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Male libido problems successfully treated with bright light
VIENNA – Daily exposure to high-intensity light early in the morning resulted in significantly improved sexual satisfaction scores and a boost in testosterone levels in men with reduced libido or erection difficulty in a randomized, placebo-controlled clinical trial, Andrea Fagiolini, MD., said at the annual meeting of the American Thyroid Association.
“We found a very strong difference in sexual satisfaction and also in blood testosterone levels with intense light therapy. Patients seemed to respond to it really well, and our placebo group didn’t respond at all,” according to Dr. Fagiolini, professor and chairman of the department of psychiatry at the University of Siena (Italy).
“It’s still early to make a general recommendation. This was a small study. We need a larger trial with more patients. But if these results are confirmed, it would be very helpful because as of now we don’t have many tools to treat sexual dysfunction. So if light therapy works, I think it may be a better option than medications like Viagra [sildenafil] or similar drugs, which have side effects,” he said in an interview.
The trial included 38 men seen at the university urology clinic with a diagnosis of primary hypoactive sexual desire or sexual arousal disorder. Half were randomized to daily use of a white fluorescent light box for 30 minutes in the morning, preferably between 7 and 8 a.m. The light box, equipped with a UV filter, was the same as that used in treating seasonal affective disorder. Light therapy for seasonal affective disorder is an established therapy in the psychiatric world, one that has proved as effective as antidepressant therapy for that condition. It is “absolutely safe and tolerable,” except in patients with eye conditions or on photosensitizing medications, the psychiatrist noted.
The control group was on the same treatment schedule, but with light boxes that had been modified through the use of a neutral-density gel filter to provide a dose of just 100 lux instead of the 10,000 lux at a distance of 1 m from the light source to the cornea generated by the active therapy light box.
The study endpoints were change from baseline through 2 weeks of therapy on a self-administered rating of sexual satisfaction on a scale of 1-10, as well as testosterone levels.
From a baseline mean self-rated sexual satisfaction score of about 2, the group exposed to daily bright light for 2 weeks had a more than threefold increase to a score of 6.3, while the controls showed no significant change.
In addition, testosterone levels in the bright light group increased from 2.1 ng/mL to 3.6 ng/mL after 2 weeks, while remaining unchanged in controls.
“Our idea for this study came from the observation that sexual satisfaction is known to increase during the spring and summer, compared to fall and winter. We thought that may have something to do with the natural daylight,” Dr. Fagiolini said.
The most likely mechanism of benefit springs from the established finding that bright light stimulates the pituitary gland to produce leutinizing hormone. This results in increased levels of testosterone and inhibition of melatonin production by the pineal gland. Decreased plasma melatonin is thought to lead to reduced serum prolactin – and high prolactin has been linked to sexual dysfunction, he explained.
The trial was conducted in the fall and winter months to avoid confounding by more natural daylight during the other seasons. But if the study results are confirmed, this therapy might well be used year-round, the psychiatrist said.
He reported having no financial conflicts of interest regarding the study, which was conducted without external funding.
VIENNA – Daily exposure to high-intensity light early in the morning resulted in significantly improved sexual satisfaction scores and a boost in testosterone levels in men with reduced libido or erection difficulty in a randomized, placebo-controlled clinical trial, Andrea Fagiolini, MD., said at the annual meeting of the American Thyroid Association.
“We found a very strong difference in sexual satisfaction and also in blood testosterone levels with intense light therapy. Patients seemed to respond to it really well, and our placebo group didn’t respond at all,” according to Dr. Fagiolini, professor and chairman of the department of psychiatry at the University of Siena (Italy).
“It’s still early to make a general recommendation. This was a small study. We need a larger trial with more patients. But if these results are confirmed, it would be very helpful because as of now we don’t have many tools to treat sexual dysfunction. So if light therapy works, I think it may be a better option than medications like Viagra [sildenafil] or similar drugs, which have side effects,” he said in an interview.
The trial included 38 men seen at the university urology clinic with a diagnosis of primary hypoactive sexual desire or sexual arousal disorder. Half were randomized to daily use of a white fluorescent light box for 30 minutes in the morning, preferably between 7 and 8 a.m. The light box, equipped with a UV filter, was the same as that used in treating seasonal affective disorder. Light therapy for seasonal affective disorder is an established therapy in the psychiatric world, one that has proved as effective as antidepressant therapy for that condition. It is “absolutely safe and tolerable,” except in patients with eye conditions or on photosensitizing medications, the psychiatrist noted.
The control group was on the same treatment schedule, but with light boxes that had been modified through the use of a neutral-density gel filter to provide a dose of just 100 lux instead of the 10,000 lux at a distance of 1 m from the light source to the cornea generated by the active therapy light box.
The study endpoints were change from baseline through 2 weeks of therapy on a self-administered rating of sexual satisfaction on a scale of 1-10, as well as testosterone levels.
From a baseline mean self-rated sexual satisfaction score of about 2, the group exposed to daily bright light for 2 weeks had a more than threefold increase to a score of 6.3, while the controls showed no significant change.
In addition, testosterone levels in the bright light group increased from 2.1 ng/mL to 3.6 ng/mL after 2 weeks, while remaining unchanged in controls.
“Our idea for this study came from the observation that sexual satisfaction is known to increase during the spring and summer, compared to fall and winter. We thought that may have something to do with the natural daylight,” Dr. Fagiolini said.
The most likely mechanism of benefit springs from the established finding that bright light stimulates the pituitary gland to produce leutinizing hormone. This results in increased levels of testosterone and inhibition of melatonin production by the pineal gland. Decreased plasma melatonin is thought to lead to reduced serum prolactin – and high prolactin has been linked to sexual dysfunction, he explained.
The trial was conducted in the fall and winter months to avoid confounding by more natural daylight during the other seasons. But if the study results are confirmed, this therapy might well be used year-round, the psychiatrist said.
He reported having no financial conflicts of interest regarding the study, which was conducted without external funding.
VIENNA – Daily exposure to high-intensity light early in the morning resulted in significantly improved sexual satisfaction scores and a boost in testosterone levels in men with reduced libido or erection difficulty in a randomized, placebo-controlled clinical trial, Andrea Fagiolini, MD., said at the annual meeting of the American Thyroid Association.
“We found a very strong difference in sexual satisfaction and also in blood testosterone levels with intense light therapy. Patients seemed to respond to it really well, and our placebo group didn’t respond at all,” according to Dr. Fagiolini, professor and chairman of the department of psychiatry at the University of Siena (Italy).
“It’s still early to make a general recommendation. This was a small study. We need a larger trial with more patients. But if these results are confirmed, it would be very helpful because as of now we don’t have many tools to treat sexual dysfunction. So if light therapy works, I think it may be a better option than medications like Viagra [sildenafil] or similar drugs, which have side effects,” he said in an interview.
The trial included 38 men seen at the university urology clinic with a diagnosis of primary hypoactive sexual desire or sexual arousal disorder. Half were randomized to daily use of a white fluorescent light box for 30 minutes in the morning, preferably between 7 and 8 a.m. The light box, equipped with a UV filter, was the same as that used in treating seasonal affective disorder. Light therapy for seasonal affective disorder is an established therapy in the psychiatric world, one that has proved as effective as antidepressant therapy for that condition. It is “absolutely safe and tolerable,” except in patients with eye conditions or on photosensitizing medications, the psychiatrist noted.
The control group was on the same treatment schedule, but with light boxes that had been modified through the use of a neutral-density gel filter to provide a dose of just 100 lux instead of the 10,000 lux at a distance of 1 m from the light source to the cornea generated by the active therapy light box.
