Somatic Disorders

SAN ANTONIO – The mindfulness-based stress reduction program developed by Jonathan Kabat-Zinn, Ph.D., appears to be beneficial to patients with early-stage breast cancer in the immediate posttreatment period as they transition to survivorship, Cecile Lengacher, Ph.D., reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

This transition is an underappreciated period of high risk for emotional distress. Many patients experience fear of recurrence while also coming to grips with changes in body image, concern for their children and other family members, and difficulties reintegrating into work and family roles, explained Dr. Lengacher of the Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa.

Because few clinical interventions addressing this challenging period are available to offer patients, Dr. Lengacher and her coworkers decided to do a nonrandomized pilot feasibility study of mindfulness-based stress reduction, the structured program developed by Dr. Kabat-Zinn of the University of Massachusetts, Worcester.

The program is designed to teach patients to self-regulate their arousal to stress through awareness of their thoughts and feelings during stressful circumstances. It emphasizes regular practice of four meditation techniques: sitting meditation, body scan, gentle Hatha yoga, and walking meditation.

The formal program entails eight 2-hour weekly group sessions, along with a minimum of 45 minutes per day 6 days per week practicing the various forms of meditation individually outside of class.

Investigators offered the program to women who had undergone lumpectomy plus radiotherapy and/or chemotherapy. Nineteen participated, and 17 completed the classes.

Thirteen of the 17 patients kept a practice diary. Entries showed they averaged 372 minutes per week in sitting meditation, 212 doing the body scan, 139 in walking meditation, and 123 minutes doing yoga.

Fifteen of the 17 patients found the program beneficial, and 13 said they could better handle stress and had improved coping skills. Serial measures of anxiety, depression, and pain were obtained, but the results are pending.

Since patients found the 8-week course too lengthy, investigators have since condensed the program to 6 weeks. A randomized trial is planned.

SAN ANTONIO – The mindfulness-based stress reduction program developed by Jonathan Kabat-Zinn, Ph.D., appears to be beneficial to patients with early-stage breast cancer in the immediate posttreatment period as they transition to survivorship, Cecile Lengacher, Ph.D., reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

This transition is an underappreciated period of high risk for emotional distress. Many patients experience fear of recurrence while also coming to grips with changes in body image, concern for their children and other family members, and difficulties reintegrating into work and family roles, explained Dr. Lengacher of the Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa.

Because few clinical interventions addressing this challenging period are available to offer patients, Dr. Lengacher and her coworkers decided to do a nonrandomized pilot feasibility study of mindfulness-based stress reduction, the structured program developed by Dr. Kabat-Zinn of the University of Massachusetts, Worcester.

The program is designed to teach patients to self-regulate their arousal to stress through awareness of their thoughts and feelings during stressful circumstances. It emphasizes regular practice of four meditation techniques: sitting meditation, body scan, gentle Hatha yoga, and walking meditation.

The formal program entails eight 2-hour weekly group sessions, along with a minimum of 45 minutes per day 6 days per week practicing the various forms of meditation individually outside of class.

Investigators offered the program to women who had undergone lumpectomy plus radiotherapy and/or chemotherapy. Nineteen participated, and 17 completed the classes.

Thirteen of the 17 patients kept a practice diary. Entries showed they averaged 372 minutes per week in sitting meditation, 212 doing the body scan, 139 in walking meditation, and 123 minutes doing yoga.

Fifteen of the 17 patients found the program beneficial, and 13 said they could better handle stress and had improved coping skills. Serial measures of anxiety, depression, and pain were obtained, but the results are pending.

Since patients found the 8-week course too lengthy, investigators have since condensed the program to 6 weeks. A randomized trial is planned.

SAN ANTONIO – The mindfulness-based stress reduction program developed by Jonathan Kabat-Zinn, Ph.D., appears to be beneficial to patients with early-stage breast cancer in the immediate posttreatment period as they transition to survivorship, Cecile Lengacher, Ph.D., reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

This transition is an underappreciated period of high risk for emotional distress. Many patients experience fear of recurrence while also coming to grips with changes in body image, concern for their children and other family members, and difficulties reintegrating into work and family roles, explained Dr. Lengacher of the Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa.

Because few clinical interventions addressing this challenging period are available to offer patients, Dr. Lengacher and her coworkers decided to do a nonrandomized pilot feasibility study of mindfulness-based stress reduction, the structured program developed by Dr. Kabat-Zinn of the University of Massachusetts, Worcester.

The program is designed to teach patients to self-regulate their arousal to stress through awareness of their thoughts and feelings during stressful circumstances. It emphasizes regular practice of four meditation techniques: sitting meditation, body scan, gentle Hatha yoga, and walking meditation.

The formal program entails eight 2-hour weekly group sessions, along with a minimum of 45 minutes per day 6 days per week practicing the various forms of meditation individually outside of class.

Investigators offered the program to women who had undergone lumpectomy plus radiotherapy and/or chemotherapy. Nineteen participated, and 17 completed the classes.

Thirteen of the 17 patients kept a practice diary. Entries showed they averaged 372 minutes per week in sitting meditation, 212 doing the body scan, 139 in walking meditation, and 123 minutes doing yoga.

Fifteen of the 17 patients found the program beneficial, and 13 said they could better handle stress and had improved coping skills. Serial measures of anxiety, depression, and pain were obtained, but the results are pending.

Since patients found the 8-week course too lengthy, investigators have since condensed the program to 6 weeks. A randomized trial is planned.

CHICAGO – The high anxiety that many women have after an acute myocardial infarction may explain their high complication rate, compared with men, and it may offer a new way to improve patient outcomes.

“Early recognition and effective treatment of anxiety immediately after a myocardial infarction may decrease morbidity and mortality,” Debra K. Moser, D.N.Sc., said while presenting a poster at the annual scientific sessions of the American Heart Association. “Anxiety is a target for intervention. “One of the things most lacking in clinical cardiology today is the assessment of anxiety and depression” in AMI patients, she said.

The Brief Symptom Inventory (BSI) is the way that Dr. Moser and her associates have measured anxiety in patients after an acute myocardial infarction (AMI), and treatment can include an anxiolytic drug as well as psychosocial interventions such as cognitive-behavioral therapy, said Dr. Moser, professor of nursing at the University of Kentucky, Lexington.

She and her associates examined the role of anxiety after AMI in 635 men and 244 women who were enrolled at several centers in the United States and four other countries. The anxiety level of all patients was measured within 72 hours of their hospital admission for their AMI using the BSI.

The BSI is a reliable and validated measure that uses six questions to measure anxiety, said Dr. Moser. Each question is rated on a scale of 0–4 (0 is the lowest level), and the scores from all six questions are summed and then averaged. A score of 0.33 or less indicates no anxiety. A score of 0.4 or more indicates clinically significant anxiety, especially if the score persists at this level over time. A score of 1.7 is what is typically seen in psychiatric patients who are hospitalized for anxiety disorders. Results from prior studies by Dr. Moser and her associates showed that about 44% of AMI patients have mild or moderate anxiety, and about 25% have a BSI score of 1.7 or higher (the remaining patients do not have anxiety).

The average post-MI BSI score among the women in this study was 0.77, compared with an average score of 0.57 among the men, a statistically significant difference. Complication rates also showed a gender split, with a rate of 33% in women and 24% in men, a significant difference. The complications included in this tally were repeat infarctions, ventricular tachycardia that was sustained or that required intervention, ventricular fibrillation, acute recurrent ischemia, heart failure, cardiogenic shock, or death.

In a multivariate analysis that controlled for clinical and demographic differences among the patients, patients who had a BSI score that indicated anxiety had a significant 66% higher rate of complications, compared with patients who were not anxious. Other significant determinants of an increased complication rate were smoking and a Killip class of II-IV. The analysis also showed that two factors were linked with significant protection against complications: treatment with a thrombolytic drug, and treatment with an anxiolytic drug, which was associated with a 44% drop in the rate of complications. The results also showed that the complication rates of men and women were similar if they were treated with an anxiolytic drug.

Typical anxiolytic drugs used on AMI patients by Dr. Moser's group include alprazolam (Xanax) and diazepam (Valium). It's important to start such drugs quickly once anxiety is first diagnosed post MI, but they can be stopped once the anxiety is relieved, often within a day. Dr. Moser recommended assessing anxiety levels early during AMI treatment, and then again when a patient is discharged from the intensive care unit, at the time of hospital discharge, at the first physician visit after hospital discharge, and then at 3, 6, and 12 months after the MI.

It's also important to use nonpharmacologic treatments too. Dr. Moser's group is testing the efficacy of cognitive-behavioral therapy in post-AMI patients.

CHICAGO – The high anxiety that many women have after an acute myocardial infarction may explain their high complication rate, compared with men, and it may offer a new way to improve patient outcomes.

“Early recognition and effective treatment of anxiety immediately after a myocardial infarction may decrease morbidity and mortality,” Debra K. Moser, D.N.Sc., said while presenting a poster at the annual scientific sessions of the American Heart Association. “Anxiety is a target for intervention. “One of the things most lacking in clinical cardiology today is the assessment of anxiety and depression” in AMI patients, she said.

The Brief Symptom Inventory (BSI) is the way that Dr. Moser and her associates have measured anxiety in patients after an acute myocardial infarction (AMI), and treatment can include an anxiolytic drug as well as psychosocial interventions such as cognitive-behavioral therapy, said Dr. Moser, professor of nursing at the University of Kentucky, Lexington.

She and her associates examined the role of anxiety after AMI in 635 men and 244 women who were enrolled at several centers in the United States and four other countries. The anxiety level of all patients was measured within 72 hours of their hospital admission for their AMI using the BSI.

The BSI is a reliable and validated measure that uses six questions to measure anxiety, said Dr. Moser. Each question is rated on a scale of 0–4 (0 is the lowest level), and the scores from all six questions are summed and then averaged. A score of 0.33 or less indicates no anxiety. A score of 0.4 or more indicates clinically significant anxiety, especially if the score persists at this level over time. A score of 1.7 is what is typically seen in psychiatric patients who are hospitalized for anxiety disorders. Results from prior studies by Dr. Moser and her associates showed that about 44% of AMI patients have mild or moderate anxiety, and about 25% have a BSI score of 1.7 or higher (the remaining patients do not have anxiety).

The average post-MI BSI score among the women in this study was 0.77, compared with an average score of 0.57 among the men, a statistically significant difference. Complication rates also showed a gender split, with a rate of 33% in women and 24% in men, a significant difference. The complications included in this tally were repeat infarctions, ventricular tachycardia that was sustained or that required intervention, ventricular fibrillation, acute recurrent ischemia, heart failure, cardiogenic shock, or death.

In a multivariate analysis that controlled for clinical and demographic differences among the patients, patients who had a BSI score that indicated anxiety had a significant 66% higher rate of complications, compared with patients who were not anxious. Other significant determinants of an increased complication rate were smoking and a Killip class of II-IV. The analysis also showed that two factors were linked with significant protection against complications: treatment with a thrombolytic drug, and treatment with an anxiolytic drug, which was associated with a 44% drop in the rate of complications. The results also showed that the complication rates of men and women were similar if they were treated with an anxiolytic drug.

Typical anxiolytic drugs used on AMI patients by Dr. Moser's group include alprazolam (Xanax) and diazepam (Valium). It's important to start such drugs quickly once anxiety is first diagnosed post MI, but they can be stopped once the anxiety is relieved, often within a day. Dr. Moser recommended assessing anxiety levels early during AMI treatment, and then again when a patient is discharged from the intensive care unit, at the time of hospital discharge, at the first physician visit after hospital discharge, and then at 3, 6, and 12 months after the MI.

