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New guidelines to focus on mixed features in depression, bipolar
WASHINGTON – A sea change is underway in how major depressive and bipolar disorders are diagnosed and treated.
Historically, the absence of an accurate, comprehensive nosology of depression has led to much suffering and confusion. People with bipolar disorder in particular are either not diagnosed early enough or are not diagnosed with the correct “flavor” of depression, according to Roger S. McIntyre, MD, author of updated treatment guidelines for bipolar depression, and the first-ever treatment guidelines for mixed features in major depressive disorder. “Twenty years ago, we would have described bipolar as episodic breakthroughs of mania and depression, with well intervals in between,” Dr. McIntyre said at Summit in Neurology & Psychiatry. “But now, we’ve really changed our fundamental thinking about bipolar disorder.”
Although reasons for the evolution in thinking are many, one of the strongest currents of change flows from the 2013 publication of the DSM-5, according to Dr. McIntyre, professor of psychiatry and pharmacology at the University of Toronto, and head of the Mood Disorders Psychopharmacology Unit at University Health Network in Toronto.
“The DSM-5’s authors took a neo-Kraepelinian view that mood disorders are dimensional,” Dr. McIntyre said in an interview. As a result, there’s been a reversal of what he called the “social construct imposed upon the cosmos of mood disorders by the DSM-III that divided that world into either depression or bipolar disorder.”
This return to thinking of mood disorders as existing on a continuum, as psychiatrist Emil Kraepelin, MD, theorized around the turn of the last century, pivots on the decision to do away with mixed states and to instead add the mixed features specifier.
“The move to mixed features is the necessary bridge between bipolar disease and major depressive disorder,” Dr. McIntyre said in the interview.
Therefore, for a period of time between the 1980 publication of the DSM-III and the DSM-5, “real-world” presentations of subsyndromal, opposite-pole symptoms that are common in major depressive disorder (MDD) and in bipolar disorder were not accounted for.
In practical terms, the addition of mixed features means that a patient with mania who presents with subsyndromal depressive symptoms would be seen, for example, to have mania with mixed features. A patient with a depressive episode who presents with subsyndromal hypomanic symptoms would be seen to have depression with mixed features. Therefore, depression with mixed features can be present not only in MDD, but in both bipolar I and II.
New treatment algorithms
This dimensional approach of assessing mixed features along a continuum could lead to better and earlier diagnosis of bipolar depression and more targeted therapies, according to Dr. McIntyre. What he thinks it won’t do is lead to an overzealousness in the overdiagnosis of bipolar depression.
“That is false. We wouldn’t say we’re not going to diagnose bowel cancer because we hear it’s overdiagnosed. But to get the diagnoses right, what we need is fidelity to diagnostic criteria.”
Enter the state of Florida. As part of its best practices for psychotherapeutic use in adults, Florida is the first state to have published evidence-based guidelines for depression with mixed features. Dr. McIntyre is one of the guidelines’ coauthors.
Antidepressants bad, olanzapine worse
Some changes to treatment algorithms might come as a surprise. Despite being among the most commonly prescribed treatments for bipolar disorder, monotherapy with antidepressants is not approved in the guidelines. “Period,” said Dr. McIntyre. “Many patients do well on antidepressants, but the most common outcome is inefficacy.”
It might be better to combine an antidepressant with an atypical antipsychotic, or a mood stabilizer to avoid treatment-emergent mania, or, more commonly, destabilization in patients who are susceptible to subsyndromal mania, he said.
In addition to mitigating symptoms of a depressive episode, atypicals can help suppress hypomanic symptoms. Dr. McIntyre said this is critical to remember, because patients with these combinations of symptoms are “the very persons who shouldn’t get an antidepressant but are also the ones most likely to be prescribed them,” according to old ways of thinking.
As for maintenance in bipolar disorder, Dr. McIntyre believes the axiom, “What gets you well keeps you well,” is a good rule of thumb when going through the algorithm. “It’s not always true, but it’s almost always true.”
Management of MDD with mixed features includes the introduction of atypicals or mood stabilizers such as lithium or lamotrigine in patients with any prior history of hypomania or mania, something Dr. McIntyre said already is beginning to happen in practice.
Olanzapine monotherapy as a first-line treatment of bipolar disorder initially was “demoted” by Dr. McIntyre and his coauthors in Florida’s bipolar treatment guidelines. In the updated version, the atypical remains a second-line therapy behind lurasidone as the recommended first-line therapy because of olanzapine’s tendency to interfere with metabolic processes. Quetiapine also is a first-line therapy, but with the qualification that it, too, could interfere with metabolic processes. Combination therapy with olanzapine plus fluoxetine is second-line.
“Lurasidone does not have the metabolic changes of quetiapine. It doesn’t make sense to treat mania and then erase 25 years of a person’s life because of weight gain,” Dr. McIntyre said.
The average lifespan of people with bipolar disorder is about 20 years shorter than it is for those without serious mental illness.
Inflammation harms cognition
The changes are indicative of how seriously the field has begun to take metabolic disturbance as an adverse event in serious mental illness. Literature on obesity as a “psycho-toxin” is growing, and Dr. McIntyre is among the pioneers.
One study by Dr. McIntyre and his colleagues, currently in press, explores how obesity-related inflammation disturbs the brain’s dopamine system, resulting in interference with executive function. Because it is well established that people with bipolar disorder are more likely to be obese (J Affect Disord. 2008 Sep;110[1-2]:149-55), they also are more susceptible to cognitive impairment than are people of normal weight, according to Dr. McIntyre.
In a 2013 study, Dr. McIntyre and his colleagues showed that a first episode of mania in a person with obesity creates the same level of cognitive impairment as that found in the brains of normal-weight individuals who have experienced five episodes of mania (Psychological Med. 2014 Feb;44[3]:533-41). “There is something about obesity that is brain toxic,” he said.
Proof of concept of this is that cognitive outcomes for people before bariatric surgery are worse than postsurgery outcomes (Am J Surg. 2014 Jun;207[6]:870-6).
Systemic inflammation elevates levels of C-reactive protein, interleukin-1, and other cytokines, and interferes with insulin signaling; all have deleterious effects on cognition, as well as metabolic health. Those disturbances negatively affect emotional regulation, sleep, appetite, and sex drive, as well as executive function, he said.
“Inflammation is a convergent system, implicated across many brain- and body-based disorders. People with bipolar disorder not only have systemic increases in inflammation, but also neuroinflammation,” Dr. McIntyre said.
Accordingly, controlling inflammation becomes essential to chronic management of depression in general and bipolar in particular since, with each successive episode of untreated mania, patients’ ability to think clearly takes a hit. “Cognitive function is the principal determinant of psychosocial function, of workplace visibility, [and] of quality of life in most patient-reported outcomes,” Dr. McIntyre said.
Cognitive impairment also can lead to a worsening of the ability to balance reward and impulse control, leading to higher rates of substance abuse or other psychiatric comorbidities after onset of bipolar disease; a vicious cycle can ensue.
“As cognitive difficulties rise, comorbidities rise. But also, some of the comorbidities we see are reflections of cognitive impairment,” Dr. McIntyre said. To wit, binge eating disorder and bulimia nervosa are common in people with bipolar disorder (J Affect Disord. 2016 Feb;191:216-2).
Citing a recent scientific statement from the American Heart Association recommending that bipolar disorder and MDD should be considered tier II risk factors for cardiovascular disease among youth, the Florida guidelines urge clinicians to regularly screen patients for cardiometabolic disorders – not only for their medical implications but for their potential to flag emergent psychiatric issues.
Pharmacotherapeutics specifically targeting neuroinflammation are not yet ready for clinical practice, but Dr. McIntyre said other, more conventional therapies are available for bipolar disorder that have anti-inflammatory properties, including selective serotonin reuptake inhibitors and lithium. “Lithium is also anti-amyloid and has an anti-suicide effect. It is a drug I would definitely use as first line.”
Some behavioral therapies also are protective against inflammation and are recommended in the guidelines. Those include attention to sleep hygiene, diet, and exercise. “Social rhythm therapy is underutilized. These patients need their day organized. They need aerobics; they need sleep,” Dr. McIntyre said.
Future is now
Although the “whole-person” approach is still nascent – seeing depression as a collection of what Dr. McIntyre said are alterations in the neural circuitry amounting to a series of “disconnection syndromes” – psychiatry already has entered a new era where disease models are more comprehensive, he said.
This new way of thinking can connect the dots between why, for example, so many people with bipolar depression also have drug and alcohol abuse. It also could help explain why in bipolar there is so much obesity, or why there is so much anxiety, he said. “We’ve moved away from the rather silly, overly simplistic notions that you have too much or too little serotonin. Or that there was too much or too little dopamine causing mania. It made for convenient sound bytes, but it was probably just superstition we were gravitating to.”
The guidelines have been peer reviewed and will be published in the Journal of Clinical Psychiatry later this year, Dr. McIntyre said.
The meeting was held by Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.
Dr. McIntyre disclosed that he has numerous industry relationships, including with AstraZeneca, Eli Lilly, Janssen Ortho, Lundbeck, Pfizer, and Shire.
On Twitter @whitneymcknight
This more holistic way of thinking about depression is one I endorse. It makes sense to conceptualize bipolar disorder as a whole body disorder rather than a condition that is specific to the brain. The clinical implications are that we need to consider integration of care approaches that can reduce stress and inflammation generally, and minimize the complications of medical conditions seen in people with bipolar disorder. Some behavioral therapies are protective against inflammation and are recommended in the guidelines. These include attention to sleep, diet, and exercise. Social rhythm therapy is underutilized, as are other types of psychosocial approaches. Appropriate access to and use of medical care to help manage medical conditions is important, and integrated medical care that considers both body and mind may be helpful.
Martha Sajatovic, MD, is the Willard Brown Chair in Neurological Outcomes Research, and director of the Neurological Outcomes Center at the University Hospitals Case Medical Center in Cleveland. She is professor of psychiatry and of neurology at Case Western Reserve University, also in Cleveland. Dr. Sajatovic reported she has several industry relationships, including with Janssen, Merck, Ortho-McNeil, and Pfizer.
This more holistic way of thinking about depression is one I endorse. It makes sense to conceptualize bipolar disorder as a whole body disorder rather than a condition that is specific to the brain. The clinical implications are that we need to consider integration of care approaches that can reduce stress and inflammation generally, and minimize the complications of medical conditions seen in people with bipolar disorder. Some behavioral therapies are protective against inflammation and are recommended in the guidelines. These include attention to sleep, diet, and exercise. Social rhythm therapy is underutilized, as are other types of psychosocial approaches. Appropriate access to and use of medical care to help manage medical conditions is important, and integrated medical care that considers both body and mind may be helpful.
Martha Sajatovic, MD, is the Willard Brown Chair in Neurological Outcomes Research, and director of the Neurological Outcomes Center at the University Hospitals Case Medical Center in Cleveland. She is professor of psychiatry and of neurology at Case Western Reserve University, also in Cleveland. Dr. Sajatovic reported she has several industry relationships, including with Janssen, Merck, Ortho-McNeil, and Pfizer.