The study endpoints were change from baseline through 2 weeks of therapy on a self-administered rating of sexual satisfaction on a scale of 1-10, as well as testosterone levels.
From a baseline mean self-rated sexual satisfaction score of about 2, the group exposed to daily bright light for 2 weeks had a more than threefold increase to a score of 6.3, while the controls showed no significant change.
In addition, testosterone levels in the bright light group increased from 2.1 ng/mL to 3.6 ng/mL after 2 weeks, while remaining unchanged in controls.
“Our idea for this study came from the observation that sexual satisfaction is known to increase during the spring and summer, compared to fall and winter. We thought that may have something to do with the natural daylight,” Dr. Fagiolini said.
The most likely mechanism of benefit springs from the established finding that bright light stimulates the pituitary gland to produce leutinizing hormone. This results in increased levels of testosterone and inhibition of melatonin production by the pineal gland. Decreased plasma melatonin is thought to lead to reduced serum prolactin – and high prolactin has been linked to sexual dysfunction, he explained.
The trial was conducted in the fall and winter months to avoid confounding by more natural daylight during the other seasons. But if the study results are confirmed, this therapy might well be used year-round, the psychiatrist said.
He reported having no financial conflicts of interest regarding the study, which was conducted without external funding.
AT THE ECNP CONGRESS
Key clinical point: Daily exposure to intense white light, an established treatment for seasonal affective disorder, also may improve male sexual dysfunction.
Major finding: After 2 weeks of daily bright light therapy, men with low libido or erection difficulty showed an improvement in self-rated sexual satisfaction from 2.1 to 6.3 on a 1-10 scale.
Data source: A randomized trial that included 38 men diagnosed with hypoactive sexual desire disorder or sexual arousal disorder who received 2 weeks of high-intensity light therapy for 30 minutes per morning or a sham placebo involving exposure to far less intense light.
Disclosures: The presenter reported having no financial conflicts of interest regarding the study, which was conducted without external funding.
Psychiatric risks quantified in siblings of mental disorder patients
VIENNA – The brothers and sisters of patients hospitalized for schizophrenia, bipolar disorder, or unipolar depression are themselves at strikingly high risk of subsequently developing not only the same disorder as their sibling, but other forms of major mental illness as well, Mark Weiser, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
He presented the results of the first comprehensive national population-based study to examine in this fashion the extent to which heritability contributes to schizophrenia and affective disorders. This nested case-control study included all siblings of 6,111 Israeli patients hospitalized for schizophrenia, schizoaffective disorder, bipolar disorder, or unipolar depression. The siblings’ rates of and reasons for subsequent psychiatric hospitalization were compared with those of 74,988 age- and gender-matched Israeli controls. All admission and discharge diagnoses were made by board-certified psychiatrists.
Siblings of individuals with schizophrenia were at 9.4-fold increased risk of subsequent hospitalization for schizophrenia, 8.5-fold relative risk for schizoaffective disorder, and 7.7-fold increased risk for bipolar disorder, compared with controls.
Moreover, siblings of patients with bipolar disorder were not only at 8.4-fold increased risk of subsequent hospitalization for that disease, they also were at 4.2-fold greater risk than controls for schizophrenia and 7.6-fold increased risk for hospitalization for other psychiatric disorders, a grab bag category that included anxiety disorders, dissociative disorder, post-traumatic stress disorder, eating disorders, pervasive developmental disorders, and personality disorders, according to Dr. Weiser, professor of psychiatry at Tel Aviv University.
Siblings of patients hospitalized for unipolar depression were at 6.2-fold relative risk of subsequent hospitalization for schizophrenia and 9.7-fold increased risk of hospitalization of other psychiatric disorders. “The bottom line of our study is it’s not a one gene/one disorder model. There’s not a gene for schizophrenia and a different gene for bipolar disorder. There are probably a bunch of different genes that increase the risk for schizophrenia but also increase risk for bipolar disorder, and the other way around,” the psychiatrist explained in an interview.
“Clinically it’s well known from the literature that if I have schizophrenia, there’s an increased chance that my brother will have it as well, so when my brother comes in having trouble, you obviously suggest that he might be developing schizophrenia. What these data imply is that if the brother of a schizophrenia patient comes in seeking help, it might not be schizophrenia, because he’s also at increased risk for bipolar disorder. So your index of suspicion should be much broader, not only for the one specific illness but for the whole idea of psychopathology in general. It’s a challenge. It demands for clinicians to be more broad-minded and to understand that these genes we’re looking for in large studies are not specific for one particular illness,” Dr. Weiser said.
This study was made possible because Israel, like Denmark, maintains multiple comprehensive national registries in which health care researchers are able to tap into and connect.
“A study like this can’t be done in the United States,” he said. “No how, no way.”
Dr. Weiser reported having no financial conflicts of interest regarding this study, which was conducted without external funding.
VIENNA – The brothers and sisters of patients hospitalized for schizophrenia, bipolar disorder, or unipolar depression are themselves at strikingly high risk of subsequently developing not only the same disorder as their sibling, but other forms of major mental illness as well, Mark Weiser, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
He presented the results of the first comprehensive national population-based study to examine in this fashion the extent to which heritability contributes to schizophrenia and affective disorders. This nested case-control study included all siblings of 6,111 Israeli patients hospitalized for schizophrenia, schizoaffective disorder, bipolar disorder, or unipolar depression. The siblings’ rates of and reasons for subsequent psychiatric hospitalization were compared with those of 74,988 age- and gender-matched Israeli controls. All admission and discharge diagnoses were made by board-certified psychiatrists.
Siblings of individuals with schizophrenia were at 9.4-fold increased risk of subsequent hospitalization for schizophrenia, 8.5-fold relative risk for schizoaffective disorder, and 7.7-fold increased risk for bipolar disorder, compared with controls.
Moreover, siblings of patients with bipolar disorder were not only at 8.4-fold increased risk of subsequent hospitalization for that disease, they also were at 4.2-fold greater risk than controls for schizophrenia and 7.6-fold increased risk for hospitalization for other psychiatric disorders, a grab bag category that included anxiety disorders, dissociative disorder, post-traumatic stress disorder, eating disorders, pervasive developmental disorders, and personality disorders, according to Dr. Weiser, professor of psychiatry at Tel Aviv University.
Siblings of patients hospitalized for unipolar depression were at 6.2-fold relative risk of subsequent hospitalization for schizophrenia and 9.7-fold increased risk of hospitalization of other psychiatric disorders. “The bottom line of our study is it’s not a one gene/one disorder model. There’s not a gene for schizophrenia and a different gene for bipolar disorder. There are probably a bunch of different genes that increase the risk for schizophrenia but also increase risk for bipolar disorder, and the other way around,” the psychiatrist explained in an interview.
“Clinically it’s well known from the literature that if I have schizophrenia, there’s an increased chance that my brother will have it as well, so when my brother comes in having trouble, you obviously suggest that he might be developing schizophrenia. What these data imply is that if the brother of a schizophrenia patient comes in seeking help, it might not be schizophrenia, because he’s also at increased risk for bipolar disorder. So your index of suspicion should be much broader, not only for the one specific illness but for the whole idea of psychopathology in general. It’s a challenge. It demands for clinicians to be more broad-minded and to understand that these genes we’re looking for in large studies are not specific for one particular illness,” Dr. Weiser said.
This study was made possible because Israel, like Denmark, maintains multiple comprehensive national registries in which health care researchers are able to tap into and connect.
“A study like this can’t be done in the United States,” he said. “No how, no way.”
