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Viewing childhood autism as a whole body disorder
Intestinal inflammation, oxidative stress, immune problems affect subsets of patients.
LAS VEGAS – When parents of children with autism ask their primary physicians about complementary and integrative medical treatments, they often get stonewalled, according to Robert L. Hendren, DO.
“They find [clinicians] usually say, ‘Don’t try that stuff. It doesn’t work,’” Dr. Hendren said at an annual psychopharmacology update held by the Nevada Psychiatric Association.
“Parents then go to two different sets of providers,” he said. One provider “tells them about complementary and integrative medicine, but is likely not a traditional physician who’s treating their autism. It’s somebody who knows about these biomedical interventions but when parents tell them that they’re using traditional interventions ... that person also says, ‘Don’t use that. That’s doesn’t work.’ Then they go see their traditional provider who might be thinking about traditional medications. But they’ve learned that they don’t want to tell them, ‘I’m considering using omega 3s or zinc.’ Regrettably, most times physicians don’t say, ‘Let’s examine that. Let’s look at the literature and see if that’s the right decision for you.’ By shutting a family down saying, ‘I don’t want to hear about that,’ it often leads the family to think: ‘How do I make a decision about this? How do I know what to do?’ ”
Dr. Hendren said clinicians are beginning to embrace the notion that autism is not just a brain disorder, but rather a whole body disorder. For example, he noted that significant subsets of people with autism have intestinal inflammation, digestive enzyme abnormalities, metabolic impairments, oxidative stress, mitochondrial dysfunction, and immunity problems that range from immune deficiency to hypersensitivity to autoimmunity. “,” said Dr. Hendren, professor of child and adolescent psychiatry at the University of California, San Francisco. “I hope that by thinking about making the body healthier, we can help kids have the very best outcomes.”
Several biomedical treatments have adequate evidence to use for many patients, he said, including melatonin, probiotics, omega 3s, and possibly vitamin D3, methyl B12, oxytocin, restrictive diets, digestive enzymes, and choline. “There are strong anecdotal reports of gluten-free diet benefits,” said Dr. Hendren, who also directs the UCSF Program for Research on Neurodevelopmental and Translational Outcomes. “Some parents I greatly respect tell me it’s the single most important thing they’ve done in their child’s health, that their GI symptoms have improved, and their overall health has improved.”
In a multisite trial called aViation, researchers are evaluating the effects of an investigational vasopressin antagonist in autistic patients aged 5-17 years. The drug works by blocking a brain receptor of the vasopressin receptor that is associated with control of stress, anxiety, affection, and aggression. “The first trial in adults showed potential benefit,” Dr. Hendren said.
No robust studies exist to suggest that medical marijuana makes a difference for patients with autism, he said, but he has several patients whose parents give their affected child medical marijuana or cannabidiol. “I have a number of families who say it’s really made a big difference for their children and for how they’re doing,” he said.
In Marin County, Calif., the Oak Hill School serves a heterogeneous population of children, adolescents, and young adults, all of whom have autism spectrum disorder (ASD) or other neurologically based disorders of relating and communicating. Students receive special education instruction and customized on-site clinical programs that might include speech/language pathology, occupational therapy, and group and individual psychotherapy. Some of the students have received recent functional behavior analyses from Dr. Hendren and his colleagues, with school staff implementing positive behavior intervention programs.
The researchers also are using metabolomics as a biomarker of outcome. “We’re using metabolomics from the urine, where we can look at these processes in different clusters and see whether our interventions make a difference or not,” said Dr. Hendren, who is a past president of the American Academy of Child and Adolescent Psychiatry. “We did one trial with sulforaphane, which is a concentrated broccoli sprout extract that helps with oxidative stress. It was initially developed to treat oxidative stress in cancer,” he said. Upcoming trials in this cohort include the use of folinic acid and CM-AT, a pancreatic digestive enzyme intended to increase levels of chymotrypsin.
“I think of autism as being a disorder where you have this person and there’s a veil of autism that comes over the top of them,” he said. “That veil is not the kid, although the kid becomes more and more expressed through that. If we can do something to lift that veil, we can do more and more to pull that child out.”
Dr. Hendren disclosed that he has received grants from Curemark, Roche, Shire, and Sunovion. He is a member of the advisory boards for Curemark, BioMarin, Janssen, and Axial Biotherapeutics.
Intestinal inflammation, oxidative stress, immune problems affect subsets of patients.
Intestinal inflammation, oxidative stress, immune problems affect subsets of patients.
LAS VEGAS – When parents of children with autism ask their primary physicians about complementary and integrative medical treatments, they often get stonewalled, according to Robert L. Hendren, DO.
“They find [clinicians] usually say, ‘Don’t try that stuff. It doesn’t work,’” Dr. Hendren said at an annual psychopharmacology update held by the Nevada Psychiatric Association.
“Parents then go to two different sets of providers,” he said. One provider “tells them about complementary and integrative medicine, but is likely not a traditional physician who’s treating their autism. It’s somebody who knows about these biomedical interventions but when parents tell them that they’re using traditional interventions ... that person also says, ‘Don’t use that. That’s doesn’t work.’ Then they go see their traditional provider who might be thinking about traditional medications. But they’ve learned that they don’t want to tell them, ‘I’m considering using omega 3s or zinc.’ Regrettably, most times physicians don’t say, ‘Let’s examine that. Let’s look at the literature and see if that’s the right decision for you.’ By shutting a family down saying, ‘I don’t want to hear about that,’ it often leads the family to think: ‘How do I make a decision about this? How do I know what to do?’ ”
Dr. Hendren said clinicians are beginning to embrace the notion that autism is not just a brain disorder, but rather a whole body disorder. For example, he noted that significant subsets of people with autism have intestinal inflammation, digestive enzyme abnormalities, metabolic impairments, oxidative stress, mitochondrial dysfunction, and immunity problems that range from immune deficiency to hypersensitivity to autoimmunity. “,” said Dr. Hendren, professor of child and adolescent psychiatry at the University of California, San Francisco. “I hope that by thinking about making the body healthier, we can help kids have the very best outcomes.”
Several biomedical treatments have adequate evidence to use for many patients, he said, including melatonin, probiotics, omega 3s, and possibly vitamin D3, methyl B12, oxytocin, restrictive diets, digestive enzymes, and choline. “There are strong anecdotal reports of gluten-free diet benefits,” said Dr. Hendren, who also directs the UCSF Program for Research on Neurodevelopmental and Translational Outcomes. “Some parents I greatly respect tell me it’s the single most important thing they’ve done in their child’s health, that their GI symptoms have improved, and their overall health has improved.”
In a multisite trial called aViation, researchers are evaluating the effects of an investigational vasopressin antagonist in autistic patients aged 5-17 years. The drug works by blocking a brain receptor of the vasopressin receptor that is associated with control of stress, anxiety, affection, and aggression. “The first trial in adults showed potential benefit,” Dr. Hendren said.
No robust studies exist to suggest that medical marijuana makes a difference for patients with autism, he said, but he has several patients whose parents give their affected child medical marijuana or cannabidiol. “I have a number of families who say it’s really made a big difference for their children and for how they’re doing,” he said.
In Marin County, Calif., the Oak Hill School serves a heterogeneous population of children, adolescents, and young adults, all of whom have autism spectrum disorder (ASD) or other neurologically based disorders of relating and communicating. Students receive special education instruction and customized on-site clinical programs that might include speech/language pathology, occupational therapy, and group and individual psychotherapy. Some of the students have received recent functional behavior analyses from Dr. Hendren and his colleagues, with school staff implementing positive behavior intervention programs.
The researchers also are using metabolomics as a biomarker of outcome. “We’re using metabolomics from the urine, where we can look at these processes in different clusters and see whether our interventions make a difference or not,” said Dr. Hendren, who is a past president of the American Academy of Child and Adolescent Psychiatry. “We did one trial with sulforaphane, which is a concentrated broccoli sprout extract that helps with oxidative stress. It was initially developed to treat oxidative stress in cancer,” he said. Upcoming trials in this cohort include the use of folinic acid and CM-AT, a pancreatic digestive enzyme intended to increase levels of chymotrypsin.
“I think of autism as being a disorder where you have this person and there’s a veil of autism that comes over the top of them,” he said. “That veil is not the kid, although the kid becomes more and more expressed through that. If we can do something to lift that veil, we can do more and more to pull that child out.”
Dr. Hendren disclosed that he has received grants from Curemark, Roche, Shire, and Sunovion. He is a member of the advisory boards for Curemark, BioMarin, Janssen, and Axial Biotherapeutics.
LAS VEGAS – When parents of children with autism ask their primary physicians about complementary and integrative medical treatments, they often get stonewalled, according to Robert L. Hendren, DO.
“They find [clinicians] usually say, ‘Don’t try that stuff. It doesn’t work,’” Dr. Hendren said at an annual psychopharmacology update held by the Nevada Psychiatric Association.
“Parents then go to two different sets of providers,” he said. One provider “tells them about complementary and integrative medicine, but is likely not a traditional physician who’s treating their autism. It’s somebody who knows about these biomedical interventions but when parents tell them that they’re using traditional interventions ... that person also says, ‘Don’t use that. That’s doesn’t work.’ Then they go see their traditional provider who might be thinking about traditional medications. But they’ve learned that they don’t want to tell them, ‘I’m considering using omega 3s or zinc.’ Regrettably, most times physicians don’t say, ‘Let’s examine that. Let’s look at the literature and see if that’s the right decision for you.’ By shutting a family down saying, ‘I don’t want to hear about that,’ it often leads the family to think: ‘How do I make a decision about this? How do I know what to do?’ ”
Dr. Hendren said clinicians are beginning to embrace the notion that autism is not just a brain disorder, but rather a whole body disorder. For example, he noted that significant subsets of people with autism have intestinal inflammation, digestive enzyme abnormalities, metabolic impairments, oxidative stress, mitochondrial dysfunction, and immunity problems that range from immune deficiency to hypersensitivity to autoimmunity. “,” said Dr. Hendren, professor of child and adolescent psychiatry at the University of California, San Francisco. “I hope that by thinking about making the body healthier, we can help kids have the very best outcomes.”
Several biomedical treatments have adequate evidence to use for many patients, he said, including melatonin, probiotics, omega 3s, and possibly vitamin D3, methyl B12, oxytocin, restrictive diets, digestive enzymes, and choline. “There are strong anecdotal reports of gluten-free diet benefits,” said Dr. Hendren, who also directs the UCSF Program for Research on Neurodevelopmental and Translational Outcomes. “Some parents I greatly respect tell me it’s the single most important thing they’ve done in their child’s health, that their GI symptoms have improved, and their overall health has improved.”
In a multisite trial called aViation, researchers are evaluating the effects of an investigational vasopressin antagonist in autistic patients aged 5-17 years. The drug works by blocking a brain receptor of the vasopressin receptor that is associated with control of stress, anxiety, affection, and aggression. “The first trial in adults showed potential benefit,” Dr. Hendren said.
No robust studies exist to suggest that medical marijuana makes a difference for patients with autism, he said, but he has several patients whose parents give their affected child medical marijuana or cannabidiol. “I have a number of families who say it’s really made a big difference for their children and for how they’re doing,” he said.
In Marin County, Calif., the Oak Hill School serves a heterogeneous population of children, adolescents, and young adults, all of whom have autism spectrum disorder (ASD) or other neurologically based disorders of relating and communicating. Students receive special education instruction and customized on-site clinical programs that might include speech/language pathology, occupational therapy, and group and individual psychotherapy. Some of the students have received recent functional behavior analyses from Dr. Hendren and his colleagues, with school staff implementing positive behavior intervention programs.
The researchers also are using metabolomics as a biomarker of outcome. “We’re using metabolomics from the urine, where we can look at these processes in different clusters and see whether our interventions make a difference or not,” said Dr. Hendren, who is a past president of the American Academy of Child and Adolescent Psychiatry. “We did one trial with sulforaphane, which is a concentrated broccoli sprout extract that helps with oxidative stress. It was initially developed to treat oxidative stress in cancer,” he said. Upcoming trials in this cohort include the use of folinic acid and CM-AT, a pancreatic digestive enzyme intended to increase levels of chymotrypsin.