This more holistic way of thinking about depression is one I endorse. It makes sense to conceptualize bipolar disorder as a whole body disorder rather than a condition that is specific to the brain. The clinical implications are that we need to consider integration of care approaches that can reduce stress and inflammation generally, and minimize the complications of medical conditions seen in people with bipolar disorder. Some behavioral therapies are protective against inflammation and are recommended in the guidelines. These include attention to sleep, diet, and exercise. Social rhythm therapy is underutilized, as are other types of psychosocial approaches. Appropriate access to and use of medical care to help manage medical conditions is important, and integrated medical care that considers both body and mind may be helpful.
Martha Sajatovic, MD, is the Willard Brown Chair in Neurological Outcomes Research, and director of the Neurological Outcomes Center at the University Hospitals Case Medical Center in Cleveland. She is professor of psychiatry and of neurology at Case Western Reserve University, also in Cleveland. Dr. Sajatovic reported she has several industry relationships, including with Janssen, Merck, Ortho-McNeil, and Pfizer.
WASHINGTON – A sea change is underway in how major depressive and bipolar disorders are diagnosed and treated.
Historically, the absence of an accurate, comprehensive nosology of depression has led to much suffering and confusion. People with bipolar disorder in particular are either not diagnosed early enough or are not diagnosed with the correct “flavor” of depression, according to Roger S. McIntyre, MD, author of updated treatment guidelines for bipolar depression, and the first-ever treatment guidelines for mixed features in major depressive disorder. “Twenty years ago, we would have described bipolar as episodic breakthroughs of mania and depression, with well intervals in between,” Dr. McIntyre said at Summit in Neurology & Psychiatry. “But now, we’ve really changed our fundamental thinking about bipolar disorder.”
Although reasons for the evolution in thinking are many, one of the strongest currents of change flows from the 2013 publication of the DSM-5, according to Dr. McIntyre, professor of psychiatry and pharmacology at the University of Toronto, and head of the Mood Disorders Psychopharmacology Unit at University Health Network in Toronto.
“The DSM-5’s authors took a neo-Kraepelinian view that mood disorders are dimensional,” Dr. McIntyre said in an interview. As a result, there’s been a reversal of what he called the “social construct imposed upon the cosmos of mood disorders by the DSM-III that divided that world into either depression or bipolar disorder.”
This return to thinking of mood disorders as existing on a continuum, as psychiatrist Emil Kraepelin, MD, theorized around the turn of the last century, pivots on the decision to do away with mixed states and to instead add the mixed features specifier.
“The move to mixed features is the necessary bridge between bipolar disease and major depressive disorder,” Dr. McIntyre said in the interview.
Therefore, for a period of time between the 1980 publication of the DSM-III and the DSM-5, “real-world” presentations of subsyndromal, opposite-pole symptoms that are common in major depressive disorder (MDD) and in bipolar disorder were not accounted for.
In practical terms, the addition of mixed features means that a patient with mania who presents with subsyndromal depressive symptoms would be seen, for example, to have mania with mixed features. A patient with a depressive episode who presents with subsyndromal hypomanic symptoms would be seen to have depression with mixed features. Therefore, depression with mixed features can be present not only in MDD, but in both bipolar I and II.
New treatment algorithms
This dimensional approach of assessing mixed features along a continuum could lead to better and earlier diagnosis of bipolar depression and more targeted therapies, according to Dr. McIntyre. What he thinks it won’t do is lead to an overzealousness in the overdiagnosis of bipolar depression.
“That is false. We wouldn’t say we’re not going to diagnose bowel cancer because we hear it’s overdiagnosed. But to get the diagnoses right, what we need is fidelity to diagnostic criteria.”
Enter the state of Florida. As part of its best practices for psychotherapeutic use in adults, Florida is the first state to have published evidence-based guidelines for depression with mixed features. Dr. McIntyre is one of the guidelines’ coauthors.
Antidepressants bad, olanzapine worse
Some changes to treatment algorithms might come as a surprise. Despite being among the most commonly prescribed treatments for bipolar disorder, monotherapy with antidepressants is not approved in the guidelines. “Period,” said Dr. McIntyre. “Many patients do well on antidepressants, but the most common outcome is inefficacy.”
It might be better to combine an antidepressant with an atypical antipsychotic, or a mood stabilizer to avoid treatment-emergent mania, or, more commonly, destabilization in patients who are susceptible to subsyndromal mania, he said.
In addition to mitigating symptoms of a depressive episode, atypicals can help suppress hypomanic symptoms. Dr. McIntyre said this is critical to remember, because patients with these combinations of symptoms are “the very persons who shouldn’t get an antidepressant but are also the ones most likely to be prescribed them,” according to old ways of thinking.
As for maintenance in bipolar disorder, Dr. McIntyre believes the axiom, “What gets you well keeps you well,” is a good rule of thumb when going through the algorithm. “It’s not always true, but it’s almost always true.”
Management of MDD with mixed features includes the introduction of atypicals or mood stabilizers such as lithium or lamotrigine in patients with any prior history of hypomania or mania, something Dr. McIntyre said already is beginning to happen in practice.
Olanzapine monotherapy as a first-line treatment of bipolar disorder initially was “demoted” by Dr. McIntyre and his coauthors in Florida’s bipolar treatment guidelines. In the updated version, the atypical remains a second-line therapy behind lurasidone as the recommended first-line therapy because of olanzapine’s tendency to interfere with metabolic processes. Quetiapine also is a first-line therapy, but with the qualification that it, too, could interfere with metabolic processes. Combination therapy with olanzapine plus fluoxetine is second-line.
“Lurasidone does not have the metabolic changes of quetiapine. It doesn’t make sense to treat mania and then erase 25 years of a person’s life because of weight gain,” Dr. McIntyre said.
The average lifespan of people with bipolar disorder is about 20 years shorter than it is for those without serious mental illness.
Inflammation harms cognition
The changes are indicative of how seriously the field has begun to take metabolic disturbance as an adverse event in serious mental illness. Literature on obesity as a “psycho-toxin” is growing, and Dr. McIntyre is among the pioneers.
One study by Dr. McIntyre and his colleagues, currently in press, explores how obesity-related inflammation disturbs the brain’s dopamine system, resulting in interference with executive function. Because it is well established that people with bipolar disorder are more likely to be obese (J Affect Disord. 2008 Sep;110[1-2]:149-55), they also are more susceptible to cognitive impairment than are people of normal weight, according to Dr. McIntyre.
In a 2013 study, Dr. McIntyre and his colleagues showed that a first episode of mania in a person with obesity creates the same level of cognitive impairment as that found in the brains of normal-weight individuals who have experienced five episodes of mania (Psychological Med. 2014 Feb;44[3]:533-41). “There is something about obesity that is brain toxic,” he said.
Proof of concept of this is that cognitive outcomes for people before bariatric surgery are worse than postsurgery outcomes (Am J Surg. 2014 Jun;207[6]:870-6).
Systemic inflammation elevates levels of C-reactive protein, interleukin-1, and other cytokines, and interferes with insulin signaling; all have deleterious effects on cognition, as well as metabolic health. Those disturbances negatively affect emotional regulation, sleep, appetite, and sex drive, as well as executive function, he said.
“Inflammation is a convergent system, implicated across many brain- and body-based disorders. People with bipolar disorder not only have systemic increases in inflammation, but also neuroinflammation,” Dr. McIntyre said.
Accordingly, controlling inflammation becomes essential to chronic management of depression in general and bipolar in particular since, with each successive episode of untreated mania, patients’ ability to think clearly takes a hit. “Cognitive function is the principal determinant of psychosocial function, of workplace visibility, [and] of quality of life in most patient-reported outcomes,” Dr. McIntyre said.
Cognitive impairment also can lead to a worsening of the ability to balance reward and impulse control, leading to higher rates of substance abuse or other psychiatric comorbidities after onset of bipolar disease; a vicious cycle can ensue.
“As cognitive difficulties rise, comorbidities rise. But also, some of the comorbidities we see are reflections of cognitive impairment,” Dr. McIntyre said. To wit, binge eating disorder and bulimia nervosa are common in people with bipolar disorder (J Affect Disord. 2016 Feb;191:216-2).
Citing a recent scientific statement from the American Heart Association recommending that bipolar disorder and MDD should be considered tier II risk factors for cardiovascular disease among youth, the Florida guidelines urge clinicians to regularly screen patients for cardiometabolic disorders – not only for their medical implications but for their potential to flag emergent psychiatric issues.
Pharmacotherapeutics specifically targeting neuroinflammation are not yet ready for clinical practice, but Dr. McIntyre said other, more conventional therapies are available for bipolar disorder that have anti-inflammatory properties, including selective serotonin reuptake inhibitors and lithium. “Lithium is also anti-amyloid and has an anti-suicide effect. It is a drug I would definitely use as first line.”
Some behavioral therapies also are protective against inflammation and are recommended in the guidelines. Those include attention to sleep hygiene, diet, and exercise. “Social rhythm therapy is underutilized. These patients need their day organized. They need aerobics; they need sleep,” Dr. McIntyre said.
Future is now
Although the “whole-person” approach is still nascent – seeing depression as a collection of what Dr. McIntyre said are alterations in the neural circuitry amounting to a series of “disconnection syndromes” – psychiatry already has entered a new era where disease models are more comprehensive, he said.
This new way of thinking can connect the dots between why, for example, so many people with bipolar depression also have drug and alcohol abuse. It also could help explain why in bipolar there is so much obesity, or why there is so much anxiety, he said. “We’ve moved away from the rather silly, overly simplistic notions that you have too much or too little serotonin. Or that there was too much or too little dopamine causing mania. It made for convenient sound bytes, but it was probably just superstition we were gravitating to.”
The guidelines have been peer reviewed and will be published in the Journal of Clinical Psychiatry later this year, Dr. McIntyre said.
The meeting was held by Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.
Dr. McIntyre disclosed that he has numerous industry relationships, including with AstraZeneca, Eli Lilly, Janssen Ortho, Lundbeck, Pfizer, and Shire.
On Twitter @whitneymcknight
WASHINGTON – A sea change is underway in how major depressive and bipolar disorders are diagnosed and treated.
Historically, the absence of an accurate, comprehensive nosology of depression has led to much suffering and confusion. People with bipolar disorder in particular are either not diagnosed early enough or are not diagnosed with the correct “flavor” of depression, according to Roger S. McIntyre, MD, author of updated treatment guidelines for bipolar depression, and the first-ever treatment guidelines for mixed features in major depressive disorder. “Twenty years ago, we would have described bipolar as episodic breakthroughs of mania and depression, with well intervals in between,” Dr. McIntyre said at Summit in Neurology & Psychiatry. “But now, we’ve really changed our fundamental thinking about bipolar disorder.”
Although reasons for the evolution in thinking are many, one of the strongest currents of change flows from the 2013 publication of the DSM-5, according to Dr. McIntyre, professor of psychiatry and pharmacology at the University of Toronto, and head of the Mood Disorders Psychopharmacology Unit at University Health Network in Toronto.
“The DSM-5’s authors took a neo-Kraepelinian view that mood disorders are dimensional,” Dr. McIntyre said in an interview. As a result, there’s been a reversal of what he called the “social construct imposed upon the cosmos of mood disorders by the DSM-III that divided that world into either depression or bipolar disorder.”