Dr. Weiser reported having no financial conflicts of interest regarding this study, which was conducted without external funding.
VIENNA – The brothers and sisters of patients hospitalized for schizophrenia, bipolar disorder, or unipolar depression are themselves at strikingly high risk of subsequently developing not only the same disorder as their sibling, but other forms of major mental illness as well, Mark Weiser, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
He presented the results of the first comprehensive national population-based study to examine in this fashion the extent to which heritability contributes to schizophrenia and affective disorders. This nested case-control study included all siblings of 6,111 Israeli patients hospitalized for schizophrenia, schizoaffective disorder, bipolar disorder, or unipolar depression. The siblings’ rates of and reasons for subsequent psychiatric hospitalization were compared with those of 74,988 age- and gender-matched Israeli controls. All admission and discharge diagnoses were made by board-certified psychiatrists.
Siblings of individuals with schizophrenia were at 9.4-fold increased risk of subsequent hospitalization for schizophrenia, 8.5-fold relative risk for schizoaffective disorder, and 7.7-fold increased risk for bipolar disorder, compared with controls.
Moreover, siblings of patients with bipolar disorder were not only at 8.4-fold increased risk of subsequent hospitalization for that disease, they also were at 4.2-fold greater risk than controls for schizophrenia and 7.6-fold increased risk for hospitalization for other psychiatric disorders, a grab bag category that included anxiety disorders, dissociative disorder, post-traumatic stress disorder, eating disorders, pervasive developmental disorders, and personality disorders, according to Dr. Weiser, professor of psychiatry at Tel Aviv University.
Siblings of patients hospitalized for unipolar depression were at 6.2-fold relative risk of subsequent hospitalization for schizophrenia and 9.7-fold increased risk of hospitalization of other psychiatric disorders. “The bottom line of our study is it’s not a one gene/one disorder model. There’s not a gene for schizophrenia and a different gene for bipolar disorder. There are probably a bunch of different genes that increase the risk for schizophrenia but also increase risk for bipolar disorder, and the other way around,” the psychiatrist explained in an interview.
“Clinically it’s well known from the literature that if I have schizophrenia, there’s an increased chance that my brother will have it as well, so when my brother comes in having trouble, you obviously suggest that he might be developing schizophrenia. What these data imply is that if the brother of a schizophrenia patient comes in seeking help, it might not be schizophrenia, because he’s also at increased risk for bipolar disorder. So your index of suspicion should be much broader, not only for the one specific illness but for the whole idea of psychopathology in general. It’s a challenge. It demands for clinicians to be more broad-minded and to understand that these genes we’re looking for in large studies are not specific for one particular illness,” Dr. Weiser said.
This study was made possible because Israel, like Denmark, maintains multiple comprehensive national registries in which health care researchers are able to tap into and connect.
“A study like this can’t be done in the United States,” he said. “No how, no way.”
Dr. Weiser reported having no financial conflicts of interest regarding this study, which was conducted without external funding.
AT THE ECNP CONGRESS
Key clinical point: Siblings of patients with schizophrenia or bipolar disorder are at sharply increased risk of subsequent hospitalization for a range of psychiatric disorders, not just what their sibling has.
Major finding: Siblings of schizophrenia patients were not only at 9.4-fold increased risk of subsequent hospitalization for schizophrenia in a national study, but also at 7.7-fold greater risk for bipolar disorder.
Data source: This nested case-control study compared psychiatric hospitalization rates for all siblings of 6,111 Israeli patients with schizophrenia, bipolar disorder, or unipolar depression to nearly 75,000 matched controls.
Disclosures: The study was conducted without external funding. The presenter reported having no financial conflicts of interest.
GAD tied to twice the risk of cancer mortality in men
VIENNA – Generalized anxiety disorder in men over age 40 was independently associated with a greater than twofold increased risk of death due to cancer during 15 years of follow-up, compared with men without the psychiatric disorder, in a large longitudinal population-based study, Olivia Remes reported at the annual congress of the European College of Neuropsychopharmacology.
In contrast, women with generalized anxiety disorder (GAD) were at no increased risk for cancer mortality, according to Ms. Remes, a PhD candidate in the department of public health and primary care at the University of Cambridge, England.
“I think an important message of this study is that anxiety is not just a personality trait,” she said in an interview. “In some cases, it may be more than worries and stress; it can represent a possible marker for future ill physical health that general practitioners and psychiatrists ought to be aware of.”
This creates a dilemma, because individuals with GAD typically are high users of health care resources. They frequently present in physicians’ offices and emergency departments with a wide range of physical complaints, including stomach pain, breathing difficulty, fatigue, nausea, or peripheral numbness.
Ms. Remes presented an analysis of 7,139 men and 8,799 women over age 40 at enrollment in the European Prospective Investigation of Cancer–Norfolk Study from the period of 1996-2000. At entry, the patients underwent a physical examination and completed numerous health-related questionnaires. Among these was the Health and Life Experiences Questionnaire (HLEQ), the responses to which enabled investigators to identify 1.8% of the men and 2.4% of women as meeting DSM-IV diagnostic criteria for GAD.
During 15 years of follow-up, 796 men and 648 women died of cancer. In multivariate analysis, men with GAD were at a 2.14-fold increased risk of death due to cancer. This analysis was extensively adjusted for potential confounders, including age, marital status, education level, socioeconomic status, major chronic physical illnesses, smoking, alcohol intake, major depressive disorder, body mass index, physical activity level, and the use of antidepressants or antihypnotic agents.
This was the first large, long-term study to examine the relationship between GAD and cancer mortality. Prior studies yielded conflicting results but were limited by small sample size and/or short follow-up, Ms. Remes said.
Even with more than 1,400 cancer deaths in the study, the sample size is too small to say whether GAD in men is preferentially associated with death due to any specific type of cancer.
Severe chronic anxiety has been linked to increased systemic inflammation, an observation that points to a possible mechanism by which GAD might increase affected individuals’ risk of fatal cancer as well as cardiovascular disease, chronic lung disease, and other conditions where inflammation figures prominently. But that doesn’t explain the gender difference in cancer mortality risk, the source of which remains speculative. It’s not the result of men being more likely to be smokers or to abuse alcohol, since those carcinogenic lifestyle factors were controlled for in the multivariate analysis, she observed.
One hypothetical possibility is that men with GAD who develop a malignancy might be more likely to delay seeking medical attention for it than might men without the anxiety disorder. Ms. Remes and her coinvestigators plan to explore this possibility in a roundabout way by analyzing the Norfolk study database looking for differences between men with and without GAD in the time from cancer diagnosis to death.
To eliminate the possibility that GAD in men might be triggered by an occult and ultimately fatal cancer, the investigators reanalyzed the Norfolk study data after excluding deaths that occurred during the first 5 years of follow-up. The results remained unchanged, according to Ms. Remes.
She reported having no financial conflicts regarding this study, which was sponsored by the U.K. Medical Research Council and Cancer Research UK.
VIENNA – Generalized anxiety disorder in men over age 40 was independently associated with a greater than twofold increased risk of death due to cancer during 15 years of follow-up, compared with men without the psychiatric disorder, in a large longitudinal population-based study, Olivia Remes reported at the annual congress of the European College of Neuropsychopharmacology.
In contrast, women with generalized anxiety disorder (GAD) were at no increased risk for cancer mortality, according to Ms. Remes, a PhD candidate in the department of public health and primary care at the University of Cambridge, England.
“I think an important message of this study is that anxiety is not just a personality trait,” she said in an interview. “In some cases, it may be more than worries and stress; it can represent a possible marker for future ill physical health that general practitioners and psychiatrists ought to be aware of.”