“I think of autism as being a disorder where you have this person and there’s a veil of autism that comes over the top of them,” he said. “That veil is not the kid, although the kid becomes more and more expressed through that. If we can do something to lift that veil, we can do more and more to pull that child out.”
Dr. Hendren disclosed that he has received grants from Curemark, Roche, Shire, and Sunovion. He is a member of the advisory boards for Curemark, BioMarin, Janssen, and Axial Biotherapeutics.
EXPERT ANALYSIS FROM NPA 2019
Genes associated with PTSD coming into focus
LAS VEGAS – Despite recent advances in the diagnosis and treatment of posttraumatic stress disorder, researchers have yet to fully understand its pathophysiology.
“We don’t know whether there is just one type of pathophysiology or if there are different mechanisms and different etiologies that contribute to the symptomatic heterogeneity that we see,” Murray B. Stein, MD, MPH, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.
“Many theories currently being studied are inflammatory theories, looking at autonomic dysregulation, glucocorticoid sensitivity, hippocampal volume/dysfunction, and cortical-amygdala circuit dysregulation.”
Dr. Stein expects clinicians to gain an improved understanding of PTSD and a myriad of other conditions in the coming years as the Million Veteran Program (MVP) gets underway. MVP researchers are building one of the world’s largest medical databases by asking 1 million veteran volunteers to provide a blood sample and complete surveys about their health, military experience, lifestyle, and other topics that might contribute to health and disease. They will study how genes influence diseases such as diabetes and cancer, and military-related illnesses, such as PTSD. “It’s an amazing study, where over the next decade, you’re going to hear research findings not just on PTSD but in other areas of mental health and physical health,” said Dr. Stein, distinguished professor of psychiatry and family medicine and public health at the University of California, San Diego. So far, he said, 700,000 veterans are enrolled.
Dr. Stein shared preliminary findings from one component of the MVP study, in which participants complete the PTSD Checklist (PCL-17), a widely used 17-item self-report measure of PTSD symptoms in the past month. Using Manhattan plot analysis, Dr. Stein and his colleagues conducted a PTSD genomewide association study based on PCL-17 total scores. They found several genes significantly associated with PTSD, including LRRIQ3, TRAIP, KCNIP4, PCDHA1, MAD1L1, TSNARE1, EXD3, MGC57346-CRHR1, and TCF4. “This is the first study in the world to find this many genes [associated with PTSD],” said Dr. Stein, a staff psychiatrist with the VA San Diego Healthcare System. “The MAD1L1 gene is also one that’s come up in schizophrenia and in major depression. In fact, if we look at genetic correlations of how PTSD is genetically associated to other disorders that have been studied in this way, like major depression and schizophrenia, we find that there is shared variation. However, there are also unique features, so we are learning what we think is true about mental disorders overall, that in some ways comorbidity is explained by genetic risk, but there are also individual specific risk factors that go with specific disorders.
“We’re exploring each of those genes.”
of any of the genes in the genome. “One of the prominent theories of PTSD is that there is an increase in CRHR1 in the brain of individuals with the disorder,” Dr. Stein said. “More than by chance, it looks like the genes that are popping up in PTSD seem to be expressed in the frontal cortex, the anterior cingulate, the cortex, the hypothalamus, the amygdala, the hippocampus, the basal ganglia, and the substantia nigra. So all of a sudden, we go from having a list of genes to knowing there’s something going on in the brain of people with PTSD that involves expression in these particular regions that we might be able to target.”
In related work using the same genetic information, Dr. Stein and his colleagues have demonstrated an association between PTSD and medium spiny neurons, which are located in the basal ganglia and make up 95% of neurons in the striatum. “They also have GABAergic projection to other parts of the brain and play a key role in motivation, reward, enforcement, and aversion,” Dr. Stein said.
Dr. Stein disclosed that he has received research support from the National Institute of Mental Health, the National Institute of Alcoholism and Alcohol Abuse, the National Institute of Neurological Disorders and Stroke, the U.S. Department of Defense, and the U.S. Department of Veterans Affairs. He also has received consulting fees from Aptinyx, Bionomics, Janssen, Neurocrine, Oxeia Biopharmaceuticals, and Resilience Therapeutics.
LAS VEGAS – Despite recent advances in the diagnosis and treatment of posttraumatic stress disorder, researchers have yet to fully understand its pathophysiology.
“We don’t know whether there is just one type of pathophysiology or if there are different mechanisms and different etiologies that contribute to the symptomatic heterogeneity that we see,” Murray B. Stein, MD, MPH, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.
“Many theories currently being studied are inflammatory theories, looking at autonomic dysregulation, glucocorticoid sensitivity, hippocampal volume/dysfunction, and cortical-amygdala circuit dysregulation.”
Dr. Stein expects clinicians to gain an improved understanding of PTSD and a myriad of other conditions in the coming years as the Million Veteran Program (MVP) gets underway. MVP researchers are building one of the world’s largest medical databases by asking 1 million veteran volunteers to provide a blood sample and complete surveys about their health, military experience, lifestyle, and other topics that might contribute to health and disease. They will study how genes influence diseases such as diabetes and cancer, and military-related illnesses, such as PTSD. “It’s an amazing study, where over the next decade, you’re going to hear research findings not just on PTSD but in other areas of mental health and physical health,” said Dr. Stein, distinguished professor of psychiatry and family medicine and public health at the University of California, San Diego. So far, he said, 700,000 veterans are enrolled.
Dr. Stein shared preliminary findings from one component of the MVP study, in which participants complete the PTSD Checklist (PCL-17), a widely used 17-item self-report measure of PTSD symptoms in the past month. Using Manhattan plot analysis, Dr. Stein and his colleagues conducted a PTSD genomewide association study based on PCL-17 total scores. They found several genes significantly associated with PTSD, including LRRIQ3, TRAIP, KCNIP4, PCDHA1, MAD1L1, TSNARE1, EXD3, MGC57346-CRHR1, and TCF4. “This is the first study in the world to find this many genes [associated with PTSD],” said Dr. Stein, a staff psychiatrist with the VA San Diego Healthcare System. “The MAD1L1 gene is also one that’s come up in schizophrenia and in major depression. In fact, if we look at genetic correlations of how PTSD is genetically associated to other disorders that have been studied in this way, like major depression and schizophrenia, we find that there is shared variation. However, there are also unique features, so we are learning what we think is true about mental disorders overall, that in some ways comorbidity is explained by genetic risk, but there are also individual specific risk factors that go with specific disorders.
“We’re exploring each of those genes.”
of any of the genes in the genome. “One of the prominent theories of PTSD is that there is an increase in CRHR1 in the brain of individuals with the disorder,” Dr. Stein said. “More than by chance, it looks like the genes that are popping up in PTSD seem to be expressed in the frontal cortex, the anterior cingulate, the cortex, the hypothalamus, the amygdala, the hippocampus, the basal ganglia, and the substantia nigra. So all of a sudden, we go from having a list of genes to knowing there’s something going on in the brain of people with PTSD that involves expression in these particular regions that we might be able to target.”
In related work using the same genetic information, Dr. Stein and his colleagues have demonstrated an association between PTSD and medium spiny neurons, which are located in the basal ganglia and make up 95% of neurons in the striatum. “They also have GABAergic projection to other parts of the brain and play a key role in motivation, reward, enforcement, and aversion,” Dr. Stein said.
Dr. Stein disclosed that he has received research support from the National Institute of Mental Health, the National Institute of Alcoholism and Alcohol Abuse, the National Institute of Neurological Disorders and Stroke, the U.S. Department of Defense, and the U.S. Department of Veterans Affairs. He also has received consulting fees from Aptinyx, Bionomics, Janssen, Neurocrine, Oxeia Biopharmaceuticals, and Resilience Therapeutics.
LAS VEGAS – Despite recent advances in the diagnosis and treatment of posttraumatic stress disorder, researchers have yet to fully understand its pathophysiology.
“We don’t know whether there is just one type of pathophysiology or if there are different mechanisms and different etiologies that contribute to the symptomatic heterogeneity that we see,” Murray B. Stein, MD, MPH, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.
“Many theories currently being studied are inflammatory theories, looking at autonomic dysregulation, glucocorticoid sensitivity, hippocampal volume/dysfunction, and cortical-amygdala circuit dysregulation.”
Dr. Stein expects clinicians to gain an improved understanding of PTSD and a myriad of other conditions in the coming years as the Million Veteran Program (MVP) gets underway. MVP researchers are building one of the world’s largest medical databases by asking 1 million veteran volunteers to provide a blood sample and complete surveys about their health, military experience, lifestyle, and other topics that might contribute to health and disease. They will study how genes influence diseases such as diabetes and cancer, and military-related illnesses, such as PTSD. “It’s an amazing study, where over the next decade, you’re going to hear research findings not just on PTSD but in other areas of mental health and physical health,” said Dr. Stein, distinguished professor of psychiatry and family medicine and public health at the University of California, San Diego. So far, he said, 700,000 veterans are enrolled.
Dr. Stein shared preliminary findings from one component of the MVP study, in which participants complete the PTSD Checklist (PCL-17), a widely used 17-item self-report measure of PTSD symptoms in the past month. Using Manhattan plot analysis, Dr. Stein and his colleagues conducted a PTSD genomewide association study based on PCL-17 total scores. They found several genes significantly associated with PTSD, including LRRIQ3, TRAIP, KCNIP4, PCDHA1, MAD1L1, TSNARE1, EXD3, MGC57346-CRHR1, and TCF4. “This is the first study in the world to find this many genes [associated with PTSD],” said Dr. Stein, a staff psychiatrist with the VA San Diego Healthcare System. “The MAD1L1 gene is also one that’s come up in schizophrenia and in major depression. In fact, if we look at genetic correlations of how PTSD is genetically associated to other disorders that have been studied in this way, like major depression and schizophrenia, we find that there is shared variation. However, there are also unique features, so we are learning what we think is true about mental disorders overall, that in some ways comorbidity is explained by genetic risk, but there are also individual specific risk factors that go with specific disorders.
“We’re exploring each of those genes.”
of any of the genes in the genome. “One of the prominent theories of PTSD is that there is an increase in CRHR1 in the brain of individuals with the disorder,” Dr. Stein said. “More than by chance, it looks like the genes that are popping up in PTSD seem to be expressed in the frontal cortex, the anterior cingulate, the cortex, the hypothalamus, the amygdala, the hippocampus, the basal ganglia, and the substantia nigra. So all of a sudden, we go from having a list of genes to knowing there’s something going on in the brain of people with PTSD that involves expression in these particular regions that we might be able to target.”
In related work using the same genetic information, Dr. Stein and his colleagues have demonstrated an association between PTSD and medium spiny neurons, which are located in the basal ganglia and make up 95% of neurons in the striatum. “They also have GABAergic projection to other parts of the brain and play a key role in motivation, reward, enforcement, and aversion,” Dr. Stein said.
Dr. Stein disclosed that he has received research support from the National Institute of Mental Health, the National Institute of Alcoholism and Alcohol Abuse, the National Institute of Neurological Disorders and Stroke, the U.S. Department of Defense, and the U.S. Department of Veterans Affairs. He also has received consulting fees from Aptinyx, Bionomics, Janssen, Neurocrine, Oxeia Biopharmaceuticals, and Resilience Therapeutics.
REPORTING FROM NPA 2019
Parsing the fine points of anxiety
Expert prescribes benzodiazepines for excessive anxiety, antidepressants for anxiety disorders
LAS VEGAS –
“People with anxiety disorders have excessive anxiety, but not everyone with excessive anxiety has a psychiatric disorder,” he said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “Any anxiety above baseline can be normal. It’s not necessarily pathological. I think that’s an important point that’s easy to overlook when we’re in clinical practice, and it affects how we approach our patients.”
Anxiety can present in a variety of ways in different individuals. Panic attacks are often the primary chief complaint, and it’s common to hear complaints from family that the person is routinely seeking reassurance. In addition, tics and twitches are not unusual in people with anxiety disorder. “Some of that is brought out by anxiety itself,” said Dr. Hudak, who is a psychiatrist at the University of Pittsburgh. Sleep disturbances or other somatic complaints also are common. “They complain of racing thoughts, increased energy, and depression,” he added. “When someone complains about depression, don’t assume they have a mood disorder. The reason people with anxiety disorders complain about depression is that it really feels awful. Anxiety is incredibly dysphoric.” Physical complaints include shortness of breath, GI distress, dizziness, vague somatic complaints, and skin or gum lesions.
