisms whereby inflammation could cause depression. Inflammatory cytokines released peripherally might reach the brain through active transport, passage through leaky regions in the blood-brain barrier, or transmission through afferent nerve fibers (vagus nerve), Dr. Miller said. There is a cytokine network in the central nervous system, and glia and microglia are the richest source of cytokines in the brain. Neurons also produce and express cytokines.

“We've learned these cytokines have access to the brain and … ultimately can change behavior,” Dr. Miller said. Inflammatory cytokines cause anhedonia, fatigue, cognitive dysfunction, and other flu-like symptoms in sick patients. In addition, researchers induced behavioral changes that resemble major depression in human and animal studies with administration of proinflammatory cytokines.

Some therapeutic cytokines cause depression. A total of 60% of patients treated with IFN-α reported depressed mood in one study (Neuropsychopharmacology 2002;26:643–52). Dr. Miller and his associates found a 45% incidence of major depression in malignant melanoma patients treated with IFN-α (N. Engl. J. Med. 2001;344:961–6).

SAN JUAN, P.R. — Growing evidence points to an association between inflammation and depression, according to a presentation at the annual meeting of the American College of Psychiatrists.

For example, depressed patients have elevated inflammatory markers—such as interleukin-6 and C-reactive protein. In fact, the levels of proinflammatory cytokines correlate with the severity of depressive symptoms in studies. In addition, administration of cytokine antagonists can effectively reverse depressive symptoms in patients, Dr. Andrew H. Miller said.

“We really stand at a point that is very exciting in terms of novel therapies and translation of research,” Dr. Miller said. “The notion quite simply is that stress or depression affects the HPA [hypothalamic-pituitary-adrenal] axis, [affects] the endocrine system, alters the immune system, and leaves patients open to diseases.”

Physicians from many specialties already recognize that inflammation plays a key role in cardiovascular disease, diabetes, metabolic syndrome, and cancer, said Dr. Miller, professor in the department of psychiatry and behavioral sciences at Emory University, Atlanta. “We did not want to be left out in terms of psychiatry,” said Dr. Miller, who also is director of the psychiatric oncology program at the Winship Cancer Institute at Emory.

There are multiple possible mechanisms whereby inflammation could cause depression. Inflammatory cytokines released peripherally might reach the brain through active transport, passage through leaky regions in the blood-brain barrier, or transmission through afferent nerve fibers (vagus nerve), Dr. Miller said. There is a cytokine network in the central nervous system, and glia and microglia are the richest source of cytokines in the brain. Neurons also produce and express cytokines.

“We've learned these cytokines have access to the brain and … ultimately can change behavior,” Dr. Miller said. Inflammatory cytokines cause anhedonia, fatigue, cognitive dysfunction, and other flu-like symptoms in sick patients. In addition, researchers induced behavioral changes that resemble major depression in human and animal studies with administration of proinflammatory cytokines.

Some therapeutic cytokines cause depression. A total of 60% of patients treated with IFN-α reported depressed mood in one study (Neuropsychopharmacology 2002;26:643–52). Dr. Miller and his associates found a 45% incidence of major depression in malignant melanoma patients treated with IFN-α (N. Engl. J. Med. 2001;344:961–6).

SAN JUAN, P.R. — Growing evidence points to an association between inflammation and depression, according to a presentation at the annual meeting of the American College of Psychiatrists.

For example, depressed patients have elevated inflammatory markers—such as interleukin-6 and C-reactive protein. In fact, the levels of proinflammatory cytokines correlate with the severity of depressive symptoms in studies. In addition, administration of cytokine antagonists can effectively reverse depressive symptoms in patients, Dr. Andrew H. Miller said.

“We really stand at a point that is very exciting in terms of novel therapies and translation of research,” Dr. Miller said. “The notion quite simply is that stress or depression affects the HPA [hypothalamic-pituitary-adrenal] axis, [affects] the endocrine system, alters the immune system, and leaves patients open to diseases.”

Physicians from many specialties already recognize that inflammation plays a key role in cardiovascular disease, diabetes, metabolic syndrome, and cancer, said Dr. Miller, professor in the department of psychiatry and behavioral sciences at Emory University, Atlanta. “We did not want to be left out in terms of psychiatry,” said Dr. Miller, who also is director of the psychiatric oncology program at the Winship Cancer Institute at Emory.

There are multiple possible mechanisms whereby inflammation could cause depression. Inflammatory cytokines released peripherally might reach the brain through active transport, passage through leaky regions in the blood-brain barrier, or transmission through afferent nerve fibers (vagus nerve), Dr. Miller said. There is a cytokine network in the central nervous system, and glia and microglia are the richest source of cytokines in the brain. Neurons also produce and express cytokines.

“We've learned these cytokines have access to the brain and … ultimately can change behavior,” Dr. Miller said. Inflammatory cytokines cause anhedonia, fatigue, cognitive dysfunction, and other flu-like symptoms in sick patients. In addition, researchers induced behavioral changes that resemble major depression in human and animal studies with administration of proinflammatory cytokines.

Some therapeutic cytokines cause depression. A total of 60% of patients treated with IFN-α reported depressed mood in one study (Neuropsychopharmacology 2002;26:643–52). Dr. Miller and his associates found a 45% incidence of major depression in malignant melanoma patients treated with IFN-α (N. Engl. J. Med. 2001;344:961–6).

MIAMI BEACH — Progesterone prevents recurrent preterm delivery to the same degree whether it is initiated earlier or later in the second trimester, according to a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

“We were thinking that those who started earlier would have some benefit. But essentially it doesn't matter if you start progesterone at 16–18 weeks or between 19 and 21 weeks,” said Dr. Gretchen Koontz of the ob.gyn. department at Wake Forest University in Winston-Salem, N.C.

In a 2003 study, researchers randomized women with a history of previous spontaneous preterm birth (before 37 weeks) to weekly injections of either 17 α-hydroxyprogesterone caproate (17P) or placebo (N. Engl. J. Med. 2003;348:2379–85). Of the 306 women who received 17P between 16 and 21 weeks' gestation, 36% delivered before 37 weeks, compared with 55% of the 153 women in the placebo group, a statistically significant difference.