This return to thinking of mood disorders as existing on a continuum, as psychiatrist Emil Kraepelin, MD, theorized around the turn of the last century, pivots on the decision to do away with mixed states and to instead add the mixed features specifier.
“The move to mixed features is the necessary bridge between bipolar disease and major depressive disorder,” Dr. McIntyre said in the interview.
Therefore, for a period of time between the 1980 publication of the DSM-III and the DSM-5, “real-world” presentations of subsyndromal, opposite-pole symptoms that are common in major depressive disorder (MDD) and in bipolar disorder were not accounted for.
In practical terms, the addition of mixed features means that a patient with mania who presents with subsyndromal depressive symptoms would be seen, for example, to have mania with mixed features. A patient with a depressive episode who presents with subsyndromal hypomanic symptoms would be seen to have depression with mixed features. Therefore, depression with mixed features can be present not only in MDD, but in both bipolar I and II.
New treatment algorithms
This dimensional approach of assessing mixed features along a continuum could lead to better and earlier diagnosis of bipolar depression and more targeted therapies, according to Dr. McIntyre. What he thinks it won’t do is lead to an overzealousness in the overdiagnosis of bipolar depression.
“That is false. We wouldn’t say we’re not going to diagnose bowel cancer because we hear it’s overdiagnosed. But to get the diagnoses right, what we need is fidelity to diagnostic criteria.”
Enter the state of Florida. As part of its best practices for psychotherapeutic use in adults, Florida is the first state to have published evidence-based guidelines for depression with mixed features. Dr. McIntyre is one of the guidelines’ coauthors.
Antidepressants bad, olanzapine worse
Some changes to treatment algorithms might come as a surprise. Despite being among the most commonly prescribed treatments for bipolar disorder, monotherapy with antidepressants is not approved in the guidelines. “Period,” said Dr. McIntyre. “Many patients do well on antidepressants, but the most common outcome is inefficacy.”
It might be better to combine an antidepressant with an atypical antipsychotic, or a mood stabilizer to avoid treatment-emergent mania, or, more commonly, destabilization in patients who are susceptible to subsyndromal mania, he said.
In addition to mitigating symptoms of a depressive episode, atypicals can help suppress hypomanic symptoms. Dr. McIntyre said this is critical to remember, because patients with these combinations of symptoms are “the very persons who shouldn’t get an antidepressant but are also the ones most likely to be prescribed them,” according to old ways of thinking.
As for maintenance in bipolar disorder, Dr. McIntyre believes the axiom, “What gets you well keeps you well,” is a good rule of thumb when going through the algorithm. “It’s not always true, but it’s almost always true.”
Management of MDD with mixed features includes the introduction of atypicals or mood stabilizers such as lithium or lamotrigine in patients with any prior history of hypomania or mania, something Dr. McIntyre said already is beginning to happen in practice.
Olanzapine monotherapy as a first-line treatment of bipolar disorder initially was “demoted” by Dr. McIntyre and his coauthors in Florida’s bipolar treatment guidelines. In the updated version, the atypical remains a second-line therapy behind lurasidone as the recommended first-line therapy because of olanzapine’s tendency to interfere with metabolic processes. Quetiapine also is a first-line therapy, but with the qualification that it, too, could interfere with metabolic processes. Combination therapy with olanzapine plus fluoxetine is second-line.
“Lurasidone does not have the metabolic changes of quetiapine. It doesn’t make sense to treat mania and then erase 25 years of a person’s life because of weight gain,” Dr. McIntyre said.
The average lifespan of people with bipolar disorder is about 20 years shorter than it is for those without serious mental illness.
Inflammation harms cognition
The changes are indicative of how seriously the field has begun to take metabolic disturbance as an adverse event in serious mental illness. Literature on obesity as a “psycho-toxin” is growing, and Dr. McIntyre is among the pioneers.
One study by Dr. McIntyre and his colleagues, currently in press, explores how obesity-related inflammation disturbs the brain’s dopamine system, resulting in interference with executive function. Because it is well established that people with bipolar disorder are more likely to be obese (J Affect Disord. 2008 Sep;110[1-2]:149-55), they also are more susceptible to cognitive impairment than are people of normal weight, according to Dr. McIntyre.
In a 2013 study, Dr. McIntyre and his colleagues showed that a first episode of mania in a person with obesity creates the same level of cognitive impairment as that found in the brains of normal-weight individuals who have experienced five episodes of mania (Psychological Med. 2014 Feb;44[3]:533-41). “There is something about obesity that is brain toxic,” he said.
Proof of concept of this is that cognitive outcomes for people before bariatric surgery are worse than postsurgery outcomes (Am J Surg. 2014 Jun;207[6]:870-6).
Systemic inflammation elevates levels of C-reactive protein, interleukin-1, and other cytokines, and interferes with insulin signaling; all have deleterious effects on cognition, as well as metabolic health. Those disturbances negatively affect emotional regulation, sleep, appetite, and sex drive, as well as executive function, he said.
“Inflammation is a convergent system, implicated across many brain- and body-based disorders. People with bipolar disorder not only have systemic increases in inflammation, but also neuroinflammation,” Dr. McIntyre said.
Accordingly, controlling inflammation becomes essential to chronic management of depression in general and bipolar in particular since, with each successive episode of untreated mania, patients’ ability to think clearly takes a hit. “Cognitive function is the principal determinant of psychosocial function, of workplace visibility, [and] of quality of life in most patient-reported outcomes,” Dr. McIntyre said.
Cognitive impairment also can lead to a worsening of the ability to balance reward and impulse control, leading to higher rates of substance abuse or other psychiatric comorbidities after onset of bipolar disease; a vicious cycle can ensue.
“As cognitive difficulties rise, comorbidities rise. But also, some of the comorbidities we see are reflections of cognitive impairment,” Dr. McIntyre said. To wit, binge eating disorder and bulimia nervosa are common in people with bipolar disorder (J Affect Disord. 2016 Feb;191:216-2).
Citing a recent scientific statement from the American Heart Association recommending that bipolar disorder and MDD should be considered tier II risk factors for cardiovascular disease among youth, the Florida guidelines urge clinicians to regularly screen patients for cardiometabolic disorders – not only for their medical implications but for their potential to flag emergent psychiatric issues.
Pharmacotherapeutics specifically targeting neuroinflammation are not yet ready for clinical practice, but Dr. McIntyre said other, more conventional therapies are available for bipolar disorder that have anti-inflammatory properties, including selective serotonin reuptake inhibitors and lithium. “Lithium is also anti-amyloid and has an anti-suicide effect. It is a drug I would definitely use as first line.”
Some behavioral therapies also are protective against inflammation and are recommended in the guidelines. Those include attention to sleep hygiene, diet, and exercise. “Social rhythm therapy is underutilized. These patients need their day organized. They need aerobics; they need sleep,” Dr. McIntyre said.
Future is now
Although the “whole-person” approach is still nascent – seeing depression as a collection of what Dr. McIntyre said are alterations in the neural circuitry amounting to a series of “disconnection syndromes” – psychiatry already has entered a new era where disease models are more comprehensive, he said.
This new way of thinking can connect the dots between why, for example, so many people with bipolar depression also have drug and alcohol abuse. It also could help explain why in bipolar there is so much obesity, or why there is so much anxiety, he said. “We’ve moved away from the rather silly, overly simplistic notions that you have too much or too little serotonin. Or that there was too much or too little dopamine causing mania. It made for convenient sound bytes, but it was probably just superstition we were gravitating to.”
The guidelines have been peer reviewed and will be published in the Journal of Clinical Psychiatry later this year, Dr. McIntyre said.
The meeting was held by Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.
Dr. McIntyre disclosed that he has numerous industry relationships, including with AstraZeneca, Eli Lilly, Janssen Ortho, Lundbeck, Pfizer, and Shire.
On Twitter @whitneymcknight
EXPERT ANALYSIS AT SUMMIT IN NEUROLOGY & PSYCHIATRY
Use simple algorithms to manage dementia
WASHINGTON – Alzheimer’s disease symptoms can be managed with simple algorithms that include ruling out other physiologic concerns and making some lifestyle modifications, according to an expert.
“These approaches are neither hopelessly complicated nor random,” Richard J. Caselli, MD, said at Summit in Neurology & Psychiatry, held by Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.
Key to diagnosis and management is to understand the differences between Alzheimer’s, dementia, and nondisabling cognitive impairment. “Alzheimer’s disease is the most common cause of dementia, but it is not synonymous with dementia,” said Dr. Caselli, a neurologist at the Mayo Clinic in Scottsdale, Ariz. “Dementia is not memory loss alone but the disabling impairment of multiple cognitive functions.”
Mild cognitive impairment typically means that a patient is still able to conduct his or her activities of daily living despite having memory (or other cognitive) problems.
Although it is possible for a traumatic event such as a family upset, hip replacement surgery, or an infection, to provoke signs of cognitive impairment, it is not usually “down to one day where all hell broke loose and ever since then, [the patient] hasn’t been the same,” Dr. Caselli said. “There are a lot of different reasons why a person can have cognitive difficulty, although with degenerative causes of dementia, it is a gradual onset problem.”
Alzheimer’s disease has a lengthy preclinical phase and can take as long as 15 years (or more) to finally present with symptoms of memory loss after onset, he added.
Changes in behavior, sleep
Behavioral changes in the patient, such as increasing paranoia, delusional states, aggression, and agitation, are an especially problematic aspect of the disease, Dr. Caselli said. Medications such as atypical and typical antipsychotics are off label, but can be effective in helping to manage psychosis and agitation, he said. Antipsychotic medications carry black box warnings from the Food and Drug Administration for use in the elderly, highlighting an increased risk of sudden death, especially in patients with underlying cardiac problems. Dr. Caselli said that, anecdotally, he had not yet seen any such severe adverse events when using atypical antipsychotics in this population, but vigilance should nonetheless be maintained. He also mentioned that pimavanserin, a selective serotonin 5-HT2A inverse agonist, recently was approved for psychosis in Parkinson’s disease, but that he so far has not had any personal experience with it.
Changes in sleep patterns also can offer clues to the type of dementia the patient may have. Pay close attention to the presence of any dream enactment behavior that may be a clue for REM sleep behavior disorder, which as been associated with Parkinson’s disease and dementia with Lewy bodies, according to Dr. Caselli.
Addressing other medical concerns such as restless legs syndrome, hypersomnolence, or nocturia can help patients get better sleep, and in turn, improve their overall disposition.
Physiologic concerns
Comorbid medical conditions such as a urinary tract infection, cancer, or end organ failure, as well as postoperative states and polypharmacy, also should be considered as potentially contributing to altered cognition. Although the physical exam for a person with Alzheimer’s disease tends to be normal, there are some types of dementia that might present with visual loss, aphasia, Parkinsonism, or signs of motor neuron disease, Dr. Caselli said.
Particularly in late-stage dementia, if patients have experienced a fracture or recently have had surgery, an abrupt decline in status could indicate they are in severe pain. “They aren’t going to be able to tell you that, though, and you will just have to be sensitive and attuned to that [possibility],” Dr. Caselli said.
Neuropsychological, other tests
A variety of widely available formal and informal tests can help evaluate a person’s orientation, learning and memory, and constructional and spatial abilities, such as accurately drawing the face of a clock. Language skills testing is important, particularly comprehension, which can be more subtle to detect but can prove key to the differential diagnosis and management.
