Somatic Disorders

MINNEAPOLIS – Adults with Arnold-Chiari type I malformations are at greater risk for sleep-disordered breathing, compared with healthy controls, based on data presented at the annual meeting of the Associated Professional Sleep Societies.

In light of this finding, “We should be screening all Arnold-Chiari I patients for sleep-disordered breathing,” said Dr. Nate Watson, a neurologist at the University of Washington, Seattle.

The displaced brain structures that characterize Arnold-Chiari I (AC-1), a benign developmental brain anomaly, can compress the brainstem, impeding breathing, he said.

To better assess the risk of sleep-disordered breathing in AC-1 patients, Dr. Watson and his colleagues compared 18 women with AC-1 (mean age 36 years) with 35 age- and sex-matched controls.

The researchers used several subjective questionnaires including the Epworth Sleepiness Scale to assess sleep-disordered breathing and sleepiness. Based on these results, the AC-1 patients were at significantly greater risk for sleep-disordered breathing, compared with controls (69% vs. 20%). Specifically, the results from the questionnaires showed that three factors–snoring, sleepiness, and obesity/hypertension–were significantly more common among AC-1 patients vs. controls, and occurred in 44% vs. 6%, 78% vs. 46%, and 64% vs. 34%, respectively.

The AC-1 patients were significantly more likely to report other symptoms associated with sleep-disordered breathing, including nighttime choking or gasping and nighttime shortness of breath, compared with controls. And when they woke up, the AC-1 patients also reported sore throats, heartburn, and headaches significantly more often than did the control patients.

In addition, the AC-1 patients reported sleeping significantly fewer hours (6.3 hours versus 7.6 hours) and taking significantly longer to fall asleep (61.4 minutes versus 18.6 minutes), compared with controls.

Consider decompressive surgery for patients if respiration is their main complaint, but remember that they need to be followed, said Dr. Watson during the discussion after his presentation. Previous studies indicate that decompression surgery makes a difference. Data from 16 consecutive patients with AC-1 malformations showed a significant improvement in the central apnea index from 14.9 to 1.3 based on full-night polysomnography conducted approximately 200 days after decompression surgery (Neurology 2006;66:136-8).

Future studies of AC-1 patients need to continue to focus on objective measures and comparison of patients before and after they have decompressive surgery, Dr. Watson said.

MINNEAPOLIS – Adults with Arnold-Chiari type I malformations are at greater risk for sleep-disordered breathing, compared with healthy controls, based on data presented at the annual meeting of the Associated Professional Sleep Societies.

In light of this finding, “We should be screening all Arnold-Chiari I patients for sleep-disordered breathing,” said Dr. Nate Watson, a neurologist at the University of Washington, Seattle.

The displaced brain structures that characterize Arnold-Chiari I (AC-1), a benign developmental brain anomaly, can compress the brainstem, impeding breathing, he said.

To better assess the risk of sleep-disordered breathing in AC-1 patients, Dr. Watson and his colleagues compared 18 women with AC-1 (mean age 36 years) with 35 age- and sex-matched controls.

The researchers used several subjective questionnaires including the Epworth Sleepiness Scale to assess sleep-disordered breathing and sleepiness. Based on these results, the AC-1 patients were at significantly greater risk for sleep-disordered breathing, compared with controls (69% vs. 20%). Specifically, the results from the questionnaires showed that three factors–snoring, sleepiness, and obesity/hypertension–were significantly more common among AC-1 patients vs. controls, and occurred in 44% vs. 6%, 78% vs. 46%, and 64% vs. 34%, respectively.

The AC-1 patients were significantly more likely to report other symptoms associated with sleep-disordered breathing, including nighttime choking or gasping and nighttime shortness of breath, compared with controls. And when they woke up, the AC-1 patients also reported sore throats, heartburn, and headaches significantly more often than did the control patients.

In addition, the AC-1 patients reported sleeping significantly fewer hours (6.3 hours versus 7.6 hours) and taking significantly longer to fall asleep (61.4 minutes versus 18.6 minutes), compared with controls.

Consider decompressive surgery for patients if respiration is their main complaint, but remember that they need to be followed, said Dr. Watson during the discussion after his presentation. Previous studies indicate that decompression surgery makes a difference. Data from 16 consecutive patients with AC-1 malformations showed a significant improvement in the central apnea index from 14.9 to 1.3 based on full-night polysomnography conducted approximately 200 days after decompression surgery (Neurology 2006;66:136-8).

Future studies of AC-1 patients need to continue to focus on objective measures and comparison of patients before and after they have decompressive surgery, Dr. Watson said.

MINNEAPOLIS – Adults with Arnold-Chiari type I malformations are at greater risk for sleep-disordered breathing, compared with healthy controls, based on data presented at the annual meeting of the Associated Professional Sleep Societies.

In light of this finding, “We should be screening all Arnold-Chiari I patients for sleep-disordered breathing,” said Dr. Nate Watson, a neurologist at the University of Washington, Seattle.

The displaced brain structures that characterize Arnold-Chiari I (AC-1), a benign developmental brain anomaly, can compress the brainstem, impeding breathing, he said.

To better assess the risk of sleep-disordered breathing in AC-1 patients, Dr. Watson and his colleagues compared 18 women with AC-1 (mean age 36 years) with 35 age- and sex-matched controls.

The researchers used several subjective questionnaires including the Epworth Sleepiness Scale to assess sleep-disordered breathing and sleepiness. Based on these results, the AC-1 patients were at significantly greater risk for sleep-disordered breathing, compared with controls (69% vs. 20%). Specifically, the results from the questionnaires showed that three factors–snoring, sleepiness, and obesity/hypertension–were significantly more common among AC-1 patients vs. controls, and occurred in 44% vs. 6%, 78% vs. 46%, and 64% vs. 34%, respectively.

The AC-1 patients were significantly more likely to report other symptoms associated with sleep-disordered breathing, including nighttime choking or gasping and nighttime shortness of breath, compared with controls. And when they woke up, the AC-1 patients also reported sore throats, heartburn, and headaches significantly more often than did the control patients.

In addition, the AC-1 patients reported sleeping significantly fewer hours (6.3 hours versus 7.6 hours) and taking significantly longer to fall asleep (61.4 minutes versus 18.6 minutes), compared with controls.

Consider decompressive surgery for patients if respiration is their main complaint, but remember that they need to be followed, said Dr. Watson during the discussion after his presentation. Previous studies indicate that decompression surgery makes a difference. Data from 16 consecutive patients with AC-1 malformations showed a significant improvement in the central apnea index from 14.9 to 1.3 based on full-night polysomnography conducted approximately 200 days after decompression surgery (Neurology 2006;66:136-8).

Future studies of AC-1 patients need to continue to focus on objective measures and comparison of patients before and after they have decompressive surgery, Dr. Watson said.

WASHINGTON – Not only does duloxetine appear to reduce the severity of pain, especially during the night, but it may also help patients with diabetic peripheral neuropathy get a better night's sleep, according to a poster presentation at the annual meeting of the American Pain Society.

After 12 weeks of treatment, patients on 60 mg of duloxetine once or twice daily had improvements in average daily pain severity, night pain severity, and pain-related sleep interference, wrote Dr. David A. Fishbain, professor of psychiatry and behavioral sciences at the University of Miami, and his colleagues at Eli Lilly, maker of duloxetine (Cymbalta).

Although causality cannot be demonstrated between duloxetine and better sleep, the findings suggest that improvements in pain will be associated with less interference in sleep, the authors wrote.

The researchers pooled data from three double-blind, placebo-controlled trials of duloxetine in patients with diabetic peripheral neuropathic pain (DPNP). In the first study, 457 patients were randomized to receive 20 mg of duloxetine once daily, 60 mg of duloxetine once or twice daily, or placebo. In studies two and three, 334 and 348 patients, respectively, were randomized to receive 60 mg of duloxetine once daily, 60 mg of duloxetine twice daily, or placebo. Although the primary efficacy measure for the studies was the reduction in the weekly mean of the 24-hour average pain score, secondary end points included average daily night pain severity (measured on an 11-point Likert scale) and the Brief Pain Inventory sleep interference item.

Patients were included in the trials if they were 18 years or older with pain because of bilateral peripheral neuropathy caused by type 1 or type 2 diabetes mellitus. Pain had to have begun in the feet with relatively symmetric onset. Diagnosis was confirmed by a score of at least three on the Michigan Neuropathy Screening Instrument. Daily pain had to be present for at least 6 months. Patients also had to have at least a 4 on the 24-hour average pain severity (11-point Likert) scale and stable glycemic control. Notably, patients with a current or recent (within the last year) diagnosis of major depressive disorder as defined by the DSM-IV were excluded from the studies.

The researchers identified a subset of nonsomnolent patients by excluding those who reported treatment-emergent somnolence or who were on concomitant sedating medications. Treatment-emergent somnolence included reports of daytime sleepiness, drowsiness, being drowsy upon awakening, excessive daytime sleepiness, a feeling of residual sleepiness, groggy, groggy and sluggish, groggy on awakening, hard to awaken, less alert on rising, sleepiness, sleepy, and somnolence.

In all three studies, 339 patients received placebo. Of these, 307 met the criteria for the nonsomnolent subset. A total of 685 patients received 60 mg or 120 mg per day of duloxetine in all three studies. Of these, 607 met the criteria for the nonsomnolent subset. Patients in the nonsomnolent/nonsedating subgroup who were on duloxetine showed improvements in daily average pain and night pain severity, compared with those on placebo. The improvements started as early as 1 week and were maintained for 12 weeks. At 12 weeks, subset patients on 60 mg of duloxetine once and twice daily had improvements in daily average pain severity of 47% and 50%, compared with 29% for those on placebo.

Also at 12 weeks, subset patients on 60 mg of duloxetine once and twice daily had improvements in night pain severity of 47% and 51%, respectively, compared with 34% for those on placebo.

WASHINGTON – Not only does duloxetine appear to reduce the severity of pain, especially during the night, but it may also help patients with diabetic peripheral neuropathy get a better night's sleep, according to a poster presentation at the annual meeting of the American Pain Society.

After 12 weeks of treatment, patients on 60 mg of duloxetine once or twice daily had improvements in average daily pain severity, night pain severity, and pain-related sleep interference, wrote Dr. David A. Fishbain, professor of psychiatry and behavioral sciences at the University of Miami, and his colleagues at Eli Lilly, maker of duloxetine (Cymbalta).

Although causality cannot be demonstrated between duloxetine and better sleep, the findings suggest that improvements in pain will be associated with less interference in sleep, the authors wrote.

The researchers pooled data from three double-blind, placebo-controlled trials of duloxetine in patients with diabetic peripheral neuropathic pain (DPNP). In the first study, 457 patients were randomized to receive 20 mg of duloxetine once daily, 60 mg of duloxetine once or twice daily, or placebo. In studies two and three, 334 and 348 patients, respectively, were randomized to receive 60 mg of duloxetine once daily, 60 mg of duloxetine twice daily, or placebo. Although the primary efficacy measure for the studies was the reduction in the weekly mean of the 24-hour average pain score, secondary end points included average daily night pain severity (measured on an 11-point Likert scale) and the Brief Pain Inventory sleep interference item.