As a secondary analysis of the original study data, Dr. Koontz compared 227 women who began weekly injections of 17P between 16 and 18 weeks, with 272 others who began 17P between weeks 19 and 21. Results showed that 36.5% of participants in the 16− to 18-week group delivered preterm, compared with 36.1% of those in the 19− to 21-week group.

MIAMI BEACH — Progesterone prevents recurrent preterm delivery to the same degree whether it is initiated earlier or later in the second trimester, according to a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

“We were thinking that those who started earlier would have some benefit. But essentially it doesn't matter if you start progesterone at 16–18 weeks or between 19 and 21 weeks,” said Dr. Gretchen Koontz of the ob.gyn. department at Wake Forest University in Winston-Salem, N.C.

In a 2003 study, researchers randomized women with a history of previous spontaneous preterm birth (before 37 weeks) to weekly injections of either 17 α-hydroxyprogesterone caproate (17P) or placebo (N. Engl. J. Med. 2003;348:2379–85). Of the 306 women who received 17P between 16 and 21 weeks' gestation, 36% delivered before 37 weeks, compared with 55% of the 153 women in the placebo group, a statistically significant difference.

As a secondary analysis of the original study data, Dr. Koontz compared 227 women who began weekly injections of 17P between 16 and 18 weeks, with 272 others who began 17P between weeks 19 and 21. Results showed that 36.5% of participants in the 16− to 18-week group delivered preterm, compared with 36.1% of those in the 19− to 21-week group.

MIAMI BEACH — Progesterone prevents recurrent preterm delivery to the same degree whether it is initiated earlier or later in the second trimester, according to a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

“We were thinking that those who started earlier would have some benefit. But essentially it doesn't matter if you start progesterone at 16–18 weeks or between 19 and 21 weeks,” said Dr. Gretchen Koontz of the ob.gyn. department at Wake Forest University in Winston-Salem, N.C.

In a 2003 study, researchers randomized women with a history of previous spontaneous preterm birth (before 37 weeks) to weekly injections of either 17 α-hydroxyprogesterone caproate (17P) or placebo (N. Engl. J. Med. 2003;348:2379–85). Of the 306 women who received 17P between 16 and 21 weeks' gestation, 36% delivered before 37 weeks, compared with 55% of the 153 women in the placebo group, a statistically significant difference.

As a secondary analysis of the original study data, Dr. Koontz compared 227 women who began weekly injections of 17P between 16 and 18 weeks, with 272 others who began 17P between weeks 19 and 21. Results showed that 36.5% of participants in the 16− to 18-week group delivered preterm, compared with 36.1% of those in the 19− to 21-week group.

MIAMI BEACH — Maternal serum α-fetoprotein is no longer an effective or cost-effective second-trimester screen for neural tube defects in an era when women routinely undergo first-trimester Down syndrome screening and subsequent ultrasound, Dr. Todd J. Rosen said at the annual meeting of the Society for Maternal-Fetal Medicine.

Before ultrasound was commonplace—back in the 1970s and 1980s—women got an α-fetoprotein (AFP) test for spina bifida and anencephaly. “Now more and more women are screening for Down syndrome in the first trimester, and it is routine for women to do an ultrasound screen as well,” said Dr. Rosen of the division of maternal-fetal medicine, Columbia University, New York.

Dr. Rosen and his associates assessed clinical and cost effectiveness of AFP testing for U.S. women who had a first-trimester Down syndrome risk assessment and second-trimester ultrasound examination. They used a decision analysis model that assumed ultrasound provides 100% detection of anencephaly and 92% detection of spina bifida (the lowest percentage reported in the literature). To put AFP testing in the most favorable light, the model assumed a 92% detection rate for spina bifida (the highest in the literature) with a 3% false-positive rate.

The model predicted an estimated 4,000 neural tube defects among the approximate 4 million births in the United States in 2003. Screening of all these women with ultrasound would detect 2,208 of the 2,400 cases of spina bifida. AFP testing would yield 120,000 positive results and detect 176 of the 192 cases of spina bifida missed by ultrasound.

“The AFP test induces anxiety—for every 10,000 women who screen positive, only 3 will have a baby with spina bifida,” Dr. Rosen said. AFP screening in women who undergo first- and second-trimester ultrasound examinations has a poor predictive value and causes more pregnancy losses from amniocentesis than cases of spina bifida it detects, he added. In addition, “by continuing to do AFP, we are spending all this money,” Dr. Rosen said.

For example, universal screening in the study cohort would cost $184 million. Because about 40% of women terminate a pregnancy because of spina bifida (in this model, 70 of 176 women), the cost becomes $2.6 million for each case prevented. Assuming that 50% of women with an elevated AFP result have amniocentesis and that the procedure's loss rate is one fetus per 250, 245 women would lose their pregnancies, he estimated.

“As doctors we are really caught. We want to do what is right for patients, but we have a high risk of malpractice [lawsuits],” Dr. Rosen said. “Because we are so wary of missing anything, we err on the side of overtesting and this can do more harm than good.”

MIAMI BEACH — Maternal serum α-fetoprotein is no longer an effective or cost-effective second-trimester screen for neural tube defects in an era when women routinely undergo first-trimester Down syndrome screening and subsequent ultrasound, Dr. Todd J. Rosen said at the annual meeting of the Society for Maternal-Fetal Medicine.

Before ultrasound was commonplace—back in the 1970s and 1980s—women got an α-fetoprotein (AFP) test for spina bifida and anencephaly. “Now more and more women are screening for Down syndrome in the first trimester, and it is routine for women to do an ultrasound screen as well,” said Dr. Rosen of the division of maternal-fetal medicine, Columbia University, New York.

Dr. Rosen and his associates assessed clinical and cost effectiveness of AFP testing for U.S. women who had a first-trimester Down syndrome risk assessment and second-trimester ultrasound examination. They used a decision analysis model that assumed ultrasound provides 100% detection of anencephaly and 92% detection of spina bifida (the lowest percentage reported in the literature). To put AFP testing in the most favorable light, the model assumed a 92% detection rate for spina bifida (the highest in the literature) with a 3% false-positive rate.

