Somatic Disorders

SCOTTSDALE, ARIZ. – Untreated sleep-disordered breathing may perpetuate posttraumatic stress disorder over a period of weeks, months, and even years, Dr. Lois E. Krahn proposed at a meeting on sleep medicine sponsored by the American College of Chest Physicians.

“Patients have a lot of sleep complaints. They have trouble falling asleep. They have nightmares, and one very interesting finding of late is they also have a fairly high rate of obstructive sleep apnea,” said Dr. Krahn, chair of the department of psychiatry and psychology at the Mayo Clinic in Scottsdale, Ariz.

In one posttraumatic stress disorder (PTSD) study cited by Dr. Krahn, subjective sleep disturbance was described as “a hallmark of PTSD” in elderly war veterans (Biol. Psychiatry 2000;47:520–5). Even though patients with untreated obstructive sleep apnea and sleep movement disorders were not included in the sample, the investigators reported finding many cases in patients screened for the study.

Dr. Krahn posited that obstructive sleep apnea may predispose some patients to wake in the middle of the night. “So that may be a feature that causes this condition [PTSD] to be perpetuated,” she said.

In an interview at the meeting, she suggested ordering polysomnography when PTSD patients do not improve with therapy. They may continue to relive their trauma at night, she said.

“Their sleep wasn't terrific before this traumatic event. Now they've got nightmares. With the combination, they have a more chronic disorder.”

Many psychiatric disorders overlap with sleep disorders, and can be difficult to distinguish, Dr. Krahn said. She suggested asking new sleep patients whether they are sleepy or fatigued during the day.

Patients who present only with daytime sleepiness are more likely to have a sleep disorder, according to Dr. Krahn. If the main complaint is fatigue or exhaustion, the differential diagnosis expands to a wide range of psychiatric and medical disorders.

Two key tools, she suggested, are the Epworth Sleepiness Scale and the clinical interview. Patients with obstructive sleep apnea or narcolepsy tend to score high on the Epworth; patients whose main complaint is fatigue score low.

The interview helps the physician tease out factors in daily life that might influence sleep. “If you have someone come to you with sleepiness, ask about their mood,” she said, suggesting simple questions such as, “Are you sad? Are you blue? Are you able to pursue your interests?”

She also recommended asking about mood if patients present with sleepiness in winter. “There is no seasonal hypersomnia,” she said, suggesting they might be suffering from seasonal affective disorder.

Similarly, Dr. Krahn noted that patients with panic disorder can have attacks during the day and at night. If attacks occur only at night, suspect sleep apnea.

People with bipolar and psychotic disorders sometimes seek help from a sleep clinic rather than a psychiatrist, according to Dr. Krahn.

To tease out bipolar disorder, Dr. Krahn suggested asking, “Have you had periods of your life where you have not needed to sleep–where you have not had more than 3 hours of sleep and you still had enough energy to function or even quite a bit of energy?”

“That is a pretty specific scenario for mania,” she said, warning that bipolar patients often resist their diagnosis. “It is more socially acceptable to have insomnia than to have bipolar disorder,” Dr. Krahn explained..

Psychotic disorders are often associated with insomnia, she said. Dr. Krahn also noted that many patients gain weight on the newer atypical antipsychotic drugs, which puts them at increased risk of obstructive sleep apnea. Educating these patients about continuous positive airway pressure therapy can be a challenge, she warned, describing a patient who was afraid of inhaling a poison gas.

SCOTTSDALE, ARIZ. – Untreated sleep-disordered breathing may perpetuate posttraumatic stress disorder over a period of weeks, months, and even years, Dr. Lois E. Krahn proposed at a meeting on sleep medicine sponsored by the American College of Chest Physicians.

“Patients have a lot of sleep complaints. They have trouble falling asleep. They have nightmares, and one very interesting finding of late is they also have a fairly high rate of obstructive sleep apnea,” said Dr. Krahn, chair of the department of psychiatry and psychology at the Mayo Clinic in Scottsdale, Ariz.

In one posttraumatic stress disorder (PTSD) study cited by Dr. Krahn, subjective sleep disturbance was described as “a hallmark of PTSD” in elderly war veterans (Biol. Psychiatry 2000;47:520–5). Even though patients with untreated obstructive sleep apnea and sleep movement disorders were not included in the sample, the investigators reported finding many cases in patients screened for the study.

Dr. Krahn posited that obstructive sleep apnea may predispose some patients to wake in the middle of the night. “So that may be a feature that causes this condition [PTSD] to be perpetuated,” she said.

In an interview at the meeting, she suggested ordering polysomnography when PTSD patients do not improve with therapy. They may continue to relive their trauma at night, she said.

“Their sleep wasn't terrific before this traumatic event. Now they've got nightmares. With the combination, they have a more chronic disorder.”

Many psychiatric disorders overlap with sleep disorders, and can be difficult to distinguish, Dr. Krahn said. She suggested asking new sleep patients whether they are sleepy or fatigued during the day.

Patients who present only with daytime sleepiness are more likely to have a sleep disorder, according to Dr. Krahn. If the main complaint is fatigue or exhaustion, the differential diagnosis expands to a wide range of psychiatric and medical disorders.

Two key tools, she suggested, are the Epworth Sleepiness Scale and the clinical interview. Patients with obstructive sleep apnea or narcolepsy tend to score high on the Epworth; patients whose main complaint is fatigue score low.

The interview helps the physician tease out factors in daily life that might influence sleep. “If you have someone come to you with sleepiness, ask about their mood,” she said, suggesting simple questions such as, “Are you sad? Are you blue? Are you able to pursue your interests?”

She also recommended asking about mood if patients present with sleepiness in winter. “There is no seasonal hypersomnia,” she said, suggesting they might be suffering from seasonal affective disorder.

Similarly, Dr. Krahn noted that patients with panic disorder can have attacks during the day and at night. If attacks occur only at night, suspect sleep apnea.

People with bipolar and psychotic disorders sometimes seek help from a sleep clinic rather than a psychiatrist, according to Dr. Krahn.

To tease out bipolar disorder, Dr. Krahn suggested asking, “Have you had periods of your life where you have not needed to sleep–where you have not had more than 3 hours of sleep and you still had enough energy to function or even quite a bit of energy?”

“That is a pretty specific scenario for mania,” she said, warning that bipolar patients often resist their diagnosis. “It is more socially acceptable to have insomnia than to have bipolar disorder,” Dr. Krahn explained..

Psychotic disorders are often associated with insomnia, she said. Dr. Krahn also noted that many patients gain weight on the newer atypical antipsychotic drugs, which puts them at increased risk of obstructive sleep apnea. Educating these patients about continuous positive airway pressure therapy can be a challenge, she warned, describing a patient who was afraid of inhaling a poison gas.

SCOTTSDALE, ARIZ. – Untreated sleep-disordered breathing may perpetuate posttraumatic stress disorder over a period of weeks, months, and even years, Dr. Lois E. Krahn proposed at a meeting on sleep medicine sponsored by the American College of Chest Physicians.

“Patients have a lot of sleep complaints. They have trouble falling asleep. They have nightmares, and one very interesting finding of late is they also have a fairly high rate of obstructive sleep apnea,” said Dr. Krahn, chair of the department of psychiatry and psychology at the Mayo Clinic in Scottsdale, Ariz.

In one posttraumatic stress disorder (PTSD) study cited by Dr. Krahn, subjective sleep disturbance was described as “a hallmark of PTSD” in elderly war veterans (Biol. Psychiatry 2000;47:520–5). Even though patients with untreated obstructive sleep apnea and sleep movement disorders were not included in the sample, the investigators reported finding many cases in patients screened for the study.

Dr. Krahn posited that obstructive sleep apnea may predispose some patients to wake in the middle of the night. “So that may be a feature that causes this condition [PTSD] to be perpetuated,” she said.

In an interview at the meeting, she suggested ordering polysomnography when PTSD patients do not improve with therapy. They may continue to relive their trauma at night, she said.

“Their sleep wasn't terrific before this traumatic event. Now they've got nightmares. With the combination, they have a more chronic disorder.”

Many psychiatric disorders overlap with sleep disorders, and can be difficult to distinguish, Dr. Krahn said. She suggested asking new sleep patients whether they are sleepy or fatigued during the day.

Patients who present only with daytime sleepiness are more likely to have a sleep disorder, according to Dr. Krahn. If the main complaint is fatigue or exhaustion, the differential diagnosis expands to a wide range of psychiatric and medical disorders.

Two key tools, she suggested, are the Epworth Sleepiness Scale and the clinical interview. Patients with obstructive sleep apnea or narcolepsy tend to score high on the Epworth; patients whose main complaint is fatigue score low.

The interview helps the physician tease out factors in daily life that might influence sleep. “If you have someone come to you with sleepiness, ask about their mood,” she said, suggesting simple questions such as, “Are you sad? Are you blue? Are you able to pursue your interests?”

She also recommended asking about mood if patients present with sleepiness in winter. “There is no seasonal hypersomnia,” she said, suggesting they might be suffering from seasonal affective disorder.

Similarly, Dr. Krahn noted that patients with panic disorder can have attacks during the day and at night. If attacks occur only at night, suspect sleep apnea.

People with bipolar and psychotic disorders sometimes seek help from a sleep clinic rather than a psychiatrist, according to Dr. Krahn.

To tease out bipolar disorder, Dr. Krahn suggested asking, “Have you had periods of your life where you have not needed to sleep–where you have not had more than 3 hours of sleep and you still had enough energy to function or even quite a bit of energy?”

“That is a pretty specific scenario for mania,” she said, warning that bipolar patients often resist their diagnosis. “It is more socially acceptable to have insomnia than to have bipolar disorder,” Dr. Krahn explained..

Psychotic disorders are often associated with insomnia, she said. Dr. Krahn also noted that many patients gain weight on the newer atypical antipsychotic drugs, which puts them at increased risk of obstructive sleep apnea. Educating these patients about continuous positive airway pressure therapy can be a challenge, she warned, describing a patient who was afraid of inhaling a poison gas.

SCOTTSDALE, ARIZ. – Obesity and obstructive sleep apnea are independent risk factors for atrial fibrillation in patients younger than 65 years of age, but not in older patients, according to a retrospective cohort study of 3,542 people who had sleep studies at the Mayo Clinic in Rochester, Minn.

Heart failure was the only independent predictor of new-onset atrial fibrillation for people 65 years of age and older in the study, which followed patients a mean of 4.7 years after an initial polysomnography.

“The ability of sleep apnea to predict the development of atrial fibrillation was dependent on the age of the patient. If they were more than 65, and they were in sinus rhythm when you did the sleep study, they didn't get atrial fibrillation,” Dr. Virend K. Somers, a coinvestigator, said at a meeting on sleep medicine sponsored by the American College of Chest Physicians.

None of the patients had atrial fibrillation before or at the time of the screenings, conducted in 1987–2003, for possible sleep disorders. All told, 133 people developed atrial fibrillation at some point after undergoing polysomnography (J. Am. Coll. Cardiol. 2007;49:565–71).

Obstructive sleep apnea was diagnosed in 2,626 people (74%), and the investigators reported it was a strong predictor (hazard ratio 2.18) of future atrial fibrillation. A total of 4.3% of patients with obstructive sleep apnea but only 2.1% without the disorder were subsequently diagnosed with atrial fibrillation.

An age-stratified analysis showed patients younger than 65 years were more vulnerable to atrial fibrillation, however, and had more risk factors. The most significant was lower oxygen levels at night (hazard ratio 3.29), but age (2.04), male gender (2.66), coronary artery disease (2.66), and body mass index (1.07) also were predictors. In older patients, heart failure had a hazard ratio of 7.68.

Why the older patients were less susceptible to atrial fibrillation is unclear, according to the authors. Dr. Somers, a professor of medicine at the Mayo Clinic, speculated that the older patients probably had undiagnosed apnea for many years.