Patients were included in the trials if they were 18 years or older with pain because of bilateral peripheral neuropathy caused by type 1 or type 2 diabetes mellitus. Pain had to have begun in the feet with relatively symmetric onset. Diagnosis was confirmed by a score of at least three on the Michigan Neuropathy Screening Instrument. Daily pain had to be present for at least 6 months. Patients also had to have at least a 4 on the 24-hour average pain severity (11-point Likert) scale and stable glycemic control. Notably, patients with a current or recent (within the last year) diagnosis of major depressive disorder as defined by the DSM-IV were excluded from the studies.

The researchers identified a subset of nonsomnolent patients by excluding those who reported treatment-emergent somnolence or who were on concomitant sedating medications. Treatment-emergent somnolence included reports of daytime sleepiness, drowsiness, being drowsy upon awakening, excessive daytime sleepiness, a feeling of residual sleepiness, groggy, groggy and sluggish, groggy on awakening, hard to awaken, less alert on rising, sleepiness, sleepy, and somnolence.

In all three studies, 339 patients received placebo. Of these, 307 met the criteria for the nonsomnolent subset. A total of 685 patients received 60 mg or 120 mg per day of duloxetine in all three studies. Of these, 607 met the criteria for the nonsomnolent subset. Patients in the nonsomnolent/nonsedating subgroup who were on duloxetine showed improvements in daily average pain and night pain severity, compared with those on placebo. The improvements started as early as 1 week and were maintained for 12 weeks. At 12 weeks, subset patients on 60 mg of duloxetine once and twice daily had improvements in daily average pain severity of 47% and 50%, compared with 29% for those on placebo.

Also at 12 weeks, subset patients on 60 mg of duloxetine once and twice daily had improvements in night pain severity of 47% and 51%, respectively, compared with 34% for those on placebo.

WASHINGTON – Not only does duloxetine appear to reduce the severity of pain, especially during the night, but it may also help patients with diabetic peripheral neuropathy get a better night's sleep, according to a poster presentation at the annual meeting of the American Pain Society.

After 12 weeks of treatment, patients on 60 mg of duloxetine once or twice daily had improvements in average daily pain severity, night pain severity, and pain-related sleep interference, wrote Dr. David A. Fishbain, professor of psychiatry and behavioral sciences at the University of Miami, and his colleagues at Eli Lilly, maker of duloxetine (Cymbalta).

Although causality cannot be demonstrated between duloxetine and better sleep, the findings suggest that improvements in pain will be associated with less interference in sleep, the authors wrote.

The researchers pooled data from three double-blind, placebo-controlled trials of duloxetine in patients with diabetic peripheral neuropathic pain (DPNP). In the first study, 457 patients were randomized to receive 20 mg of duloxetine once daily, 60 mg of duloxetine once or twice daily, or placebo. In studies two and three, 334 and 348 patients, respectively, were randomized to receive 60 mg of duloxetine once daily, 60 mg of duloxetine twice daily, or placebo. Although the primary efficacy measure for the studies was the reduction in the weekly mean of the 24-hour average pain score, secondary end points included average daily night pain severity (measured on an 11-point Likert scale) and the Brief Pain Inventory sleep interference item.

Patients were included in the trials if they were 18 years or older with pain because of bilateral peripheral neuropathy caused by type 1 or type 2 diabetes mellitus. Pain had to have begun in the feet with relatively symmetric onset. Diagnosis was confirmed by a score of at least three on the Michigan Neuropathy Screening Instrument. Daily pain had to be present for at least 6 months. Patients also had to have at least a 4 on the 24-hour average pain severity (11-point Likert) scale and stable glycemic control. Notably, patients with a current or recent (within the last year) diagnosis of major depressive disorder as defined by the DSM-IV were excluded from the studies.

The researchers identified a subset of nonsomnolent patients by excluding those who reported treatment-emergent somnolence or who were on concomitant sedating medications. Treatment-emergent somnolence included reports of daytime sleepiness, drowsiness, being drowsy upon awakening, excessive daytime sleepiness, a feeling of residual sleepiness, groggy, groggy and sluggish, groggy on awakening, hard to awaken, less alert on rising, sleepiness, sleepy, and somnolence.

In all three studies, 339 patients received placebo. Of these, 307 met the criteria for the nonsomnolent subset. A total of 685 patients received 60 mg or 120 mg per day of duloxetine in all three studies. Of these, 607 met the criteria for the nonsomnolent subset. Patients in the nonsomnolent/nonsedating subgroup who were on duloxetine showed improvements in daily average pain and night pain severity, compared with those on placebo. The improvements started as early as 1 week and were maintained for 12 weeks. At 12 weeks, subset patients on 60 mg of duloxetine once and twice daily had improvements in daily average pain severity of 47% and 50%, compared with 29% for those on placebo.

Also at 12 weeks, subset patients on 60 mg of duloxetine once and twice daily had improvements in night pain severity of 47% and 51%, respectively, compared with 34% for those on placebo.

WASHINGTON – Psychiatric comorbidities and a history of abuse are often associated with functional gastrointestinal problems, said Dr. Kevin W. Olden at the annual meeting of the American Academy of Clinical Psychiatrists.

“There is no doubt that psychiatry has a lot to offer patients with irritable bowel syndrome and the entire spectrum of gastrointestinal disorders,” said Dr. Olden, director of the division of gastroenterology and hepatology, University of Arkansas, Little Rock.

Four psychiatric diagnoses that are often present in patients with functional gastrointestinal disorders are panic disorder, generalized anxiety disorder, mood disorders (mainly depression), and somatoform disorders. As many as 44% of patients with IBS meet the diagnostic criteria for panic disorder, Dr. Olden noted (Gastroenterol. Clin. N. Am. 2003;32:477-506). In addition, Dr. Olden cited a study in which major depression was identified in 30%-90% of patients with irritable bowel syndrome. The presence of depression can influence patients' ability to seek care for IBS and their ability to cope with it, he said.

The impact of abuse on subsequent psychological problems and comorbid functional gastrointestinal disorders is an area worthy of further research, Dr. Olden said. In a survey of 206 patients who presented to a GI clinic, more than half of the patients with functional GI problems reported a history of abuse, and significantly more of these patients reported abuse, compared with those who had organic GI problems (53% vs. 37%) (Ann. Intern. Med. 1990;113:828-33).

When treatment with antidepressants relieves the gastrointestinal symptoms in some patients, they report fewer physician visits and improved ability to perform daily activities, Dr. Olden said.

WASHINGTON – Psychiatric comorbidities and a history of abuse are often associated with functional gastrointestinal problems, said Dr. Kevin W. Olden at the annual meeting of the American Academy of Clinical Psychiatrists.

“There is no doubt that psychiatry has a lot to offer patients with irritable bowel syndrome and the entire spectrum of gastrointestinal disorders,” said Dr. Olden, director of the division of gastroenterology and hepatology, University of Arkansas, Little Rock.

Four psychiatric diagnoses that are often present in patients with functional gastrointestinal disorders are panic disorder, generalized anxiety disorder, mood disorders (mainly depression), and somatoform disorders. As many as 44% of patients with IBS meet the diagnostic criteria for panic disorder, Dr. Olden noted (Gastroenterol. Clin. N. Am. 2003;32:477-506). In addition, Dr. Olden cited a study in which major depression was identified in 30%-90% of patients with irritable bowel syndrome. The presence of depression can influence patients' ability to seek care for IBS and their ability to cope with it, he said.

The impact of abuse on subsequent psychological problems and comorbid functional gastrointestinal disorders is an area worthy of further research, Dr. Olden said. In a survey of 206 patients who presented to a GI clinic, more than half of the patients with functional GI problems reported a history of abuse, and significantly more of these patients reported abuse, compared with those who had organic GI problems (53% vs. 37%) (Ann. Intern. Med. 1990;113:828-33).

When treatment with antidepressants relieves the gastrointestinal symptoms in some patients, they report fewer physician visits and improved ability to perform daily activities, Dr. Olden said.

WASHINGTON – Psychiatric comorbidities and a history of abuse are often associated with functional gastrointestinal problems, said Dr. Kevin W. Olden at the annual meeting of the American Academy of Clinical Psychiatrists.

“There is no doubt that psychiatry has a lot to offer patients with irritable bowel syndrome and the entire spectrum of gastrointestinal disorders,” said Dr. Olden, director of the division of gastroenterology and hepatology, University of Arkansas, Little Rock.

Four psychiatric diagnoses that are often present in patients with functional gastrointestinal disorders are panic disorder, generalized anxiety disorder, mood disorders (mainly depression), and somatoform disorders. As many as 44% of patients with IBS meet the diagnostic criteria for panic disorder, Dr. Olden noted (Gastroenterol. Clin. N. Am. 2003;32:477-506). In addition, Dr. Olden cited a study in which major depression was identified in 30%-90% of patients with irritable bowel syndrome. The presence of depression can influence patients' ability to seek care for IBS and their ability to cope with it, he said.

The impact of abuse on subsequent psychological problems and comorbid functional gastrointestinal disorders is an area worthy of further research, Dr. Olden said. In a survey of 206 patients who presented to a GI clinic, more than half of the patients with functional GI problems reported a history of abuse, and significantly more of these patients reported abuse, compared with those who had organic GI problems (53% vs. 37%) (Ann. Intern. Med. 1990;113:828-33).

When treatment with antidepressants relieves the gastrointestinal symptoms in some patients, they report fewer physician visits and improved ability to perform daily activities, Dr. Olden said.

Depression severely impairs the recovery of heart rate variability after acute coronary syndrome, reported Dr. Alexander H. Glassman of Columbia University, New York, and his associates.

In addition, heart rate variability (HRV) continues to decline in patients whose depression does not respond to sertraline (Zoloft), while it ceases to decline in those who do respond to sertraline. It is not yet known whether this cardiac benefit is attributable to a pharmacologic effect of the antidepressant, to improvement of the depressive illness, or to a combination of both, the researchers said.

“What is clear is that depression is associated with biological changes involving increased heart rate, inflammatory response, plasma norepinephrine, platelet reactivity, decreased heart rate variability, and now, absent post-ACS-HRV recovery, all of which [are] associated with life-threatening consequences,” said Dr. Glassman and his associates.

“From a clinician's point of view, patients with depression after myocardial infarction … should be both carefully watched and aggressively treated, because they are at an elevated cardiac risk and less likely to get better spontaneously,” they noted (Arch. Gen. Psychiatry 2007;64:1025–31).

The researchers used data from 258 subjects who participated in the SADHART study to examine the effects of depression and of antidepressant therapy on heart rate variability. SADHART (Sertraline Antidepressant Heart Attack Randomized Trial), which took place in 1997–2001, compared sertraline with placebo in patients with major depressive disorder who were hospitalized after ACS.

In the general population, HRV falls abruptly during acute coronary episodes and recovers gradually but incompletely in the following weeks. However, Dr. Glassman and his associates found that HRV failed to recover in ACS patients with major depression.

The decline in HRV leveled off or improved slightly in those who responded to sertraline and in those whose mood improved spontaneously, but continued to decline in patients who received placebo or who failed to respond to sertraline, the investigators said.

Even patients who responded to sertraline showed only one-third as much HRV recovery as is reported in the literature among ACS patients who do not have depression. Thus, even successful selective serotonin reuptake inhibitor therapy “may not fully eliminate the autonomic risk associated with major depressive disorder,” the investigators added.

Dr. Glassman served as a member of the steering committee for SADHART. He also has been a consultant for and has received honoraria from Pfizer Inc., which markets sertraline and provided partial support for the study.