Neuropsychological testing can reveal different patterns of cognitive impairment. For example, tests sensitive to mental or physical speed can help indicate whether a person has vascular dementia or Parkinson’s disease, two forms of impairment that involve slower cognition. Contrast this with people in the beginning stages of Alzheimer’s, who tend to be much less affected on such tests, Dr. Caselli said.
The conventional wisdom is that brain imaging often yields little diagnostic information in Alzheimer’s, but Dr. Caselli showed examples of tumors, strokes, focal atrophy, and amyloid angiopathy, as imaged abnormalities interfering with cognition. “Imaging in dementia is an important thing to do.”
Meanwhile, don’t ignore the basic lab tests such as blood counts, blood sugar, metabolic panels, and so forth. “Most of the time you don’t find these things, but sometimes you do,” Dr. Caselli said, noting that other clinical tests such as those used for a variety of encephalopathies or fungal infections also can be useful. “I am looking for something I can fix, not just reinforce that the 82-year-old man in front of me with a 2-year history of progressive memory loss has Alzheimer’s.”
There is a wide range of other differential diagnoses to consider testing for in the appropriate setting related to vascular, inflammatory, infectious, nutritional, neoplastic, metabolic, and other pathophysiologic processes. Just remember, it isn’t always Alzheimer’s, and because we can’t ‘fix’ Alzheimer’s, it’s important to make sure we have ruled out all other reasonable possibilities,” Dr. Caselli said. Keep in mind there is a lot of mixed pathology in dementia, he added.
Genetic testing can be important in patients with early-onset Alzheimer’s and a family history because there are several known disease-causing autosomal dominant mutations that, if identified in the patient, may have implications for first-degree relatives, including children. Young adult children have important life decisions to make that could be influenced by their own genetic status. Genetic testing is less likely to be helpful in patients with late-onset dementia with or without a family history, because the results will not alter management. Biomarkers can indicate the actual presence of pathology, but at this point, do not offer a reliable time frame for the evolution of symptoms, he said.
Dr. Caselli receives research funding from Merck as well as the National Institute on Aging.
On Twitter @whitneymcknight
WASHINGTON – Alzheimer’s disease symptoms can be managed with simple algorithms that include ruling out other physiologic concerns and making some lifestyle modifications, according to an expert.
“These approaches are neither hopelessly complicated nor random,” Richard J. Caselli, MD, said at Summit in Neurology & Psychiatry, held by Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.
Key to diagnosis and management is to understand the differences between Alzheimer’s, dementia, and nondisabling cognitive impairment. “Alzheimer’s disease is the most common cause of dementia, but it is not synonymous with dementia,” said Dr. Caselli, a neurologist at the Mayo Clinic in Scottsdale, Ariz. “Dementia is not memory loss alone but the disabling impairment of multiple cognitive functions.”
Mild cognitive impairment typically means that a patient is still able to conduct his or her activities of daily living despite having memory (or other cognitive) problems.
Although it is possible for a traumatic event such as a family upset, hip replacement surgery, or an infection, to provoke signs of cognitive impairment, it is not usually “down to one day where all hell broke loose and ever since then, [the patient] hasn’t been the same,” Dr. Caselli said. “There are a lot of different reasons why a person can have cognitive difficulty, although with degenerative causes of dementia, it is a gradual onset problem.”
Alzheimer’s disease has a lengthy preclinical phase and can take as long as 15 years (or more) to finally present with symptoms of memory loss after onset, he added.
Changes in behavior, sleep
Behavioral changes in the patient, such as increasing paranoia, delusional states, aggression, and agitation, are an especially problematic aspect of the disease, Dr. Caselli said. Medications such as atypical and typical antipsychotics are off label, but can be effective in helping to manage psychosis and agitation, he said. Antipsychotic medications carry black box warnings from the Food and Drug Administration for use in the elderly, highlighting an increased risk of sudden death, especially in patients with underlying cardiac problems. Dr. Caselli said that, anecdotally, he had not yet seen any such severe adverse events when using atypical antipsychotics in this population, but vigilance should nonetheless be maintained. He also mentioned that pimavanserin, a selective serotonin 5-HT2A inverse agonist, recently was approved for psychosis in Parkinson’s disease, but that he so far has not had any personal experience with it.
Changes in sleep patterns also can offer clues to the type of dementia the patient may have. Pay close attention to the presence of any dream enactment behavior that may be a clue for REM sleep behavior disorder, which as been associated with Parkinson’s disease and dementia with Lewy bodies, according to Dr. Caselli.
Addressing other medical concerns such as restless legs syndrome, hypersomnolence, or nocturia can help patients get better sleep, and in turn, improve their overall disposition.
Physiologic concerns
Comorbid medical conditions such as a urinary tract infection, cancer, or end organ failure, as well as postoperative states and polypharmacy, also should be considered as potentially contributing to altered cognition. Although the physical exam for a person with Alzheimer’s disease tends to be normal, there are some types of dementia that might present with visual loss, aphasia, Parkinsonism, or signs of motor neuron disease, Dr. Caselli said.
Particularly in late-stage dementia, if patients have experienced a fracture or recently have had surgery, an abrupt decline in status could indicate they are in severe pain. “They aren’t going to be able to tell you that, though, and you will just have to be sensitive and attuned to that [possibility],” Dr. Caselli said.
Neuropsychological, other tests
A variety of widely available formal and informal tests can help evaluate a person’s orientation, learning and memory, and constructional and spatial abilities, such as accurately drawing the face of a clock. Language skills testing is important, particularly comprehension, which can be more subtle to detect but can prove key to the differential diagnosis and management.
Neuropsychological testing can reveal different patterns of cognitive impairment. For example, tests sensitive to mental or physical speed can help indicate whether a person has vascular dementia or Parkinson’s disease, two forms of impairment that involve slower cognition. Contrast this with people in the beginning stages of Alzheimer’s, who tend to be much less affected on such tests, Dr. Caselli said.
The conventional wisdom is that brain imaging often yields little diagnostic information in Alzheimer’s, but Dr. Caselli showed examples of tumors, strokes, focal atrophy, and amyloid angiopathy, as imaged abnormalities interfering with cognition. “Imaging in dementia is an important thing to do.”
Meanwhile, don’t ignore the basic lab tests such as blood counts, blood sugar, metabolic panels, and so forth. “Most of the time you don’t find these things, but sometimes you do,” Dr. Caselli said, noting that other clinical tests such as those used for a variety of encephalopathies or fungal infections also can be useful. “I am looking for something I can fix, not just reinforce that the 82-year-old man in front of me with a 2-year history of progressive memory loss has Alzheimer’s.”
There is a wide range of other differential diagnoses to consider testing for in the appropriate setting related to vascular, inflammatory, infectious, nutritional, neoplastic, metabolic, and other pathophysiologic processes. Just remember, it isn’t always Alzheimer’s, and because we can’t ‘fix’ Alzheimer’s, it’s important to make sure we have ruled out all other reasonable possibilities,” Dr. Caselli said. Keep in mind there is a lot of mixed pathology in dementia, he added.
Genetic testing can be important in patients with early-onset Alzheimer’s and a family history because there are several known disease-causing autosomal dominant mutations that, if identified in the patient, may have implications for first-degree relatives, including children. Young adult children have important life decisions to make that could be influenced by their own genetic status. Genetic testing is less likely to be helpful in patients with late-onset dementia with or without a family history, because the results will not alter management. Biomarkers can indicate the actual presence of pathology, but at this point, do not offer a reliable time frame for the evolution of symptoms, he said.
Dr. Caselli receives research funding from Merck as well as the National Institute on Aging.
On Twitter @whitneymcknight
WASHINGTON – Alzheimer’s disease symptoms can be managed with simple algorithms that include ruling out other physiologic concerns and making some lifestyle modifications, according to an expert.
“These approaches are neither hopelessly complicated nor random,” Richard J. Caselli, MD, said at Summit in Neurology & Psychiatry, held by Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.
Key to diagnosis and management is to understand the differences between Alzheimer’s, dementia, and nondisabling cognitive impairment. “Alzheimer’s disease is the most common cause of dementia, but it is not synonymous with dementia,” said Dr. Caselli, a neurologist at the Mayo Clinic in Scottsdale, Ariz. “Dementia is not memory loss alone but the disabling impairment of multiple cognitive functions.”
Mild cognitive impairment typically means that a patient is still able to conduct his or her activities of daily living despite having memory (or other cognitive) problems.
Although it is possible for a traumatic event such as a family upset, hip replacement surgery, or an infection, to provoke signs of cognitive impairment, it is not usually “down to one day where all hell broke loose and ever since then, [the patient] hasn’t been the same,” Dr. Caselli said. “There are a lot of different reasons why a person can have cognitive difficulty, although with degenerative causes of dementia, it is a gradual onset problem.”
Alzheimer’s disease has a lengthy preclinical phase and can take as long as 15 years (or more) to finally present with symptoms of memory loss after onset, he added.
Changes in behavior, sleep
Behavioral changes in the patient, such as increasing paranoia, delusional states, aggression, and agitation, are an especially problematic aspect of the disease, Dr. Caselli said. Medications such as atypical and typical antipsychotics are off label, but can be effective in helping to manage psychosis and agitation, he said. Antipsychotic medications carry black box warnings from the Food and Drug Administration for use in the elderly, highlighting an increased risk of sudden death, especially in patients with underlying cardiac problems. Dr. Caselli said that, anecdotally, he had not yet seen any such severe adverse events when using atypical antipsychotics in this population, but vigilance should nonetheless be maintained. He also mentioned that pimavanserin, a selective serotonin 5-HT2A inverse agonist, recently was approved for psychosis in Parkinson’s disease, but that he so far has not had any personal experience with it.
Changes in sleep patterns also can offer clues to the type of dementia the patient may have. Pay close attention to the presence of any dream enactment behavior that may be a clue for REM sleep behavior disorder, which as been associated with Parkinson’s disease and dementia with Lewy bodies, according to Dr. Caselli.
Addressing other medical concerns such as restless legs syndrome, hypersomnolence, or nocturia can help patients get better sleep, and in turn, improve their overall disposition.
Physiologic concerns
Comorbid medical conditions such as a urinary tract infection, cancer, or end organ failure, as well as postoperative states and polypharmacy, also should be considered as potentially contributing to altered cognition. Although the physical exam for a person with Alzheimer’s disease tends to be normal, there are some types of dementia that might present with visual loss, aphasia, Parkinsonism, or signs of motor neuron disease, Dr. Caselli said.
Particularly in late-stage dementia, if patients have experienced a fracture or recently have had surgery, an abrupt decline in status could indicate they are in severe pain. “They aren’t going to be able to tell you that, though, and you will just have to be sensitive and attuned to that [possibility],” Dr. Caselli said.
Neuropsychological, other tests
A variety of widely available formal and informal tests can help evaluate a person’s orientation, learning and memory, and constructional and spatial abilities, such as accurately drawing the face of a clock. Language skills testing is important, particularly comprehension, which can be more subtle to detect but can prove key to the differential diagnosis and management.
Neuropsychological testing can reveal different patterns of cognitive impairment. For example, tests sensitive to mental or physical speed can help indicate whether a person has vascular dementia or Parkinson’s disease, two forms of impairment that involve slower cognition. Contrast this with people in the beginning stages of Alzheimer’s, who tend to be much less affected on such tests, Dr. Caselli said.