“If you have sleep apnea and you last to 65–70 years without developing atrial fibrillation, you are going to be okay–you are going to live longer,” he said. “But if you are susceptible to the damage that sleep apnea does to your cardiovascular system, you will develop atrial fibrillation earlier on.”

Dr. Somers is a consultant for Cardiac Concepts and is coinvestigator on a grant from the ResMed Foundation, which funded the study. The present study, for which the lead author is Dr. Apoor Gami, follows earlier research at the Mayo Clinic that showed an association between obstructive sleep apnea and atrial fibrillation.

In one study, Dr. Gami, Dr. Somers, and coinvestigators found obstructive sleep apnea was “strikingly more prevalent” (odds ratio 2.19) in atrial fibrillation patients than in general cardiology patients. About half (49%) of 151 patients who underwent electrocardioversion for atrial fibrillation had obstructive sleep apnea vs. about a third (32%) of 312 patients treated for other heart conditions (Circulation 2004;110:364–7).

In a study of patients who underwent electrocardioversion, Dr. Somers' group found atrial fibrillation was more likely to recur if obstructive sleep apnea was not treated (Circulation 2003;107:2589–94). Within 12 months, 82% of 27 untreated or inadequately treated apnea patients had their apnea recur, vs. 42% of 12 apnea patients treated with continuous positive airway pressure and 53% of the control group.

Dr. Somers noted that risk doubled in the apnea population when the condition went untreated, and in the 25 apnea patients who received no treatment, nocturnal oxygen saturation fell to lower levels in patients who had a recurrence of atrial fibrillation.

Does Sleep Apnea Treatment Prevent Heart Disease?

Despite presenting strong evidence of an association between obstructive sleep apnea and cardiovascular disease, Dr. Somers was careful not to say that treating the sleep disorder would prevent heart disease.

“Beyond lowering blood pressure and perhaps increasing EF [ejection fraction] in people with heart failure, treating sleep apnea has not been proven to prevent any cardiovascular end points,” he said.

“We have no evidence that treating sleep apnea will prevent a cardiac death, a heart attack, a stroke, or anything,” he said. “All we have now are soft end points–blood pressure, [and] heart rate.”

Many markers of heart disease–notably hypertension, elevated levels of C-reactive protein, and systemic inflammation–occur with sleep apnea, according to Dr. Somers. Consequently, he maintained, it makes sense that an untreated apnea could lead to cardiovascular disease.

Moreover, in addition to his work showing a link with atrial fibrillation, he cited studies associating sleep disorders with hypertension, sudden cardiac death, and heart failure. Among these findings, he noted the following:

▸ Apnea can cause hypertension, and hypertension becomes worse if apnea is not treated (N. Engl. J. Med. 2000;342:1378–84).

▸ Obstructive sleep apnea patients were two to three times more likely to have a first-degree relative who died of a heart attack or suddenly of an unexplained cause, according to a review of 500 people by Dr. Somers and his colleagues.

▸ Although 6 a.m.–11 a.m. is the peak time for sudden cardiac deaths in the general population, 46% of the sudden cardiac deaths in people with obstructive sleep apnea occurred between midnight and 6 a.m. (N. Engl. J. Med. 2005;352:1206–14).

About 10% of heart failure patients have obstructive sleep apnea and 40% have central sleep apnea, Dr. Somers added, attributing the data to studies conducted during the 1990s. “Since then,” he said, “patients are substantially fatter, and we think there are more obstructive apneas in heart failure patients than there used to be.”

Although Dr. Somers believes in treating sleep disorders to prevent heart disease, he added that his colleagues in cardiology won't be convinced until cause and effect is proved.

As for randomized controlled trials providing that proof, a major obstacle emerged in a question from the audience at the meeting. Institutional review boards are not likely to approve a trial that allows a sleep disorder to go untreated because the patient is randomized to a control group.

SCOTTSDALE, ARIZ. – Obesity and obstructive sleep apnea are independent risk factors for atrial fibrillation in patients younger than 65 years of age, but not in older patients, according to a retrospective cohort study of 3,542 people who had sleep studies at the Mayo Clinic in Rochester, Minn.

Heart failure was the only independent predictor of new-onset atrial fibrillation for people 65 years of age and older in the study, which followed patients a mean of 4.7 years after an initial polysomnography.

“The ability of sleep apnea to predict the development of atrial fibrillation was dependent on the age of the patient. If they were more than 65, and they were in sinus rhythm when you did the sleep study, they didn't get atrial fibrillation,” Dr. Virend K. Somers, a coinvestigator, said at a meeting on sleep medicine sponsored by the American College of Chest Physicians.

None of the patients had atrial fibrillation before or at the time of the screenings, conducted in 1987–2003, for possible sleep disorders. All told, 133 people developed atrial fibrillation at some point after undergoing polysomnography (J. Am. Coll. Cardiol. 2007;49:565–71).

Obstructive sleep apnea was diagnosed in 2,626 people (74%), and the investigators reported it was a strong predictor (hazard ratio 2.18) of future atrial fibrillation. A total of 4.3% of patients with obstructive sleep apnea but only 2.1% without the disorder were subsequently diagnosed with atrial fibrillation.

An age-stratified analysis showed patients younger than 65 years were more vulnerable to atrial fibrillation, however, and had more risk factors. The most significant was lower oxygen levels at night (hazard ratio 3.29), but age (2.04), male gender (2.66), coronary artery disease (2.66), and body mass index (1.07) also were predictors. In older patients, heart failure had a hazard ratio of 7.68.

Why the older patients were less susceptible to atrial fibrillation is unclear, according to the authors. Dr. Somers, a professor of medicine at the Mayo Clinic, speculated that the older patients probably had undiagnosed apnea for many years.

“If you have sleep apnea and you last to 65–70 years without developing atrial fibrillation, you are going to be okay–you are going to live longer,” he said. “But if you are susceptible to the damage that sleep apnea does to your cardiovascular system, you will develop atrial fibrillation earlier on.”

Dr. Somers is a consultant for Cardiac Concepts and is coinvestigator on a grant from the ResMed Foundation, which funded the study. The present study, for which the lead author is Dr. Apoor Gami, follows earlier research at the Mayo Clinic that showed an association between obstructive sleep apnea and atrial fibrillation.

In one study, Dr. Gami, Dr. Somers, and coinvestigators found obstructive sleep apnea was “strikingly more prevalent” (odds ratio 2.19) in atrial fibrillation patients than in general cardiology patients. About half (49%) of 151 patients who underwent electrocardioversion for atrial fibrillation had obstructive sleep apnea vs. about a third (32%) of 312 patients treated for other heart conditions (Circulation 2004;110:364–7).

In a study of patients who underwent electrocardioversion, Dr. Somers' group found atrial fibrillation was more likely to recur if obstructive sleep apnea was not treated (Circulation 2003;107:2589–94). Within 12 months, 82% of 27 untreated or inadequately treated apnea patients had their apnea recur, vs. 42% of 12 apnea patients treated with continuous positive airway pressure and 53% of the control group.

Dr. Somers noted that risk doubled in the apnea population when the condition went untreated, and in the 25 apnea patients who received no treatment, nocturnal oxygen saturation fell to lower levels in patients who had a recurrence of atrial fibrillation.

Does Sleep Apnea Treatment Prevent Heart Disease?

Despite presenting strong evidence of an association between obstructive sleep apnea and cardiovascular disease, Dr. Somers was careful not to say that treating the sleep disorder would prevent heart disease.

“Beyond lowering blood pressure and perhaps increasing EF [ejection fraction] in people with heart failure, treating sleep apnea has not been proven to prevent any cardiovascular end points,” he said.

“We have no evidence that treating sleep apnea will prevent a cardiac death, a heart attack, a stroke, or anything,” he said. “All we have now are soft end points–blood pressure, [and] heart rate.”

Many markers of heart disease–notably hypertension, elevated levels of C-reactive protein, and systemic inflammation–occur with sleep apnea, according to Dr. Somers. Consequently, he maintained, it makes sense that an untreated apnea could lead to cardiovascular disease.

Moreover, in addition to his work showing a link with atrial fibrillation, he cited studies associating sleep disorders with hypertension, sudden cardiac death, and heart failure. Among these findings, he noted the following:

▸ Apnea can cause hypertension, and hypertension becomes worse if apnea is not treated (N. Engl. J. Med. 2000;342:1378–84).

▸ Obstructive sleep apnea patients were two to three times more likely to have a first-degree relative who died of a heart attack or suddenly of an unexplained cause, according to a review of 500 people by Dr. Somers and his colleagues.

▸ Although 6 a.m.–11 a.m. is the peak time for sudden cardiac deaths in the general population, 46% of the sudden cardiac deaths in people with obstructive sleep apnea occurred between midnight and 6 a.m. (N. Engl. J. Med. 2005;352:1206–14).

About 10% of heart failure patients have obstructive sleep apnea and 40% have central sleep apnea, Dr. Somers added, attributing the data to studies conducted during the 1990s. “Since then,” he said, “patients are substantially fatter, and we think there are more obstructive apneas in heart failure patients than there used to be.”

Although Dr. Somers believes in treating sleep disorders to prevent heart disease, he added that his colleagues in cardiology won't be convinced until cause and effect is proved.

As for randomized controlled trials providing that proof, a major obstacle emerged in a question from the audience at the meeting. Institutional review boards are not likely to approve a trial that allows a sleep disorder to go untreated because the patient is randomized to a control group.

SCOTTSDALE, ARIZ. – Obesity and obstructive sleep apnea are independent risk factors for atrial fibrillation in patients younger than 65 years of age, but not in older patients, according to a retrospective cohort study of 3,542 people who had sleep studies at the Mayo Clinic in Rochester, Minn.

Heart failure was the only independent predictor of new-onset atrial fibrillation for people 65 years of age and older in the study, which followed patients a mean of 4.7 years after an initial polysomnography.

“The ability of sleep apnea to predict the development of atrial fibrillation was dependent on the age of the patient. If they were more than 65, and they were in sinus rhythm when you did the sleep study, they didn't get atrial fibrillation,” Dr. Virend K. Somers, a coinvestigator, said at a meeting on sleep medicine sponsored by the American College of Chest Physicians.

None of the patients had atrial fibrillation before or at the time of the screenings, conducted in 1987–2003, for possible sleep disorders. All told, 133 people developed atrial fibrillation at some point after undergoing polysomnography (J. Am. Coll. Cardiol. 2007;49:565–71).

Obstructive sleep apnea was diagnosed in 2,626 people (74%), and the investigators reported it was a strong predictor (hazard ratio 2.18) of future atrial fibrillation. A total of 4.3% of patients with obstructive sleep apnea but only 2.1% without the disorder were subsequently diagnosed with atrial fibrillation.

An age-stratified analysis showed patients younger than 65 years were more vulnerable to atrial fibrillation, however, and had more risk factors. The most significant was lower oxygen levels at night (hazard ratio 3.29), but age (2.04), male gender (2.66), coronary artery disease (2.66), and body mass index (1.07) also were predictors. In older patients, heart failure had a hazard ratio of 7.68.

Why the older patients were less susceptible to atrial fibrillation is unclear, according to the authors. Dr. Somers, a professor of medicine at the Mayo Clinic, speculated that the older patients probably had undiagnosed apnea for many years.

“If you have sleep apnea and you last to 65–70 years without developing atrial fibrillation, you are going to be okay–you are going to live longer,” he said. “But if you are susceptible to the damage that sleep apnea does to your cardiovascular system, you will develop atrial fibrillation earlier on.”

Dr. Somers is a consultant for Cardiac Concepts and is coinvestigator on a grant from the ResMed Foundation, which funded the study. The present study, for which the lead author is Dr. Apoor Gami, follows earlier research at the Mayo Clinic that showed an association between obstructive sleep apnea and atrial fibrillation.