Depression severely impairs the recovery of heart rate variability after acute coronary syndrome, reported Dr. Alexander H. Glassman of Columbia University, New York, and his associates.

In addition, heart rate variability (HRV) continues to decline in patients whose depression does not respond to sertraline (Zoloft), while it ceases to decline in those who do respond to sertraline. It is not yet known whether this cardiac benefit is attributable to a pharmacologic effect of the antidepressant, to improvement of the depressive illness, or to a combination of both, the researchers said.

“What is clear is that depression is associated with biological changes involving increased heart rate, inflammatory response, plasma norepinephrine, platelet reactivity, decreased heart rate variability, and now, absent post-ACS-HRV recovery, all of which [are] associated with life-threatening consequences,” said Dr. Glassman and his associates.

“From a clinician's point of view, patients with depression after myocardial infarction … should be both carefully watched and aggressively treated, because they are at an elevated cardiac risk and less likely to get better spontaneously,” they noted (Arch. Gen. Psychiatry 2007;64:1025–31).

The researchers used data from 258 subjects who participated in the SADHART study to examine the effects of depression and of antidepressant therapy on heart rate variability. SADHART (Sertraline Antidepressant Heart Attack Randomized Trial), which took place in 1997–2001, compared sertraline with placebo in patients with major depressive disorder who were hospitalized after ACS.

In the general population, HRV falls abruptly during acute coronary episodes and recovers gradually but incompletely in the following weeks. However, Dr. Glassman and his associates found that HRV failed to recover in ACS patients with major depression.

The decline in HRV leveled off or improved slightly in those who responded to sertraline and in those whose mood improved spontaneously, but continued to decline in patients who received placebo or who failed to respond to sertraline, the investigators said.

Even patients who responded to sertraline showed only one-third as much HRV recovery as is reported in the literature among ACS patients who do not have depression. Thus, even successful selective serotonin reuptake inhibitor therapy “may not fully eliminate the autonomic risk associated with major depressive disorder,” the investigators added.

Dr. Glassman served as a member of the steering committee for SADHART. He also has been a consultant for and has received honoraria from Pfizer Inc., which markets sertraline and provided partial support for the study.

Depression severely impairs the recovery of heart rate variability after acute coronary syndrome, reported Dr. Alexander H. Glassman of Columbia University, New York, and his associates.

In addition, heart rate variability (HRV) continues to decline in patients whose depression does not respond to sertraline (Zoloft), while it ceases to decline in those who do respond to sertraline. It is not yet known whether this cardiac benefit is attributable to a pharmacologic effect of the antidepressant, to improvement of the depressive illness, or to a combination of both, the researchers said.

“What is clear is that depression is associated with biological changes involving increased heart rate, inflammatory response, plasma norepinephrine, platelet reactivity, decreased heart rate variability, and now, absent post-ACS-HRV recovery, all of which [are] associated with life-threatening consequences,” said Dr. Glassman and his associates.

“From a clinician's point of view, patients with depression after myocardial infarction … should be both carefully watched and aggressively treated, because they are at an elevated cardiac risk and less likely to get better spontaneously,” they noted (Arch. Gen. Psychiatry 2007;64:1025–31).

The researchers used data from 258 subjects who participated in the SADHART study to examine the effects of depression and of antidepressant therapy on heart rate variability. SADHART (Sertraline Antidepressant Heart Attack Randomized Trial), which took place in 1997–2001, compared sertraline with placebo in patients with major depressive disorder who were hospitalized after ACS.

In the general population, HRV falls abruptly during acute coronary episodes and recovers gradually but incompletely in the following weeks. However, Dr. Glassman and his associates found that HRV failed to recover in ACS patients with major depression.

The decline in HRV leveled off or improved slightly in those who responded to sertraline and in those whose mood improved spontaneously, but continued to decline in patients who received placebo or who failed to respond to sertraline, the investigators said.

Even patients who responded to sertraline showed only one-third as much HRV recovery as is reported in the literature among ACS patients who do not have depression. Thus, even successful selective serotonin reuptake inhibitor therapy “may not fully eliminate the autonomic risk associated with major depressive disorder,” the investigators added.

Dr. Glassman served as a member of the steering committee for SADHART. He also has been a consultant for and has received honoraria from Pfizer Inc., which markets sertraline and provided partial support for the study.

MINNEAPOLIS – Women with no history of sleep disorders often report sleep problems–especially difficulty falling asleep–as they undergo menopause. Their complaints were validated by a sleep study of more than 700 women presented at the annual meeting of the Associated Professional Sleep Societies.

“These data provide, for the first time, objective findings to support this common sleep complaint in postmenopausal women,” asserted Edward O. Bixler, Ph.D., who is vice chair of the sleep research division at Pennsylvania State University in Hershey.

To confirm the association between menopause and poor sleep and to seek a possible mechanism for this connection, Dr. Bixler and his colleagues conducted single-night polysomnographies on 715 women with a mean age of 49 years. Of these, 400 women were premenopausal, 120 were postmenopausal and using hormone therapy (HT), and 195 were postmenopausal but not using HT.

Women sleep as well as or better than men until they reach menopause, but sleep needs change with age, Dr. Bixler noted.

With this fact in mind, the researchers used a group of 609 men who were at least 45 years old (with an average age of 49 years) as controls for the study. The average body mass index for both genders was 26.9 kg/m

The results of the single-night sleep test showed that the postmenopausal women who were not on hormone therapy took an average of 15 minutes longer to fall asleep, compared with women who were on HT, and an average of 10 minutes longer to fall asleep compared with the men. These differences were statistically significant.

The average time it took for the male controls to fall asleep was not significantly different from that of premenopausal women (a difference of 1.6 minutes) or of postmenopausal women who were taking hormone therapy (a difference of 5.6 minutes).

“What was unexpected was that we didn't find an increase in daytime sleepiness,” Dr. Bixler noted. He proposed that the lack of daytime sleepiness might be a result of the reduced need for sleep that is a natural part of aging. “As you age, you are less likely to be sleepy during the day even though you are sleeping less at night,” he said.

When the researchers looked at slow wave sleep, which is associated with the brain's ability to recharge, think, and remember, they found no differences between premenopausal women and male controls.

Postmenopausal women who didn't use HT, however, were twice as likely to have slow wave sleep as were male controls, and postmenopausal women who used HT were four times as likely to have slow wave sleep as were male controls. Therefore, postmenopausal women who used HT were twice as likely to have slow wave sleep as were women who didn't use HT.

The data suggest that sleep latency is a valid symptom among menopausal women without a history of sleep disorders, especially among those who are not using HT. Based on these findings, menopausal women may be at increased risk for developing chronic insomnia that may require treatment, Dr. Bixler added.

“We would speculate that [menopausal changes] may be triggers for the onset of primary insomnia in vulnerable women,” he said.

MINNEAPOLIS – Women with no history of sleep disorders often report sleep problems–especially difficulty falling asleep–as they undergo menopause. Their complaints were validated by a sleep study of more than 700 women presented at the annual meeting of the Associated Professional Sleep Societies.

“These data provide, for the first time, objective findings to support this common sleep complaint in postmenopausal women,” asserted Edward O. Bixler, Ph.D., who is vice chair of the sleep research division at Pennsylvania State University in Hershey.

To confirm the association between menopause and poor sleep and to seek a possible mechanism for this connection, Dr. Bixler and his colleagues conducted single-night polysomnographies on 715 women with a mean age of 49 years. Of these, 400 women were premenopausal, 120 were postmenopausal and using hormone therapy (HT), and 195 were postmenopausal but not using HT.

Women sleep as well as or better than men until they reach menopause, but sleep needs change with age, Dr. Bixler noted.

With this fact in mind, the researchers used a group of 609 men who were at least 45 years old (with an average age of 49 years) as controls for the study. The average body mass index for both genders was 26.9 kg/m

The results of the single-night sleep test showed that the postmenopausal women who were not on hormone therapy took an average of 15 minutes longer to fall asleep, compared with women who were on HT, and an average of 10 minutes longer to fall asleep compared with the men. These differences were statistically significant.

The average time it took for the male controls to fall asleep was not significantly different from that of premenopausal women (a difference of 1.6 minutes) or of postmenopausal women who were taking hormone therapy (a difference of 5.6 minutes).

“What was unexpected was that we didn't find an increase in daytime sleepiness,” Dr. Bixler noted. He proposed that the lack of daytime sleepiness might be a result of the reduced need for sleep that is a natural part of aging. “As you age, you are less likely to be sleepy during the day even though you are sleeping less at night,” he said.

When the researchers looked at slow wave sleep, which is associated with the brain's ability to recharge, think, and remember, they found no differences between premenopausal women and male controls.

Postmenopausal women who didn't use HT, however, were twice as likely to have slow wave sleep as were male controls, and postmenopausal women who used HT were four times as likely to have slow wave sleep as were male controls. Therefore, postmenopausal women who used HT were twice as likely to have slow wave sleep as were women who didn't use HT.

The data suggest that sleep latency is a valid symptom among menopausal women without a history of sleep disorders, especially among those who are not using HT. Based on these findings, menopausal women may be at increased risk for developing chronic insomnia that may require treatment, Dr. Bixler added.

“We would speculate that [menopausal changes] may be triggers for the onset of primary insomnia in vulnerable women,” he said.

MINNEAPOLIS – Women with no history of sleep disorders often report sleep problems–especially difficulty falling asleep–as they undergo menopause. Their complaints were validated by a sleep study of more than 700 women presented at the annual meeting of the Associated Professional Sleep Societies.

“These data provide, for the first time, objective findings to support this common sleep complaint in postmenopausal women,” asserted Edward O. Bixler, Ph.D., who is vice chair of the sleep research division at Pennsylvania State University in Hershey.

To confirm the association between menopause and poor sleep and to seek a possible mechanism for this connection, Dr. Bixler and his colleagues conducted single-night polysomnographies on 715 women with a mean age of 49 years. Of these, 400 women were premenopausal, 120 were postmenopausal and using hormone therapy (HT), and 195 were postmenopausal but not using HT.

Women sleep as well as or better than men until they reach menopause, but sleep needs change with age, Dr. Bixler noted.

With this fact in mind, the researchers used a group of 609 men who were at least 45 years old (with an average age of 49 years) as controls for the study. The average body mass index for both genders was 26.9 kg/m

The results of the single-night sleep test showed that the postmenopausal women who were not on hormone therapy took an average of 15 minutes longer to fall asleep, compared with women who were on HT, and an average of 10 minutes longer to fall asleep compared with the men. These differences were statistically significant.

The average time it took for the male controls to fall asleep was not significantly different from that of premenopausal women (a difference of 1.6 minutes) or of postmenopausal women who were taking hormone therapy (a difference of 5.6 minutes).

“What was unexpected was that we didn't find an increase in daytime sleepiness,” Dr. Bixler noted. He proposed that the lack of daytime sleepiness might be a result of the reduced need for sleep that is a natural part of aging. “As you age, you are less likely to be sleepy during the day even though you are sleeping less at night,” he said.

When the researchers looked at slow wave sleep, which is associated with the brain's ability to recharge, think, and remember, they found no differences between premenopausal women and male controls.

Postmenopausal women who didn't use HT, however, were twice as likely to have slow wave sleep as were male controls, and postmenopausal women who used HT were four times as likely to have slow wave sleep as were male controls. Therefore, postmenopausal women who used HT were twice as likely to have slow wave sleep as were women who didn't use HT.

