Somatic Disorders

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

NASHVILLE, TENN. – Treatment with methylphenidate safely reduced fatigue and depression in hospice patients in a controlled study with 30 patients.

“Treatment with methylphenidate may restore coping modalities that are compromised in patients with advanced illness,” Dr. Christopher Kerr and associates reported in a poster at the annual meeting of the American Academy of Hospice and Palliative Medicine. “Methylphenidate's efficacy appeared to go beyond improving depression, because depression was not the sole factor that predicted a reduction in fatigue,” they said. The drug's efficacy exceeded acting as a stimulant because it also reduced anxiety and promoted sleep.

The study included patients with a terminal illness who had symptoms of fatigue for at least 2 weeks and a fatigue score of at least 4 on the Edmonton Symptom Assessment Scale (ESAS). The study excluded patients with a history of seizures or cardiac arrhythmias, patients with dementia, psychosis, cognitive impairment, severe hepatic or renal dysfunction, and patients treated with antidepressant medication.

Patients were randomized to treatment with 5 mg of methylphenidate b.i.d. or placebo for 2 weeks. The methylphenidate dosage could be increased by 5 mg/day every few days based on patient responses and adverse effects. During the study, the dosage of methylphenidate used ranged from 10 mg to 40 mg/day. Patients were assessed after 3, 7, and 14 days of treatment.

After 14 days, the average ESAS fatigue score among the 15 patients treated with methylphenidate fell from 7.4 at baseline to 2.69, a statistically significant difference. Among the 15 patients treated with placebo, the average score fell from 6.93 at baseline to 6.58, a nonsignificant difference, reported Dr. Kerr, medical director of Hospice Buffalo (N.Y.) Home Care, and his associates.

The patients showed a similar pattern of changes in fatigue when assessed by two other measures: the Piper Fatigue scale, and the Visual Analog Scale for Fatigue. Reductions in fatigue among patients getting methylphenidate occurred in a dose-dependent manner, and began to appear 3 days after the start of treatment.

The drug also was effective at reducing depression scores. Among the patients treated with methylphenidate, the average score on the Beck Depression Inventory scale fell by 22% after 14 days of treatment, compared with baseline, the average score on the Center for Epidemiologic Studies-Depression Scale fell by 33%, and the average ESAS depression score fell by 35%. Changes from baseline in the placebo group were much smaller.

Improvements also were seen in additional scores measured with the ESAS, including scores for well-being, anxiety, and pain. Methylphenidate treatment did not significantly improve functional status.

Vital signs were not changed in patients taking methylphenidate for 2 weeks, and adverse effects were minor. The drug was not discontinued in any patient because of toxicity. Methylphenidate treatment was associated with worsening nausea.

NASHVILLE, TENN. – Treatment with methylphenidate safely reduced fatigue and depression in hospice patients in a controlled study with 30 patients.

“Treatment with methylphenidate may restore coping modalities that are compromised in patients with advanced illness,” Dr. Christopher Kerr and associates reported in a poster at the annual meeting of the American Academy of Hospice and Palliative Medicine. “Methylphenidate's efficacy appeared to go beyond improving depression, because depression was not the sole factor that predicted a reduction in fatigue,” they said. The drug's efficacy exceeded acting as a stimulant because it also reduced anxiety and promoted sleep.

The study included patients with a terminal illness who had symptoms of fatigue for at least 2 weeks and a fatigue score of at least 4 on the Edmonton Symptom Assessment Scale (ESAS). The study excluded patients with a history of seizures or cardiac arrhythmias, patients with dementia, psychosis, cognitive impairment, severe hepatic or renal dysfunction, and patients treated with antidepressant medication.

Patients were randomized to treatment with 5 mg of methylphenidate b.i.d. or placebo for 2 weeks. The methylphenidate dosage could be increased by 5 mg/day every few days based on patient responses and adverse effects. During the study, the dosage of methylphenidate used ranged from 10 mg to 40 mg/day. Patients were assessed after 3, 7, and 14 days of treatment.

After 14 days, the average ESAS fatigue score among the 15 patients treated with methylphenidate fell from 7.4 at baseline to 2.69, a statistically significant difference. Among the 15 patients treated with placebo, the average score fell from 6.93 at baseline to 6.58, a nonsignificant difference, reported Dr. Kerr, medical director of Hospice Buffalo (N.Y.) Home Care, and his associates.

The patients showed a similar pattern of changes in fatigue when assessed by two other measures: the Piper Fatigue scale, and the Visual Analog Scale for Fatigue. Reductions in fatigue among patients getting methylphenidate occurred in a dose-dependent manner, and began to appear 3 days after the start of treatment.

The drug also was effective at reducing depression scores. Among the patients treated with methylphenidate, the average score on the Beck Depression Inventory scale fell by 22% after 14 days of treatment, compared with baseline, the average score on the Center for Epidemiologic Studies-Depression Scale fell by 33%, and the average ESAS depression score fell by 35%. Changes from baseline in the placebo group were much smaller.

Improvements also were seen in additional scores measured with the ESAS, including scores for well-being, anxiety, and pain. Methylphenidate treatment did not significantly improve functional status.

Vital signs were not changed in patients taking methylphenidate for 2 weeks, and adverse effects were minor. The drug was not discontinued in any patient because of toxicity. Methylphenidate treatment was associated with worsening nausea.

NASHVILLE, TENN. – Treatment with methylphenidate safely reduced fatigue and depression in hospice patients in a controlled study with 30 patients.

“Treatment with methylphenidate may restore coping modalities that are compromised in patients with advanced illness,” Dr. Christopher Kerr and associates reported in a poster at the annual meeting of the American Academy of Hospice and Palliative Medicine. “Methylphenidate's efficacy appeared to go beyond improving depression, because depression was not the sole factor that predicted a reduction in fatigue,” they said. The drug's efficacy exceeded acting as a stimulant because it also reduced anxiety and promoted sleep.

The study included patients with a terminal illness who had symptoms of fatigue for at least 2 weeks and a fatigue score of at least 4 on the Edmonton Symptom Assessment Scale (ESAS). The study excluded patients with a history of seizures or cardiac arrhythmias, patients with dementia, psychosis, cognitive impairment, severe hepatic or renal dysfunction, and patients treated with antidepressant medication.

Patients were randomized to treatment with 5 mg of methylphenidate b.i.d. or placebo for 2 weeks. The methylphenidate dosage could be increased by 5 mg/day every few days based on patient responses and adverse effects. During the study, the dosage of methylphenidate used ranged from 10 mg to 40 mg/day. Patients were assessed after 3, 7, and 14 days of treatment.

After 14 days, the average ESAS fatigue score among the 15 patients treated with methylphenidate fell from 7.4 at baseline to 2.69, a statistically significant difference. Among the 15 patients treated with placebo, the average score fell from 6.93 at baseline to 6.58, a nonsignificant difference, reported Dr. Kerr, medical director of Hospice Buffalo (N.Y.) Home Care, and his associates.

The patients showed a similar pattern of changes in fatigue when assessed by two other measures: the Piper Fatigue scale, and the Visual Analog Scale for Fatigue. Reductions in fatigue among patients getting methylphenidate occurred in a dose-dependent manner, and began to appear 3 days after the start of treatment.

The drug also was effective at reducing depression scores. Among the patients treated with methylphenidate, the average score on the Beck Depression Inventory scale fell by 22% after 14 days of treatment, compared with baseline, the average score on the Center for Epidemiologic Studies-Depression Scale fell by 33%, and the average ESAS depression score fell by 35%. Changes from baseline in the placebo group were much smaller.

Improvements also were seen in additional scores measured with the ESAS, including scores for well-being, anxiety, and pain. Methylphenidate treatment did not significantly improve functional status.

Vital signs were not changed in patients taking methylphenidate for 2 weeks, and adverse effects were minor. The drug was not discontinued in any patient because of toxicity. Methylphenidate treatment was associated with worsening nausea.

TUCSON, ARIZ. – Nutritional rehabilitation may require involuntary hospitalization in patients with eating disorders. “These behaviors can be easily defined as self-harming behaviors, and these patients can and should be committed if they fall below a certain weight,” Dr. Chelsea Chesen reported at a psychopharmacology conference sponsored by the University of Arizona.

The most important rules for a psychiatrist are to put safety first, take a multidisciplinary approach rather than going it alone, and create an individualized treatment plan.

Weight goals should be realistic, but there also needs to be an understanding that, should the patient fail to meet the goal, there will be certain consequences, including hospitalization. A weight gain of 0.5–1.5 pounds/week is appropriate for outpatients, and 2–3 pounds/week for inpatients, said Dr. Chesen, of the psychiatry department at the university.

Clinicians should consult with a nutritionist, if possible, to develop regular, structured diets for their patients. They also might want to adopt a behavioral contract with the patient or the patient's parent for eating meals and choosing foods. Anxiolytics given 30–60 minutes before meals can help patients with anxiety about eating.