The model predicted an estimated 4,000 neural tube defects among the approximate 4 million births in the United States in 2003. Screening of all these women with ultrasound would detect 2,208 of the 2,400 cases of spina bifida. AFP testing would yield 120,000 positive results and detect 176 of the 192 cases of spina bifida missed by ultrasound.

“The AFP test induces anxiety—for every 10,000 women who screen positive, only 3 will have a baby with spina bifida,” Dr. Rosen said. AFP screening in women who undergo first- and second-trimester ultrasound examinations has a poor predictive value and causes more pregnancy losses from amniocentesis than cases of spina bifida it detects, he added. In addition, “by continuing to do AFP, we are spending all this money,” Dr. Rosen said.

For example, universal screening in the study cohort would cost $184 million. Because about 40% of women terminate a pregnancy because of spina bifida (in this model, 70 of 176 women), the cost becomes $2.6 million for each case prevented. Assuming that 50% of women with an elevated AFP result have amniocentesis and that the procedure's loss rate is one fetus per 250, 245 women would lose their pregnancies, he estimated.

“As doctors we are really caught. We want to do what is right for patients, but we have a high risk of malpractice [lawsuits],” Dr. Rosen said. “Because we are so wary of missing anything, we err on the side of overtesting and this can do more harm than good.”

MIAMI BEACH — Maternal serum α-fetoprotein is no longer an effective or cost-effective second-trimester screen for neural tube defects in an era when women routinely undergo first-trimester Down syndrome screening and subsequent ultrasound, Dr. Todd J. Rosen said at the annual meeting of the Society for Maternal-Fetal Medicine.

Before ultrasound was commonplace—back in the 1970s and 1980s—women got an α-fetoprotein (AFP) test for spina bifida and anencephaly. “Now more and more women are screening for Down syndrome in the first trimester, and it is routine for women to do an ultrasound screen as well,” said Dr. Rosen of the division of maternal-fetal medicine, Columbia University, New York.

Dr. Rosen and his associates assessed clinical and cost effectiveness of AFP testing for U.S. women who had a first-trimester Down syndrome risk assessment and second-trimester ultrasound examination. They used a decision analysis model that assumed ultrasound provides 100% detection of anencephaly and 92% detection of spina bifida (the lowest percentage reported in the literature). To put AFP testing in the most favorable light, the model assumed a 92% detection rate for spina bifida (the highest in the literature) with a 3% false-positive rate.

The model predicted an estimated 4,000 neural tube defects among the approximate 4 million births in the United States in 2003. Screening of all these women with ultrasound would detect 2,208 of the 2,400 cases of spina bifida. AFP testing would yield 120,000 positive results and detect 176 of the 192 cases of spina bifida missed by ultrasound.

“The AFP test induces anxiety—for every 10,000 women who screen positive, only 3 will have a baby with spina bifida,” Dr. Rosen said. AFP screening in women who undergo first- and second-trimester ultrasound examinations has a poor predictive value and causes more pregnancy losses from amniocentesis than cases of spina bifida it detects, he added. In addition, “by continuing to do AFP, we are spending all this money,” Dr. Rosen said.

For example, universal screening in the study cohort would cost $184 million. Because about 40% of women terminate a pregnancy because of spina bifida (in this model, 70 of 176 women), the cost becomes $2.6 million for each case prevented. Assuming that 50% of women with an elevated AFP result have amniocentesis and that the procedure's loss rate is one fetus per 250, 245 women would lose their pregnancies, he estimated.

“As doctors we are really caught. We want to do what is right for patients, but we have a high risk of malpractice [lawsuits],” Dr. Rosen said. “Because we are so wary of missing anything, we err on the side of overtesting and this can do more harm than good.”

SAN JUAN, P.R. — A selective serotonin reuptake inhibitor can enhance killer lymphocyte activity against HIV infection, according to preliminary study findings.

Depression may raise the risk of morbidity and mortality in patients with many medical conditions, including HIV infection. In addition, depression has been linked to immune function deficits, such as decreased natural killer cell activity, according to a presentation at the annual meeting of the American College of Psychiatrists.

In normal physiology, natural killer cells defend against viral infections and eliminate neoplastic cells. Natural killer cells are a focus of the ongoing HIV in Women: Depression and Immunity study, funded by the National Institute of Mental Health.

In this study of 40 women, a blood sample was obtained from each subject, and the researchers then treated the sample with citalopram and/or a substance P antagonist (an experimental agent); they then measured natural killer cell activity in vitro. They found that such treatment could reverse the detrimental effect of HIV on natural killer cell activity.

These preliminary data are “hot off the press,” Dr. Dwight L. Evans said. “Next we need to look at this in a real in vivo situation.”

These findings “suggest that killer lymphocyte antiviral activity is enhanced by an SSRI and the substance P antagonist,” said Dr. Evans, the Ruth Meltzer Professor and chair of psychiatry at the University of Pennsylvania in Philadelphia.

“The reason we focused on natural killer cells—or killer lymphocytes as they are now known—is they kill or lyse HIV-1 infected cells and secrete chemokines and cytokines,” Dr. Evans said.

Cytotoxic T lymphocytes also lyse HIV-infected cells and secrete HIV-suppressive factors. Severe life stress decreases both these natural killer cells and cytotoxic T lymphocytes, he added.

In another study, Dr. Evans and his associates found that resolution of major depression was associated with increased natural killer cell activity in HIV-seropositive women (Am. J. Psychiatry 2005;162:2125–30).

The investigators assessed 57 women over 2 years and found that variations in natural killer cell levels corresponded to changes in depression status and ratings on the 17-item Hamilton Depression Rating Scale. Major depression in 11 participants resolved over time, with a simultaneous and significant increase in natural killer cell activity, which returned to normal levels.

“This study suggests that depression may impair certain aspects of innate cellular immunity relevant to delaying the progression of HIV disease and that these alterations are reversible with the resolution of a depressive episode,” the authors wrote. “We don't know if this is a resolution of depression or if it's a direct effect of the treatment on the immune system,” Dr. Evans added.