The data suggest that sleep latency is a valid symptom among menopausal women without a history of sleep disorders, especially among those who are not using HT. Based on these findings, menopausal women may be at increased risk for developing chronic insomnia that may require treatment, Dr. Bixler added.

“We would speculate that [menopausal changes] may be triggers for the onset of primary insomnia in vulnerable women,” he said.

CHICAGO – Women with migraine who have experienced emotional abuse, either recently or in the past, report higher levels of comorbid depression and headache-related disability, Dr. Gretchen E. Tietjen said at the annual meeting of the American Headache Society.

The finding stimulates even more provocative questions about the connections between body and mind, she said. “Changes in the brain due to past abuse have been well documented,” said Dr. Tietjen, professor and chair of the department of neurology at the University of Toledo, Ohio. “You can't separate mental and physical health in these women. What we would like to know is how these changes affect headache and depression, and the common neurobiology that links them.”

She administered a survey that examined a history of emotional, physical, and sexual abuse, as well as headache characteristics, disability, somatic symptoms, and depression, to 1,032 women who sought care at a headache clinic. She divided the description of emotional abuse into six categories: threatening, aggressive, harassing, intimidating, isolating, and coercive/controlling.

Of the study group, 593 (57%) reported episodic headache (96% with migraine). The remainder reported chronic headache (87% with migraine).

Many of the women (43%) reported that they had experienced some kind of emotional abuse, and 6% of the group reported having been exposed to all six types. More than a third of the patients (37%) also reported a history of sexual abuse, with 18% describing a childhood or adolescent experience.

Dr. Tietjen saw a dose-response relationship: The more types of abuse the woman had experienced, the more severe or frequent her headaches and the greater number of additional symptoms she reported. Among those who denied a history of physical or sexual abuse, emotional abuse was associated with higher depression scores, which increased with an increase in the number of types of emotional abuse experienced.

Women who reported remote physical or sexual abuse seemed particularly vulnerable to the effects of later emotional abuse, with greater depression levels, higher stress, more somatic symptoms, and greater headache-related disability. All of these scores exhibited a dose-response relationship to the number of abusive behaviors the women experienced.

Questions about past and current abuse–both physical and emotional–should be part of a headache work-up for every patient, Dr. Tietjen said. “First, if a person is in an unsafe environment, we want to try and get her out. But a history of this experience may also change the type of therapy we offer.”

These patients may respond well to cognitive-behavioral and physical therapy as adjunctive treatments, Dr. Tietjen said.

CHICAGO – Women with migraine who have experienced emotional abuse, either recently or in the past, report higher levels of comorbid depression and headache-related disability, Dr. Gretchen E. Tietjen said at the annual meeting of the American Headache Society.

The finding stimulates even more provocative questions about the connections between body and mind, she said. “Changes in the brain due to past abuse have been well documented,” said Dr. Tietjen, professor and chair of the department of neurology at the University of Toledo, Ohio. “You can't separate mental and physical health in these women. What we would like to know is how these changes affect headache and depression, and the common neurobiology that links them.”

She administered a survey that examined a history of emotional, physical, and sexual abuse, as well as headache characteristics, disability, somatic symptoms, and depression, to 1,032 women who sought care at a headache clinic. She divided the description of emotional abuse into six categories: threatening, aggressive, harassing, intimidating, isolating, and coercive/controlling.

Of the study group, 593 (57%) reported episodic headache (96% with migraine). The remainder reported chronic headache (87% with migraine).

Many of the women (43%) reported that they had experienced some kind of emotional abuse, and 6% of the group reported having been exposed to all six types. More than a third of the patients (37%) also reported a history of sexual abuse, with 18% describing a childhood or adolescent experience.

Dr. Tietjen saw a dose-response relationship: The more types of abuse the woman had experienced, the more severe or frequent her headaches and the greater number of additional symptoms she reported. Among those who denied a history of physical or sexual abuse, emotional abuse was associated with higher depression scores, which increased with an increase in the number of types of emotional abuse experienced.

Women who reported remote physical or sexual abuse seemed particularly vulnerable to the effects of later emotional abuse, with greater depression levels, higher stress, more somatic symptoms, and greater headache-related disability. All of these scores exhibited a dose-response relationship to the number of abusive behaviors the women experienced.

Questions about past and current abuse–both physical and emotional–should be part of a headache work-up for every patient, Dr. Tietjen said. “First, if a person is in an unsafe environment, we want to try and get her out. But a history of this experience may also change the type of therapy we offer.”

These patients may respond well to cognitive-behavioral and physical therapy as adjunctive treatments, Dr. Tietjen said.

CHICAGO – Women with migraine who have experienced emotional abuse, either recently or in the past, report higher levels of comorbid depression and headache-related disability, Dr. Gretchen E. Tietjen said at the annual meeting of the American Headache Society.

The finding stimulates even more provocative questions about the connections between body and mind, she said. “Changes in the brain due to past abuse have been well documented,” said Dr. Tietjen, professor and chair of the department of neurology at the University of Toledo, Ohio. “You can't separate mental and physical health in these women. What we would like to know is how these changes affect headache and depression, and the common neurobiology that links them.”

She administered a survey that examined a history of emotional, physical, and sexual abuse, as well as headache characteristics, disability, somatic symptoms, and depression, to 1,032 women who sought care at a headache clinic. She divided the description of emotional abuse into six categories: threatening, aggressive, harassing, intimidating, isolating, and coercive/controlling.

Of the study group, 593 (57%) reported episodic headache (96% with migraine). The remainder reported chronic headache (87% with migraine).

Many of the women (43%) reported that they had experienced some kind of emotional abuse, and 6% of the group reported having been exposed to all six types. More than a third of the patients (37%) also reported a history of sexual abuse, with 18% describing a childhood or adolescent experience.

Dr. Tietjen saw a dose-response relationship: The more types of abuse the woman had experienced, the more severe or frequent her headaches and the greater number of additional symptoms she reported. Among those who denied a history of physical or sexual abuse, emotional abuse was associated with higher depression scores, which increased with an increase in the number of types of emotional abuse experienced.

Women who reported remote physical or sexual abuse seemed particularly vulnerable to the effects of later emotional abuse, with greater depression levels, higher stress, more somatic symptoms, and greater headache-related disability. All of these scores exhibited a dose-response relationship to the number of abusive behaviors the women experienced.

Questions about past and current abuse–both physical and emotional–should be part of a headache work-up for every patient, Dr. Tietjen said. “First, if a person is in an unsafe environment, we want to try and get her out. But a history of this experience may also change the type of therapy we offer.”

These patients may respond well to cognitive-behavioral and physical therapy as adjunctive treatments, Dr. Tietjen said.

Older adults who report a high degree of depressive symptoms are more likely to develop type 2 diabetes than are those without depressive symptoms, according to Mercedes R. Carnethon, Ph.D., of Northwestern University, Chicago, and her associates in the Cardiovascular Health Study.

Several studies have found an association between depressive symptoms or clinical depression and diabetes, but this is the first to examine the issue in a population of people over age 65, who have a high prevalence of both disorders, Dr. Carnethon and her associates said (Arch. Intern. Med. 2007;167:802–7).

The researchers assessed data on 4,681 participants in the Cardiovascular Health Study, which took place from 1989 to 1999. Depressive symptoms had been evaluated annually using the 10-item Center for Epidemiological Studies Depression Scale.

A minimum score of 0 for each item would indicate that the subject experienced that depressive symptom never or rarely, and a maximum score of 3 for each item would indicate that the subject experienced that symptom most of the time or always. Total scores of 8 or more points, out of a possible maximum of 30 points, were considered high.

Twenty percent of the participants had high depressive symptom scores on at least one occasion. The proportion of subjects who were overweight or obese–a factor that could potentially confound the association with diabetes–was similar across those who had low, intermediate, or high depressive symptom scores.

New-onset diabetes was determined by the subjects' use of insulin or oral diabetes medications and by fasting glucose levels that were measured on two occasions during follow-up. A total of 234 subjects developed diabetes.

A high number of depressive symptoms on a single occasion, a significant increase in such symptoms over time, and persistently high symptoms over time all were associated with an excess incidence of diabetes, the investigators said.

The strongest link with diabetes was found when depressive symptom scores rose by at least 5 points over time.

“These findings were present across demographic strata and persisted with statistical adjustment for known correlates of depression and diabetes, such as BMI [body mass index], physical activity, cigarette smoking, alcohol intake, and C-reactive protein level,” Dr. Carnethon and her associates said.

In summary, high depressive symptoms might be connected to the development of diabetes in older adults, and this association might not be attributable solely to adverse health behaviors or weight gain. “The pathophysiologic mechanism for this association remains unclear,” they said.

Inflammation is often proposed as a likely mechanism, because inflammatory markers are associated with both diabetes and depression. However, the findings of this study showed no attenuation of the link between the two disorders when the data were adjusted for C-reactive protein levels.

This suggests that “other biological mechanisms previously proposed, such as hypothalamic-pituitary-adrenal axis dysregulation and sympathetic nervous system stimulation, may be more salient,” they added.

Older adults who report a high degree of depressive symptoms are more likely to develop type 2 diabetes than are those without depressive symptoms, according to Mercedes R. Carnethon, Ph.D., of Northwestern University, Chicago, and her associates in the Cardiovascular Health Study.

Several studies have found an association between depressive symptoms or clinical depression and diabetes, but this is the first to examine the issue in a population of people over age 65, who have a high prevalence of both disorders, Dr. Carnethon and her associates said (Arch. Intern. Med. 2007;167:802–7).

The researchers assessed data on 4,681 participants in the Cardiovascular Health Study, which took place from 1989 to 1999. Depressive symptoms had been evaluated annually using the 10-item Center for Epidemiological Studies Depression Scale.

A minimum score of 0 for each item would indicate that the subject experienced that depressive symptom never or rarely, and a maximum score of 3 for each item would indicate that the subject experienced that symptom most of the time or always. Total scores of 8 or more points, out of a possible maximum of 30 points, were considered high.

Twenty percent of the participants had high depressive symptom scores on at least one occasion. The proportion of subjects who were overweight or obese–a factor that could potentially confound the association with diabetes–was similar across those who had low, intermediate, or high depressive symptom scores.

New-onset diabetes was determined by the subjects' use of insulin or oral diabetes medications and by fasting glucose levels that were measured on two occasions during follow-up. A total of 234 subjects developed diabetes.

A high number of depressive symptoms on a single occasion, a significant increase in such symptoms over time, and persistently high symptoms over time all were associated with an excess incidence of diabetes, the investigators said.

The strongest link with diabetes was found when depressive symptom scores rose by at least 5 points over time.

“These findings were present across demographic strata and persisted with statistical adjustment for known correlates of depression and diabetes, such as BMI [body mass index], physical activity, cigarette smoking, alcohol intake, and C-reactive protein level,” Dr. Carnethon and her associates said.

In summary, high depressive symptoms might be connected to the development of diabetes in older adults, and this association might not be attributable solely to adverse health behaviors or weight gain. “The pathophysiologic mechanism for this association remains unclear,” they said.

Inflammation is often proposed as a likely mechanism, because inflammatory markers are associated with both diabetes and depression. However, the findings of this study showed no attenuation of the link between the two disorders when the data were adjusted for C-reactive protein levels.

This suggests that “other biological mechanisms previously proposed, such as hypothalamic-pituitary-adrenal axis dysregulation and sympathetic nervous system stimulation, may be more salient,” they added.

