Somatic Disorders

BETHESDA, MD. – When it comes to managing chronic pain, Dr. Daniel J. Clauw said physicians have been looking in the wrong places.

"There is no chronic pain state where degree of damage or inflammation in the periphery correlates well with level of pain. Yet, the diagnostic algorithms or paradigms that everyone uses for treating chronic pain still assume that all pain is nociceptive. What we see in the peripheral tissues is not necessarily what our patients are experiencing," said Dr. Clauw, director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor.

Historically, it has been assumed that when there was a disparity between peripheral findings and pain, psychological factors were at work. But the current view of chronic pain is that while it may originate from peripheral nociceptive input or nerve damage, central neuronal factors – at least some of them genetically determined – are nearly always playing a role in leading to interindividual differences in pain sensitivity, which are in turn closely associated with clinical outcomes.

For instance, population-based studies have shown that 30%-40% of individuals with radiographic evidence of severe damage from osteoarthritis are pain free, while 10% of those with normal radiographs have severe pain (Br. J. Rheumatol. 1997;36:726-8). Psychological factors explain very little of the variance between symptoms and structure (Arthritis Care Res. 1998;11:60-5), suggesting that central mechanisms involved in pain processing are at work, Dr. Clauw said at the workshop, sponsored by the University of Michigan and the National Institutes of Health.

Of course, individuals with osteoarthritis and rheumatoid arthritis will often have evidence of nociceptive input, while those with fibromyalgia have more prominent central factors. But no chronic pain state is solely due to any one of these mechanisms, he said.

"The scientific paradigm shift requires that we rethink everything from diagnostics and treatment approaches – which currently place an unjustified importance on treating peripheral factors," he said.

The new paradigm suggests that, regardless of the specific diagnosis, "central pain states" including fibromyalgia, rheumatoid arthritis, osteoarthritis, lupus, and low back pain all tend to share certain characteristics that can be better assessed by asking questions than by physical examination.

Showing patients a body diagram and asking them to label all the areas where they have pain is a simple assessment tool for multifocal pain. Also, ask about previous pain and other somatic symptoms such as fatigue, memory difficulty, mood disorders, and sleep disturbances, all common in the context of central pain but not with pain that is solely peripheral.

Is the pain triggered or exacerbated by stressors, such as psychological stress, infections, or physical trauma? Was there a salient stressor in the patient’s early life, such as an auto accident or the death of a loved one? All are common among patients with central pain, said Dr. Clauw, professor of anesthesiology and medicine (rheumatology) at the university.

Because these patients tend to have global sensory processing problems, asking about hypersensitivity to bright lights, odors, or noises will also help confirm the "central" diagnosis. Take a family history of pain as well, as there are strong familial and genetic linkages among the chronic pain syndromes, at least among women (Psychol. Med. 2009;39:497-505).

Physical examination is likely to be normal except for diffuse tenderness and nonspecific neurologic signs (Arthritis Rheum. 2009;60:2839-44). "This is why, historically, patients with fibromyalgia haven’t been believed," Dr. Clauw commented.

As for treatment, it is becoming increasingly clear that peripherally-acting pharmacologic agents such as opioids, corticosteroids, and nonsteroidal anti-inflammatory drugs simply do not work in central pain states.

Far more effective for fibromyalgia – and most likely other central pain states as well – are dual reuptake inhibitors such as tricyclic compounds (amitriptyline, cyclobenzaprine), serotonin-norepinephrine reuptake inhibitors (milnacipran, duloxetine), gamma hydroxybutyrate, and gabapentin. There is also modest evidence supporting the use of tramadol, selective serotonin reuptake inhibitors, and dopamine agonists (JAMA 2004;292:2388-95).

Nonpharmacologic therapies are also beneficial, including cognitive-behavioral therapy, exercise, and sleep hygiene (Best Pract. Res. Clin. Rheumatol. 2003;17:685-701).

Despite an abundance of emerging data to support the new way of thinking about chronic pain, Dr. Clauw said he thinks that shifting to a new management strategy could be difficult. "It takes a long time for people trained in one way of thinking to think differently. This isn’t just a new drug or a new device. This is a major paradigm shift."

Dr. Clauw disclosed that he is a consultant for Pfizer, Forest, Eli Lilly, Pierre Fabre Laboratories, Cypress Biosciences, Wyeth, UCB, AstraZeneca, Merck, Johnson & Johnson, Nuvo, and Jazz. He said he has also received research support from Pfizer, Cypress, and Forest.

BETHESDA, MD. – When it comes to managing chronic pain, Dr. Daniel J. Clauw said physicians have been looking in the wrong places.

"There is no chronic pain state where degree of damage or inflammation in the periphery correlates well with level of pain. Yet, the diagnostic algorithms or paradigms that everyone uses for treating chronic pain still assume that all pain is nociceptive. What we see in the peripheral tissues is not necessarily what our patients are experiencing," said Dr. Clauw, director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor.

Historically, it has been assumed that when there was a disparity between peripheral findings and pain, psychological factors were at work. But the current view of chronic pain is that while it may originate from peripheral nociceptive input or nerve damage, central neuronal factors – at least some of them genetically determined – are nearly always playing a role in leading to interindividual differences in pain sensitivity, which are in turn closely associated with clinical outcomes.

For instance, population-based studies have shown that 30%-40% of individuals with radiographic evidence of severe damage from osteoarthritis are pain free, while 10% of those with normal radiographs have severe pain (Br. J. Rheumatol. 1997;36:726-8). Psychological factors explain very little of the variance between symptoms and structure (Arthritis Care Res. 1998;11:60-5), suggesting that central mechanisms involved in pain processing are at work, Dr. Clauw said at the workshop, sponsored by the University of Michigan and the National Institutes of Health.

Of course, individuals with osteoarthritis and rheumatoid arthritis will often have evidence of nociceptive input, while those with fibromyalgia have more prominent central factors. But no chronic pain state is solely due to any one of these mechanisms, he said.

"The scientific paradigm shift requires that we rethink everything from diagnostics and treatment approaches – which currently place an unjustified importance on treating peripheral factors," he said.

The new paradigm suggests that, regardless of the specific diagnosis, "central pain states" including fibromyalgia, rheumatoid arthritis, osteoarthritis, lupus, and low back pain all tend to share certain characteristics that can be better assessed by asking questions than by physical examination.

Showing patients a body diagram and asking them to label all the areas where they have pain is a simple assessment tool for multifocal pain. Also, ask about previous pain and other somatic symptoms such as fatigue, memory difficulty, mood disorders, and sleep disturbances, all common in the context of central pain but not with pain that is solely peripheral.

Is the pain triggered or exacerbated by stressors, such as psychological stress, infections, or physical trauma? Was there a salient stressor in the patient’s early life, such as an auto accident or the death of a loved one? All are common among patients with central pain, said Dr. Clauw, professor of anesthesiology and medicine (rheumatology) at the university.

Because these patients tend to have global sensory processing problems, asking about hypersensitivity to bright lights, odors, or noises will also help confirm the "central" diagnosis. Take a family history of pain as well, as there are strong familial and genetic linkages among the chronic pain syndromes, at least among women (Psychol. Med. 2009;39:497-505).

Physical examination is likely to be normal except for diffuse tenderness and nonspecific neurologic signs (Arthritis Rheum. 2009;60:2839-44). "This is why, historically, patients with fibromyalgia haven’t been believed," Dr. Clauw commented.

As for treatment, it is becoming increasingly clear that peripherally-acting pharmacologic agents such as opioids, corticosteroids, and nonsteroidal anti-inflammatory drugs simply do not work in central pain states.

Far more effective for fibromyalgia – and most likely other central pain states as well – are dual reuptake inhibitors such as tricyclic compounds (amitriptyline, cyclobenzaprine), serotonin-norepinephrine reuptake inhibitors (milnacipran, duloxetine), gamma hydroxybutyrate, and gabapentin. There is also modest evidence supporting the use of tramadol, selective serotonin reuptake inhibitors, and dopamine agonists (JAMA 2004;292:2388-95).

Nonpharmacologic therapies are also beneficial, including cognitive-behavioral therapy, exercise, and sleep hygiene (Best Pract. Res. Clin. Rheumatol. 2003;17:685-701).

Despite an abundance of emerging data to support the new way of thinking about chronic pain, Dr. Clauw said he thinks that shifting to a new management strategy could be difficult. "It takes a long time for people trained in one way of thinking to think differently. This isn’t just a new drug or a new device. This is a major paradigm shift."

Dr. Clauw disclosed that he is a consultant for Pfizer, Forest, Eli Lilly, Pierre Fabre Laboratories, Cypress Biosciences, Wyeth, UCB, AstraZeneca, Merck, Johnson & Johnson, Nuvo, and Jazz. He said he has also received research support from Pfizer, Cypress, and Forest.

BETHESDA, MD. – When it comes to managing chronic pain, Dr. Daniel J. Clauw said physicians have been looking in the wrong places.

"There is no chronic pain state where degree of damage or inflammation in the periphery correlates well with level of pain. Yet, the diagnostic algorithms or paradigms that everyone uses for treating chronic pain still assume that all pain is nociceptive. What we see in the peripheral tissues is not necessarily what our patients are experiencing," said Dr. Clauw, director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor.

Historically, it has been assumed that when there was a disparity between peripheral findings and pain, psychological factors were at work. But the current view of chronic pain is that while it may originate from peripheral nociceptive input or nerve damage, central neuronal factors – at least some of them genetically determined – are nearly always playing a role in leading to interindividual differences in pain sensitivity, which are in turn closely associated with clinical outcomes.

For instance, population-based studies have shown that 30%-40% of individuals with radiographic evidence of severe damage from osteoarthritis are pain free, while 10% of those with normal radiographs have severe pain (Br. J. Rheumatol. 1997;36:726-8). Psychological factors explain very little of the variance between symptoms and structure (Arthritis Care Res. 1998;11:60-5), suggesting that central mechanisms involved in pain processing are at work, Dr. Clauw said at the workshop, sponsored by the University of Michigan and the National Institutes of Health.

Of course, individuals with osteoarthritis and rheumatoid arthritis will often have evidence of nociceptive input, while those with fibromyalgia have more prominent central factors. But no chronic pain state is solely due to any one of these mechanisms, he said.

"The scientific paradigm shift requires that we rethink everything from diagnostics and treatment approaches – which currently place an unjustified importance on treating peripheral factors," he said.

The new paradigm suggests that, regardless of the specific diagnosis, "central pain states" including fibromyalgia, rheumatoid arthritis, osteoarthritis, lupus, and low back pain all tend to share certain characteristics that can be better assessed by asking questions than by physical examination.

Showing patients a body diagram and asking them to label all the areas where they have pain is a simple assessment tool for multifocal pain. Also, ask about previous pain and other somatic symptoms such as fatigue, memory difficulty, mood disorders, and sleep disturbances, all common in the context of central pain but not with pain that is solely peripheral.

Is the pain triggered or exacerbated by stressors, such as psychological stress, infections, or physical trauma? Was there a salient stressor in the patient’s early life, such as an auto accident or the death of a loved one? All are common among patients with central pain, said Dr. Clauw, professor of anesthesiology and medicine (rheumatology) at the university.

Because these patients tend to have global sensory processing problems, asking about hypersensitivity to bright lights, odors, or noises will also help confirm the "central" diagnosis. Take a family history of pain as well, as there are strong familial and genetic linkages among the chronic pain syndromes, at least among women (Psychol. Med. 2009;39:497-505).

Physical examination is likely to be normal except for diffuse tenderness and nonspecific neurologic signs (Arthritis Rheum. 2009;60:2839-44). "This is why, historically, patients with fibromyalgia haven’t been believed," Dr. Clauw commented.

As for treatment, it is becoming increasingly clear that peripherally-acting pharmacologic agents such as opioids, corticosteroids, and nonsteroidal anti-inflammatory drugs simply do not work in central pain states.

Far more effective for fibromyalgia – and most likely other central pain states as well – are dual reuptake inhibitors such as tricyclic compounds (amitriptyline, cyclobenzaprine), serotonin-norepinephrine reuptake inhibitors (milnacipran, duloxetine), gamma hydroxybutyrate, and gabapentin. There is also modest evidence supporting the use of tramadol, selective serotonin reuptake inhibitors, and dopamine agonists (JAMA 2004;292:2388-95).