It's also important to use nonpharmacologic treatments too. Dr. Moser's group is testing the efficacy of cognitive-behavioral therapy in post-AMI patients.

CHICAGO – The high anxiety that many women have after an acute myocardial infarction may explain their high complication rate, compared with men, and it may offer a new way to improve patient outcomes.

“Early recognition and effective treatment of anxiety immediately after a myocardial infarction may decrease morbidity and mortality,” Debra K. Moser, D.N.Sc., said while presenting a poster at the annual scientific sessions of the American Heart Association. “Anxiety is a target for intervention. “One of the things most lacking in clinical cardiology today is the assessment of anxiety and depression” in AMI patients, she said.

The Brief Symptom Inventory (BSI) is the way that Dr. Moser and her associates have measured anxiety in patients after an acute myocardial infarction (AMI), and treatment can include an anxiolytic drug as well as psychosocial interventions such as cognitive-behavioral therapy, said Dr. Moser, professor of nursing at the University of Kentucky, Lexington.

She and her associates examined the role of anxiety after AMI in 635 men and 244 women who were enrolled at several centers in the United States and four other countries. The anxiety level of all patients was measured within 72 hours of their hospital admission for their AMI using the BSI.

The BSI is a reliable and validated measure that uses six questions to measure anxiety, said Dr. Moser. Each question is rated on a scale of 0–4 (0 is the lowest level), and the scores from all six questions are summed and then averaged. A score of 0.33 or less indicates no anxiety. A score of 0.4 or more indicates clinically significant anxiety, especially if the score persists at this level over time. A score of 1.7 is what is typically seen in psychiatric patients who are hospitalized for anxiety disorders. Results from prior studies by Dr. Moser and her associates showed that about 44% of AMI patients have mild or moderate anxiety, and about 25% have a BSI score of 1.7 or higher (the remaining patients do not have anxiety).

The average post-MI BSI score among the women in this study was 0.77, compared with an average score of 0.57 among the men, a statistically significant difference. Complication rates also showed a gender split, with a rate of 33% in women and 24% in men, a significant difference. The complications included in this tally were repeat infarctions, ventricular tachycardia that was sustained or that required intervention, ventricular fibrillation, acute recurrent ischemia, heart failure, cardiogenic shock, or death.

In a multivariate analysis that controlled for clinical and demographic differences among the patients, patients who had a BSI score that indicated anxiety had a significant 66% higher rate of complications, compared with patients who were not anxious. Other significant determinants of an increased complication rate were smoking and a Killip class of II-IV. The analysis also showed that two factors were linked with significant protection against complications: treatment with a thrombolytic drug, and treatment with an anxiolytic drug, which was associated with a 44% drop in the rate of complications. The results also showed that the complication rates of men and women were similar if they were treated with an anxiolytic drug.

Typical anxiolytic drugs used on AMI patients by Dr. Moser's group include alprazolam (Xanax) and diazepam (Valium). It's important to start such drugs quickly once anxiety is first diagnosed post MI, but they can be stopped once the anxiety is relieved, often within a day. Dr. Moser recommended assessing anxiety levels early during AMI treatment, and then again when a patient is discharged from the intensive care unit, at the time of hospital discharge, at the first physician visit after hospital discharge, and then at 3, 6, and 12 months after the MI.

It's also important to use nonpharmacologic treatments too. Dr. Moser's group is testing the efficacy of cognitive-behavioral therapy in post-AMI patients.

SALT LAKE CITY – Continuous positive airway pressure adherence rates are suboptimal, findings from a study of sleep clinic patients suggest.

Of 528 adults diagnosed with obstructive sleep apnea and followed for a mean of 5 months, 63% had relatively poor adherence (use of less than 4 hours per night), 21% had adequate adherence (use of 4–6 hours per night), and only 16% had optimal adherence (use of more than 6 hours per night). Mean adherence was 3.1 hours per night, Carl Stepnowsky, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies.

Adherence was specifically defined as use at the prescribed pressure, and was measured by an internal clock. Baseline disease severity correlated with higher levels of adherence.

Patients had a mean age of 59 years, and most had moderate to severe obstructive sleep apnea, with a mean apnea-hypopnea index of 38.8 events per night. Mean change scores (0.68 pounds in weight, -1.6 mm Hg in diastolic blood pressure, and -2.6 mm Hg in systolic blood pressure) were not statistically different from zero, noted Dr. Stepnowsky of the VA San Diego Healthcare System.

The findings are of concern, he said, because suboptimal use of continuous positive airway pressure therapy leads to ineffective treatment and can increase the risk of morbidity and mortality.

A closer look at adherence rates showed that patterns of adherence were established as early as the first night of therapy, suggesting that preexisting factors might explain these patterns. Further studies in large, U.S.-based populations are needed to replicate these findings, as are studies to help identify the factors associated with adherence and to develop tools for improvement, he said.

SALT LAKE CITY – Continuous positive airway pressure adherence rates are suboptimal, findings from a study of sleep clinic patients suggest.

Of 528 adults diagnosed with obstructive sleep apnea and followed for a mean of 5 months, 63% had relatively poor adherence (use of less than 4 hours per night), 21% had adequate adherence (use of 4–6 hours per night), and only 16% had optimal adherence (use of more than 6 hours per night). Mean adherence was 3.1 hours per night, Carl Stepnowsky, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies.

Adherence was specifically defined as use at the prescribed pressure, and was measured by an internal clock. Baseline disease severity correlated with higher levels of adherence.

Patients had a mean age of 59 years, and most had moderate to severe obstructive sleep apnea, with a mean apnea-hypopnea index of 38.8 events per night. Mean change scores (0.68 pounds in weight, -1.6 mm Hg in diastolic blood pressure, and -2.6 mm Hg in systolic blood pressure) were not statistically different from zero, noted Dr. Stepnowsky of the VA San Diego Healthcare System.

The findings are of concern, he said, because suboptimal use of continuous positive airway pressure therapy leads to ineffective treatment and can increase the risk of morbidity and mortality.

A closer look at adherence rates showed that patterns of adherence were established as early as the first night of therapy, suggesting that preexisting factors might explain these patterns. Further studies in large, U.S.-based populations are needed to replicate these findings, as are studies to help identify the factors associated with adherence and to develop tools for improvement, he said.

SALT LAKE CITY – Continuous positive airway pressure adherence rates are suboptimal, findings from a study of sleep clinic patients suggest.

Of 528 adults diagnosed with obstructive sleep apnea and followed for a mean of 5 months, 63% had relatively poor adherence (use of less than 4 hours per night), 21% had adequate adherence (use of 4–6 hours per night), and only 16% had optimal adherence (use of more than 6 hours per night). Mean adherence was 3.1 hours per night, Carl Stepnowsky, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies.

Adherence was specifically defined as use at the prescribed pressure, and was measured by an internal clock. Baseline disease severity correlated with higher levels of adherence.

Patients had a mean age of 59 years, and most had moderate to severe obstructive sleep apnea, with a mean apnea-hypopnea index of 38.8 events per night. Mean change scores (0.68 pounds in weight, -1.6 mm Hg in diastolic blood pressure, and -2.6 mm Hg in systolic blood pressure) were not statistically different from zero, noted Dr. Stepnowsky of the VA San Diego Healthcare System.

The findings are of concern, he said, because suboptimal use of continuous positive airway pressure therapy leads to ineffective treatment and can increase the risk of morbidity and mortality.

A closer look at adherence rates showed that patterns of adherence were established as early as the first night of therapy, suggesting that preexisting factors might explain these patterns. Further studies in large, U.S.-based populations are needed to replicate these findings, as are studies to help identify the factors associated with adherence and to develop tools for improvement, he said.

ORLANDO – Ramelteon is effective for a subset of patients with insomnia, according to a presentation at a psychopharmacology congress sponsored by the Neuroscience Education Institute. In addition, because the agent works on melatonin receptors, a potential off-label use is for patients with shift-work disorder.

Ramelteon (Rozerem, Takeda Pharmaceuticals) targets the melatonin receptors MT1 and MT2. The agent is approximately 10 times more potent than melatonin. Other approved drugs promote sleep by increasing γ-aminobutyric acid (GABA), which is normally released by the suprachiasmatic nucleus in the brain.

“Ramelteon is a very interesting drug. It is the first on the market for sleep that does not work on the GABA system,” Dr. Wallace B. Mendelson said. The melatonin receptor agonist is a very shortacting drug with a half-life of 1 to 2 hours. “It is very potent for helping people fall asleep but not as effective for those who wake up early. So it's for a subset of patients.”

The Food and Drug Administration approved ramelteon for treatment of insomnia characterized by difficulty with sleep onset. “It is not a DEA classified substance, only a hypnotic without potential for dependence,” said Dr. Mendelson, psychopharmacology consultant for many pharmaceutical companies, including Takeda Pharmaceuticals North America Inc.

A delay to peak therapeutic effect is another distinction of ramelteon, compared with benzodiazepines and newer, nonbenzodiazepine GABA agonists such as zolpidem (Ambien, Sanofi-Aventis) or eszopiclone (Lunesta, Sepracor).

“It can take up to a week for full effect, so caution patients that they may not feel tired right away,” said Dr. Mendelson, who is also a consultant, an adviser, and on the speakers' bureau for Sanofi-Aventis and Sepracor Inc.

People with shift-work sleep disorder can experience excessive daytime sleepiness because their body rhythm stays the same but the world changes around them, Dr. Mendelson said.

“No one knows why some people are more susceptible to this, except it is harder to adapt to nighttime shift work as you get older.”

Pharmacotherapy with a sleep aid might be sufficient for a shift worker who complains only of sleepiness or trouble going off to sleep, Dr. Mendelson said. However, “if they are having trouble with both sleep and waking, it might make sense to try to help them shift to the new time. One way is to use melatonin.” Exogenous melatonin can shift circadian rhythms. Melatonin taken in the evening can shift a person's circadian rhythm earlier while melatonin in the morning can shift it later, he said.

“I have a real issue with the quality and standardization of melatonin. It's not consistent, which is why I prefer a drug like Rozerem,” Dr. Mendelson said. “Rozerem is not indicated for this, but some research indicates it can shift circadian rhythm with off-label use similar to melatonin.”

Another option for circadian rhythm adjustment is bright light therapy. “I like bright light therapy because it's more benign–but it works the opposite.” In the morning, the therapy pushes circadian rhythm phase earlier, and at night, it pushes it later.

Insomnia rarely occurs alone, Dr. Mendelson said. “About 80% of insomnia patients you see have some other disorder. The old name was secondary insomnia. Us sleep guys are now calling this comorbid insomnia.”

Ramelteon might be an appropriate choice for patients with sleep apnea, Dr. Mendelson said. A significant minority of sleep apnea will present with insomnia as the primary complaint. “We need to carefully diagnose because most of the agents we prescribe for insomnia can make sleep apnea worse, except ramelteon or the tricyclic antidepressants.”

The probability of diagnosing a psychiatric disorder increases among patients who complain of insomnia (Sleep Med. 2005;6:549–53). In this study, a survey of 200 general hospital patients indicated 57% reported insomnia and 50% reported at least one psychiatric disorder. Insomnia can play a major role in several psychiatric illnesses, especially depression, Dr. Mendelson said. “Targeting insomnia with sleep aids and behavioral therapy can improve outcomes.” Insomnia may also signal depression onset. “On average, 41% of people will have insomnia preceding depression.”