Older adults who report a high degree of depressive symptoms are more likely to develop type 2 diabetes than are those without depressive symptoms, according to Mercedes R. Carnethon, Ph.D., of Northwestern University, Chicago, and her associates in the Cardiovascular Health Study.

Several studies have found an association between depressive symptoms or clinical depression and diabetes, but this is the first to examine the issue in a population of people over age 65, who have a high prevalence of both disorders, Dr. Carnethon and her associates said (Arch. Intern. Med. 2007;167:802–7).

The researchers assessed data on 4,681 participants in the Cardiovascular Health Study, which took place from 1989 to 1999. Depressive symptoms had been evaluated annually using the 10-item Center for Epidemiological Studies Depression Scale.

A minimum score of 0 for each item would indicate that the subject experienced that depressive symptom never or rarely, and a maximum score of 3 for each item would indicate that the subject experienced that symptom most of the time or always. Total scores of 8 or more points, out of a possible maximum of 30 points, were considered high.

Twenty percent of the participants had high depressive symptom scores on at least one occasion. The proportion of subjects who were overweight or obese–a factor that could potentially confound the association with diabetes–was similar across those who had low, intermediate, or high depressive symptom scores.

New-onset diabetes was determined by the subjects' use of insulin or oral diabetes medications and by fasting glucose levels that were measured on two occasions during follow-up. A total of 234 subjects developed diabetes.

A high number of depressive symptoms on a single occasion, a significant increase in such symptoms over time, and persistently high symptoms over time all were associated with an excess incidence of diabetes, the investigators said.

The strongest link with diabetes was found when depressive symptom scores rose by at least 5 points over time.

“These findings were present across demographic strata and persisted with statistical adjustment for known correlates of depression and diabetes, such as BMI [body mass index], physical activity, cigarette smoking, alcohol intake, and C-reactive protein level,” Dr. Carnethon and her associates said.

In summary, high depressive symptoms might be connected to the development of diabetes in older adults, and this association might not be attributable solely to adverse health behaviors or weight gain. “The pathophysiologic mechanism for this association remains unclear,” they said.

Inflammation is often proposed as a likely mechanism, because inflammatory markers are associated with both diabetes and depression. However, the findings of this study showed no attenuation of the link between the two disorders when the data were adjusted for C-reactive protein levels.

This suggests that “other biological mechanisms previously proposed, such as hypothalamic-pituitary-adrenal axis dysregulation and sympathetic nervous system stimulation, may be more salient,” they added.

MINNEAPOLIS – Treatment with both eszopiclone and escitalopram significantly improved the symptoms of insomnia and anxiety–compared with escitalopram alone, according to data from 595 adults presented at the annual meeting of the Associated Professional Sleep Societies.

Results from a pair of studies supported by Sepracor Inc. showed that the eszopiclone/escitalopram combination was well tolerated and significantly improved not only anxiety but also the length and quality of sleep. Because insomnia often coexists with generalized anxiety disorder, a double-duty treatment regimen would be helpful for patients who suffer from both conditions, the researchers noted.

All study participants met criteria for generalized anxiety disorder and insomnia. All of them received 10 mg escitalopram (Lexapro) daily for 10 weeks. At the same time, 294 were randomized to receive 3 mg eszopiclone (Lunesta), while 301 received placebo for 8 weeks, followed by a 2-week discontinuation period.

Overall, patients who took the combination therapy showed significant improvements in mood and anxiety symptoms based on their Clinical Global Impression scale and the Hamilton Anxiety scale scores after 1, 2, 4, 6, 8, and 10 weeks of treatment, Dr. Mark H. Pollack reported. Dr. Pollack, director of the Center for Anxiety and Traumatic Stress Disorders at Massachusetts General Hospital, Boston, conducted the study.

Similarly, scores on the 17-item Hamilton Rating Scale for Depression (HAM-D17) were significantly better in the combination therapy group at all evaluation points. Anxiety remission rates were higher in the combination therapy group, too, compared with the placebo group (42% vs. 36%), said Dr. Pollack, who serves on the advisory boards of and has received support for research from several pharmaceutical companies, including that of Sepracor.

In a second study of the same group of patients, presented by Dr. W. Vaughn McCall, professor and chairman of the department of psychiatry and behavioral medicine at Wake Forest University, Winston-Salem, N.C., significantly more patients who received combination therapy had no clinically meaningful insomnia at 8 weeks, compared with the escitalopram-only patients (47% vs. 33%).

In addition, combination therapy patients took significantly less time to fall asleep, slept longer, and scored significantly better on the insomnia severity index than did the escitalopram-only group, said Dr. McCall, who serves on Sepracor's speakers' bureau and its advisory board.

The adverse event rates were similar in both groups during the study period (78% for the combination group and 68% for the escitalopram-only group) and were identical (16%) during the 2-week discontinuation period. Overall the treatment was well tolerated, and no patients showed evidence of rebound insomnia as a result of the medications.

The most common adverse events reported in at least 10% of the combination therapy group were unpleasant taste (24%), headache (19%), dry mouth (16%), and sleepiness (11%); the most common adverse events reported in the escitalopram-only group were headache (15%) and nausea (15%).

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MINNEAPOLIS – Treatment with both eszopiclone and escitalopram significantly improved the symptoms of insomnia and anxiety–compared with escitalopram alone, according to data from 595 adults presented at the annual meeting of the Associated Professional Sleep Societies.

Results from a pair of studies supported by Sepracor Inc. showed that the eszopiclone/escitalopram combination was well tolerated and significantly improved not only anxiety but also the length and quality of sleep. Because insomnia often coexists with generalized anxiety disorder, a double-duty treatment regimen would be helpful for patients who suffer from both conditions, the researchers noted.

All study participants met criteria for generalized anxiety disorder and insomnia. All of them received 10 mg escitalopram (Lexapro) daily for 10 weeks. At the same time, 294 were randomized to receive 3 mg eszopiclone (Lunesta), while 301 received placebo for 8 weeks, followed by a 2-week discontinuation period.

Overall, patients who took the combination therapy showed significant improvements in mood and anxiety symptoms based on their Clinical Global Impression scale and the Hamilton Anxiety scale scores after 1, 2, 4, 6, 8, and 10 weeks of treatment, Dr. Mark H. Pollack reported. Dr. Pollack, director of the Center for Anxiety and Traumatic Stress Disorders at Massachusetts General Hospital, Boston, conducted the study.

Similarly, scores on the 17-item Hamilton Rating Scale for Depression (HAM-D17) were significantly better in the combination therapy group at all evaluation points. Anxiety remission rates were higher in the combination therapy group, too, compared with the placebo group (42% vs. 36%), said Dr. Pollack, who serves on the advisory boards of and has received support for research from several pharmaceutical companies, including that of Sepracor.

In a second study of the same group of patients, presented by Dr. W. Vaughn McCall, professor and chairman of the department of psychiatry and behavioral medicine at Wake Forest University, Winston-Salem, N.C., significantly more patients who received combination therapy had no clinically meaningful insomnia at 8 weeks, compared with the escitalopram-only patients (47% vs. 33%).

In addition, combination therapy patients took significantly less time to fall asleep, slept longer, and scored significantly better on the insomnia severity index than did the escitalopram-only group, said Dr. McCall, who serves on Sepracor's speakers' bureau and its advisory board.

The adverse event rates were similar in both groups during the study period (78% for the combination group and 68% for the escitalopram-only group) and were identical (16%) during the 2-week discontinuation period. Overall the treatment was well tolerated, and no patients showed evidence of rebound insomnia as a result of the medications.

The most common adverse events reported in at least 10% of the combination therapy group were unpleasant taste (24%), headache (19%), dry mouth (16%), and sleepiness (11%); the most common adverse events reported in the escitalopram-only group were headache (15%) and nausea (15%).

ELSEVIER GLOBAL MEDICAL NEWS

MINNEAPOLIS – Treatment with both eszopiclone and escitalopram significantly improved the symptoms of insomnia and anxiety–compared with escitalopram alone, according to data from 595 adults presented at the annual meeting of the Associated Professional Sleep Societies.

Results from a pair of studies supported by Sepracor Inc. showed that the eszopiclone/escitalopram combination was well tolerated and significantly improved not only anxiety but also the length and quality of sleep. Because insomnia often coexists with generalized anxiety disorder, a double-duty treatment regimen would be helpful for patients who suffer from both conditions, the researchers noted.

All study participants met criteria for generalized anxiety disorder and insomnia. All of them received 10 mg escitalopram (Lexapro) daily for 10 weeks. At the same time, 294 were randomized to receive 3 mg eszopiclone (Lunesta), while 301 received placebo for 8 weeks, followed by a 2-week discontinuation period.

Overall, patients who took the combination therapy showed significant improvements in mood and anxiety symptoms based on their Clinical Global Impression scale and the Hamilton Anxiety scale scores after 1, 2, 4, 6, 8, and 10 weeks of treatment, Dr. Mark H. Pollack reported. Dr. Pollack, director of the Center for Anxiety and Traumatic Stress Disorders at Massachusetts General Hospital, Boston, conducted the study.

Similarly, scores on the 17-item Hamilton Rating Scale for Depression (HAM-D17) were significantly better in the combination therapy group at all evaluation points. Anxiety remission rates were higher in the combination therapy group, too, compared with the placebo group (42% vs. 36%), said Dr. Pollack, who serves on the advisory boards of and has received support for research from several pharmaceutical companies, including that of Sepracor.

In a second study of the same group of patients, presented by Dr. W. Vaughn McCall, professor and chairman of the department of psychiatry and behavioral medicine at Wake Forest University, Winston-Salem, N.C., significantly more patients who received combination therapy had no clinically meaningful insomnia at 8 weeks, compared with the escitalopram-only patients (47% vs. 33%).

In addition, combination therapy patients took significantly less time to fall asleep, slept longer, and scored significantly better on the insomnia severity index than did the escitalopram-only group, said Dr. McCall, who serves on Sepracor's speakers' bureau and its advisory board.

The adverse event rates were similar in both groups during the study period (78% for the combination group and 68% for the escitalopram-only group) and were identical (16%) during the 2-week discontinuation period. Overall the treatment was well tolerated, and no patients showed evidence of rebound insomnia as a result of the medications.

The most common adverse events reported in at least 10% of the combination therapy group were unpleasant taste (24%), headache (19%), dry mouth (16%), and sleepiness (11%); the most common adverse events reported in the escitalopram-only group were headache (15%) and nausea (15%).

ELSEVIER GLOBAL MEDICAL NEWS

OTTAWA – A new, nonhormonal drug was safe and effective for reducing the incidence and severity of vasomotor symptoms of menopause in a series of three pivotal trials with a total of about 1,700 women.

If the drug, desvenlafaxine succinate, a serotonin-norepinephrine reuptake inhibitor (SNRI), is approved by the Food and Drug Administration, “it will be the first nonhormonal drug approved for treating hot flashes and nighttime awakenings,” Dr. Margery Gass said at the annual clinical meeting of the Society of Obstetricians and Gynaecologists of Canada. She and her colleague, Dr. Sophie Olivier, presented the data in five separate reports at the meeting.

“Women and their physicians are seeking an alternative to estrogen. What's exciting is that this drug seems effective against hot flashes and mood, the things that trouble women during menopause,” commented meeting attendee Dr. Jennifer Blake, chief of ob.gyn. at Sunnybrook Health Sciences Centre, Toronto.