He went on to note that individuals with excessive anxiety virtually never lose consciousness. “The exception is blood/injection/injury phobia,” he said. “That’s the only case in which anxiety will cause loss of consciousness. It happens in virtually no other setting. Ondine’s curse while falling asleep is another symptom that only occurs with anxiety. It’s a sensation that you have to remember to breathe, and breathing is no longer automatic. There are medical conditions that cause Ondine’s curse. However, the patient who complains of Ondine’s curse as they’re falling asleep is pathognomonic for anxiety.”
Dr. Hudak said panic attacks, a discrete period of fear or discomfort, rarely last more than 30 minutes.
“I view panic attacks in three flavors,” he said. “Some people have the cardiovascular flavor with shortness of breath and heart palpitations. Some have what I call the neurological flavor, where the predominant symptoms seem to be dizziness and tingling. Other people have GI flavor, with gut pain, nausea, and diarrhea. Panic attacks are not a psychiatric disorder. It’s a qualifier for any psychiatric disorder.”
Social anxiety disorder, meanwhile, presents as two completely distinct and separate illnesses that have nothing in common with each other.
“The performance subtype of social anxiety really presents like a simple phobia,” Dr. Hudak said. “The treatment for that is really behavioral therapy and cognitive-behavioral therapy, and rarely the use of medications. The generalized type presents with intrusive, [obsessive-compulsive disorder]–like thoughts. Affected individuals describe themselves as ‘paranoid’ or feeling that they are being scrutinized. The categorical versus dimensional diagnosis is being debated.” Individuals with generalized anxiety disorder, on the other hand, have excessive and pervasive worry and anxiety present more days than not for a 6-month period. “The individual finds it difficult to control the worry,” he said. Somatic symptoms include restlessness, fatigue, difficulty concentrating, irritability, muscle tension, and insomnia. Different studies show the prevalence rate between 3% and 8%, affecting more women than men.
The medical work-up for excessive anxiety should consist of history and physical exam, complete blood count, the Chem-7 metabolic test, thyroid-stimulating hormone, and EKG if indicated. Both medications and behavioral therapy are used in the treatment of anxiety disorders. Many patients require both in order to achieve maximum treatment response. “Often, people with less severe illnesses can be managed with therapy alone,” Dr. Hudak said.
“In more severe cases, medications can help reduce symptoms to the point where therapy is easier to perform. The bottom line here is that at no time should you treat someone with an anxiety disorder with medications alone. Behavioral therapy is at least as effective as medications, and perhaps more so.”
Many trials of anxiety medications are of short duration and therefore lack evidence of long-term improvement, he said. Commonly used scales often include nonspecific items such as arousal score that can be reduced by sedating medications without improving the actual disorder. If someone has excessive anxiety that is not part of a primary anxiety disorder, Dr. Hudak typically prescribes benzodiazepines. “If someone is anxious because a loved one died, or if they’re nervous about their wedding day, or about taking a board exam, benzos can be used,” he said. “For someone who has an anxiety disorder, I virtually never use benzodiazepines. I generally use medications in the antidepressant category. I probably initiate fewer than five benzodiazepine prescriptions per year for anxiety disorder. There is also data to suggest that using benzodiazepines in patients with anxiety disorder may make cognitive-behavioral therapy more difficult.”
According to Dr. Hudak, selective serotonin reuptake inhibitors seem to have the largest evidence base in panic disorder and are first-line pharmacotherapy for both panic disorder and generalized anxiety disorder, while tricyclic antidepressants (TCAs) usually are considered a second-line therapy. “There is good data behind MAO inhibitors, and there is increasingly good data behind [selective norepinephrine reuptake inhibitors],” he said. “If someone has failed a trial of SSRIs, you may consider trying an SNRI before a TCA. However, I would try multiple SSRIs before ruling out that class of medications. I have had people fail five SSRIs and respond dramatically to the sixth SSRI.”
Dr. Hudak disclosed that he receives royalties from the Cambridge University Press.
Expert prescribes benzodiazepines for excessive anxiety, antidepressants for anxiety disorders
Expert prescribes benzodiazepines for excessive anxiety, antidepressants for anxiety disorders
LAS VEGAS –
“People with anxiety disorders have excessive anxiety, but not everyone with excessive anxiety has a psychiatric disorder,” he said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “Any anxiety above baseline can be normal. It’s not necessarily pathological. I think that’s an important point that’s easy to overlook when we’re in clinical practice, and it affects how we approach our patients.”
Anxiety can present in a variety of ways in different individuals. Panic attacks are often the primary chief complaint, and it’s common to hear complaints from family that the person is routinely seeking reassurance. In addition, tics and twitches are not unusual in people with anxiety disorder. “Some of that is brought out by anxiety itself,” said Dr. Hudak, who is a psychiatrist at the University of Pittsburgh. Sleep disturbances or other somatic complaints also are common. “They complain of racing thoughts, increased energy, and depression,” he added. “When someone complains about depression, don’t assume they have a mood disorder. The reason people with anxiety disorders complain about depression is that it really feels awful. Anxiety is incredibly dysphoric.” Physical complaints include shortness of breath, GI distress, dizziness, vague somatic complaints, and skin or gum lesions.
He went on to note that individuals with excessive anxiety virtually never lose consciousness. “The exception is blood/injection/injury phobia,” he said. “That’s the only case in which anxiety will cause loss of consciousness. It happens in virtually no other setting. Ondine’s curse while falling asleep is another symptom that only occurs with anxiety. It’s a sensation that you have to remember to breathe, and breathing is no longer automatic. There are medical conditions that cause Ondine’s curse. However, the patient who complains of Ondine’s curse as they’re falling asleep is pathognomonic for anxiety.”
Dr. Hudak said panic attacks, a discrete period of fear or discomfort, rarely last more than 30 minutes.
“I view panic attacks in three flavors,” he said. “Some people have the cardiovascular flavor with shortness of breath and heart palpitations. Some have what I call the neurological flavor, where the predominant symptoms seem to be dizziness and tingling. Other people have GI flavor, with gut pain, nausea, and diarrhea. Panic attacks are not a psychiatric disorder. It’s a qualifier for any psychiatric disorder.”
Social anxiety disorder, meanwhile, presents as two completely distinct and separate illnesses that have nothing in common with each other.
“The performance subtype of social anxiety really presents like a simple phobia,” Dr. Hudak said. “The treatment for that is really behavioral therapy and cognitive-behavioral therapy, and rarely the use of medications. The generalized type presents with intrusive, [obsessive-compulsive disorder]–like thoughts. Affected individuals describe themselves as ‘paranoid’ or feeling that they are being scrutinized. The categorical versus dimensional diagnosis is being debated.” Individuals with generalized anxiety disorder, on the other hand, have excessive and pervasive worry and anxiety present more days than not for a 6-month period. “The individual finds it difficult to control the worry,” he said. Somatic symptoms include restlessness, fatigue, difficulty concentrating, irritability, muscle tension, and insomnia. Different studies show the prevalence rate between 3% and 8%, affecting more women than men.
The medical work-up for excessive anxiety should consist of history and physical exam, complete blood count, the Chem-7 metabolic test, thyroid-stimulating hormone, and EKG if indicated. Both medications and behavioral therapy are used in the treatment of anxiety disorders. Many patients require both in order to achieve maximum treatment response. “Often, people with less severe illnesses can be managed with therapy alone,” Dr. Hudak said.
“In more severe cases, medications can help reduce symptoms to the point where therapy is easier to perform. The bottom line here is that at no time should you treat someone with an anxiety disorder with medications alone. Behavioral therapy is at least as effective as medications, and perhaps more so.”
Many trials of anxiety medications are of short duration and therefore lack evidence of long-term improvement, he said. Commonly used scales often include nonspecific items such as arousal score that can be reduced by sedating medications without improving the actual disorder. If someone has excessive anxiety that is not part of a primary anxiety disorder, Dr. Hudak typically prescribes benzodiazepines. “If someone is anxious because a loved one died, or if they’re nervous about their wedding day, or about taking a board exam, benzos can be used,” he said. “For someone who has an anxiety disorder, I virtually never use benzodiazepines. I generally use medications in the antidepressant category. I probably initiate fewer than five benzodiazepine prescriptions per year for anxiety disorder. There is also data to suggest that using benzodiazepines in patients with anxiety disorder may make cognitive-behavioral therapy more difficult.”
According to Dr. Hudak, selective serotonin reuptake inhibitors seem to have the largest evidence base in panic disorder and are first-line pharmacotherapy for both panic disorder and generalized anxiety disorder, while tricyclic antidepressants (TCAs) usually are considered a second-line therapy. “There is good data behind MAO inhibitors, and there is increasingly good data behind [selective norepinephrine reuptake inhibitors],” he said. “If someone has failed a trial of SSRIs, you may consider trying an SNRI before a TCA. However, I would try multiple SSRIs before ruling out that class of medications. I have had people fail five SSRIs and respond dramatically to the sixth SSRI.”
Dr. Hudak disclosed that he receives royalties from the Cambridge University Press.
LAS VEGAS –
“People with anxiety disorders have excessive anxiety, but not everyone with excessive anxiety has a psychiatric disorder,” he said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “Any anxiety above baseline can be normal. It’s not necessarily pathological. I think that’s an important point that’s easy to overlook when we’re in clinical practice, and it affects how we approach our patients.”
Anxiety can present in a variety of ways in different individuals. Panic attacks are often the primary chief complaint, and it’s common to hear complaints from family that the person is routinely seeking reassurance. In addition, tics and twitches are not unusual in people with anxiety disorder. “Some of that is brought out by anxiety itself,” said Dr. Hudak, who is a psychiatrist at the University of Pittsburgh. Sleep disturbances or other somatic complaints also are common. “They complain of racing thoughts, increased energy, and depression,” he added. “When someone complains about depression, don’t assume they have a mood disorder. The reason people with anxiety disorders complain about depression is that it really feels awful. Anxiety is incredibly dysphoric.” Physical complaints include shortness of breath, GI distress, dizziness, vague somatic complaints, and skin or gum lesions.
He went on to note that individuals with excessive anxiety virtually never lose consciousness. “The exception is blood/injection/injury phobia,” he said. “That’s the only case in which anxiety will cause loss of consciousness. It happens in virtually no other setting. Ondine’s curse while falling asleep is another symptom that only occurs with anxiety. It’s a sensation that you have to remember to breathe, and breathing is no longer automatic. There are medical conditions that cause Ondine’s curse. However, the patient who complains of Ondine’s curse as they’re falling asleep is pathognomonic for anxiety.”
Dr. Hudak said panic attacks, a discrete period of fear or discomfort, rarely last more than 30 minutes.
“I view panic attacks in three flavors,” he said. “Some people have the cardiovascular flavor with shortness of breath and heart palpitations. Some have what I call the neurological flavor, where the predominant symptoms seem to be dizziness and tingling. Other people have GI flavor, with gut pain, nausea, and diarrhea. Panic attacks are not a psychiatric disorder. It’s a qualifier for any psychiatric disorder.”
Social anxiety disorder, meanwhile, presents as two completely distinct and separate illnesses that have nothing in common with each other.
“The performance subtype of social anxiety really presents like a simple phobia,” Dr. Hudak said. “The treatment for that is really behavioral therapy and cognitive-behavioral therapy, and rarely the use of medications. The generalized type presents with intrusive, [obsessive-compulsive disorder]–like thoughts. Affected individuals describe themselves as ‘paranoid’ or feeling that they are being scrutinized. The categorical versus dimensional diagnosis is being debated.” Individuals with generalized anxiety disorder, on the other hand, have excessive and pervasive worry and anxiety present more days than not for a 6-month period. “The individual finds it difficult to control the worry,” he said. Somatic symptoms include restlessness, fatigue, difficulty concentrating, irritability, muscle tension, and insomnia. Different studies show the prevalence rate between 3% and 8%, affecting more women than men.
The medical work-up for excessive anxiety should consist of history and physical exam, complete blood count, the Chem-7 metabolic test, thyroid-stimulating hormone, and EKG if indicated. Both medications and behavioral therapy are used in the treatment of anxiety disorders. Many patients require both in order to achieve maximum treatment response. “Often, people with less severe illnesses can be managed with therapy alone,” Dr. Hudak said.