It is particularly important to encourage patients with anorexia to eat small, frequent meals, typically about six a day. “Part of the reason for that is that they will be extremely uncomfortable physically if they take in a large amount of food because their gut won't know what to do with it, and it takes time to literally process the food,” she said.

Some patients referred to Dr. Chesen have been on total parenteral nutrition, but this approach doesn't teach the gut to work properly for the long term and can cause liver abnormalities, she said.

If nasogastric feeding is necessary, she recommends using the smallest tube possible, such as a pediatric tube, and feeding continuously over 24 hours at the slowest possible rate. A bolus or gastrostomy tube should not be used to administer feedings.

Too-rapid refeeding is a major problem in patients with anorexia, because their bodies can become overwhelmed with the sudden intake of nutrients, leading to severe fluid retention, electrolyte disturbances, arrhythmias, seizures, coma, and death. “You want to be really gentle and really slow,” Dr. Chesen said. “Keep in mind that they didn't get this way overnight, so you're not going to get them healthy overnight.”

Physical examinations and laboratory evaluations should be performed every 2 weeks, especially in patients who are severely malnourished at the start of treatment. Clinicians should be aware that during refeeding, changes in body shape and clothing fit can trigger severe anxiety or depression.

All patients with eating disorders should take a multivitamin plus vitamin D and calcium. Because of the risk of death secondary to cardiac arrhythmias in patients with anorexia, clinicians should consider oral vitamin K supplementation, which has been shown to normalize the QT interval. “I'm not saying you should put every anorexic on potassium, but they should have an EKG, and their potassium levels should be followed by their primary care physician,” she said.

TUCSON, ARIZ. – Nutritional rehabilitation may require involuntary hospitalization in patients with eating disorders. “These behaviors can be easily defined as self-harming behaviors, and these patients can and should be committed if they fall below a certain weight,” Dr. Chelsea Chesen reported at a psychopharmacology conference sponsored by the University of Arizona.

The most important rules for a psychiatrist are to put safety first, take a multidisciplinary approach rather than going it alone, and create an individualized treatment plan.

Weight goals should be realistic, but there also needs to be an understanding that, should the patient fail to meet the goal, there will be certain consequences, including hospitalization. A weight gain of 0.5–1.5 pounds/week is appropriate for outpatients, and 2–3 pounds/week for inpatients, said Dr. Chesen, of the psychiatry department at the university.

Clinicians should consult with a nutritionist, if possible, to develop regular, structured diets for their patients. They also might want to adopt a behavioral contract with the patient or the patient's parent for eating meals and choosing foods. Anxiolytics given 30–60 minutes before meals can help patients with anxiety about eating.

It is particularly important to encourage patients with anorexia to eat small, frequent meals, typically about six a day. “Part of the reason for that is that they will be extremely uncomfortable physically if they take in a large amount of food because their gut won't know what to do with it, and it takes time to literally process the food,” she said.

Some patients referred to Dr. Chesen have been on total parenteral nutrition, but this approach doesn't teach the gut to work properly for the long term and can cause liver abnormalities, she said.

If nasogastric feeding is necessary, she recommends using the smallest tube possible, such as a pediatric tube, and feeding continuously over 24 hours at the slowest possible rate. A bolus or gastrostomy tube should not be used to administer feedings.

Too-rapid refeeding is a major problem in patients with anorexia, because their bodies can become overwhelmed with the sudden intake of nutrients, leading to severe fluid retention, electrolyte disturbances, arrhythmias, seizures, coma, and death. “You want to be really gentle and really slow,” Dr. Chesen said. “Keep in mind that they didn't get this way overnight, so you're not going to get them healthy overnight.”

Physical examinations and laboratory evaluations should be performed every 2 weeks, especially in patients who are severely malnourished at the start of treatment. Clinicians should be aware that during refeeding, changes in body shape and clothing fit can trigger severe anxiety or depression.

All patients with eating disorders should take a multivitamin plus vitamin D and calcium. Because of the risk of death secondary to cardiac arrhythmias in patients with anorexia, clinicians should consider oral vitamin K supplementation, which has been shown to normalize the QT interval. “I'm not saying you should put every anorexic on potassium, but they should have an EKG, and their potassium levels should be followed by their primary care physician,” she said.

TUCSON, ARIZ. – Nutritional rehabilitation may require involuntary hospitalization in patients with eating disorders. “These behaviors can be easily defined as self-harming behaviors, and these patients can and should be committed if they fall below a certain weight,” Dr. Chelsea Chesen reported at a psychopharmacology conference sponsored by the University of Arizona.

The most important rules for a psychiatrist are to put safety first, take a multidisciplinary approach rather than going it alone, and create an individualized treatment plan.

Weight goals should be realistic, but there also needs to be an understanding that, should the patient fail to meet the goal, there will be certain consequences, including hospitalization. A weight gain of 0.5–1.5 pounds/week is appropriate for outpatients, and 2–3 pounds/week for inpatients, said Dr. Chesen, of the psychiatry department at the university.

Clinicians should consult with a nutritionist, if possible, to develop regular, structured diets for their patients. They also might want to adopt a behavioral contract with the patient or the patient's parent for eating meals and choosing foods. Anxiolytics given 30–60 minutes before meals can help patients with anxiety about eating.

It is particularly important to encourage patients with anorexia to eat small, frequent meals, typically about six a day. “Part of the reason for that is that they will be extremely uncomfortable physically if they take in a large amount of food because their gut won't know what to do with it, and it takes time to literally process the food,” she said.

Some patients referred to Dr. Chesen have been on total parenteral nutrition, but this approach doesn't teach the gut to work properly for the long term and can cause liver abnormalities, she said.

If nasogastric feeding is necessary, she recommends using the smallest tube possible, such as a pediatric tube, and feeding continuously over 24 hours at the slowest possible rate. A bolus or gastrostomy tube should not be used to administer feedings.

Too-rapid refeeding is a major problem in patients with anorexia, because their bodies can become overwhelmed with the sudden intake of nutrients, leading to severe fluid retention, electrolyte disturbances, arrhythmias, seizures, coma, and death. “You want to be really gentle and really slow,” Dr. Chesen said. “Keep in mind that they didn't get this way overnight, so you're not going to get them healthy overnight.”

Physical examinations and laboratory evaluations should be performed every 2 weeks, especially in patients who are severely malnourished at the start of treatment. Clinicians should be aware that during refeeding, changes in body shape and clothing fit can trigger severe anxiety or depression.

All patients with eating disorders should take a multivitamin plus vitamin D and calcium. Because of the risk of death secondary to cardiac arrhythmias in patients with anorexia, clinicians should consider oral vitamin K supplementation, which has been shown to normalize the QT interval. “I'm not saying you should put every anorexic on potassium, but they should have an EKG, and their potassium levels should be followed by their primary care physician,” she said.

Anorexia nervosa is a heritable psychiatric disorder with warning signs that can be identified decades before the onset of the illness, the largest twin study on the disorder shows.

“Genes play a substantial role in the development of this illness; there is a clear biological component,” said lead author Cynthia M. Bulik, Ph.D., in a teleconference about the new research (Arch. Gen. Psychiatry 2006;63:305–12).

The findings are good news for patients and their families, said Dr. Bulik, the William R. and Jeanne H. Jordan Distinguished Professor of Eating Disorders at the University of North Carolina, Chapel Hill.

“We have gone through too much time where parents have been blamed. Now families and patients can be liberated and empowered,” Dr. Bulik said. “This helps them understand they are fighting their biology.”

The study included 31,406 twins from the Swedish Twin Registry. The twins, born during 1935–1958, were sent a questionnaire in 1973 that assessed demographics, physical illnesses, physical activity level, personality, stress, and work exposures. Seven potential predictors of the development of anorexia nervosa (AN) were evaluated in the questionnaire, including body mass index, gastric problems, excessive exercise, perceived life stress, neuroticism, and extraversion. Zygosity information also was obtained.

The subjects were then interviewed in 1998–2002 at a median age of 54.6 years to establish who had gone on to develop AN, and to determine the predictors.

The study found that 1.2% of the females and 0.29% of the males met diagnostic criteria for a lifetime history of AN, a prevalence in line with other studies of the disorder. However, when the cohort was divided into those born in 1944 or earlier, and those born in 1945 or later, there was evidence of an increasing prevalence in women (0.65% prevalence in the older female cohort, compared with 1.56% in the younger group). Prevalence rates did not change for men.

Examining the incidence of AN as it related to zygosity, the researchers found a much higher concordance rate for AN among monozygotic twins than among dizygotic twins–signaling a clear genetic component, Dr. Bulik said. The analysis revealed that genetics accounted for 56% of an individual's risk of developing the disorder, unique environment accounted for 38%, and shared environment accounted for 5%.