Researchers are assessing other potential mechanisms that may influence immunity and HIV disease progression, including hyperactivity of the hypothalamic-pituitary-adrenal axis and increases in substance P. Studies have shown that HIV-positive men have elevated substance P levels, compared with HIV-negative men, Dr. Evans said.

“Depression is really bad for the brain, bad for the body,” Dr. Evans said. The physiologic changes that have been associated with depression include suppression of cell-mediated immunity, decreased neurogenesis in the brain, decreased heart rate variability, increased platelets, hyperactivity of the hypothalamic-pituitary-adrenal axis, and increased insulin resistance.

Dr. Evans has published an article on the topic titled, “Mood Disorders in the Medically Ill: Scientific Review and Recommendations” (Biol. Psychiatry 2005;58:175–89). “We're trying to get this issue in front of our other colleagues in medicine,” he commented.

SAN JUAN, P.R. — A selective serotonin reuptake inhibitor can enhance killer lymphocyte activity against HIV infection, according to preliminary study findings.

Depression may raise the risk of morbidity and mortality in patients with many medical conditions, including HIV infection. In addition, depression has been linked to immune function deficits, such as decreased natural killer cell activity, according to a presentation at the annual meeting of the American College of Psychiatrists.

In normal physiology, natural killer cells defend against viral infections and eliminate neoplastic cells. Natural killer cells are a focus of the ongoing HIV in Women: Depression and Immunity study, funded by the National Institute of Mental Health.

In this study of 40 women, a blood sample was obtained from each subject, and the researchers then treated the sample with citalopram and/or a substance P antagonist (an experimental agent); they then measured natural killer cell activity in vitro. They found that such treatment could reverse the detrimental effect of HIV on natural killer cell activity.

These preliminary data are “hot off the press,” Dr. Dwight L. Evans said. “Next we need to look at this in a real in vivo situation.”

These findings “suggest that killer lymphocyte antiviral activity is enhanced by an SSRI and the substance P antagonist,” said Dr. Evans, the Ruth Meltzer Professor and chair of psychiatry at the University of Pennsylvania in Philadelphia.

“The reason we focused on natural killer cells—or killer lymphocytes as they are now known—is they kill or lyse HIV-1 infected cells and secrete chemokines and cytokines,” Dr. Evans said.

Cytotoxic T lymphocytes also lyse HIV-infected cells and secrete HIV-suppressive factors. Severe life stress decreases both these natural killer cells and cytotoxic T lymphocytes, he added.

In another study, Dr. Evans and his associates found that resolution of major depression was associated with increased natural killer cell activity in HIV-seropositive women (Am. J. Psychiatry 2005;162:2125–30).

The investigators assessed 57 women over 2 years and found that variations in natural killer cell levels corresponded to changes in depression status and ratings on the 17-item Hamilton Depression Rating Scale. Major depression in 11 participants resolved over time, with a simultaneous and significant increase in natural killer cell activity, which returned to normal levels.

“This study suggests that depression may impair certain aspects of innate cellular immunity relevant to delaying the progression of HIV disease and that these alterations are reversible with the resolution of a depressive episode,” the authors wrote. “We don't know if this is a resolution of depression or if it's a direct effect of the treatment on the immune system,” Dr. Evans added.

Researchers are assessing other potential mechanisms that may influence immunity and HIV disease progression, including hyperactivity of the hypothalamic-pituitary-adrenal axis and increases in substance P. Studies have shown that HIV-positive men have elevated substance P levels, compared with HIV-negative men, Dr. Evans said.

“Depression is really bad for the brain, bad for the body,” Dr. Evans said. The physiologic changes that have been associated with depression include suppression of cell-mediated immunity, decreased neurogenesis in the brain, decreased heart rate variability, increased platelets, hyperactivity of the hypothalamic-pituitary-adrenal axis, and increased insulin resistance.

Dr. Evans has published an article on the topic titled, “Mood Disorders in the Medically Ill: Scientific Review and Recommendations” (Biol. Psychiatry 2005;58:175–89). “We're trying to get this issue in front of our other colleagues in medicine,” he commented.

SAN JUAN, P.R. — A selective serotonin reuptake inhibitor can enhance killer lymphocyte activity against HIV infection, according to preliminary study findings.

Depression may raise the risk of morbidity and mortality in patients with many medical conditions, including HIV infection. In addition, depression has been linked to immune function deficits, such as decreased natural killer cell activity, according to a presentation at the annual meeting of the American College of Psychiatrists.

In normal physiology, natural killer cells defend against viral infections and eliminate neoplastic cells. Natural killer cells are a focus of the ongoing HIV in Women: Depression and Immunity study, funded by the National Institute of Mental Health.

In this study of 40 women, a blood sample was obtained from each subject, and the researchers then treated the sample with citalopram and/or a substance P antagonist (an experimental agent); they then measured natural killer cell activity in vitro. They found that such treatment could reverse the detrimental effect of HIV on natural killer cell activity.

These preliminary data are “hot off the press,” Dr. Dwight L. Evans said. “Next we need to look at this in a real in vivo situation.”

These findings “suggest that killer lymphocyte antiviral activity is enhanced by an SSRI and the substance P antagonist,” said Dr. Evans, the Ruth Meltzer Professor and chair of psychiatry at the University of Pennsylvania in Philadelphia.

“The reason we focused on natural killer cells—or killer lymphocytes as they are now known—is they kill or lyse HIV-1 infected cells and secrete chemokines and cytokines,” Dr. Evans said.

Cytotoxic T lymphocytes also lyse HIV-infected cells and secrete HIV-suppressive factors. Severe life stress decreases both these natural killer cells and cytotoxic T lymphocytes, he added.

In another study, Dr. Evans and his associates found that resolution of major depression was associated with increased natural killer cell activity in HIV-seropositive women (Am. J. Psychiatry 2005;162:2125–30).

The investigators assessed 57 women over 2 years and found that variations in natural killer cell levels corresponded to changes in depression status and ratings on the 17-item Hamilton Depression Rating Scale. Major depression in 11 participants resolved over time, with a simultaneous and significant increase in natural killer cell activity, which returned to normal levels.