This creates a dilemma, because individuals with GAD typically are high users of health care resources. They frequently present in physicians’ offices and emergency departments with a wide range of physical complaints, including stomach pain, breathing difficulty, fatigue, nausea, or peripheral numbness.
Ms. Remes presented an analysis of 7,139 men and 8,799 women over age 40 at enrollment in the European Prospective Investigation of Cancer–Norfolk Study from the period of 1996-2000. At entry, the patients underwent a physical examination and completed numerous health-related questionnaires. Among these was the Health and Life Experiences Questionnaire (HLEQ), the responses to which enabled investigators to identify 1.8% of the men and 2.4% of women as meeting DSM-IV diagnostic criteria for GAD.
During 15 years of follow-up, 796 men and 648 women died of cancer. In multivariate analysis, men with GAD were at a 2.14-fold increased risk of death due to cancer. This analysis was extensively adjusted for potential confounders, including age, marital status, education level, socioeconomic status, major chronic physical illnesses, smoking, alcohol intake, major depressive disorder, body mass index, physical activity level, and the use of antidepressants or antihypnotic agents.
This was the first large, long-term study to examine the relationship between GAD and cancer mortality. Prior studies yielded conflicting results but were limited by small sample size and/or short follow-up, Ms. Remes said.
Even with more than 1,400 cancer deaths in the study, the sample size is too small to say whether GAD in men is preferentially associated with death due to any specific type of cancer.
Severe chronic anxiety has been linked to increased systemic inflammation, an observation that points to a possible mechanism by which GAD might increase affected individuals’ risk of fatal cancer as well as cardiovascular disease, chronic lung disease, and other conditions where inflammation figures prominently. But that doesn’t explain the gender difference in cancer mortality risk, the source of which remains speculative. It’s not the result of men being more likely to be smokers or to abuse alcohol, since those carcinogenic lifestyle factors were controlled for in the multivariate analysis, she observed.
One hypothetical possibility is that men with GAD who develop a malignancy might be more likely to delay seeking medical attention for it than might men without the anxiety disorder. Ms. Remes and her coinvestigators plan to explore this possibility in a roundabout way by analyzing the Norfolk study database looking for differences between men with and without GAD in the time from cancer diagnosis to death.
To eliminate the possibility that GAD in men might be triggered by an occult and ultimately fatal cancer, the investigators reanalyzed the Norfolk study data after excluding deaths that occurred during the first 5 years of follow-up. The results remained unchanged, according to Ms. Remes.
She reported having no financial conflicts regarding this study, which was sponsored by the U.K. Medical Research Council and Cancer Research UK.
VIENNA – Generalized anxiety disorder in men over age 40 was independently associated with a greater than twofold increased risk of death due to cancer during 15 years of follow-up, compared with men without the psychiatric disorder, in a large longitudinal population-based study, Olivia Remes reported at the annual congress of the European College of Neuropsychopharmacology.
In contrast, women with generalized anxiety disorder (GAD) were at no increased risk for cancer mortality, according to Ms. Remes, a PhD candidate in the department of public health and primary care at the University of Cambridge, England.
“I think an important message of this study is that anxiety is not just a personality trait,” she said in an interview. “In some cases, it may be more than worries and stress; it can represent a possible marker for future ill physical health that general practitioners and psychiatrists ought to be aware of.”
This creates a dilemma, because individuals with GAD typically are high users of health care resources. They frequently present in physicians’ offices and emergency departments with a wide range of physical complaints, including stomach pain, breathing difficulty, fatigue, nausea, or peripheral numbness.
Ms. Remes presented an analysis of 7,139 men and 8,799 women over age 40 at enrollment in the European Prospective Investigation of Cancer–Norfolk Study from the period of 1996-2000. At entry, the patients underwent a physical examination and completed numerous health-related questionnaires. Among these was the Health and Life Experiences Questionnaire (HLEQ), the responses to which enabled investigators to identify 1.8% of the men and 2.4% of women as meeting DSM-IV diagnostic criteria for GAD.
During 15 years of follow-up, 796 men and 648 women died of cancer. In multivariate analysis, men with GAD were at a 2.14-fold increased risk of death due to cancer. This analysis was extensively adjusted for potential confounders, including age, marital status, education level, socioeconomic status, major chronic physical illnesses, smoking, alcohol intake, major depressive disorder, body mass index, physical activity level, and the use of antidepressants or antihypnotic agents.
This was the first large, long-term study to examine the relationship between GAD and cancer mortality. Prior studies yielded conflicting results but were limited by small sample size and/or short follow-up, Ms. Remes said.
Even with more than 1,400 cancer deaths in the study, the sample size is too small to say whether GAD in men is preferentially associated with death due to any specific type of cancer.
Severe chronic anxiety has been linked to increased systemic inflammation, an observation that points to a possible mechanism by which GAD might increase affected individuals’ risk of fatal cancer as well as cardiovascular disease, chronic lung disease, and other conditions where inflammation figures prominently. But that doesn’t explain the gender difference in cancer mortality risk, the source of which remains speculative. It’s not the result of men being more likely to be smokers or to abuse alcohol, since those carcinogenic lifestyle factors were controlled for in the multivariate analysis, she observed.
One hypothetical possibility is that men with GAD who develop a malignancy might be more likely to delay seeking medical attention for it than might men without the anxiety disorder. Ms. Remes and her coinvestigators plan to explore this possibility in a roundabout way by analyzing the Norfolk study database looking for differences between men with and without GAD in the time from cancer diagnosis to death.
To eliminate the possibility that GAD in men might be triggered by an occult and ultimately fatal cancer, the investigators reanalyzed the Norfolk study data after excluding deaths that occurred during the first 5 years of follow-up. The results remained unchanged, according to Ms. Remes.
She reported having no financial conflicts regarding this study, which was sponsored by the U.K. Medical Research Council and Cancer Research UK.
AT THE ECNP CONGRESS
Key clinical point: Men with generalized anxiety disorder are more than twice as likely to die from cancer, compared with men without the disorder.
Major finding: Men over age 40 with generalized anxiety disorder were 2.14 times more likely to die of cancer within 15 years than were those without the disorder.
Data source: A longitudinal, population-based study of nearly 16,000 Norfolk, England–area adults aged 40 or older who were followed for 15 years.
Disclosures: The U.K. Medical Research Council and Cancer Research UK sponsored the study. The presenter reported having no financial conflicts of interest.
OCD undertreatment: Is Internet-based CBT the answer?
VIENNA – Christian Rück, MD, believes he has seen the future of treatment for obsessive-compulsive disorder, and it’s Internet-based cognitive-behavioral therapy.
The numbers tell the tale. Obsessive-compulsive disorder (OCD) affects 2% of the general population. It’s an often disabling condition marked by shame and stigma. Major practice guidelines recommend cognitive-behavioral therapy (CBT) as the evidence-based first-line nonpharmacologic therapy. Yet only 5%-10% of OCD patients ever receive conventional face-to-face CBT because of the severe shortage and geographic maldistribution of therapists trained in its use, the psychiatrist observed at the annual congress of the European College of Neuropsychopharmacology.
Thus, a huge unmet need exists for treatment access. And persuasive evidence now exists that Internet-based CBT (I-CBT) for OCD can be provided effectively, safely, and in an extremely cost-effective fashion. Indeed, it takes up very little therapist time – an average of 6-10 minutes per patient per week devoted to reading and answering participants’ emails. And since the therapist’s main role in this treatment approach is simply to encourage patient engagement in the structured online program, I-CBT readily lends itself to use by primary care physicians and other nonspecialists, according to Dr. Rück, a psychiatrist at the Karolinska Institute in Stockholm.