“In more severe cases, medications can help reduce symptoms to the point where therapy is easier to perform. The bottom line here is that at no time should you treat someone with an anxiety disorder with medications alone. Behavioral therapy is at least as effective as medications, and perhaps more so.”
Many trials of anxiety medications are of short duration and therefore lack evidence of long-term improvement, he said. Commonly used scales often include nonspecific items such as arousal score that can be reduced by sedating medications without improving the actual disorder. If someone has excessive anxiety that is not part of a primary anxiety disorder, Dr. Hudak typically prescribes benzodiazepines. “If someone is anxious because a loved one died, or if they’re nervous about their wedding day, or about taking a board exam, benzos can be used,” he said. “For someone who has an anxiety disorder, I virtually never use benzodiazepines. I generally use medications in the antidepressant category. I probably initiate fewer than five benzodiazepine prescriptions per year for anxiety disorder. There is also data to suggest that using benzodiazepines in patients with anxiety disorder may make cognitive-behavioral therapy more difficult.”
According to Dr. Hudak, selective serotonin reuptake inhibitors seem to have the largest evidence base in panic disorder and are first-line pharmacotherapy for both panic disorder and generalized anxiety disorder, while tricyclic antidepressants (TCAs) usually are considered a second-line therapy. “There is good data behind MAO inhibitors, and there is increasingly good data behind [selective norepinephrine reuptake inhibitors],” he said. “If someone has failed a trial of SSRIs, you may consider trying an SNRI before a TCA. However, I would try multiple SSRIs before ruling out that class of medications. I have had people fail five SSRIs and respond dramatically to the sixth SSRI.”
Dr. Hudak disclosed that he receives royalties from the Cambridge University Press.
EXPERT ANALYSIS FROM NPA 2019
Accurately predicting ADHD’s trajectory deemed almost impossible
LAS VEGAS – Despite the strides that clinicians like Anthony L. Rostain, MD, have made in better understanding and treating patients with ADHD, it remains virtually impossible to predict how a child with the disorder will fare in adulthood.
“We cannot predict the trajectory of the disorder,” Dr. Rostain said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “We’re still learning about the variables that affect clinical course. There are many determinants to the trajectory.”
Dr. Rostain, professor of psychiatry and pediatrics at the University of Pennsylvania, Philadelphia, said ADHD commonly presents with numerous other neurodevelopmental disorders and with comorbid psychiatric conditions like bipolar disorder and anxiety.
“In psychiatry, we tend to see the more complicated patients, the ones with multiple comorbidities,” he said. “The most important change in the way we think about people with ADHD has to do with the growing emphasis on how it affects executive functions, in particular the cognitive, affective, and behavioral consequences of executive dysfunction. In this growingly complex world, with what some describe as ‘distracted minds’ emerging from being immersed in all our technology, it’s sometimes hard to tell: Is this person distracted because they’re always looking at their cell phone, or do they have intrinsic difficulty with managing attention?
“That’s going to become a greater challenge as children grow up in this world filled with shiny screens and devices that make [it] easier to connect with others but also harder to set a goal and follow it to its conclusion.”
ADHD changes over time, Dr. Rostain continued, but there is no single theory or biological explanation to explain its heterogeneity. “There is no cookie-cutter approach; you have to individualize when you are treating the individual in your office,” he said.
It is widely accepted that ADHD arises from biological factors, but social factors likely influence the degree of impairment, risk for comorbid disorders, and access to resources, said Dr. Rostain, who is also codirector of the developmental neuropsychiatry program at The Children’s Hospital of Philadelphia and medical director of the Adult ADHD Treatment and Research Program at Penn Medicine.
he said. “If there were one thing we could do to prevent ADHD, it might be to prevent pregnant women from drinking or to reduce poverty and violence, but that’s beyond the scope of this talk.”
He also noted that, because of epigenetics, ADHD risk factors express themselves early in some individuals and later in others. “We’re convinced that developmental disorders unfold in a nonlinear fashion,” he said. “Life [with ADHD] is curvy, not a straight line.”
Numerous studies of ADHD neurobiology have demonstrated frontal subcortical and cerebellar dysfunction – smaller striatal structures in particular. “In MRI studies, we also see difficulties with the differential maturation of important neural circuits, along with the persistence of cortical thickening where it should be thinning,” Dr. Rostain said. He went on to note that the normal brain consists of three main networks: the salience network, “which tells us whether to pay attention or to relax,” the attention and control network, and the default mode network, “which is where our mind goes when we’re daydreaming,” he said. “All of us are constantly switching between attention and daydreaming. That’s normal. In ADHD, the balance and synchrony between the default mode and the attention network is disrupted. Individuals with ADHD either remain too long in the default mode, or their attentional system isn’t powered up enough to keep them paying attention and following through during nonrewarding tasks.”
The presentation of ADHD symptoms tends to differ in children, compared with adults. For example, children with the disorder tend to be squirmy, can’t sit still, are restless, and can’t play or work quietly. On the other hand, adults tend to complain about inefficiencies at work, not being able to finish projects, not being able to sit through meetings. They tend to drive too quickly, and they often talk excessively, and make inappropriate comments. “The symptoms of ADHD emerge from disruptions or inefficiencies in basic functions, whether those are executive functions or motivational processes,” he said. “All of this is thought to be the result of genetic unfolding throughout the lifespan.”
The goal of ADHD medical therapy is to alter catecholamine tone in the prefrontal cortex, an area of the brain “designed to help us guide our thinking toward distal goals and navigate the world around us,” Dr. Rostain said. “It allows us also to inhibit actions that are task-irrelevant or are not serving our purposes. It also enable us to regulate emotions.” In his opinion, the medical treatment of ADHD should focus on helping the prefrontal cortex function optimally. “How much we can do – that remains to be seen – but that’s really where the action is,” he said. “From a functional standpoint, that’s what are we trying to achieve. When we have guided attention and when our responses to the world are appropriate, we can say that we’re ‘in the zone.’ That means we can listen, understand, make sense of the world, and deviate or shift direction if something gets in the way of our goals. Our responses should be flexible. We should be able to say, ‘That doesn’t work? Let me try something else.’ This indicates that the norepinephrine and dopamine circuits of the frontal cortex are optimally operating.”
On the other hand, individuals with ADHD find themselves in what Dr. Rostain described as an “unguided attention state” characterized by distraction and poor impulse control. “We also see it in people who are sleep deprived,” he said. “This could be untreated ADHD. If we treat ADHD properly, we move individuals into the optimal zone. But if we overdo it, if our medications are prescribed at doses that are higher than optimal, what you then see is excessive stimulation of the norepinephrine and dopamine systems. This leads to misguided attention, overfocusing, and mental inflexibility. People in this state report extreme amounts of stress and distress.”
Dr. Rostain recommends that medication plans be embedded in a comprehensive treatment approach that starts with psychoeducation. “When treating ADHD, we’re not going to turn a lion into a lamb, and we’re not going to make someone want to study if they don’t like school,” he said. “One of my patients, a college student, told me that, with the medication I prescribed for him, he was able to sit down and read for the first time for 3 hours straight. I said, ‘Great. Did you read your physics book? He said, No. I read Wired magazine.’ So while he was very focused, he didn’t concentrate on what he needed to focus on.”
Dr. Rostain supports the notion of a triad model of care with psychosocial interventions, medical interventions, and educational/workplace interventions “to improve the performance of demanded tasks, and to achieve a sense of being supported by that environment rather than being criticized,” he said. “If you ask most adults with ADHD what school was like, what will they tell you? They usually say it was bad or terrible, like a prison. If you ask them to describe it, they may have trouble remembering a lot of it, because it was so difficult for them.”
Dr. Rostain reported having received scientific advisory board honoraria from Shire, Ironshore, and Arbor. He also has received consultant honoraria from Major League Baseball, the National Football League, and from SUNY/Upstate.
LAS VEGAS – Despite the strides that clinicians like Anthony L. Rostain, MD, have made in better understanding and treating patients with ADHD, it remains virtually impossible to predict how a child with the disorder will fare in adulthood.
“We cannot predict the trajectory of the disorder,” Dr. Rostain said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “We’re still learning about the variables that affect clinical course. There are many determinants to the trajectory.”
Dr. Rostain, professor of psychiatry and pediatrics at the University of Pennsylvania, Philadelphia, said ADHD commonly presents with numerous other neurodevelopmental disorders and with comorbid psychiatric conditions like bipolar disorder and anxiety.
“In psychiatry, we tend to see the more complicated patients, the ones with multiple comorbidities,” he said. “The most important change in the way we think about people with ADHD has to do with the growing emphasis on how it affects executive functions, in particular the cognitive, affective, and behavioral consequences of executive dysfunction. In this growingly complex world, with what some describe as ‘distracted minds’ emerging from being immersed in all our technology, it’s sometimes hard to tell: Is this person distracted because they’re always looking at their cell phone, or do they have intrinsic difficulty with managing attention?
“That’s going to become a greater challenge as children grow up in this world filled with shiny screens and devices that make [it] easier to connect with others but also harder to set a goal and follow it to its conclusion.”
ADHD changes over time, Dr. Rostain continued, but there is no single theory or biological explanation to explain its heterogeneity. “There is no cookie-cutter approach; you have to individualize when you are treating the individual in your office,” he said.
It is widely accepted that ADHD arises from biological factors, but social factors likely influence the degree of impairment, risk for comorbid disorders, and access to resources, said Dr. Rostain, who is also codirector of the developmental neuropsychiatry program at The Children’s Hospital of Philadelphia and medical director of the Adult ADHD Treatment and Research Program at Penn Medicine.
he said. “If there were one thing we could do to prevent ADHD, it might be to prevent pregnant women from drinking or to reduce poverty and violence, but that’s beyond the scope of this talk.”
He also noted that, because of epigenetics, ADHD risk factors express themselves early in some individuals and later in others. “We’re convinced that developmental disorders unfold in a nonlinear fashion,” he said. “Life [with ADHD] is curvy, not a straight line.”
Numerous studies of ADHD neurobiology have demonstrated frontal subcortical and cerebellar dysfunction – smaller striatal structures in particular. “In MRI studies, we also see difficulties with the differential maturation of important neural circuits, along with the persistence of cortical thickening where it should be thinning,” Dr. Rostain said. He went on to note that the normal brain consists of three main networks: the salience network, “which tells us whether to pay attention or to relax,” the attention and control network, and the default mode network, “which is where our mind goes when we’re daydreaming,” he said. “All of us are constantly switching between attention and daydreaming. That’s normal. In ADHD, the balance and synchrony between the default mode and the attention network is disrupted. Individuals with ADHD either remain too long in the default mode, or their attentional system isn’t powered up enough to keep them paying attention and following through during nonrewarding tasks.”
The presentation of ADHD symptoms tends to differ in children, compared with adults. For example, children with the disorder tend to be squirmy, can’t sit still, are restless, and can’t play or work quietly. On the other hand, adults tend to complain about inefficiencies at work, not being able to finish projects, not being able to sit through meetings. They tend to drive too quickly, and they often talk excessively, and make inappropriate comments. “The symptoms of ADHD emerge from disruptions or inefficiencies in basic functions, whether those are executive functions or motivational processes,” he said. “All of this is thought to be the result of genetic unfolding throughout the lifespan.”
The goal of ADHD medical therapy is to alter catecholamine tone in the prefrontal cortex, an area of the brain “designed to help us guide our thinking toward distal goals and navigate the world around us,” Dr. Rostain said. “It allows us also to inhibit actions that are task-irrelevant or are not serving our purposes. It also enable us to regulate emotions.” In his opinion, the medical treatment of ADHD should focus on helping the prefrontal cortex function optimally. “How much we can do – that remains to be seen – but that’s really where the action is,” he said. “From a functional standpoint, that’s what are we trying to achieve. When we have guided attention and when our responses to the world are appropriate, we can say that we’re ‘in the zone.’ That means we can listen, understand, make sense of the world, and deviate or shift direction if something gets in the way of our goals. Our responses should be flexible. We should be able to say, ‘That doesn’t work? Let me try something else.’ This indicates that the norepinephrine and dopamine circuits of the frontal cortex are optimally operating.”