“This study suggests that depression may impair certain aspects of innate cellular immunity relevant to delaying the progression of HIV disease and that these alterations are reversible with the resolution of a depressive episode,” the authors wrote. “We don't know if this is a resolution of depression or if it's a direct effect of the treatment on the immune system,” Dr. Evans added.

Researchers are assessing other potential mechanisms that may influence immunity and HIV disease progression, including hyperactivity of the hypothalamic-pituitary-adrenal axis and increases in substance P. Studies have shown that HIV-positive men have elevated substance P levels, compared with HIV-negative men, Dr. Evans said.

“Depression is really bad for the brain, bad for the body,” Dr. Evans said. The physiologic changes that have been associated with depression include suppression of cell-mediated immunity, decreased neurogenesis in the brain, decreased heart rate variability, increased platelets, hyperactivity of the hypothalamic-pituitary-adrenal axis, and increased insulin resistance.

Dr. Evans has published an article on the topic titled, “Mood Disorders in the Medically Ill: Scientific Review and Recommendations” (Biol. Psychiatry 2005;58:175–89). “We're trying to get this issue in front of our other colleagues in medicine,” he commented.

SAN JUAN, P.R. — Virtual reality exposure therapy shows promise for relieving symptoms of posttraumatic stress disorder in Vietnam veterans, according to a study. Based on the findings, the principal investigator is now field testing the same high-tech approach with American soldiers in Iraq.

“We've used this as a new way to do exposure therapy,” said Barbara O. Rothbaum, Ph.D., at the annual meeting of the American College of Psychiatrists.

With virtual reality, “the person experiences a sense of presence. It's immersive, so it's more than simply a multimedia experience.”

In the Vietnam veteran study, participants donned a virtual reality headset and experienced a virtual Vietnam War clip (J. Clin. Psychiatry, in press). To more closely simulate actual combat, each veteran stood or sat on a platform above a vibrating speaker during the therapy session.

“People got better; we see it as a slice, or part, of the treatment,” said Dr. Rothbaum, director of the trauma and anxiety recovery program, department of psychiatry and behavioral sciences, at Emory University in Atlanta.

Dr. Rothbaum and her associates observed good end-state functioning immediately post therapy and at 6-month follow-up with virtual reality among 10 Vietnam veterans with posttraumatic stress disorder (PTSD). For example, 70% had good functioning after virtual reality exposure, compared with 50% after eye movement desensitization and reprocessing exposure (EMDR). EMDR is a form of exposure combined with saccadic eye movement—patients follow the therapist's finger while a traumatic story is recounted. At 6 months, the figures were 78% for virtual reality and 35% for EMDR, said Dr. Rothbaum.

“We're just about to start a study of Iraqi veterans with a series of virtual realty images we can individualize for patients,” Dr. Rothbaum said.

The virtual reality application was developed at the University of Southern California's Institute for Creative Technologies by Skip Rizzo, Ph.D., and Jarrell Pair, in collaboration with Ken Graap at Virtually Better Inc. in Atlanta.

It is unknown whether a combination of exposure therapy and medication for PTSD would enhance outcomes. Once field testing is complete, participants in the Iraq war veteran study will take D-cycloserine (Seromycin), alprazolam (Xanax), or a placebo before each virtual reality exposure “to see how they do,” Dr. Rothbaum said.

Several research teams around the world are using virtual reality for treating PTSD, Dr. Rothbaum said. For example, investigators at Cornell University, Ithaca, N.Y., and the University of Washington, Seattle, are simulating the World Trade Center attacks; researchers at the University of Washington and the University of Haifa, in Israel, are simulating terrorist bus bombings; University of Buffalo, N.Y., investigators are simulating motor vehicle accidents; and investigators at the University of Lusofona in Portugal are creating a virtual Angola.

SAN JUAN, P.R. — Virtual reality exposure therapy shows promise for relieving symptoms of posttraumatic stress disorder in Vietnam veterans, according to a study. Based on the findings, the principal investigator is now field testing the same high-tech approach with American soldiers in Iraq.

“We've used this as a new way to do exposure therapy,” said Barbara O. Rothbaum, Ph.D., at the annual meeting of the American College of Psychiatrists.

With virtual reality, “the person experiences a sense of presence. It's immersive, so it's more than simply a multimedia experience.”

In the Vietnam veteran study, participants donned a virtual reality headset and experienced a virtual Vietnam War clip (J. Clin. Psychiatry, in press). To more closely simulate actual combat, each veteran stood or sat on a platform above a vibrating speaker during the therapy session.

“People got better; we see it as a slice, or part, of the treatment,” said Dr. Rothbaum, director of the trauma and anxiety recovery program, department of psychiatry and behavioral sciences, at Emory University in Atlanta.

Dr. Rothbaum and her associates observed good end-state functioning immediately post therapy and at 6-month follow-up with virtual reality among 10 Vietnam veterans with posttraumatic stress disorder (PTSD). For example, 70% had good functioning after virtual reality exposure, compared with 50% after eye movement desensitization and reprocessing exposure (EMDR). EMDR is a form of exposure combined with saccadic eye movement—patients follow the therapist's finger while a traumatic story is recounted. At 6 months, the figures were 78% for virtual reality and 35% for EMDR, said Dr. Rothbaum.

“We're just about to start a study of Iraqi veterans with a series of virtual realty images we can individualize for patients,” Dr. Rothbaum said.

The virtual reality application was developed at the University of Southern California's Institute for Creative Technologies by Skip Rizzo, Ph.D., and Jarrell Pair, in collaboration with Ken Graap at Virtually Better Inc. in Atlanta.

It is unknown whether a combination of exposure therapy and medication for PTSD would enhance outcomes. Once field testing is complete, participants in the Iraq war veteran study will take D-cycloserine (Seromycin), alprazolam (Xanax), or a placebo before each virtual reality exposure “to see how they do,” Dr. Rothbaum said.