ORLANDO – Ramelteon is effective for a subset of patients with insomnia, according to a presentation at a psychopharmacology congress sponsored by the Neuroscience Education Institute. In addition, because the agent works on melatonin receptors, a potential off-label use is for patients with shift-work disorder.

Ramelteon (Rozerem, Takeda Pharmaceuticals) targets the melatonin receptors MT1 and MT2. The agent is approximately 10 times more potent than melatonin. Other approved drugs promote sleep by increasing γ-aminobutyric acid (GABA), which is normally released by the suprachiasmatic nucleus in the brain.

“Ramelteon is a very interesting drug. It is the first on the market for sleep that does not work on the GABA system,” Dr. Wallace B. Mendelson said. The melatonin receptor agonist is a very shortacting drug with a half-life of 1 to 2 hours. “It is very potent for helping people fall asleep but not as effective for those who wake up early. So it's for a subset of patients.”

The Food and Drug Administration approved ramelteon for treatment of insomnia characterized by difficulty with sleep onset. “It is not a DEA classified substance, only a hypnotic without potential for dependence,” said Dr. Mendelson, psychopharmacology consultant for many pharmaceutical companies, including Takeda Pharmaceuticals North America Inc.

A delay to peak therapeutic effect is another distinction of ramelteon, compared with benzodiazepines and newer, nonbenzodiazepine GABA agonists such as zolpidem (Ambien, Sanofi-Aventis) or eszopiclone (Lunesta, Sepracor).

“It can take up to a week for full effect, so caution patients that they may not feel tired right away,” said Dr. Mendelson, who is also a consultant, an adviser, and on the speakers' bureau for Sanofi-Aventis and Sepracor Inc.

People with shift-work sleep disorder can experience excessive daytime sleepiness because their body rhythm stays the same but the world changes around them, Dr. Mendelson said.

“No one knows why some people are more susceptible to this, except it is harder to adapt to nighttime shift work as you get older.”

Pharmacotherapy with a sleep aid might be sufficient for a shift worker who complains only of sleepiness or trouble going off to sleep, Dr. Mendelson said. However, “if they are having trouble with both sleep and waking, it might make sense to try to help them shift to the new time. One way is to use melatonin.” Exogenous melatonin can shift circadian rhythms. Melatonin taken in the evening can shift a person's circadian rhythm earlier while melatonin in the morning can shift it later, he said.

“I have a real issue with the quality and standardization of melatonin. It's not consistent, which is why I prefer a drug like Rozerem,” Dr. Mendelson said. “Rozerem is not indicated for this, but some research indicates it can shift circadian rhythm with off-label use similar to melatonin.”

Another option for circadian rhythm adjustment is bright light therapy. “I like bright light therapy because it's more benign–but it works the opposite.” In the morning, the therapy pushes circadian rhythm phase earlier, and at night, it pushes it later.

Insomnia rarely occurs alone, Dr. Mendelson said. “About 80% of insomnia patients you see have some other disorder. The old name was secondary insomnia. Us sleep guys are now calling this comorbid insomnia.”

Ramelteon might be an appropriate choice for patients with sleep apnea, Dr. Mendelson said. A significant minority of sleep apnea will present with insomnia as the primary complaint. “We need to carefully diagnose because most of the agents we prescribe for insomnia can make sleep apnea worse, except ramelteon or the tricyclic antidepressants.”

The probability of diagnosing a psychiatric disorder increases among patients who complain of insomnia (Sleep Med. 2005;6:549–53). In this study, a survey of 200 general hospital patients indicated 57% reported insomnia and 50% reported at least one psychiatric disorder. Insomnia can play a major role in several psychiatric illnesses, especially depression, Dr. Mendelson said. “Targeting insomnia with sleep aids and behavioral therapy can improve outcomes.” Insomnia may also signal depression onset. “On average, 41% of people will have insomnia preceding depression.”

ORLANDO – Ramelteon is effective for a subset of patients with insomnia, according to a presentation at a psychopharmacology congress sponsored by the Neuroscience Education Institute. In addition, because the agent works on melatonin receptors, a potential off-label use is for patients with shift-work disorder.

Ramelteon (Rozerem, Takeda Pharmaceuticals) targets the melatonin receptors MT1 and MT2. The agent is approximately 10 times more potent than melatonin. Other approved drugs promote sleep by increasing γ-aminobutyric acid (GABA), which is normally released by the suprachiasmatic nucleus in the brain.

“Ramelteon is a very interesting drug. It is the first on the market for sleep that does not work on the GABA system,” Dr. Wallace B. Mendelson said. The melatonin receptor agonist is a very shortacting drug with a half-life of 1 to 2 hours. “It is very potent for helping people fall asleep but not as effective for those who wake up early. So it's for a subset of patients.”

The Food and Drug Administration approved ramelteon for treatment of insomnia characterized by difficulty with sleep onset. “It is not a DEA classified substance, only a hypnotic without potential for dependence,” said Dr. Mendelson, psychopharmacology consultant for many pharmaceutical companies, including Takeda Pharmaceuticals North America Inc.

A delay to peak therapeutic effect is another distinction of ramelteon, compared with benzodiazepines and newer, nonbenzodiazepine GABA agonists such as zolpidem (Ambien, Sanofi-Aventis) or eszopiclone (Lunesta, Sepracor).

“It can take up to a week for full effect, so caution patients that they may not feel tired right away,” said Dr. Mendelson, who is also a consultant, an adviser, and on the speakers' bureau for Sanofi-Aventis and Sepracor Inc.

People with shift-work sleep disorder can experience excessive daytime sleepiness because their body rhythm stays the same but the world changes around them, Dr. Mendelson said.

“No one knows why some people are more susceptible to this, except it is harder to adapt to nighttime shift work as you get older.”

Pharmacotherapy with a sleep aid might be sufficient for a shift worker who complains only of sleepiness or trouble going off to sleep, Dr. Mendelson said. However, “if they are having trouble with both sleep and waking, it might make sense to try to help them shift to the new time. One way is to use melatonin.” Exogenous melatonin can shift circadian rhythms. Melatonin taken in the evening can shift a person's circadian rhythm earlier while melatonin in the morning can shift it later, he said.

“I have a real issue with the quality and standardization of melatonin. It's not consistent, which is why I prefer a drug like Rozerem,” Dr. Mendelson said. “Rozerem is not indicated for this, but some research indicates it can shift circadian rhythm with off-label use similar to melatonin.”

Another option for circadian rhythm adjustment is bright light therapy. “I like bright light therapy because it's more benign–but it works the opposite.” In the morning, the therapy pushes circadian rhythm phase earlier, and at night, it pushes it later.

Insomnia rarely occurs alone, Dr. Mendelson said. “About 80% of insomnia patients you see have some other disorder. The old name was secondary insomnia. Us sleep guys are now calling this comorbid insomnia.”

Ramelteon might be an appropriate choice for patients with sleep apnea, Dr. Mendelson said. A significant minority of sleep apnea will present with insomnia as the primary complaint. “We need to carefully diagnose because most of the agents we prescribe for insomnia can make sleep apnea worse, except ramelteon or the tricyclic antidepressants.”

The probability of diagnosing a psychiatric disorder increases among patients who complain of insomnia (Sleep Med. 2005;6:549–53). In this study, a survey of 200 general hospital patients indicated 57% reported insomnia and 50% reported at least one psychiatric disorder. Insomnia can play a major role in several psychiatric illnesses, especially depression, Dr. Mendelson said. “Targeting insomnia with sleep aids and behavioral therapy can improve outcomes.” Insomnia may also signal depression onset. “On average, 41% of people will have insomnia preceding depression.”

SALT LAKE CITY – Studies consistently show a link between obstructive sleep apnea and stroke, with the most recent data showing that sleep apnea is an independent risk factor for stroke and death.

The cumulative data in regard to sleep apnea and stroke suggest that patients with sleep apnea should be treated with continuous positive airway pressure (CPAP) or other measures, Dr. Vahid Mohsenin said at the annual meeting of the Associated Professional Sleep Societies.

The evidence supporting the efficacy of CPAP is overwhelming–with good compliance, efficacy is about 90%–and the expectation is that treatment will reduce the risk of stroke, although more research is needed to confirm this, said Dr. Mohsenin, professor of medicine and director of the Yale Center for Sleep Medicine, Yale University, New Haven, Conn.

In fact, a guideline from the American Heart Association/American Stroke Association Stroke Council for the primary prevention of ischemic stroke was updated earlier this year to incorporate new information about stroke prevention, including data on the role of sleep-disordered breathing in stroke. The guideline was initially published in 2001.

Although the guideline stops short of making specific treatment recommendations, and instead states that treatment should be individualized, it does address patient evaluation. It is reasonable that patients and their bed partners be questioned about symptoms of sleep-disordered breathing and that appropriate patients be referred to a sleep specialist for further evaluation, the guideline states.

This is particularly important if the patient has drug-resistant hypertension or certain risk factors for stroke, such as abdominal obesity and hypertension (Stroke 2006;37:1583–633).

In making its recommendation, the AHA/ASA Stroke Council cited data from several studies, including a case-control study of 181 patients, which showed an association between excessive daytime sleepiness (likely caused by obstructive sleep apnea) and stroke (odds ratio 3.07).

The council also cited a 10-year observational study of more than 1,600 men, which showed that those with severe obstructive sleep apnea-hypopnea had an increased risk of fatal and nonfatal cardiovascular events including stroke, compared with healthy individuals (OR 2.87 and 3.17, respectively).

The guideline noted that there are a number of biologically plausible mechanisms for a link between sleep apnea and stroke; Dr. Mohsenin agreed.

Several studies suggest that the mechanism by which sleep-disordered breathing increases stroke risk is by “leading to or worsening hypertension and heart disease and possibly by causing reductions in cerebral blood flow, altered cerebral autoregulation, impaired endothelial function, accelerated atherogenesis, hypercoagulability, inflammation, and paradoxical embolism in patients with patent foramen ovale,” the guideline states.

But the real question, Dr. Mohsenin said, is whether there is an independent association between sleep apnea and stroke, and a recent study on which he was an author shows that there is indeed such an association.

In the observational cohort study of 697 patients with obstructive sleep apnea and 325 controls (mean apnea-hypopnea index of 35 vs. 2 in the patients and controls, respectively), obstructive sleep apnea was found to have a statistically significant association with stroke or death (hazard ratio of 1.91) after adjustment for numerous factors, including age, sex, race, smoking status, alcohol consumption, body mass index, diabetes, hyperlipidemia, atrial fibrillation, and hypertension.

A trend analysis also showed a significant dose-response relationship between sleep apnea severity at baseline and development of a composite end point of stroke or death from any cause (N. Engl. J. Med. 2005;353:2034–41).

While randomized controlled trials are needed to firmly establish a causal link between sleep apnea and stroke–to “put the last nail in the coffin and say, 'ok, sleep apnea is indeed a cause of stroke in a high-risk patient population,'” as Dr. Mohsenin put it, the findings increasingly suggest this is the case. Also, sleep apnea occurs as commonly in transient ischemic attack as it does in stroke, further underscoring the need for sleep apnea treatment in affected patients, he noted.

Additionally, a number of studies have shown that sleep apnea is associated with worse functional outcomes in stroke patients, Dr. Mohsenin said.