On the other hand, individuals with ADHD find themselves in what Dr. Rostain described as an “unguided attention state” characterized by distraction and poor impulse control. “We also see it in people who are sleep deprived,” he said. “This could be untreated ADHD. If we treat ADHD properly, we move individuals into the optimal zone. But if we overdo it, if our medications are prescribed at doses that are higher than optimal, what you then see is excessive stimulation of the norepinephrine and dopamine systems. This leads to misguided attention, overfocusing, and mental inflexibility. People in this state report extreme amounts of stress and distress.”
Dr. Rostain recommends that medication plans be embedded in a comprehensive treatment approach that starts with psychoeducation. “When treating ADHD, we’re not going to turn a lion into a lamb, and we’re not going to make someone want to study if they don’t like school,” he said. “One of my patients, a college student, told me that, with the medication I prescribed for him, he was able to sit down and read for the first time for 3 hours straight. I said, ‘Great. Did you read your physics book? He said, No. I read Wired magazine.’ So while he was very focused, he didn’t concentrate on what he needed to focus on.”
Dr. Rostain supports the notion of a triad model of care with psychosocial interventions, medical interventions, and educational/workplace interventions “to improve the performance of demanded tasks, and to achieve a sense of being supported by that environment rather than being criticized,” he said. “If you ask most adults with ADHD what school was like, what will they tell you? They usually say it was bad or terrible, like a prison. If you ask them to describe it, they may have trouble remembering a lot of it, because it was so difficult for them.”
Dr. Rostain reported having received scientific advisory board honoraria from Shire, Ironshore, and Arbor. He also has received consultant honoraria from Major League Baseball, the National Football League, and from SUNY/Upstate.
LAS VEGAS – Despite the strides that clinicians like Anthony L. Rostain, MD, have made in better understanding and treating patients with ADHD, it remains virtually impossible to predict how a child with the disorder will fare in adulthood.
“We cannot predict the trajectory of the disorder,” Dr. Rostain said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “We’re still learning about the variables that affect clinical course. There are many determinants to the trajectory.”
Dr. Rostain, professor of psychiatry and pediatrics at the University of Pennsylvania, Philadelphia, said ADHD commonly presents with numerous other neurodevelopmental disorders and with comorbid psychiatric conditions like bipolar disorder and anxiety.
“In psychiatry, we tend to see the more complicated patients, the ones with multiple comorbidities,” he said. “The most important change in the way we think about people with ADHD has to do with the growing emphasis on how it affects executive functions, in particular the cognitive, affective, and behavioral consequences of executive dysfunction. In this growingly complex world, with what some describe as ‘distracted minds’ emerging from being immersed in all our technology, it’s sometimes hard to tell: Is this person distracted because they’re always looking at their cell phone, or do they have intrinsic difficulty with managing attention?
“That’s going to become a greater challenge as children grow up in this world filled with shiny screens and devices that make [it] easier to connect with others but also harder to set a goal and follow it to its conclusion.”
ADHD changes over time, Dr. Rostain continued, but there is no single theory or biological explanation to explain its heterogeneity. “There is no cookie-cutter approach; you have to individualize when you are treating the individual in your office,” he said.
It is widely accepted that ADHD arises from biological factors, but social factors likely influence the degree of impairment, risk for comorbid disorders, and access to resources, said Dr. Rostain, who is also codirector of the developmental neuropsychiatry program at The Children’s Hospital of Philadelphia and medical director of the Adult ADHD Treatment and Research Program at Penn Medicine.
he said. “If there were one thing we could do to prevent ADHD, it might be to prevent pregnant women from drinking or to reduce poverty and violence, but that’s beyond the scope of this talk.”
He also noted that, because of epigenetics, ADHD risk factors express themselves early in some individuals and later in others. “We’re convinced that developmental disorders unfold in a nonlinear fashion,” he said. “Life [with ADHD] is curvy, not a straight line.”
Numerous studies of ADHD neurobiology have demonstrated frontal subcortical and cerebellar dysfunction – smaller striatal structures in particular. “In MRI studies, we also see difficulties with the differential maturation of important neural circuits, along with the persistence of cortical thickening where it should be thinning,” Dr. Rostain said. He went on to note that the normal brain consists of three main networks: the salience network, “which tells us whether to pay attention or to relax,” the attention and control network, and the default mode network, “which is where our mind goes when we’re daydreaming,” he said. “All of us are constantly switching between attention and daydreaming. That’s normal. In ADHD, the balance and synchrony between the default mode and the attention network is disrupted. Individuals with ADHD either remain too long in the default mode, or their attentional system isn’t powered up enough to keep them paying attention and following through during nonrewarding tasks.”
The presentation of ADHD symptoms tends to differ in children, compared with adults. For example, children with the disorder tend to be squirmy, can’t sit still, are restless, and can’t play or work quietly. On the other hand, adults tend to complain about inefficiencies at work, not being able to finish projects, not being able to sit through meetings. They tend to drive too quickly, and they often talk excessively, and make inappropriate comments. “The symptoms of ADHD emerge from disruptions or inefficiencies in basic functions, whether those are executive functions or motivational processes,” he said. “All of this is thought to be the result of genetic unfolding throughout the lifespan.”
The goal of ADHD medical therapy is to alter catecholamine tone in the prefrontal cortex, an area of the brain “designed to help us guide our thinking toward distal goals and navigate the world around us,” Dr. Rostain said. “It allows us also to inhibit actions that are task-irrelevant or are not serving our purposes. It also enable us to regulate emotions.” In his opinion, the medical treatment of ADHD should focus on helping the prefrontal cortex function optimally. “How much we can do – that remains to be seen – but that’s really where the action is,” he said. “From a functional standpoint, that’s what are we trying to achieve. When we have guided attention and when our responses to the world are appropriate, we can say that we’re ‘in the zone.’ That means we can listen, understand, make sense of the world, and deviate or shift direction if something gets in the way of our goals. Our responses should be flexible. We should be able to say, ‘That doesn’t work? Let me try something else.’ This indicates that the norepinephrine and dopamine circuits of the frontal cortex are optimally operating.”
On the other hand, individuals with ADHD find themselves in what Dr. Rostain described as an “unguided attention state” characterized by distraction and poor impulse control. “We also see it in people who are sleep deprived,” he said. “This could be untreated ADHD. If we treat ADHD properly, we move individuals into the optimal zone. But if we overdo it, if our medications are prescribed at doses that are higher than optimal, what you then see is excessive stimulation of the norepinephrine and dopamine systems. This leads to misguided attention, overfocusing, and mental inflexibility. People in this state report extreme amounts of stress and distress.”
Dr. Rostain recommends that medication plans be embedded in a comprehensive treatment approach that starts with psychoeducation. “When treating ADHD, we’re not going to turn a lion into a lamb, and we’re not going to make someone want to study if they don’t like school,” he said. “One of my patients, a college student, told me that, with the medication I prescribed for him, he was able to sit down and read for the first time for 3 hours straight. I said, ‘Great. Did you read your physics book? He said, No. I read Wired magazine.’ So while he was very focused, he didn’t concentrate on what he needed to focus on.”
Dr. Rostain supports the notion of a triad model of care with psychosocial interventions, medical interventions, and educational/workplace interventions “to improve the performance of demanded tasks, and to achieve a sense of being supported by that environment rather than being criticized,” he said. “If you ask most adults with ADHD what school was like, what will they tell you? They usually say it was bad or terrible, like a prison. If you ask them to describe it, they may have trouble remembering a lot of it, because it was so difficult for them.”
Dr. Rostain reported having received scientific advisory board honoraria from Shire, Ironshore, and Arbor. He also has received consultant honoraria from Major League Baseball, the National Football League, and from SUNY/Upstate.
REPORTING FROM NPA 2019
Antipsychotics show no link to increased risk of major congenital malformations
LAS VEGAS – Assessing the risk of major congenital malformations related to antipsychotic exposure requires detailed assessment of other sources of risk, including those related to the diagnosis and associated behaviors, according to Jonathan M. Meyer, MD.
However, the largest study to date showed no significant difference in rates of major congenital malformations for those with one or more prescriptions for atypical antipsychotics in the first trimester, compared with pregnancies with no first trimester antipsychotic exposure.
In the U.S. general population, the estimated risk of major birth defects is 2%-4%, Dr. Meyer, a clinical professor of psychiatry at the University of California, San Diego, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.
Medications represent one source of risk for major congenital malformations in patients with psychiatric illness. Other factors include lifestyle factors such substance abuse and smoking, diet and physical activity, adherence with medical/prenatal care regimens, general medical disease burden, and unknown genetic risk because of the illness itself.
Until recently, published studies examining antipsychotic exposure and the risk for congenital malformations have been flawed because of numerous factors, Dr. Meyer said, including the small sample size of live births, absence of systematic collection of risk data prior to and during pregnancy, and failure to examine all possible covariates that might moderate the risk potentially attributable to the medication itself.
For example, researchers led by Frank Habermann, PhD, prospectively evaluated three cohorts who were followed in a psychiatry consultation in Freiburg, Germany: 453 women who received atypical antipsychotics in the first trimester of pregnancy (group A); 238 women who received typical antipsychotics in the first trimester of pregnancy (group B); and 1,104 women who had no records of treatment with medications associated with harmful fetal effects (group C).
Covariates included maternal age, alcohol consumption, smoking habits, number of previous spontaneous abortions, number of previous malformed children, and gestational week at delivery (J Clin Psychopharmacol. 2013;33[4]:453-62).
The researchers found that 5.2% of women in group A gave birth to a child with a major congenital malformation, compared with 5% in group B and 2.5% in group C. Nonsignificant associations were observed between group A vs. B (adjusted odds ratio, 1.26; 95% confidence interval, 0.57-2.82) and group B vs. C (adjusted OR, 1.71; 95% CI, 0.78-3.76). The only significant association noted was between group A and C (adjusted OR, 2.17; 95% CI, 1.20-3.91). However, Dr. Meyer emphasized limitations of the study, including its small sample size and certain missing covariates, including illegal substance use.
In addition, since subjects were enrolled in a consultation clinic, surveillance bias might have detected a higher number of CV malformations. “I don’t have a lot of confidence in this study because there were enormous sources of risk that were not controlled for,” said Dr. Meyer, who is also a psychopharmacology consultant for the California State Department of Hospitals.
In a separate study, researchers led by Lee S. Cohen, MD, assessed data from 487 women in the National Pregnancy Registry for Atypical Antipsychotics based at the Massachusetts General Hospital Center for Women’s Health, Boston. Of the 487 women, 353 were on atypical antipsychotics and 134 served as controls (Am J Psychiatry. 2016;73[3]:263-70). Medical records were obtained at baseline, month 7, and postpartum for 82% of subjects, which left 303 women in the final analysis. Covariates included demographic characteristics, medication use and dosage changes, social habits including smoking, use of alcohol and illicit drugs, medical and psychiatric history, and family history of birth defects.
Of 214 live births with first-trimester exposure to atypical antipsychotics, three major malformations were confirmed, while among the control group of 89 women, one major malformation was confirmed. The absolute risk of major malformations was 1.4% for exposed infants and 1.1% for unexposed infants. Meanwhile, the OR for major malformations comparing exposed infants was 1.25, which did not reach statistical significance (95% CI, 0.13-12.19). Limitations of the study include the small sample size of live births and the low overall rate of malformations, said Dr. Meyer. “This group of women living in the Boston area might not be representative of the general population based on the extremely low rates of congenital malformations for both cohorts in this study,” he commented.
In what Dr. Meyer said was the most robust study of its kind to date, researchers led by Krista F. Huybrechts, MS, PhD, drew from Medicaid data from 2000-2010 and included only women who were enrolled from 3 months before their last menstrual period through at least 1 month after delivery (JAMA Psychiatry. 2016;73[9]:938-46). The sample consisted of 1,341,715 pregnancies. Among those pregnancies, 9,258 women filled at least one prescription for an atypical antipsychotic, and 733 filled at least one prescription for a typical antipsychotic, for a total of 9,991 pregnancies. The researchers used propensity score matching to match for risk of antipsychotic exposure. They also balanced the antipsychotic-exposed and nonexposed groups for covariates that might be related to the outcome of interest (major congenital malformations), including (but not limited to) calendar year, age, race, smoking history, multiple gestation, indications for antipsychotic use, other maternal morbidity, concomitant medication use, and general markers of illness burden in the 3 months prior to pregnancy.