Several research teams around the world are using virtual reality for treating PTSD, Dr. Rothbaum said. For example, investigators at Cornell University, Ithaca, N.Y., and the University of Washington, Seattle, are simulating the World Trade Center attacks; researchers at the University of Washington and the University of Haifa, in Israel, are simulating terrorist bus bombings; University of Buffalo, N.Y., investigators are simulating motor vehicle accidents; and investigators at the University of Lusofona in Portugal are creating a virtual Angola.

SAN JUAN, P.R. — Virtual reality exposure therapy shows promise for relieving symptoms of posttraumatic stress disorder in Vietnam veterans, according to a study. Based on the findings, the principal investigator is now field testing the same high-tech approach with American soldiers in Iraq.

“We've used this as a new way to do exposure therapy,” said Barbara O. Rothbaum, Ph.D., at the annual meeting of the American College of Psychiatrists.

With virtual reality, “the person experiences a sense of presence. It's immersive, so it's more than simply a multimedia experience.”

In the Vietnam veteran study, participants donned a virtual reality headset and experienced a virtual Vietnam War clip (J. Clin. Psychiatry, in press). To more closely simulate actual combat, each veteran stood or sat on a platform above a vibrating speaker during the therapy session.

“People got better; we see it as a slice, or part, of the treatment,” said Dr. Rothbaum, director of the trauma and anxiety recovery program, department of psychiatry and behavioral sciences, at Emory University in Atlanta.

Dr. Rothbaum and her associates observed good end-state functioning immediately post therapy and at 6-month follow-up with virtual reality among 10 Vietnam veterans with posttraumatic stress disorder (PTSD). For example, 70% had good functioning after virtual reality exposure, compared with 50% after eye movement desensitization and reprocessing exposure (EMDR). EMDR is a form of exposure combined with saccadic eye movement—patients follow the therapist's finger while a traumatic story is recounted. At 6 months, the figures were 78% for virtual reality and 35% for EMDR, said Dr. Rothbaum.

“We're just about to start a study of Iraqi veterans with a series of virtual realty images we can individualize for patients,” Dr. Rothbaum said.

The virtual reality application was developed at the University of Southern California's Institute for Creative Technologies by Skip Rizzo, Ph.D., and Jarrell Pair, in collaboration with Ken Graap at Virtually Better Inc. in Atlanta.

It is unknown whether a combination of exposure therapy and medication for PTSD would enhance outcomes. Once field testing is complete, participants in the Iraq war veteran study will take D-cycloserine (Seromycin), alprazolam (Xanax), or a placebo before each virtual reality exposure “to see how they do,” Dr. Rothbaum said.

Several research teams around the world are using virtual reality for treating PTSD, Dr. Rothbaum said. For example, investigators at Cornell University, Ithaca, N.Y., and the University of Washington, Seattle, are simulating the World Trade Center attacks; researchers at the University of Washington and the University of Haifa, in Israel, are simulating terrorist bus bombings; University of Buffalo, N.Y., investigators are simulating motor vehicle accidents; and investigators at the University of Lusofona in Portugal are creating a virtual Angola.

SAN JUAN, P.R. — A selective serotonin reuptake inhibitor can enhance killer lymphocyte activity against HIV infection, according to preliminary study findings.

Depression may raise the risk of morbidity and mortality in patients with many medical conditions, including HIV infection. In addition, depression has been linked to immune function deficits, such as decreased natural killer cell activity, according to a presentation at the annual meeting of the American College of Psychiatrists.

In normal physiology, natural killer cells defend against viral infections and eliminate neoplastic cells. Natural killer cells are a focus of the ongoing HIV in Women: Depression and Immunity study, funded by the National Institute of Mental Health.

In this study of 40 women, a blood sample was obtained from each subject, and the researchers then treated the sample with citalopram and/or a substance P antagonist (an experimental agent); they then measured natural killer cell activity in vitro. They found that such treatment could reverse the detrimental effect of HIV on natural killer cell activity.

These preliminary data are “hot off the press,” Dr. Dwight L. Evans said. “Next we need to look at this in a real in vivo situation.”

“These findings … suggest that killer lymphocyte antiviral activity is enhanced by an SSRI and the substance P antagonist,” said Dr. Evans, the Ruth Meltzer Professor and chair of psychiatry at the University of Pennsylvania in Philadelphia.

“The reason we focused on natural killer cells—or killer lymphocytes as they are now known—is they kill or lyse HIV-1 infected cells and secrete chemokines and cytokines,” Dr. Evans said.

Cytotoxic T lymphocytes also lyse HIV-infected cells and secrete HIV-suppressive factors. Severe life stress decreases both these natural killer cells and cytotoxic T lymphocytes, he added.

In another study, Dr. Evans and his associates found that resolution of major depression was associated with increased natural killer cell activity in HIV-seropositive women (Am. J. Psychiatry 2005;162:2125–30).

The investigators assessed 57 women over 2 years and found that variations in natural killer cell levels corresponded to changes in depression status and ratings on the 17-item Hamilton Depression Rating Scale. Major depression in 11 participants resolved over time, with a simultaneous and significant increase in natural killer cell activity, which returned to normal levels.

“This study suggests that depression may impair certain aspects of innate cellular immunity relevant to delaying the progression of HIV disease and that these alterations are reversible with the resolution of a depressive episode,” the authors wrote.

SAN JUAN, P.R. — A selective serotonin reuptake inhibitor can enhance killer lymphocyte activity against HIV infection, according to preliminary study findings.

Depression may raise the risk of morbidity and mortality in patients with many medical conditions, including HIV infection. In addition, depression has been linked to immune function deficits, such as decreased natural killer cell activity, according to a presentation at the annual meeting of the American College of Psychiatrists.

In normal physiology, natural killer cells defend against viral infections and eliminate neoplastic cells. Natural killer cells are a focus of the ongoing HIV in Women: Depression and Immunity study, funded by the National Institute of Mental Health.

In this study of 40 women, a blood sample was obtained from each subject, and the researchers then treated the sample with citalopram and/or a substance P antagonist (an experimental agent); they then measured natural killer cell activity in vitro. They found that such treatment could reverse the detrimental effect of HIV on natural killer cell activity.