Patients with stroke who have sleep apnea have been shown to have more delirium, depression, impaired functional capacity, longer rehabilitation time, and longer hospitalization, he said.

“Sleep apnea does affect the outcome of stroke,” he said, noting that in some studies these effects lasted out to 12 months.

Patients who have had a stroke should be evaluated for sleep disordered breathing, he advised.

In addition, patients using long-term CPAP should be reevaluated for residual symptoms of the disorder to ensure adequate treatment and compliance, he added.

SALT LAKE CITY – Studies consistently show a link between obstructive sleep apnea and stroke, with the most recent data showing that sleep apnea is an independent risk factor for stroke and death.

The cumulative data in regard to sleep apnea and stroke suggest that patients with sleep apnea should be treated with continuous positive airway pressure (CPAP) or other measures, Dr. Vahid Mohsenin said at the annual meeting of the Associated Professional Sleep Societies.

The evidence supporting the efficacy of CPAP is overwhelming–with good compliance, efficacy is about 90%–and the expectation is that treatment will reduce the risk of stroke, although more research is needed to confirm this, said Dr. Mohsenin, professor of medicine and director of the Yale Center for Sleep Medicine, Yale University, New Haven, Conn.

In fact, a guideline from the American Heart Association/American Stroke Association Stroke Council for the primary prevention of ischemic stroke was updated earlier this year to incorporate new information about stroke prevention, including data on the role of sleep-disordered breathing in stroke. The guideline was initially published in 2001.

Although the guideline stops short of making specific treatment recommendations, and instead states that treatment should be individualized, it does address patient evaluation. It is reasonable that patients and their bed partners be questioned about symptoms of sleep-disordered breathing and that appropriate patients be referred to a sleep specialist for further evaluation, the guideline states.

This is particularly important if the patient has drug-resistant hypertension or certain risk factors for stroke, such as abdominal obesity and hypertension (Stroke 2006;37:1583–633).

In making its recommendation, the AHA/ASA Stroke Council cited data from several studies, including a case-control study of 181 patients, which showed an association between excessive daytime sleepiness (likely caused by obstructive sleep apnea) and stroke (odds ratio 3.07).

The council also cited a 10-year observational study of more than 1,600 men, which showed that those with severe obstructive sleep apnea-hypopnea had an increased risk of fatal and nonfatal cardiovascular events including stroke, compared with healthy individuals (OR 2.87 and 3.17, respectively).

The guideline noted that there are a number of biologically plausible mechanisms for a link between sleep apnea and stroke; Dr. Mohsenin agreed.

Several studies suggest that the mechanism by which sleep-disordered breathing increases stroke risk is by “leading to or worsening hypertension and heart disease and possibly by causing reductions in cerebral blood flow, altered cerebral autoregulation, impaired endothelial function, accelerated atherogenesis, hypercoagulability, inflammation, and paradoxical embolism in patients with patent foramen ovale,” the guideline states.

But the real question, Dr. Mohsenin said, is whether there is an independent association between sleep apnea and stroke, and a recent study on which he was an author shows that there is indeed such an association.

In the observational cohort study of 697 patients with obstructive sleep apnea and 325 controls (mean apnea-hypopnea index of 35 vs. 2 in the patients and controls, respectively), obstructive sleep apnea was found to have a statistically significant association with stroke or death (hazard ratio of 1.91) after adjustment for numerous factors, including age, sex, race, smoking status, alcohol consumption, body mass index, diabetes, hyperlipidemia, atrial fibrillation, and hypertension.

A trend analysis also showed a significant dose-response relationship between sleep apnea severity at baseline and development of a composite end point of stroke or death from any cause (N. Engl. J. Med. 2005;353:2034–41).

While randomized controlled trials are needed to firmly establish a causal link between sleep apnea and stroke–to “put the last nail in the coffin and say, 'ok, sleep apnea is indeed a cause of stroke in a high-risk patient population,'” as Dr. Mohsenin put it, the findings increasingly suggest this is the case. Also, sleep apnea occurs as commonly in transient ischemic attack as it does in stroke, further underscoring the need for sleep apnea treatment in affected patients, he noted.

Additionally, a number of studies have shown that sleep apnea is associated with worse functional outcomes in stroke patients, Dr. Mohsenin said.

Patients with stroke who have sleep apnea have been shown to have more delirium, depression, impaired functional capacity, longer rehabilitation time, and longer hospitalization, he said.

“Sleep apnea does affect the outcome of stroke,” he said, noting that in some studies these effects lasted out to 12 months.

Patients who have had a stroke should be evaluated for sleep disordered breathing, he advised.

In addition, patients using long-term CPAP should be reevaluated for residual symptoms of the disorder to ensure adequate treatment and compliance, he added.

SALT LAKE CITY – Studies consistently show a link between obstructive sleep apnea and stroke, with the most recent data showing that sleep apnea is an independent risk factor for stroke and death.

The cumulative data in regard to sleep apnea and stroke suggest that patients with sleep apnea should be treated with continuous positive airway pressure (CPAP) or other measures, Dr. Vahid Mohsenin said at the annual meeting of the Associated Professional Sleep Societies.

The evidence supporting the efficacy of CPAP is overwhelming–with good compliance, efficacy is about 90%–and the expectation is that treatment will reduce the risk of stroke, although more research is needed to confirm this, said Dr. Mohsenin, professor of medicine and director of the Yale Center for Sleep Medicine, Yale University, New Haven, Conn.

In fact, a guideline from the American Heart Association/American Stroke Association Stroke Council for the primary prevention of ischemic stroke was updated earlier this year to incorporate new information about stroke prevention, including data on the role of sleep-disordered breathing in stroke. The guideline was initially published in 2001.

Although the guideline stops short of making specific treatment recommendations, and instead states that treatment should be individualized, it does address patient evaluation. It is reasonable that patients and their bed partners be questioned about symptoms of sleep-disordered breathing and that appropriate patients be referred to a sleep specialist for further evaluation, the guideline states.

This is particularly important if the patient has drug-resistant hypertension or certain risk factors for stroke, such as abdominal obesity and hypertension (Stroke 2006;37:1583–633).

In making its recommendation, the AHA/ASA Stroke Council cited data from several studies, including a case-control study of 181 patients, which showed an association between excessive daytime sleepiness (likely caused by obstructive sleep apnea) and stroke (odds ratio 3.07).

The council also cited a 10-year observational study of more than 1,600 men, which showed that those with severe obstructive sleep apnea-hypopnea had an increased risk of fatal and nonfatal cardiovascular events including stroke, compared with healthy individuals (OR 2.87 and 3.17, respectively).

The guideline noted that there are a number of biologically plausible mechanisms for a link between sleep apnea and stroke; Dr. Mohsenin agreed.

Several studies suggest that the mechanism by which sleep-disordered breathing increases stroke risk is by “leading to or worsening hypertension and heart disease and possibly by causing reductions in cerebral blood flow, altered cerebral autoregulation, impaired endothelial function, accelerated atherogenesis, hypercoagulability, inflammation, and paradoxical embolism in patients with patent foramen ovale,” the guideline states.

But the real question, Dr. Mohsenin said, is whether there is an independent association between sleep apnea and stroke, and a recent study on which he was an author shows that there is indeed such an association.

In the observational cohort study of 697 patients with obstructive sleep apnea and 325 controls (mean apnea-hypopnea index of 35 vs. 2 in the patients and controls, respectively), obstructive sleep apnea was found to have a statistically significant association with stroke or death (hazard ratio of 1.91) after adjustment for numerous factors, including age, sex, race, smoking status, alcohol consumption, body mass index, diabetes, hyperlipidemia, atrial fibrillation, and hypertension.

A trend analysis also showed a significant dose-response relationship between sleep apnea severity at baseline and development of a composite end point of stroke or death from any cause (N. Engl. J. Med. 2005;353:2034–41).

While randomized controlled trials are needed to firmly establish a causal link between sleep apnea and stroke–to “put the last nail in the coffin and say, 'ok, sleep apnea is indeed a cause of stroke in a high-risk patient population,'” as Dr. Mohsenin put it, the findings increasingly suggest this is the case. Also, sleep apnea occurs as commonly in transient ischemic attack as it does in stroke, further underscoring the need for sleep apnea treatment in affected patients, he noted.

Additionally, a number of studies have shown that sleep apnea is associated with worse functional outcomes in stroke patients, Dr. Mohsenin said.

Patients with stroke who have sleep apnea have been shown to have more delirium, depression, impaired functional capacity, longer rehabilitation time, and longer hospitalization, he said.

“Sleep apnea does affect the outcome of stroke,” he said, noting that in some studies these effects lasted out to 12 months.

Patients who have had a stroke should be evaluated for sleep disordered breathing, he advised.

In addition, patients using long-term CPAP should be reevaluated for residual symptoms of the disorder to ensure adequate treatment and compliance, he added.

CHICAGO – Episodes of extreme anger were linked to ventricular arrhythmias and shocks from implantable cardioverter defibrillators in a study with more than 1,000 patients.

Although the findings do not prove that severe anger triggers arrhythmias, the results are suggestive enough for physicians to advise patients with implantable cardioverter defibrillators (ICDs) to try to stay calm and avoid moments of rage, Dr. Christine A. Albert said while presenting a poster at the annual scientific sessions of the American Heart Association.

“I think that just knowing about the relationship [between anger and shocks] may help people [with ICDs] modify their behavior,” said Dr. Albert, director of the Center for Arrhythmia Prevention at Brigham and Women's Hospital, Boston. “There is a lot of anxiety associated with getting shocks. Patients ask what they can do to minimize their shocks.”

Dr. Albert stopped short of recommending interventions in patients with ICDs who have trouble controlling their anger, but she suggested that physicians may want to refer certain patients to a psychiatrist.

The Triggers of Ventricular Arrhythmia (TOVA) study was done at seven centers in the United States. Patients who had received ICDs were interviewed regarding their usual frequency of anger at entry into the study and at follow-up visits. In addition, following an ICD discharge, patients were interviewed within 72 hours of the shock to collect information on their emotional state during the period just before the shock. Most patients were on an antiarrhythmic drug; about 60% received a β-blocker, and about 25% were taking amiodarone.

During a median follow-up of 562 days, 1,149 patients in the study had a total of 414 shocks, of which 324 were triggered by ventricular tachycardia or fibrillation. Postshock interviews were completed within 72 hours of the episode for 197 of the ventricular arrhythmia shocks, in 161 patients.

Patients were asked to characterize their emotional state on a scale of 1–7, with 1 defined as calm, 4 defined as moderately angry, 5 defined as very angry, 6 defined as furious, and 7 defined as enraged. Of the 197 shocks, 12 (6%) occurred after an episode that the patients classified as grade 4–7 anger.

In a case-crossover analysis, patients who had grade-4 anger or higher had a fivefold increased risk of receiving a shock during the first 30 minutes after the episode, compared with patients who were not as angry. Patients with grade-5 anger or higher had about a 30-fold increased risk of a shock during the first 30 minutes after the episode, and within the first 2 hours after the episode their risk of a shock was elevated about 10-fold compared with calmer patients, Dr. Albert reported.

The effect was magnified in patients with worse ventricular function at baseline, in those who previously received an ICD shock, in patients who had received their ICD within the prior 6 months, and in patients who were employed.