Data from these studies were submitted by the drug's developer, Wyeth, to the FDA in June 2006, and–as of late June of this year–action by the FDA for the indication of moderate to severe menopausal vasomotor symptoms was still pending. Last January, the FDA told Wyeth that desvenlafaxine was approvable for the indication of major depressive disorder, but final approval for that use is also still pending. A Wyeth spokeswoman said that the company plans to market the drug with the trade name Pristiq for both indications.

The largest of the three pivotal trials enrolled 689 women who reported having 50 or more moderate or severe hot flash episodes a week. Patients were randomized to daily desvenlafaxine dosages of 50, 100, 150, or 200 mg, or placebo, and were scheduled to receive 52 weeks of treatment. The primary efficacy end point was the number and severity of hot flashes after 12 weeks of treatment, and the number of nighttime awakenings. Efficacy data were available for 620 of the enrolled women.

At baseline, these women had an average of about 11 hot flash episodes daily, with an average severity of 2.4 points (with measurements defined as severe [3 points], moderate [2 points], and mild [1 point]). They also reported an average of 3.7 awakenings a night.

Treatment with desvenlafaxine was most effective in this study at the 100-mg/day level. The 145 women on that dosage reported an average daily reduction of 1.76 hot flash episodes, compared with placebo, and an average drop in episode severity of 0.33 points, compared with the placebo effect. The frequency of nighttime awakenings fell by 0.56 episodes a night, compared with the placebo group. All of these changes were statistically significant compared with placebo, reported Dr. Gass, of the department of ob.gyn. at the University of Cincinnati. Dr. Gass disclosed that she receives compensation as a consultant to Wyeth. In Wyeth's submissions to the FDA, it has proposed 100 mg/day as the recommended dosage, she said.

The placebo effect was substantial. The 77 women in the placebo group reported an average reduction of 6.3 hot flash episodes a day compared with their baseline number, an average drop in hot flash severity of 0.5 points, and an average drop in awakenings of 2.2 episodes a night.

To assess the clinical significance of the effect of desvenlafaxine, researchers gave patients a questionnaire about their satisfaction with treatment. Significantly more women were satisfied with treatment when taking 100 mg desvenlafaxine daily, compared with those in the placebo group. (See box above.)

The researchers also ran another analysis to gauge the meaning of the treatment effect that they measured. They evaluated the difference in treatment responses based on whether the women rated themselves as dissatisfied, neutral, or satisfied with their treatment response. The average increment in response between the women who self-rated themselves as neutral to the treatment, and those who were satisfied, was an additional reduction in hot flash episodes of 1.64 per day. Dr. Gass and her associates called this the “treatment satisfaction threshold.” The difference between neutral and satisfied was an average drop in hot flash severity of 0.2 points, and an average decrease in awakenings of 0.42 episodes per night.

Notably, the 100-mg/day dosage of desvenlafaxine produced a drop in all three measures, compared with placebo, that exceeded all three of these treatment satisfaction thresholds, said Dr. Gass, who is also director of the Menopause and Osteoporosis Center at the University of Cincinnati Medical Center.

“What was very interesting is they looked at patient satisfaction levels and showed a clinically meaningful difference from the drug compared with placebo,” commented Dr. Blake, who is also a professor and associate chair of medicine at the University of Toronto.

The efficacy of the 100-mg dosage was confirmed in a second study that included 484 women who were randomized to either 100 mg or 150 mg desvenlafaxine daily or placebo, and were treated for 26 weeks. Again, the primary efficacy end points were measured after 12 weeks of treatment. The data from this second study were presented in a combined analysis with data from the first study, so that the total group included 843 women: 307 who received 100 mg/day desvenlafaxine, 281 who received 150 mg/day, and 255 who received placebo.

The findings for number and severity of daily hot flashes and number of nighttime awakenings were similar to the results from the first study. The analysis also included a more detailed look at the effect of treatment on sleep. Women who received either the 100- or 150-mg dosage had significant increases in the number of minutes slept and in their self-reported sleep quality, compared with placebo patients, reported Dr. Olivier, senior director for clinical research and development at Wyeth.

This report also included data on mood, based on the Profile of Mood States (POMS) questionnaire. The lower the POMS score, the better a person's mood; a normal score is about 20 points or lower. At baseline, the women in the combined study had an average score of about 27.

After 12 weeks of treatment, the POMS scores had dropped by an average of about 19 points in the women treated with desvenlafaxine, compared with an average fall of about 12 points among women in the placebo group, a statistically significant difference.

The ability of desvenlafaxine treatment to improve the POMS score is likely due to both a direct antidepressant effect of the drug and to a secondary effect mediated by reduced vasomotor symptoms and improved sleep quality, Dr. Olivier said.

The third study involved 508 women who were randomized to daily treatment with 100 mg desvenlafaxine, 2.5 mg tibolone, or placebo and were treated for 12 weeks. Tibolone (Xyvion), a synthetic hormone that is a selective estrogen-receptor modulator, is not approved for use in the United States but is approved for use in Europe and elsewhere. In this study, the 100-mg dosage of desvenlafaxine was not significantly different from placebo for reducing the frequency and severity of hot flashes and nighttime awakenings, and this dosage of desvenlafaxine was significantly worse than tibolone.

“As expected, tibolone was much more effective than the SNRI” for relieving vasomotor symptoms, Dr. Olivier said.

But in an analysis that combined the efficacy data collected in all three studies, the 100-mg/day and 150-mg/day dosages were each significantly better than placebo for reducing vasomotor symptoms. In addition, treatment with these dosages of desvenlafaxine produced the full treatment effect within 7 days of the start of treatment. In contrast, in the placebo group, the full effect of treatment was not seen until 4 weeks had elapsed.

The safety analysis involved a total of 1,131 patients treated with desvenlafaxine, including 495 treated for at least 12 weeks with the 100-mg/day dosage and 336 women treated with 150 mg/day. This analysis included 612 women assigned to treatment with desvenlafaxine for 52 weeks, including 155 women on 100 mg/day and 157 assigned to 150 mg/day.

The results showed that desvenlafaxine was generally safe and well tolerated, with an adverse effect profile similar to those of other SNRIs. The most common adverse events reported with desvenlafaxine were dizziness, headache, and nausea. Discontinuation related to adverse events occurred in 48% of the desvenlafaxine patients, compared with 25% of the placebo patients.

The safety analysis included a detailed assessment of the effect of desvenlafaxine on sexual function in the 689 women assigned to treatment for 52 weeks. Sexual function was scored for arousal, desire, orgasm, and an overall measure; there was no statistically significant change in any of these measures, compared with placebo, Dr. Gass reported. Similar findings were made in a subgroup of 348 women who reported being sexually active before and during the study.

In addition, individual episodes of sexual dysfunction–abnormal orgasm, decreased libido, abnormal sexual function, or anorgasmia–were tallied for each of the treatment groups in this study. There was a suggestion of a dose-dependent relationship in the overall incidence of these events. (See box at left.) However, the rate of events in each treatment group was not significantly different from that in the placebo group, and there was no statistically significant trend in the dose-related incidence of these events. The rate in the women taking 100 mg/day desvenlafaxine was 3.9%, compared with 1.3% in the placebo group, Dr. Gass said.

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

OTTAWA – A new, nonhormonal drug was safe and effective for reducing the incidence and severity of vasomotor symptoms of menopause in a series of three pivotal trials with a total of about 1,700 women.

If the drug, desvenlafaxine succinate, a serotonin-norepinephrine reuptake inhibitor (SNRI), is approved by the Food and Drug Administration, “it will be the first nonhormonal drug approved for treating hot flashes and nighttime awakenings,” Dr. Margery Gass said at the annual clinical meeting of the Society of Obstetricians and Gynaecologists of Canada. She and her colleague, Dr. Sophie Olivier, presented the data in five separate reports at the meeting.

“Women and their physicians are seeking an alternative to estrogen. What's exciting is that this drug seems effective against hot flashes and mood, the things that trouble women during menopause,” commented meeting attendee Dr. Jennifer Blake, chief of ob.gyn. at Sunnybrook Health Sciences Centre, Toronto.

Data from these studies were submitted by the drug's developer, Wyeth, to the FDA in June 2006, and–as of late June of this year–action by the FDA for the indication of moderate to severe menopausal vasomotor symptoms was still pending. Last January, the FDA told Wyeth that desvenlafaxine was approvable for the indication of major depressive disorder, but final approval for that use is also still pending. A Wyeth spokeswoman said that the company plans to market the drug with the trade name Pristiq for both indications.

The largest of the three pivotal trials enrolled 689 women who reported having 50 or more moderate or severe hot flash episodes a week. Patients were randomized to daily desvenlafaxine dosages of 50, 100, 150, or 200 mg, or placebo, and were scheduled to receive 52 weeks of treatment. The primary efficacy end point was the number and severity of hot flashes after 12 weeks of treatment, and the number of nighttime awakenings. Efficacy data were available for 620 of the enrolled women.

At baseline, these women had an average of about 11 hot flash episodes daily, with an average severity of 2.4 points (with measurements defined as severe [3 points], moderate [2 points], and mild [1 point]). They also reported an average of 3.7 awakenings a night.

Treatment with desvenlafaxine was most effective in this study at the 100-mg/day level. The 145 women on that dosage reported an average daily reduction of 1.76 hot flash episodes, compared with placebo, and an average drop in episode severity of 0.33 points, compared with the placebo effect. The frequency of nighttime awakenings fell by 0.56 episodes a night, compared with the placebo group. All of these changes were statistically significant compared with placebo, reported Dr. Gass, of the department of ob.gyn. at the University of Cincinnati. Dr. Gass disclosed that she receives compensation as a consultant to Wyeth. In Wyeth's submissions to the FDA, it has proposed 100 mg/day as the recommended dosage, she said.

The placebo effect was substantial. The 77 women in the placebo group reported an average reduction of 6.3 hot flash episodes a day compared with their baseline number, an average drop in hot flash severity of 0.5 points, and an average drop in awakenings of 2.2 episodes a night.

To assess the clinical significance of the effect of desvenlafaxine, researchers gave patients a questionnaire about their satisfaction with treatment. Significantly more women were satisfied with treatment when taking 100 mg desvenlafaxine daily, compared with those in the placebo group. (See box above.)

The researchers also ran another analysis to gauge the meaning of the treatment effect that they measured. They evaluated the difference in treatment responses based on whether the women rated themselves as dissatisfied, neutral, or satisfied with their treatment response. The average increment in response between the women who self-rated themselves as neutral to the treatment, and those who were satisfied, was an additional reduction in hot flash episodes of 1.64 per day. Dr. Gass and her associates called this the “treatment satisfaction threshold.” The difference between neutral and satisfied was an average drop in hot flash severity of 0.2 points, and an average decrease in awakenings of 0.42 episodes per night.

Notably, the 100-mg/day dosage of desvenlafaxine produced a drop in all three measures, compared with placebo, that exceeded all three of these treatment satisfaction thresholds, said Dr. Gass, who is also director of the Menopause and Osteoporosis Center at the University of Cincinnati Medical Center.

“What was very interesting is they looked at patient satisfaction levels and showed a clinically meaningful difference from the drug compared with placebo,” commented Dr. Blake, who is also a professor and associate chair of medicine at the University of Toronto.