These preliminary data are “hot off the press,” Dr. Dwight L. Evans said. “Next we need to look at this in a real in vivo situation.”

“These findings … suggest that killer lymphocyte antiviral activity is enhanced by an SSRI and the substance P antagonist,” said Dr. Evans, the Ruth Meltzer Professor and chair of psychiatry at the University of Pennsylvania in Philadelphia.

“The reason we focused on natural killer cells—or killer lymphocytes as they are now known—is they kill or lyse HIV-1 infected cells and secrete chemokines and cytokines,” Dr. Evans said.

Cytotoxic T lymphocytes also lyse HIV-infected cells and secrete HIV-suppressive factors. Severe life stress decreases both these natural killer cells and cytotoxic T lymphocytes, he added.

In another study, Dr. Evans and his associates found that resolution of major depression was associated with increased natural killer cell activity in HIV-seropositive women (Am. J. Psychiatry 2005;162:2125–30).

The investigators assessed 57 women over 2 years and found that variations in natural killer cell levels corresponded to changes in depression status and ratings on the 17-item Hamilton Depression Rating Scale. Major depression in 11 participants resolved over time, with a simultaneous and significant increase in natural killer cell activity, which returned to normal levels.

“This study suggests that depression may impair certain aspects of innate cellular immunity relevant to delaying the progression of HIV disease and that these alterations are reversible with the resolution of a depressive episode,” the authors wrote.

SAN JUAN, P.R. — A selective serotonin reuptake inhibitor can enhance killer lymphocyte activity against HIV infection, according to preliminary study findings.

Depression may raise the risk of morbidity and mortality in patients with many medical conditions, including HIV infection. In addition, depression has been linked to immune function deficits, such as decreased natural killer cell activity, according to a presentation at the annual meeting of the American College of Psychiatrists.

In normal physiology, natural killer cells defend against viral infections and eliminate neoplastic cells. Natural killer cells are a focus of the ongoing HIV in Women: Depression and Immunity study, funded by the National Institute of Mental Health.

In this study of 40 women, a blood sample was obtained from each subject, and the researchers then treated the sample with citalopram and/or a substance P antagonist (an experimental agent); they then measured natural killer cell activity in vitro. They found that such treatment could reverse the detrimental effect of HIV on natural killer cell activity.

These preliminary data are “hot off the press,” Dr. Dwight L. Evans said. “Next we need to look at this in a real in vivo situation.”

“These findings … suggest that killer lymphocyte antiviral activity is enhanced by an SSRI and the substance P antagonist,” said Dr. Evans, the Ruth Meltzer Professor and chair of psychiatry at the University of Pennsylvania in Philadelphia.

“The reason we focused on natural killer cells—or killer lymphocytes as they are now known—is they kill or lyse HIV-1 infected cells and secrete chemokines and cytokines,” Dr. Evans said.

Cytotoxic T lymphocytes also lyse HIV-infected cells and secrete HIV-suppressive factors. Severe life stress decreases both these natural killer cells and cytotoxic T lymphocytes, he added.

In another study, Dr. Evans and his associates found that resolution of major depression was associated with increased natural killer cell activity in HIV-seropositive women (Am. J. Psychiatry 2005;162:2125–30).

The investigators assessed 57 women over 2 years and found that variations in natural killer cell levels corresponded to changes in depression status and ratings on the 17-item Hamilton Depression Rating Scale. Major depression in 11 participants resolved over time, with a simultaneous and significant increase in natural killer cell activity, which returned to normal levels.

“This study suggests that depression may impair certain aspects of innate cellular immunity relevant to delaying the progression of HIV disease and that these alterations are reversible with the resolution of a depressive episode,” the authors wrote.

MIAMI BEACH – Sodium oxybate significantly lessened daytime sleepiness and decreased frequency of sleep attacks in people with narcolepsy concurrently taking stimulants, compared with placebo, according to study findings presented at the annual meeting of the American Academy of Neurology.

Previous studies have shown that nightly administration of sodium oxybate (Xyrem, Orphan Medical) effectively treated cataplexy in people with narcolepsy (Sleep 2003;26:31–5; Sleep 2002;25:42–9).

The Food and Drug Administration approved the agent for treatment of cataplexy, a sudden loss of muscle tone associated with narcolepsy, in July 2002. Researchers in the two studies observed that the drug also decreased excessive daytime sleepiness.

To confirm this effect, Dr. Michael J. Thorpy conducted an 8-week, double-blind, placebo-controlled trial of adult narcolepsy patients from 42 sleep clinics in the United States, Canada, and Europe. Participants, after being weaned from anticataplectic medications, were randomized to receive 4.5 g, 6 g, or 9 g of sodium oxybate or placebo nightly.

The drug was administered in two equally divided doses at bedtime and 2.5–4 hours later. Sodium oxybate was increased weekly in 1.5-g increments up to the final dose, with the total treatment lasting 28 days.

There were 228 patients in the intent-to-treat population, half randomized to treatment and half to placebo. A total of 206 completed the 8-week study. The majority (78%) remained on steady doses of preexisting stimulant medications.

“I don't think we know the mechanism of action. We understand GABA-B [gamma-aminobutyric acid B] mechanism regarding nighttime sleep. Sodium oxybate affects a number of neurotransmitter systems, and tends to depress dopamine at night,” Dr. Thorpy, director of the Sleep-Wake Disorders Center at the Montefiore Medical Center, New York, said in response to a question from the audience. Dr. Thorpy received support from Orphan Medical Inc., sponsor of the study.

Dr. Thorpy used the Maintenance of Wakefulness Test (MWT) as an objective measure of excessive daytime sleepiness, and the Epworth Sleepiness Scale (ESS) for a subjective assessment. Participants also kept diaries to record the incidence of sleep attacks. Changes in MWT scores at 8 weeks were significant, compared with baseline for patients receiving the final doses of either 4.5 g or 9 g. “Compared with placebo, patients treated with sodium oxybate showed a significant median increase in more than 10 minutes in MWT at the 9-g dose,” Dr. Thorpy said.