This information is promising in the search for targeted prevention and medical treatments for AN, she said. “Research like this shows [AN] is not a sociocultural disorder. We need to look elsewhere. We need to look at genes.” She said other work in this field has identified several genes on chromosome 1 that might be involved in the development of AN and could be medication targets.

“I am perplexed and disappointed that we don't have medication for AN, and this is in part because we have not yet explained the biology adequately,” she said.

The study also found that of the potential predictors of AN assessed in the 1973 questionnaire, only neuroticism was predictive of the development of the disorder. The finding is notable because there have been few “truly prospective” risk-factor studies of AN, Dr. Bulik noted in the study. “What remains unknown is whether neuroticism is a nonspecific predictor of the development of psychopathology in general or whether it is specifically predictive of the emergence of AN.”

ELSEVIER GLOBAL MEDICAL NEWS

Anorexia nervosa is a heritable psychiatric disorder with warning signs that can be identified decades before the onset of the illness, the largest twin study on the disorder shows.

“Genes play a substantial role in the development of this illness; there is a clear biological component,” said lead author Cynthia M. Bulik, Ph.D., in a teleconference about the new research (Arch. Gen. Psychiatry 2006;63:305–12).

The findings are good news for patients and their families, said Dr. Bulik, the William R. and Jeanne H. Jordan Distinguished Professor of Eating Disorders at the University of North Carolina, Chapel Hill.

“We have gone through too much time where parents have been blamed. Now families and patients can be liberated and empowered,” Dr. Bulik said. “This helps them understand they are fighting their biology.”

The study included 31,406 twins from the Swedish Twin Registry. The twins, born during 1935–1958, were sent a questionnaire in 1973 that assessed demographics, physical illnesses, physical activity level, personality, stress, and work exposures. Seven potential predictors of the development of anorexia nervosa (AN) were evaluated in the questionnaire, including body mass index, gastric problems, excessive exercise, perceived life stress, neuroticism, and extraversion. Zygosity information also was obtained.

The subjects were then interviewed in 1998–2002 at a median age of 54.6 years to establish who had gone on to develop AN, and to determine the predictors.

The study found that 1.2% of the females and 0.29% of the males met diagnostic criteria for a lifetime history of AN, a prevalence in line with other studies of the disorder. However, when the cohort was divided into those born in 1944 or earlier, and those born in 1945 or later, there was evidence of an increasing prevalence in women (0.65% prevalence in the older female cohort, compared with 1.56% in the younger group). Prevalence rates did not change for men.

Examining the incidence of AN as it related to zygosity, the researchers found a much higher concordance rate for AN among monozygotic twins than among dizygotic twins–signaling a clear genetic component, Dr. Bulik said. The analysis revealed that genetics accounted for 56% of an individual's risk of developing the disorder, unique environment accounted for 38%, and shared environment accounted for 5%.

This information is promising in the search for targeted prevention and medical treatments for AN, she said. “Research like this shows [AN] is not a sociocultural disorder. We need to look elsewhere. We need to look at genes.” She said other work in this field has identified several genes on chromosome 1 that might be involved in the development of AN and could be medication targets.

“I am perplexed and disappointed that we don't have medication for AN, and this is in part because we have not yet explained the biology adequately,” she said.

The study also found that of the potential predictors of AN assessed in the 1973 questionnaire, only neuroticism was predictive of the development of the disorder. The finding is notable because there have been few “truly prospective” risk-factor studies of AN, Dr. Bulik noted in the study. “What remains unknown is whether neuroticism is a nonspecific predictor of the development of psychopathology in general or whether it is specifically predictive of the emergence of AN.”

ELSEVIER GLOBAL MEDICAL NEWS

Anorexia nervosa is a heritable psychiatric disorder with warning signs that can be identified decades before the onset of the illness, the largest twin study on the disorder shows.

“Genes play a substantial role in the development of this illness; there is a clear biological component,” said lead author Cynthia M. Bulik, Ph.D., in a teleconference about the new research (Arch. Gen. Psychiatry 2006;63:305–12).

The findings are good news for patients and their families, said Dr. Bulik, the William R. and Jeanne H. Jordan Distinguished Professor of Eating Disorders at the University of North Carolina, Chapel Hill.

“We have gone through too much time where parents have been blamed. Now families and patients can be liberated and empowered,” Dr. Bulik said. “This helps them understand they are fighting their biology.”

The study included 31,406 twins from the Swedish Twin Registry. The twins, born during 1935–1958, were sent a questionnaire in 1973 that assessed demographics, physical illnesses, physical activity level, personality, stress, and work exposures. Seven potential predictors of the development of anorexia nervosa (AN) were evaluated in the questionnaire, including body mass index, gastric problems, excessive exercise, perceived life stress, neuroticism, and extraversion. Zygosity information also was obtained.

The subjects were then interviewed in 1998–2002 at a median age of 54.6 years to establish who had gone on to develop AN, and to determine the predictors.

The study found that 1.2% of the females and 0.29% of the males met diagnostic criteria for a lifetime history of AN, a prevalence in line with other studies of the disorder. However, when the cohort was divided into those born in 1944 or earlier, and those born in 1945 or later, there was evidence of an increasing prevalence in women (0.65% prevalence in the older female cohort, compared with 1.56% in the younger group). Prevalence rates did not change for men.

Examining the incidence of AN as it related to zygosity, the researchers found a much higher concordance rate for AN among monozygotic twins than among dizygotic twins–signaling a clear genetic component, Dr. Bulik said. The analysis revealed that genetics accounted for 56% of an individual's risk of developing the disorder, unique environment accounted for 38%, and shared environment accounted for 5%.

This information is promising in the search for targeted prevention and medical treatments for AN, she said. “Research like this shows [AN] is not a sociocultural disorder. We need to look elsewhere. We need to look at genes.” She said other work in this field has identified several genes on chromosome 1 that might be involved in the development of AN and could be medication targets.

“I am perplexed and disappointed that we don't have medication for AN, and this is in part because we have not yet explained the biology adequately,” she said.

The study also found that of the potential predictors of AN assessed in the 1973 questionnaire, only neuroticism was predictive of the development of the disorder. The finding is notable because there have been few “truly prospective” risk-factor studies of AN, Dr. Bulik noted in the study. “What remains unknown is whether neuroticism is a nonspecific predictor of the development of psychopathology in general or whether it is specifically predictive of the emergence of AN.”

ELSEVIER GLOBAL MEDICAL NEWS

DENVER – Phobic anxiety was significantly associated with both ventricular arrhythmia and mortality in coronary artery disease patients during a median 3-year follow-up, said Lana Watkins, Ph.D., at the annual meeting of the American Psychosomatic Society.

The relationship between sudden cardiac death and phobic anxiety in particular has not been well studied, Dr. Watkins noted. She and her colleagues at Duke University Medical Center in Durham, N.C., evaluated 941 adult patients who were being treated for coronary artery disease. A majority of these patients were white males. About a third of the patients did not have high school diplomas, and smoking and obesity were common among patients in the study.

The highest number of arrhythmias occurred among those patients with the highest levels of phobic anxiety based on the Crown-Crisp index, which rates eight types of phobias, including fear of heights, crowds, and closed spaces.

Overall, the highest tertile of phobic anxiety scores had twice as many females as males, and a higher level of phobic anxiety was significantly associated with female sex, minority status, increased body mass index, and younger age.

Despite the finding of an association between phobic anxiety and ventricular arrhythmias, no significant relationship was found between phobic anxiety and sudden cardiac death, Dr. Watkins noted. During a follow-up period, 134 patients died, and 46 of these met the criteria for sudden cardiac death. Sudden cardiac death was defined as death within 72 hours of collapse, in order to account for deaths of patients who lived alone.

However, mortality was highest among patients with high levels of phobic anxiety, Dr. Watkins said. The predictability of phobic anxiety for both mortality and an increased risk of ventricular arrhythmias was maintained in a regression analysis after other predictors of mortality including age, gender, education level, and comorbidities were adjusted for.

DENVER – Phobic anxiety was significantly associated with both ventricular arrhythmia and mortality in coronary artery disease patients during a median 3-year follow-up, said Lana Watkins, Ph.D., at the annual meeting of the American Psychosomatic Society.

The relationship between sudden cardiac death and phobic anxiety in particular has not been well studied, Dr. Watkins noted. She and her colleagues at Duke University Medical Center in Durham, N.C., evaluated 941 adult patients who were being treated for coronary artery disease. A majority of these patients were white males. About a third of the patients did not have high school diplomas, and smoking and obesity were common among patients in the study.

The highest number of arrhythmias occurred among those patients with the highest levels of phobic anxiety based on the Crown-Crisp index, which rates eight types of phobias, including fear of heights, crowds, and closed spaces.