The atypical antipsychotics used included quetiapine (n = 4,221), followed by aripiprazole (n = 1,756), risperidone (n = 1,566), olanzapine (n = 1,394), and ziprasidone (n = 697). The absolute risks for congenital malformations per 1,000 live-born infants was 38.2 (95% CI, 26.6-54.7) for those treated with typicals and 44.5 (95% CI, 40.5-48.9) for those treated with atypicals versus 32.7 (95% CI, 32.4-33.0) for untreated women. In the fully adjusted analysis, the risk ratio was not statistically different for those exposed to atypical antipsychotics, compared with the control group, for malformations overall (relative risk, 1.05; 95% CI, 0.96-1.16) nor for cardiac malformations (RR, 1.06; 95% CI, 0.90-1.24). However, the risk remained elevated for risperidone for overall malformations (RR, 1.26; 1.02-1.56) and cardiac malformations (RR, 1.26; 95% CI, 0.88-1.81).
When Dr. Huybrechts and her colleagues redefined exposure as having filled two more prescriptions or having at least a 1-day supply in the first trimester, the results did not meaningfully change. However, the association appeared to strengthen somewhat for risperidone when filling two or more prescriptions (RR, 1.46 for any malformation; 95% CI, 1.01-2.10; RR, 1.87 for cardiac malformations; 95% CI, 1.09-3.19). The researchers observed no evidence of a dose-response relationship for any of the individual antipsychotics except risperidone. Risperidone dosages of 2 mg/day or more were associated with an increased risk for cardiac malformation (RR, 2.08; 95% CI, 1.32-3.28).
“The small increase in absolute risk and RR for malformations observed with risperidone should be interpreted with caution because no apparent biological mechanism can readily explain this outcome and the possibility of a chance finding cannot be ruled out,” the authors wrote in their study. “This finding should therefore be interpreted as a potential safety signal that will require follow-up in other studies.”
If the finding in this study is replicated, Dr. Meyer said, a number needed to harm analysis suggests that compared with no antipsychotic use. “Given the risks of bad outcomes that might occur related to medication switching or nonadherence, the risk-benefit ratio may tilt towards continuing risperidone, especially when a long-acting injectable [LAI] antipsychotic is needed in someone who responds to risperidone and either doesn’t respond to or tolerate the medications available in other LAI preparations such aripiprazole, haloperidol, or fluphenazine,” he said. “This need to balance the risks of exacerbating the mental disorder and the extremely small chance of an adverse pregnancy outcome is part of a clinical discussion one should have with the patient and her family.”
Dr. Meyer reported having received speaking or advising fees from Acadia, Alkermes, Allergan, Intracellular Therapies, Merck, Neurocrine, Otsuka America, Sunovion, and Teva.
LAS VEGAS – Assessing the risk of major congenital malformations related to antipsychotic exposure requires detailed assessment of other sources of risk, including those related to the diagnosis and associated behaviors, according to Jonathan M. Meyer, MD.
However, the largest study to date showed no significant difference in rates of major congenital malformations for those with one or more prescriptions for atypical antipsychotics in the first trimester, compared with pregnancies with no first trimester antipsychotic exposure.
In the U.S. general population, the estimated risk of major birth defects is 2%-4%, Dr. Meyer, a clinical professor of psychiatry at the University of California, San Diego, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.
Medications represent one source of risk for major congenital malformations in patients with psychiatric illness. Other factors include lifestyle factors such substance abuse and smoking, diet and physical activity, adherence with medical/prenatal care regimens, general medical disease burden, and unknown genetic risk because of the illness itself.
Until recently, published studies examining antipsychotic exposure and the risk for congenital malformations have been flawed because of numerous factors, Dr. Meyer said, including the small sample size of live births, absence of systematic collection of risk data prior to and during pregnancy, and failure to examine all possible covariates that might moderate the risk potentially attributable to the medication itself.
For example, researchers led by Frank Habermann, PhD, prospectively evaluated three cohorts who were followed in a psychiatry consultation in Freiburg, Germany: 453 women who received atypical antipsychotics in the first trimester of pregnancy (group A); 238 women who received typical antipsychotics in the first trimester of pregnancy (group B); and 1,104 women who had no records of treatment with medications associated with harmful fetal effects (group C).
Covariates included maternal age, alcohol consumption, smoking habits, number of previous spontaneous abortions, number of previous malformed children, and gestational week at delivery (J Clin Psychopharmacol. 2013;33[4]:453-62).
The researchers found that 5.2% of women in group A gave birth to a child with a major congenital malformation, compared with 5% in group B and 2.5% in group C. Nonsignificant associations were observed between group A vs. B (adjusted odds ratio, 1.26; 95% confidence interval, 0.57-2.82) and group B vs. C (adjusted OR, 1.71; 95% CI, 0.78-3.76). The only significant association noted was between group A and C (adjusted OR, 2.17; 95% CI, 1.20-3.91). However, Dr. Meyer emphasized limitations of the study, including its small sample size and certain missing covariates, including illegal substance use.
In addition, since subjects were enrolled in a consultation clinic, surveillance bias might have detected a higher number of CV malformations. “I don’t have a lot of confidence in this study because there were enormous sources of risk that were not controlled for,” said Dr. Meyer, who is also a psychopharmacology consultant for the California State Department of Hospitals.
In a separate study, researchers led by Lee S. Cohen, MD, assessed data from 487 women in the National Pregnancy Registry for Atypical Antipsychotics based at the Massachusetts General Hospital Center for Women’s Health, Boston. Of the 487 women, 353 were on atypical antipsychotics and 134 served as controls (Am J Psychiatry. 2016;73[3]:263-70). Medical records were obtained at baseline, month 7, and postpartum for 82% of subjects, which left 303 women in the final analysis. Covariates included demographic characteristics, medication use and dosage changes, social habits including smoking, use of alcohol and illicit drugs, medical and psychiatric history, and family history of birth defects.
Of 214 live births with first-trimester exposure to atypical antipsychotics, three major malformations were confirmed, while among the control group of 89 women, one major malformation was confirmed. The absolute risk of major malformations was 1.4% for exposed infants and 1.1% for unexposed infants. Meanwhile, the OR for major malformations comparing exposed infants was 1.25, which did not reach statistical significance (95% CI, 0.13-12.19). Limitations of the study include the small sample size of live births and the low overall rate of malformations, said Dr. Meyer. “This group of women living in the Boston area might not be representative of the general population based on the extremely low rates of congenital malformations for both cohorts in this study,” he commented.
In what Dr. Meyer said was the most robust study of its kind to date, researchers led by Krista F. Huybrechts, MS, PhD, drew from Medicaid data from 2000-2010 and included only women who were enrolled from 3 months before their last menstrual period through at least 1 month after delivery (JAMA Psychiatry. 2016;73[9]:938-46). The sample consisted of 1,341,715 pregnancies. Among those pregnancies, 9,258 women filled at least one prescription for an atypical antipsychotic, and 733 filled at least one prescription for a typical antipsychotic, for a total of 9,991 pregnancies. The researchers used propensity score matching to match for risk of antipsychotic exposure. They also balanced the antipsychotic-exposed and nonexposed groups for covariates that might be related to the outcome of interest (major congenital malformations), including (but not limited to) calendar year, age, race, smoking history, multiple gestation, indications for antipsychotic use, other maternal morbidity, concomitant medication use, and general markers of illness burden in the 3 months prior to pregnancy.
The atypical antipsychotics used included quetiapine (n = 4,221), followed by aripiprazole (n = 1,756), risperidone (n = 1,566), olanzapine (n = 1,394), and ziprasidone (n = 697). The absolute risks for congenital malformations per 1,000 live-born infants was 38.2 (95% CI, 26.6-54.7) for those treated with typicals and 44.5 (95% CI, 40.5-48.9) for those treated with atypicals versus 32.7 (95% CI, 32.4-33.0) for untreated women. In the fully adjusted analysis, the risk ratio was not statistically different for those exposed to atypical antipsychotics, compared with the control group, for malformations overall (relative risk, 1.05; 95% CI, 0.96-1.16) nor for cardiac malformations (RR, 1.06; 95% CI, 0.90-1.24). However, the risk remained elevated for risperidone for overall malformations (RR, 1.26; 1.02-1.56) and cardiac malformations (RR, 1.26; 95% CI, 0.88-1.81).
When Dr. Huybrechts and her colleagues redefined exposure as having filled two more prescriptions or having at least a 1-day supply in the first trimester, the results did not meaningfully change. However, the association appeared to strengthen somewhat for risperidone when filling two or more prescriptions (RR, 1.46 for any malformation; 95% CI, 1.01-2.10; RR, 1.87 for cardiac malformations; 95% CI, 1.09-3.19). The researchers observed no evidence of a dose-response relationship for any of the individual antipsychotics except risperidone. Risperidone dosages of 2 mg/day or more were associated with an increased risk for cardiac malformation (RR, 2.08; 95% CI, 1.32-3.28).
“The small increase in absolute risk and RR for malformations observed with risperidone should be interpreted with caution because no apparent biological mechanism can readily explain this outcome and the possibility of a chance finding cannot be ruled out,” the authors wrote in their study. “This finding should therefore be interpreted as a potential safety signal that will require follow-up in other studies.”
If the finding in this study is replicated, Dr. Meyer said, a number needed to harm analysis suggests that compared with no antipsychotic use. “Given the risks of bad outcomes that might occur related to medication switching or nonadherence, the risk-benefit ratio may tilt towards continuing risperidone, especially when a long-acting injectable [LAI] antipsychotic is needed in someone who responds to risperidone and either doesn’t respond to or tolerate the medications available in other LAI preparations such aripiprazole, haloperidol, or fluphenazine,” he said. “This need to balance the risks of exacerbating the mental disorder and the extremely small chance of an adverse pregnancy outcome is part of a clinical discussion one should have with the patient and her family.”
Dr. Meyer reported having received speaking or advising fees from Acadia, Alkermes, Allergan, Intracellular Therapies, Merck, Neurocrine, Otsuka America, Sunovion, and Teva.
LAS VEGAS – Assessing the risk of major congenital malformations related to antipsychotic exposure requires detailed assessment of other sources of risk, including those related to the diagnosis and associated behaviors, according to Jonathan M. Meyer, MD.
However, the largest study to date showed no significant difference in rates of major congenital malformations for those with one or more prescriptions for atypical antipsychotics in the first trimester, compared with pregnancies with no first trimester antipsychotic exposure.
In the U.S. general population, the estimated risk of major birth defects is 2%-4%, Dr. Meyer, a clinical professor of psychiatry at the University of California, San Diego, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.
Medications represent one source of risk for major congenital malformations in patients with psychiatric illness. Other factors include lifestyle factors such substance abuse and smoking, diet and physical activity, adherence with medical/prenatal care regimens, general medical disease burden, and unknown genetic risk because of the illness itself.
Until recently, published studies examining antipsychotic exposure and the risk for congenital malformations have been flawed because of numerous factors, Dr. Meyer said, including the small sample size of live births, absence of systematic collection of risk data prior to and during pregnancy, and failure to examine all possible covariates that might moderate the risk potentially attributable to the medication itself.
For example, researchers led by Frank Habermann, PhD, prospectively evaluated three cohorts who were followed in a psychiatry consultation in Freiburg, Germany: 453 women who received atypical antipsychotics in the first trimester of pregnancy (group A); 238 women who received typical antipsychotics in the first trimester of pregnancy (group B); and 1,104 women who had no records of treatment with medications associated with harmful fetal effects (group C).
Covariates included maternal age, alcohol consumption, smoking habits, number of previous spontaneous abortions, number of previous malformed children, and gestational week at delivery (J Clin Psychopharmacol. 2013;33[4]:453-62).
The researchers found that 5.2% of women in group A gave birth to a child with a major congenital malformation, compared with 5% in group B and 2.5% in group C. Nonsignificant associations were observed between group A vs. B (adjusted odds ratio, 1.26; 95% confidence interval, 0.57-2.82) and group B vs. C (adjusted OR, 1.71; 95% CI, 0.78-3.76). The only significant association noted was between group A and C (adjusted OR, 2.17; 95% CI, 1.20-3.91). However, Dr. Meyer emphasized limitations of the study, including its small sample size and certain missing covariates, including illegal substance use.