In one study, Dr. Gami, Dr. Somers, and coinvestigators found obstructive sleep apnea was “strikingly more prevalent” (odds ratio 2.19) in atrial fibrillation patients than in general cardiology patients. About half (49%) of 151 patients who underwent electrocardioversion for atrial fibrillation had obstructive sleep apnea vs. about a third (32%) of 312 patients treated for other heart conditions (Circulation 2004;110:364–7).

In a study of patients who underwent electrocardioversion, Dr. Somers' group found atrial fibrillation was more likely to recur if obstructive sleep apnea was not treated (Circulation 2003;107:2589–94). Within 12 months, 82% of 27 untreated or inadequately treated apnea patients had their apnea recur, vs. 42% of 12 apnea patients treated with continuous positive airway pressure and 53% of the control group.

Dr. Somers noted that risk doubled in the apnea population when the condition went untreated, and in the 25 apnea patients who received no treatment, nocturnal oxygen saturation fell to lower levels in patients who had a recurrence of atrial fibrillation.

Does Sleep Apnea Treatment Prevent Heart Disease?

Despite presenting strong evidence of an association between obstructive sleep apnea and cardiovascular disease, Dr. Somers was careful not to say that treating the sleep disorder would prevent heart disease.

“Beyond lowering blood pressure and perhaps increasing EF [ejection fraction] in people with heart failure, treating sleep apnea has not been proven to prevent any cardiovascular end points,” he said.

“We have no evidence that treating sleep apnea will prevent a cardiac death, a heart attack, a stroke, or anything,” he said. “All we have now are soft end points–blood pressure, [and] heart rate.”

Many markers of heart disease–notably hypertension, elevated levels of C-reactive protein, and systemic inflammation–occur with sleep apnea, according to Dr. Somers. Consequently, he maintained, it makes sense that an untreated apnea could lead to cardiovascular disease.

Moreover, in addition to his work showing a link with atrial fibrillation, he cited studies associating sleep disorders with hypertension, sudden cardiac death, and heart failure. Among these findings, he noted the following:

▸ Apnea can cause hypertension, and hypertension becomes worse if apnea is not treated (N. Engl. J. Med. 2000;342:1378–84).

▸ Obstructive sleep apnea patients were two to three times more likely to have a first-degree relative who died of a heart attack or suddenly of an unexplained cause, according to a review of 500 people by Dr. Somers and his colleagues.

▸ Although 6 a.m.–11 a.m. is the peak time for sudden cardiac deaths in the general population, 46% of the sudden cardiac deaths in people with obstructive sleep apnea occurred between midnight and 6 a.m. (N. Engl. J. Med. 2005;352:1206–14).

About 10% of heart failure patients have obstructive sleep apnea and 40% have central sleep apnea, Dr. Somers added, attributing the data to studies conducted during the 1990s. “Since then,” he said, “patients are substantially fatter, and we think there are more obstructive apneas in heart failure patients than there used to be.”

Although Dr. Somers believes in treating sleep disorders to prevent heart disease, he added that his colleagues in cardiology won't be convinced until cause and effect is proved.

As for randomized controlled trials providing that proof, a major obstacle emerged in a question from the audience at the meeting. Institutional review boards are not likely to approve a trial that allows a sleep disorder to go untreated because the patient is randomized to a control group.

TUCSON, ARIZ. – A psychiatric intervention conducted by specially trained oncology nurses significantly reduced depression for cancer patients enrolled in a clinical trial presented at the annual meeting of the Academy of Psychosomatic Medicine.

Dr. Michael Sharpe reported that patients randomized to problem-solving therapy reached lower mean scores on the Symptom Checklist-20 (SCL-20) and were more likely to achieve a 50% reduction in clinical symptoms, compared with patients given optimized usual care. The randomized group also had twice the rate of complete remission.

“That tells us we can make a difference in depression in cancer patients with this kind of model,” said Dr. Sharpe, a professor of psychological medicine and symptoms research at the University of Edinburgh where the 200-patient trial was conducted.

Depression is common but poorly managed in cancer patients, according to Dr. Sharpe. It is associated with nonadherence to cancer treatment, increased medical costs, and suicide, he said. Yet it is often not detected or, if recognized, discounted as a normal response to having cancer.

“We still have the view of some primary care doctors that if you've got cancer, you've got depression–that it's normal,” he said.

Therefore, the investigators recruited oncology nurses in an attempt to integrate depression care into cancer care. A psychiatrist supervised the nurses, who coordinated drug treatment, delivered psychological treatment, and monitored patient progress.

As described by Dr. Sharpe, the psychological component was a problem-solving therapy in which the patients would list cancer and noncancer concerns. They would choose one concern to focus on with the nurse, identifying what a solution would look like and brainstorming on how to achieve it. Next, they would choose and try out a strategy.

One nurse worked full time in a pilot study testing the model. A full day of depression and cancer care turned out to be “too much,” Dr. Sharpe said. Therefore, nurses worked half-time in the randomized trial.

Selection and training of nurses without a psychiatric background was also a challenge. “We had problems. We recruited people who could not do it,” Dr. Sharpe said. “We had a core of three nurses who did treatment. One could not do it and had to leave.”

The trial population was drawn from a pool of patients who underwent computerized screening for depression before consultation with their oncologists. Depression diagnoses were based on subsequent structured clinical interviews of patients who scored above 14 on the Hospital Anxiety and Depression Scale.

Two hundred patients were randomized: 99 to optimized usual care and 101 to optimized usual care plus the Symptom Management Research Trials (SMaRT) intervention by the oncology nurses. Dr. Sharpe noted that primary care physicians were notified of all depression diagnoses and could prescribe antidepressants to patients in both groups.

Breast cancer was the most common malignancy, accounting for more than 40% of the patients enrolled. The study population was generally female with an average age of 56 years. About two-thirds were disease free, and more than 80% were visiting oncologists for follow-up care after completing cancer therapy.

Data analysis was done at 3 months' follow-up for all 99 usual-care patients and 97 who received the added intervention (4 patients, including 2 who died, were excluded because of incomplete data).

The intervention group had lower mean SCL-20 scores, compared with the usual-care group: 1.25 vs. 1.54. More than half (53%) of the intervention group achieved a 50% clinical reduction of depression symptoms compared with about a third (34%) of the control group. Twice as many had a complete remission on the SCL-20: 29% vs. 14%. Remission rates were also significantly higher based on structured clinical interviews: 67% vs. 45%, respectively.

Although he did not report statistics in detail, Dr. Sharpe said the effects “were maintained and possibly increased” at 6 months. The next step, he said, will be to duplicate the study with more nurses and patients at multiple centers.

Depression is poorly managed in cancer patients. It is associated with nonadherence to cancer treatment. DR. SHARPE

ELSEVIER GLOBAL MEDICAL NEWS

TUCSON, ARIZ. – A psychiatric intervention conducted by specially trained oncology nurses significantly reduced depression for cancer patients enrolled in a clinical trial presented at the annual meeting of the Academy of Psychosomatic Medicine.

Dr. Michael Sharpe reported that patients randomized to problem-solving therapy reached lower mean scores on the Symptom Checklist-20 (SCL-20) and were more likely to achieve a 50% reduction in clinical symptoms, compared with patients given optimized usual care. The randomized group also had twice the rate of complete remission.

“That tells us we can make a difference in depression in cancer patients with this kind of model,” said Dr. Sharpe, a professor of psychological medicine and symptoms research at the University of Edinburgh where the 200-patient trial was conducted.

Depression is common but poorly managed in cancer patients, according to Dr. Sharpe. It is associated with nonadherence to cancer treatment, increased medical costs, and suicide, he said. Yet it is often not detected or, if recognized, discounted as a normal response to having cancer.

“We still have the view of some primary care doctors that if you've got cancer, you've got depression–that it's normal,” he said.

Therefore, the investigators recruited oncology nurses in an attempt to integrate depression care into cancer care. A psychiatrist supervised the nurses, who coordinated drug treatment, delivered psychological treatment, and monitored patient progress.

As described by Dr. Sharpe, the psychological component was a problem-solving therapy in which the patients would list cancer and noncancer concerns. They would choose one concern to focus on with the nurse, identifying what a solution would look like and brainstorming on how to achieve it. Next, they would choose and try out a strategy.

One nurse worked full time in a pilot study testing the model. A full day of depression and cancer care turned out to be “too much,” Dr. Sharpe said. Therefore, nurses worked half-time in the randomized trial.

Selection and training of nurses without a psychiatric background was also a challenge. “We had problems. We recruited people who could not do it,” Dr. Sharpe said. “We had a core of three nurses who did treatment. One could not do it and had to leave.”

The trial population was drawn from a pool of patients who underwent computerized screening for depression before consultation with their oncologists. Depression diagnoses were based on subsequent structured clinical interviews of patients who scored above 14 on the Hospital Anxiety and Depression Scale.

Two hundred patients were randomized: 99 to optimized usual care and 101 to optimized usual care plus the Symptom Management Research Trials (SMaRT) intervention by the oncology nurses. Dr. Sharpe noted that primary care physicians were notified of all depression diagnoses and could prescribe antidepressants to patients in both groups.

Breast cancer was the most common malignancy, accounting for more than 40% of the patients enrolled. The study population was generally female with an average age of 56 years. About two-thirds were disease free, and more than 80% were visiting oncologists for follow-up care after completing cancer therapy.

Data analysis was done at 3 months' follow-up for all 99 usual-care patients and 97 who received the added intervention (4 patients, including 2 who died, were excluded because of incomplete data).

The intervention group had lower mean SCL-20 scores, compared with the usual-care group: 1.25 vs. 1.54. More than half (53%) of the intervention group achieved a 50% clinical reduction of depression symptoms compared with about a third (34%) of the control group. Twice as many had a complete remission on the SCL-20: 29% vs. 14%. Remission rates were also significantly higher based on structured clinical interviews: 67% vs. 45%, respectively.

Although he did not report statistics in detail, Dr. Sharpe said the effects “were maintained and possibly increased” at 6 months. The next step, he said, will be to duplicate the study with more nurses and patients at multiple centers.

Depression is poorly managed in cancer patients. It is associated with nonadherence to cancer treatment. DR. SHARPE

ELSEVIER GLOBAL MEDICAL NEWS

TUCSON, ARIZ. – A psychiatric intervention conducted by specially trained oncology nurses significantly reduced depression for cancer patients enrolled in a clinical trial presented at the annual meeting of the Academy of Psychosomatic Medicine.

Dr. Michael Sharpe reported that patients randomized to problem-solving therapy reached lower mean scores on the Symptom Checklist-20 (SCL-20) and were more likely to achieve a 50% reduction in clinical symptoms, compared with patients given optimized usual care. The randomized group also had twice the rate of complete remission.

“That tells us we can make a difference in depression in cancer patients with this kind of model,” said Dr. Sharpe, a professor of psychological medicine and symptoms research at the University of Edinburgh where the 200-patient trial was conducted.

Depression is common but poorly managed in cancer patients, according to Dr. Sharpe. It is associated with nonadherence to cancer treatment, increased medical costs, and suicide, he said. Yet it is often not detected or, if recognized, discounted as a normal response to having cancer.

“We still have the view of some primary care doctors that if you've got cancer, you've got depression–that it's normal,” he said.

Therefore, the investigators recruited oncology nurses in an attempt to integrate depression care into cancer care. A psychiatrist supervised the nurses, who coordinated drug treatment, delivered psychological treatment, and monitored patient progress.

As described by Dr. Sharpe, the psychological component was a problem-solving therapy in which the patients would list cancer and noncancer concerns. They would choose one concern to focus on with the nurse, identifying what a solution would look like and brainstorming on how to achieve it. Next, they would choose and try out a strategy.

One nurse worked full time in a pilot study testing the model. A full day of depression and cancer care turned out to be “too much,” Dr. Sharpe said. Therefore, nurses worked half-time in the randomized trial.

Selection and training of nurses without a psychiatric background was also a challenge. “We had problems. We recruited people who could not do it,” Dr. Sharpe said. “We had a core of three nurses who did treatment. One could not do it and had to leave.”