The efficacy of the 100-mg dosage was confirmed in a second study that included 484 women who were randomized to either 100 mg or 150 mg desvenlafaxine daily or placebo, and were treated for 26 weeks. Again, the primary efficacy end points were measured after 12 weeks of treatment. The data from this second study were presented in a combined analysis with data from the first study, so that the total group included 843 women: 307 who received 100 mg/day desvenlafaxine, 281 who received 150 mg/day, and 255 who received placebo.

The findings for number and severity of daily hot flashes and number of nighttime awakenings were similar to the results from the first study. The analysis also included a more detailed look at the effect of treatment on sleep. Women who received either the 100- or 150-mg dosage had significant increases in the number of minutes slept and in their self-reported sleep quality, compared with placebo patients, reported Dr. Olivier, senior director for clinical research and development at Wyeth.

This report also included data on mood, based on the Profile of Mood States (POMS) questionnaire. The lower the POMS score, the better a person's mood; a normal score is about 20 points or lower. At baseline, the women in the combined study had an average score of about 27.

After 12 weeks of treatment, the POMS scores had dropped by an average of about 19 points in the women treated with desvenlafaxine, compared with an average fall of about 12 points among women in the placebo group, a statistically significant difference.

The ability of desvenlafaxine treatment to improve the POMS score is likely due to both a direct antidepressant effect of the drug and to a secondary effect mediated by reduced vasomotor symptoms and improved sleep quality, Dr. Olivier said.

The third study involved 508 women who were randomized to daily treatment with 100 mg desvenlafaxine, 2.5 mg tibolone, or placebo and were treated for 12 weeks. Tibolone (Xyvion), a synthetic hormone that is a selective estrogen-receptor modulator, is not approved for use in the United States but is approved for use in Europe and elsewhere. In this study, the 100-mg dosage of desvenlafaxine was not significantly different from placebo for reducing the frequency and severity of hot flashes and nighttime awakenings, and this dosage of desvenlafaxine was significantly worse than tibolone.

“As expected, tibolone was much more effective than the SNRI” for relieving vasomotor symptoms, Dr. Olivier said.

But in an analysis that combined the efficacy data collected in all three studies, the 100-mg/day and 150-mg/day dosages were each significantly better than placebo for reducing vasomotor symptoms. In addition, treatment with these dosages of desvenlafaxine produced the full treatment effect within 7 days of the start of treatment. In contrast, in the placebo group, the full effect of treatment was not seen until 4 weeks had elapsed.

The safety analysis involved a total of 1,131 patients treated with desvenlafaxine, including 495 treated for at least 12 weeks with the 100-mg/day dosage and 336 women treated with 150 mg/day. This analysis included 612 women assigned to treatment with desvenlafaxine for 52 weeks, including 155 women on 100 mg/day and 157 assigned to 150 mg/day.

The results showed that desvenlafaxine was generally safe and well tolerated, with an adverse effect profile similar to those of other SNRIs. The most common adverse events reported with desvenlafaxine were dizziness, headache, and nausea. Discontinuation related to adverse events occurred in 48% of the desvenlafaxine patients, compared with 25% of the placebo patients.

The safety analysis included a detailed assessment of the effect of desvenlafaxine on sexual function in the 689 women assigned to treatment for 52 weeks. Sexual function was scored for arousal, desire, orgasm, and an overall measure; there was no statistically significant change in any of these measures, compared with placebo, Dr. Gass reported. Similar findings were made in a subgroup of 348 women who reported being sexually active before and during the study.

In addition, individual episodes of sexual dysfunction–abnormal orgasm, decreased libido, abnormal sexual function, or anorgasmia–were tallied for each of the treatment groups in this study. There was a suggestion of a dose-dependent relationship in the overall incidence of these events. (See box at left.) However, the rate of events in each treatment group was not significantly different from that in the placebo group, and there was no statistically significant trend in the dose-related incidence of these events. The rate in the women taking 100 mg/day desvenlafaxine was 3.9%, compared with 1.3% in the placebo group, Dr. Gass said.

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

OTTAWA – A new, nonhormonal drug was safe and effective for reducing the incidence and severity of vasomotor symptoms of menopause in a series of three pivotal trials with a total of about 1,700 women.

If the drug, desvenlafaxine succinate, a serotonin-norepinephrine reuptake inhibitor (SNRI), is approved by the Food and Drug Administration, “it will be the first nonhormonal drug approved for treating hot flashes and nighttime awakenings,” Dr. Margery Gass said at the annual clinical meeting of the Society of Obstetricians and Gynaecologists of Canada. She and her colleague, Dr. Sophie Olivier, presented the data in five separate reports at the meeting.

“Women and their physicians are seeking an alternative to estrogen. What's exciting is that this drug seems effective against hot flashes and mood, the things that trouble women during menopause,” commented meeting attendee Dr. Jennifer Blake, chief of ob.gyn. at Sunnybrook Health Sciences Centre, Toronto.

Data from these studies were submitted by the drug's developer, Wyeth, to the FDA in June 2006, and–as of late June of this year–action by the FDA for the indication of moderate to severe menopausal vasomotor symptoms was still pending. Last January, the FDA told Wyeth that desvenlafaxine was approvable for the indication of major depressive disorder, but final approval for that use is also still pending. A Wyeth spokeswoman said that the company plans to market the drug with the trade name Pristiq for both indications.

The largest of the three pivotal trials enrolled 689 women who reported having 50 or more moderate or severe hot flash episodes a week. Patients were randomized to daily desvenlafaxine dosages of 50, 100, 150, or 200 mg, or placebo, and were scheduled to receive 52 weeks of treatment. The primary efficacy end point was the number and severity of hot flashes after 12 weeks of treatment, and the number of nighttime awakenings. Efficacy data were available for 620 of the enrolled women.

At baseline, these women had an average of about 11 hot flash episodes daily, with an average severity of 2.4 points (with measurements defined as severe [3 points], moderate [2 points], and mild [1 point]). They also reported an average of 3.7 awakenings a night.

Treatment with desvenlafaxine was most effective in this study at the 100-mg/day level. The 145 women on that dosage reported an average daily reduction of 1.76 hot flash episodes, compared with placebo, and an average drop in episode severity of 0.33 points, compared with the placebo effect. The frequency of nighttime awakenings fell by 0.56 episodes a night, compared with the placebo group. All of these changes were statistically significant compared with placebo, reported Dr. Gass, of the department of ob.gyn. at the University of Cincinnati. Dr. Gass disclosed that she receives compensation as a consultant to Wyeth. In Wyeth's submissions to the FDA, it has proposed 100 mg/day as the recommended dosage, she said.

The placebo effect was substantial. The 77 women in the placebo group reported an average reduction of 6.3 hot flash episodes a day compared with their baseline number, an average drop in hot flash severity of 0.5 points, and an average drop in awakenings of 2.2 episodes a night.

To assess the clinical significance of the effect of desvenlafaxine, researchers gave patients a questionnaire about their satisfaction with treatment. Significantly more women were satisfied with treatment when taking 100 mg desvenlafaxine daily, compared with those in the placebo group. (See box above.)

The researchers also ran another analysis to gauge the meaning of the treatment effect that they measured. They evaluated the difference in treatment responses based on whether the women rated themselves as dissatisfied, neutral, or satisfied with their treatment response. The average increment in response between the women who self-rated themselves as neutral to the treatment, and those who were satisfied, was an additional reduction in hot flash episodes of 1.64 per day. Dr. Gass and her associates called this the “treatment satisfaction threshold.” The difference between neutral and satisfied was an average drop in hot flash severity of 0.2 points, and an average decrease in awakenings of 0.42 episodes per night.

Notably, the 100-mg/day dosage of desvenlafaxine produced a drop in all three measures, compared with placebo, that exceeded all three of these treatment satisfaction thresholds, said Dr. Gass, who is also director of the Menopause and Osteoporosis Center at the University of Cincinnati Medical Center.

“What was very interesting is they looked at patient satisfaction levels and showed a clinically meaningful difference from the drug compared with placebo,” commented Dr. Blake, who is also a professor and associate chair of medicine at the University of Toronto.

The efficacy of the 100-mg dosage was confirmed in a second study that included 484 women who were randomized to either 100 mg or 150 mg desvenlafaxine daily or placebo, and were treated for 26 weeks. Again, the primary efficacy end points were measured after 12 weeks of treatment. The data from this second study were presented in a combined analysis with data from the first study, so that the total group included 843 women: 307 who received 100 mg/day desvenlafaxine, 281 who received 150 mg/day, and 255 who received placebo.

The findings for number and severity of daily hot flashes and number of nighttime awakenings were similar to the results from the first study. The analysis also included a more detailed look at the effect of treatment on sleep. Women who received either the 100- or 150-mg dosage had significant increases in the number of minutes slept and in their self-reported sleep quality, compared with placebo patients, reported Dr. Olivier, senior director for clinical research and development at Wyeth.

This report also included data on mood, based on the Profile of Mood States (POMS) questionnaire. The lower the POMS score, the better a person's mood; a normal score is about 20 points or lower. At baseline, the women in the combined study had an average score of about 27.

After 12 weeks of treatment, the POMS scores had dropped by an average of about 19 points in the women treated with desvenlafaxine, compared with an average fall of about 12 points among women in the placebo group, a statistically significant difference.

The ability of desvenlafaxine treatment to improve the POMS score is likely due to both a direct antidepressant effect of the drug and to a secondary effect mediated by reduced vasomotor symptoms and improved sleep quality, Dr. Olivier said.

The third study involved 508 women who were randomized to daily treatment with 100 mg desvenlafaxine, 2.5 mg tibolone, or placebo and were treated for 12 weeks. Tibolone (Xyvion), a synthetic hormone that is a selective estrogen-receptor modulator, is not approved for use in the United States but is approved for use in Europe and elsewhere. In this study, the 100-mg dosage of desvenlafaxine was not significantly different from placebo for reducing the frequency and severity of hot flashes and nighttime awakenings, and this dosage of desvenlafaxine was significantly worse than tibolone.

“As expected, tibolone was much more effective than the SNRI” for relieving vasomotor symptoms, Dr. Olivier said.

But in an analysis that combined the efficacy data collected in all three studies, the 100-mg/day and 150-mg/day dosages were each significantly better than placebo for reducing vasomotor symptoms. In addition, treatment with these dosages of desvenlafaxine produced the full treatment effect within 7 days of the start of treatment. In contrast, in the placebo group, the full effect of treatment was not seen until 4 weeks had elapsed.

The safety analysis involved a total of 1,131 patients treated with desvenlafaxine, including 495 treated for at least 12 weeks with the 100-mg/day dosage and 336 women treated with 150 mg/day. This analysis included 612 women assigned to treatment with desvenlafaxine for 52 weeks, including 155 women on 100 mg/day and 157 assigned to 150 mg/day.

The results showed that desvenlafaxine was generally safe and well tolerated, with an adverse effect profile similar to those of other SNRIs. The most common adverse events reported with desvenlafaxine were dizziness, headache, and nausea. Discontinuation related to adverse events occurred in 48% of the desvenlafaxine patients, compared with 25% of the placebo patients.

The safety analysis included a detailed assessment of the effect of desvenlafaxine on sexual function in the 689 women assigned to treatment for 52 weeks. Sexual function was scored for arousal, desire, orgasm, and an overall measure; there was no statistically significant change in any of these measures, compared with placebo, Dr. Gass reported. Similar findings were made in a subgroup of 348 women who reported being sexually active before and during the study.