In addition, since subjects were enrolled in a consultation clinic, surveillance bias might have detected a higher number of CV malformations. “I don’t have a lot of confidence in this study because there were enormous sources of risk that were not controlled for,” said Dr. Meyer, who is also a psychopharmacology consultant for the California State Department of Hospitals.
In a separate study, researchers led by Lee S. Cohen, MD, assessed data from 487 women in the National Pregnancy Registry for Atypical Antipsychotics based at the Massachusetts General Hospital Center for Women’s Health, Boston. Of the 487 women, 353 were on atypical antipsychotics and 134 served as controls (Am J Psychiatry. 2016;73[3]:263-70). Medical records were obtained at baseline, month 7, and postpartum for 82% of subjects, which left 303 women in the final analysis. Covariates included demographic characteristics, medication use and dosage changes, social habits including smoking, use of alcohol and illicit drugs, medical and psychiatric history, and family history of birth defects.
Of 214 live births with first-trimester exposure to atypical antipsychotics, three major malformations were confirmed, while among the control group of 89 women, one major malformation was confirmed. The absolute risk of major malformations was 1.4% for exposed infants and 1.1% for unexposed infants. Meanwhile, the OR for major malformations comparing exposed infants was 1.25, which did not reach statistical significance (95% CI, 0.13-12.19). Limitations of the study include the small sample size of live births and the low overall rate of malformations, said Dr. Meyer. “This group of women living in the Boston area might not be representative of the general population based on the extremely low rates of congenital malformations for both cohorts in this study,” he commented.
In what Dr. Meyer said was the most robust study of its kind to date, researchers led by Krista F. Huybrechts, MS, PhD, drew from Medicaid data from 2000-2010 and included only women who were enrolled from 3 months before their last menstrual period through at least 1 month after delivery (JAMA Psychiatry. 2016;73[9]:938-46). The sample consisted of 1,341,715 pregnancies. Among those pregnancies, 9,258 women filled at least one prescription for an atypical antipsychotic, and 733 filled at least one prescription for a typical antipsychotic, for a total of 9,991 pregnancies. The researchers used propensity score matching to match for risk of antipsychotic exposure. They also balanced the antipsychotic-exposed and nonexposed groups for covariates that might be related to the outcome of interest (major congenital malformations), including (but not limited to) calendar year, age, race, smoking history, multiple gestation, indications for antipsychotic use, other maternal morbidity, concomitant medication use, and general markers of illness burden in the 3 months prior to pregnancy.
The atypical antipsychotics used included quetiapine (n = 4,221), followed by aripiprazole (n = 1,756), risperidone (n = 1,566), olanzapine (n = 1,394), and ziprasidone (n = 697). The absolute risks for congenital malformations per 1,000 live-born infants was 38.2 (95% CI, 26.6-54.7) for those treated with typicals and 44.5 (95% CI, 40.5-48.9) for those treated with atypicals versus 32.7 (95% CI, 32.4-33.0) for untreated women. In the fully adjusted analysis, the risk ratio was not statistically different for those exposed to atypical antipsychotics, compared with the control group, for malformations overall (relative risk, 1.05; 95% CI, 0.96-1.16) nor for cardiac malformations (RR, 1.06; 95% CI, 0.90-1.24). However, the risk remained elevated for risperidone for overall malformations (RR, 1.26; 1.02-1.56) and cardiac malformations (RR, 1.26; 95% CI, 0.88-1.81).
When Dr. Huybrechts and her colleagues redefined exposure as having filled two more prescriptions or having at least a 1-day supply in the first trimester, the results did not meaningfully change. However, the association appeared to strengthen somewhat for risperidone when filling two or more prescriptions (RR, 1.46 for any malformation; 95% CI, 1.01-2.10; RR, 1.87 for cardiac malformations; 95% CI, 1.09-3.19). The researchers observed no evidence of a dose-response relationship for any of the individual antipsychotics except risperidone. Risperidone dosages of 2 mg/day or more were associated with an increased risk for cardiac malformation (RR, 2.08; 95% CI, 1.32-3.28).
“The small increase in absolute risk and RR for malformations observed with risperidone should be interpreted with caution because no apparent biological mechanism can readily explain this outcome and the possibility of a chance finding cannot be ruled out,” the authors wrote in their study. “This finding should therefore be interpreted as a potential safety signal that will require follow-up in other studies.”
If the finding in this study is replicated, Dr. Meyer said, a number needed to harm analysis suggests that compared with no antipsychotic use. “Given the risks of bad outcomes that might occur related to medication switching or nonadherence, the risk-benefit ratio may tilt towards continuing risperidone, especially when a long-acting injectable [LAI] antipsychotic is needed in someone who responds to risperidone and either doesn’t respond to or tolerate the medications available in other LAI preparations such aripiprazole, haloperidol, or fluphenazine,” he said. “This need to balance the risks of exacerbating the mental disorder and the extremely small chance of an adverse pregnancy outcome is part of a clinical discussion one should have with the patient and her family.”
Dr. Meyer reported having received speaking or advising fees from Acadia, Alkermes, Allergan, Intracellular Therapies, Merck, Neurocrine, Otsuka America, Sunovion, and Teva.
EXPERT ANALYSIS FROM NPA 2019
Postpartum depression often tricky to diagnose
LAS VEGAS – Diagnosing postpartum depression can be tricky because of the wide range of body changes that occur during the postpartum period, but vigilance is warranted with mothers who express a lack of sleep and a lack of social support.
at an annual psychopharmacology update held by the Nevada Psychiatric Association. “This gives you information about depression and insomnia. Make sure to ask about anxiety symptoms. Also ask about any thoughts of suicide or harming the infant, and support from family and friends when she’s under stress and taking care of the baby.”
According to Dr. Friedman, a perinatal and forensic psychiatrist at Case Western Reserve University, Cleveland, social risk factors for postpartum depression (PPD) include being a victim of intimate partner violence and/or abuse, negative life events, decreased social support, relationship issues, and socioeconomic status. Psychological risk factors include anxiety/depression in pregnancy, personal or family history of PPD, and substance misuse. Biological risk factors include medical illness, multiple births, and having an infant with low birth weight/prematurity.
PPD affects 10%-20% of new mothers and peaks at 12 weeks. Postpartum psychosis, meanwhile, occurs in about 1-2 of every 1,000 deliveries. Anxiety comorbidity is common.
In the neonatal intensive care unit (NICU), PPD rates might increase from 28% to 70% depending on the study. Risk factors include personal or family history, disturbed relationships, unfavorable socioeconomic factors, and stressful life events. Obstetrical risk factors might include conception by assisted reproductive technologies and having a stillbirth in the year before conception. NICU-specific risk factors include less-effective coping strategies, greater perception of maternal role disruption, and decreased perception of nursing support. “A lot of mothers [in the NICU] talk to me about being on a roller roaster every day about what’s going to happen with their baby,” Dr. Friedman said.
The most widely used measure to screen for PPD is the 10-item self-rating Edinburgh Postnatal Depression Scale . A total score of 10 or more is considered a flag for the need to follow up for possible depressive symptoms. She advises clinicians to pay particular attention to how patients respond to item No. 10 on the scale, which reads, “The thought of harming myself has occurred to me.” (Optional answers range from “Yes, quite often” to “Never.”) She also recommends administering the screen at both pediatric and obstetrical office visits, “because mothers are more likely to attend a pediatrics appointment than her own [postpartum] follow-up.”
The differential diagnosis of PPD includes the baby blues, postpartum psychosis, postpartum anxiety/PTSD, medical causes, substance use disorder, and PPD in bipolar disorder. Baby blues is not synonymous with PPD. It affects the majority (50%-80%) of new mothers and is characterized by emotional sensitivity, mood lability, and irritability. It usually occurs within 5 days and resolves by the second week post partum.
Postpartum psychosis (PPP) occurs in about 1-2 of every 1,000 deliveries, typically in the first 2 weeks after delivery. The onset occurs rapidly, and PPP is most frequently correlated with bipolar disorder over time. PPP itself is characterized by grandiose bizarre delusions, mood lability, hallucinations, confusion, and disorganized behavior. “This can occur as a new onset of mental illness as well, so getting collateral information about her behaviors is important,” she said.
Dr. Friedman explained that those events occur post partum largely because of sleep deprivation and increasing stress as the woman adjusts to a mothering role. Hormonal shifts also occur, with a drop in estrogen levels. Obstetrical complications also might factor in.
Postpartum obsessive-compulsive disorder (OCD) is commonly comorbid with PPD and is distinguished by ego-dystonic intrusive thoughts. The mother might have intense distress that she is going to harm the infant and might start to avoid holding the baby out of concern. “Common things I’ve heard from women with postpartum OCD are: ‘I’m afraid I’m going to put the baby in the microwave or in the oven instead of dinner’ or ‘I’m afraid I’m going to leave the baby in the car overnight and she’ll freeze to death,’ ” she said.
Postpartum PTSD can be triggered by a traumatic event experience in the birthing process, such as an emergency C-section. Affected mothers avoid the infant and hospital, “reexperience” the trauma, are easily startled, irritable, and disconnected. Dr. Friedman also noted that early parental PTSD symptoms predict sleep and eating problems in childhood and less sensitive/more controlling maternal behaviors.
Medical conditions that mimic PPD include anemia, thyroid disease, hypoactive delirium, infections, and alcohol/substance use disorder.
The best available data show that mothers with PPD are more withdrawn, disengaged, display more hostility, and are more likely to have disrupted attachment with their babies, Dr. Friedman said. They also are less likely to employ healthy child development practices and to breastfeed. Untreated depression might lead to psychotic symptoms, suicide, or homicide. Paternal PPD also occurs in an estimated 10% of fathers and is moderately correlated with maternal PPD.
Potential risks of PPD include impaired bonding, attachment disturbance, language development, cognitive skills, and behavior problems.
Potential risks of untreated PPD include child neglect or abuse because of active symptoms, suicide, and psychotic or maltreatment-related infanticide. “If the mother is taking about harming herself, I often ask: ‘Have you thought of what would happen to your baby if you were to take your own life?’ ” Dr. Friedman offered. Peripartum suicide risk is lower than in the general female population, but it represents about 20% of peripartum deaths. Overdose is the most common method. “However, uncommon and dramatic methods are more common in this population,” she said. “Teens and stigmatized single mothers are at greater risk.”
Dr. Friedman noted that clinicians face risk of a malpractice lawsuit if they fail to treat, abandon the patient, fail to provide informed consent, and if there are bad outcomes. The best approach is to proactively communicate with the patient, partner, pediatrics, and obstetrics. “Conduct an individual risk-benefit assessment with the individual patient’s history,” she advised. “Don’t do anything knee jerk. Consult when needed, document, and consider lactation and future pregnancy possibility in women of reproductive age.”
Nonpharmacologic therapy might be the first line of treatment for mild to moderate symptoms. Options include cognitive-behavioral therapy, interpersonal psychotherapy, family therapy, psychodynamic psychotherapy, and supportive psychotherapy. She recommends close follow-up and conducting a careful medication history. Electroconvulsive therapy remains a possibility.
If medication use is warranted, “weigh the benefits of breastfeeding with the usually low drug exposure of the infant,” Dr. Friedman advised. “We want to use the least number of medications at an effective dose to optimize treatment. Newer medications have less perinatal data. Sertraline and paroxetine are usually the preferred selective serotonin reuptake inhibitors in lactation. However, fluoxetine or citalopram might be used depending on the patient’s response history/use in pregnancy.”
Dr. Friedman reported no disclosures.
LAS VEGAS – Diagnosing postpartum depression can be tricky because of the wide range of body changes that occur during the postpartum period, but vigilance is warranted with mothers who express a lack of sleep and a lack of social support.
at an annual psychopharmacology update held by the Nevada Psychiatric Association. “This gives you information about depression and insomnia. Make sure to ask about anxiety symptoms. Also ask about any thoughts of suicide or harming the infant, and support from family and friends when she’s under stress and taking care of the baby.”