The trial population was drawn from a pool of patients who underwent computerized screening for depression before consultation with their oncologists. Depression diagnoses were based on subsequent structured clinical interviews of patients who scored above 14 on the Hospital Anxiety and Depression Scale.

Two hundred patients were randomized: 99 to optimized usual care and 101 to optimized usual care plus the Symptom Management Research Trials (SMaRT) intervention by the oncology nurses. Dr. Sharpe noted that primary care physicians were notified of all depression diagnoses and could prescribe antidepressants to patients in both groups.

Breast cancer was the most common malignancy, accounting for more than 40% of the patients enrolled. The study population was generally female with an average age of 56 years. About two-thirds were disease free, and more than 80% were visiting oncologists for follow-up care after completing cancer therapy.

Data analysis was done at 3 months' follow-up for all 99 usual-care patients and 97 who received the added intervention (4 patients, including 2 who died, were excluded because of incomplete data).

The intervention group had lower mean SCL-20 scores, compared with the usual-care group: 1.25 vs. 1.54. More than half (53%) of the intervention group achieved a 50% clinical reduction of depression symptoms compared with about a third (34%) of the control group. Twice as many had a complete remission on the SCL-20: 29% vs. 14%. Remission rates were also significantly higher based on structured clinical interviews: 67% vs. 45%, respectively.

Although he did not report statistics in detail, Dr. Sharpe said the effects “were maintained and possibly increased” at 6 months. The next step, he said, will be to duplicate the study with more nurses and patients at multiple centers.

Depression is poorly managed in cancer patients. It is associated with nonadherence to cancer treatment. DR. SHARPE

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO – Treatment outcomes for obese patients with binge-eating disorder differ by disease severity and negative affect, a large study of patients with this disorder shows.

“We are trying to identify a particular subset of the population [that responds to a particular treatment],” Denise E. Wilfley, Ph.D., director of the Weight Management and Eating Disorders Program at Washington University in St. Louis, said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

The study evaluated three treatments for binge-eating disorder (BED): interpersonal therapy (IPT), behavioral weight loss (BWL), and guided self-help (GSH). “This is the first study to compare three different treatments for binge-eating disorder,” Dr. Wilfley said. Participants were also stratified by high versus low negative affect and by severity of bingeing.

According to the DSM-IV, people with BED eat a large amount of food with loss of control on at least 2 days a week for at least 6 months; they do not regularly engage in compensatory behaviors.

Dr. Wilfley said people with this disorder tend to have low self-esteem and very high rates of health care use, traits similar to people with anorexia and bulimia nervosa. But unlike people with those conditions, people with BED are more likely to be male and less likely to be white. Given the large amount of food they consume, people with BED are associated with overweight or obesity. “They're not just obese individuals,” said Dr. Wilfley, also professor of psychiatry at the university. “They are obese individuals with an eating disorder.”

The trial involved 205 participants and was conducted at three sites: Stanford (Calif.) University (data coordinating center), Washington University (clinical site), and Rutgers University (clinical site) in Piscataway, N.J. Participants were at least 18 years old, met the DSM-IV criteria for BED, and had a body mass index (BMI) between 27 and 45 kg/m

In terms of race, 82% were white, 13% were black, 4% were Hispanic, and 1% was Native American. Slightly more than half of the participants were college educated, and the average BMI among the participants was 36.4.

The participants were randomized to one of the three treatments. Participants in both the interpersonal therapy and the behavioral weight loss groups had 20 60-minute therapy sessions over a 24-week period. Those in the guided self-help group used bibliotherapy. They were asked to read “Overcoming Binge Eating,” by Dr. Christopher G. Fairburn (New York: the Guilford Press, 1995), a book aimed at teaching behavior change. This group also had one 55-minute and nine 25-minute therapy sessions over 24 weeks. The IPT group included 75 patients, the BWL group had 64 patients, and the GSH group had 66 patients. There were no significant differences in patient characteristics among the three groups.

The researchers used the Beck Depression Inventory to stratify the participants according to high negative affect (HNA) and low negative affect (LNA). Although they were apt to stay with interpersonal therapy, patients with HNA were significantly more likely to drop out of the behavioral weight loss treatment group than those with LNA. Those with LNA were much more likely to drop out of guided self-help.

Overall, treatment retention rates were significantly better among those treated with interpersonal therapy (93%) than with behavioral weight loss (72%) and guided self-help (70%). Patients in BWL had a significantly better short-term weight loss than those in the other two groups, but this advantage disappeared by the 1-year follow-up.

The primary outcome measures in the trial were binge frequency and remission rates, defined as no binge eating in 28 days. The results showed that all three treatments had similar outcomes in treating binge eating disorder, associated eating disorders, and general psychopathology after 24 weeks.

The researchers followed the patients for 24 months and have analyzed the results for the first 12 months. The posttreatment data showed that interpersonal therapy was superior to the two other treatment options in those patients with severe binge eating. In addition, HNA participants were more likely to do poorly on binge eating outcomes when the behavioral weight loss approach was used, compared with the IPT or guided self-help approach, over the course of the 1-year follow-up period.

CHICAGO – Treatment outcomes for obese patients with binge-eating disorder differ by disease severity and negative affect, a large study of patients with this disorder shows.

“We are trying to identify a particular subset of the population [that responds to a particular treatment],” Denise E. Wilfley, Ph.D., director of the Weight Management and Eating Disorders Program at Washington University in St. Louis, said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

The study evaluated three treatments for binge-eating disorder (BED): interpersonal therapy (IPT), behavioral weight loss (BWL), and guided self-help (GSH). “This is the first study to compare three different treatments for binge-eating disorder,” Dr. Wilfley said. Participants were also stratified by high versus low negative affect and by severity of bingeing.

According to the DSM-IV, people with BED eat a large amount of food with loss of control on at least 2 days a week for at least 6 months; they do not regularly engage in compensatory behaviors.

Dr. Wilfley said people with this disorder tend to have low self-esteem and very high rates of health care use, traits similar to people with anorexia and bulimia nervosa. But unlike people with those conditions, people with BED are more likely to be male and less likely to be white. Given the large amount of food they consume, people with BED are associated with overweight or obesity. “They're not just obese individuals,” said Dr. Wilfley, also professor of psychiatry at the university. “They are obese individuals with an eating disorder.”

The trial involved 205 participants and was conducted at three sites: Stanford (Calif.) University (data coordinating center), Washington University (clinical site), and Rutgers University (clinical site) in Piscataway, N.J. Participants were at least 18 years old, met the DSM-IV criteria for BED, and had a body mass index (BMI) between 27 and 45 kg/m

In terms of race, 82% were white, 13% were black, 4% were Hispanic, and 1% was Native American. Slightly more than half of the participants were college educated, and the average BMI among the participants was 36.4.

The participants were randomized to one of the three treatments. Participants in both the interpersonal therapy and the behavioral weight loss groups had 20 60-minute therapy sessions over a 24-week period. Those in the guided self-help group used bibliotherapy. They were asked to read “Overcoming Binge Eating,” by Dr. Christopher G. Fairburn (New York: the Guilford Press, 1995), a book aimed at teaching behavior change. This group also had one 55-minute and nine 25-minute therapy sessions over 24 weeks. The IPT group included 75 patients, the BWL group had 64 patients, and the GSH group had 66 patients. There were no significant differences in patient characteristics among the three groups.

The researchers used the Beck Depression Inventory to stratify the participants according to high negative affect (HNA) and low negative affect (LNA). Although they were apt to stay with interpersonal therapy, patients with HNA were significantly more likely to drop out of the behavioral weight loss treatment group than those with LNA. Those with LNA were much more likely to drop out of guided self-help.

Overall, treatment retention rates were significantly better among those treated with interpersonal therapy (93%) than with behavioral weight loss (72%) and guided self-help (70%). Patients in BWL had a significantly better short-term weight loss than those in the other two groups, but this advantage disappeared by the 1-year follow-up.

The primary outcome measures in the trial were binge frequency and remission rates, defined as no binge eating in 28 days. The results showed that all three treatments had similar outcomes in treating binge eating disorder, associated eating disorders, and general psychopathology after 24 weeks.

The researchers followed the patients for 24 months and have analyzed the results for the first 12 months. The posttreatment data showed that interpersonal therapy was superior to the two other treatment options in those patients with severe binge eating. In addition, HNA participants were more likely to do poorly on binge eating outcomes when the behavioral weight loss approach was used, compared with the IPT or guided self-help approach, over the course of the 1-year follow-up period.

CHICAGO – Treatment outcomes for obese patients with binge-eating disorder differ by disease severity and negative affect, a large study of patients with this disorder shows.

“We are trying to identify a particular subset of the population [that responds to a particular treatment],” Denise E. Wilfley, Ph.D., director of the Weight Management and Eating Disorders Program at Washington University in St. Louis, said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

The study evaluated three treatments for binge-eating disorder (BED): interpersonal therapy (IPT), behavioral weight loss (BWL), and guided self-help (GSH). “This is the first study to compare three different treatments for binge-eating disorder,” Dr. Wilfley said. Participants were also stratified by high versus low negative affect and by severity of bingeing.

According to the DSM-IV, people with BED eat a large amount of food with loss of control on at least 2 days a week for at least 6 months; they do not regularly engage in compensatory behaviors.

Dr. Wilfley said people with this disorder tend to have low self-esteem and very high rates of health care use, traits similar to people with anorexia and bulimia nervosa. But unlike people with those conditions, people with BED are more likely to be male and less likely to be white. Given the large amount of food they consume, people with BED are associated with overweight or obesity. “They're not just obese individuals,” said Dr. Wilfley, also professor of psychiatry at the university. “They are obese individuals with an eating disorder.”

The trial involved 205 participants and was conducted at three sites: Stanford (Calif.) University (data coordinating center), Washington University (clinical site), and Rutgers University (clinical site) in Piscataway, N.J. Participants were at least 18 years old, met the DSM-IV criteria for BED, and had a body mass index (BMI) between 27 and 45 kg/m

In terms of race, 82% were white, 13% were black, 4% were Hispanic, and 1% was Native American. Slightly more than half of the participants were college educated, and the average BMI among the participants was 36.4.

The participants were randomized to one of the three treatments. Participants in both the interpersonal therapy and the behavioral weight loss groups had 20 60-minute therapy sessions over a 24-week period. Those in the guided self-help group used bibliotherapy. They were asked to read “Overcoming Binge Eating,” by Dr. Christopher G. Fairburn (New York: the Guilford Press, 1995), a book aimed at teaching behavior change. This group also had one 55-minute and nine 25-minute therapy sessions over 24 weeks. The IPT group included 75 patients, the BWL group had 64 patients, and the GSH group had 66 patients. There were no significant differences in patient characteristics among the three groups.

The researchers used the Beck Depression Inventory to stratify the participants according to high negative affect (HNA) and low negative affect (LNA). Although they were apt to stay with interpersonal therapy, patients with HNA were significantly more likely to drop out of the behavioral weight loss treatment group than those with LNA. Those with LNA were much more likely to drop out of guided self-help.

Overall, treatment retention rates were significantly better among those treated with interpersonal therapy (93%) than with behavioral weight loss (72%) and guided self-help (70%). Patients in BWL had a significantly better short-term weight loss than those in the other two groups, but this advantage disappeared by the 1-year follow-up.

The primary outcome measures in the trial were binge frequency and remission rates, defined as no binge eating in 28 days. The results showed that all three treatments had similar outcomes in treating binge eating disorder, associated eating disorders, and general psychopathology after 24 weeks.

The researchers followed the patients for 24 months and have analyzed the results for the first 12 months. The posttreatment data showed that interpersonal therapy was superior to the two other treatment options in those patients with severe binge eating. In addition, HNA participants were more likely to do poorly on binge eating outcomes when the behavioral weight loss approach was used, compared with the IPT or guided self-help approach, over the course of the 1-year follow-up period.