In addition, individual episodes of sexual dysfunction–abnormal orgasm, decreased libido, abnormal sexual function, or anorgasmia–were tallied for each of the treatment groups in this study. There was a suggestion of a dose-dependent relationship in the overall incidence of these events. (See box at left.) However, the rate of events in each treatment group was not significantly different from that in the placebo group, and there was no statistically significant trend in the dose-related incidence of these events. The rate in the women taking 100 mg/day desvenlafaxine was 3.9%, compared with 1.3% in the placebo group, Dr. Gass said.

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON – Judicious use of antidepressants can ameliorate the psychiatric stressors that exacerbate moderate to severe irritable bowel syndrome symptoms, Dr. Douglas A. Drossman said at a meeting on neurogastroenterology and motility.

These agents can also act directly in the gut to control bowel dysfunction, said Dr. Drossman, codirector of the University of North Carolina Center for Functional GI and Motility Disorders, in Chapel Hill. “The more severe the IBS, the more likely the patient is to have comorbid psychosocial factors,” Dr. Drossman said. “Any treatment that might reduce the stressor itself or the interpretation of the stressor through psychological pathways or through antidepressants is likely to have some benefit.”

One of the first hurdles is to confront maladaptive negative beliefs a patient may have that can undermine good outcomes. Patients who feel that they have no control over their symptoms, who “catastrophize” and believe their condition will never get better, or who have a history of abuse have poorer outcomes–regardless of their treatment or condition, Dr. Drossman said.

He urges clinicians to establish a productive physician/patient relationship at the outset by identifying patient worries, providing reassurance, explaining the physiologic basis of symptoms, setting realistic treatment goals and time frames, and addressing cost concerns.

When choosing an antidepressant for irritable bowel syndrome (IBS), clinicians must consider the medication class and features of a particular medication within the class. Tricyclic antidepressants (TCAs) with noradrenergic activity are useful for IBS with diarrhea, especially for those patients with comorbid pain and depression. Dr. Drossman does not favor TCAs such as amitriptyline, which may cause side effects that limit tolerability through anticholinergic and antihistaminergic effects. Instead, he recommends desipramine or nortriptyline.

Selective serotonin reuptake inhibitors (SSRIs) are a good choice for patients with IBS with constipation who may also have depression, panic or anxiety symptoms, or obsessive-compulsive disorders. This makes SSRIs appropriate for housebound patients who fear having an IBS episode while away from home. Dr. Drossman tends to stay away from short-acting agents such as paroxetine (Paxil), in order to minimize discontinuation side effects. He prefers medium-acting citalopram (Celexa) or escitalopram (Lexapro), or long-acting fluoxetine. SSRIs tend to have negligible effects on noradrenergic receptors and thus do not provide pain relief and may cause agitation because of serotonergic bursts when treatment is initiated, Dr. Drossman said.

Duloxetine (Cymbalta), a serotonin norepinephrine reuptake inhibitor (SNRI), has potent effects on noradrenergic and serotonergic receptors and minor effects on histaminergic and cholinergic systems. Because duloxetine is indicated for treating depression and managing neuropathic pain associated with diabetic peripheral neuropathy, it may be of particular benefit for a depressed IBS patient with prominent pain symptoms.

Sometimes, antipsychotics have a place in IBS management, Dr. Drossman said. “We are seeing an increasing use of antipsychotics in the primary care sector for conditions like anxiety and personality disorders–agents that [primary care physicians] would never have thought about touching years ago,” he said.

Dr. Drossman uses quetiapine (Seroquel) for sedation to treat extreme anxiety and comorbid bipolar and personality disorders, and as augmentation with antidepressants, giving a 50–200-mg dose before bedtime–well below the typical antipsychotic dose of 400 mg. However, he cautions that physicians should consider psychiatric consultation before making this treatment decision.

Dr. Drossman begins pharmacotherapy after symptomatic medical treatment and stress reduction techniques such as exercise and yoga fail. He starts with a low dose of a TCA, SSRI, or SNRI for 4–6 weeks, reevaluates the patient, increases the dose if necessary, and continues treatment for an additional 4–6 weeks. If symptoms are not controlled adequately, he may augment therapy by adding a drug from another class, such as buspirone, which has bowel-relaxing effects, or refer to a psychiatrist.

BOSTON – Judicious use of antidepressants can ameliorate the psychiatric stressors that exacerbate moderate to severe irritable bowel syndrome symptoms, Dr. Douglas A. Drossman said at a meeting on neurogastroenterology and motility.

These agents can also act directly in the gut to control bowel dysfunction, said Dr. Drossman, codirector of the University of North Carolina Center for Functional GI and Motility Disorders, in Chapel Hill. “The more severe the IBS, the more likely the patient is to have comorbid psychosocial factors,” Dr. Drossman said. “Any treatment that might reduce the stressor itself or the interpretation of the stressor through psychological pathways or through antidepressants is likely to have some benefit.”

One of the first hurdles is to confront maladaptive negative beliefs a patient may have that can undermine good outcomes. Patients who feel that they have no control over their symptoms, who “catastrophize” and believe their condition will never get better, or who have a history of abuse have poorer outcomes–regardless of their treatment or condition, Dr. Drossman said.

He urges clinicians to establish a productive physician/patient relationship at the outset by identifying patient worries, providing reassurance, explaining the physiologic basis of symptoms, setting realistic treatment goals and time frames, and addressing cost concerns.

When choosing an antidepressant for irritable bowel syndrome (IBS), clinicians must consider the medication class and features of a particular medication within the class. Tricyclic antidepressants (TCAs) with noradrenergic activity are useful for IBS with diarrhea, especially for those patients with comorbid pain and depression. Dr. Drossman does not favor TCAs such as amitriptyline, which may cause side effects that limit tolerability through anticholinergic and antihistaminergic effects. Instead, he recommends desipramine or nortriptyline.

Selective serotonin reuptake inhibitors (SSRIs) are a good choice for patients with IBS with constipation who may also have depression, panic or anxiety symptoms, or obsessive-compulsive disorders. This makes SSRIs appropriate for housebound patients who fear having an IBS episode while away from home. Dr. Drossman tends to stay away from short-acting agents such as paroxetine (Paxil), in order to minimize discontinuation side effects. He prefers medium-acting citalopram (Celexa) or escitalopram (Lexapro), or long-acting fluoxetine. SSRIs tend to have negligible effects on noradrenergic receptors and thus do not provide pain relief and may cause agitation because of serotonergic bursts when treatment is initiated, Dr. Drossman said.

Duloxetine (Cymbalta), a serotonin norepinephrine reuptake inhibitor (SNRI), has potent effects on noradrenergic and serotonergic receptors and minor effects on histaminergic and cholinergic systems. Because duloxetine is indicated for treating depression and managing neuropathic pain associated with diabetic peripheral neuropathy, it may be of particular benefit for a depressed IBS patient with prominent pain symptoms.

Sometimes, antipsychotics have a place in IBS management, Dr. Drossman said. “We are seeing an increasing use of antipsychotics in the primary care sector for conditions like anxiety and personality disorders–agents that [primary care physicians] would never have thought about touching years ago,” he said.

Dr. Drossman uses quetiapine (Seroquel) for sedation to treat extreme anxiety and comorbid bipolar and personality disorders, and as augmentation with antidepressants, giving a 50–200-mg dose before bedtime–well below the typical antipsychotic dose of 400 mg. However, he cautions that physicians should consider psychiatric consultation before making this treatment decision.

Dr. Drossman begins pharmacotherapy after symptomatic medical treatment and stress reduction techniques such as exercise and yoga fail. He starts with a low dose of a TCA, SSRI, or SNRI for 4–6 weeks, reevaluates the patient, increases the dose if necessary, and continues treatment for an additional 4–6 weeks. If symptoms are not controlled adequately, he may augment therapy by adding a drug from another class, such as buspirone, which has bowel-relaxing effects, or refer to a psychiatrist.

BOSTON – Judicious use of antidepressants can ameliorate the psychiatric stressors that exacerbate moderate to severe irritable bowel syndrome symptoms, Dr. Douglas A. Drossman said at a meeting on neurogastroenterology and motility.

These agents can also act directly in the gut to control bowel dysfunction, said Dr. Drossman, codirector of the University of North Carolina Center for Functional GI and Motility Disorders, in Chapel Hill. “The more severe the IBS, the more likely the patient is to have comorbid psychosocial factors,” Dr. Drossman said. “Any treatment that might reduce the stressor itself or the interpretation of the stressor through psychological pathways or through antidepressants is likely to have some benefit.”

One of the first hurdles is to confront maladaptive negative beliefs a patient may have that can undermine good outcomes. Patients who feel that they have no control over their symptoms, who “catastrophize” and believe their condition will never get better, or who have a history of abuse have poorer outcomes–regardless of their treatment or condition, Dr. Drossman said.

He urges clinicians to establish a productive physician/patient relationship at the outset by identifying patient worries, providing reassurance, explaining the physiologic basis of symptoms, setting realistic treatment goals and time frames, and addressing cost concerns.

When choosing an antidepressant for irritable bowel syndrome (IBS), clinicians must consider the medication class and features of a particular medication within the class. Tricyclic antidepressants (TCAs) with noradrenergic activity are useful for IBS with diarrhea, especially for those patients with comorbid pain and depression. Dr. Drossman does not favor TCAs such as amitriptyline, which may cause side effects that limit tolerability through anticholinergic and antihistaminergic effects. Instead, he recommends desipramine or nortriptyline.

Selective serotonin reuptake inhibitors (SSRIs) are a good choice for patients with IBS with constipation who may also have depression, panic or anxiety symptoms, or obsessive-compulsive disorders. This makes SSRIs appropriate for housebound patients who fear having an IBS episode while away from home. Dr. Drossman tends to stay away from short-acting agents such as paroxetine (Paxil), in order to minimize discontinuation side effects. He prefers medium-acting citalopram (Celexa) or escitalopram (Lexapro), or long-acting fluoxetine. SSRIs tend to have negligible effects on noradrenergic receptors and thus do not provide pain relief and may cause agitation because of serotonergic bursts when treatment is initiated, Dr. Drossman said.

Duloxetine (Cymbalta), a serotonin norepinephrine reuptake inhibitor (SNRI), has potent effects on noradrenergic and serotonergic receptors and minor effects on histaminergic and cholinergic systems. Because duloxetine is indicated for treating depression and managing neuropathic pain associated with diabetic peripheral neuropathy, it may be of particular benefit for a depressed IBS patient with prominent pain symptoms.

Sometimes, antipsychotics have a place in IBS management, Dr. Drossman said. “We are seeing an increasing use of antipsychotics in the primary care sector for conditions like anxiety and personality disorders–agents that [primary care physicians] would never have thought about touching years ago,” he said.

Dr. Drossman uses quetiapine (Seroquel) for sedation to treat extreme anxiety and comorbid bipolar and personality disorders, and as augmentation with antidepressants, giving a 50–200-mg dose before bedtime–well below the typical antipsychotic dose of 400 mg. However, he cautions that physicians should consider psychiatric consultation before making this treatment decision.

Dr. Drossman begins pharmacotherapy after symptomatic medical treatment and stress reduction techniques such as exercise and yoga fail. He starts with a low dose of a TCA, SSRI, or SNRI for 4–6 weeks, reevaluates the patient, increases the dose if necessary, and continues treatment for an additional 4–6 weeks. If symptoms are not controlled adequately, he may augment therapy by adding a drug from another class, such as buspirone, which has bowel-relaxing effects, or refer to a psychiatrist.