Overall, the highest tertile of phobic anxiety scores had twice as many females as males, and a higher level of phobic anxiety was significantly associated with female sex, minority status, increased body mass index, and younger age.

Despite the finding of an association between phobic anxiety and ventricular arrhythmias, no significant relationship was found between phobic anxiety and sudden cardiac death, Dr. Watkins noted. During a follow-up period, 134 patients died, and 46 of these met the criteria for sudden cardiac death. Sudden cardiac death was defined as death within 72 hours of collapse, in order to account for deaths of patients who lived alone.

However, mortality was highest among patients with high levels of phobic anxiety, Dr. Watkins said. The predictability of phobic anxiety for both mortality and an increased risk of ventricular arrhythmias was maintained in a regression analysis after other predictors of mortality including age, gender, education level, and comorbidities were adjusted for.

DENVER – Phobic anxiety was significantly associated with both ventricular arrhythmia and mortality in coronary artery disease patients during a median 3-year follow-up, said Lana Watkins, Ph.D., at the annual meeting of the American Psychosomatic Society.

The relationship between sudden cardiac death and phobic anxiety in particular has not been well studied, Dr. Watkins noted. She and her colleagues at Duke University Medical Center in Durham, N.C., evaluated 941 adult patients who were being treated for coronary artery disease. A majority of these patients were white males. About a third of the patients did not have high school diplomas, and smoking and obesity were common among patients in the study.

The highest number of arrhythmias occurred among those patients with the highest levels of phobic anxiety based on the Crown-Crisp index, which rates eight types of phobias, including fear of heights, crowds, and closed spaces.

Overall, the highest tertile of phobic anxiety scores had twice as many females as males, and a higher level of phobic anxiety was significantly associated with female sex, minority status, increased body mass index, and younger age.

Despite the finding of an association between phobic anxiety and ventricular arrhythmias, no significant relationship was found between phobic anxiety and sudden cardiac death, Dr. Watkins noted. During a follow-up period, 134 patients died, and 46 of these met the criteria for sudden cardiac death. Sudden cardiac death was defined as death within 72 hours of collapse, in order to account for deaths of patients who lived alone.

However, mortality was highest among patients with high levels of phobic anxiety, Dr. Watkins said. The predictability of phobic anxiety for both mortality and an increased risk of ventricular arrhythmias was maintained in a regression analysis after other predictors of mortality including age, gender, education level, and comorbidities were adjusted for.

DENVER – End-stage liver disease was associated with significant deficits in memory, abstract thought, sustained attention, and executive function in a study of 104 adult patients, Tina Meyer, Ph.D., reported in a poster presented at the annual meeting of the American Psychosomatic Society.

“We want to enlighten the surgeons and primary care doctors that cognitive decline can indicate serious liver problems,” Dr. Meyer said in an interview. She and her colleagues in the Transplant Institute at the Henry Ford Health System in Detroit enrolled liver disease patients who met medical and psychosocial criteria for a transplant. About half (51%) were male, 74% were white, and the average age was 54 years. The patients' mean score on the model for end-stage liver disease (MELD) was 11.3.

The participants completed a cognitive assessment including the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), which estimates brain function in five different domains: immediate memory, delayed memory, visuospatial abilities, language, and attention.

Overall, scores on the RBANS were below average on the subtests of immediate memory, visuospatial abilities, and attention. After the investigators controlled for education levels, higher MELD scores were significantly associated with lower scores on the immediate memory and delayed memory subtests of RBANS, as well as with lower scores on the Mini-Mental State Exam, the Shipley Institute of Living Scale, and the Trail-Making Test, parts A and B.

DENVER – End-stage liver disease was associated with significant deficits in memory, abstract thought, sustained attention, and executive function in a study of 104 adult patients, Tina Meyer, Ph.D., reported in a poster presented at the annual meeting of the American Psychosomatic Society.

“We want to enlighten the surgeons and primary care doctors that cognitive decline can indicate serious liver problems,” Dr. Meyer said in an interview. She and her colleagues in the Transplant Institute at the Henry Ford Health System in Detroit enrolled liver disease patients who met medical and psychosocial criteria for a transplant. About half (51%) were male, 74% were white, and the average age was 54 years. The patients' mean score on the model for end-stage liver disease (MELD) was 11.3.

The participants completed a cognitive assessment including the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), which estimates brain function in five different domains: immediate memory, delayed memory, visuospatial abilities, language, and attention.

Overall, scores on the RBANS were below average on the subtests of immediate memory, visuospatial abilities, and attention. After the investigators controlled for education levels, higher MELD scores were significantly associated with lower scores on the immediate memory and delayed memory subtests of RBANS, as well as with lower scores on the Mini-Mental State Exam, the Shipley Institute of Living Scale, and the Trail-Making Test, parts A and B.

DENVER – End-stage liver disease was associated with significant deficits in memory, abstract thought, sustained attention, and executive function in a study of 104 adult patients, Tina Meyer, Ph.D., reported in a poster presented at the annual meeting of the American Psychosomatic Society.

“We want to enlighten the surgeons and primary care doctors that cognitive decline can indicate serious liver problems,” Dr. Meyer said in an interview. She and her colleagues in the Transplant Institute at the Henry Ford Health System in Detroit enrolled liver disease patients who met medical and psychosocial criteria for a transplant. About half (51%) were male, 74% were white, and the average age was 54 years. The patients' mean score on the model for end-stage liver disease (MELD) was 11.3.

The participants completed a cognitive assessment including the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), which estimates brain function in five different domains: immediate memory, delayed memory, visuospatial abilities, language, and attention.

Overall, scores on the RBANS were below average on the subtests of immediate memory, visuospatial abilities, and attention. After the investigators controlled for education levels, higher MELD scores were significantly associated with lower scores on the immediate memory and delayed memory subtests of RBANS, as well as with lower scores on the Mini-Mental State Exam, the Shipley Institute of Living Scale, and the Trail-Making Test, parts A and B.

SAN JUAN, P.R. – Sleep disorders become more common with increasing age, but effective behavioral and pharmacologic therapies are available, sleep experts said at the annual meeting of the American Association for Geriatric Psychiatry.

“Most older adults are not being treated for their insomnia, and most older adults won't get a diagnosis of insomnia,” despite the high prevalence of the disorder among this age group, said Dr. Phyllis C. Zee, medical director of the Sleep Disorders Center at Northwestern Memorial Hospital in Chicago.

There are several age-related changes in sleep architecture. The number of awakenings during sleep time increases, especially in the early morning. The amount of light sleep is increased, and the amount of deep sleep is decreased. There also is a decrease in REM sleep, said Dr. Zee, who also serves as a professor of neurology, neurobiology, and physiology at Northwestern University, Chicago.

Two major mechanisms regulate sleep in humans: the homeostatic drive and the circadian drive. Control of the circadian system resides in the suprachiasmatic nucleus, which provides timing information for physiologic, hormonal, and behavioral rhythms.

Several changes in circadian sleep rhythms come with age. The amplitude of circadian rhythms decreases, while the variability of circadian rhythms increases. “There's also a very noticeable advance in [the] phase of circadian rhythms,” Dr. Zee said. Severe disruptions of the sleep/wake cycle often occur among older adults with dementia and in those in nursing homes.

The homeostatic drive for sleep depends on accumulating enough hours of wakefulness to trigger sleep, and this drive is reset during sleep. It's thought that the homeostatic drive is regulated by the ventrolateral preoptic area of the hypothalamus.

It's important to understand these sleep mechanisms when treating sleep disorders. “There is not a thing you can do to make yourself go to sleep. … What you can do is arrange the circumstances and timing of your wakefulness in a way that makes the involuntary process of sleep more likely,” said Dr. Daniel J. Buysse, medical director of the sleep evaluation center at the Western Psychiatric Institute and Clinic of the University of Pittsburgh

“Sleep hygiene education is without a doubt the most widely employed and … the least efficacious” of the behavioral treatments for insomnia, Dr. Buysse said. Most patients are already aware of many of the suggestions for good sleep hygiene, such as avoiding caffeine before bed.

To understand the patient's sleep habits, behavioral therapists start by asking about average time in bed, average rise time, total time in bed, time to fall asleep, amount of wakefulness during the night, and total wake time.

Using this information, they calculate the average amount of total sleep (total time in bed minus total wake time). For most individuals with insomnia, there is a discrepancy between the total amount of sleep that they get and the total amount of time they spend in bed, said Dr. Buysse, also a professor of psychiatry at the University of Pittsburgh.

Several common elements are involved in behavioral treatments for insomnia: monitoring sleep-wake patterns, reinforcing associations between bed and sleep, limiting awake time in bed, establishing a regular sleep-wake schedule, and using voluntary behavior to influence the involuntary physiologic process of sleep.

To help patients minimize insomnia, he advised doing the following:

▸ Restrict time in bed.

▸ Establish a regular wake time.