CHICAGO – An investigational gabapentin prodrug may be an effective therapy for symptoms and sleep problems associated with restless legs syndrome, Dr. Arthur S. Walters reported at the annual meeting of the American Neurological Association.

The active compound gabapentin has already been shown to improve the sensory and motor symptoms of restless legs syndrome (RLS) and decrease periodic leg movements during sleep, but the drug is approved only for treating epilepsy and postherpetic neuralgia, according to Dr. Walters of the Seton Hall University School of Graduate Medical Education, Edison, N.J.

The gabapentin prodrug XP13512 has several potential advantages over standard gabapentin for treating RLS: The agent has linear pharmacokinetics, doesn't reach a saturation point, and is formulated for sustained release. The capacity for once-daily dosing differentiates gabapentin prodrug XP13512 from the active compound gabapentin (Neurontin), which cannot be manufactured in a sustained-release delivery and must be taken three to four times per day, Dr. Walters discussed on his poster at the meeting.

XenoPort Inc., the drug's manufacturer, has sponsored two phase II, randomized, double-blind trials. One of these trials was a crossover study with 38 patients testing 1,800 mg XP13512 against placebo. The other trial compared XP13512 at 600 mg and 1,200 mg and placebo in 95 patients without any crossover. In both studies, patients had RLS symptoms at least 4 nights during a 7-day baseline period and had a score of at least 15 (out of a possible 40) on the International RLS Study Group rating scale (IRLS). Most patients were white, and mean age was about 50 years.

Compared with patients given placebo, patients treated with the gabapentin prodrug had significantly greater improvement (decreases) in IRLS scores at doses of 1,800 mg (20.4–8.4 vs. 20.4–18.5) and 1,200 mg (22.4–6.3 vs. 22.4–13.5) at the end of the 2-week trial. The patients who received XP13512 at 1,200 mg also had significantly greater improvement than those who received 600 mg. Clinical global impressions of change from both patients and investigators followed the same trend and were significantly in favor of patients who received XP13512, reported Dr. Walters, who received compensation for consulting with XenoPort.

Polysomnographic assessments in the crossover study found that patients had significantly more total sleep time (25 minutes) while receiving the gabapentin prodrug than with placebo. In both studies, patients who received XP13512 had significantly fewer awakenings and spent less time awake per night because of RLS symptoms.

More than 30% of patients who received either 1,200 mg or 1,800 mg of XP13512 experienced somnolence. Dizziness also occurred in 28% of patients at 1,800 mg and in 18% at 1,200 mg. In most cases, the events were transient and mild. Other adverse events occurred at much lower rates, and none were serious.

CHICAGO – An investigational gabapentin prodrug may be an effective therapy for symptoms and sleep problems associated with restless legs syndrome, Dr. Arthur S. Walters reported at the annual meeting of the American Neurological Association.

The active compound gabapentin has already been shown to improve the sensory and motor symptoms of restless legs syndrome (RLS) and decrease periodic leg movements during sleep, but the drug is approved only for treating epilepsy and postherpetic neuralgia, according to Dr. Walters of the Seton Hall University School of Graduate Medical Education, Edison, N.J.

The gabapentin prodrug XP13512 has several potential advantages over standard gabapentin for treating RLS: The agent has linear pharmacokinetics, doesn't reach a saturation point, and is formulated for sustained release. The capacity for once-daily dosing differentiates gabapentin prodrug XP13512 from the active compound gabapentin (Neurontin), which cannot be manufactured in a sustained-release delivery and must be taken three to four times per day, Dr. Walters discussed on his poster at the meeting.

XenoPort Inc., the drug's manufacturer, has sponsored two phase II, randomized, double-blind trials. One of these trials was a crossover study with 38 patients testing 1,800 mg XP13512 against placebo. The other trial compared XP13512 at 600 mg and 1,200 mg and placebo in 95 patients without any crossover. In both studies, patients had RLS symptoms at least 4 nights during a 7-day baseline period and had a score of at least 15 (out of a possible 40) on the International RLS Study Group rating scale (IRLS). Most patients were white, and mean age was about 50 years.

Compared with patients given placebo, patients treated with the gabapentin prodrug had significantly greater improvement (decreases) in IRLS scores at doses of 1,800 mg (20.4–8.4 vs. 20.4–18.5) and 1,200 mg (22.4–6.3 vs. 22.4–13.5) at the end of the 2-week trial. The patients who received XP13512 at 1,200 mg also had significantly greater improvement than those who received 600 mg. Clinical global impressions of change from both patients and investigators followed the same trend and were significantly in favor of patients who received XP13512, reported Dr. Walters, who received compensation for consulting with XenoPort.

Polysomnographic assessments in the crossover study found that patients had significantly more total sleep time (25 minutes) while receiving the gabapentin prodrug than with placebo. In both studies, patients who received XP13512 had significantly fewer awakenings and spent less time awake per night because of RLS symptoms.

More than 30% of patients who received either 1,200 mg or 1,800 mg of XP13512 experienced somnolence. Dizziness also occurred in 28% of patients at 1,800 mg and in 18% at 1,200 mg. In most cases, the events were transient and mild. Other adverse events occurred at much lower rates, and none were serious.

CHICAGO – An investigational gabapentin prodrug may be an effective therapy for symptoms and sleep problems associated with restless legs syndrome, Dr. Arthur S. Walters reported at the annual meeting of the American Neurological Association.

The active compound gabapentin has already been shown to improve the sensory and motor symptoms of restless legs syndrome (RLS) and decrease periodic leg movements during sleep, but the drug is approved only for treating epilepsy and postherpetic neuralgia, according to Dr. Walters of the Seton Hall University School of Graduate Medical Education, Edison, N.J.

The gabapentin prodrug XP13512 has several potential advantages over standard gabapentin for treating RLS: The agent has linear pharmacokinetics, doesn't reach a saturation point, and is formulated for sustained release. The capacity for once-daily dosing differentiates gabapentin prodrug XP13512 from the active compound gabapentin (Neurontin), which cannot be manufactured in a sustained-release delivery and must be taken three to four times per day, Dr. Walters discussed on his poster at the meeting.

XenoPort Inc., the drug's manufacturer, has sponsored two phase II, randomized, double-blind trials. One of these trials was a crossover study with 38 patients testing 1,800 mg XP13512 against placebo. The other trial compared XP13512 at 600 mg and 1,200 mg and placebo in 95 patients without any crossover. In both studies, patients had RLS symptoms at least 4 nights during a 7-day baseline period and had a score of at least 15 (out of a possible 40) on the International RLS Study Group rating scale (IRLS). Most patients were white, and mean age was about 50 years.

Compared with patients given placebo, patients treated with the gabapentin prodrug had significantly greater improvement (decreases) in IRLS scores at doses of 1,800 mg (20.4–8.4 vs. 20.4–18.5) and 1,200 mg (22.4–6.3 vs. 22.4–13.5) at the end of the 2-week trial. The patients who received XP13512 at 1,200 mg also had significantly greater improvement than those who received 600 mg. Clinical global impressions of change from both patients and investigators followed the same trend and were significantly in favor of patients who received XP13512, reported Dr. Walters, who received compensation for consulting with XenoPort.

Polysomnographic assessments in the crossover study found that patients had significantly more total sleep time (25 minutes) while receiving the gabapentin prodrug than with placebo. In both studies, patients who received XP13512 had significantly fewer awakenings and spent less time awake per night because of RLS symptoms.

More than 30% of patients who received either 1,200 mg or 1,800 mg of XP13512 experienced somnolence. Dizziness also occurred in 28% of patients at 1,800 mg and in 18% at 1,200 mg. In most cases, the events were transient and mild. Other adverse events occurred at much lower rates, and none were serious.

INDIANAPOLIS – Parents of children with inflammatory bowel disease perceive the effects of their children's illness more intensely than do the children themselves, according to Carin L. Cunningham, Ph.D.

“Treating physicians need to be aware of how the parents of children with inflammatory bowel disease are managing, because parental anxiety increases the child's anxiety,” Dr. Cunningham said during a poster session at the annual meeting of the Midwest Society for Pediatric Research.

Parents fret that their children may not lead normal lives or participate in normal activities, or that they may not be able to start a family of their own, Dr. Cunningham said in an interview.

“These concerns are most prevalent among parents who do not have IBD themselves,” explained Dr. Cunningham, a pediatric psychologist at the Rainbow Babies and Children's Hospital and Case Western Reserve University in Cleveland.

The study examined the health-related quality of life (HRQOL) of children and adolescents with inflammatory bowel disease (IBD), compared with the HRQOL of physically healthy peers, with emphasis on the effects of IBD and steroidal side effects.

The HRQOL scores of 49 children and adolescents (aged 10–18 years) with IBD and their parents, who completed the Child Health Questionnaire, were compared with those of healthy children.

“To our knowledge, this is the first study to describe the impact of IBD on HRQOL based on both a standardized measure and a controlled comparison of U.S. children and adolescents with IBD and physically healthy [peers] who were recruited from the same setting,” Dr. Cunningham and her associates said.

There are alternative interpretations of the discrepant findings between parent versus child reports of the impact of IBD on HRQOL, according to the investigators. “It is possible that children and adolescents with IBD are coping relatively well with the stressors of their condition and are not experiencing a significant impact of IBD-related problems on their HRQOL.”

Another possibility is that young people may deny or minimize the impact of IBD.

The study also found that:

▸ Caregivers of children with IBD reported that their children's physical and psychological health was more limited and that they experienced more worry and greater interference with their personal time, compared with caregivers of healthy children.

▸ Children and adolescents with IBD reported worse HRQOL than physically healthy children in only one domain, that of general health.

▸ Limitations in HRQOL were greatest in children who experienced more frequent IBD-related symptoms together with symptoms of steroidal side effects.

This suggests that children on steroids suffer the most, Dr. Cunningham said. “They become cushingoid, they gain weight, and often there's acne or stretch marks. This results in a lot of teasing from other kids, and these patients tell me they would rather have the pain of the illness than deal with the side effects of steroid medications.”

“Guidance counselors in Cleveland-area schools told me that kids will talk about their sex lives and drug use, but they won't open up about IBD, which is a bathroom issue,” she added.

INDIANAPOLIS – Parents of children with inflammatory bowel disease perceive the effects of their children's illness more intensely than do the children themselves, according to Carin L. Cunningham, Ph.D.

“Treating physicians need to be aware of how the parents of children with inflammatory bowel disease are managing, because parental anxiety increases the child's anxiety,” Dr. Cunningham said during a poster session at the annual meeting of the Midwest Society for Pediatric Research.

Parents fret that their children may not lead normal lives or participate in normal activities, or that they may not be able to start a family of their own, Dr. Cunningham said in an interview.

“These concerns are most prevalent among parents who do not have IBD themselves,” explained Dr. Cunningham, a pediatric psychologist at the Rainbow Babies and Children's Hospital and Case Western Reserve University in Cleveland.

The study examined the health-related quality of life (HRQOL) of children and adolescents with inflammatory bowel disease (IBD), compared with the HRQOL of physically healthy peers, with emphasis on the effects of IBD and steroidal side effects.

The HRQOL scores of 49 children and adolescents (aged 10–18 years) with IBD and their parents, who completed the Child Health Questionnaire, were compared with those of healthy children.

“To our knowledge, this is the first study to describe the impact of IBD on HRQOL based on both a standardized measure and a controlled comparison of U.S. children and adolescents with IBD and physically healthy [peers] who were recruited from the same setting,” Dr. Cunningham and her associates said.

There are alternative interpretations of the discrepant findings between parent versus child reports of the impact of IBD on HRQOL, according to the investigators. “It is possible that children and adolescents with IBD are coping relatively well with the stressors of their condition and are not experiencing a significant impact of IBD-related problems on their HRQOL.”

Another possibility is that young people may deny or minimize the impact of IBD.

The study also found that:

▸ Caregivers of children with IBD reported that their children's physical and psychological health was more limited and that they experienced more worry and greater interference with their personal time, compared with caregivers of healthy children.