The conventional wisdom is that brain imaging often yields little diagnostic information in Alzheimer’s, but Dr. Caselli showed examples of tumors, strokes, focal atrophy, and amyloid angiopathy, as imaged abnormalities interfering with cognition. “Imaging in dementia is an important thing to do.”
Meanwhile, don’t ignore the basic lab tests such as blood counts, blood sugar, metabolic panels, and so forth. “Most of the time you don’t find these things, but sometimes you do,” Dr. Caselli said, noting that other clinical tests such as those used for a variety of encephalopathies or fungal infections also can be useful. “I am looking for something I can fix, not just reinforce that the 82-year-old man in front of me with a 2-year history of progressive memory loss has Alzheimer’s.”
There is a wide range of other differential diagnoses to consider testing for in the appropriate setting related to vascular, inflammatory, infectious, nutritional, neoplastic, metabolic, and other pathophysiologic processes. Just remember, it isn’t always Alzheimer’s, and because we can’t ‘fix’ Alzheimer’s, it’s important to make sure we have ruled out all other reasonable possibilities,” Dr. Caselli said. Keep in mind there is a lot of mixed pathology in dementia, he added.
Genetic testing can be important in patients with early-onset Alzheimer’s and a family history because there are several known disease-causing autosomal dominant mutations that, if identified in the patient, may have implications for first-degree relatives, including children. Young adult children have important life decisions to make that could be influenced by their own genetic status. Genetic testing is less likely to be helpful in patients with late-onset dementia with or without a family history, because the results will not alter management. Biomarkers can indicate the actual presence of pathology, but at this point, do not offer a reliable time frame for the evolution of symptoms, he said.
Dr. Caselli receives research funding from Merck as well as the National Institute on Aging.
On Twitter @whitneymcknight
EXPERT ANALYSIS AT SUMMIT IN NEUROLOGY & PSYCHIATRY
New data propel headache neuromodulation devices toward approval
WASHINGTON – Encouraging data on an external vagal nerve stimulator and a minimally invasive system that targets the sphenopalatine ganglion are propelling the two neuromodulation devices toward approval for headache, Stewart J. Tepper, MD, said at the Summit in Neurology & Psychiatry.
“This would bring to four the number of devices we now have available to us to treat headache,” said Dr. Tepper, director of research at the Dartmouth Headache Clinic, Lebanon, N.H. Two types are already available in the United States: a trigeminal nerve stimulator approved for migraine prevention and two brands of transcranial magnetic stimulators approved for acute treatment of migraine with aura.
Noninvasive vagal nerve stimulator
The gammaCore device (electroCore Medical) could be approved for cluster headache this year, Dr. Tepper said. A company spokesman said the company submitted its pivotal trial data to the Food and Drug Administration in 2015, but couldn’t offer any insight into how far the process has progressed.
“That application is currently under review, and we look forward to the FDA’s decision when it comes,” Eric Liebler, electroCore vice president for scientific, medical, and governmental affairs, said in an interview.
The gammaCore device is an external vagal nerve stimulator already approved in Canada and Europe for the treatment of primary headache disorders. In April 2016, it was approved in the United Kingdom as well, Dr. Tepper said at the meeting, sponsored by the Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.
The device is a small, handheld unit that the patient uses twice each day, and which transmits mild current to the vagal nerve. It’s activated over the carotid pulse point on the neck for about 90 seconds. It’s thought to work by suppressing excessive extracellular glutamate and suppressing cortical spreading depression, Dr. Tepper said.
The most recent data for the gammaCore device, presented at the annual meeting of the American Headache Society (AHS) in June, suggest that it could also be beneficial in chronic headache and in menstrual migraine.
A 12-week, open-label study of 51 women with menstrual migraine looked at pain intensity, analgesic use, and migraine disability. Women used the device prophylactically, six stimulations each day for 3 days before and after the onset of menstruation. The mean number of menstrual migraine days each month declined significantly from 7.2 to 4.7. About 40% of the group had at least a 50% reduction in migraine days. Pain intensity also decreased significantly, as well as did the number of doses of analgesics. There were significant improvements on both the Headache Impact Test and Migraine Disability Assessment. One subject discontinued treatment due to dizziness during stimulation.
An 8-week study on cluster headache was published in May and updated at the AHS meeting. Investigators randomized 87 patients with cluster headache to standard therapy alone or plus the gammaCore device. The PREVA (Prevention and Acute treatment of chronic cluster headache) study determined that dual therapy reduced the number of weekly attacks by four, compared with standard therapy. A total of 40% of patients experienced at least a 50% response rate, compared with 8% of controls. A subanalysis presented at the AHS meeting showed that 18% of the dual-therapy group experienced at least a 75% response rate.
Implantable sphenopalatine ganglion stimulator
Dr. Tepper is particularly excited about the Pulsante device, an implantable, wireless sphenopalatine ganglion (SPG) stimulator manufactured by Autonomic Technologies, which he called “a dramatic change in paradigm,” for the treatment of cluster headaches.
The system consists of a neurostimulator about the size of an almond and a lead with six electrodes. It’s inserted under local anesthetic via a small incision in the upper gum on the side in which the patient experiences symptoms. The electrodes are positioned along the SPG nerve and the neurostimulator is affixed to the zygomatic process.
A handheld wireless controller placed against the cheek activates the device and controls the intensity of stimulation, which is thought to work by blocking signals to the postganglionic parasympathetic fibers. Those fibers innervate facial structures and the cerebral and meningeal blood vessels and are implicated in the pain and accompanying autonomic symptoms of a cluster headache attack.
“You can literally see this device working right before your eyes,” he said. “Patients having a cluster attack will exhibit ptosis, red watering eyes, nose running, and as soon as the device is turned on, you see the lid come up, the eye turn white, and the tearing and runny nose stop. This is an objective correlate to a subjective pain response. It’s dramatic and exciting.”
The pivotal Pathway CH-1study that led to European Union approval was small – just 43 patients – but found that half the cluster attacks could be terminated within 15 minutes of onset. About half of the patients, who had a decades-long history of cluster headaches, experienced close to a 90% reduction in attack frequency.
The latest Pulsante data were also presented in June at the AHS meeting. Two papers – one with 24-month data from the pivotal trial, and one with 12-month data from an ongoing registry study – were overwhelmingly positive, Dr. Tepper said.
The 24-month follow-up data to the pivotal study found that 61% of patients experienced a therapeutic response to SPG stimulation. Most attacks (79%) responded to stimulation alone without the need for abortive therapy. Most patients (64%) also experienced clinical improvements in preventive medication use. Twenty-one were able to reduce or even eliminate the use of preventive medications.
The registry study provided data on 85 patients. Of these, 68% experienced at least a 50% reduction in attack frequency; some reported close to a 90% reduction. A third of patients actually experienced some period of remission, and some patients who were not initially responders became responders after a year of treatment. Acute medication use declined by 52% overall and by 82% in those considered therapeutic responders.
“These data are extremely encouraging,” Dr. Tepper said.
Adverse events are minimal and most are related to implantation. A safety study of 99 patients found that adverse events included sensory disbranch, pain, and swelling, which resolved in 90 days.
The U.S. Pathway CH-2 Cluster Headache Study is now underway and aims to enroll 120 patients. “If the data are positive on this, the company will go ahead and pursue U.S. approval,” Dr. Tepper said.
Dr. Tepper has received personal remuneration and research funding from a number of pharmaceutical companies. He holds stock in Autonomic Technologies.
On Twitter @alz_gal
WASHINGTON – Encouraging data on an external vagal nerve stimulator and a minimally invasive system that targets the sphenopalatine ganglion are propelling the two neuromodulation devices toward approval for headache, Stewart J. Tepper, MD, said at the Summit in Neurology & Psychiatry.
“This would bring to four the number of devices we now have available to us to treat headache,” said Dr. Tepper, director of research at the Dartmouth Headache Clinic, Lebanon, N.H. Two types are already available in the United States: a trigeminal nerve stimulator approved for migraine prevention and two brands of transcranial magnetic stimulators approved for acute treatment of migraine with aura.
Noninvasive vagal nerve stimulator
The gammaCore device (electroCore Medical) could be approved for cluster headache this year, Dr. Tepper said. A company spokesman said the company submitted its pivotal trial data to the Food and Drug Administration in 2015, but couldn’t offer any insight into how far the process has progressed.
“That application is currently under review, and we look forward to the FDA’s decision when it comes,” Eric Liebler, electroCore vice president for scientific, medical, and governmental affairs, said in an interview.
The gammaCore device is an external vagal nerve stimulator already approved in Canada and Europe for the treatment of primary headache disorders. In April 2016, it was approved in the United Kingdom as well, Dr. Tepper said at the meeting, sponsored by the Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.
The device is a small, handheld unit that the patient uses twice each day, and which transmits mild current to the vagal nerve. It’s activated over the carotid pulse point on the neck for about 90 seconds. It’s thought to work by suppressing excessive extracellular glutamate and suppressing cortical spreading depression, Dr. Tepper said.
The most recent data for the gammaCore device, presented at the annual meeting of the American Headache Society (AHS) in June, suggest that it could also be beneficial in chronic headache and in menstrual migraine.
A 12-week, open-label study of 51 women with menstrual migraine looked at pain intensity, analgesic use, and migraine disability. Women used the device prophylactically, six stimulations each day for 3 days before and after the onset of menstruation. The mean number of menstrual migraine days each month declined significantly from 7.2 to 4.7. About 40% of the group had at least a 50% reduction in migraine days. Pain intensity also decreased significantly, as well as did the number of doses of analgesics. There were significant improvements on both the Headache Impact Test and Migraine Disability Assessment. One subject discontinued treatment due to dizziness during stimulation.
An 8-week study on cluster headache was published in May and updated at the AHS meeting. Investigators randomized 87 patients with cluster headache to standard therapy alone or plus the gammaCore device. The PREVA (Prevention and Acute treatment of chronic cluster headache) study determined that dual therapy reduced the number of weekly attacks by four, compared with standard therapy. A total of 40% of patients experienced at least a 50% response rate, compared with 8% of controls. A subanalysis presented at the AHS meeting showed that 18% of the dual-therapy group experienced at least a 75% response rate.
Implantable sphenopalatine ganglion stimulator
Dr. Tepper is particularly excited about the Pulsante device, an implantable, wireless sphenopalatine ganglion (SPG) stimulator manufactured by Autonomic Technologies, which he called “a dramatic change in paradigm,” for the treatment of cluster headaches.
The system consists of a neurostimulator about the size of an almond and a lead with six electrodes. It’s inserted under local anesthetic via a small incision in the upper gum on the side in which the patient experiences symptoms. The electrodes are positioned along the SPG nerve and the neurostimulator is affixed to the zygomatic process.
A handheld wireless controller placed against the cheek activates the device and controls the intensity of stimulation, which is thought to work by blocking signals to the postganglionic parasympathetic fibers. Those fibers innervate facial structures and the cerebral and meningeal blood vessels and are implicated in the pain and accompanying autonomic symptoms of a cluster headache attack.