Nonpharmacologic therapies are also beneficial, including cognitive-behavioral therapy, exercise, and sleep hygiene (Best Pract. Res. Clin. Rheumatol. 2003;17:685-701).

Despite an abundance of emerging data to support the new way of thinking about chronic pain, Dr. Clauw said he thinks that shifting to a new management strategy could be difficult. "It takes a long time for people trained in one way of thinking to think differently. This isn’t just a new drug or a new device. This is a major paradigm shift."

Dr. Clauw disclosed that he is a consultant for Pfizer, Forest, Eli Lilly, Pierre Fabre Laboratories, Cypress Biosciences, Wyeth, UCB, AstraZeneca, Merck, Johnson & Johnson, Nuvo, and Jazz. He said he has also received research support from Pfizer, Cypress, and Forest.

The association between diabetes and depression is bidirectional in middle-age women, with the presence of either disease significantly raising the risk that the other also will develop, according to a report in the Archives of Internal Medicine.

Moreover, diabetes raises the risk of depression, and depression raises the risk of diabetes, independently of other known risk factors such as adiposity that are common to both diseases, said An Pan, Ph.D., of Harvard School of Public Health, Boston, and his associates.

To date, "only a few" studies have examined the association between diabetes and depression simultaneously, and their results have been inconsistent. "Therefore, we took advantage of repeated measurements of lifestyle risk factors and disease occurrences during 10 years of follow-up in a large prospective cohort" – the Nurses’ Health Study – to address the bidirectional relationship.

The NHS involved female registered nurses residing in 11 states who were followed every 2 years via health questionnaires. Dr. Pan and his colleagues assessed a subset of 65,381 NHS participants who were aged 50-75 years in 1996 and were followed until 2006.

Depressive symptoms were categorized according to the women’s scores on the Mental Health Index 5, whether depression had been diagnosed by a physician and whether they used antidepressants. Diabetes was categorized as requiring no medications, only oral hypoglycemic agents, or insulin therapy.

During follow-up, 2,844 incident cases of diabetes were documented. The risk of developing diabetes was significantly higher in women who had depressive symptoms than in those who did not.

In addition, this rise in diabetes risk showed a "dose-response relationship" with worsening depressive symptoms, such that diabetes risk increased significantly as scores on the MHI-5 rose.

This association between depression and diabetes remained significant, although it was markedly attenuated, when the data were adjusted to account for body mass index (BMI) and lifestyle factors, particularly physical activity.

In a separate analysis of the same data, 7,415 study subjects developed incident clinical depression during follow-up. Compared with women who did not have diabetes, women with diabetes had a relative risk of developing clinical depression of 1.44, the investigators said (Arch. Intern. Med. 2010;170:1884-91).

Controlling for major comorbidities such as hypertension and coronary heart disease attenuated this association, but it remained significant.

In addition, the risk of developing clinical depression also showed a dose-response relationship with worsening diabetes symptoms. Women with diabetes who were not taking any medication had a relative risk of 1.36; those taking oral agents only had a relative risk of 1.42; and those taking insulin had a relative risk of 1.78 of developing clinical depression.

These findings show that depression and diabetes "are closely related to each other, and this reciprocal association also depends on the severity and treatment of each condition. All the associations were independent of sociodemographic, diet, and lifestyle factors," Dr. Pan and his associates said.

Since depression and diabetes both are highly prevalent in the middle-age and elderly populations, particularly among women, "proper lifestyle interventions including adequate weight management and regular physical activity are recommended to lower the risk of both conditions," they noted.

The reasons underlying the bidirectional association are not yet understood. It is possible that antidepressant use might be a contributing factor to diabetes risk. Antidepressants might exert some clinical effects on glucose homeostasis, and they are known to cause weight gain. However, the link between depression and diabetes was significant independent of BMI, so the possibility that antidepressants might exert some other metabolic effect warrants further investigation, the researchers said.

Alternatively, biochemical changes directly caused by diabetes or its treatment might contribute to depression. It also is possible that the stresses associated with chronic diabetes and its debilitating consequences also contribute to depression.

This study was somewhat limited in that the NHS cohort was 94% white, well educated, and well versed on health issues. The results might not be generalizable to other populations, they added.

This study was supported by the National Institutes of Health, the National Alliance for Research on Schizophrenia & Depression, and the Fonds de la recherche en santé du Québec. No financial conflicts of interest were reported.

The association between diabetes and depression is bidirectional in middle-age women, with the presence of either disease significantly raising the risk that the other also will develop, according to a report in the Archives of Internal Medicine.

Moreover, diabetes raises the risk of depression, and depression raises the risk of diabetes, independently of other known risk factors such as adiposity that are common to both diseases, said An Pan, Ph.D., of Harvard School of Public Health, Boston, and his associates.

To date, "only a few" studies have examined the association between diabetes and depression simultaneously, and their results have been inconsistent. "Therefore, we took advantage of repeated measurements of lifestyle risk factors and disease occurrences during 10 years of follow-up in a large prospective cohort" – the Nurses’ Health Study – to address the bidirectional relationship.

The NHS involved female registered nurses residing in 11 states who were followed every 2 years via health questionnaires. Dr. Pan and his colleagues assessed a subset of 65,381 NHS participants who were aged 50-75 years in 1996 and were followed until 2006.

Depressive symptoms were categorized according to the women’s scores on the Mental Health Index 5, whether depression had been diagnosed by a physician and whether they used antidepressants. Diabetes was categorized as requiring no medications, only oral hypoglycemic agents, or insulin therapy.

During follow-up, 2,844 incident cases of diabetes were documented. The risk of developing diabetes was significantly higher in women who had depressive symptoms than in those who did not.

In addition, this rise in diabetes risk showed a "dose-response relationship" with worsening depressive symptoms, such that diabetes risk increased significantly as scores on the MHI-5 rose.

This association between depression and diabetes remained significant, although it was markedly attenuated, when the data were adjusted to account for body mass index (BMI) and lifestyle factors, particularly physical activity.

In a separate analysis of the same data, 7,415 study subjects developed incident clinical depression during follow-up. Compared with women who did not have diabetes, women with diabetes had a relative risk of developing clinical depression of 1.44, the investigators said (Arch. Intern. Med. 2010;170:1884-91).

Controlling for major comorbidities such as hypertension and coronary heart disease attenuated this association, but it remained significant.

In addition, the risk of developing clinical depression also showed a dose-response relationship with worsening diabetes symptoms. Women with diabetes who were not taking any medication had a relative risk of 1.36; those taking oral agents only had a relative risk of 1.42; and those taking insulin had a relative risk of 1.78 of developing clinical depression.

These findings show that depression and diabetes "are closely related to each other, and this reciprocal association also depends on the severity and treatment of each condition. All the associations were independent of sociodemographic, diet, and lifestyle factors," Dr. Pan and his associates said.

Since depression and diabetes both are highly prevalent in the middle-age and elderly populations, particularly among women, "proper lifestyle interventions including adequate weight management and regular physical activity are recommended to lower the risk of both conditions," they noted.

The reasons underlying the bidirectional association are not yet understood. It is possible that antidepressant use might be a contributing factor to diabetes risk. Antidepressants might exert some clinical effects on glucose homeostasis, and they are known to cause weight gain. However, the link between depression and diabetes was significant independent of BMI, so the possibility that antidepressants might exert some other metabolic effect warrants further investigation, the researchers said.

Alternatively, biochemical changes directly caused by diabetes or its treatment might contribute to depression. It also is possible that the stresses associated with chronic diabetes and its debilitating consequences also contribute to depression.

This study was somewhat limited in that the NHS cohort was 94% white, well educated, and well versed on health issues. The results might not be generalizable to other populations, they added.

This study was supported by the National Institutes of Health, the National Alliance for Research on Schizophrenia & Depression, and the Fonds de la recherche en santé du Québec. No financial conflicts of interest were reported.

The association between diabetes and depression is bidirectional in middle-age women, with the presence of either disease significantly raising the risk that the other also will develop, according to a report in the Archives of Internal Medicine.

Moreover, diabetes raises the risk of depression, and depression raises the risk of diabetes, independently of other known risk factors such as adiposity that are common to both diseases, said An Pan, Ph.D., of Harvard School of Public Health, Boston, and his associates.

To date, "only a few" studies have examined the association between diabetes and depression simultaneously, and their results have been inconsistent. "Therefore, we took advantage of repeated measurements of lifestyle risk factors and disease occurrences during 10 years of follow-up in a large prospective cohort" – the Nurses’ Health Study – to address the bidirectional relationship.

The NHS involved female registered nurses residing in 11 states who were followed every 2 years via health questionnaires. Dr. Pan and his colleagues assessed a subset of 65,381 NHS participants who were aged 50-75 years in 1996 and were followed until 2006.

Depressive symptoms were categorized according to the women’s scores on the Mental Health Index 5, whether depression had been diagnosed by a physician and whether they used antidepressants. Diabetes was categorized as requiring no medications, only oral hypoglycemic agents, or insulin therapy.

During follow-up, 2,844 incident cases of diabetes were documented. The risk of developing diabetes was significantly higher in women who had depressive symptoms than in those who did not.

In addition, this rise in diabetes risk showed a "dose-response relationship" with worsening depressive symptoms, such that diabetes risk increased significantly as scores on the MHI-5 rose.

This association between depression and diabetes remained significant, although it was markedly attenuated, when the data were adjusted to account for body mass index (BMI) and lifestyle factors, particularly physical activity.

In a separate analysis of the same data, 7,415 study subjects developed incident clinical depression during follow-up. Compared with women who did not have diabetes, women with diabetes had a relative risk of developing clinical depression of 1.44, the investigators said (Arch. Intern. Med. 2010;170:1884-91).

Controlling for major comorbidities such as hypertension and coronary heart disease attenuated this association, but it remained significant.

In addition, the risk of developing clinical depression also showed a dose-response relationship with worsening diabetes symptoms. Women with diabetes who were not taking any medication had a relative risk of 1.36; those taking oral agents only had a relative risk of 1.42; and those taking insulin had a relative risk of 1.78 of developing clinical depression.

These findings show that depression and diabetes "are closely related to each other, and this reciprocal association also depends on the severity and treatment of each condition. All the associations were independent of sociodemographic, diet, and lifestyle factors," Dr. Pan and his associates said.

Since depression and diabetes both are highly prevalent in the middle-age and elderly populations, particularly among women, "proper lifestyle interventions including adequate weight management and regular physical activity are recommended to lower the risk of both conditions," they noted.

The reasons underlying the bidirectional association are not yet understood. It is possible that antidepressant use might be a contributing factor to diabetes risk. Antidepressants might exert some clinical effects on glucose homeostasis, and they are known to cause weight gain. However, the link between depression and diabetes was significant independent of BMI, so the possibility that antidepressants might exert some other metabolic effect warrants further investigation, the researchers said.

Alternatively, biochemical changes directly caused by diabetes or its treatment might contribute to depression. It also is possible that the stresses associated with chronic diabetes and its debilitating consequences also contribute to depression.

This study was somewhat limited in that the NHS cohort was 94% white, well educated, and well versed on health issues. The results might not be generalizable to other populations, they added.

This study was supported by the National Institutes of Health, the National Alliance for Research on Schizophrenia & Depression, and the Fonds de la recherche en santé du Québec. No financial conflicts of interest were reported.

LOS ANGELES – There is very little evidence – and in some cases none at all – to support common pharmacologic treatments for anorexia and bulimia nervosa, according to Michael Strober, Ph.D.

Eating disorders "are the black hole of pharmacotherapy in psychiatry. There’s not much at this point in time we have to offer," Dr. Strober, director of the eating disorders program at the UCLA Neuropsychiatric Institute and Hospital, reported.

For anorexia nervosa, evidence is stronger for family-based therapy in which families are taught to help a child eat and maintain weight.

Cognitive-behavioral therapy (CBT) is more effective than drugs for bulimia nervosa and remains its treatment of choice, said Dr. Strober, who estimated he’s treated more than 8,000 eating disorder patients during a career dating back to 1975.

Although selective serotonin reuptake inhibitors (SSRIs) are widely used to treat anorexia, "there is absolutely not a speck of evidence that these drugs, in the acutely malnourished state, are effective," or that they help maintain weight gain, said Dr. Strober, who also serves as director of the adolescent mood disorders program at the institute.