Baseline ESS scores were “around 19, suggesting a lot of sleepiness,” Dr. Thorpy said. The 6-g and 9-g treatment groups experienced statistically significant decreases in median ESS scores after 8 weeks, compared with baseline.

The weekly incidence of inadvertent naps was 14 to 18 overall at baseline. There were statistically significant reductions in these sleep attacks in the 6-g and 9-g groups, a mean of 6.5 fewer naps with treatment, compared with placebo.

MIAMI BEACH – Sodium oxybate significantly lessened daytime sleepiness and decreased frequency of sleep attacks in people with narcolepsy concurrently taking stimulants, compared with placebo, according to study findings presented at the annual meeting of the American Academy of Neurology.

Previous studies have shown that nightly administration of sodium oxybate (Xyrem, Orphan Medical) effectively treated cataplexy in people with narcolepsy (Sleep 2003;26:31–5; Sleep 2002;25:42–9).

The Food and Drug Administration approved the agent for treatment of cataplexy, a sudden loss of muscle tone associated with narcolepsy, in July 2002. Researchers in the two studies observed that the drug also decreased excessive daytime sleepiness.

To confirm this effect, Dr. Michael J. Thorpy conducted an 8-week, double-blind, placebo-controlled trial of adult narcolepsy patients from 42 sleep clinics in the United States, Canada, and Europe. Participants, after being weaned from anticataplectic medications, were randomized to receive 4.5 g, 6 g, or 9 g of sodium oxybate or placebo nightly.

The drug was administered in two equally divided doses at bedtime and 2.5–4 hours later. Sodium oxybate was increased weekly in 1.5-g increments up to the final dose, with the total treatment lasting 28 days.

There were 228 patients in the intent-to-treat population, half randomized to treatment and half to placebo. A total of 206 completed the 8-week study. The majority (78%) remained on steady doses of preexisting stimulant medications.

“I don't think we know the mechanism of action. We understand GABA-B [gamma-aminobutyric acid B] mechanism regarding nighttime sleep. Sodium oxybate affects a number of neurotransmitter systems, and tends to depress dopamine at night,” Dr. Thorpy, director of the Sleep-Wake Disorders Center at the Montefiore Medical Center, New York, said in response to a question from the audience. Dr. Thorpy received support from Orphan Medical Inc., sponsor of the study.

Dr. Thorpy used the Maintenance of Wakefulness Test (MWT) as an objective measure of excessive daytime sleepiness, and the Epworth Sleepiness Scale (ESS) for a subjective assessment. Participants also kept diaries to record the incidence of sleep attacks. Changes in MWT scores at 8 weeks were significant, compared with baseline for patients receiving the final doses of either 4.5 g or 9 g. “Compared with placebo, patients treated with sodium oxybate showed a significant median increase in more than 10 minutes in MWT at the 9-g dose,” Dr. Thorpy said.

Baseline ESS scores were “around 19, suggesting a lot of sleepiness,” Dr. Thorpy said. The 6-g and 9-g treatment groups experienced statistically significant decreases in median ESS scores after 8 weeks, compared with baseline.

The weekly incidence of inadvertent naps was 14 to 18 overall at baseline. There were statistically significant reductions in these sleep attacks in the 6-g and 9-g groups, a mean of 6.5 fewer naps with treatment, compared with placebo.

MIAMI BEACH – Sodium oxybate significantly lessened daytime sleepiness and decreased frequency of sleep attacks in people with narcolepsy concurrently taking stimulants, compared with placebo, according to study findings presented at the annual meeting of the American Academy of Neurology.

Previous studies have shown that nightly administration of sodium oxybate (Xyrem, Orphan Medical) effectively treated cataplexy in people with narcolepsy (Sleep 2003;26:31–5; Sleep 2002;25:42–9).

The Food and Drug Administration approved the agent for treatment of cataplexy, a sudden loss of muscle tone associated with narcolepsy, in July 2002. Researchers in the two studies observed that the drug also decreased excessive daytime sleepiness.

To confirm this effect, Dr. Michael J. Thorpy conducted an 8-week, double-blind, placebo-controlled trial of adult narcolepsy patients from 42 sleep clinics in the United States, Canada, and Europe. Participants, after being weaned from anticataplectic medications, were randomized to receive 4.5 g, 6 g, or 9 g of sodium oxybate or placebo nightly.

The drug was administered in two equally divided doses at bedtime and 2.5–4 hours later. Sodium oxybate was increased weekly in 1.5-g increments up to the final dose, with the total treatment lasting 28 days.

There were 228 patients in the intent-to-treat population, half randomized to treatment and half to placebo. A total of 206 completed the 8-week study. The majority (78%) remained on steady doses of preexisting stimulant medications.

“I don't think we know the mechanism of action. We understand GABA-B [gamma-aminobutyric acid B] mechanism regarding nighttime sleep. Sodium oxybate affects a number of neurotransmitter systems, and tends to depress dopamine at night,” Dr. Thorpy, director of the Sleep-Wake Disorders Center at the Montefiore Medical Center, New York, said in response to a question from the audience. Dr. Thorpy received support from Orphan Medical Inc., sponsor of the study.

Dr. Thorpy used the Maintenance of Wakefulness Test (MWT) as an objective measure of excessive daytime sleepiness, and the Epworth Sleepiness Scale (ESS) for a subjective assessment. Participants also kept diaries to record the incidence of sleep attacks. Changes in MWT scores at 8 weeks were significant, compared with baseline for patients receiving the final doses of either 4.5 g or 9 g. “Compared with placebo, patients treated with sodium oxybate showed a significant median increase in more than 10 minutes in MWT at the 9-g dose,” Dr. Thorpy said.

Baseline ESS scores were “around 19, suggesting a lot of sleepiness,” Dr. Thorpy said. The 6-g and 9-g treatment groups experienced statistically significant decreases in median ESS scores after 8 weeks, compared with baseline.

The weekly incidence of inadvertent naps was 14 to 18 overall at baseline. There were statistically significant reductions in these sleep attacks in the 6-g and 9-g groups, a mean of 6.5 fewer naps with treatment, compared with placebo.