“You can literally see this device working right before your eyes,” he said. “Patients having a cluster attack will exhibit ptosis, red watering eyes, nose running, and as soon as the device is turned on, you see the lid come up, the eye turn white, and the tearing and runny nose stop. This is an objective correlate to a subjective pain response. It’s dramatic and exciting.”
The pivotal Pathway CH-1study that led to European Union approval was small – just 43 patients – but found that half the cluster attacks could be terminated within 15 minutes of onset. About half of the patients, who had a decades-long history of cluster headaches, experienced close to a 90% reduction in attack frequency.
The latest Pulsante data were also presented in June at the AHS meeting. Two papers – one with 24-month data from the pivotal trial, and one with 12-month data from an ongoing registry study – were overwhelmingly positive, Dr. Tepper said.
The 24-month follow-up data to the pivotal study found that 61% of patients experienced a therapeutic response to SPG stimulation. Most attacks (79%) responded to stimulation alone without the need for abortive therapy. Most patients (64%) also experienced clinical improvements in preventive medication use. Twenty-one were able to reduce or even eliminate the use of preventive medications.
The registry study provided data on 85 patients. Of these, 68% experienced at least a 50% reduction in attack frequency; some reported close to a 90% reduction. A third of patients actually experienced some period of remission, and some patients who were not initially responders became responders after a year of treatment. Acute medication use declined by 52% overall and by 82% in those considered therapeutic responders.
“These data are extremely encouraging,” Dr. Tepper said.
Adverse events are minimal and most are related to implantation. A safety study of 99 patients found that adverse events included sensory disbranch, pain, and swelling, which resolved in 90 days.
The U.S. Pathway CH-2 Cluster Headache Study is now underway and aims to enroll 120 patients. “If the data are positive on this, the company will go ahead and pursue U.S. approval,” Dr. Tepper said.
Dr. Tepper has received personal remuneration and research funding from a number of pharmaceutical companies. He holds stock in Autonomic Technologies.
On Twitter @alz_gal
WASHINGTON – Encouraging data on an external vagal nerve stimulator and a minimally invasive system that targets the sphenopalatine ganglion are propelling the two neuromodulation devices toward approval for headache, Stewart J. Tepper, MD, said at the Summit in Neurology & Psychiatry.
“This would bring to four the number of devices we now have available to us to treat headache,” said Dr. Tepper, director of research at the Dartmouth Headache Clinic, Lebanon, N.H. Two types are already available in the United States: a trigeminal nerve stimulator approved for migraine prevention and two brands of transcranial magnetic stimulators approved for acute treatment of migraine with aura.
Noninvasive vagal nerve stimulator
The gammaCore device (electroCore Medical) could be approved for cluster headache this year, Dr. Tepper said. A company spokesman said the company submitted its pivotal trial data to the Food and Drug Administration in 2015, but couldn’t offer any insight into how far the process has progressed.
“That application is currently under review, and we look forward to the FDA’s decision when it comes,” Eric Liebler, electroCore vice president for scientific, medical, and governmental affairs, said in an interview.
The gammaCore device is an external vagal nerve stimulator already approved in Canada and Europe for the treatment of primary headache disorders. In April 2016, it was approved in the United Kingdom as well, Dr. Tepper said at the meeting, sponsored by the Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.
The device is a small, handheld unit that the patient uses twice each day, and which transmits mild current to the vagal nerve. It’s activated over the carotid pulse point on the neck for about 90 seconds. It’s thought to work by suppressing excessive extracellular glutamate and suppressing cortical spreading depression, Dr. Tepper said.
The most recent data for the gammaCore device, presented at the annual meeting of the American Headache Society (AHS) in June, suggest that it could also be beneficial in chronic headache and in menstrual migraine.
A 12-week, open-label study of 51 women with menstrual migraine looked at pain intensity, analgesic use, and migraine disability. Women used the device prophylactically, six stimulations each day for 3 days before and after the onset of menstruation. The mean number of menstrual migraine days each month declined significantly from 7.2 to 4.7. About 40% of the group had at least a 50% reduction in migraine days. Pain intensity also decreased significantly, as well as did the number of doses of analgesics. There were significant improvements on both the Headache Impact Test and Migraine Disability Assessment. One subject discontinued treatment due to dizziness during stimulation.
An 8-week study on cluster headache was published in May and updated at the AHS meeting. Investigators randomized 87 patients with cluster headache to standard therapy alone or plus the gammaCore device. The PREVA (Prevention and Acute treatment of chronic cluster headache) study determined that dual therapy reduced the number of weekly attacks by four, compared with standard therapy. A total of 40% of patients experienced at least a 50% response rate, compared with 8% of controls. A subanalysis presented at the AHS meeting showed that 18% of the dual-therapy group experienced at least a 75% response rate.
Implantable sphenopalatine ganglion stimulator
Dr. Tepper is particularly excited about the Pulsante device, an implantable, wireless sphenopalatine ganglion (SPG) stimulator manufactured by Autonomic Technologies, which he called “a dramatic change in paradigm,” for the treatment of cluster headaches.
The system consists of a neurostimulator about the size of an almond and a lead with six electrodes. It’s inserted under local anesthetic via a small incision in the upper gum on the side in which the patient experiences symptoms. The electrodes are positioned along the SPG nerve and the neurostimulator is affixed to the zygomatic process.
A handheld wireless controller placed against the cheek activates the device and controls the intensity of stimulation, which is thought to work by blocking signals to the postganglionic parasympathetic fibers. Those fibers innervate facial structures and the cerebral and meningeal blood vessels and are implicated in the pain and accompanying autonomic symptoms of a cluster headache attack.
“You can literally see this device working right before your eyes,” he said. “Patients having a cluster attack will exhibit ptosis, red watering eyes, nose running, and as soon as the device is turned on, you see the lid come up, the eye turn white, and the tearing and runny nose stop. This is an objective correlate to a subjective pain response. It’s dramatic and exciting.”
The pivotal Pathway CH-1study that led to European Union approval was small – just 43 patients – but found that half the cluster attacks could be terminated within 15 minutes of onset. About half of the patients, who had a decades-long history of cluster headaches, experienced close to a 90% reduction in attack frequency.
The latest Pulsante data were also presented in June at the AHS meeting. Two papers – one with 24-month data from the pivotal trial, and one with 12-month data from an ongoing registry study – were overwhelmingly positive, Dr. Tepper said.
The 24-month follow-up data to the pivotal study found that 61% of patients experienced a therapeutic response to SPG stimulation. Most attacks (79%) responded to stimulation alone without the need for abortive therapy. Most patients (64%) also experienced clinical improvements in preventive medication use. Twenty-one were able to reduce or even eliminate the use of preventive medications.
The registry study provided data on 85 patients. Of these, 68% experienced at least a 50% reduction in attack frequency; some reported close to a 90% reduction. A third of patients actually experienced some period of remission, and some patients who were not initially responders became responders after a year of treatment. Acute medication use declined by 52% overall and by 82% in those considered therapeutic responders.
“These data are extremely encouraging,” Dr. Tepper said.
Adverse events are minimal and most are related to implantation. A safety study of 99 patients found that adverse events included sensory disbranch, pain, and swelling, which resolved in 90 days.
The U.S. Pathway CH-2 Cluster Headache Study is now underway and aims to enroll 120 patients. “If the data are positive on this, the company will go ahead and pursue U.S. approval,” Dr. Tepper said.
Dr. Tepper has received personal remuneration and research funding from a number of pharmaceutical companies. He holds stock in Autonomic Technologies.
On Twitter @alz_gal
AT SUMMIT IN NEUROLOGY & PSYCHIATRY
Maximize depression treatment efforts with measurement-based care
WASHINGTON – Challenging patients with depression to stay engaged in their recovery while rigorously monitoring and measuring their treatment response can mean the difference between remission or resistance, according to an expert.
“We all wish for better treatments, but we really don’t have any coming available to us in the near future, so our task is to do as well as we can with what we have,” Michael E. Thase, MD, professor of psychiatry at the University of Pennsylvania, Philadelphia, said at Summit in Neurology & Psychiatry.
“We know far too well that there is a large gap between what we might be able to accomplish and what actually happens in clinical practice,” Dr. Thase said.
To close that gap, start with evaluating what can be done to combat patient nonadherence. A 2007 study indicated that just under 20% of patients adhere to antidepressant medication guidelines (Prim Care Companion J Clin Psychiatry. 2007;9[2]:91-9.), and according to Dr. Thase, less than 10% of patients being seen for depression in primary care actually fill their prescriptions.
“Don’t delude yourself that these patients drop out of treatment because they no longer need it. They drop out mostly because they have gotten disgusted, disappointed, or discouraged,” said Dr. Thase, attributing the high rate of nonadherence to the nature of depression itself.
“Depression is a state of pessimism, low confidence, and of not really feeling capable.”
Helping patients overcome their reluctance to follow treatment guidelines begins with accurately assessing their symptom severity. Patients who rate 4 or less on the Patient Health Questionnaire–9 (PHQ-9), which is based on the DSM-IV, are considered in remission or not to have severe depression. Similarly, patients who score 5 or less on the Quick Inventory of Depressive Symptomatology (QIDS) are not considered in the danger zone.
The severity ratings included in the DSM-5 can help clinicians pinpoint the level of depression a patient is experiencing, as can a therapeutic relationship with the patient and the family, Dr. Thase said at the summit, held by Global Academy for Medical Education.
He urged clinicians to monitor adherence routinely by asking patients whether or not they have filled or refilled their prescriptions. It is helpful to ask patients about missing doses and whether they are feeling any improvement, he said.
“It’s a very simple process: You keep track of the patients. Chase after them if they don’t follow through. If you’re not keeping track, the patients think [what they do] doesn’t matter,” Dr. Thase said.
A 2010 study of chronic depression treatment in primary care practices showed that compared with regular care, aggressive monitoring of patient adherence and outcomes in 728 adults with depression resulted in better remission rates across 18 months of treatment. At 6 months 43.4% of patients who had been contacted regularly by nursing and social worker staff were in remission, compared with 33.3% of the 78 who had received regular care (P = .11). At 12 months, the results were 52% vs. 33.9% (P = .012), and at 18 months remission was reported in 49.2% vs. 27.3% (P = .004) (Ann Fam Med. 2010 Sep;8[5]:387-96).
By being alert to side effects, using a rating scale to measure symptom reduction, and not staying “locked” into the idea that all treatments require 6-8 weeks before patients see any improvement, clinicians can boost chances for adherence – and thus for remission – since patients who don’t improve in the first 2 weeks have just a 15% chance for improvement, Dr. Thase said. “You need 6-8 weeks to get to the maximum titration. That old 8-week rule applies mostly to patients who are showing improvement by week 2.”
If by week 2, the patient is not tolerating the medication’s side effects and has no symptom reduction, then move on to the next medication, Dr. Thase said, emphasizing the importance of seeing patients at least twice monthly. “If we’re only seeing a patient once a month, we’ve already fallen behind in the up-titration part, and we’ve missed the opportunity for early intervention if the patient is having side effects.”