There is slight evidence for the atypical antipsychotic, olanzapine (Zyprexa).

In a trial funded by the drug’s maker, Eli Lilly, 16 anorexia patients were randomized to outpatient day treatment plus olanzapine, and 18 to day treatment plus placebo.

The mean body mass index was low-normal in both groups at the end of 13 weeks (19.66 kg/m2 in the placebo group vs. 20.30 in the olanzapine group). However, placebo patients started with a lower mean BMI of 15.93, compared with 16.39 among olanzapine patients.

Also, at week 13, 55.6% of placebo patients but 87.5% of olanzapine patients achieved the target BMI of 18.5 (Am. J. Psychiatry 2008;165:1281-8).

The differences were "not very dramatic," but were statistically significant, Dr. Strober said.

"We have no idea what the mechanism is. We don’t know if it’s mediated by improved psychological state or weight gain associated with olanzapine," he said.

Given the lack of data, Dr. Strober said that he and his colleagues typically refeed anorexia inpatients for a few weeks, and only then add atypical antipsychotics if they aren’t managing well.

"I generally think [they] have more of an effect than the SSRIs, although we have patients receiving SSRIs who report less anxiety and psychological discomfort with weight gain," Dr. Strober said.

In general, however, "I have never seen a robust clinical effect of these agents," he said.

For bulimia, antidepressants have been shown to help.

"Regardless of the antidepressant used, in the majority of published studies – we really don’t know how many unpublished studies have been buried – active drug separates from placebo," Dr. Strober said.

"What this means is that about 60%-65% of people randomized to active treatment report a response (defined as a 50% or greater reduction in the frequency of binge eating)," compared with placebo responses of about 35%-40%, he said.

"We get remission rates – which means no bingeing or purging the last 2 weeks of the trial – of about 10% on active drug, maybe 0%-3% on placebo," he said.

However, about 50% of responders "have a recurrence of their symptoms" within 5 months, "so these are not very effective drugs for the majority of patients," Dr. Strober said.

CBT does better: "After 12-16 weeks, we get response rates (defined in the same way) that are roughly 65%-70%. You get about 35%-38% that are fully remitted, and that response tends to be more durable," he said.

Evidence also supports family-based therapy (FBT) for anorexia nervosa.

In a recent study, 121 subjects aged 12-18 years with mild to moderate illness – the trial excluded patients below 75% of their ideal body weight – were randomized to either individual therapy or FBT.

At the end of treatment and at 12 months’ follow-up, body weights were normal in about half of FBT patients but only in about a quarter of individual therapy patients (Arch. Gen. Psychiatry 2010;67:1025-32).

"There’s a signal here, I think – a powerful signal," Dr. Strober said. "This is a meaningful difference."

Family-based therapy "is an important treatment. We don’t really know what the ingredient is; we just know that this has been helpful for a number of families, but you really have to be very skilled in working with these people," he said.

Dr. Strober said he has no disclosures.

LOS ANGELES – There is very little evidence – and in some cases none at all – to support common pharmacologic treatments for anorexia and bulimia nervosa, according to Michael Strober, Ph.D.

Eating disorders "are the black hole of pharmacotherapy in psychiatry. There’s not much at this point in time we have to offer," Dr. Strober, director of the eating disorders program at the UCLA Neuropsychiatric Institute and Hospital, reported.

For anorexia nervosa, evidence is stronger for family-based therapy in which families are taught to help a child eat and maintain weight.

Cognitive-behavioral therapy (CBT) is more effective than drugs for bulimia nervosa and remains its treatment of choice, said Dr. Strober, who estimated he’s treated more than 8,000 eating disorder patients during a career dating back to 1975.

Although selective serotonin reuptake inhibitors (SSRIs) are widely used to treat anorexia, "there is absolutely not a speck of evidence that these drugs, in the acutely malnourished state, are effective," or that they help maintain weight gain, said Dr. Strober, who also serves as director of the adolescent mood disorders program at the institute.

There is slight evidence for the atypical antipsychotic, olanzapine (Zyprexa).

In a trial funded by the drug’s maker, Eli Lilly, 16 anorexia patients were randomized to outpatient day treatment plus olanzapine, and 18 to day treatment plus placebo.

The mean body mass index was low-normal in both groups at the end of 13 weeks (19.66 kg/m2 in the placebo group vs. 20.30 in the olanzapine group). However, placebo patients started with a lower mean BMI of 15.93, compared with 16.39 among olanzapine patients.

Also, at week 13, 55.6% of placebo patients but 87.5% of olanzapine patients achieved the target BMI of 18.5 (Am. J. Psychiatry 2008;165:1281-8).

The differences were "not very dramatic," but were statistically significant, Dr. Strober said.

"We have no idea what the mechanism is. We don’t know if it’s mediated by improved psychological state or weight gain associated with olanzapine," he said.

Given the lack of data, Dr. Strober said that he and his colleagues typically refeed anorexia inpatients for a few weeks, and only then add atypical antipsychotics if they aren’t managing well.

"I generally think [they] have more of an effect than the SSRIs, although we have patients receiving SSRIs who report less anxiety and psychological discomfort with weight gain," Dr. Strober said.

In general, however, "I have never seen a robust clinical effect of these agents," he said.

For bulimia, antidepressants have been shown to help.

"Regardless of the antidepressant used, in the majority of published studies – we really don’t know how many unpublished studies have been buried – active drug separates from placebo," Dr. Strober said.

"What this means is that about 60%-65% of people randomized to active treatment report a response (defined as a 50% or greater reduction in the frequency of binge eating)," compared with placebo responses of about 35%-40%, he said.

"We get remission rates – which means no bingeing or purging the last 2 weeks of the trial – of about 10% on active drug, maybe 0%-3% on placebo," he said.

However, about 50% of responders "have a recurrence of their symptoms" within 5 months, "so these are not very effective drugs for the majority of patients," Dr. Strober said.

CBT does better: "After 12-16 weeks, we get response rates (defined in the same way) that are roughly 65%-70%. You get about 35%-38% that are fully remitted, and that response tends to be more durable," he said.

Evidence also supports family-based therapy (FBT) for anorexia nervosa.

In a recent study, 121 subjects aged 12-18 years with mild to moderate illness – the trial excluded patients below 75% of their ideal body weight – were randomized to either individual therapy or FBT.

At the end of treatment and at 12 months’ follow-up, body weights were normal in about half of FBT patients but only in about a quarter of individual therapy patients (Arch. Gen. Psychiatry 2010;67:1025-32).

"There’s a signal here, I think – a powerful signal," Dr. Strober said. "This is a meaningful difference."

Family-based therapy "is an important treatment. We don’t really know what the ingredient is; we just know that this has been helpful for a number of families, but you really have to be very skilled in working with these people," he said.

Dr. Strober said he has no disclosures.

LOS ANGELES – There is very little evidence – and in some cases none at all – to support common pharmacologic treatments for anorexia and bulimia nervosa, according to Michael Strober, Ph.D.

Eating disorders "are the black hole of pharmacotherapy in psychiatry. There’s not much at this point in time we have to offer," Dr. Strober, director of the eating disorders program at the UCLA Neuropsychiatric Institute and Hospital, reported.

For anorexia nervosa, evidence is stronger for family-based therapy in which families are taught to help a child eat and maintain weight.

Cognitive-behavioral therapy (CBT) is more effective than drugs for bulimia nervosa and remains its treatment of choice, said Dr. Strober, who estimated he’s treated more than 8,000 eating disorder patients during a career dating back to 1975.

Although selective serotonin reuptake inhibitors (SSRIs) are widely used to treat anorexia, "there is absolutely not a speck of evidence that these drugs, in the acutely malnourished state, are effective," or that they help maintain weight gain, said Dr. Strober, who also serves as director of the adolescent mood disorders program at the institute.

There is slight evidence for the atypical antipsychotic, olanzapine (Zyprexa).

In a trial funded by the drug’s maker, Eli Lilly, 16 anorexia patients were randomized to outpatient day treatment plus olanzapine, and 18 to day treatment plus placebo.

The mean body mass index was low-normal in both groups at the end of 13 weeks (19.66 kg/m2 in the placebo group vs. 20.30 in the olanzapine group). However, placebo patients started with a lower mean BMI of 15.93, compared with 16.39 among olanzapine patients.

Also, at week 13, 55.6% of placebo patients but 87.5% of olanzapine patients achieved the target BMI of 18.5 (Am. J. Psychiatry 2008;165:1281-8).

The differences were "not very dramatic," but were statistically significant, Dr. Strober said.

"We have no idea what the mechanism is. We don’t know if it’s mediated by improved psychological state or weight gain associated with olanzapine," he said.

Given the lack of data, Dr. Strober said that he and his colleagues typically refeed anorexia inpatients for a few weeks, and only then add atypical antipsychotics if they aren’t managing well.

"I generally think [they] have more of an effect than the SSRIs, although we have patients receiving SSRIs who report less anxiety and psychological discomfort with weight gain," Dr. Strober said.

In general, however, "I have never seen a robust clinical effect of these agents," he said.

For bulimia, antidepressants have been shown to help.

"Regardless of the antidepressant used, in the majority of published studies – we really don’t know how many unpublished studies have been buried – active drug separates from placebo," Dr. Strober said.

"What this means is that about 60%-65% of people randomized to active treatment report a response (defined as a 50% or greater reduction in the frequency of binge eating)," compared with placebo responses of about 35%-40%, he said.

"We get remission rates – which means no bingeing or purging the last 2 weeks of the trial – of about 10% on active drug, maybe 0%-3% on placebo," he said.

However, about 50% of responders "have a recurrence of their symptoms" within 5 months, "so these are not very effective drugs for the majority of patients," Dr. Strober said.

CBT does better: "After 12-16 weeks, we get response rates (defined in the same way) that are roughly 65%-70%. You get about 35%-38% that are fully remitted, and that response tends to be more durable," he said.

Evidence also supports family-based therapy (FBT) for anorexia nervosa.

In a recent study, 121 subjects aged 12-18 years with mild to moderate illness – the trial excluded patients below 75% of their ideal body weight – were randomized to either individual therapy or FBT.

At the end of treatment and at 12 months’ follow-up, body weights were normal in about half of FBT patients but only in about a quarter of individual therapy patients (Arch. Gen. Psychiatry 2010;67:1025-32).

"There’s a signal here, I think – a powerful signal," Dr. Strober said. "This is a meaningful difference."

Family-based therapy "is an important treatment. We don’t really know what the ingredient is; we just know that this has been helpful for a number of families, but you really have to be very skilled in working with these people," he said.

Dr. Strober said he has no disclosures.

SAN ANTONIO — Body mass index is strongly correlated with self-reported days of insufficient sleep per month among U.S. adults, according to a large national study.

The study included 384,020 U.S. adults who participated in the Centers for Disease Control and Prevention’s 2008 Behavioral Risk Factor Surveillance System survey, the world’s largest telephone health survey. The 2008 version included this question: "During the past 30 days, for about how many days have you felt you did not get enough rest or sleep?"

Days of insufficient sleep followed a linear trend across body mass index (BMI) categories. Among the 36.8% of respondents who were normal weight or underweight, the mean number of days of insufficient sleep in the past month was 7.9. The 36.4% of the population who were overweight averaged 8.4 days. For the 17.1% who were obese class I with a BMI of at least 30 and less than 35 kg/m2, it was 9.4 days. And the 3.5% of adults were obese class III with a BMI of 40 kg/m2 or more averaged 11.1 days of insufficient sleep per month, Anne G. Wheaton reported at the meeting.

Twenty-five percent of normal-weight respondents indicated they had 14 or more days of insufficient sleep in the past 30 days. This proportion rose steadily through the BMI categories, reaching 37.1% among individuals who were obese class III, added Ms. Wheaton of the CDC.

In a multivariate regression analysis adjusted for demographic variables, physical activity, and smoking, respondents who were obese class I, II, or III were, respectively, 1.4-fold, 1.6-fold, and 1.8-fold more likely than were normal-weight individuals to have had at least 14 days of insufficient sleep in the past 30 days.

The implication of this study, she said, is that insufficient sleep should be addressed in weight reduction programs, and excess weight ought to be considered in developing programs to address sleep disorders.