▸ Go to bed only when sleepy.

▸ Stay in bed only when asleep.

By putting these suggestions into practice, a patient's total time in bed should be equal to the total sleep time, plus about 30 minutes, Dr. Buysse said. He and his colleagues have tested the effect of these changes in sleep behavior on sleep quality in a small study of 13 patients who made these changes, compared with 12 subjects who received basic sleep information. Those in the active treatment group showed a significant improvement in sleep quality, while those in the control group showed no change.

In addition, those in the active treatment group also showed improvement in sleep latency–how long it takes to fall asleep–and waking after sleep onset, while controls did not.

Pharmacologic management of acute and chronic insomnia includes benzodiazepine receptor agonists, melatonin, melatonin receptor agonists, and antidepressants.

In 2005, a National Institutes of Health state-of-the-science panel noted that hypnotics are efficacious in the short-term treatment of insomnia. However, with the exception of eszopiclone, the benefits of these agents have not been studied for long-term use.

Zaleplon (Sonata), zolpidem (Ambien), and eszopiclone (Lunesta)–benzodiazepine receptor agonists–are all indicated for the treatment of insomnia.

“These drugs differ [from benzodiazepines] mainly in terms of their pharmacokinetics,” said Dr. Buysse. Otherwise, these drugs are quite similar to benzodiazepines. One note of caution, however: Benzodiazepines and related drugs have been shown to be a risk factor for falls.

Ramelteon, a melatonin receptor agonist, “takes advantage of the circadian system that secretes melatonin at night,” Dr. Buysse said. Ramelteon is short acting and has an active metabolite. Caution should be used with this drug when prescribed for patients also taking fluvoxamine, which inhibits some of the enzymes that degrade ramelteon.

Ramelteon has been shown to reduce sleep latency and increase total sleep time in both younger and older adults. The drug appears to be less effective on wakefulness after sleep onset.

Ramelteon “has fewer side effects of the sort that characterize benzodiazepine receptor agonists,” Dr. Buysse said. In addition, the drug is unscheduled.

Trazodone, an antidepressant, seems to improve sleep continuity. “When it's been assessed in insomnia, there have been variable results. Typically, it decreases wakefulness during the night but doesn't have as much effect on the time to fall asleep,” Dr. Buysse said.

He recommends starting pharmacotherapy with a short-acting benzodiazepine receptor agonist or ramelteon. If that doesn't work, he recommends using a low-dose (20–50 mg) antidepressant such as trazodone, amitriptyline, or doxepin. As a last resort, he suggests combining a benzodiazepine receptor agonist with an antidepressant.

SAN JUAN, P.R. – Sleep disorders become more common with increasing age, but effective behavioral and pharmacologic therapies are available, sleep experts said at the annual meeting of the American Association for Geriatric Psychiatry.

“Most older adults are not being treated for their insomnia, and most older adults won't get a diagnosis of insomnia,” despite the high prevalence of the disorder among this age group, said Dr. Phyllis C. Zee, medical director of the Sleep Disorders Center at Northwestern Memorial Hospital in Chicago.

There are several age-related changes in sleep architecture. The number of awakenings during sleep time increases, especially in the early morning. The amount of light sleep is increased, and the amount of deep sleep is decreased. There also is a decrease in REM sleep, said Dr. Zee, who also serves as a professor of neurology, neurobiology, and physiology at Northwestern University, Chicago.

Two major mechanisms regulate sleep in humans: the homeostatic drive and the circadian drive. Control of the circadian system resides in the suprachiasmatic nucleus, which provides timing information for physiologic, hormonal, and behavioral rhythms.

Several changes in circadian sleep rhythms come with age. The amplitude of circadian rhythms decreases, while the variability of circadian rhythms increases. “There's also a very noticeable advance in [the] phase of circadian rhythms,” Dr. Zee said. Severe disruptions of the sleep/wake cycle often occur among older adults with dementia and in those in nursing homes.

The homeostatic drive for sleep depends on accumulating enough hours of wakefulness to trigger sleep, and this drive is reset during sleep. It's thought that the homeostatic drive is regulated by the ventrolateral preoptic area of the hypothalamus.

It's important to understand these sleep mechanisms when treating sleep disorders. “There is not a thing you can do to make yourself go to sleep. … What you can do is arrange the circumstances and timing of your wakefulness in a way that makes the involuntary process of sleep more likely,” said Dr. Daniel J. Buysse, medical director of the sleep evaluation center at the Western Psychiatric Institute and Clinic of the University of Pittsburgh

“Sleep hygiene education is without a doubt the most widely employed and … the least efficacious” of the behavioral treatments for insomnia, Dr. Buysse said. Most patients are already aware of many of the suggestions for good sleep hygiene, such as avoiding caffeine before bed.

To understand the patient's sleep habits, behavioral therapists start by asking about average time in bed, average rise time, total time in bed, time to fall asleep, amount of wakefulness during the night, and total wake time.

Using this information, they calculate the average amount of total sleep (total time in bed minus total wake time). For most individuals with insomnia, there is a discrepancy between the total amount of sleep that they get and the total amount of time they spend in bed, said Dr. Buysse, also a professor of psychiatry at the University of Pittsburgh.

Several common elements are involved in behavioral treatments for insomnia: monitoring sleep-wake patterns, reinforcing associations between bed and sleep, limiting awake time in bed, establishing a regular sleep-wake schedule, and using voluntary behavior to influence the involuntary physiologic process of sleep.

To help patients minimize insomnia, he advised doing the following:

▸ Restrict time in bed.

▸ Establish a regular wake time.

▸ Go to bed only when sleepy.

▸ Stay in bed only when asleep.

By putting these suggestions into practice, a patient's total time in bed should be equal to the total sleep time, plus about 30 minutes, Dr. Buysse said. He and his colleagues have tested the effect of these changes in sleep behavior on sleep quality in a small study of 13 patients who made these changes, compared with 12 subjects who received basic sleep information. Those in the active treatment group showed a significant improvement in sleep quality, while those in the control group showed no change.

In addition, those in the active treatment group also showed improvement in sleep latency–how long it takes to fall asleep–and waking after sleep onset, while controls did not.

Pharmacologic management of acute and chronic insomnia includes benzodiazepine receptor agonists, melatonin, melatonin receptor agonists, and antidepressants.

In 2005, a National Institutes of Health state-of-the-science panel noted that hypnotics are efficacious in the short-term treatment of insomnia. However, with the exception of eszopiclone, the benefits of these agents have not been studied for long-term use.

Zaleplon (Sonata), zolpidem (Ambien), and eszopiclone (Lunesta)–benzodiazepine receptor agonists–are all indicated for the treatment of insomnia.

“These drugs differ [from benzodiazepines] mainly in terms of their pharmacokinetics,” said Dr. Buysse. Otherwise, these drugs are quite similar to benzodiazepines. One note of caution, however: Benzodiazepines and related drugs have been shown to be a risk factor for falls.

Ramelteon, a melatonin receptor agonist, “takes advantage of the circadian system that secretes melatonin at night,” Dr. Buysse said. Ramelteon is short acting and has an active metabolite. Caution should be used with this drug when prescribed for patients also taking fluvoxamine, which inhibits some of the enzymes that degrade ramelteon.

Ramelteon has been shown to reduce sleep latency and increase total sleep time in both younger and older adults. The drug appears to be less effective on wakefulness after sleep onset.

Ramelteon “has fewer side effects of the sort that characterize benzodiazepine receptor agonists,” Dr. Buysse said. In addition, the drug is unscheduled.

Trazodone, an antidepressant, seems to improve sleep continuity. “When it's been assessed in insomnia, there have been variable results. Typically, it decreases wakefulness during the night but doesn't have as much effect on the time to fall asleep,” Dr. Buysse said.

He recommends starting pharmacotherapy with a short-acting benzodiazepine receptor agonist or ramelteon. If that doesn't work, he recommends using a low-dose (20–50 mg) antidepressant such as trazodone, amitriptyline, or doxepin. As a last resort, he suggests combining a benzodiazepine receptor agonist with an antidepressant.

SAN JUAN, P.R. – Sleep disorders become more common with increasing age, but effective behavioral and pharmacologic therapies are available, sleep experts said at the annual meeting of the American Association for Geriatric Psychiatry.

“Most older adults are not being treated for their insomnia, and most older adults won't get a diagnosis of insomnia,” despite the high prevalence of the disorder among this age group, said Dr. Phyllis C. Zee, medical director of the Sleep Disorders Center at Northwestern Memorial Hospital in Chicago.

There are several age-related changes in sleep architecture. The number of awakenings during sleep time increases, especially in the early morning. The amount of light sleep is increased, and the amount of deep sleep is decreased. There also is a decrease in REM sleep, said Dr. Zee, who also serves as a professor of neurology, neurobiology, and physiology at Northwestern University, Chicago.