According to Dr. Friedman, a perinatal and forensic psychiatrist at Case Western Reserve University, Cleveland, social risk factors for postpartum depression (PPD) include being a victim of intimate partner violence and/or abuse, negative life events, decreased social support, relationship issues, and socioeconomic status. Psychological risk factors include anxiety/depression in pregnancy, personal or family history of PPD, and substance misuse. Biological risk factors include medical illness, multiple births, and having an infant with low birth weight/prematurity.
PPD affects 10%-20% of new mothers and peaks at 12 weeks. Postpartum psychosis, meanwhile, occurs in about 1-2 of every 1,000 deliveries. Anxiety comorbidity is common.
In the neonatal intensive care unit (NICU), PPD rates might increase from 28% to 70% depending on the study. Risk factors include personal or family history, disturbed relationships, unfavorable socioeconomic factors, and stressful life events. Obstetrical risk factors might include conception by assisted reproductive technologies and having a stillbirth in the year before conception. NICU-specific risk factors include less-effective coping strategies, greater perception of maternal role disruption, and decreased perception of nursing support. “A lot of mothers [in the NICU] talk to me about being on a roller roaster every day about what’s going to happen with their baby,” Dr. Friedman said.
The most widely used measure to screen for PPD is the 10-item self-rating Edinburgh Postnatal Depression Scale . A total score of 10 or more is considered a flag for the need to follow up for possible depressive symptoms. She advises clinicians to pay particular attention to how patients respond to item No. 10 on the scale, which reads, “The thought of harming myself has occurred to me.” (Optional answers range from “Yes, quite often” to “Never.”) She also recommends administering the screen at both pediatric and obstetrical office visits, “because mothers are more likely to attend a pediatrics appointment than her own [postpartum] follow-up.”
The differential diagnosis of PPD includes the baby blues, postpartum psychosis, postpartum anxiety/PTSD, medical causes, substance use disorder, and PPD in bipolar disorder. Baby blues is not synonymous with PPD. It affects the majority (50%-80%) of new mothers and is characterized by emotional sensitivity, mood lability, and irritability. It usually occurs within 5 days and resolves by the second week post partum.
Postpartum psychosis (PPP) occurs in about 1-2 of every 1,000 deliveries, typically in the first 2 weeks after delivery. The onset occurs rapidly, and PPP is most frequently correlated with bipolar disorder over time. PPP itself is characterized by grandiose bizarre delusions, mood lability, hallucinations, confusion, and disorganized behavior. “This can occur as a new onset of mental illness as well, so getting collateral information about her behaviors is important,” she said.
Dr. Friedman explained that those events occur post partum largely because of sleep deprivation and increasing stress as the woman adjusts to a mothering role. Hormonal shifts also occur, with a drop in estrogen levels. Obstetrical complications also might factor in.
Postpartum obsessive-compulsive disorder (OCD) is commonly comorbid with PPD and is distinguished by ego-dystonic intrusive thoughts. The mother might have intense distress that she is going to harm the infant and might start to avoid holding the baby out of concern. “Common things I’ve heard from women with postpartum OCD are: ‘I’m afraid I’m going to put the baby in the microwave or in the oven instead of dinner’ or ‘I’m afraid I’m going to leave the baby in the car overnight and she’ll freeze to death,’ ” she said.
Postpartum PTSD can be triggered by a traumatic event experience in the birthing process, such as an emergency C-section. Affected mothers avoid the infant and hospital, “reexperience” the trauma, are easily startled, irritable, and disconnected. Dr. Friedman also noted that early parental PTSD symptoms predict sleep and eating problems in childhood and less sensitive/more controlling maternal behaviors.
Medical conditions that mimic PPD include anemia, thyroid disease, hypoactive delirium, infections, and alcohol/substance use disorder.
The best available data show that mothers with PPD are more withdrawn, disengaged, display more hostility, and are more likely to have disrupted attachment with their babies, Dr. Friedman said. They also are less likely to employ healthy child development practices and to breastfeed. Untreated depression might lead to psychotic symptoms, suicide, or homicide. Paternal PPD also occurs in an estimated 10% of fathers and is moderately correlated with maternal PPD.
Potential risks of PPD include impaired bonding, attachment disturbance, language development, cognitive skills, and behavior problems.
Potential risks of untreated PPD include child neglect or abuse because of active symptoms, suicide, and psychotic or maltreatment-related infanticide. “If the mother is taking about harming herself, I often ask: ‘Have you thought of what would happen to your baby if you were to take your own life?’ ” Dr. Friedman offered. Peripartum suicide risk is lower than in the general female population, but it represents about 20% of peripartum deaths. Overdose is the most common method. “However, uncommon and dramatic methods are more common in this population,” she said. “Teens and stigmatized single mothers are at greater risk.”
Dr. Friedman noted that clinicians face risk of a malpractice lawsuit if they fail to treat, abandon the patient, fail to provide informed consent, and if there are bad outcomes. The best approach is to proactively communicate with the patient, partner, pediatrics, and obstetrics. “Conduct an individual risk-benefit assessment with the individual patient’s history,” she advised. “Don’t do anything knee jerk. Consult when needed, document, and consider lactation and future pregnancy possibility in women of reproductive age.”
Nonpharmacologic therapy might be the first line of treatment for mild to moderate symptoms. Options include cognitive-behavioral therapy, interpersonal psychotherapy, family therapy, psychodynamic psychotherapy, and supportive psychotherapy. She recommends close follow-up and conducting a careful medication history. Electroconvulsive therapy remains a possibility.
If medication use is warranted, “weigh the benefits of breastfeeding with the usually low drug exposure of the infant,” Dr. Friedman advised. “We want to use the least number of medications at an effective dose to optimize treatment. Newer medications have less perinatal data. Sertraline and paroxetine are usually the preferred selective serotonin reuptake inhibitors in lactation. However, fluoxetine or citalopram might be used depending on the patient’s response history/use in pregnancy.”
Dr. Friedman reported no disclosures.
LAS VEGAS – Diagnosing postpartum depression can be tricky because of the wide range of body changes that occur during the postpartum period, but vigilance is warranted with mothers who express a lack of sleep and a lack of social support.
at an annual psychopharmacology update held by the Nevada Psychiatric Association. “This gives you information about depression and insomnia. Make sure to ask about anxiety symptoms. Also ask about any thoughts of suicide or harming the infant, and support from family and friends when she’s under stress and taking care of the baby.”
According to Dr. Friedman, a perinatal and forensic psychiatrist at Case Western Reserve University, Cleveland, social risk factors for postpartum depression (PPD) include being a victim of intimate partner violence and/or abuse, negative life events, decreased social support, relationship issues, and socioeconomic status. Psychological risk factors include anxiety/depression in pregnancy, personal or family history of PPD, and substance misuse. Biological risk factors include medical illness, multiple births, and having an infant with low birth weight/prematurity.
PPD affects 10%-20% of new mothers and peaks at 12 weeks. Postpartum psychosis, meanwhile, occurs in about 1-2 of every 1,000 deliveries. Anxiety comorbidity is common.
In the neonatal intensive care unit (NICU), PPD rates might increase from 28% to 70% depending on the study. Risk factors include personal or family history, disturbed relationships, unfavorable socioeconomic factors, and stressful life events. Obstetrical risk factors might include conception by assisted reproductive technologies and having a stillbirth in the year before conception. NICU-specific risk factors include less-effective coping strategies, greater perception of maternal role disruption, and decreased perception of nursing support. “A lot of mothers [in the NICU] talk to me about being on a roller roaster every day about what’s going to happen with their baby,” Dr. Friedman said.
The most widely used measure to screen for PPD is the 10-item self-rating Edinburgh Postnatal Depression Scale . A total score of 10 or more is considered a flag for the need to follow up for possible depressive symptoms. She advises clinicians to pay particular attention to how patients respond to item No. 10 on the scale, which reads, “The thought of harming myself has occurred to me.” (Optional answers range from “Yes, quite often” to “Never.”) She also recommends administering the screen at both pediatric and obstetrical office visits, “because mothers are more likely to attend a pediatrics appointment than her own [postpartum] follow-up.”
The differential diagnosis of PPD includes the baby blues, postpartum psychosis, postpartum anxiety/PTSD, medical causes, substance use disorder, and PPD in bipolar disorder. Baby blues is not synonymous with PPD. It affects the majority (50%-80%) of new mothers and is characterized by emotional sensitivity, mood lability, and irritability. It usually occurs within 5 days and resolves by the second week post partum.
Postpartum psychosis (PPP) occurs in about 1-2 of every 1,000 deliveries, typically in the first 2 weeks after delivery. The onset occurs rapidly, and PPP is most frequently correlated with bipolar disorder over time. PPP itself is characterized by grandiose bizarre delusions, mood lability, hallucinations, confusion, and disorganized behavior. “This can occur as a new onset of mental illness as well, so getting collateral information about her behaviors is important,” she said.
Dr. Friedman explained that those events occur post partum largely because of sleep deprivation and increasing stress as the woman adjusts to a mothering role. Hormonal shifts also occur, with a drop in estrogen levels. Obstetrical complications also might factor in.
Postpartum obsessive-compulsive disorder (OCD) is commonly comorbid with PPD and is distinguished by ego-dystonic intrusive thoughts. The mother might have intense distress that she is going to harm the infant and might start to avoid holding the baby out of concern. “Common things I’ve heard from women with postpartum OCD are: ‘I’m afraid I’m going to put the baby in the microwave or in the oven instead of dinner’ or ‘I’m afraid I’m going to leave the baby in the car overnight and she’ll freeze to death,’ ” she said.
Postpartum PTSD can be triggered by a traumatic event experience in the birthing process, such as an emergency C-section. Affected mothers avoid the infant and hospital, “reexperience” the trauma, are easily startled, irritable, and disconnected. Dr. Friedman also noted that early parental PTSD symptoms predict sleep and eating problems in childhood and less sensitive/more controlling maternal behaviors.
Medical conditions that mimic PPD include anemia, thyroid disease, hypoactive delirium, infections, and alcohol/substance use disorder.
The best available data show that mothers with PPD are more withdrawn, disengaged, display more hostility, and are more likely to have disrupted attachment with their babies, Dr. Friedman said. They also are less likely to employ healthy child development practices and to breastfeed. Untreated depression might lead to psychotic symptoms, suicide, or homicide. Paternal PPD also occurs in an estimated 10% of fathers and is moderately correlated with maternal PPD.
Potential risks of PPD include impaired bonding, attachment disturbance, language development, cognitive skills, and behavior problems.
Potential risks of untreated PPD include child neglect or abuse because of active symptoms, suicide, and psychotic or maltreatment-related infanticide. “If the mother is taking about harming herself, I often ask: ‘Have you thought of what would happen to your baby if you were to take your own life?’ ” Dr. Friedman offered. Peripartum suicide risk is lower than in the general female population, but it represents about 20% of peripartum deaths. Overdose is the most common method. “However, uncommon and dramatic methods are more common in this population,” she said. “Teens and stigmatized single mothers are at greater risk.”
Dr. Friedman noted that clinicians face risk of a malpractice lawsuit if they fail to treat, abandon the patient, fail to provide informed consent, and if there are bad outcomes. The best approach is to proactively communicate with the patient, partner, pediatrics, and obstetrics. “Conduct an individual risk-benefit assessment with the individual patient’s history,” she advised. “Don’t do anything knee jerk. Consult when needed, document, and consider lactation and future pregnancy possibility in women of reproductive age.”
Nonpharmacologic therapy might be the first line of treatment for mild to moderate symptoms. Options include cognitive-behavioral therapy, interpersonal psychotherapy, family therapy, psychodynamic psychotherapy, and supportive psychotherapy. She recommends close follow-up and conducting a careful medication history. Electroconvulsive therapy remains a possibility.
If medication use is warranted, “weigh the benefits of breastfeeding with the usually low drug exposure of the infant,” Dr. Friedman advised. “We want to use the least number of medications at an effective dose to optimize treatment. Newer medications have less perinatal data. Sertraline and paroxetine are usually the preferred selective serotonin reuptake inhibitors in lactation. However, fluoxetine or citalopram might be used depending on the patient’s response history/use in pregnancy.”
Dr. Friedman reported no disclosures.
EXPERT ANALYSIS FROM NPA 2019