This study was supported by a grant from the Association for Prevention Teaching and Research, and the CDC.

Ms. Wheaton reported no financial conflicts.

SAN ANTONIO — Body mass index is strongly correlated with self-reported days of insufficient sleep per month among U.S. adults, according to a large national study.

The study included 384,020 U.S. adults who participated in the Centers for Disease Control and Prevention’s 2008 Behavioral Risk Factor Surveillance System survey, the world’s largest telephone health survey. The 2008 version included this question: "During the past 30 days, for about how many days have you felt you did not get enough rest or sleep?"

Days of insufficient sleep followed a linear trend across body mass index (BMI) categories. Among the 36.8% of respondents who were normal weight or underweight, the mean number of days of insufficient sleep in the past month was 7.9. The 36.4% of the population who were overweight averaged 8.4 days. For the 17.1% who were obese class I with a BMI of at least 30 and less than 35 kg/m2, it was 9.4 days. And the 3.5% of adults were obese class III with a BMI of 40 kg/m2 or more averaged 11.1 days of insufficient sleep per month, Anne G. Wheaton reported at the meeting.

Twenty-five percent of normal-weight respondents indicated they had 14 or more days of insufficient sleep in the past 30 days. This proportion rose steadily through the BMI categories, reaching 37.1% among individuals who were obese class III, added Ms. Wheaton of the CDC.

In a multivariate regression analysis adjusted for demographic variables, physical activity, and smoking, respondents who were obese class I, II, or III were, respectively, 1.4-fold, 1.6-fold, and 1.8-fold more likely than were normal-weight individuals to have had at least 14 days of insufficient sleep in the past 30 days.

The implication of this study, she said, is that insufficient sleep should be addressed in weight reduction programs, and excess weight ought to be considered in developing programs to address sleep disorders.

This study was supported by a grant from the Association for Prevention Teaching and Research, and the CDC.

Ms. Wheaton reported no financial conflicts.

SAN ANTONIO — Body mass index is strongly correlated with self-reported days of insufficient sleep per month among U.S. adults, according to a large national study.

The study included 384,020 U.S. adults who participated in the Centers for Disease Control and Prevention’s 2008 Behavioral Risk Factor Surveillance System survey, the world’s largest telephone health survey. The 2008 version included this question: "During the past 30 days, for about how many days have you felt you did not get enough rest or sleep?"

Days of insufficient sleep followed a linear trend across body mass index (BMI) categories. Among the 36.8% of respondents who were normal weight or underweight, the mean number of days of insufficient sleep in the past month was 7.9. The 36.4% of the population who were overweight averaged 8.4 days. For the 17.1% who were obese class I with a BMI of at least 30 and less than 35 kg/m2, it was 9.4 days. And the 3.5% of adults were obese class III with a BMI of 40 kg/m2 or more averaged 11.1 days of insufficient sleep per month, Anne G. Wheaton reported at the meeting.

Twenty-five percent of normal-weight respondents indicated they had 14 or more days of insufficient sleep in the past 30 days. This proportion rose steadily through the BMI categories, reaching 37.1% among individuals who were obese class III, added Ms. Wheaton of the CDC.

In a multivariate regression analysis adjusted for demographic variables, physical activity, and smoking, respondents who were obese class I, II, or III were, respectively, 1.4-fold, 1.6-fold, and 1.8-fold more likely than were normal-weight individuals to have had at least 14 days of insufficient sleep in the past 30 days.

The implication of this study, she said, is that insufficient sleep should be addressed in weight reduction programs, and excess weight ought to be considered in developing programs to address sleep disorders.

This study was supported by a grant from the Association for Prevention Teaching and Research, and the CDC.

Ms. Wheaton reported no financial conflicts.

VANCOUVER, B.C. – Recent research on the use of home testing for the diagnosis of obstructive sleep apnea and initiation of therapy suggests that "home testing is here to stay," Dr. Charles W. Atwood Jr. told attendees at the meeting.

For more than 30 years, physicians have relied on the traditional polysomnography performed in the sleep laboratory to diagnose sleep apnea, according to Dr. Atwood. But with growing awareness of the condition and its prevalence, the number of people needing testing could overwhelm capacity.

"If you take the millions and millions and millions of people in the United States alone who have sleep apnea and try to feed them through the relatively small funnel of traditional sleep labs, then you are going to have big bottlenecks," he said, adding that such bottlenecks already exist in some areas.

However, home-testing devices must meet certain key requirements before they are ready for widespread use. For example, they have to be simpler than those used in the lab. "Perhaps we can get by with fewer [physiological] signals, but we need to understand what the key signals are," commented Dr. Atwood, a pulmonologist and sleep medicine specialist with the VA Pittsburgh Healthcare System and the University of Pittsburgh Medical Center.

Home testing devices will also need to be accurate, with high sensitivity and specificity, and "there is no single device I would say today that is perfect in both these regards," he noted. Finally, they must be easy to use and durable, given the demands of in-home use.

Roughly 95 studies conducted between 1990 and 2006 evaluated home testing (also called portable monitoring) for the diagnosis of obstructive sleep apnea. Collectively, they had some limitations, such as their single-site nature, small and usually homogeneous populations, and varying degrees of rigor in design.

"And they frequently focused on the highest-risk subjects: These were middle-aged men who were overweight, snored, and were sleepy, so [they were] the very low-hanging fruit for typical sleep apnea," Dr. Atwood said.

These studies showed mixed results when it came to the diagnostic performance of home testing relative to lab testing. "There is no perfect study, at least so far, in this area, but some have come pretty close," he commented.

Three more recent studies suggest that home testing is at least not inferior to lab testing for sleep apnea diagnosis and initiation of continuous positive airway pressure (CPAP) therapy, according to Dr. Atwood.

In the first study, conducted among 68 people with a high likelihood of sleep apnea, the apnea-hypopnea index on CPAP and Sleep Apnea Quality of Life Index scores at 3 months did not differ significantly between a sleep lab approach and an ambulatory approach (Ann. Intern. Med. 2007;146:157-66). The rate of adherence to CPAP was better with the latter.

In the second study, which involved 102 patients with sleep apnea symptoms and no major comorbidities, all of a variety of sleep and quality of life outcomes after 4 weeks of CPAP were similar with a standard lab diagnosis and treatment approach vs. a home approach (Chest 2010;138:257-63).

The third study, the Veterans Sleep Apnea Treatment Trial (VSATT), is the largest study of home testing in North America to date, according to Dr. Atwood, who is one of the principal investigators.

"The VA is ill equipped to manage sleep apnea in a conventional way because we have relatively few numbers of traditional sleep labs, and those sleep labs that do exist tend to be kind of small," he noted. Also, there are geographic disparities, with some veterans having virtually no access to sleep labs.

"Our study differed from basically all of the other studies in the literature in that we had very broad inclusion criteria and very nonrestrictive exclusion criteria," Dr. Atwood noted. For example, patients with comorbidities could participate as long as their condition was stable.

The patients were randomized to lab testing or home testing, followed by initiation of CPAP for those with positive results.

Among the 223 who were started on CPAP, the home and lab groups had similar demographics. The average apnea-hypopnea index was 41 for the former and 45 for the latter. The Functional Outcomes of Sleep Questionnaire (FOSQ) total score was about 15 in each group.

Results showed that the mean adjusted improvement in FOSQ total score between baseline and 3 months was identical in the two groups, at 1.79 points. And within each group, patients had significant improvements in the total score as well as its individual components.

Both home and lab groups also had significant improvements on the Epworth Sleepiness Scale (–2.6 and –2.9, respectively), the mental health component of the 12-item Short Form Health Survey (+2.5 and +3.0), and the Center for Epidemiologic Studies–Depression scale (–1.4 and –2.2). Neither group improved significantly on the psychovigilance task or the physical health component of the 12-item Short Form Health Survey.

When it came to adherence, which was monitored with smart cards, the mean adjusted number of CPAP hours daily was 3.42 in the home group and 2.99 in the lab group, a difference that was not significant. Cost-effectiveness analyses are still ongoing.

"We concluded that the functional improvement with CPAP for sleep apnea is not worse when treated in the home setting vs. the sleep lab," Dr. Atwood said. "We believe that the implication is that home-based sleep apnea diagnosis and initiation of CPAP therapy is an effective way to treat sleep apnea."

Despite all of the accumulating favorable findings for home testing, Dr. Atwood was skeptical that it will entirely replace laboratory polysomnography.

"Home sleep apnea testing is part of the future, but it’s unlikely to be the whole future," he contended. "The way to think about home sleep apnea testing now is not ‘either/or,’ but really to begin to integrate home sleep testing with full polysomnography in a clinically rational way."

Dr. Atwood reported that he received research support from Embla, Resmed, and Respironics, and is a consultant to Embla and Itamar Medical, all of which manufacture testing and treatment devices for sleep disorders.

VANCOUVER, B.C. – Recent research on the use of home testing for the diagnosis of obstructive sleep apnea and initiation of therapy suggests that "home testing is here to stay," Dr. Charles W. Atwood Jr. told attendees at the meeting.

For more than 30 years, physicians have relied on the traditional polysomnography performed in the sleep laboratory to diagnose sleep apnea, according to Dr. Atwood. But with growing awareness of the condition and its prevalence, the number of people needing testing could overwhelm capacity.

"If you take the millions and millions and millions of people in the United States alone who have sleep apnea and try to feed them through the relatively small funnel of traditional sleep labs, then you are going to have big bottlenecks," he said, adding that such bottlenecks already exist in some areas.

However, home-testing devices must meet certain key requirements before they are ready for widespread use. For example, they have to be simpler than those used in the lab. "Perhaps we can get by with fewer [physiological] signals, but we need to understand what the key signals are," commented Dr. Atwood, a pulmonologist and sleep medicine specialist with the VA Pittsburgh Healthcare System and the University of Pittsburgh Medical Center.

Home testing devices will also need to be accurate, with high sensitivity and specificity, and "there is no single device I would say today that is perfect in both these regards," he noted. Finally, they must be easy to use and durable, given the demands of in-home use.

Roughly 95 studies conducted between 1990 and 2006 evaluated home testing (also called portable monitoring) for the diagnosis of obstructive sleep apnea. Collectively, they had some limitations, such as their single-site nature, small and usually homogeneous populations, and varying degrees of rigor in design.

"And they frequently focused on the highest-risk subjects: These were middle-aged men who were overweight, snored, and were sleepy, so [they were] the very low-hanging fruit for typical sleep apnea," Dr. Atwood said.

These studies showed mixed results when it came to the diagnostic performance of home testing relative to lab testing. "There is no perfect study, at least so far, in this area, but some have come pretty close," he commented.

Three more recent studies suggest that home testing is at least not inferior to lab testing for sleep apnea diagnosis and initiation of continuous positive airway pressure (CPAP) therapy, according to Dr. Atwood.

In the first study, conducted among 68 people with a high likelihood of sleep apnea, the apnea-hypopnea index on CPAP and Sleep Apnea Quality of Life Index scores at 3 months did not differ significantly between a sleep lab approach and an ambulatory approach (Ann. Intern. Med. 2007;146:157-66). The rate of adherence to CPAP was better with the latter.

In the second study, which involved 102 patients with sleep apnea symptoms and no major comorbidities, all of a variety of sleep and quality of life outcomes after 4 weeks of CPAP were similar with a standard lab diagnosis and treatment approach vs. a home approach (Chest 2010;138:257-63).

The third study, the Veterans Sleep Apnea Treatment Trial (VSATT), is the largest study of home testing in North America to date, according to Dr. Atwood, who is one of the principal investigators.

"The VA is ill equipped to manage sleep apnea in a conventional way because we have relatively few numbers of traditional sleep labs, and those sleep labs that do exist tend to be kind of small," he noted. Also, there are geographic disparities, with some veterans having virtually no access to sleep labs.

"Our study differed from basically all of the other studies in the literature in that we had very broad inclusion criteria and very nonrestrictive exclusion criteria," Dr. Atwood noted. For example, patients with comorbidities could participate as long as their condition was stable.

The patients were randomized to lab testing or home testing, followed by initiation of CPAP for those with positive results.

Among the 223 who were started on CPAP, the home and lab groups had similar demographics. The average apnea-hypopnea index was 41 for the former and 45 for the latter. The Functional Outcomes of Sleep Questionnaire (FOSQ) total score was about 15 in each group.