“The vast majority of OCD patients have access to nothing. To me, I-CBT provides us with a unique opportunity to sustain quality of care but still make it very widely available. It’s sort of like serving a top-notch lobster meal at McDonald’s prices,” he said.
Over the past 15 years, I-CBT programs have been developed and proven effective in more than 150 randomized controlled trials for a wide range of psychiatric and medical conditions, including depression, panic disorder, social phobia, severe health anxiety and other anxiety disorders, erectile dysfunction, atrial fibrillation, fibromyalgia, irritable bowel syndrome, and insomnia.
More recently, Dr. Rück and his coinvestigators have pioneered the development of I-CBT as an evidence-based treatment for OCD. They now are in the process of doing the same for body dysmorphic disorder, a related condition that’s often particularly challenging to treat successfully.
The investigators’ first large randomized controlled trial of I-CBT for OCD included 101 patients with a mean 18-year history of the disorder. They were assigned to 10 weeks of the online therapy or to an online supportive care control arm. Mean scores on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) improved from 21.4 at baseline to 12.9 upon completion of the I-CBT program and 12.6 at follow-up 4 months post treatment. Sixty percent of the I-CBT group demonstrated clinically significant improvement, compared with 6% of controls (Psychol Med. 2012 Oct;42[10]:2193-203).
The benefit proved durable, as demonstrated in an extension study with periodic follow-up out to 24 months post completion of the I-CBT program. The incorporation of an Internet-based booster program in one arm of the follow-up protocol protected against relapses (Psychol Med. 2014 Oct;44[13]2877-87).
Dr. Rück and his coinvestigators also have shown in a 128-patient, double-blind trial that d-cycloserine, a partial N-methyl-d-aspartate agonist that promotes fear extinction, augmented the response to I-CBT for OCD, but only in the subgroup not on concomitant antidepressant therapy. The remission rate was 60% at 3 months follow-up post I-CBT in antidepressant-free patients on d-cycloserine, compared with just 24% in d-cycloserine recipients taking antidepressants during I-CBT. Apparently, antidepressants blunt d-cycloserine’s fear-extinction effect (JAMA Psychiatry. 2015 Jul;72[7]:659-67).
The program content of I-CBT is the same as in conventional manualized CBT, but without the face-to-face contact. The I-CBT program consists of 10-15 weekly chapters or modules. There is homework, worksheets, and titrated exposures to fear-eliciting situations. Progress to the next module is contingent upon completion of the previous one, with the patient being required to successfully answer questions that show mastery of the material.
Most patients rate the program favorably. They like not having to show up in the therapist’s office week after week.
“One of the advantages of I-CBT is you can interact every day. If your exposure goes wrong you don’t have to wait 6 days until your next face-to-face appointment with your therapist; you can actually get treatment right away and in that way increase the speed of progress,” Dr. Rück observed.
Also, if the patient forgets a basic concept, he or she can go back and reread.
“Everything is saved. This makes it very easy to supervise. There’s nothing going on that can’t be seen. Isaac M. Marks, MD, an early OCD researcher at Imperial College London, once said that one of the greatest advantages of I-CBT is that the therapist can’t sleep with the patient,” Dr. Rück recalled.
His research group is now in the midst of a clinical trial designed to answer two key questions: Is I-CBT for OCD as effective as face-to-face CBT? And is the therapist really necessary in order to achieve optimal outcomes in I-CBT?
“It would be a kind of shock to us if all our therapist impact is for nothing, but we’ll find out soon,” he promised.
Dr. Rück and his coinvestigators recently developed a program for therapist-supervised I-CBT for patients with body dysmorphic disorder (BDD). In a single-blind pilot clinical trial involving 94 adults with BDD, the clinical response rate at 6 months of follow-up as defined by at least a 30% reduction from baseline in scores on the BDD–Y-BOCS was 56% in the I-CBT arm and 13% in controls assigned to online supportive care. The number needed to treat was impressively low, at 2.3. And those results were achieved by clinical psychology students having no prior experience with BDD, although they were closely supervised by an experienced clinician (BMJ. 2016 Feb 2;352:i241.
Dr. Rück has been disappointed to find that physicians, psychotherapists, and health care systems have been slow to embrace I-CBT for the conditions where there is solid supportive randomized trial evidence. I-CBT has been implemented within health care systems only in Australia and Stockholm County, the places where most of the research has been conducted.
“The literature has been around for about 15 years now, and we are noticing that the rollout of this is terribly slow. I’m starting to think that the health care system itself is one of the most problematic roadblocks, especially with regard to reimbursement issues. Maybe I-CBT should be offered outside of the health care system. Sometimes I think Google would do this better than a nationalized health care system,” the psychiatrist mused.
He reported having no financial conflicts of interest regarding his presentation.
VIENNA – Christian Rück, MD, believes he has seen the future of treatment for obsessive-compulsive disorder, and it’s Internet-based cognitive-behavioral therapy.
The numbers tell the tale. Obsessive-compulsive disorder (OCD) affects 2% of the general population. It’s an often disabling condition marked by shame and stigma. Major practice guidelines recommend cognitive-behavioral therapy (CBT) as the evidence-based first-line nonpharmacologic therapy. Yet only 5%-10% of OCD patients ever receive conventional face-to-face CBT because of the severe shortage and geographic maldistribution of therapists trained in its use, the psychiatrist observed at the annual congress of the European College of Neuropsychopharmacology.
Thus, a huge unmet need exists for treatment access. And persuasive evidence now exists that Internet-based CBT (I-CBT) for OCD can be provided effectively, safely, and in an extremely cost-effective fashion. Indeed, it takes up very little therapist time – an average of 6-10 minutes per patient per week devoted to reading and answering participants’ emails. And since the therapist’s main role in this treatment approach is simply to encourage patient engagement in the structured online program, I-CBT readily lends itself to use by primary care physicians and other nonspecialists, according to Dr. Rück, a psychiatrist at the Karolinska Institute in Stockholm.
“The vast majority of OCD patients have access to nothing. To me, I-CBT provides us with a unique opportunity to sustain quality of care but still make it very widely available. It’s sort of like serving a top-notch lobster meal at McDonald’s prices,” he said.
Over the past 15 years, I-CBT programs have been developed and proven effective in more than 150 randomized controlled trials for a wide range of psychiatric and medical conditions, including depression, panic disorder, social phobia, severe health anxiety and other anxiety disorders, erectile dysfunction, atrial fibrillation, fibromyalgia, irritable bowel syndrome, and insomnia.
More recently, Dr. Rück and his coinvestigators have pioneered the development of I-CBT as an evidence-based treatment for OCD. They now are in the process of doing the same for body dysmorphic disorder, a related condition that’s often particularly challenging to treat successfully.
The investigators’ first large randomized controlled trial of I-CBT for OCD included 101 patients with a mean 18-year history of the disorder. They were assigned to 10 weeks of the online therapy or to an online supportive care control arm. Mean scores on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) improved from 21.4 at baseline to 12.9 upon completion of the I-CBT program and 12.6 at follow-up 4 months post treatment. Sixty percent of the I-CBT group demonstrated clinically significant improvement, compared with 6% of controls (Psychol Med. 2012 Oct;42[10]:2193-203).
The benefit proved durable, as demonstrated in an extension study with periodic follow-up out to 24 months post completion of the I-CBT program. The incorporation of an Internet-based booster program in one arm of the follow-up protocol protected against relapses (Psychol Med. 2014 Oct;44[13]2877-87).