Two major mechanisms regulate sleep in humans: the homeostatic drive and the circadian drive. Control of the circadian system resides in the suprachiasmatic nucleus, which provides timing information for physiologic, hormonal, and behavioral rhythms.

Several changes in circadian sleep rhythms come with age. The amplitude of circadian rhythms decreases, while the variability of circadian rhythms increases. “There's also a very noticeable advance in [the] phase of circadian rhythms,” Dr. Zee said. Severe disruptions of the sleep/wake cycle often occur among older adults with dementia and in those in nursing homes.

The homeostatic drive for sleep depends on accumulating enough hours of wakefulness to trigger sleep, and this drive is reset during sleep. It's thought that the homeostatic drive is regulated by the ventrolateral preoptic area of the hypothalamus.

It's important to understand these sleep mechanisms when treating sleep disorders. “There is not a thing you can do to make yourself go to sleep. … What you can do is arrange the circumstances and timing of your wakefulness in a way that makes the involuntary process of sleep more likely,” said Dr. Daniel J. Buysse, medical director of the sleep evaluation center at the Western Psychiatric Institute and Clinic of the University of Pittsburgh

“Sleep hygiene education is without a doubt the most widely employed and … the least efficacious” of the behavioral treatments for insomnia, Dr. Buysse said. Most patients are already aware of many of the suggestions for good sleep hygiene, such as avoiding caffeine before bed.

To understand the patient's sleep habits, behavioral therapists start by asking about average time in bed, average rise time, total time in bed, time to fall asleep, amount of wakefulness during the night, and total wake time.

Using this information, they calculate the average amount of total sleep (total time in bed minus total wake time). For most individuals with insomnia, there is a discrepancy between the total amount of sleep that they get and the total amount of time they spend in bed, said Dr. Buysse, also a professor of psychiatry at the University of Pittsburgh.

Several common elements are involved in behavioral treatments for insomnia: monitoring sleep-wake patterns, reinforcing associations between bed and sleep, limiting awake time in bed, establishing a regular sleep-wake schedule, and using voluntary behavior to influence the involuntary physiologic process of sleep.

To help patients minimize insomnia, he advised doing the following:

▸ Restrict time in bed.

▸ Establish a regular wake time.

▸ Go to bed only when sleepy.

▸ Stay in bed only when asleep.

By putting these suggestions into practice, a patient's total time in bed should be equal to the total sleep time, plus about 30 minutes, Dr. Buysse said. He and his colleagues have tested the effect of these changes in sleep behavior on sleep quality in a small study of 13 patients who made these changes, compared with 12 subjects who received basic sleep information. Those in the active treatment group showed a significant improvement in sleep quality, while those in the control group showed no change.

In addition, those in the active treatment group also showed improvement in sleep latency–how long it takes to fall asleep–and waking after sleep onset, while controls did not.

Pharmacologic management of acute and chronic insomnia includes benzodiazepine receptor agonists, melatonin, melatonin receptor agonists, and antidepressants.

In 2005, a National Institutes of Health state-of-the-science panel noted that hypnotics are efficacious in the short-term treatment of insomnia. However, with the exception of eszopiclone, the benefits of these agents have not been studied for long-term use.

Zaleplon (Sonata), zolpidem (Ambien), and eszopiclone (Lunesta)–benzodiazepine receptor agonists–are all indicated for the treatment of insomnia.

“These drugs differ [from benzodiazepines] mainly in terms of their pharmacokinetics,” said Dr. Buysse. Otherwise, these drugs are quite similar to benzodiazepines. One note of caution, however: Benzodiazepines and related drugs have been shown to be a risk factor for falls.

Ramelteon, a melatonin receptor agonist, “takes advantage of the circadian system that secretes melatonin at night,” Dr. Buysse said. Ramelteon is short acting and has an active metabolite. Caution should be used with this drug when prescribed for patients also taking fluvoxamine, which inhibits some of the enzymes that degrade ramelteon.

Ramelteon has been shown to reduce sleep latency and increase total sleep time in both younger and older adults. The drug appears to be less effective on wakefulness after sleep onset.

Ramelteon “has fewer side effects of the sort that characterize benzodiazepine receptor agonists,” Dr. Buysse said. In addition, the drug is unscheduled.

Trazodone, an antidepressant, seems to improve sleep continuity. “When it's been assessed in insomnia, there have been variable results. Typically, it decreases wakefulness during the night but doesn't have as much effect on the time to fall asleep,” Dr. Buysse said.

He recommends starting pharmacotherapy with a short-acting benzodiazepine receptor agonist or ramelteon. If that doesn't work, he recommends using a low-dose (20–50 mg) antidepressant such as trazodone, amitriptyline, or doxepin. As a last resort, he suggests combining a benzodiazepine receptor agonist with an antidepressant.

DALLAS – Depression boosted the risk for stroke in a study of more than 4,000 elderly people followed for 10 years.

People with the highest depression scores at baseline had twice the incidence of a cerebrovascular event or transient ischemic attack during follow-up, compared with people who had no depression, Dr. Abraham A. Ariyo reported at the annual scientific sessions of the American Heart Association.

This finding follows a prior analysis of the same group of people showing that depression boosted the risk for coronary artery disease, said Dr. Ariyo, director of HeartMasters in Dallas.

The Cardiovascular Health Study Collaborative Research Group enrolled 4,483 men and women aged 65 or older who were completely free of any clinical sign of cardiovascular disease at baseline. The study also excluded patients who were treated with an antidepressant. All participants were assessed for depression using a modified version of the Center for Epidemiologic Studies Depression Scale.

Participants were categorized into quartiles based on their scores. Those with a score of zero had no depression. The next quartile included people with a score of 1–5, followed by quartiles with scores of 6–10, 11–15, and 16 and over. In 10.3 years of follow-up, 533 people had a stroke, and an additional 1,359 died.

In a multivariate analysis, the incidence of stroke was related to depression scores. Compared with people who had a score of zero, those with a score of 1–5 had 19% more strokes, those with a score of 6–10 had 57% more strokes, those with a score of 11–15 had 78% more strokes, and people with a score of 16–30 had twice as many strokes.

An analysis of death rates showed a similar pattern. People with scores of 6–10 had a 27% higher death rate; those with scores of 11–15 had a 73% higher mortality; and those with scores of 16 or more had 86% more deaths.

Several mechanisms may explain how depression affects stroke rates and mortality, Dr. Ariyo said. Depressed people are less physically active and engage in more unsafe behaviors, such as smoking. Also, depressed people have increased levels of circulating platelets, fibrinogen, and other factors that raise thrombogenicity.

Depression also boosts serum levels of steroids, free fatty acids, and other factors that are proinflammatory and proatherogenic.

DALLAS – Depression boosted the risk for stroke in a study of more than 4,000 elderly people followed for 10 years.

People with the highest depression scores at baseline had twice the incidence of a cerebrovascular event or transient ischemic attack during follow-up, compared with people who had no depression, Dr. Abraham A. Ariyo reported at the annual scientific sessions of the American Heart Association.

This finding follows a prior analysis of the same group of people showing that depression boosted the risk for coronary artery disease, said Dr. Ariyo, director of HeartMasters in Dallas.

The Cardiovascular Health Study Collaborative Research Group enrolled 4,483 men and women aged 65 or older who were completely free of any clinical sign of cardiovascular disease at baseline. The study also excluded patients who were treated with an antidepressant. All participants were assessed for depression using a modified version of the Center for Epidemiologic Studies Depression Scale.

Participants were categorized into quartiles based on their scores. Those with a score of zero had no depression. The next quartile included people with a score of 1–5, followed by quartiles with scores of 6–10, 11–15, and 16 and over. In 10.3 years of follow-up, 533 people had a stroke, and an additional 1,359 died.

In a multivariate analysis, the incidence of stroke was related to depression scores. Compared with people who had a score of zero, those with a score of 1–5 had 19% more strokes, those with a score of 6–10 had 57% more strokes, those with a score of 11–15 had 78% more strokes, and people with a score of 16–30 had twice as many strokes.

An analysis of death rates showed a similar pattern. People with scores of 6–10 had a 27% higher death rate; those with scores of 11–15 had a 73% higher mortality; and those with scores of 16 or more had 86% more deaths.

Several mechanisms may explain how depression affects stroke rates and mortality, Dr. Ariyo said. Depressed people are less physically active and engage in more unsafe behaviors, such as smoking. Also, depressed people have increased levels of circulating platelets, fibrinogen, and other factors that raise thrombogenicity.

Depression also boosts serum levels of steroids, free fatty acids, and other factors that are proinflammatory and proatherogenic.

DALLAS – Depression boosted the risk for stroke in a study of more than 4,000 elderly people followed for 10 years.