Results showed that the mean adjusted improvement in FOSQ total score between baseline and 3 months was identical in the two groups, at 1.79 points. And within each group, patients had significant improvements in the total score as well as its individual components.

Both home and lab groups also had significant improvements on the Epworth Sleepiness Scale (–2.6 and –2.9, respectively), the mental health component of the 12-item Short Form Health Survey (+2.5 and +3.0), and the Center for Epidemiologic Studies–Depression scale (–1.4 and –2.2). Neither group improved significantly on the psychovigilance task or the physical health component of the 12-item Short Form Health Survey.

When it came to adherence, which was monitored with smart cards, the mean adjusted number of CPAP hours daily was 3.42 in the home group and 2.99 in the lab group, a difference that was not significant. Cost-effectiveness analyses are still ongoing.

"We concluded that the functional improvement with CPAP for sleep apnea is not worse when treated in the home setting vs. the sleep lab," Dr. Atwood said. "We believe that the implication is that home-based sleep apnea diagnosis and initiation of CPAP therapy is an effective way to treat sleep apnea."

Despite all of the accumulating favorable findings for home testing, Dr. Atwood was skeptical that it will entirely replace laboratory polysomnography.

"Home sleep apnea testing is part of the future, but it’s unlikely to be the whole future," he contended. "The way to think about home sleep apnea testing now is not ‘either/or,’ but really to begin to integrate home sleep testing with full polysomnography in a clinically rational way."

Dr. Atwood reported that he received research support from Embla, Resmed, and Respironics, and is a consultant to Embla and Itamar Medical, all of which manufacture testing and treatment devices for sleep disorders.

VANCOUVER, B.C. – Recent research on the use of home testing for the diagnosis of obstructive sleep apnea and initiation of therapy suggests that "home testing is here to stay," Dr. Charles W. Atwood Jr. told attendees at the meeting.

For more than 30 years, physicians have relied on the traditional polysomnography performed in the sleep laboratory to diagnose sleep apnea, according to Dr. Atwood. But with growing awareness of the condition and its prevalence, the number of people needing testing could overwhelm capacity.

"If you take the millions and millions and millions of people in the United States alone who have sleep apnea and try to feed them through the relatively small funnel of traditional sleep labs, then you are going to have big bottlenecks," he said, adding that such bottlenecks already exist in some areas.

However, home-testing devices must meet certain key requirements before they are ready for widespread use. For example, they have to be simpler than those used in the lab. "Perhaps we can get by with fewer [physiological] signals, but we need to understand what the key signals are," commented Dr. Atwood, a pulmonologist and sleep medicine specialist with the VA Pittsburgh Healthcare System and the University of Pittsburgh Medical Center.

Home testing devices will also need to be accurate, with high sensitivity and specificity, and "there is no single device I would say today that is perfect in both these regards," he noted. Finally, they must be easy to use and durable, given the demands of in-home use.

Roughly 95 studies conducted between 1990 and 2006 evaluated home testing (also called portable monitoring) for the diagnosis of obstructive sleep apnea. Collectively, they had some limitations, such as their single-site nature, small and usually homogeneous populations, and varying degrees of rigor in design.

"And they frequently focused on the highest-risk subjects: These were middle-aged men who were overweight, snored, and were sleepy, so [they were] the very low-hanging fruit for typical sleep apnea," Dr. Atwood said.

These studies showed mixed results when it came to the diagnostic performance of home testing relative to lab testing. "There is no perfect study, at least so far, in this area, but some have come pretty close," he commented.

Three more recent studies suggest that home testing is at least not inferior to lab testing for sleep apnea diagnosis and initiation of continuous positive airway pressure (CPAP) therapy, according to Dr. Atwood.

In the first study, conducted among 68 people with a high likelihood of sleep apnea, the apnea-hypopnea index on CPAP and Sleep Apnea Quality of Life Index scores at 3 months did not differ significantly between a sleep lab approach and an ambulatory approach (Ann. Intern. Med. 2007;146:157-66). The rate of adherence to CPAP was better with the latter.

In the second study, which involved 102 patients with sleep apnea symptoms and no major comorbidities, all of a variety of sleep and quality of life outcomes after 4 weeks of CPAP were similar with a standard lab diagnosis and treatment approach vs. a home approach (Chest 2010;138:257-63).

The third study, the Veterans Sleep Apnea Treatment Trial (VSATT), is the largest study of home testing in North America to date, according to Dr. Atwood, who is one of the principal investigators.

"The VA is ill equipped to manage sleep apnea in a conventional way because we have relatively few numbers of traditional sleep labs, and those sleep labs that do exist tend to be kind of small," he noted. Also, there are geographic disparities, with some veterans having virtually no access to sleep labs.

"Our study differed from basically all of the other studies in the literature in that we had very broad inclusion criteria and very nonrestrictive exclusion criteria," Dr. Atwood noted. For example, patients with comorbidities could participate as long as their condition was stable.

The patients were randomized to lab testing or home testing, followed by initiation of CPAP for those with positive results.

Among the 223 who were started on CPAP, the home and lab groups had similar demographics. The average apnea-hypopnea index was 41 for the former and 45 for the latter. The Functional Outcomes of Sleep Questionnaire (FOSQ) total score was about 15 in each group.

Results showed that the mean adjusted improvement in FOSQ total score between baseline and 3 months was identical in the two groups, at 1.79 points. And within each group, patients had significant improvements in the total score as well as its individual components.

Both home and lab groups also had significant improvements on the Epworth Sleepiness Scale (–2.6 and –2.9, respectively), the mental health component of the 12-item Short Form Health Survey (+2.5 and +3.0), and the Center for Epidemiologic Studies–Depression scale (–1.4 and –2.2). Neither group improved significantly on the psychovigilance task or the physical health component of the 12-item Short Form Health Survey.

When it came to adherence, which was monitored with smart cards, the mean adjusted number of CPAP hours daily was 3.42 in the home group and 2.99 in the lab group, a difference that was not significant. Cost-effectiveness analyses are still ongoing.

"We concluded that the functional improvement with CPAP for sleep apnea is not worse when treated in the home setting vs. the sleep lab," Dr. Atwood said. "We believe that the implication is that home-based sleep apnea diagnosis and initiation of CPAP therapy is an effective way to treat sleep apnea."

Despite all of the accumulating favorable findings for home testing, Dr. Atwood was skeptical that it will entirely replace laboratory polysomnography.

"Home sleep apnea testing is part of the future, but it’s unlikely to be the whole future," he contended. "The way to think about home sleep apnea testing now is not ‘either/or,’ but really to begin to integrate home sleep testing with full polysomnography in a clinically rational way."

Dr. Atwood reported that he received research support from Embla, Resmed, and Respironics, and is a consultant to Embla and Itamar Medical, all of which manufacture testing and treatment devices for sleep disorders.

CHICAGO – Women who report high psychological job strain have a 40% increased risk of cardiovascular disease, according to a large, 10-year prospective study.

High job strain is defined by a demanding job, often involving time pressure and conflict, coupled with little decision-making authority or opportunity for personal growth.

But women with high job strain weren’t the only group at increased risk for acute MI and other cardiovascular events in this analysis of more than 17,000 working women participating in the Women’s Health Study. Those with active job strain defined as high-demand work featuring a high sense of control, based on Robert Karasek’s 14-item job strain model used in this study, had a 60% increase in total cardiovascular events compared with those reporting low job strain, Natalie Slopen, Sc.D., reported at the meeting.

This last point regarding the cardiovascular risks associated with active job strain should be near and dear to the hearts of female physicians. Many, perhaps most, physicians fit within the Karasek active job strain category, noted Dr. Slopen, a postdoctoral research fellow in the department of society, human development, and health at Harvard School of Public Health, Boston.

The Women’s Health Study involves 17,415 female, mostly white, health professionals in good health at an average age of 57 years at enrollment in what was initially a randomized, placebo-controlled clinical trial of vitamin E and aspirin for primary prevention of cancer and cardiovascular disease. The study is now in the observational phase with 10 years of follow-up, during which 517 clinically verified nonfatal MIs, strokes, coronary revascularization procedures, and cardiovascular deaths have occurred.

In a Cox proportional hazards model adjusted for age, race, socioeconomic status, and study drug assignment, the 3,529 women who reported high job strain at baseline had a 90% increased risk of MI, a 40% increase in coronary revascularization, and a 40% increase in total cardiovascular events, compared with the 4,161 female health professionals with low job strain.

The 3,736 women who reported active job strain had a 60% increase in total cardiovascular events compared with the low job strain group.

The investigators also inquired about job insecurity. At baseline, 19% of Women’s Health Study participants indicated they were concerned about future job loss. Contrary to the study hypothesis, however, no independent association was found between job insecurity and subsequent development of cardiovascular disease.

An important clinical implication of this study is that it may be useful for physicians to ask about job stress as part of their total health assessment of women employed outside the home. Women with high job strain or active job strain can be counseled that there are data to support several beneficial interventions. These include maintaining a physically active lifestyle to help burn off psychological stress, engaging in social support networks to aid in coping with work strain, and reserving time every day – as little as 10-15 minutes – for some form of relaxation. It’s also important to limit the intrusion of work activities outside the workplace; e-mail is a big offender in this regard, according to Dr. Slopen.

The Women’s Health Study is funded by the National Institutes of Health. Dr. Slopen declared having no relevant financial disclosures.

CHICAGO – Women who report high psychological job strain have a 40% increased risk of cardiovascular disease, according to a large, 10-year prospective study.

High job strain is defined by a demanding job, often involving time pressure and conflict, coupled with little decision-making authority or opportunity for personal growth.

But women with high job strain weren’t the only group at increased risk for acute MI and other cardiovascular events in this analysis of more than 17,000 working women participating in the Women’s Health Study. Those with active job strain defined as high-demand work featuring a high sense of control, based on Robert Karasek’s 14-item job strain model used in this study, had a 60% increase in total cardiovascular events compared with those reporting low job strain, Natalie Slopen, Sc.D., reported at the meeting.

This last point regarding the cardiovascular risks associated with active job strain should be near and dear to the hearts of female physicians. Many, perhaps most, physicians fit within the Karasek active job strain category, noted Dr. Slopen, a postdoctoral research fellow in the department of society, human development, and health at Harvard School of Public Health, Boston.

The Women’s Health Study involves 17,415 female, mostly white, health professionals in good health at an average age of 57 years at enrollment in what was initially a randomized, placebo-controlled clinical trial of vitamin E and aspirin for primary prevention of cancer and cardiovascular disease. The study is now in the observational phase with 10 years of follow-up, during which 517 clinically verified nonfatal MIs, strokes, coronary revascularization procedures, and cardiovascular deaths have occurred.

In a Cox proportional hazards model adjusted for age, race, socioeconomic status, and study drug assignment, the 3,529 women who reported high job strain at baseline had a 90% increased risk of MI, a 40% increase in coronary revascularization, and a 40% increase in total cardiovascular events, compared with the 4,161 female health professionals with low job strain.

The 3,736 women who reported active job strain had a 60% increase in total cardiovascular events compared with the low job strain group.

The investigators also inquired about job insecurity. At baseline, 19% of Women’s Health Study participants indicated they were concerned about future job loss. Contrary to the study hypothesis, however, no independent association was found between job insecurity and subsequent development of cardiovascular disease.

An important clinical implication of this study is that it may be useful for physicians to ask about job stress as part of their total health assessment of women employed outside the home. Women with high job strain or active job strain can be counseled that there are data to support several beneficial interventions. These include maintaining a physically active lifestyle to help burn off psychological stress, engaging in social support networks to aid in coping with work strain, and reserving time every day – as little as 10-15 minutes – for some form of relaxation. It’s also important to limit the intrusion of work activities outside the workplace; e-mail is a big offender in this regard, according to Dr. Slopen.

The Women’s Health Study is funded by the National Institutes of Health. Dr. Slopen declared having no relevant financial disclosures.

CHICAGO – Women who report high psychological job strain have a 40% increased risk of cardiovascular disease, according to a large, 10-year prospective study.

High job strain is defined by a demanding job, often involving time pressure and conflict, coupled with little decision-making authority or opportunity for personal growth.