Dr. Rück and his coinvestigators also have shown in a 128-patient, double-blind trial that d-cycloserine, a partial N-methyl-d-aspartate agonist that promotes fear extinction, augmented the response to I-CBT for OCD, but only in the subgroup not on concomitant antidepressant therapy. The remission rate was 60% at 3 months follow-up post I-CBT in antidepressant-free patients on d-cycloserine, compared with just 24% in d-cycloserine recipients taking antidepressants during I-CBT. Apparently, antidepressants blunt d-cycloserine’s fear-extinction effect (JAMA Psychiatry. 2015 Jul;72[7]:659-67).
The program content of I-CBT is the same as in conventional manualized CBT, but without the face-to-face contact. The I-CBT program consists of 10-15 weekly chapters or modules. There is homework, worksheets, and titrated exposures to fear-eliciting situations. Progress to the next module is contingent upon completion of the previous one, with the patient being required to successfully answer questions that show mastery of the material.
Most patients rate the program favorably. They like not having to show up in the therapist’s office week after week.
“One of the advantages of I-CBT is you can interact every day. If your exposure goes wrong you don’t have to wait 6 days until your next face-to-face appointment with your therapist; you can actually get treatment right away and in that way increase the speed of progress,” Dr. Rück observed.
Also, if the patient forgets a basic concept, he or she can go back and reread.
“Everything is saved. This makes it very easy to supervise. There’s nothing going on that can’t be seen. Isaac M. Marks, MD, an early OCD researcher at Imperial College London, once said that one of the greatest advantages of I-CBT is that the therapist can’t sleep with the patient,” Dr. Rück recalled.
His research group is now in the midst of a clinical trial designed to answer two key questions: Is I-CBT for OCD as effective as face-to-face CBT? And is the therapist really necessary in order to achieve optimal outcomes in I-CBT?
“It would be a kind of shock to us if all our therapist impact is for nothing, but we’ll find out soon,” he promised.
Dr. Rück and his coinvestigators recently developed a program for therapist-supervised I-CBT for patients with body dysmorphic disorder (BDD). In a single-blind pilot clinical trial involving 94 adults with BDD, the clinical response rate at 6 months of follow-up as defined by at least a 30% reduction from baseline in scores on the BDD–Y-BOCS was 56% in the I-CBT arm and 13% in controls assigned to online supportive care. The number needed to treat was impressively low, at 2.3. And those results were achieved by clinical psychology students having no prior experience with BDD, although they were closely supervised by an experienced clinician (BMJ. 2016 Feb 2;352:i241.
Dr. Rück has been disappointed to find that physicians, psychotherapists, and health care systems have been slow to embrace I-CBT for the conditions where there is solid supportive randomized trial evidence. I-CBT has been implemented within health care systems only in Australia and Stockholm County, the places where most of the research has been conducted.
“The literature has been around for about 15 years now, and we are noticing that the rollout of this is terribly slow. I’m starting to think that the health care system itself is one of the most problematic roadblocks, especially with regard to reimbursement issues. Maybe I-CBT should be offered outside of the health care system. Sometimes I think Google would do this better than a nationalized health care system,” the psychiatrist mused.
He reported having no financial conflicts of interest regarding his presentation.
VIENNA – Christian Rück, MD, believes he has seen the future of treatment for obsessive-compulsive disorder, and it’s Internet-based cognitive-behavioral therapy.
The numbers tell the tale. Obsessive-compulsive disorder (OCD) affects 2% of the general population. It’s an often disabling condition marked by shame and stigma. Major practice guidelines recommend cognitive-behavioral therapy (CBT) as the evidence-based first-line nonpharmacologic therapy. Yet only 5%-10% of OCD patients ever receive conventional face-to-face CBT because of the severe shortage and geographic maldistribution of therapists trained in its use, the psychiatrist observed at the annual congress of the European College of Neuropsychopharmacology.
Thus, a huge unmet need exists for treatment access. And persuasive evidence now exists that Internet-based CBT (I-CBT) for OCD can be provided effectively, safely, and in an extremely cost-effective fashion. Indeed, it takes up very little therapist time – an average of 6-10 minutes per patient per week devoted to reading and answering participants’ emails. And since the therapist’s main role in this treatment approach is simply to encourage patient engagement in the structured online program, I-CBT readily lends itself to use by primary care physicians and other nonspecialists, according to Dr. Rück, a psychiatrist at the Karolinska Institute in Stockholm.
“The vast majority of OCD patients have access to nothing. To me, I-CBT provides us with a unique opportunity to sustain quality of care but still make it very widely available. It’s sort of like serving a top-notch lobster meal at McDonald’s prices,” he said.
Over the past 15 years, I-CBT programs have been developed and proven effective in more than 150 randomized controlled trials for a wide range of psychiatric and medical conditions, including depression, panic disorder, social phobia, severe health anxiety and other anxiety disorders, erectile dysfunction, atrial fibrillation, fibromyalgia, irritable bowel syndrome, and insomnia.
More recently, Dr. Rück and his coinvestigators have pioneered the development of I-CBT as an evidence-based treatment for OCD. They now are in the process of doing the same for body dysmorphic disorder, a related condition that’s often particularly challenging to treat successfully.
The investigators’ first large randomized controlled trial of I-CBT for OCD included 101 patients with a mean 18-year history of the disorder. They were assigned to 10 weeks of the online therapy or to an online supportive care control arm. Mean scores on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) improved from 21.4 at baseline to 12.9 upon completion of the I-CBT program and 12.6 at follow-up 4 months post treatment. Sixty percent of the I-CBT group demonstrated clinically significant improvement, compared with 6% of controls (Psychol Med. 2012 Oct;42[10]:2193-203).
The benefit proved durable, as demonstrated in an extension study with periodic follow-up out to 24 months post completion of the I-CBT program. The incorporation of an Internet-based booster program in one arm of the follow-up protocol protected against relapses (Psychol Med. 2014 Oct;44[13]2877-87).
Dr. Rück and his coinvestigators also have shown in a 128-patient, double-blind trial that d-cycloserine, a partial N-methyl-d-aspartate agonist that promotes fear extinction, augmented the response to I-CBT for OCD, but only in the subgroup not on concomitant antidepressant therapy. The remission rate was 60% at 3 months follow-up post I-CBT in antidepressant-free patients on d-cycloserine, compared with just 24% in d-cycloserine recipients taking antidepressants during I-CBT. Apparently, antidepressants blunt d-cycloserine’s fear-extinction effect (JAMA Psychiatry. 2015 Jul;72[7]:659-67).
The program content of I-CBT is the same as in conventional manualized CBT, but without the face-to-face contact. The I-CBT program consists of 10-15 weekly chapters or modules. There is homework, worksheets, and titrated exposures to fear-eliciting situations. Progress to the next module is contingent upon completion of the previous one, with the patient being required to successfully answer questions that show mastery of the material.
Most patients rate the program favorably. They like not having to show up in the therapist’s office week after week.
“One of the advantages of I-CBT is you can interact every day. If your exposure goes wrong you don’t have to wait 6 days until your next face-to-face appointment with your therapist; you can actually get treatment right away and in that way increase the speed of progress,” Dr. Rück observed.
Also, if the patient forgets a basic concept, he or she can go back and reread.
“Everything is saved. This makes it very easy to supervise. There’s nothing going on that can’t be seen. Isaac M. Marks, MD, an early OCD researcher at Imperial College London, once said that one of the greatest advantages of I-CBT is that the therapist can’t sleep with the patient,” Dr. Rück recalled.