Algorithms for choosing depression treatments should be a “fact of life,” he said. Start with the safest, easiest to tolerate, and least expensive of the available antidepressants, such as escitalopram and fluoxetine before working through the second- and third-line therapies and adjunctive therapies, all of which have greater risk profiles as you move through them. This algorithmic approach has been shown to result in patients scoring at least 10 points higher on a depression rating scale (JAMA Psychiatry. 2004;61:[7]669-80), which Dr. Thase said is equivalent to about a 30% higher chance of remission. “Don’t go over and over with the simple treatments that aren’t [evoking] a response. Move briskly on to the more complex treatments until patients respond.”
Treatment algorithms can include psychotherapies, either in combination with pharmacotherapy or as monotherapy. He encouraged clinicians to refer to the American Psychiatric Association (APA) practice guideline for depression for more details. The absence of depressive symptoms alone is not indicative of remission, according to the guideline, which Dr. Thase coauthored. The presence of positive emotions and resilience, along with a sense of control over emotions and hope for the future, indicates remission.
If after applying those methods a patient remains depressed and has been negatively screened for bipolar disorder, the use of tricyclics or monoamine oxidase inhibitors (MAOIs) may be appropriate. “MAOIs account for less than 1 in every 1,000 prescriptions for antidepressants, yet for people who don’t respond to modern antidepressants, they still can carry a 30%-40% response rate. So, if you don’t prescribe them yourself, please get access to someone who does,” Dr. Thase said.
The tenets of measurement-based care are essentially the lessons learned from the landmark Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, which sought to address how pharmacologic care for depression could be delivered based on adequate dosing, attenuation of symptoms, fewer side effects, and other factors (Am J Psychiatry. 2006;163:1905-17).
Now,10 years later, measurement-based treatment is still finding its way into practice, Dr. Thase said in an interview. “But, there’s no reason to be unduly pessimistic. Ten years ago, depression screening was in the same position, and now it is both considered to be the standard of care and is widely done.”
Dr. Thase reported having extensive industry relationships, noting that he has been involved in the development of nearly every drug for the treatment of mood disorders. Global Academy and this news organization are owned by the same company.
On Twitter @whitneymcknight
Ten years ago, the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study highlighted the importance of close monitoring of patients with depression. This is best done with a team-based approach; it’s best suited to handle issues of compliance, side effects, efficacy, and close follow-up. The team may consist of a psychotherapist, nurse, and, possibly, a pharmacist – in addition to the internist, Nitin S. Damle, MD, said in an interview.
 |
| Courtesy American College of Physicians Dr. Nitin S. Damle |
Integrating behavioral health into primary care practices involves structure, which includes office visits – even every 2 weeks until stable – follow-up phone calls by the nurse to assess adherence and problems with medication, and a pharmacist to track refill rates and side effects, and to recommend changes to medication due to lack of efficacy or side effects, he said.
Treatment algorithms are an effective means to find the most effective and safest medication, and screening with PHQ-9 and even QIDS has become more common in the primary care office. Still, the adaption of measurement-based care has been slow, partly because of the absence of adequate funding for an integrated primary care team-based approach to mental illness. Now there is no mechanism to cover the costs of personnel and infrastructure to provide for the level of monitoring and treatment that measurement-based care requires, according to Dr. Damle.
Health plans need to review the evidence, such as that from the STAR*D and other studies, and create funding mechanisms so that their members stay healthy and avoid complications of mental illness.
Dr. Damle is president of the American College of Physicians and clinical associate professor of medicine at Brown University, Providence, R.I. He has no relevant disclosures.
Ten years ago, the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study highlighted the importance of close monitoring of patients with depression. This is best done with a team-based approach; it’s best suited to handle issues of compliance, side effects, efficacy, and close follow-up. The team may consist of a psychotherapist, nurse, and, possibly, a pharmacist – in addition to the internist, Nitin S. Damle, MD, said in an interview.
|
| Courtesy American College of Physicians Dr. Nitin S. Damle |
Integrating behavioral health into primary care practices involves structure, which includes office visits – even every 2 weeks until stable – follow-up phone calls by the nurse to assess adherence and problems with medication, and a pharmacist to track refill rates and side effects, and to recommend changes to medication due to lack of efficacy or side effects, he said.
Treatment algorithms are an effective means to find the most effective and safest medication, and screening with PHQ-9 and even QIDS has become more common in the primary care office. Still, the adaption of measurement-based care has been slow, partly because of the absence of adequate funding for an integrated primary care team-based approach to mental illness. Now there is no mechanism to cover the costs of personnel and infrastructure to provide for the level of monitoring and treatment that measurement-based care requires, according to Dr. Damle.
Health plans need to review the evidence, such as that from the STAR*D and other studies, and create funding mechanisms so that their members stay healthy and avoid complications of mental illness.
Dr. Damle is president of the American College of Physicians and clinical associate professor of medicine at Brown University, Providence, R.I. He has no relevant disclosures.
Ten years ago, the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study highlighted the importance of close monitoring of patients with depression. This is best done with a team-based approach; it’s best suited to handle issues of compliance, side effects, efficacy, and close follow-up. The team may consist of a psychotherapist, nurse, and, possibly, a pharmacist – in addition to the internist, Nitin S. Damle, MD, said in an interview.
|
| Courtesy American College of Physicians Dr. Nitin S. Damle |
Integrating behavioral health into primary care practices involves structure, which includes office visits – even every 2 weeks until stable – follow-up phone calls by the nurse to assess adherence and problems with medication, and a pharmacist to track refill rates and side effects, and to recommend changes to medication due to lack of efficacy or side effects, he said.
Treatment algorithms are an effective means to find the most effective and safest medication, and screening with PHQ-9 and even QIDS has become more common in the primary care office. Still, the adaption of measurement-based care has been slow, partly because of the absence of adequate funding for an integrated primary care team-based approach to mental illness. Now there is no mechanism to cover the costs of personnel and infrastructure to provide for the level of monitoring and treatment that measurement-based care requires, according to Dr. Damle.
Health plans need to review the evidence, such as that from the STAR*D and other studies, and create funding mechanisms so that their members stay healthy and avoid complications of mental illness.
Dr. Damle is president of the American College of Physicians and clinical associate professor of medicine at Brown University, Providence, R.I. He has no relevant disclosures.
WASHINGTON – Challenging patients with depression to stay engaged in their recovery while rigorously monitoring and measuring their treatment response can mean the difference between remission or resistance, according to an expert.
“We all wish for better treatments, but we really don’t have any coming available to us in the near future, so our task is to do as well as we can with what we have,” Michael E. Thase, MD, professor of psychiatry at the University of Pennsylvania, Philadelphia, said at Summit in Neurology & Psychiatry.
“We know far too well that there is a large gap between what we might be able to accomplish and what actually happens in clinical practice,” Dr. Thase said.
To close that gap, start with evaluating what can be done to combat patient nonadherence. A 2007 study indicated that just under 20% of patients adhere to antidepressant medication guidelines (Prim Care Companion J Clin Psychiatry. 2007;9[2]:91-9.), and according to Dr. Thase, less than 10% of patients being seen for depression in primary care actually fill their prescriptions.
“Don’t delude yourself that these patients drop out of treatment because they no longer need it. They drop out mostly because they have gotten disgusted, disappointed, or discouraged,” said Dr. Thase, attributing the high rate of nonadherence to the nature of depression itself.
“Depression is a state of pessimism, low confidence, and of not really feeling capable.”
Helping patients overcome their reluctance to follow treatment guidelines begins with accurately assessing their symptom severity. Patients who rate 4 or less on the Patient Health Questionnaire–9 (PHQ-9), which is based on the DSM-IV, are considered in remission or not to have severe depression. Similarly, patients who score 5 or less on the Quick Inventory of Depressive Symptomatology (QIDS) are not considered in the danger zone.
The severity ratings included in the DSM-5 can help clinicians pinpoint the level of depression a patient is experiencing, as can a therapeutic relationship with the patient and the family, Dr. Thase said at the summit, held by Global Academy for Medical Education.
He urged clinicians to monitor adherence routinely by asking patients whether or not they have filled or refilled their prescriptions. It is helpful to ask patients about missing doses and whether they are feeling any improvement, he said.
“It’s a very simple process: You keep track of the patients. Chase after them if they don’t follow through. If you’re not keeping track, the patients think [what they do] doesn’t matter,” Dr. Thase said.
A 2010 study of chronic depression treatment in primary care practices showed that compared with regular care, aggressive monitoring of patient adherence and outcomes in 728 adults with depression resulted in better remission rates across 18 months of treatment. At 6 months 43.4% of patients who had been contacted regularly by nursing and social worker staff were in remission, compared with 33.3% of the 78 who had received regular care (P = .11). At 12 months, the results were 52% vs. 33.9% (P = .012), and at 18 months remission was reported in 49.2% vs. 27.3% (P = .004) (Ann Fam Med. 2010 Sep;8[5]:387-96).
By being alert to side effects, using a rating scale to measure symptom reduction, and not staying “locked” into the idea that all treatments require 6-8 weeks before patients see any improvement, clinicians can boost chances for adherence – and thus for remission – since patients who don’t improve in the first 2 weeks have just a 15% chance for improvement, Dr. Thase said. “You need 6-8 weeks to get to the maximum titration. That old 8-week rule applies mostly to patients who are showing improvement by week 2.”
If by week 2, the patient is not tolerating the medication’s side effects and has no symptom reduction, then move on to the next medication, Dr. Thase said, emphasizing the importance of seeing patients at least twice monthly. “If we’re only seeing a patient once a month, we’ve already fallen behind in the up-titration part, and we’ve missed the opportunity for early intervention if the patient is having side effects.”
Algorithms for choosing depression treatments should be a “fact of life,” he said. Start with the safest, easiest to tolerate, and least expensive of the available antidepressants, such as escitalopram and fluoxetine before working through the second- and third-line therapies and adjunctive therapies, all of which have greater risk profiles as you move through them. This algorithmic approach has been shown to result in patients scoring at least 10 points higher on a depression rating scale (JAMA Psychiatry. 2004;61:[7]669-80), which Dr. Thase said is equivalent to about a 30% higher chance of remission. “Don’t go over and over with the simple treatments that aren’t [evoking] a response. Move briskly on to the more complex treatments until patients respond.”
Treatment algorithms can include psychotherapies, either in combination with pharmacotherapy or as monotherapy. He encouraged clinicians to refer to the American Psychiatric Association (APA) practice guideline for depression for more details. The absence of depressive symptoms alone is not indicative of remission, according to the guideline, which Dr. Thase coauthored. The presence of positive emotions and resilience, along with a sense of control over emotions and hope for the future, indicates remission.
If after applying those methods a patient remains depressed and has been negatively screened for bipolar disorder, the use of tricyclics or monoamine oxidase inhibitors (MAOIs) may be appropriate. “MAOIs account for less than 1 in every 1,000 prescriptions for antidepressants, yet for people who don’t respond to modern antidepressants, they still can carry a 30%-40% response rate. So, if you don’t prescribe them yourself, please get access to someone who does,” Dr. Thase said.
The tenets of measurement-based care are essentially the lessons learned from the landmark Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, which sought to address how pharmacologic care for depression could be delivered based on adequate dosing, attenuation of symptoms, fewer side effects, and other factors (Am J Psychiatry. 2006;163:1905-17).
Now,10 years later, measurement-based treatment is still finding its way into practice, Dr. Thase said in an interview. “But, there’s no reason to be unduly pessimistic. Ten years ago, depression screening was in the same position, and now it is both considered to be the standard of care and is widely done.”