But women with high job strain weren’t the only group at increased risk for acute MI and other cardiovascular events in this analysis of more than 17,000 working women participating in the Women’s Health Study. Those with active job strain defined as high-demand work featuring a high sense of control, based on Robert Karasek’s 14-item job strain model used in this study, had a 60% increase in total cardiovascular events compared with those reporting low job strain, Natalie Slopen, Sc.D., reported at the meeting.

This last point regarding the cardiovascular risks associated with active job strain should be near and dear to the hearts of female physicians. Many, perhaps most, physicians fit within the Karasek active job strain category, noted Dr. Slopen, a postdoctoral research fellow in the department of society, human development, and health at Harvard School of Public Health, Boston.

The Women’s Health Study involves 17,415 female, mostly white, health professionals in good health at an average age of 57 years at enrollment in what was initially a randomized, placebo-controlled clinical trial of vitamin E and aspirin for primary prevention of cancer and cardiovascular disease. The study is now in the observational phase with 10 years of follow-up, during which 517 clinically verified nonfatal MIs, strokes, coronary revascularization procedures, and cardiovascular deaths have occurred.

In a Cox proportional hazards model adjusted for age, race, socioeconomic status, and study drug assignment, the 3,529 women who reported high job strain at baseline had a 90% increased risk of MI, a 40% increase in coronary revascularization, and a 40% increase in total cardiovascular events, compared with the 4,161 female health professionals with low job strain.

The 3,736 women who reported active job strain had a 60% increase in total cardiovascular events compared with the low job strain group.

The investigators also inquired about job insecurity. At baseline, 19% of Women’s Health Study participants indicated they were concerned about future job loss. Contrary to the study hypothesis, however, no independent association was found between job insecurity and subsequent development of cardiovascular disease.

An important clinical implication of this study is that it may be useful for physicians to ask about job stress as part of their total health assessment of women employed outside the home. Women with high job strain or active job strain can be counseled that there are data to support several beneficial interventions. These include maintaining a physically active lifestyle to help burn off psychological stress, engaging in social support networks to aid in coping with work strain, and reserving time every day – as little as 10-15 minutes – for some form of relaxation. It’s also important to limit the intrusion of work activities outside the workplace; e-mail is a big offender in this regard, according to Dr. Slopen.

The Women’s Health Study is funded by the National Institutes of Health. Dr. Slopen declared having no relevant financial disclosures.

CASE: Nude and mute

Mr. M, age 45, is found naked outside his apartment. He has a history of schizophrenia, paranoid type, hypertension, and diet-controlled type 2 diabetes mellitus. His schizophrenia has been treated with ziprasidone, 160 mg/d, but 2 months ago he stopped taking his medication and seeing his psychiatrist. He does not respond to questions from police and is taken to a local emergency department for medical workup of altered mental status.

Mr. M is noted to have bilateral conjunctival discharge and a white blood cell (WBC) count of 15,000/mm³. Vital signs, physical examination, laboratory studies, and head CT are otherwise within normal limits. Mr. M is medically cleared for his 15^th admission to our inpatient psychiatric facility in the last 7 years. He is divorced, has 2 adult sons, and receives Social Security disability benefits.

Mr. M is alert but guarded and mute and appears to be internally preoccupied. His mood is euthymic and his facial expressions do not vary much and are similar to a blank stare. His grooming and hygiene are poor, but there is no evidence of delusions or suicidal or homicidal ideation. He paces around the unit or sits in his bed staring straight ahead, occasionally mouthing inaudible words but remaining nonverbal.

Mr. M is restarted on his previous dose of ziprasidone and referred to the primary care physician in our inpatient psychiatric facility for further evaluation. His admission vitals and laboratory values show a platelet count of 124,000/mm³, glucose of 113 mg/dL, triglycerides of 160 mg/dL, high-density lipoprotein of 37 mg/dL, and hemoglobin A_1c of 6%. Mr. M needs help drinking fluids but resists solid foods as well as medications, including lorazepam, 3 mg/d, and most scheduled doses of ziprasidone. On day 3, Mr. M’s extremities are rigid and he has poor oral intake. We diagnose Mr. M with catatonia based on his immobility, negativity, and mutism.

The authors’ observations

The literature describes >40 signs of catatonia.^1-11 According to DSM-IV-TR, catatonia may occur in the context of schizophrenia, a mood disorder, or a general medical condition. DSM-IV-TR criteria for catatonia include:

• motor immobility as evidenced by catalepsy or stupor
• excessive motor activity
• extreme negativism or mutism
• peculiarities of voluntary movements as evidenced by posturing, stereotypic movements, or grimacing
• echolalia or echopraxia.¹²

Only 2 signs are necessary to meet the diagnostic criteria for catatonia.^11,12 Several catatonia rating scales—including the Bush-Francis Catatonia Rating Scale (BFCRS)—have been found to be highly reliable for screening for and rating the severity of catatonia. Such tools also can be used serially to monitor treatment efficacy. The BFCRS takes 5 minutes to administer; the screen is considered positive if ≥2 of the first 14 items on the scale are present.¹³ Mr. M exhibits immobility and mutism, which are the most common signs of catatonia.

In patients with catatonia, poor oral intake may result in malnutrition that often requires parenteral nutrition or intravenous fluids^1,10 and dehydration that may lead to dental caries, gum disease, constipation, and ileus.¹ Pneumonia may occur secondary to atelectasis or buildup of respiratory secretions and possibly aspiration.⁷ Vaginal infections may develop secondary to poor hygiene.¹ Immobility and malnutrition may lead to infection and decubitus ulcers.¹ Finally, immobility also may cause urinary incontinence,^2,10 nerve palsies, flexion contractions, and rhabdomyolysis.¹

EVALUATION: Venous complications

On day 3, Mr. M is referred to a local emergency department, where he is assessed for delirium and dehydration because of increased WBC count and diaphoresis. The medical staff finds bilateral pulmonary embolisms and a deep vein thrombosis (DVT) of his left lower leg.

The authors’ observations

Catatonia is associated with an increased risk of venous thromboembolism because of the increased risk of venous stasis and hypercoagulability, both elements of Virchow’s triad for thrombogenesis.^1-10,14,15 The third element of Virchow’s triad, vascular injury, does not appear to directly increase the risk for thromboembolic events in catatonic states.

Catatonia-specific causes for venous stasis include immobility, prolonged use of physical restraints, and sedation as a side effect of antipsychotic use.¹⁶

Causes for hypercoagulability during catatonic states include:

• increased catecholamine levels during excited states³
• hyperhomocysteinemia secondary to poor diet, smoking, and/or high caffeine consumption¹⁶
• increased anticardiolipin and/or anti-phospholipid antibody levels secondary to use of specific antipsychotics, such as chlorpromazine and clozapine¹⁶
• increased platelet aggregation secondary to hyperprolactinemia caused by low-potency conventional antipsychotics, such as chlorpromazine^16,17
• increased platelet activation caused by altered levels of platelet serotonin in depressed patients.¹⁸

Patients taking low-potency conventional antipsychotics may have a 7-fold greater risk for thromboembolic events compared with those who do not use these medications.¹⁶

Reducing thromboembolic risk

Diagnose catatonia early. Treating symptoms of catatonia early with benzodiazepines (and, in refractory cases, with electroconvulsive therapy) prevents immobility, thereby decreasing the risk of thromboembolic events.^3,11 It may be useful to minimize antipsychotic use.

Monitor activity levels. Fatal thromboembolic events may appear early in the course of catatonia before risk factors associated with thromboembolic events are evident.⁴ However, these events may be more common when the patient resumes movement.³ Monitor patients’ activity status and encourage ambulation throughout treatment.

Monitor vital signs for signs of pulmonary embolism, including hypoxia, tachycardia, tachypnea, and fever. Take serial pulse oximetry and, if indicated, arterial blood gas measurements to monitor hemoglobin oxygen saturation. Be vigilant for other signs and symptoms of pulmonary embolism and DVT (Table).

Consider prophylactic treatment. Some studies recommend prophylaxis against thromboembolic events in catatonic patients.^3-6,10,15 These measures include:

• intravenous fluids
• nasogastric tube feeding
• physical examinations to assess for signs of DVT
• support stockings
• sequential/pneumatic compression devices
• physical therapy or range-of-motion exercises
• complete anticoagulation during immobility, although there are no data that support using anticoagulation medications in catatonic patients who have not yet experienced a thromboembolic event.

Consider prophylactic antithrombotic treatment in catatonic patients and other immobile inpatients who have risk factors for thromboembolic events.^9,16 Although it has not been rigorously tested, the Algorithm suggested by Malý et al¹⁵ can serve as a guideline for determining the need for prophylaxis against venous thromboembolism in psychiatric inpatient settings.

Table

Signs and symptoms of deep vein thrombosis and pulmonary embolism

Algorithm

Does my patient need venous thromboembolism prophylaxis?

OUTCOME: Stable and speaking

In the hospital, Mr. M remains immobile and mute for several days. The hospital’s psychiatric consult team recommends lorazepam, 3 mg/d, to address his catatonia. Mr. M improves and begins speaking and eating after starting lorazepam, but becomes agitated, banging his head against walls and threatening to jump out the window. Because this puts him at risk for trauma, Mr. M is not a good candidate for warfarin therapy, and an inferior vena cava filter is placed on an emergency basis. Later, a Dobhoff tube is placed for feeding and administering oral medications.

Mr. M’s catatonic state gradually improves and he begins to respond to the staff with short phrases, eats all of his food, and accepts oral medications. He is transferred back to our inpatient psychiatric facility with haloperidol, 10 mg/d, lorazepam, 3 mg/d, and benztro-pine, 2 mg/d, in addition to sulfacetamide eye drops for bilateral conjunctivitis. At our facility, we start him on warfarin, 5 mg/d, and closely monitor his international normalized ratio levels, with a plan to remove the inferior vena cava filter after 6 months of anticoagulation therapy. Mr. M remains at our facility for 3 weeks to stabilize his medications and is discharged to his apartment.

Six months after being discharged from our facility, Mr. M is stable at an intensive outpatient mental health program.

Related Resources

• Fink M, Taylor MA. Catatonia: a clinician’s guide to diagnosis and treatment. Cambridge, United Kingdom: Cambridge University Press; 2003.
• Snow V, Qaseem A, Barry P, et al, and American College of Physicians; American Academy of Family Physicians Panel on Deep Venous Thrombosis/Pulmonary Embolism. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007;146(3):204-210.

Drug Brand Names

• Benztropine • Cogentin
• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Haloperidol • Haldol
• Lorazepam • Ativan
• Sulfacetamide • Sulamyd
• Warfarin • Coumadin
• Ziprasidone • Geodon

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Nude and mute

Mr. M, age 45, is found naked outside his apartment. He has a history of schizophrenia, paranoid type, hypertension, and diet-controlled type 2 diabetes mellitus. His schizophrenia has been treated with ziprasidone, 160 mg/d, but 2 months ago he stopped taking his medication and seeing his psychiatrist. He does not respond to questions from police and is taken to a local emergency department for medical workup of altered mental status.

Mr. M is noted to have bilateral conjunctival discharge and a white blood cell (WBC) count of 15,000/mm³. Vital signs, physical examination, laboratory studies, and head CT are otherwise within normal limits. Mr. M is medically cleared for his 15^th admission to our inpatient psychiatric facility in the last 7 years. He is divorced, has 2 adult sons, and receives Social Security disability benefits.

Mr. M is alert but guarded and mute and appears to be internally preoccupied. His mood is euthymic and his facial expressions do not vary much and are similar to a blank stare. His grooming and hygiene are poor, but there is no evidence of delusions or suicidal or homicidal ideation. He paces around the unit or sits in his bed staring straight ahead, occasionally mouthing inaudible words but remaining nonverbal.

Mr. M is restarted on his previous dose of ziprasidone and referred to the primary care physician in our inpatient psychiatric facility for further evaluation. His admission vitals and laboratory values show a platelet count of 124,000/mm³, glucose of 113 mg/dL, triglycerides of 160 mg/dL, high-density lipoprotein of 37 mg/dL, and hemoglobin A_1c of 6%. Mr. M needs help drinking fluids but resists solid foods as well as medications, including lorazepam, 3 mg/d, and most scheduled doses of ziprasidone. On day 3, Mr. M’s extremities are rigid and he has poor oral intake. We diagnose Mr. M with catatonia based on his immobility, negativity, and mutism.