His research group is now in the midst of a clinical trial designed to answer two key questions: Is I-CBT for OCD as effective as face-to-face CBT? And is the therapist really necessary in order to achieve optimal outcomes in I-CBT?
“It would be a kind of shock to us if all our therapist impact is for nothing, but we’ll find out soon,” he promised.
Dr. Rück and his coinvestigators recently developed a program for therapist-supervised I-CBT for patients with body dysmorphic disorder (BDD). In a single-blind pilot clinical trial involving 94 adults with BDD, the clinical response rate at 6 months of follow-up as defined by at least a 30% reduction from baseline in scores on the BDD–Y-BOCS was 56% in the I-CBT arm and 13% in controls assigned to online supportive care. The number needed to treat was impressively low, at 2.3. And those results were achieved by clinical psychology students having no prior experience with BDD, although they were closely supervised by an experienced clinician (BMJ. 2016 Feb 2;352:i241.
Dr. Rück has been disappointed to find that physicians, psychotherapists, and health care systems have been slow to embrace I-CBT for the conditions where there is solid supportive randomized trial evidence. I-CBT has been implemented within health care systems only in Australia and Stockholm County, the places where most of the research has been conducted.
“The literature has been around for about 15 years now, and we are noticing that the rollout of this is terribly slow. I’m starting to think that the health care system itself is one of the most problematic roadblocks, especially with regard to reimbursement issues. Maybe I-CBT should be offered outside of the health care system. Sometimes I think Google would do this better than a nationalized health care system,” the psychiatrist mused.
He reported having no financial conflicts of interest regarding his presentation.
EXPERT ANALYSIS At THE ECNP CONGRESS
EPO improves cognitive impairment in depression
VIENNA – Recombinant human erythropoietin appears to be a cognitive enhancer in patients with unipolar or bipolar depression accompanied by cognitive impairment, Kamilla W. Miskowiak, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.
She presented a pooled analysis of her two pilot randomized, placebo-controlled clinical trials totaling 79 patients with treatment-resistant unipolar or partly remitted bipolar depression associated with baseline cognitive impairment. She found that 8 weeks of once-weekly intravenous infusions of high-dose human recombinant erythropoetin (Epogen), also known as epoetin alfa (EPO), resulted in clinically meaningful improvement in cognition 1 week post treatment, as measured on neuropsychological tests assessing the speed of complex cognitive processing, verbal memory, attention span, concentration, working memory, and strategic planning ability. Saline infusions had no effect.
Moreover, follow-up testing conducted 6 weeks after the final treatment session showed continued full maintenance of the initial cognitive gains, which averaged an 11% improvement over baseline. The full duration of effect will be determined in the next round of studies, which will feature 12 weeks of EPO and 6 months of off-treatment follow-up, added Dr. Miskowiak, a senior research psychologist at the University of Copenhagen.
In an interview, she emphasized that the mechanism of benefit doesn’t appear to be related to EPO’s signature ability to boost red blood cell (RBC) production and raise hemoglobin levels. After all, she noted, RBCs were back to normal within 2 weeks after treatment ended, yet the objective cognitive improvements continued. Instead, the mechanism involves EPO’s capacity to enhance brain neuroplasticity, an effect that was demonstrated first in animal studies and subsequently in Dr. Miskowiak’s clinical trials.
“We did MRI functional and structural brain scans at baseline and after completion of treatment, and we saw that EPO increased left hippocampal volume. In fact, it was the structural change in hippocampal volume in response to EPO that was the single strongest predictor of cognitive improvement in multivariate analyses adjusted for age, illness chronicity, depressive symptom severity, gender, and other factors,” according to Dr. Miskowiak.
Physicians who use EPO to treat anemia might blanch at the doses of EPO administered to improve cognitive impairments in patients with affective disorders. Instead of giving 50-100 U/kg of body weight several times per week, as is common in treating anemia, the patients in her studies typically received 40,000 U/wk.
“We used much, much higher doses than are given to affect the bone marrow in patients with anemia, because only about 1% of the IV dose passes across the blood/brain barrier,” she explained.
Because EPO, even in conventional doses, is associated with an increased risk of blood clots, patients were ineligible for the cognition-improvement trials if they had a history of venous thromboembolism, coronary disease, or cancer. Moreover, their RBC and platelet activity levels were monitored on a weekly basis. No untoward effects were seen, Dr. Miskowiak continued.
“Patients really liked coming in for this therapy. Many of them were quite chronic, with years of illness, yet adherence was excellent,” she said.
Early in the developmental pipeline are an intranasal variant of EPO and a carbamylated EPO designed to cross the blood/brain barrier efficiently in order to achieve direct brain neuroplasticity-stimulating effects with minimal impact on RBC production.
Dr. Miskowiak stressed that EPO as a treatment for cognitive dysfunction associated with affective disorders is not ready for prime time use in clinical practice. The next round of randomized, placebo-controlled clinical trials, due to start early in 2017, will attempt to replicate her pilot study findings while pinning down the optimal dosing regimen. The new trials will feature longer off-treatment follow-up as well as quality-of-life measures and an economic analysis that includes assessment of the ability to return to work.
“This therapy may be attractive from an economic perspective,” according to the psychologist. “I don’t see this as first-line therapy in clinical practice, though,” she added. “It will be reserved for the more severely cognitively impaired patients.”
Eduard Vieta, MD, professor and chair of the department of psychiatry and psychology at the University of Barcelona, commented that cognitive impairment is now recognized as a core aspect of affective disorders. There is a huge unmet need for treatments that address this disease aspect. The drugs now available for treatment of bipolar disorder and unipolar depression don’t improve the associated cognitive impairments. Indeed, up to 40% of patients in remission from major depressive disorder and 70% in remission from bipolar disorder continue to experience neurocognitive symptoms.
Dr. Miskowiak’s work was funded by the Danish Ministry of Science, Innovation, and Higher Education. She reported having no relevant financial conflicts of interest.
VIENNA – Recombinant human erythropoietin appears to be a cognitive enhancer in patients with unipolar or bipolar depression accompanied by cognitive impairment, Kamilla W. Miskowiak, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.
She presented a pooled analysis of her two pilot randomized, placebo-controlled clinical trials totaling 79 patients with treatment-resistant unipolar or partly remitted bipolar depression associated with baseline cognitive impairment. She found that 8 weeks of once-weekly intravenous infusions of high-dose human recombinant erythropoetin (Epogen), also known as epoetin alfa (EPO), resulted in clinically meaningful improvement in cognition 1 week post treatment, as measured on neuropsychological tests assessing the speed of complex cognitive processing, verbal memory, attention span, concentration, working memory, and strategic planning ability. Saline infusions had no effect.
Moreover, follow-up testing conducted 6 weeks after the final treatment session showed continued full maintenance of the initial cognitive gains, which averaged an 11% improvement over baseline. The full duration of effect will be determined in the next round of studies, which will feature 12 weeks of EPO and 6 months of off-treatment follow-up, added Dr. Miskowiak, a senior research psychologist at the University of Copenhagen.
In an interview, she emphasized that the mechanism of benefit doesn’t appear to be related to EPO’s signature ability to boost red blood cell (RBC) production and raise hemoglobin levels. After all, she noted, RBCs were back to normal within 2 weeks after treatment ended, yet the objective cognitive improvements continued. Instead, the mechanism involves EPO’s capacity to enhance brain neuroplasticity, an effect that was demonstrated first in animal studies and subsequently in Dr. Miskowiak’s clinical trials.