People with the highest depression scores at baseline had twice the incidence of a cerebrovascular event or transient ischemic attack during follow-up, compared with people who had no depression, Dr. Abraham A. Ariyo reported at the annual scientific sessions of the American Heart Association.

This finding follows a prior analysis of the same group of people showing that depression boosted the risk for coronary artery disease, said Dr. Ariyo, director of HeartMasters in Dallas.

The Cardiovascular Health Study Collaborative Research Group enrolled 4,483 men and women aged 65 or older who were completely free of any clinical sign of cardiovascular disease at baseline. The study also excluded patients who were treated with an antidepressant. All participants were assessed for depression using a modified version of the Center for Epidemiologic Studies Depression Scale.

Participants were categorized into quartiles based on their scores. Those with a score of zero had no depression. The next quartile included people with a score of 1–5, followed by quartiles with scores of 6–10, 11–15, and 16 and over. In 10.3 years of follow-up, 533 people had a stroke, and an additional 1,359 died.

In a multivariate analysis, the incidence of stroke was related to depression scores. Compared with people who had a score of zero, those with a score of 1–5 had 19% more strokes, those with a score of 6–10 had 57% more strokes, those with a score of 11–15 had 78% more strokes, and people with a score of 16–30 had twice as many strokes.

An analysis of death rates showed a similar pattern. People with scores of 6–10 had a 27% higher death rate; those with scores of 11–15 had a 73% higher mortality; and those with scores of 16 or more had 86% more deaths.

Several mechanisms may explain how depression affects stroke rates and mortality, Dr. Ariyo said. Depressed people are less physically active and engage in more unsafe behaviors, such as smoking. Also, depressed people have increased levels of circulating platelets, fibrinogen, and other factors that raise thrombogenicity.

Depression also boosts serum levels of steroids, free fatty acids, and other factors that are proinflammatory and proatherogenic.

DENVER – Age and low hostility are independent predictors of high blood pressure in women over a 10-year period, suggesting a link between certain personality traits and disease development, Jocelyne Leclerc reported in a poster presentation at the annual meeting of the American Psychosomatic Society.

Ms. Leclerc and her colleagues at the University of British Columbia, Vancouver, compared the results of ambulatory blood pressure monitoring and personality questionnaires of 112 healthy adults at baseline and again after 10 years. The study group included 54 men and 63 women; the average age was 40 years at baseline. Average blood pressure monitoring was conducted on predetermined days when the patients did not expect significant stressful events.

Overall, blood pressure and personality traits remained stable over the 10 years. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly correlated with depression at baseline. Baseline hostility predicted increased DBP 10 years later, and baseline SBP predicted hostility 10 years later.

Gender and family history may moderate the impact of personality on blood pressure, the investigators noted in the recently published study (Pers. Individ. Diff. 2006;40:1313–21).

Increased age and low hostility significantly predicted SBP among women, while high levels of self-deception were the only significant predictors of SBP and DBP over time among men.

“The observation of low hostility in women predicting high BP appears quite surprising,” the investigators noted. This finding suggests a need to consider “possibly differential adaptiveness of the same personality features of women and men.”

Among individuals with a family history of high blood pressure, age and high levels of self-deception were significant predictors of SBP, while self-deception was the lone significant predictor of DBP. Among those without a family history of high blood pressure, only age was a significant predictor of SBP, and no variables were significant predictors of DBP.

DENVER – Age and low hostility are independent predictors of high blood pressure in women over a 10-year period, suggesting a link between certain personality traits and disease development, Jocelyne Leclerc reported in a poster presentation at the annual meeting of the American Psychosomatic Society.

Ms. Leclerc and her colleagues at the University of British Columbia, Vancouver, compared the results of ambulatory blood pressure monitoring and personality questionnaires of 112 healthy adults at baseline and again after 10 years. The study group included 54 men and 63 women; the average age was 40 years at baseline. Average blood pressure monitoring was conducted on predetermined days when the patients did not expect significant stressful events.

Overall, blood pressure and personality traits remained stable over the 10 years. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly correlated with depression at baseline. Baseline hostility predicted increased DBP 10 years later, and baseline SBP predicted hostility 10 years later.

Gender and family history may moderate the impact of personality on blood pressure, the investigators noted in the recently published study (Pers. Individ. Diff. 2006;40:1313–21).

Increased age and low hostility significantly predicted SBP among women, while high levels of self-deception were the only significant predictors of SBP and DBP over time among men.

“The observation of low hostility in women predicting high BP appears quite surprising,” the investigators noted. This finding suggests a need to consider “possibly differential adaptiveness of the same personality features of women and men.”

Among individuals with a family history of high blood pressure, age and high levels of self-deception were significant predictors of SBP, while self-deception was the lone significant predictor of DBP. Among those without a family history of high blood pressure, only age was a significant predictor of SBP, and no variables were significant predictors of DBP.

DENVER – Age and low hostility are independent predictors of high blood pressure in women over a 10-year period, suggesting a link between certain personality traits and disease development, Jocelyne Leclerc reported in a poster presentation at the annual meeting of the American Psychosomatic Society.

Ms. Leclerc and her colleagues at the University of British Columbia, Vancouver, compared the results of ambulatory blood pressure monitoring and personality questionnaires of 112 healthy adults at baseline and again after 10 years. The study group included 54 men and 63 women; the average age was 40 years at baseline. Average blood pressure monitoring was conducted on predetermined days when the patients did not expect significant stressful events.

Overall, blood pressure and personality traits remained stable over the 10 years. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly correlated with depression at baseline. Baseline hostility predicted increased DBP 10 years later, and baseline SBP predicted hostility 10 years later.

Gender and family history may moderate the impact of personality on blood pressure, the investigators noted in the recently published study (Pers. Individ. Diff. 2006;40:1313–21).

Increased age and low hostility significantly predicted SBP among women, while high levels of self-deception were the only significant predictors of SBP and DBP over time among men.

“The observation of low hostility in women predicting high BP appears quite surprising,” the investigators noted. This finding suggests a need to consider “possibly differential adaptiveness of the same personality features of women and men.”

Among individuals with a family history of high blood pressure, age and high levels of self-deception were significant predictors of SBP, while self-deception was the lone significant predictor of DBP. Among those without a family history of high blood pressure, only age was a significant predictor of SBP, and no variables were significant predictors of DBP.

SANTA ANA PUEBLO, N.M. – People with restless legs syndrome were three times more likely to have a major depressive disorder in a study of 1,071 Baltimore residents reported by Dr. Hochang Benjamin Lee at the annual meeting of the Academy of Psychosomatic Medicine.

Investigators from Johns Hopkins University in Baltimore found major depressive disorder in 8 of 42 patients (19%) diagnosed with restless legs syndrome (RLS). Only 8.4% of those without RLS met the DSM-IV criteria for depression in diagnostic interviews.

“Depression and anxiety are common in RLS, and vice versa,” said Dr. Lee of the Neuropsychiatry and Memory Group at Johns Hopkins. Previous population-based studies suggested a connection, he said, but the new study is “probably the most definitive.”

Dr. Lee described numerous overlaps between the two disorders, both of which are diagnosed on the basis of subjective reports from the patient. He said the two conditions have similar prevalence in the community, occur twice as often in women as in men, present with diurnal variation, and tend to run in families. Both also have a high placebo response rate in treatment trials.

Additionally, six of the nine symptoms that the DSM-IV lists for major depressive disorder are common in RLS patients, Dr. Lee said. He cited depressed mood, diminished interest, fatigue or loss of energy, diminished concentration, psychomotor retardation, and insomnia or excessive sleepiness. Indeed, he suggested asking depressed patients who complain of insomnia or excessive sleepiness whether they experience “a creepy crawling feeling” in their legs.

Noting that no guidelines exist for managing depression in RLS patients, Dr. Lee recommended the following strategy:

▸ If an RLS patient presents with mild depression or dysthymia, treat the RLS first and see whether mood-related symptoms improve. If the patient continues to have depressive symptoms, treat these as well.

▸ If a severe major depressive disorder occurs along with mild RLS, treat the depression first, preferably with agents that are not SSRIs or tricyclic antidepressants.

▸ If both RLS and depression are severe, however, consider treating the conditions simultaneously, but avoid using most dopamine agonists for RLS because of the possibility of the rare side effect of psychosis.

“Careful consideration is needed for treatment of major depressive disorder in patients with restless legs syndrome,” Dr. Lee warned. He ruled out many medications, saying that SSRIs and tricyclic antidepressants should be avoided whenever possible. Both can exacerbate periodic limb movements, which occur in 80%–90% of RLS patients, according to Dr. Lee.

He suggested nefazodone, trazodone, and bupropion as alternatives. These agents have not been reported to exacerbate periodic limb movements, and they may produce improvement. Mirtazapine is sometimes recommended for depression in RLS patients, he added, but reports are conflicting.