The authors’ observations

The literature describes >40 signs of catatonia.^1-11 According to DSM-IV-TR, catatonia may occur in the context of schizophrenia, a mood disorder, or a general medical condition. DSM-IV-TR criteria for catatonia include:

• motor immobility as evidenced by catalepsy or stupor
• excessive motor activity
• extreme negativism or mutism
• peculiarities of voluntary movements as evidenced by posturing, stereotypic movements, or grimacing
• echolalia or echopraxia.¹²

Only 2 signs are necessary to meet the diagnostic criteria for catatonia.^11,12 Several catatonia rating scales—including the Bush-Francis Catatonia Rating Scale (BFCRS)—have been found to be highly reliable for screening for and rating the severity of catatonia. Such tools also can be used serially to monitor treatment efficacy. The BFCRS takes 5 minutes to administer; the screen is considered positive if ≥2 of the first 14 items on the scale are present.¹³ Mr. M exhibits immobility and mutism, which are the most common signs of catatonia.

In patients with catatonia, poor oral intake may result in malnutrition that often requires parenteral nutrition or intravenous fluids^1,10 and dehydration that may lead to dental caries, gum disease, constipation, and ileus.¹ Pneumonia may occur secondary to atelectasis or buildup of respiratory secretions and possibly aspiration.⁷ Vaginal infections may develop secondary to poor hygiene.¹ Immobility and malnutrition may lead to infection and decubitus ulcers.¹ Finally, immobility also may cause urinary incontinence,^2,10 nerve palsies, flexion contractions, and rhabdomyolysis.¹

EVALUATION: Venous complications

On day 3, Mr. M is referred to a local emergency department, where he is assessed for delirium and dehydration because of increased WBC count and diaphoresis. The medical staff finds bilateral pulmonary embolisms and a deep vein thrombosis (DVT) of his left lower leg.

The authors’ observations

Catatonia is associated with an increased risk of venous thromboembolism because of the increased risk of venous stasis and hypercoagulability, both elements of Virchow’s triad for thrombogenesis.^1-10,14,15 The third element of Virchow’s triad, vascular injury, does not appear to directly increase the risk for thromboembolic events in catatonic states.

Catatonia-specific causes for venous stasis include immobility, prolonged use of physical restraints, and sedation as a side effect of antipsychotic use.¹⁶

Causes for hypercoagulability during catatonic states include:

• increased catecholamine levels during excited states³
• hyperhomocysteinemia secondary to poor diet, smoking, and/or high caffeine consumption¹⁶
• increased anticardiolipin and/or anti-phospholipid antibody levels secondary to use of specific antipsychotics, such as chlorpromazine and clozapine¹⁶
• increased platelet aggregation secondary to hyperprolactinemia caused by low-potency conventional antipsychotics, such as chlorpromazine^16,17
• increased platelet activation caused by altered levels of platelet serotonin in depressed patients.¹⁸

Patients taking low-potency conventional antipsychotics may have a 7-fold greater risk for thromboembolic events compared with those who do not use these medications.¹⁶

Reducing thromboembolic risk

Diagnose catatonia early. Treating symptoms of catatonia early with benzodiazepines (and, in refractory cases, with electroconvulsive therapy) prevents immobility, thereby decreasing the risk of thromboembolic events.^3,11 It may be useful to minimize antipsychotic use.

Monitor activity levels. Fatal thromboembolic events may appear early in the course of catatonia before risk factors associated with thromboembolic events are evident.⁴ However, these events may be more common when the patient resumes movement.³ Monitor patients’ activity status and encourage ambulation throughout treatment.

Monitor vital signs for signs of pulmonary embolism, including hypoxia, tachycardia, tachypnea, and fever. Take serial pulse oximetry and, if indicated, arterial blood gas measurements to monitor hemoglobin oxygen saturation. Be vigilant for other signs and symptoms of pulmonary embolism and DVT (Table).

Consider prophylactic treatment. Some studies recommend prophylaxis against thromboembolic events in catatonic patients.^3-6,10,15 These measures include:

• intravenous fluids
• nasogastric tube feeding
• physical examinations to assess for signs of DVT
• support stockings
• sequential/pneumatic compression devices
• physical therapy or range-of-motion exercises
• complete anticoagulation during immobility, although there are no data that support using anticoagulation medications in catatonic patients who have not yet experienced a thromboembolic event.

Consider prophylactic antithrombotic treatment in catatonic patients and other immobile inpatients who have risk factors for thromboembolic events.^9,16 Although it has not been rigorously tested, the Algorithm suggested by Malý et al¹⁵ can serve as a guideline for determining the need for prophylaxis against venous thromboembolism in psychiatric inpatient settings.

Table

Signs and symptoms of deep vein thrombosis and pulmonary embolism

Algorithm

Does my patient need venous thromboembolism prophylaxis?

OUTCOME: Stable and speaking

In the hospital, Mr. M remains immobile and mute for several days. The hospital’s psychiatric consult team recommends lorazepam, 3 mg/d, to address his catatonia. Mr. M improves and begins speaking and eating after starting lorazepam, but becomes agitated, banging his head against walls and threatening to jump out the window. Because this puts him at risk for trauma, Mr. M is not a good candidate for warfarin therapy, and an inferior vena cava filter is placed on an emergency basis. Later, a Dobhoff tube is placed for feeding and administering oral medications.

Mr. M’s catatonic state gradually improves and he begins to respond to the staff with short phrases, eats all of his food, and accepts oral medications. He is transferred back to our inpatient psychiatric facility with haloperidol, 10 mg/d, lorazepam, 3 mg/d, and benztro-pine, 2 mg/d, in addition to sulfacetamide eye drops for bilateral conjunctivitis. At our facility, we start him on warfarin, 5 mg/d, and closely monitor his international normalized ratio levels, with a plan to remove the inferior vena cava filter after 6 months of anticoagulation therapy. Mr. M remains at our facility for 3 weeks to stabilize his medications and is discharged to his apartment.

Six months after being discharged from our facility, Mr. M is stable at an intensive outpatient mental health program.

Related Resources

• Fink M, Taylor MA. Catatonia: a clinician’s guide to diagnosis and treatment. Cambridge, United Kingdom: Cambridge University Press; 2003.
• Snow V, Qaseem A, Barry P, et al, and American College of Physicians; American Academy of Family Physicians Panel on Deep Venous Thrombosis/Pulmonary Embolism. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007;146(3):204-210.

Drug Brand Names

• Benztropine • Cogentin
• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Haloperidol • Haldol
• Lorazepam • Ativan
• Sulfacetamide • Sulamyd
• Warfarin • Coumadin
• Ziprasidone • Geodon

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Nude and mute

Mr. M, age 45, is found naked outside his apartment. He has a history of schizophrenia, paranoid type, hypertension, and diet-controlled type 2 diabetes mellitus. His schizophrenia has been treated with ziprasidone, 160 mg/d, but 2 months ago he stopped taking his medication and seeing his psychiatrist. He does not respond to questions from police and is taken to a local emergency department for medical workup of altered mental status.

Mr. M is noted to have bilateral conjunctival discharge and a white blood cell (WBC) count of 15,000/mm³. Vital signs, physical examination, laboratory studies, and head CT are otherwise within normal limits. Mr. M is medically cleared for his 15^th admission to our inpatient psychiatric facility in the last 7 years. He is divorced, has 2 adult sons, and receives Social Security disability benefits.

Mr. M is alert but guarded and mute and appears to be internally preoccupied. His mood is euthymic and his facial expressions do not vary much and are similar to a blank stare. His grooming and hygiene are poor, but there is no evidence of delusions or suicidal or homicidal ideation. He paces around the unit or sits in his bed staring straight ahead, occasionally mouthing inaudible words but remaining nonverbal.

Mr. M is restarted on his previous dose of ziprasidone and referred to the primary care physician in our inpatient psychiatric facility for further evaluation. His admission vitals and laboratory values show a platelet count of 124,000/mm³, glucose of 113 mg/dL, triglycerides of 160 mg/dL, high-density lipoprotein of 37 mg/dL, and hemoglobin A_1c of 6%. Mr. M needs help drinking fluids but resists solid foods as well as medications, including lorazepam, 3 mg/d, and most scheduled doses of ziprasidone. On day 3, Mr. M’s extremities are rigid and he has poor oral intake. We diagnose Mr. M with catatonia based on his immobility, negativity, and mutism.

The authors’ observations

The literature describes >40 signs of catatonia.^1-11 According to DSM-IV-TR, catatonia may occur in the context of schizophrenia, a mood disorder, or a general medical condition. DSM-IV-TR criteria for catatonia include:

• motor immobility as evidenced by catalepsy or stupor
• excessive motor activity
• extreme negativism or mutism
• peculiarities of voluntary movements as evidenced by posturing, stereotypic movements, or grimacing
• echolalia or echopraxia.¹²

Only 2 signs are necessary to meet the diagnostic criteria for catatonia.^11,12 Several catatonia rating scales—including the Bush-Francis Catatonia Rating Scale (BFCRS)—have been found to be highly reliable for screening for and rating the severity of catatonia. Such tools also can be used serially to monitor treatment efficacy. The BFCRS takes 5 minutes to administer; the screen is considered positive if ≥2 of the first 14 items on the scale are present.¹³ Mr. M exhibits immobility and mutism, which are the most common signs of catatonia.

In patients with catatonia, poor oral intake may result in malnutrition that often requires parenteral nutrition or intravenous fluids^1,10 and dehydration that may lead to dental caries, gum disease, constipation, and ileus.¹ Pneumonia may occur secondary to atelectasis or buildup of respiratory secretions and possibly aspiration.⁷ Vaginal infections may develop secondary to poor hygiene.¹ Immobility and malnutrition may lead to infection and decubitus ulcers.¹ Finally, immobility also may cause urinary incontinence,^2,10 nerve palsies, flexion contractions, and rhabdomyolysis.¹

EVALUATION: Venous complications

On day 3, Mr. M is referred to a local emergency department, where he is assessed for delirium and dehydration because of increased WBC count and diaphoresis. The medical staff finds bilateral pulmonary embolisms and a deep vein thrombosis (DVT) of his left lower leg.

The authors’ observations

Catatonia is associated with an increased risk of venous thromboembolism because of the increased risk of venous stasis and hypercoagulability, both elements of Virchow’s triad for thrombogenesis.^1-10,14,15 The third element of Virchow’s triad, vascular injury, does not appear to directly increase the risk for thromboembolic events in catatonic states.

Catatonia-specific causes for venous stasis include immobility, prolonged use of physical restraints, and sedation as a side effect of antipsychotic use.¹⁶

Causes for hypercoagulability during catatonic states include:

• increased catecholamine levels during excited states³
• hyperhomocysteinemia secondary to poor diet, smoking, and/or high caffeine consumption¹⁶
• increased anticardiolipin and/or anti-phospholipid antibody levels secondary to use of specific antipsychotics, such as chlorpromazine and clozapine¹⁶
• increased platelet aggregation secondary to hyperprolactinemia caused by low-potency conventional antipsychotics, such as chlorpromazine^16,17
• increased platelet activation caused by altered levels of platelet serotonin in depressed patients.¹⁸

Patients taking low-potency conventional antipsychotics may have a 7-fold greater risk for thromboembolic events compared with those who do not use these medications.¹⁶

Reducing thromboembolic risk

Diagnose catatonia early. Treating symptoms of catatonia early with benzodiazepines (and, in refractory cases, with electroconvulsive therapy) prevents immobility, thereby decreasing the risk of thromboembolic events.^3,11 It may be useful to minimize antipsychotic use.

Monitor activity levels. Fatal thromboembolic events may appear early in the course of catatonia before risk factors associated with thromboembolic events are evident.⁴ However, these events may be more common when the patient resumes movement.³ Monitor patients’ activity status and encourage ambulation throughout treatment.

Monitor vital signs for signs of pulmonary embolism, including hypoxia, tachycardia, tachypnea, and fever. Take serial pulse oximetry and, if indicated, arterial blood gas measurements to monitor hemoglobin oxygen saturation. Be vigilant for other signs and symptoms of pulmonary embolism and DVT (Table).