▸ Children and adolescents with IBD reported worse HRQOL than physically healthy children in only one domain, that of general health.

▸ Limitations in HRQOL were greatest in children who experienced more frequent IBD-related symptoms together with symptoms of steroidal side effects.

This suggests that children on steroids suffer the most, Dr. Cunningham said. “They become cushingoid, they gain weight, and often there's acne or stretch marks. This results in a lot of teasing from other kids, and these patients tell me they would rather have the pain of the illness than deal with the side effects of steroid medications.”

“Guidance counselors in Cleveland-area schools told me that kids will talk about their sex lives and drug use, but they won't open up about IBD, which is a bathroom issue,” she added.

INDIANAPOLIS – Parents of children with inflammatory bowel disease perceive the effects of their children's illness more intensely than do the children themselves, according to Carin L. Cunningham, Ph.D.

“Treating physicians need to be aware of how the parents of children with inflammatory bowel disease are managing, because parental anxiety increases the child's anxiety,” Dr. Cunningham said during a poster session at the annual meeting of the Midwest Society for Pediatric Research.

Parents fret that their children may not lead normal lives or participate in normal activities, or that they may not be able to start a family of their own, Dr. Cunningham said in an interview.

“These concerns are most prevalent among parents who do not have IBD themselves,” explained Dr. Cunningham, a pediatric psychologist at the Rainbow Babies and Children's Hospital and Case Western Reserve University in Cleveland.

The study examined the health-related quality of life (HRQOL) of children and adolescents with inflammatory bowel disease (IBD), compared with the HRQOL of physically healthy peers, with emphasis on the effects of IBD and steroidal side effects.

The HRQOL scores of 49 children and adolescents (aged 10–18 years) with IBD and their parents, who completed the Child Health Questionnaire, were compared with those of healthy children.

“To our knowledge, this is the first study to describe the impact of IBD on HRQOL based on both a standardized measure and a controlled comparison of U.S. children and adolescents with IBD and physically healthy [peers] who were recruited from the same setting,” Dr. Cunningham and her associates said.

There are alternative interpretations of the discrepant findings between parent versus child reports of the impact of IBD on HRQOL, according to the investigators. “It is possible that children and adolescents with IBD are coping relatively well with the stressors of their condition and are not experiencing a significant impact of IBD-related problems on their HRQOL.”

Another possibility is that young people may deny or minimize the impact of IBD.

The study also found that:

▸ Caregivers of children with IBD reported that their children's physical and psychological health was more limited and that they experienced more worry and greater interference with their personal time, compared with caregivers of healthy children.

▸ Children and adolescents with IBD reported worse HRQOL than physically healthy children in only one domain, that of general health.

▸ Limitations in HRQOL were greatest in children who experienced more frequent IBD-related symptoms together with symptoms of steroidal side effects.

This suggests that children on steroids suffer the most, Dr. Cunningham said. “They become cushingoid, they gain weight, and often there's acne or stretch marks. This results in a lot of teasing from other kids, and these patients tell me they would rather have the pain of the illness than deal with the side effects of steroid medications.”

“Guidance counselors in Cleveland-area schools told me that kids will talk about their sex lives and drug use, but they won't open up about IBD, which is a bathroom issue,” she added.

People who have severe mental illness are at double to triple the risk of dying from coronary heart disease or stroke at all ages, compared with people who are not mentally ill, reported David P.J. Osborn, Ph.D., and his associates.

The social deprivation of the severely mentally ill and their higher rate of smoking do not explain this increased cardiovascular risk, and their use of antipsychotic medications “is only part of the explanation.” The exact mechanism underlying this increased vulnerability remains unknown, the researchers said.

Noting that the true burden of physical disease among the severely mentally ill has never been established, Dr. Osborn and his associates at the Royal Free and University College London tried to estimate the risks of heart disease, stroke, and cancer death using data from the United Kingdom's General Practice Research Database. “Precise estimation of the true population risk for CVD [cardiovascular disease] or cancer mortality requires data from large, representative populations followed up for periods long enough to include sufficient observed deaths,” they pointed out.

The GPRD covered some 8 million patients treated in 741 general practices throughout the United Kingdom between 1987 and 2002, and the sample included almost all those with severe mental illness at the time.

Compared with more than 300,000 randomly selected, matched control subjects who were free from severe mental illness, the 46,136 subjects with schizophrenia, schizoaffective disorder, bipolar disorder, delusional disorder, or other nonorganic psychoses showed triple the rate of death from coronary heart disease before age 50 and double the rate at aged 50–75 years.

Similarly, stroke mortality was 2.5 times higher in mentally ill people younger than 50 years and twice as high in those aged 50–75 years than it was in the controls, the investigators said (Arch. Gen. Psychiatry 2007;64:242–9).

In contrast, mortality from six of the seven most common cancers in the United Kingdom–colorectal, breast, prostate, stomach, esophageal, and pancreatic cancers–was no different between the control subjects and the mentally ill. Mortality from the seventh common malignancy, respiratory cancer, initially was higher in the severely mentally ill. However, after the data were adjusted to account for smoking and social deprivation, that difference was no longer significant.

Mentally ill people who did not take antipsychotic medications were at increased risk of coronary heart disease and stroke, and those who did take the medications were at even higher risk. People who took the highest doses were at the highest risk of cardiovascular death.

This dose-response relationship could be attributable to adverse drug effects at higher doses, or it could be that higher doses are simply a marker of the severity of mental illness, which itself may raise mortality risk, Dr. Osborn and his associates said.

The reasons why severe mental illness puts people at higher risk of CVD mortality remain unclear. It is possible that mentally ill patients may be less likely to present with CVD symptoms, to be correctly diagnosed, to be given correct treatment, and to adhere to treatment, the researchers said.

These findings underscore the fact that people with severe mental illness must be monitored for somatic conditions. Although the management of blood pressure, glucose levels, cholesterol levels, smoking, diet, and exercise may be best accomplished in the primary care setting, “psychiatric health care professionals cannot be viewed as exempt from responsibility for physical health monitoring,” Dr. Osborn and his associates noted.

People who have severe mental illness are at double to triple the risk of dying from coronary heart disease or stroke at all ages, compared with people who are not mentally ill, reported David P.J. Osborn, Ph.D., and his associates.

The social deprivation of the severely mentally ill and their higher rate of smoking do not explain this increased cardiovascular risk, and their use of antipsychotic medications “is only part of the explanation.” The exact mechanism underlying this increased vulnerability remains unknown, the researchers said.

Noting that the true burden of physical disease among the severely mentally ill has never been established, Dr. Osborn and his associates at the Royal Free and University College London tried to estimate the risks of heart disease, stroke, and cancer death using data from the United Kingdom's General Practice Research Database. “Precise estimation of the true population risk for CVD [cardiovascular disease] or cancer mortality requires data from large, representative populations followed up for periods long enough to include sufficient observed deaths,” they pointed out.

The GPRD covered some 8 million patients treated in 741 general practices throughout the United Kingdom between 1987 and 2002, and the sample included almost all those with severe mental illness at the time.

Compared with more than 300,000 randomly selected, matched control subjects who were free from severe mental illness, the 46,136 subjects with schizophrenia, schizoaffective disorder, bipolar disorder, delusional disorder, or other nonorganic psychoses showed triple the rate of death from coronary heart disease before age 50 and double the rate at aged 50–75 years.

Similarly, stroke mortality was 2.5 times higher in mentally ill people younger than 50 years and twice as high in those aged 50–75 years than it was in the controls, the investigators said (Arch. Gen. Psychiatry 2007;64:242–9).

In contrast, mortality from six of the seven most common cancers in the United Kingdom–colorectal, breast, prostate, stomach, esophageal, and pancreatic cancers–was no different between the control subjects and the mentally ill. Mortality from the seventh common malignancy, respiratory cancer, initially was higher in the severely mentally ill. However, after the data were adjusted to account for smoking and social deprivation, that difference was no longer significant.

Mentally ill people who did not take antipsychotic medications were at increased risk of coronary heart disease and stroke, and those who did take the medications were at even higher risk. People who took the highest doses were at the highest risk of cardiovascular death.

This dose-response relationship could be attributable to adverse drug effects at higher doses, or it could be that higher doses are simply a marker of the severity of mental illness, which itself may raise mortality risk, Dr. Osborn and his associates said.

The reasons why severe mental illness puts people at higher risk of CVD mortality remain unclear. It is possible that mentally ill patients may be less likely to present with CVD symptoms, to be correctly diagnosed, to be given correct treatment, and to adhere to treatment, the researchers said.

These findings underscore the fact that people with severe mental illness must be monitored for somatic conditions. Although the management of blood pressure, glucose levels, cholesterol levels, smoking, diet, and exercise may be best accomplished in the primary care setting, “psychiatric health care professionals cannot be viewed as exempt from responsibility for physical health monitoring,” Dr. Osborn and his associates noted.

People who have severe mental illness are at double to triple the risk of dying from coronary heart disease or stroke at all ages, compared with people who are not mentally ill, reported David P.J. Osborn, Ph.D., and his associates.

The social deprivation of the severely mentally ill and their higher rate of smoking do not explain this increased cardiovascular risk, and their use of antipsychotic medications “is only part of the explanation.” The exact mechanism underlying this increased vulnerability remains unknown, the researchers said.

Noting that the true burden of physical disease among the severely mentally ill has never been established, Dr. Osborn and his associates at the Royal Free and University College London tried to estimate the risks of heart disease, stroke, and cancer death using data from the United Kingdom's General Practice Research Database. “Precise estimation of the true population risk for CVD [cardiovascular disease] or cancer mortality requires data from large, representative populations followed up for periods long enough to include sufficient observed deaths,” they pointed out.

The GPRD covered some 8 million patients treated in 741 general practices throughout the United Kingdom between 1987 and 2002, and the sample included almost all those with severe mental illness at the time.

Compared with more than 300,000 randomly selected, matched control subjects who were free from severe mental illness, the 46,136 subjects with schizophrenia, schizoaffective disorder, bipolar disorder, delusional disorder, or other nonorganic psychoses showed triple the rate of death from coronary heart disease before age 50 and double the rate at aged 50–75 years.

Similarly, stroke mortality was 2.5 times higher in mentally ill people younger than 50 years and twice as high in those aged 50–75 years than it was in the controls, the investigators said (Arch. Gen. Psychiatry 2007;64:242–9).

In contrast, mortality from six of the seven most common cancers in the United Kingdom–colorectal, breast, prostate, stomach, esophageal, and pancreatic cancers–was no different between the control subjects and the mentally ill. Mortality from the seventh common malignancy, respiratory cancer, initially was higher in the severely mentally ill. However, after the data were adjusted to account for smoking and social deprivation, that difference was no longer significant.

Mentally ill people who did not take antipsychotic medications were at increased risk of coronary heart disease and stroke, and those who did take the medications were at even higher risk. People who took the highest doses were at the highest risk of cardiovascular death.

This dose-response relationship could be attributable to adverse drug effects at higher doses, or it could be that higher doses are simply a marker of the severity of mental illness, which itself may raise mortality risk, Dr. Osborn and his associates said.

The reasons why severe mental illness puts people at higher risk of CVD mortality remain unclear. It is possible that mentally ill patients may be less likely to present with CVD symptoms, to be correctly diagnosed, to be given correct treatment, and to adhere to treatment, the researchers said.

These findings underscore the fact that people with severe mental illness must be monitored for somatic conditions. Although the management of blood pressure, glucose levels, cholesterol levels, smoking, diet, and exercise may be best accomplished in the primary care setting, “psychiatric health care professionals cannot be viewed as exempt from responsibility for physical health monitoring,” Dr. Osborn and his associates noted.

SCOTTSDALE, ARIZ. – Even mild sleep disorders have the potential to affect fetal outcomes during pregnancy, Dr. Susan M. Harding advised at a meeting on sleep medicine sponsored by the American College of Chest Physicians.