Regarding adjunctive treatments for RLS, he said that antipsychotic medications generally exacerbate the syndrome. While atypical antipsychotic agents are less likely to do so, he said there have been reports of risperidone, quetiapine, and olanzapine worsening RLS. Aripiprazole might be worth a trial in this movement disorder, given that it is a partial dopamine agonist.

Anticonvulsants do not usually worsen RLS symptoms, according to Dr. Lee. He described gabapentin and carbamazepine as “viable alternatives” for treating RLS. Valproic acid and lamotrigine also may be helpful, he said, but anecdotal reports suggest lithium can exacerbate RLS and periodic leg movements.

Benzodiazepines, particularly clonazepam, may be used as an adjunctive RLS treatment, Dr. Lee said, but he warned that antihistamines such as Benadryl are poorly tolerated in this patient population.

Dopamine agonists are increasingly an option for treatment of RLS, but he said ergot-derived dopamine agonists should be avoided. He cited the possibility of heart valve abnormalities and other side effects. Instead, he suggested a trial of dopamine agonists that are not derived from ergot such as pramipexole and ropinirole.

Dr. Lee added, however, that high doses of dopamine agonists have been linked to hallucinations, compulsive gambling, and psychiatric side effects in Parkinson's disease patients.

SANTA ANA PUEBLO, N.M. – People with restless legs syndrome were three times more likely to have a major depressive disorder in a study of 1,071 Baltimore residents reported by Dr. Hochang Benjamin Lee at the annual meeting of the Academy of Psychosomatic Medicine.

Investigators from Johns Hopkins University in Baltimore found major depressive disorder in 8 of 42 patients (19%) diagnosed with restless legs syndrome (RLS). Only 8.4% of those without RLS met the DSM-IV criteria for depression in diagnostic interviews.

“Depression and anxiety are common in RLS, and vice versa,” said Dr. Lee of the Neuropsychiatry and Memory Group at Johns Hopkins. Previous population-based studies suggested a connection, he said, but the new study is “probably the most definitive.”

Dr. Lee described numerous overlaps between the two disorders, both of which are diagnosed on the basis of subjective reports from the patient. He said the two conditions have similar prevalence in the community, occur twice as often in women as in men, present with diurnal variation, and tend to run in families. Both also have a high placebo response rate in treatment trials.

Additionally, six of the nine symptoms that the DSM-IV lists for major depressive disorder are common in RLS patients, Dr. Lee said. He cited depressed mood, diminished interest, fatigue or loss of energy, diminished concentration, psychomotor retardation, and insomnia or excessive sleepiness. Indeed, he suggested asking depressed patients who complain of insomnia or excessive sleepiness whether they experience “a creepy crawling feeling” in their legs.

Noting that no guidelines exist for managing depression in RLS patients, Dr. Lee recommended the following strategy:

▸ If an RLS patient presents with mild depression or dysthymia, treat the RLS first and see whether mood-related symptoms improve. If the patient continues to have depressive symptoms, treat these as well.

▸ If a severe major depressive disorder occurs along with mild RLS, treat the depression first, preferably with agents that are not SSRIs or tricyclic antidepressants.

▸ If both RLS and depression are severe, however, consider treating the conditions simultaneously, but avoid using most dopamine agonists for RLS because of the possibility of the rare side effect of psychosis.

“Careful consideration is needed for treatment of major depressive disorder in patients with restless legs syndrome,” Dr. Lee warned. He ruled out many medications, saying that SSRIs and tricyclic antidepressants should be avoided whenever possible. Both can exacerbate periodic limb movements, which occur in 80%–90% of RLS patients, according to Dr. Lee.

He suggested nefazodone, trazodone, and bupropion as alternatives. These agents have not been reported to exacerbate periodic limb movements, and they may produce improvement. Mirtazapine is sometimes recommended for depression in RLS patients, he added, but reports are conflicting.

Regarding adjunctive treatments for RLS, he said that antipsychotic medications generally exacerbate the syndrome. While atypical antipsychotic agents are less likely to do so, he said there have been reports of risperidone, quetiapine, and olanzapine worsening RLS. Aripiprazole might be worth a trial in this movement disorder, given that it is a partial dopamine agonist.

Anticonvulsants do not usually worsen RLS symptoms, according to Dr. Lee. He described gabapentin and carbamazepine as “viable alternatives” for treating RLS. Valproic acid and lamotrigine also may be helpful, he said, but anecdotal reports suggest lithium can exacerbate RLS and periodic leg movements.

Benzodiazepines, particularly clonazepam, may be used as an adjunctive RLS treatment, Dr. Lee said, but he warned that antihistamines such as Benadryl are poorly tolerated in this patient population.

Dopamine agonists are increasingly an option for treatment of RLS, but he said ergot-derived dopamine agonists should be avoided. He cited the possibility of heart valve abnormalities and other side effects. Instead, he suggested a trial of dopamine agonists that are not derived from ergot such as pramipexole and ropinirole.

Dr. Lee added, however, that high doses of dopamine agonists have been linked to hallucinations, compulsive gambling, and psychiatric side effects in Parkinson's disease patients.

SANTA ANA PUEBLO, N.M. – People with restless legs syndrome were three times more likely to have a major depressive disorder in a study of 1,071 Baltimore residents reported by Dr. Hochang Benjamin Lee at the annual meeting of the Academy of Psychosomatic Medicine.

Investigators from Johns Hopkins University in Baltimore found major depressive disorder in 8 of 42 patients (19%) diagnosed with restless legs syndrome (RLS). Only 8.4% of those without RLS met the DSM-IV criteria for depression in diagnostic interviews.

“Depression and anxiety are common in RLS, and vice versa,” said Dr. Lee of the Neuropsychiatry and Memory Group at Johns Hopkins. Previous population-based studies suggested a connection, he said, but the new study is “probably the most definitive.”

Dr. Lee described numerous overlaps between the two disorders, both of which are diagnosed on the basis of subjective reports from the patient. He said the two conditions have similar prevalence in the community, occur twice as often in women as in men, present with diurnal variation, and tend to run in families. Both also have a high placebo response rate in treatment trials.

Additionally, six of the nine symptoms that the DSM-IV lists for major depressive disorder are common in RLS patients, Dr. Lee said. He cited depressed mood, diminished interest, fatigue or loss of energy, diminished concentration, psychomotor retardation, and insomnia or excessive sleepiness. Indeed, he suggested asking depressed patients who complain of insomnia or excessive sleepiness whether they experience “a creepy crawling feeling” in their legs.

Noting that no guidelines exist for managing depression in RLS patients, Dr. Lee recommended the following strategy:

▸ If an RLS patient presents with mild depression or dysthymia, treat the RLS first and see whether mood-related symptoms improve. If the patient continues to have depressive symptoms, treat these as well.

▸ If a severe major depressive disorder occurs along with mild RLS, treat the depression first, preferably with agents that are not SSRIs or tricyclic antidepressants.

▸ If both RLS and depression are severe, however, consider treating the conditions simultaneously, but avoid using most dopamine agonists for RLS because of the possibility of the rare side effect of psychosis.

“Careful consideration is needed for treatment of major depressive disorder in patients with restless legs syndrome,” Dr. Lee warned. He ruled out many medications, saying that SSRIs and tricyclic antidepressants should be avoided whenever possible. Both can exacerbate periodic limb movements, which occur in 80%–90% of RLS patients, according to Dr. Lee.

He suggested nefazodone, trazodone, and bupropion as alternatives. These agents have not been reported to exacerbate periodic limb movements, and they may produce improvement. Mirtazapine is sometimes recommended for depression in RLS patients, he added, but reports are conflicting.

Regarding adjunctive treatments for RLS, he said that antipsychotic medications generally exacerbate the syndrome. While atypical antipsychotic agents are less likely to do so, he said there have been reports of risperidone, quetiapine, and olanzapine worsening RLS. Aripiprazole might be worth a trial in this movement disorder, given that it is a partial dopamine agonist.

Anticonvulsants do not usually worsen RLS symptoms, according to Dr. Lee. He described gabapentin and carbamazepine as “viable alternatives” for treating RLS. Valproic acid and lamotrigine also may be helpful, he said, but anecdotal reports suggest lithium can exacerbate RLS and periodic leg movements.

Benzodiazepines, particularly clonazepam, may be used as an adjunctive RLS treatment, Dr. Lee said, but he warned that antihistamines such as Benadryl are poorly tolerated in this patient population.

Dopamine agonists are increasingly an option for treatment of RLS, but he said ergot-derived dopamine agonists should be avoided. He cited the possibility of heart valve abnormalities and other side effects. Instead, he suggested a trial of dopamine agonists that are not derived from ergot such as pramipexole and ropinirole.

Dr. Lee added, however, that high doses of dopamine agonists have been linked to hallucinations, compulsive gambling, and psychiatric side effects in Parkinson's disease patients.