Consider prophylactic treatment. Some studies recommend prophylaxis against thromboembolic events in catatonic patients.^3-6,10,15 These measures include:

• intravenous fluids
• nasogastric tube feeding
• physical examinations to assess for signs of DVT
• support stockings
• sequential/pneumatic compression devices
• physical therapy or range-of-motion exercises
• complete anticoagulation during immobility, although there are no data that support using anticoagulation medications in catatonic patients who have not yet experienced a thromboembolic event.

Consider prophylactic antithrombotic treatment in catatonic patients and other immobile inpatients who have risk factors for thromboembolic events.^9,16 Although it has not been rigorously tested, the Algorithm suggested by Malý et al¹⁵ can serve as a guideline for determining the need for prophylaxis against venous thromboembolism in psychiatric inpatient settings.

Table

Signs and symptoms of deep vein thrombosis and pulmonary embolism

Algorithm

Does my patient need venous thromboembolism prophylaxis?

OUTCOME: Stable and speaking

In the hospital, Mr. M remains immobile and mute for several days. The hospital’s psychiatric consult team recommends lorazepam, 3 mg/d, to address his catatonia. Mr. M improves and begins speaking and eating after starting lorazepam, but becomes agitated, banging his head against walls and threatening to jump out the window. Because this puts him at risk for trauma, Mr. M is not a good candidate for warfarin therapy, and an inferior vena cava filter is placed on an emergency basis. Later, a Dobhoff tube is placed for feeding and administering oral medications.

Mr. M’s catatonic state gradually improves and he begins to respond to the staff with short phrases, eats all of his food, and accepts oral medications. He is transferred back to our inpatient psychiatric facility with haloperidol, 10 mg/d, lorazepam, 3 mg/d, and benztro-pine, 2 mg/d, in addition to sulfacetamide eye drops for bilateral conjunctivitis. At our facility, we start him on warfarin, 5 mg/d, and closely monitor his international normalized ratio levels, with a plan to remove the inferior vena cava filter after 6 months of anticoagulation therapy. Mr. M remains at our facility for 3 weeks to stabilize his medications and is discharged to his apartment.

Six months after being discharged from our facility, Mr. M is stable at an intensive outpatient mental health program.

Related Resources

• Fink M, Taylor MA. Catatonia: a clinician’s guide to diagnosis and treatment. Cambridge, United Kingdom: Cambridge University Press; 2003.
• Snow V, Qaseem A, Barry P, et al, and American College of Physicians; American Academy of Family Physicians Panel on Deep Venous Thrombosis/Pulmonary Embolism. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007;146(3):204-210.

Drug Brand Names

• Benztropine • Cogentin
• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Haloperidol • Haldol
• Lorazepam • Ativan
• Sulfacetamide • Sulamyd
• Warfarin • Coumadin
• Ziprasidone • Geodon

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Major Finding: SPI-positive patients were significantly more likely than were SPI-negative patients to have a depressive disorder diagnosis (80% vs. 19%, respectively), previous psychiatric history (90% vs. 27%), and to currently use psychotropic medications (50% vs. 13%), all risk factors for suicide.

Data Source: Analysis of 58 consecutive adults at an inpatient epilepsy service.

Disclosures: The authors disclosed no conflicts of interest.

CHICAGO – A past psychiatric history, depressive disorder diagnosis, and current use of psychotropic medications were significantly associated with a higher potential for suicidal behavior.

“Suicide risk in patients with epilepsy reflects the higher incidence of psychiatric comorbidity in this population rather than any neurologic or demographic factor,” reported Robert C. Doss, Psy.D., and Dr. Patricia E. Penovich, of the Minnesota Epilepsy Group in St. Paul. This finding confirms what has been established in previous research.

About 30% of people with epilepsy have a major depressive disorder, and research suggests that about 50% of the time they are never treated for the problem, according to the Epilepsy Foundation.

Moreover, the suicide rate in persons with epilepsy is on average 12%, compared with about 1% in the general population (Epilepsy Behav. 2003;4:[Suppl. 3]S31–8). Given the prevalence of this problem and the 2008 warning by the Food and Drug Administration regarding the association between suicidality and antiepileptic drugs, further understanding of this matter is urgently needed, Dr. Doss and Dr. Penovich reported in a poster at the conference.

Upon admission, the 58 patients in the sample underwent long-term video-EEG, neuropsychological testing, personality assessment using the Personality Assessment Inventory, social work evaluation, and if indicated, psychology and/or psychiatry consultation.

Ten patients (mean age, 36 years) showed clinical elevations on the inventory's Suicide Potential Index (SPI) and 48 patients (mean age, 38 years) did not. The SPI consists of 20 features on the inventory that tap what are described as key risk factors for completed suicide in the suicidality literature.

Patients with a positive SPI were significantly more likely than were those with a negative SPI to have a depressive disorder diagnosis (80% vs. 19%, respectively), to have a previous psychiatric history (90% vs. 27%), and to currently use psychotropic medications (50% vs. 13%), Dr. Doss and Dr. Penovich reported.

No other variables, including age, gender, education, duration of epilepsy, temporal lobe epilepsy, complex partial seizures, other neurologic history, epilepsy surgery, number of anti-epileptic drugs, seizure frequency, anxiety disorder diagnosis, or cognitive status were found to significantly differentiate the two groups.

The lifetime prevalence rate of suicide and suicide attempts has been reported to be particularly high in patients with temporal lobe epilepsy and those who have had epilepsy surgery when compared with the general population, but neither risk factor stood out in the current analysis. Temporal lobe epilepsy was present in 30% of the SPI-positive group, compared with 55% of the SPI-negative group, and epilepsy surgery in 20%, compared with 10%.

Also, the number of antiepileptic drugs was similar in both groups at 2.0 and 1.8.

“Routine care of persons with epilepsy should include screening for both current and past psychiatric symptoms,” the authors concluded. “Particular attention should be paid to persons with epilepsy with a clear psychiatric history.”

The conference was jointly sponsored by the EDDC and the office of continuing education of Elsevier, which owns this news organization.

Major Finding: SPI-positive patients were significantly more likely than were SPI-negative patients to have a depressive disorder diagnosis (80% vs. 19%, respectively), previous psychiatric history (90% vs. 27%), and to currently use psychotropic medications (50% vs. 13%), all risk factors for suicide.

Data Source: Analysis of 58 consecutive adults at an inpatient epilepsy service.

Disclosures: The authors disclosed no conflicts of interest.

CHICAGO – A past psychiatric history, depressive disorder diagnosis, and current use of psychotropic medications were significantly associated with a higher potential for suicidal behavior.

“Suicide risk in patients with epilepsy reflects the higher incidence of psychiatric comorbidity in this population rather than any neurologic or demographic factor,” reported Robert C. Doss, Psy.D., and Dr. Patricia E. Penovich, of the Minnesota Epilepsy Group in St. Paul. This finding confirms what has been established in previous research.

About 30% of people with epilepsy have a major depressive disorder, and research suggests that about 50% of the time they are never treated for the problem, according to the Epilepsy Foundation.

Moreover, the suicide rate in persons with epilepsy is on average 12%, compared with about 1% in the general population (Epilepsy Behav. 2003;4:[Suppl. 3]S31–8). Given the prevalence of this problem and the 2008 warning by the Food and Drug Administration regarding the association between suicidality and antiepileptic drugs, further understanding of this matter is urgently needed, Dr. Doss and Dr. Penovich reported in a poster at the conference.

Upon admission, the 58 patients in the sample underwent long-term video-EEG, neuropsychological testing, personality assessment using the Personality Assessment Inventory, social work evaluation, and if indicated, psychology and/or psychiatry consultation.

Ten patients (mean age, 36 years) showed clinical elevations on the inventory's Suicide Potential Index (SPI) and 48 patients (mean age, 38 years) did not. The SPI consists of 20 features on the inventory that tap what are described as key risk factors for completed suicide in the suicidality literature.

Patients with a positive SPI were significantly more likely than were those with a negative SPI to have a depressive disorder diagnosis (80% vs. 19%, respectively), to have a previous psychiatric history (90% vs. 27%), and to currently use psychotropic medications (50% vs. 13%), Dr. Doss and Dr. Penovich reported.

No other variables, including age, gender, education, duration of epilepsy, temporal lobe epilepsy, complex partial seizures, other neurologic history, epilepsy surgery, number of anti-epileptic drugs, seizure frequency, anxiety disorder diagnosis, or cognitive status were found to significantly differentiate the two groups.

The lifetime prevalence rate of suicide and suicide attempts has been reported to be particularly high in patients with temporal lobe epilepsy and those who have had epilepsy surgery when compared with the general population, but neither risk factor stood out in the current analysis. Temporal lobe epilepsy was present in 30% of the SPI-positive group, compared with 55% of the SPI-negative group, and epilepsy surgery in 20%, compared with 10%.

Also, the number of antiepileptic drugs was similar in both groups at 2.0 and 1.8.

“Routine care of persons with epilepsy should include screening for both current and past psychiatric symptoms,” the authors concluded. “Particular attention should be paid to persons with epilepsy with a clear psychiatric history.”

The conference was jointly sponsored by the EDDC and the office of continuing education of Elsevier, which owns this news organization.

Major Finding: SPI-positive patients were significantly more likely than were SPI-negative patients to have a depressive disorder diagnosis (80% vs. 19%, respectively), previous psychiatric history (90% vs. 27%), and to currently use psychotropic medications (50% vs. 13%), all risk factors for suicide.

Data Source: Analysis of 58 consecutive adults at an inpatient epilepsy service.

Disclosures: The authors disclosed no conflicts of interest.

CHICAGO – A past psychiatric history, depressive disorder diagnosis, and current use of psychotropic medications were significantly associated with a higher potential for suicidal behavior.

“Suicide risk in patients with epilepsy reflects the higher incidence of psychiatric comorbidity in this population rather than any neurologic or demographic factor,” reported Robert C. Doss, Psy.D., and Dr. Patricia E. Penovich, of the Minnesota Epilepsy Group in St. Paul. This finding confirms what has been established in previous research.

About 30% of people with epilepsy have a major depressive disorder, and research suggests that about 50% of the time they are never treated for the problem, according to the Epilepsy Foundation.

Moreover, the suicide rate in persons with epilepsy is on average 12%, compared with about 1% in the general population (Epilepsy Behav. 2003;4:[Suppl. 3]S31–8). Given the prevalence of this problem and the 2008 warning by the Food and Drug Administration regarding the association between suicidality and antiepileptic drugs, further understanding of this matter is urgently needed, Dr. Doss and Dr. Penovich reported in a poster at the conference.

Upon admission, the 58 patients in the sample underwent long-term video-EEG, neuropsychological testing, personality assessment using the Personality Assessment Inventory, social work evaluation, and if indicated, psychology and/or psychiatry consultation.

Ten patients (mean age, 36 years) showed clinical elevations on the inventory's Suicide Potential Index (SPI) and 48 patients (mean age, 38 years) did not. The SPI consists of 20 features on the inventory that tap what are described as key risk factors for completed suicide in the suicidality literature.

Patients with a positive SPI were significantly more likely than were those with a negative SPI to have a depressive disorder diagnosis (80% vs. 19%, respectively), to have a previous psychiatric history (90% vs. 27%), and to currently use psychotropic medications (50% vs. 13%), Dr. Doss and Dr. Penovich reported.

No other variables, including age, gender, education, duration of epilepsy, temporal lobe epilepsy, complex partial seizures, other neurologic history, epilepsy surgery, number of anti-epileptic drugs, seizure frequency, anxiety disorder diagnosis, or cognitive status were found to significantly differentiate the two groups.

The lifetime prevalence rate of suicide and suicide attempts has been reported to be particularly high in patients with temporal lobe epilepsy and those who have had epilepsy surgery when compared with the general population, but neither risk factor stood out in the current analysis. Temporal lobe epilepsy was present in 30% of the SPI-positive group, compared with 55% of the SPI-negative group, and epilepsy surgery in 20%, compared with 10%.

Also, the number of antiepileptic drugs was similar in both groups at 2.0 and 1.8.

“Routine care of persons with epilepsy should include screening for both current and past psychiatric symptoms,” the authors concluded. “Particular attention should be paid to persons with epilepsy with a clear psychiatric history.”

The conference was jointly sponsored by the EDDC and the office of continuing education of Elsevier, which owns this news organization.