Recent research suggests that obstructive sleep apnea might impact hypertension in pregnant women with preeclampsia, according to Dr. Harding, professor of medicine at the University of Alabama, Birmingham, and medical director of the Sleep/Wake Disorders Center there.

Other studies cited by Dr. Harding show a higher risk of lower-birth-weight babies in women who work night shifts, and increases in labor duration and in cesarean section rates when women sleep poorly.

Potential relationships between sleep and pregnancy are “a really ripe area” in need of more research, she noted.

Dr. Harding cited a Swedish study of 502 singleton pregnancies that diagnosed hypertension in 14% of 113 snorers but in only 6% of 389 nonsnorers (Chest 2000;117:137–41). Preeclampsia also was significantly more prevalent, occurring in 10% of snorers vs. 4% of women who did not snore.

The investigators concluded that habitual snoring is an independent predictor of hypertension (odds ratio 2.03) and growth retardation (OR 3.45). Dr. Harding noted that snorers' babies were significantly more likely to have Apgar scores of 7 or lower at 1 minute after birth (12.4% vs. 3.6%) and to be small for gestational age (7.1% vs. 2.6%). Only 4% of women snored before becoming pregnant, whereas 23% snored during their final week of pregnancy.

Another study cited by Dr. Harding delivered continuous positive airways pressure (CPAP) to 11 pregnant women with severe preeclampsia and findings of upper airway resistance syndrome (Am. J. Respir. Crit. Care Med. 2000;162:252–7). CPAP reduced blood pressure in these women.

The shift-work study reviewed 41,150 pregnancies in a Danish database (Am. J. Obstet. Gynecol. 2004;191:285–91). Dr. Harding said women on permanent night shifts had a higher risk of post-term birth (OR 1.35) and delivering a low-birth-weight baby at term (OR 1.80).

She also cited an American study of 131 women in their ninth month of pregnancy (Am. J. Obstet. Gynecol. 2004;191:2041–6). Women who slept fewer than 6 hours each night had longer durations of labor (29 hours vs. 18 hours) and a higher cesarean rate (37% vs. 11%), compared with those who slept more hours. Longer labors and higher cesarean rates also were linked with disrupted sleep.

Although these studies are not conclusive, Dr. Harding said the evidence so far is sufficiently strong that physicians should consider screening pregnant women for obstructive sleep apnea, especially when hypertension is an issue. She noted that CPAP requirements of women treated for obstructive sleep apnea could change during pregnancy and need to be monitored.

Treating two other sleep disorders–restless leg syndrome (RLS) and narcolepsy–is problematic because modafinil and medications used in treating these disorders are contraindicated during pregnancy, according to Dr. Harding. Pregnancy is a risk factor for development of RLS. Up to a third of pregnant women will have RLS symptoms, she said, most often during the last trimester. Symptoms usually resolve within 10 days of giving birth.

Dr. Harding recommended educating women being treated for RLS or other sleep disorders about the need to discontinue modafinil, stimulants, and other medications prior to becoming pregnant. She called on physicians to assess risks, such as patients' driving when drowsy, if drug therapies are stopped. “Off medication, they may have significant problems,” she said.

To prevent RLS during pregnancy, she suggested that all women take folate supplements. Also, about 30% of women are iron deficient at the outset of their pregnancies, she said; third-trimester RLS has been linked to low serum folate and ferritin levels.

Consider testing pregnant women for obstructive sleep apnea, especially when hypertension is an issue. DR. HARDING

SCOTTSDALE, ARIZ. – Even mild sleep disorders have the potential to affect fetal outcomes during pregnancy, Dr. Susan M. Harding advised at a meeting on sleep medicine sponsored by the American College of Chest Physicians.

Recent research suggests that obstructive sleep apnea might impact hypertension in pregnant women with preeclampsia, according to Dr. Harding, professor of medicine at the University of Alabama, Birmingham, and medical director of the Sleep/Wake Disorders Center there.

Other studies cited by Dr. Harding show a higher risk of lower-birth-weight babies in women who work night shifts, and increases in labor duration and in cesarean section rates when women sleep poorly.

Potential relationships between sleep and pregnancy are “a really ripe area” in need of more research, she noted.

Dr. Harding cited a Swedish study of 502 singleton pregnancies that diagnosed hypertension in 14% of 113 snorers but in only 6% of 389 nonsnorers (Chest 2000;117:137–41). Preeclampsia also was significantly more prevalent, occurring in 10% of snorers vs. 4% of women who did not snore.

The investigators concluded that habitual snoring is an independent predictor of hypertension (odds ratio 2.03) and growth retardation (OR 3.45). Dr. Harding noted that snorers' babies were significantly more likely to have Apgar scores of 7 or lower at 1 minute after birth (12.4% vs. 3.6%) and to be small for gestational age (7.1% vs. 2.6%). Only 4% of women snored before becoming pregnant, whereas 23% snored during their final week of pregnancy.

Another study cited by Dr. Harding delivered continuous positive airways pressure (CPAP) to 11 pregnant women with severe preeclampsia and findings of upper airway resistance syndrome (Am. J. Respir. Crit. Care Med. 2000;162:252–7). CPAP reduced blood pressure in these women.

The shift-work study reviewed 41,150 pregnancies in a Danish database (Am. J. Obstet. Gynecol. 2004;191:285–91). Dr. Harding said women on permanent night shifts had a higher risk of post-term birth (OR 1.35) and delivering a low-birth-weight baby at term (OR 1.80).

She also cited an American study of 131 women in their ninth month of pregnancy (Am. J. Obstet. Gynecol. 2004;191:2041–6). Women who slept fewer than 6 hours each night had longer durations of labor (29 hours vs. 18 hours) and a higher cesarean rate (37% vs. 11%), compared with those who slept more hours. Longer labors and higher cesarean rates also were linked with disrupted sleep.

Although these studies are not conclusive, Dr. Harding said the evidence so far is sufficiently strong that physicians should consider screening pregnant women for obstructive sleep apnea, especially when hypertension is an issue. She noted that CPAP requirements of women treated for obstructive sleep apnea could change during pregnancy and need to be monitored.

Treating two other sleep disorders–restless leg syndrome (RLS) and narcolepsy–is problematic because modafinil and medications used in treating these disorders are contraindicated during pregnancy, according to Dr. Harding. Pregnancy is a risk factor for development of RLS. Up to a third of pregnant women will have RLS symptoms, she said, most often during the last trimester. Symptoms usually resolve within 10 days of giving birth.

Dr. Harding recommended educating women being treated for RLS or other sleep disorders about the need to discontinue modafinil, stimulants, and other medications prior to becoming pregnant. She called on physicians to assess risks, such as patients' driving when drowsy, if drug therapies are stopped. “Off medication, they may have significant problems,” she said.

To prevent RLS during pregnancy, she suggested that all women take folate supplements. Also, about 30% of women are iron deficient at the outset of their pregnancies, she said; third-trimester RLS has been linked to low serum folate and ferritin levels.

Consider testing pregnant women for obstructive sleep apnea, especially when hypertension is an issue. DR. HARDING

SCOTTSDALE, ARIZ. – Even mild sleep disorders have the potential to affect fetal outcomes during pregnancy, Dr. Susan M. Harding advised at a meeting on sleep medicine sponsored by the American College of Chest Physicians.

Recent research suggests that obstructive sleep apnea might impact hypertension in pregnant women with preeclampsia, according to Dr. Harding, professor of medicine at the University of Alabama, Birmingham, and medical director of the Sleep/Wake Disorders Center there.

Other studies cited by Dr. Harding show a higher risk of lower-birth-weight babies in women who work night shifts, and increases in labor duration and in cesarean section rates when women sleep poorly.

Potential relationships between sleep and pregnancy are “a really ripe area” in need of more research, she noted.

Dr. Harding cited a Swedish study of 502 singleton pregnancies that diagnosed hypertension in 14% of 113 snorers but in only 6% of 389 nonsnorers (Chest 2000;117:137–41). Preeclampsia also was significantly more prevalent, occurring in 10% of snorers vs. 4% of women who did not snore.

The investigators concluded that habitual snoring is an independent predictor of hypertension (odds ratio 2.03) and growth retardation (OR 3.45). Dr. Harding noted that snorers' babies were significantly more likely to have Apgar scores of 7 or lower at 1 minute after birth (12.4% vs. 3.6%) and to be small for gestational age (7.1% vs. 2.6%). Only 4% of women snored before becoming pregnant, whereas 23% snored during their final week of pregnancy.

Another study cited by Dr. Harding delivered continuous positive airways pressure (CPAP) to 11 pregnant women with severe preeclampsia and findings of upper airway resistance syndrome (Am. J. Respir. Crit. Care Med. 2000;162:252–7). CPAP reduced blood pressure in these women.

The shift-work study reviewed 41,150 pregnancies in a Danish database (Am. J. Obstet. Gynecol. 2004;191:285–91). Dr. Harding said women on permanent night shifts had a higher risk of post-term birth (OR 1.35) and delivering a low-birth-weight baby at term (OR 1.80).

She also cited an American study of 131 women in their ninth month of pregnancy (Am. J. Obstet. Gynecol. 2004;191:2041–6). Women who slept fewer than 6 hours each night had longer durations of labor (29 hours vs. 18 hours) and a higher cesarean rate (37% vs. 11%), compared with those who slept more hours. Longer labors and higher cesarean rates also were linked with disrupted sleep.

Although these studies are not conclusive, Dr. Harding said the evidence so far is sufficiently strong that physicians should consider screening pregnant women for obstructive sleep apnea, especially when hypertension is an issue. She noted that CPAP requirements of women treated for obstructive sleep apnea could change during pregnancy and need to be monitored.

Treating two other sleep disorders–restless leg syndrome (RLS) and narcolepsy–is problematic because modafinil and medications used in treating these disorders are contraindicated during pregnancy, according to Dr. Harding. Pregnancy is a risk factor for development of RLS. Up to a third of pregnant women will have RLS symptoms, she said, most often during the last trimester. Symptoms usually resolve within 10 days of giving birth.

Dr. Harding recommended educating women being treated for RLS or other sleep disorders about the need to discontinue modafinil, stimulants, and other medications prior to becoming pregnant. She called on physicians to assess risks, such as patients' driving when drowsy, if drug therapies are stopped. “Off medication, they may have significant problems,” she said.

To prevent RLS during pregnancy, she suggested that all women take folate supplements. Also, about 30% of women are iron deficient at the outset of their pregnancies, she said; third-trimester RLS has been linked to low serum folate and ferritin levels.

Consider testing pregnant women for obstructive sleep apnea, especially when hypertension is an issue. DR. HARDING

MONTREAL – Oral appliances are equally effective as continuous positive airway pressure therapy in patients with mild to moderate obstructive sleep apnea, but not in those with severe disease, according to a randomized trial.

“We've now shown clearly that oral appliances are a viable option that can be considered alongside CPAP [continuous positive airway pressure] therapy in mild to moderate cases,” Dr. Aarnoud Hoekema said in an interview. “Oral appliances are still a subject of much debate. In some clinics, they are used as secondary therapy only when CPAP therapy fails. Other clinics might use them only in patients with mild sleep apnea.”

His study, which he presented at the Eighth World Congress on Sleep Apnea, randomized 103 patients with obstructive sleep apnea to either CPAP (52) or oral appliance therapy (51).

Treatment effectiveness was evaluated by polysomnography after 8 weeks, and was defined as either a reduction in the apnea-hypopnea index (AHI) to below 5, or an AHI reduction to below 20 if this represented at least a 50% reduction in AHI and also rendered the patient symptom free.

A total of 50 patients were classified as having mild to moderate sleep apnea, defined as an AHI of between 5 and 30, while the remaining 53 patients had severe disease, with an AHI of more than 30, reported Dr. Hoekema, who is a dentist and research associate in the department of oral and maxillofacial surgery and maxillofacial prosthetics at Groningen University Hospital in Groningen, the Netherlands.