Dr. Thase reported having extensive industry relationships, noting that he has been involved in the development of nearly every drug for the treatment of mood disorders. Global Academy and this news organization are owned by the same company.
On Twitter @whitneymcknight
WASHINGTON – Challenging patients with depression to stay engaged in their recovery while rigorously monitoring and measuring their treatment response can mean the difference between remission or resistance, according to an expert.
“We all wish for better treatments, but we really don’t have any coming available to us in the near future, so our task is to do as well as we can with what we have,” Michael E. Thase, MD, professor of psychiatry at the University of Pennsylvania, Philadelphia, said at Summit in Neurology & Psychiatry.
“We know far too well that there is a large gap between what we might be able to accomplish and what actually happens in clinical practice,” Dr. Thase said.
To close that gap, start with evaluating what can be done to combat patient nonadherence. A 2007 study indicated that just under 20% of patients adhere to antidepressant medication guidelines (Prim Care Companion J Clin Psychiatry. 2007;9[2]:91-9.), and according to Dr. Thase, less than 10% of patients being seen for depression in primary care actually fill their prescriptions.
“Don’t delude yourself that these patients drop out of treatment because they no longer need it. They drop out mostly because they have gotten disgusted, disappointed, or discouraged,” said Dr. Thase, attributing the high rate of nonadherence to the nature of depression itself.
“Depression is a state of pessimism, low confidence, and of not really feeling capable.”
Helping patients overcome their reluctance to follow treatment guidelines begins with accurately assessing their symptom severity. Patients who rate 4 or less on the Patient Health Questionnaire–9 (PHQ-9), which is based on the DSM-IV, are considered in remission or not to have severe depression. Similarly, patients who score 5 or less on the Quick Inventory of Depressive Symptomatology (QIDS) are not considered in the danger zone.
The severity ratings included in the DSM-5 can help clinicians pinpoint the level of depression a patient is experiencing, as can a therapeutic relationship with the patient and the family, Dr. Thase said at the summit, held by Global Academy for Medical Education.
He urged clinicians to monitor adherence routinely by asking patients whether or not they have filled or refilled their prescriptions. It is helpful to ask patients about missing doses and whether they are feeling any improvement, he said.
“It’s a very simple process: You keep track of the patients. Chase after them if they don’t follow through. If you’re not keeping track, the patients think [what they do] doesn’t matter,” Dr. Thase said.
A 2010 study of chronic depression treatment in primary care practices showed that compared with regular care, aggressive monitoring of patient adherence and outcomes in 728 adults with depression resulted in better remission rates across 18 months of treatment. At 6 months 43.4% of patients who had been contacted regularly by nursing and social worker staff were in remission, compared with 33.3% of the 78 who had received regular care (P = .11). At 12 months, the results were 52% vs. 33.9% (P = .012), and at 18 months remission was reported in 49.2% vs. 27.3% (P = .004) (Ann Fam Med. 2010 Sep;8[5]:387-96).
By being alert to side effects, using a rating scale to measure symptom reduction, and not staying “locked” into the idea that all treatments require 6-8 weeks before patients see any improvement, clinicians can boost chances for adherence – and thus for remission – since patients who don’t improve in the first 2 weeks have just a 15% chance for improvement, Dr. Thase said. “You need 6-8 weeks to get to the maximum titration. That old 8-week rule applies mostly to patients who are showing improvement by week 2.”
If by week 2, the patient is not tolerating the medication’s side effects and has no symptom reduction, then move on to the next medication, Dr. Thase said, emphasizing the importance of seeing patients at least twice monthly. “If we’re only seeing a patient once a month, we’ve already fallen behind in the up-titration part, and we’ve missed the opportunity for early intervention if the patient is having side effects.”
Algorithms for choosing depression treatments should be a “fact of life,” he said. Start with the safest, easiest to tolerate, and least expensive of the available antidepressants, such as escitalopram and fluoxetine before working through the second- and third-line therapies and adjunctive therapies, all of which have greater risk profiles as you move through them. This algorithmic approach has been shown to result in patients scoring at least 10 points higher on a depression rating scale (JAMA Psychiatry. 2004;61:[7]669-80), which Dr. Thase said is equivalent to about a 30% higher chance of remission. “Don’t go over and over with the simple treatments that aren’t [evoking] a response. Move briskly on to the more complex treatments until patients respond.”
Treatment algorithms can include psychotherapies, either in combination with pharmacotherapy or as monotherapy. He encouraged clinicians to refer to the American Psychiatric Association (APA) practice guideline for depression for more details. The absence of depressive symptoms alone is not indicative of remission, according to the guideline, which Dr. Thase coauthored. The presence of positive emotions and resilience, along with a sense of control over emotions and hope for the future, indicates remission.
If after applying those methods a patient remains depressed and has been negatively screened for bipolar disorder, the use of tricyclics or monoamine oxidase inhibitors (MAOIs) may be appropriate. “MAOIs account for less than 1 in every 1,000 prescriptions for antidepressants, yet for people who don’t respond to modern antidepressants, they still can carry a 30%-40% response rate. So, if you don’t prescribe them yourself, please get access to someone who does,” Dr. Thase said.
The tenets of measurement-based care are essentially the lessons learned from the landmark Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, which sought to address how pharmacologic care for depression could be delivered based on adequate dosing, attenuation of symptoms, fewer side effects, and other factors (Am J Psychiatry. 2006;163:1905-17).
Now,10 years later, measurement-based treatment is still finding its way into practice, Dr. Thase said in an interview. “But, there’s no reason to be unduly pessimistic. Ten years ago, depression screening was in the same position, and now it is both considered to be the standard of care and is widely done.”
Dr. Thase reported having extensive industry relationships, noting that he has been involved in the development of nearly every drug for the treatment of mood disorders. Global Academy and this news organization are owned by the same company.
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM SUMMIT OF NEUROLOGY & PSYCHIATRY
AUDIO: New bipolar disorder algorithm changes ranking of first-line therapies
WASHINGTON – In 2015, the Florida Agency for Health Care Administration published clinical guidelines for numerous psychiatric conditions, including bipolar disorder, demoting several first-line therapies, and promoting others.
Because the authors of the Florida Best Practice Psychotherapeutic Medication Guidelines for Adults agreed that inflammation is a mechanism of action in bipolar disorder, they adopted an approach to care that seeks to avoid inflammation at all costs.
“Some medications create metabolic disturbances, which can be disruptive to the inflammatory milieu,” said Roger McIntyre, MD, a professor of psychiatry and pharmacology at the University of Toronto, and head of the Mood Disorders Psychopharmacology Unit at the University Health Network, Toronto. Dr. McIntyre, one of the coauthors of the guidelines, discussed why the combination of olanzapine and fluoxetine has been deferred in the algorithm, why other medications have moved further up, why antidepressants also are lower in the order of priority, and why psychoeducation, social rhythm therapy, and lifestyle changes have been emphasized more than ever before.
“There is no way our bipolar patients are going to achieve their goals with medication alone,” Dr. McIntyre said at the meeting, held by the Global Academy for Medical Education. In addition, Dr. McIntyre outlined why adding bipolar screening in the primary care setting is critical in 2016, and called the new recommendations “the most up-to-date guidelines for treating bipolar disorder, and the new nosology of major depression disorder with mixed features.”
To access the Florida Best Practice Psychotherapeutic Medication Guidelines for Adults online, visit the Florida Medicaid Drug Therapy Management Program for Behavioral Health website.
Dr. McIntyre has numerous industry relationships, including research funding from Eli Lilly, Janssen-Ortho, Astra-Zeneca; Pfizer, and Lundbeck. Global Academy and this news organization are owned by the same company.
On Twitter @whitneymcknight
WASHINGTON – In 2015, the Florida Agency for Health Care Administration published clinical guidelines for numerous psychiatric conditions, including bipolar disorder, demoting several first-line therapies, and promoting others.
Because the authors of the Florida Best Practice Psychotherapeutic Medication Guidelines for Adults agreed that inflammation is a mechanism of action in bipolar disorder, they adopted an approach to care that seeks to avoid inflammation at all costs.
“Some medications create metabolic disturbances, which can be disruptive to the inflammatory milieu,” said Roger McIntyre, MD, a professor of psychiatry and pharmacology at the University of Toronto, and head of the Mood Disorders Psychopharmacology Unit at the University Health Network, Toronto. Dr. McIntyre, one of the coauthors of the guidelines, discussed why the combination of olanzapine and fluoxetine has been deferred in the algorithm, why other medications have moved further up, why antidepressants also are lower in the order of priority, and why psychoeducation, social rhythm therapy, and lifestyle changes have been emphasized more than ever before.
“There is no way our bipolar patients are going to achieve their goals with medication alone,” Dr. McIntyre said at the meeting, held by the Global Academy for Medical Education. In addition, Dr. McIntyre outlined why adding bipolar screening in the primary care setting is critical in 2016, and called the new recommendations “the most up-to-date guidelines for treating bipolar disorder, and the new nosology of major depression disorder with mixed features.”
To access the Florida Best Practice Psychotherapeutic Medication Guidelines for Adults online, visit the Florida Medicaid Drug Therapy Management Program for Behavioral Health website.
Dr. McIntyre has numerous industry relationships, including research funding from Eli Lilly, Janssen-Ortho, Astra-Zeneca; Pfizer, and Lundbeck. Global Academy and this news organization are owned by the same company.
On Twitter @whitneymcknight
WASHINGTON – In 2015, the Florida Agency for Health Care Administration published clinical guidelines for numerous psychiatric conditions, including bipolar disorder, demoting several first-line therapies, and promoting others.
Because the authors of the Florida Best Practice Psychotherapeutic Medication Guidelines for Adults agreed that inflammation is a mechanism of action in bipolar disorder, they adopted an approach to care that seeks to avoid inflammation at all costs.
“Some medications create metabolic disturbances, which can be disruptive to the inflammatory milieu,” said Roger McIntyre, MD, a professor of psychiatry and pharmacology at the University of Toronto, and head of the Mood Disorders Psychopharmacology Unit at the University Health Network, Toronto. Dr. McIntyre, one of the coauthors of the guidelines, discussed why the combination of olanzapine and fluoxetine has been deferred in the algorithm, why other medications have moved further up, why antidepressants also are lower in the order of priority, and why psychoeducation, social rhythm therapy, and lifestyle changes have been emphasized more than ever before.
“There is no way our bipolar patients are going to achieve their goals with medication alone,” Dr. McIntyre said at the meeting, held by the Global Academy for Medical Education. In addition, Dr. McIntyre outlined why adding bipolar screening in the primary care setting is critical in 2016, and called the new recommendations “the most up-to-date guidelines for treating bipolar disorder, and the new nosology of major depression disorder with mixed features.”
To access the Florida Best Practice Psychotherapeutic Medication Guidelines for Adults online, visit the Florida Medicaid Drug Therapy Management Program for Behavioral Health website.
Dr. McIntyre has numerous industry relationships, including research funding from Eli Lilly, Janssen-Ortho, Astra-Zeneca; Pfizer, and Lundbeck. Global Academy and this news organization are owned by the same company.
On Twitter @whitneymcknight
AT SUMMIT IN NEUROLOGY & PSYCHIATRY