“We did MRI functional and structural brain scans at baseline and after completion of treatment, and we saw that EPO increased left hippocampal volume. In fact, it was the structural change in hippocampal volume in response to EPO that was the single strongest predictor of cognitive improvement in multivariate analyses adjusted for age, illness chronicity, depressive symptom severity, gender, and other factors,” according to Dr. Miskowiak.
Physicians who use EPO to treat anemia might blanch at the doses of EPO administered to improve cognitive impairments in patients with affective disorders. Instead of giving 50-100 U/kg of body weight several times per week, as is common in treating anemia, the patients in her studies typically received 40,000 U/wk.
“We used much, much higher doses than are given to affect the bone marrow in patients with anemia, because only about 1% of the IV dose passes across the blood/brain barrier,” she explained.
Because EPO, even in conventional doses, is associated with an increased risk of blood clots, patients were ineligible for the cognition-improvement trials if they had a history of venous thromboembolism, coronary disease, or cancer. Moreover, their RBC and platelet activity levels were monitored on a weekly basis. No untoward effects were seen, Dr. Miskowiak continued.
“Patients really liked coming in for this therapy. Many of them were quite chronic, with years of illness, yet adherence was excellent,” she said.
Early in the developmental pipeline are an intranasal variant of EPO and a carbamylated EPO designed to cross the blood/brain barrier efficiently in order to achieve direct brain neuroplasticity-stimulating effects with minimal impact on RBC production.
Dr. Miskowiak stressed that EPO as a treatment for cognitive dysfunction associated with affective disorders is not ready for prime time use in clinical practice. The next round of randomized, placebo-controlled clinical trials, due to start early in 2017, will attempt to replicate her pilot study findings while pinning down the optimal dosing regimen. The new trials will feature longer off-treatment follow-up as well as quality-of-life measures and an economic analysis that includes assessment of the ability to return to work.
“This therapy may be attractive from an economic perspective,” according to the psychologist. “I don’t see this as first-line therapy in clinical practice, though,” she added. “It will be reserved for the more severely cognitively impaired patients.”
Eduard Vieta, MD, professor and chair of the department of psychiatry and psychology at the University of Barcelona, commented that cognitive impairment is now recognized as a core aspect of affective disorders. There is a huge unmet need for treatments that address this disease aspect. The drugs now available for treatment of bipolar disorder and unipolar depression don’t improve the associated cognitive impairments. Indeed, up to 40% of patients in remission from major depressive disorder and 70% in remission from bipolar disorder continue to experience neurocognitive symptoms.
Dr. Miskowiak’s work was funded by the Danish Ministry of Science, Innovation, and Higher Education. She reported having no relevant financial conflicts of interest.
VIENNA – Recombinant human erythropoietin appears to be a cognitive enhancer in patients with unipolar or bipolar depression accompanied by cognitive impairment, Kamilla W. Miskowiak, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.
She presented a pooled analysis of her two pilot randomized, placebo-controlled clinical trials totaling 79 patients with treatment-resistant unipolar or partly remitted bipolar depression associated with baseline cognitive impairment. She found that 8 weeks of once-weekly intravenous infusions of high-dose human recombinant erythropoetin (Epogen), also known as epoetin alfa (EPO), resulted in clinically meaningful improvement in cognition 1 week post treatment, as measured on neuropsychological tests assessing the speed of complex cognitive processing, verbal memory, attention span, concentration, working memory, and strategic planning ability. Saline infusions had no effect.
Moreover, follow-up testing conducted 6 weeks after the final treatment session showed continued full maintenance of the initial cognitive gains, which averaged an 11% improvement over baseline. The full duration of effect will be determined in the next round of studies, which will feature 12 weeks of EPO and 6 months of off-treatment follow-up, added Dr. Miskowiak, a senior research psychologist at the University of Copenhagen.
In an interview, she emphasized that the mechanism of benefit doesn’t appear to be related to EPO’s signature ability to boost red blood cell (RBC) production and raise hemoglobin levels. After all, she noted, RBCs were back to normal within 2 weeks after treatment ended, yet the objective cognitive improvements continued. Instead, the mechanism involves EPO’s capacity to enhance brain neuroplasticity, an effect that was demonstrated first in animal studies and subsequently in Dr. Miskowiak’s clinical trials.
“We did MRI functional and structural brain scans at baseline and after completion of treatment, and we saw that EPO increased left hippocampal volume. In fact, it was the structural change in hippocampal volume in response to EPO that was the single strongest predictor of cognitive improvement in multivariate analyses adjusted for age, illness chronicity, depressive symptom severity, gender, and other factors,” according to Dr. Miskowiak.
Physicians who use EPO to treat anemia might blanch at the doses of EPO administered to improve cognitive impairments in patients with affective disorders. Instead of giving 50-100 U/kg of body weight several times per week, as is common in treating anemia, the patients in her studies typically received 40,000 U/wk.
“We used much, much higher doses than are given to affect the bone marrow in patients with anemia, because only about 1% of the IV dose passes across the blood/brain barrier,” she explained.
Because EPO, even in conventional doses, is associated with an increased risk of blood clots, patients were ineligible for the cognition-improvement trials if they had a history of venous thromboembolism, coronary disease, or cancer. Moreover, their RBC and platelet activity levels were monitored on a weekly basis. No untoward effects were seen, Dr. Miskowiak continued.
“Patients really liked coming in for this therapy. Many of them were quite chronic, with years of illness, yet adherence was excellent,” she said.
Early in the developmental pipeline are an intranasal variant of EPO and a carbamylated EPO designed to cross the blood/brain barrier efficiently in order to achieve direct brain neuroplasticity-stimulating effects with minimal impact on RBC production.
Dr. Miskowiak stressed that EPO as a treatment for cognitive dysfunction associated with affective disorders is not ready for prime time use in clinical practice. The next round of randomized, placebo-controlled clinical trials, due to start early in 2017, will attempt to replicate her pilot study findings while pinning down the optimal dosing regimen. The new trials will feature longer off-treatment follow-up as well as quality-of-life measures and an economic analysis that includes assessment of the ability to return to work.
“This therapy may be attractive from an economic perspective,” according to the psychologist. “I don’t see this as first-line therapy in clinical practice, though,” she added. “It will be reserved for the more severely cognitively impaired patients.”
Eduard Vieta, MD, professor and chair of the department of psychiatry and psychology at the University of Barcelona, commented that cognitive impairment is now recognized as a core aspect of affective disorders. There is a huge unmet need for treatments that address this disease aspect. The drugs now available for treatment of bipolar disorder and unipolar depression don’t improve the associated cognitive impairments. Indeed, up to 40% of patients in remission from major depressive disorder and 70% in remission from bipolar disorder continue to experience neurocognitive symptoms.
Dr. Miskowiak’s work was funded by the Danish Ministry of Science, Innovation, and Higher Education. She reported having no relevant financial conflicts of interest.
AT THE ECNP CONGRESS
Key clinical point: Recombinant human erythropoietin enhances brain neuroplasticity and achieves measurable improvements in cognitive impairment associated with unipolar or bipolar depression.
Major finding: Patients with cognitive impairment related to unipolar or bipolar depression responded to a series of infusions of recombinant human erythropoietin with a significant improvement in neuropsychological test scores that was maintained unabated 6 weeks after their final infusion.
Data source: A retrospective analysis of pooled data from two randomized, placebo-controlled trials totaling 79 patients with unipolar or bipolar depression.
Disclosures: This work was funded by the Danish Ministry of Science, Innovation, and Higher Education. The presenter reported having no relevant financial conflicts of interest.