Overall, the study found that treatment was effective for most patients in both the oral appliance (76.5%) and the CPAP (82.7%) groups. In this comparison of the groups, oral appliance therapy met the predefined criterion for noninferiority, Dr. Hoekema said. But when the results were subanalyzed based on the severity of sleep apnea, oral appliance therapy was inferior in patients with severe disease, resulting in a 69% success rate, compared with 85% for CPAP. In the subgroup of patients with mild to moderate disease, oral appliance therapy was not inferior, with an 84% success rate, compared with an 80% success rate among patients using CPAP.

In mild to moderate patients, it might make sense to consider oral appliances first, he said.

MONTREAL – Oral appliances are equally effective as continuous positive airway pressure therapy in patients with mild to moderate obstructive sleep apnea, but not in those with severe disease, according to a randomized trial.

“We've now shown clearly that oral appliances are a viable option that can be considered alongside CPAP [continuous positive airway pressure] therapy in mild to moderate cases,” Dr. Aarnoud Hoekema said in an interview. “Oral appliances are still a subject of much debate. In some clinics, they are used as secondary therapy only when CPAP therapy fails. Other clinics might use them only in patients with mild sleep apnea.”

His study, which he presented at the Eighth World Congress on Sleep Apnea, randomized 103 patients with obstructive sleep apnea to either CPAP (52) or oral appliance therapy (51).

Treatment effectiveness was evaluated by polysomnography after 8 weeks, and was defined as either a reduction in the apnea-hypopnea index (AHI) to below 5, or an AHI reduction to below 20 if this represented at least a 50% reduction in AHI and also rendered the patient symptom free.

A total of 50 patients were classified as having mild to moderate sleep apnea, defined as an AHI of between 5 and 30, while the remaining 53 patients had severe disease, with an AHI of more than 30, reported Dr. Hoekema, who is a dentist and research associate in the department of oral and maxillofacial surgery and maxillofacial prosthetics at Groningen University Hospital in Groningen, the Netherlands.

Overall, the study found that treatment was effective for most patients in both the oral appliance (76.5%) and the CPAP (82.7%) groups. In this comparison of the groups, oral appliance therapy met the predefined criterion for noninferiority, Dr. Hoekema said. But when the results were subanalyzed based on the severity of sleep apnea, oral appliance therapy was inferior in patients with severe disease, resulting in a 69% success rate, compared with 85% for CPAP. In the subgroup of patients with mild to moderate disease, oral appliance therapy was not inferior, with an 84% success rate, compared with an 80% success rate among patients using CPAP.

In mild to moderate patients, it might make sense to consider oral appliances first, he said.

MONTREAL – Oral appliances are equally effective as continuous positive airway pressure therapy in patients with mild to moderate obstructive sleep apnea, but not in those with severe disease, according to a randomized trial.

“We've now shown clearly that oral appliances are a viable option that can be considered alongside CPAP [continuous positive airway pressure] therapy in mild to moderate cases,” Dr. Aarnoud Hoekema said in an interview. “Oral appliances are still a subject of much debate. In some clinics, they are used as secondary therapy only when CPAP therapy fails. Other clinics might use them only in patients with mild sleep apnea.”

His study, which he presented at the Eighth World Congress on Sleep Apnea, randomized 103 patients with obstructive sleep apnea to either CPAP (52) or oral appliance therapy (51).

Treatment effectiveness was evaluated by polysomnography after 8 weeks, and was defined as either a reduction in the apnea-hypopnea index (AHI) to below 5, or an AHI reduction to below 20 if this represented at least a 50% reduction in AHI and also rendered the patient symptom free.

A total of 50 patients were classified as having mild to moderate sleep apnea, defined as an AHI of between 5 and 30, while the remaining 53 patients had severe disease, with an AHI of more than 30, reported Dr. Hoekema, who is a dentist and research associate in the department of oral and maxillofacial surgery and maxillofacial prosthetics at Groningen University Hospital in Groningen, the Netherlands.

Overall, the study found that treatment was effective for most patients in both the oral appliance (76.5%) and the CPAP (82.7%) groups. In this comparison of the groups, oral appliance therapy met the predefined criterion for noninferiority, Dr. Hoekema said. But when the results were subanalyzed based on the severity of sleep apnea, oral appliance therapy was inferior in patients with severe disease, resulting in a 69% success rate, compared with 85% for CPAP. In the subgroup of patients with mild to moderate disease, oral appliance therapy was not inferior, with an 84% success rate, compared with an 80% success rate among patients using CPAP.

In mild to moderate patients, it might make sense to consider oral appliances first, he said.

ATLANTA – A biopsychosocial approach may offer the most effective way to manage chronic pain in patients with a comorbid mood or substance use disorder without compromising recovery processes, Martin D. Cheatle, Ph.D., said at the Southeastern conference on alcohol and drug addiction.

The key is treating the whole patient, and treating the disorders concurrently rather than sequentially. A patient who goes through detox but goes home in pain is at high risk for returning to narcotics abuse, and the effects of depression and anxiety on pain and treatment outcomes, and vice versa, also have to be considered, said Dr. Cheatle of the Behavioral Medicine Center, Reading (Pa.) Hospital and Medical Center.

The biopsychosocial model involves the use of evidence-based medication management along with cognitive-behavioral therapy and an exercise/physical therapy program with a goal of empowering the patient to take charge of the pain. Relaxation and thought focus techniques, and development of adaptive resources such as coping skills, strength, and stamina can help in providing that empowerment.

Also key to success is community support via a network of specially trained primary care doctors and specialists working together in the patient's interest.

Programs incorporating this approach have been shown to improve treatment outcomes, promote return to gainful employment, reduce pain, and increase functionality. For example, a study of 123 patients at the Behavioral Medicine Center showed that from admission to 1.5 years following completion of a 3-week residential behaviorally based pain program including rehabilitation and group cognitive-behavioral therapy, the use of opioids, benzodiazepines, nonsteroidal anti-inflammatories, and antidepressants dropped dramatically, and the use of over-the-counter treatments for pain increased.

The frequency of walking and cycling significantly increased, and depression scores dramatically decreased. Pain scores were reduced by half, Dr. Cheatle said.

Further, employment increased from 5% to 74%, and health care utilization dropped by 78%.

It is important to note that the population which completed the treatment program was a motivated population–nonmotivated patients dropped out early–thus the findings are somewhat skewed, but the approach does appear to be of benefit, he said.

As for the use of opioids for the treatment of pain in patients with a substance use disorder or substance abuse history, these drugs aren't necessarily contraindicated. Data are lacking, but noncompliance with prescription nonopioid drugs, insistence on rapid release formulations of pain medication, complaints of pain at varying body sites (initial treatment for back pain and a later call with tooth pain), and numerous phone calls or clinic/emergency department visits requesting pain medication are among the signs of an increased risk for substance abuse.

History of substance abuse, smoking, or psychiatric disorders also should be considered when deciding the best approach for treating pain.

A patient who goes through detox but goes home in pain is at high risk for returning to narcotics abuse. DR. CHEATLE

ATLANTA – A biopsychosocial approach may offer the most effective way to manage chronic pain in patients with a comorbid mood or substance use disorder without compromising recovery processes, Martin D. Cheatle, Ph.D., said at the Southeastern conference on alcohol and drug addiction.

The key is treating the whole patient, and treating the disorders concurrently rather than sequentially. A patient who goes through detox but goes home in pain is at high risk for returning to narcotics abuse, and the effects of depression and anxiety on pain and treatment outcomes, and vice versa, also have to be considered, said Dr. Cheatle of the Behavioral Medicine Center, Reading (Pa.) Hospital and Medical Center.

The biopsychosocial model involves the use of evidence-based medication management along with cognitive-behavioral therapy and an exercise/physical therapy program with a goal of empowering the patient to take charge of the pain. Relaxation and thought focus techniques, and development of adaptive resources such as coping skills, strength, and stamina can help in providing that empowerment.

Also key to success is community support via a network of specially trained primary care doctors and specialists working together in the patient's interest.

Programs incorporating this approach have been shown to improve treatment outcomes, promote return to gainful employment, reduce pain, and increase functionality. For example, a study of 123 patients at the Behavioral Medicine Center showed that from admission to 1.5 years following completion of a 3-week residential behaviorally based pain program including rehabilitation and group cognitive-behavioral therapy, the use of opioids, benzodiazepines, nonsteroidal anti-inflammatories, and antidepressants dropped dramatically, and the use of over-the-counter treatments for pain increased.

The frequency of walking and cycling significantly increased, and depression scores dramatically decreased. Pain scores were reduced by half, Dr. Cheatle said.

Further, employment increased from 5% to 74%, and health care utilization dropped by 78%.

It is important to note that the population which completed the treatment program was a motivated population–nonmotivated patients dropped out early–thus the findings are somewhat skewed, but the approach does appear to be of benefit, he said.

As for the use of opioids for the treatment of pain in patients with a substance use disorder or substance abuse history, these drugs aren't necessarily contraindicated. Data are lacking, but noncompliance with prescription nonopioid drugs, insistence on rapid release formulations of pain medication, complaints of pain at varying body sites (initial treatment for back pain and a later call with tooth pain), and numerous phone calls or clinic/emergency department visits requesting pain medication are among the signs of an increased risk for substance abuse.

History of substance abuse, smoking, or psychiatric disorders also should be considered when deciding the best approach for treating pain.

A patient who goes through detox but goes home in pain is at high risk for returning to narcotics abuse. DR. CHEATLE

ATLANTA – A biopsychosocial approach may offer the most effective way to manage chronic pain in patients with a comorbid mood or substance use disorder without compromising recovery processes, Martin D. Cheatle, Ph.D., said at the Southeastern conference on alcohol and drug addiction.

The key is treating the whole patient, and treating the disorders concurrently rather than sequentially. A patient who goes through detox but goes home in pain is at high risk for returning to narcotics abuse, and the effects of depression and anxiety on pain and treatment outcomes, and vice versa, also have to be considered, said Dr. Cheatle of the Behavioral Medicine Center, Reading (Pa.) Hospital and Medical Center.

The biopsychosocial model involves the use of evidence-based medication management along with cognitive-behavioral therapy and an exercise/physical therapy program with a goal of empowering the patient to take charge of the pain. Relaxation and thought focus techniques, and development of adaptive resources such as coping skills, strength, and stamina can help in providing that empowerment.

Also key to success is community support via a network of specially trained primary care doctors and specialists working together in the patient's interest.

Programs incorporating this approach have been shown to improve treatment outcomes, promote return to gainful employment, reduce pain, and increase functionality. For example, a study of 123 patients at the Behavioral Medicine Center showed that from admission to 1.5 years following completion of a 3-week residential behaviorally based pain program including rehabilitation and group cognitive-behavioral therapy, the use of opioids, benzodiazepines, nonsteroidal anti-inflammatories, and antidepressants dropped dramatically, and the use of over-the-counter treatments for pain increased.

The frequency of walking and cycling significantly increased, and depression scores dramatically decreased. Pain scores were reduced by half, Dr. Cheatle said.

Further, employment increased from 5% to 74%, and health care utilization dropped by 78%.

It is important to note that the population which completed the treatment program was a motivated population–nonmotivated patients dropped out early–thus the findings are somewhat skewed, but the approach does appear to be of benefit, he said.

As for the use of opioids for the treatment of pain in patients with a substance use disorder or substance abuse history, these drugs aren't necessarily contraindicated. Data are lacking, but noncompliance with prescription nonopioid drugs, insistence on rapid release formulations of pain medication, complaints of pain at varying body sites (initial treatment for back pain and a later call with tooth pain), and numerous phone calls or clinic/emergency department visits requesting pain medication are among the signs of an increased risk for substance abuse.

History of substance abuse, smoking, or psychiatric disorders also should be considered when deciding the best approach for treating pain.

A patient who goes through detox but goes home in pain is at high risk for returning to narcotics abuse. DR. CHEATLE