It's not surprising that anger has this effect. Prior findings showed that the simulation of anger in patients with coronary heart disease who were asked to perform mental arithmetic can cause electrophysiologic instability, measured by a change in the T-wave alternans. And a similar link between anger and ICD shocks was seen in a much smaller (49 patients), earlier study. All of the findings suggest that something occurs during anger to make the heart more electrically unstable. And anger activates the sympathetic nervous system, which also probably plays a role in arrhythmias, Dr. Albert said.

CHICAGO – Episodes of extreme anger were linked to ventricular arrhythmias and shocks from implantable cardioverter defibrillators in a study with more than 1,000 patients.

Although the findings do not prove that severe anger triggers arrhythmias, the results are suggestive enough for physicians to advise patients with implantable cardioverter defibrillators (ICDs) to try to stay calm and avoid moments of rage, Dr. Christine A. Albert said while presenting a poster at the annual scientific sessions of the American Heart Association.

“I think that just knowing about the relationship [between anger and shocks] may help people [with ICDs] modify their behavior,” said Dr. Albert, director of the Center for Arrhythmia Prevention at Brigham and Women's Hospital, Boston. “There is a lot of anxiety associated with getting shocks. Patients ask what they can do to minimize their shocks.”

Dr. Albert stopped short of recommending interventions in patients with ICDs who have trouble controlling their anger, but she suggested that physicians may want to refer certain patients to a psychiatrist.

The Triggers of Ventricular Arrhythmia (TOVA) study was done at seven centers in the United States. Patients who had received ICDs were interviewed regarding their usual frequency of anger at entry into the study and at follow-up visits. In addition, following an ICD discharge, patients were interviewed within 72 hours of the shock to collect information on their emotional state during the period just before the shock. Most patients were on an antiarrhythmic drug; about 60% received a β-blocker, and about 25% were taking amiodarone.

During a median follow-up of 562 days, 1,149 patients in the study had a total of 414 shocks, of which 324 were triggered by ventricular tachycardia or fibrillation. Postshock interviews were completed within 72 hours of the episode for 197 of the ventricular arrhythmia shocks, in 161 patients.

Patients were asked to characterize their emotional state on a scale of 1–7, with 1 defined as calm, 4 defined as moderately angry, 5 defined as very angry, 6 defined as furious, and 7 defined as enraged. Of the 197 shocks, 12 (6%) occurred after an episode that the patients classified as grade 4–7 anger.

In a case-crossover analysis, patients who had grade-4 anger or higher had a fivefold increased risk of receiving a shock during the first 30 minutes after the episode, compared with patients who were not as angry. Patients with grade-5 anger or higher had about a 30-fold increased risk of a shock during the first 30 minutes after the episode, and within the first 2 hours after the episode their risk of a shock was elevated about 10-fold compared with calmer patients, Dr. Albert reported.

The effect was magnified in patients with worse ventricular function at baseline, in those who previously received an ICD shock, in patients who had received their ICD within the prior 6 months, and in patients who were employed.

It's not surprising that anger has this effect. Prior findings showed that the simulation of anger in patients with coronary heart disease who were asked to perform mental arithmetic can cause electrophysiologic instability, measured by a change in the T-wave alternans. And a similar link between anger and ICD shocks was seen in a much smaller (49 patients), earlier study. All of the findings suggest that something occurs during anger to make the heart more electrically unstable. And anger activates the sympathetic nervous system, which also probably plays a role in arrhythmias, Dr. Albert said.

CHICAGO – Episodes of extreme anger were linked to ventricular arrhythmias and shocks from implantable cardioverter defibrillators in a study with more than 1,000 patients.

Although the findings do not prove that severe anger triggers arrhythmias, the results are suggestive enough for physicians to advise patients with implantable cardioverter defibrillators (ICDs) to try to stay calm and avoid moments of rage, Dr. Christine A. Albert said while presenting a poster at the annual scientific sessions of the American Heart Association.

“I think that just knowing about the relationship [between anger and shocks] may help people [with ICDs] modify their behavior,” said Dr. Albert, director of the Center for Arrhythmia Prevention at Brigham and Women's Hospital, Boston. “There is a lot of anxiety associated with getting shocks. Patients ask what they can do to minimize their shocks.”

Dr. Albert stopped short of recommending interventions in patients with ICDs who have trouble controlling their anger, but she suggested that physicians may want to refer certain patients to a psychiatrist.

The Triggers of Ventricular Arrhythmia (TOVA) study was done at seven centers in the United States. Patients who had received ICDs were interviewed regarding their usual frequency of anger at entry into the study and at follow-up visits. In addition, following an ICD discharge, patients were interviewed within 72 hours of the shock to collect information on their emotional state during the period just before the shock. Most patients were on an antiarrhythmic drug; about 60% received a β-blocker, and about 25% were taking amiodarone.

During a median follow-up of 562 days, 1,149 patients in the study had a total of 414 shocks, of which 324 were triggered by ventricular tachycardia or fibrillation. Postshock interviews were completed within 72 hours of the episode for 197 of the ventricular arrhythmia shocks, in 161 patients.

Patients were asked to characterize their emotional state on a scale of 1–7, with 1 defined as calm, 4 defined as moderately angry, 5 defined as very angry, 6 defined as furious, and 7 defined as enraged. Of the 197 shocks, 12 (6%) occurred after an episode that the patients classified as grade 4–7 anger.

In a case-crossover analysis, patients who had grade-4 anger or higher had a fivefold increased risk of receiving a shock during the first 30 minutes after the episode, compared with patients who were not as angry. Patients with grade-5 anger or higher had about a 30-fold increased risk of a shock during the first 30 minutes after the episode, and within the first 2 hours after the episode their risk of a shock was elevated about 10-fold compared with calmer patients, Dr. Albert reported.

The effect was magnified in patients with worse ventricular function at baseline, in those who previously received an ICD shock, in patients who had received their ICD within the prior 6 months, and in patients who were employed.

It's not surprising that anger has this effect. Prior findings showed that the simulation of anger in patients with coronary heart disease who were asked to perform mental arithmetic can cause electrophysiologic instability, measured by a change in the T-wave alternans. And a similar link between anger and ICD shocks was seen in a much smaller (49 patients), earlier study. All of the findings suggest that something occurs during anger to make the heart more electrically unstable. And anger activates the sympathetic nervous system, which also probably plays a role in arrhythmias, Dr. Albert said.

PARIS – Pooled data from two clinical trials of eszopiclone suggest that elderly insomniacs have more difficulty staying asleep than falling asleep, Judy Caron, Ph.D., reported at the annual congress of the European College of Neuropsychopharmacology.

Before treatment, time to sleep onset was similar across patients aged 18–85, according to Dr. Caron, vice president of product development at Sepracor Inc. in Marlborough, Mass. People 60 years of age and older were awake roughly a third more of the time, however, compared with younger patients. Dr. Caron documented this difference using data on wake time after sleep onset.

In both age groups, measures of sleep onset and sleep maintenance improved significantly with eszopiclone (Lunesta), a sedative hypnotic approved by the U.S. Food and Drug Administration in April 2005 for long-term treatment of insomnia.

“Sleep maintenance really is the major sleep disruption that occurs in the elderly,” Dr. Caron said.

Her presentation drew upon a database of 1,616 insomniacs who participated in two 6-month-long, placebo-controlled trials of eszopiclone. The trials enrolled 1,441 patients aged 18–59 and 175 older patients. Most in both age groups were on the active drug.

Pooled analyses of these studies found daytime alertness, ability to function, and sense of physical well-being to be comparable in both age groups, with similar improvements when treated with eszopiclone. She did not present the data, but Dr. Caron said elderly patients were found to nap less when their insomnia was treated.

She reported adverse events were slightly higher in the elderly on eszopiclone, however, occurring in 90% of older patients vs. 77% of those under the age of 60. Dr. Caron attributed the higher adverse event rate in the elderly primarily to central nervous system events. These occurred in 37% of older patients, compared with 27% of those under the age of 60.

“What is remarkable is there is no difference in terms of accidental injury in the older age group,” she added. About 7% of the elderly and 6% of the younger patients had accidental injuries during the trials.

Insomnia increases with age, Dr. Caron said. The prevalence of insomnia rises from 10% of young adults to 20%–30% in middle age to 33%–55% in those above the age of 65. It is comorbid in 85%–90% of cases, she said.

Worldwide, she estimated that 40% of people suffer from insomnia. Yet, she said, only one in eight patients seek treatment, and physicians rarely ask whether patients are getting enough sleep.

Older patients, who have a significant problem in terms of sleep, especially are undertreated, Dr. Caron said.

Worldwide, 40% of people suffer from insomnia, but only one in eight patients seek treatment. DR. CARON

PARIS – Pooled data from two clinical trials of eszopiclone suggest that elderly insomniacs have more difficulty staying asleep than falling asleep, Judy Caron, Ph.D., reported at the annual congress of the European College of Neuropsychopharmacology.

Before treatment, time to sleep onset was similar across patients aged 18–85, according to Dr. Caron, vice president of product development at Sepracor Inc. in Marlborough, Mass. People 60 years of age and older were awake roughly a third more of the time, however, compared with younger patients. Dr. Caron documented this difference using data on wake time after sleep onset.

In both age groups, measures of sleep onset and sleep maintenance improved significantly with eszopiclone (Lunesta), a sedative hypnotic approved by the U.S. Food and Drug Administration in April 2005 for long-term treatment of insomnia.

“Sleep maintenance really is the major sleep disruption that occurs in the elderly,” Dr. Caron said.

Her presentation drew upon a database of 1,616 insomniacs who participated in two 6-month-long, placebo-controlled trials of eszopiclone. The trials enrolled 1,441 patients aged 18–59 and 175 older patients. Most in both age groups were on the active drug.

Pooled analyses of these studies found daytime alertness, ability to function, and sense of physical well-being to be comparable in both age groups, with similar improvements when treated with eszopiclone. She did not present the data, but Dr. Caron said elderly patients were found to nap less when their insomnia was treated.

She reported adverse events were slightly higher in the elderly on eszopiclone, however, occurring in 90% of older patients vs. 77% of those under the age of 60. Dr. Caron attributed the higher adverse event rate in the elderly primarily to central nervous system events. These occurred in 37% of older patients, compared with 27% of those under the age of 60.

“What is remarkable is there is no difference in terms of accidental injury in the older age group,” she added. About 7% of the elderly and 6% of the younger patients had accidental injuries during the trials.

Insomnia increases with age, Dr. Caron said. The prevalence of insomnia rises from 10% of young adults to 20%–30% in middle age to 33%–55% in those above the age of 65. It is comorbid in 85%–90% of cases, she said.

Worldwide, she estimated that 40% of people suffer from insomnia. Yet, she said, only one in eight patients seek treatment, and physicians rarely ask whether patients are getting enough sleep.

Older patients, who have a significant problem in terms of sleep, especially are undertreated, Dr. Caron said.

Worldwide, 40% of people suffer from insomnia, but only one in eight patients seek treatment. DR. CARON

PARIS – Pooled data from two clinical trials of eszopiclone suggest that elderly insomniacs have more difficulty staying asleep than falling asleep, Judy Caron, Ph.D., reported at the annual congress of the European College of Neuropsychopharmacology.

Before treatment, time to sleep onset was similar across patients aged 18–85, according to Dr. Caron, vice president of product development at Sepracor Inc. in Marlborough, Mass. People 60 years of age and older were awake roughly a third more of the time, however, compared with younger patients. Dr. Caron documented this difference using data on wake time after sleep onset.

In both age groups, measures of sleep onset and sleep maintenance improved significantly with eszopiclone (Lunesta), a sedative hypnotic approved by the U.S. Food and Drug Administration in April 2005 for long-term treatment of insomnia.

“Sleep maintenance really is the major sleep disruption that occurs in the elderly,” Dr. Caron said.

Her presentation drew upon a database of 1,616 insomniacs who participated in two 6-month-long, placebo-controlled trials of eszopiclone. The trials enrolled 1,441 patients aged 18–59 and 175 older patients. Most in both age groups were on the active drug.

Pooled analyses of these studies found daytime alertness, ability to function, and sense of physical well-being to be comparable in both age groups, with similar improvements when treated with eszopiclone. She did not present the data, but Dr. Caron said elderly patients were found to nap less when their insomnia was treated.

She reported adverse events were slightly higher in the elderly on eszopiclone, however, occurring in 90% of older patients vs. 77% of those under the age of 60. Dr. Caron attributed the higher adverse event rate in the elderly primarily to central nervous system events. These occurred in 37% of older patients, compared with 27% of those under the age of 60.

“What is remarkable is there is no difference in terms of accidental injury in the older age group,” she added. About 7% of the elderly and 6% of the younger patients had accidental injuries during the trials.

Insomnia increases with age, Dr. Caron said. The prevalence of insomnia rises from 10% of young adults to 20%–30% in middle age to 33%–55% in those above the age of 65. It is comorbid in 85%–90% of cases, she said.

Worldwide, she estimated that 40% of people suffer from insomnia. Yet, she said, only one in eight patients seek treatment, and physicians rarely ask whether patients are getting enough sleep.

Older patients, who have a significant problem in terms of sleep, especially are undertreated, Dr. Caron said.

Worldwide, 40% of people suffer from insomnia, but only one in eight patients seek treatment. DR. CARON

CHICAGO – Self-oriented and socially prescribed perfectionism in female college students who also have body dissatisfaction are important factors putting these women at risk for eating disorders, Christina A. Downey said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

“Body dissatisfaction was the strongest predictor of eating disorders,” said Ms. Downey, a graduate student at the University of Michigan in Ann Arbor.

The study evaluated 310 women enrolled in a psychology class at a large university. Of the original sample, 307 turned in complete questionnaires.

The age of the participants ranged from 18 to 38 years, with a mean of 19 years. Of the 310 women, 189 (61%) were white, 36 (12%) were black, 9 (3%) were Hispanic, 53 (17%) were Asian American/Pacific Islander, 1 (0.3%) was in the category of Native American/Inuit/Alaska Native, 19 (6%) identified as being Other, and 3 (1%) gave no indication of racial/ethnic group. In the present sample, body mass index (BMI) ranged from 15.34 kg/m

The researchers used the Multidimensional Perfectionism Scale (MPS) to measure perfectionism. They also used items deemed by a panel to be related to weight from the Body Areas Satisfaction (BAS) scale from the Multidimensional Body-Self Relations Questionnaire to measure body dissatisfaction.

In addition to these scales, the researchers used the Positive and Negative Affect Scale to measure negative affect. To measure for eating disturbances, they used the bulimia scale of the Eating Disorders Inventory and the dieting scale of the Eating Attitudes Test.

The results, as measured by the EAT-Dieting and EDI-Bulimia scales, respectively, showed that both self-oriented and socially prescribed perfectionism were associated with greater dieting and bulimic symptoms. However, the association between MPS-Social and EDI-Bulimia scores was found to be greater than the association between MPS-Self and EDI-Bulimia scores (rs = .32 versus .20, respectively, z = 2.26, p = .01), indicating that socially prescribed perfectionism is more strongly involved in bulimic symptoms than is self-oriented perfectionism.

Moreover, the association between MPS-Social and EDI-Bulimia scores was found to be greater than the association between MPS-Social and EAT-Dieting scores.

The researchers also found that both self-oriented and socially prescribed perfectionism were found to be associated with greater negative affect and greater body dissatisfaction. They determined, however, that the association between MPS-Social and BAS-Weight scores was greater than the association between MPS-Self and BAS-Weight scores.

They also found that negative affect was associated with both more dieting and more bulimic symptoms.

Ms. Downey concluded that the interactions between perfectionism and body dissatisfaction were extremely important, and that the presence or lack of body dissatisfaction could be a clue to the presence of eating disorders in college-aged women. “We found no relationship between perfectionism and eating disorders in the highly bodily satisfied group,” she added.

On the other hand, clinicians should be aware of how powerfully perfectionism and body dissatisfaction can interact together in young women. “The interaction between socially prescribed perfectionism and eating disturbance was clinically important, as it points to a particularly dangerous combination of personality traits and cognition in predicting serious symptoms of an eating disorder,” Ms. Downey said in an interview.

CHICAGO – Self-oriented and socially prescribed perfectionism in female college students who also have body dissatisfaction are important factors putting these women at risk for eating disorders, Christina A. Downey said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

“Body dissatisfaction was the strongest predictor of eating disorders,” said Ms. Downey, a graduate student at the University of Michigan in Ann Arbor.

The study evaluated 310 women enrolled in a psychology class at a large university. Of the original sample, 307 turned in complete questionnaires.

The age of the participants ranged from 18 to 38 years, with a mean of 19 years. Of the 310 women, 189 (61%) were white, 36 (12%) were black, 9 (3%) were Hispanic, 53 (17%) were Asian American/Pacific Islander, 1 (0.3%) was in the category of Native American/Inuit/Alaska Native, 19 (6%) identified as being Other, and 3 (1%) gave no indication of racial/ethnic group. In the present sample, body mass index (BMI) ranged from 15.34 kg/m

The researchers used the Multidimensional Perfectionism Scale (MPS) to measure perfectionism. They also used items deemed by a panel to be related to weight from the Body Areas Satisfaction (BAS) scale from the Multidimensional Body-Self Relations Questionnaire to measure body dissatisfaction.

In addition to these scales, the researchers used the Positive and Negative Affect Scale to measure negative affect. To measure for eating disturbances, they used the bulimia scale of the Eating Disorders Inventory and the dieting scale of the Eating Attitudes Test.

The results, as measured by the EAT-Dieting and EDI-Bulimia scales, respectively, showed that both self-oriented and socially prescribed perfectionism were associated with greater dieting and bulimic symptoms. However, the association between MPS-Social and EDI-Bulimia scores was found to be greater than the association between MPS-Self and EDI-Bulimia scores (rs = .32 versus .20, respectively, z = 2.26, p = .01), indicating that socially prescribed perfectionism is more strongly involved in bulimic symptoms than is self-oriented perfectionism.

Moreover, the association between MPS-Social and EDI-Bulimia scores was found to be greater than the association between MPS-Social and EAT-Dieting scores.

The researchers also found that both self-oriented and socially prescribed perfectionism were found to be associated with greater negative affect and greater body dissatisfaction. They determined, however, that the association between MPS-Social and BAS-Weight scores was greater than the association between MPS-Self and BAS-Weight scores.

They also found that negative affect was associated with both more dieting and more bulimic symptoms.

Ms. Downey concluded that the interactions between perfectionism and body dissatisfaction were extremely important, and that the presence or lack of body dissatisfaction could be a clue to the presence of eating disorders in college-aged women. “We found no relationship between perfectionism and eating disorders in the highly bodily satisfied group,” she added.

On the other hand, clinicians should be aware of how powerfully perfectionism and body dissatisfaction can interact together in young women. “The interaction between socially prescribed perfectionism and eating disturbance was clinically important, as it points to a particularly dangerous combination of personality traits and cognition in predicting serious symptoms of an eating disorder,” Ms. Downey said in an interview.

CHICAGO – Self-oriented and socially prescribed perfectionism in female college students who also have body dissatisfaction are important factors putting these women at risk for eating disorders, Christina A. Downey said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

“Body dissatisfaction was the strongest predictor of eating disorders,” said Ms. Downey, a graduate student at the University of Michigan in Ann Arbor.

The study evaluated 310 women enrolled in a psychology class at a large university. Of the original sample, 307 turned in complete questionnaires.

The age of the participants ranged from 18 to 38 years, with a mean of 19 years. Of the 310 women, 189 (61%) were white, 36 (12%) were black, 9 (3%) were Hispanic, 53 (17%) were Asian American/Pacific Islander, 1 (0.3%) was in the category of Native American/Inuit/Alaska Native, 19 (6%) identified as being Other, and 3 (1%) gave no indication of racial/ethnic group. In the present sample, body mass index (BMI) ranged from 15.34 kg/m

The researchers used the Multidimensional Perfectionism Scale (MPS) to measure perfectionism. They also used items deemed by a panel to be related to weight from the Body Areas Satisfaction (BAS) scale from the Multidimensional Body-Self Relations Questionnaire to measure body dissatisfaction.

In addition to these scales, the researchers used the Positive and Negative Affect Scale to measure negative affect. To measure for eating disturbances, they used the bulimia scale of the Eating Disorders Inventory and the dieting scale of the Eating Attitudes Test.

The results, as measured by the EAT-Dieting and EDI-Bulimia scales, respectively, showed that both self-oriented and socially prescribed perfectionism were associated with greater dieting and bulimic symptoms. However, the association between MPS-Social and EDI-Bulimia scores was found to be greater than the association between MPS-Self and EDI-Bulimia scores (rs = .32 versus .20, respectively, z = 2.26, p = .01), indicating that socially prescribed perfectionism is more strongly involved in bulimic symptoms than is self-oriented perfectionism.

Moreover, the association between MPS-Social and EDI-Bulimia scores was found to be greater than the association between MPS-Social and EAT-Dieting scores.

The researchers also found that both self-oriented and socially prescribed perfectionism were found to be associated with greater negative affect and greater body dissatisfaction. They determined, however, that the association between MPS-Social and BAS-Weight scores was greater than the association between MPS-Self and BAS-Weight scores.

They also found that negative affect was associated with both more dieting and more bulimic symptoms.

Ms. Downey concluded that the interactions between perfectionism and body dissatisfaction were extremely important, and that the presence or lack of body dissatisfaction could be a clue to the presence of eating disorders in college-aged women. “We found no relationship between perfectionism and eating disorders in the highly bodily satisfied group,” she added.

On the other hand, clinicians should be aware of how powerfully perfectionism and body dissatisfaction can interact together in young women. “The interaction between socially prescribed perfectionism and eating disturbance was clinically important, as it points to a particularly dangerous combination of personality traits and cognition in predicting serious symptoms of an eating disorder,” Ms. Downey said in an interview.

Dr. Amanda A. Beck and her colleagues were puzzled by some of their patients at the University of New Mexico's Sleep Disorders Center in Albuquerque. The patients took methadone, but they did not have histories of drug abuse. They were middle-class baby boomers under treatment for chronic pain, and their nighttime breathing problems were severe.

They needed a variable positive airway pressure device, the VPAP Adapt, recently approved for the treatment of central sleep apnea, mixed sleep apnea, and periodic breathing. “We are getting this very complicated sleep-disordered breathing, which used not to be in our lexicon,” Dr. Beck, director of adult services, said at a university-sponsored psychiatric symposium, where she described her center's experience as a red flag for methadone prescribers.

Concern about accidental deaths from methadone use is long-standing. Reports linking methadone to sleep-disordered breathing are a recent and, as yet, poorly understood phenomenon. Dr. Beck said her group and other sleep centers are documenting cases of sleep-disordered breathing in methadone patients, now estimated at one per week in her clinic.

The Food and Drug Administration has responded to concern over methadone related deaths and complications with an advisory. (See related story, p. 2.)

Several studies of the complication have been published, but most accounts are anecdotal. Some reports focus on patients on methadone maintenance, while others address the growing number of people taking opioids for chronic pain. (See box.)

Emerging Evidence

In 2003, physicians at the Intermountain Sleep Disorders Center in Salt Lake City described ataxic breathing, central apnea, sustained hypoxemia, and other abnormalities in three patients on long-term opioid therapy for pain (Chest 2003;123:632–9).

That article spurred Dr. Lynn R. Webster to order sleep studies on patients prescribed opioid therapies at the Lifetree Pain Clinic in Salt Lake City. Dr. Webster, medical director of the clinic and its affiliated research center, presented polysomnography data on 152 patients at the American Academy of Pain meeting in February 2006.

Three-fourths of the patients had an abnormal apnea-hypopnea index, including 42% with obstructive sleep apnea, 12% with central sleep apnea, and 21% with mixed obstructive and central sleep apnea. One-third of the patients had been prescribed methadone and long-acting opioids; 4% took only methadone, according to the abstract.

In another study that Dr. Webster presented at the same meeting, he compared polysomnography data on 73 opioid-naive primary care patients who had been referred for sleep studies with data on 139 asymptomatic chronic pain patients taking opioids. In both groups, 36% of the patients had severe sleep apnea.

Obstructive sleep apnea was more common in the primary care patients at 89%, vs. 77% of cases in the pain group. Central sleep apnea, a more severe condition, occurred more in the pain patients: 32%, vs. 6% of the primary care cases.

As a result of his ongoing research, Dr. Webster has become a campaigner for more conservative use of methadone. “No one was aware this was a problem. Most pain practices would not ordinarily order sleep studies,” he said in an interview with this newspaper.

Dr. Webster emphasized that he is not opposed to methadone use for pain management. “But patients and physicians need to understand it is not like other opioids.”

Recent reports have also associated methadone with poor sleep quality in addiction patients at maintenance programs.

A U.S. study reported that 84% of 225 patients were “poor” sleepers with Pittsburgh Sleep Quality Index scores of 6 or higher (J. Subst. Abuse Treat. 2004;26:175–80).

Israeli researchers found that 75% of 102 patients were poor sleepers (Drug Alcohol Depend. 2006;82:103–10).

Searching for Mechanisms

Looking for sleep-disordered breathing (SDB), an Australian group reported that 30% of 50 stable methadone maintenance patients had central sleep apnea.

Blood methadone level was significantly associated with severity but was only a minor contributing factor, explaining just 12% of the variability. The authors speculated that central sleep apnea in the population “may be multifactorial in nature and related to abnormalities of the central controller and central and peripheral metabolic control mechanisms” (Chest 2005;128:1348–56).

Abnormalities in both waking hypoxic and hypercapnic ventilatory responses in the methadone patients would lead to this instability, Dr. Harry Teichtahl, who is director of respiratory and sleep disorders medicine at Western Health in Victoria, said in an interview.

Instability in carbon dioxide ventilatory responses may be involved in SDB in asymptomatic patients, continued Dr. Teichtahl, of the University of Melbourne.

His study showed a high prevalence of central sleep apnea, he said, but the patients had no more obstructive sleep apnea than a normal control group did.

Risky Business

Last July, researchers from the CDC reported that increases in prescriptions for opioid analgesics paralleled and may have contributed to an annual 18% increase in unintentional drug-poisoning deaths from 1990 to 2002.

From 1999 to 2002, the number of death certificates listing methadone poisoning rose by 213%, according to Dr. Leonard Jduring this period, while sales through narcotics treatment programs rose only 43% (Pharmacoepidemiol. Drug Saf. 2006;15:618–27).

'We are getting this very complicated sleep-disordered breathing, which used not to be in our lexicon.' DR. BECK

Methadone Prescribing on the Rise

Not without irony, Dr. Webster said physicians turned to methadone for treatment of pain in part because they believed it was safer than other opioids and less likely to bring regulatory sanctions. When OxyContin abuse became a public policy issue, they saw methadone as a drug with little street value or abuse potential.

“Physicians think it is safe because it has been used for addiction so many years,” he said.

Health insurers also appear to have played a role. Methadone is the cheapest opioid by far. One estimate puts the monthly cost to pharmacists as $8 for an oral dose of 5 mg taken three times a day, based on wholesale prices. In comparison, chronic pain therapy with generic sustained-release morphine would cost $101.50; MS Contin, $113.50; OxyContin, $176.50; and Duragesic, $154 (Am. Fam. Physician 2005; 71:1353–8).

Confronted with such steep price differences, some health plans reportedly have made methadone their drug of choice when an opioid is prescribed for pain. In many cases, Dr. Beck said, that is why methadone is being prescribed to older pain patients with comorbidities and other medications that can interact with methadone.

“It is really irresponsible of insurers and HMOs, of anyone who sets up a formulary that [designates] the most dangerous in its entire category as the first-line agent to be used. I think that is unconscionable,” she said.

Formularies also are responsible for an increase in methadone prescribing by primary care physicians who are not familiar with its unique characteristics, according to Dr. Howard A. Heit, a chronic pain specialist certified in addiction medicine who practices in Fairfax, Va. “Are we forcing doctors to use a medication that they don't have the knowledge to use, which could be fraught with major complications, which will cost more in the long run?” he asked during an interview.

Dr. Heit served on a U.S. Substance Abuse and Mental Services Administration panel that reported in 2004 on nationwide increases in methadone-related deaths. The panel cited as a likely factor a fivefold increase from 1998 to 2002 in the volume of methadone distributed through pharmacies. The risk of apnea was not considered because it was not an issue at that time, he said.

Dr. Amanda A. Beck and her colleagues were puzzled by some of their patients at the University of New Mexico's Sleep Disorders Center in Albuquerque. The patients took methadone, but they did not have histories of drug abuse. They were middle-class baby boomers under treatment for chronic pain, and their nighttime breathing problems were severe.

They needed a variable positive airway pressure device, the VPAP Adapt, recently approved for the treatment of central sleep apnea, mixed sleep apnea, and periodic breathing. “We are getting this very complicated sleep-disordered breathing, which used not to be in our lexicon,” Dr. Beck, director of adult services, said at a university-sponsored psychiatric symposium, where she described her center's experience as a red flag for methadone prescribers.

Concern about accidental deaths from methadone use is long-standing. Reports linking methadone to sleep-disordered breathing are a recent and, as yet, poorly understood phenomenon. Dr. Beck said her group and other sleep centers are documenting cases of sleep-disordered breathing in methadone patients, now estimated at one per week in her clinic.

The Food and Drug Administration has responded to concern over methadone related deaths and complications with an advisory. (See related story, p. 2.)

Several studies of the complication have been published, but most accounts are anecdotal. Some reports focus on patients on methadone maintenance, while others address the growing number of people taking opioids for chronic pain. (See box.)

Emerging Evidence

In 2003, physicians at the Intermountain Sleep Disorders Center in Salt Lake City described ataxic breathing, central apnea, sustained hypoxemia, and other abnormalities in three patients on long-term opioid therapy for pain (Chest 2003;123:632–9).

That article spurred Dr. Lynn R. Webster to order sleep studies on patients prescribed opioid therapies at the Lifetree Pain Clinic in Salt Lake City. Dr. Webster, medical director of the clinic and its affiliated research center, presented polysomnography data on 152 patients at the American Academy of Pain meeting in February 2006.

Three-fourths of the patients had an abnormal apnea-hypopnea index, including 42% with obstructive sleep apnea, 12% with central sleep apnea, and 21% with mixed obstructive and central sleep apnea. One-third of the patients had been prescribed methadone and long-acting opioids; 4% took only methadone, according to the abstract.

In another study that Dr. Webster presented at the same meeting, he compared polysomnography data on 73 opioid-naive primary care patients who had been referred for sleep studies with data on 139 asymptomatic chronic pain patients taking opioids. In both groups, 36% of the patients had severe sleep apnea.

Obstructive sleep apnea was more common in the primary care patients at 89%, vs. 77% of cases in the pain group. Central sleep apnea, a more severe condition, occurred more in the pain patients: 32%, vs. 6% of the primary care cases.

As a result of his ongoing research, Dr. Webster has become a campaigner for more conservative use of methadone. “No one was aware this was a problem. Most pain practices would not ordinarily order sleep studies,” he said in an interview with this newspaper.

Dr. Webster emphasized that he is not opposed to methadone use for pain management. “But patients and physicians need to understand it is not like other opioids.”

Recent reports have also associated methadone with poor sleep quality in addiction patients at maintenance programs.

A U.S. study reported that 84% of 225 patients were “poor” sleepers with Pittsburgh Sleep Quality Index scores of 6 or higher (J. Subst. Abuse Treat. 2004;26:175–80).

Israeli researchers found that 75% of 102 patients were poor sleepers (Drug Alcohol Depend. 2006;82:103–10).

Searching for Mechanisms

Looking for sleep-disordered breathing (SDB), an Australian group reported that 30% of 50 stable methadone maintenance patients had central sleep apnea.

Blood methadone level was significantly associated with severity but was only a minor contributing factor, explaining just 12% of the variability. The authors speculated that central sleep apnea in the population “may be multifactorial in nature and related to abnormalities of the central controller and central and peripheral metabolic control mechanisms” (Chest 2005;128:1348–56).

Abnormalities in both waking hypoxic and hypercapnic ventilatory responses in the methadone patients would lead to this instability, Dr. Harry Teichtahl, who is director of respiratory and sleep disorders medicine at Western Health in Victoria, said in an interview.

Instability in carbon dioxide ventilatory responses may be involved in SDB in asymptomatic patients, continued Dr. Teichtahl, of the University of Melbourne.

His study showed a high prevalence of central sleep apnea, he said, but the patients had no more obstructive sleep apnea than a normal control group did.

Risky Business

Last July, researchers from the CDC reported that increases in prescriptions for opioid analgesics paralleled and may have contributed to an annual 18% increase in unintentional drug-poisoning deaths from 1990 to 2002.

From 1999 to 2002, the number of death certificates listing methadone poisoning rose by 213%, according to Dr. Leonard Jduring this period, while sales through narcotics treatment programs rose only 43% (Pharmacoepidemiol. Drug Saf. 2006;15:618–27).

'We are getting this very complicated sleep-disordered breathing, which used not to be in our lexicon.' DR. BECK

Methadone Prescribing on the Rise

Not without irony, Dr. Webster said physicians turned to methadone for treatment of pain in part because they believed it was safer than other opioids and less likely to bring regulatory sanctions. When OxyContin abuse became a public policy issue, they saw methadone as a drug with little street value or abuse potential.

“Physicians think it is safe because it has been used for addiction so many years,” he said.

Health insurers also appear to have played a role. Methadone is the cheapest opioid by far. One estimate puts the monthly cost to pharmacists as $8 for an oral dose of 5 mg taken three times a day, based on wholesale prices. In comparison, chronic pain therapy with generic sustained-release morphine would cost $101.50; MS Contin, $113.50; OxyContin, $176.50; and Duragesic, $154 (Am. Fam. Physician 2005; 71:1353–8).

Confronted with such steep price differences, some health plans reportedly have made methadone their drug of choice when an opioid is prescribed for pain. In many cases, Dr. Beck said, that is why methadone is being prescribed to older pain patients with comorbidities and other medications that can interact with methadone.

“It is really irresponsible of insurers and HMOs, of anyone who sets up a formulary that [designates] the most dangerous in its entire category as the first-line agent to be used. I think that is unconscionable,” she said.

Formularies also are responsible for an increase in methadone prescribing by primary care physicians who are not familiar with its unique characteristics, according to Dr. Howard A. Heit, a chronic pain specialist certified in addiction medicine who practices in Fairfax, Va. “Are we forcing doctors to use a medication that they don't have the knowledge to use, which could be fraught with major complications, which will cost more in the long run?” he asked during an interview.

Dr. Heit served on a U.S. Substance Abuse and Mental Services Administration panel that reported in 2004 on nationwide increases in methadone-related deaths. The panel cited as a likely factor a fivefold increase from 1998 to 2002 in the volume of methadone distributed through pharmacies. The risk of apnea was not considered because it was not an issue at that time, he said.

Dr. Amanda A. Beck and her colleagues were puzzled by some of their patients at the University of New Mexico's Sleep Disorders Center in Albuquerque. The patients took methadone, but they did not have histories of drug abuse. They were middle-class baby boomers under treatment for chronic pain, and their nighttime breathing problems were severe.

They needed a variable positive airway pressure device, the VPAP Adapt, recently approved for the treatment of central sleep apnea, mixed sleep apnea, and periodic breathing. “We are getting this very complicated sleep-disordered breathing, which used not to be in our lexicon,” Dr. Beck, director of adult services, said at a university-sponsored psychiatric symposium, where she described her center's experience as a red flag for methadone prescribers.

Concern about accidental deaths from methadone use is long-standing. Reports linking methadone to sleep-disordered breathing are a recent and, as yet, poorly understood phenomenon. Dr. Beck said her group and other sleep centers are documenting cases of sleep-disordered breathing in methadone patients, now estimated at one per week in her clinic.

The Food and Drug Administration has responded to concern over methadone related deaths and complications with an advisory. (See related story, p. 2.)

Several studies of the complication have been published, but most accounts are anecdotal. Some reports focus on patients on methadone maintenance, while others address the growing number of people taking opioids for chronic pain. (See box.)

Emerging Evidence

In 2003, physicians at the Intermountain Sleep Disorders Center in Salt Lake City described ataxic breathing, central apnea, sustained hypoxemia, and other abnormalities in three patients on long-term opioid therapy for pain (Chest 2003;123:632–9).

That article spurred Dr. Lynn R. Webster to order sleep studies on patients prescribed opioid therapies at the Lifetree Pain Clinic in Salt Lake City. Dr. Webster, medical director of the clinic and its affiliated research center, presented polysomnography data on 152 patients at the American Academy of Pain meeting in February 2006.

Three-fourths of the patients had an abnormal apnea-hypopnea index, including 42% with obstructive sleep apnea, 12% with central sleep apnea, and 21% with mixed obstructive and central sleep apnea. One-third of the patients had been prescribed methadone and long-acting opioids; 4% took only methadone, according to the abstract.

In another study that Dr. Webster presented at the same meeting, he compared polysomnography data on 73 opioid-naive primary care patients who had been referred for sleep studies with data on 139 asymptomatic chronic pain patients taking opioids. In both groups, 36% of the patients had severe sleep apnea.

Obstructive sleep apnea was more common in the primary care patients at 89%, vs. 77% of cases in the pain group. Central sleep apnea, a more severe condition, occurred more in the pain patients: 32%, vs. 6% of the primary care cases.

As a result of his ongoing research, Dr. Webster has become a campaigner for more conservative use of methadone. “No one was aware this was a problem. Most pain practices would not ordinarily order sleep studies,” he said in an interview with this newspaper.

Dr. Webster emphasized that he is not opposed to methadone use for pain management. “But patients and physicians need to understand it is not like other opioids.”

Recent reports have also associated methadone with poor sleep quality in addiction patients at maintenance programs.

A U.S. study reported that 84% of 225 patients were “poor” sleepers with Pittsburgh Sleep Quality Index scores of 6 or higher (J. Subst. Abuse Treat. 2004;26:175–80).

Israeli researchers found that 75% of 102 patients were poor sleepers (Drug Alcohol Depend. 2006;82:103–10).

Searching for Mechanisms

Looking for sleep-disordered breathing (SDB), an Australian group reported that 30% of 50 stable methadone maintenance patients had central sleep apnea.

Blood methadone level was significantly associated with severity but was only a minor contributing factor, explaining just 12% of the variability. The authors speculated that central sleep apnea in the population “may be multifactorial in nature and related to abnormalities of the central controller and central and peripheral metabolic control mechanisms” (Chest 2005;128:1348–56).

Abnormalities in both waking hypoxic and hypercapnic ventilatory responses in the methadone patients would lead to this instability, Dr. Harry Teichtahl, who is director of respiratory and sleep disorders medicine at Western Health in Victoria, said in an interview.

Instability in carbon dioxide ventilatory responses may be involved in SDB in asymptomatic patients, continued Dr. Teichtahl, of the University of Melbourne.

His study showed a high prevalence of central sleep apnea, he said, but the patients had no more obstructive sleep apnea than a normal control group did.

Risky Business

Last July, researchers from the CDC reported that increases in prescriptions for opioid analgesics paralleled and may have contributed to an annual 18% increase in unintentional drug-poisoning deaths from 1990 to 2002.

From 1999 to 2002, the number of death certificates listing methadone poisoning rose by 213%, according to Dr. Leonard Jduring this period, while sales through narcotics treatment programs rose only 43% (Pharmacoepidemiol. Drug Saf. 2006;15:618–27).

'We are getting this very complicated sleep-disordered breathing, which used not to be in our lexicon.' DR. BECK

Methadone Prescribing on the Rise

Not without irony, Dr. Webster said physicians turned to methadone for treatment of pain in part because they believed it was safer than other opioids and less likely to bring regulatory sanctions. When OxyContin abuse became a public policy issue, they saw methadone as a drug with little street value or abuse potential.

“Physicians think it is safe because it has been used for addiction so many years,” he said.

Health insurers also appear to have played a role. Methadone is the cheapest opioid by far. One estimate puts the monthly cost to pharmacists as $8 for an oral dose of 5 mg taken three times a day, based on wholesale prices. In comparison, chronic pain therapy with generic sustained-release morphine would cost $101.50; MS Contin, $113.50; OxyContin, $176.50; and Duragesic, $154 (Am. Fam. Physician 2005; 71:1353–8).

Confronted with such steep price differences, some health plans reportedly have made methadone their drug of choice when an opioid is prescribed for pain. In many cases, Dr. Beck said, that is why methadone is being prescribed to older pain patients with comorbidities and other medications that can interact with methadone.

“It is really irresponsible of insurers and HMOs, of anyone who sets up a formulary that [designates] the most dangerous in its entire category as the first-line agent to be used. I think that is unconscionable,” she said.

Formularies also are responsible for an increase in methadone prescribing by primary care physicians who are not familiar with its unique characteristics, according to Dr. Howard A. Heit, a chronic pain specialist certified in addiction medicine who practices in Fairfax, Va. “Are we forcing doctors to use a medication that they don't have the knowledge to use, which could be fraught with major complications, which will cost more in the long run?” he asked during an interview.

Dr. Heit served on a U.S. Substance Abuse and Mental Services Administration panel that reported in 2004 on nationwide increases in methadone-related deaths. The panel cited as a likely factor a fivefold increase from 1998 to 2002 in the volume of methadone distributed through pharmacies. The risk of apnea was not considered because it was not an issue at that time, he said.

SALT LAKE CITY – Increased caffeine intake was associated with better cognitive functioning in patients with obstructive sleep apnea, according to the results of a small study.

In 42 patients with untreated obstructive sleep apnea, a statistically significant inverse relationship was found between caffeine intake and a global deficit score that was derived from an aggregate measure of neuropsychological functioning, Dr. Daniel Norman reported at the annual meeting of the Associated Professional Sleep Societies.

The association persisted after controlling for body mass index and apnea-hypopnea index, said Dr. Norman of the University of California, San Diego.

Patients had a mean apnea-hypopnea index of 63 episodes per hour, indicating severe sleep apnea. The neuropsychological assessment battery included tests of speed of information processing, executive functioning, memory skills, verbal skills, and attention and working memory domains.

Caffeine intake was assessed using a detailed instrument that has been shown to characterize usual caffeine consumption based on 24-hour recall.

Daily caffeine intake in cognitively impaired patients was one-sixth that of non-cognitively impaired patients (30 mg vs. 180 mg), Dr. Norman said. Previous findings that obstructive sleep apnea patients consume three times the caffeine of nonapneic individuals on a daily basis led to speculation that those with sleep apnea were self-medicating with caffeine to counteract daytime sleepiness. Caffeine has been shown to enhance cognition, and the findings of the current study suggest this is an additional effect experienced by those who use caffeine for that purpose.

SALT LAKE CITY – Increased caffeine intake was associated with better cognitive functioning in patients with obstructive sleep apnea, according to the results of a small study.

In 42 patients with untreated obstructive sleep apnea, a statistically significant inverse relationship was found between caffeine intake and a global deficit score that was derived from an aggregate measure of neuropsychological functioning, Dr. Daniel Norman reported at the annual meeting of the Associated Professional Sleep Societies.

The association persisted after controlling for body mass index and apnea-hypopnea index, said Dr. Norman of the University of California, San Diego.

Patients had a mean apnea-hypopnea index of 63 episodes per hour, indicating severe sleep apnea. The neuropsychological assessment battery included tests of speed of information processing, executive functioning, memory skills, verbal skills, and attention and working memory domains.

Caffeine intake was assessed using a detailed instrument that has been shown to characterize usual caffeine consumption based on 24-hour recall.

Daily caffeine intake in cognitively impaired patients was one-sixth that of non-cognitively impaired patients (30 mg vs. 180 mg), Dr. Norman said. Previous findings that obstructive sleep apnea patients consume three times the caffeine of nonapneic individuals on a daily basis led to speculation that those with sleep apnea were self-medicating with caffeine to counteract daytime sleepiness. Caffeine has been shown to enhance cognition, and the findings of the current study suggest this is an additional effect experienced by those who use caffeine for that purpose.

SALT LAKE CITY – Increased caffeine intake was associated with better cognitive functioning in patients with obstructive sleep apnea, according to the results of a small study.

In 42 patients with untreated obstructive sleep apnea, a statistically significant inverse relationship was found between caffeine intake and a global deficit score that was derived from an aggregate measure of neuropsychological functioning, Dr. Daniel Norman reported at the annual meeting of the Associated Professional Sleep Societies.

The association persisted after controlling for body mass index and apnea-hypopnea index, said Dr. Norman of the University of California, San Diego.

Patients had a mean apnea-hypopnea index of 63 episodes per hour, indicating severe sleep apnea. The neuropsychological assessment battery included tests of speed of information processing, executive functioning, memory skills, verbal skills, and attention and working memory domains.

Caffeine intake was assessed using a detailed instrument that has been shown to characterize usual caffeine consumption based on 24-hour recall.

Daily caffeine intake in cognitively impaired patients was one-sixth that of non-cognitively impaired patients (30 mg vs. 180 mg), Dr. Norman said. Previous findings that obstructive sleep apnea patients consume three times the caffeine of nonapneic individuals on a daily basis led to speculation that those with sleep apnea were self-medicating with caffeine to counteract daytime sleepiness. Caffeine has been shown to enhance cognition, and the findings of the current study suggest this is an additional effect experienced by those who use caffeine for that purpose.