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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
Mood and behavior are different targets for irritability in children
BROOKLYN, N.Y. – As a target of therapy in children with a psychiatric disorder, irritability expressed as grumpy mood or anger should be uncoupled from irritability expressed as threatening behavior, according to an exploration of this common clinical issue at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“Irritability is like fever,” reported Gabrielle A. Carlson, MD, professor of psychiatry and pediatrics, State University of New York at Stony Brook. “It is a nonspecific symptom that only tells you that something is wrong.”
Irritability might be nothing more than a negative mood, but it also can be the source of explosive aggression, leading to tantrums and destructive behaviors, according to Dr. Carlson. She placed them into two different categories when considering treatment. Irritability leading to annoyance, grumpiness, withdrawal, or persistent anger is characterized as the “internalizing” or “tonic” form of the symptom. As opposed to the aggressive subtype, the tonic form is more closely associated with depression or anxiety. Irritability leading to extreme verbal outbursts or physical violence is characterized as the “externalizing” or “phasic” form, Dr. Carlson said. This type of irritability, defined by behavior more than mood, might signal disruptive mood dysregulation disorder (DMDD). But it is important to recognize that DMDD can overlap with other conditions, such as attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, oppositional defiant disorder (ODD), and autism spectrum disorders.
In defining the impact of treatments on tonic versus phasic symptoms of irritability within the context of the underlying diagnoses, studies have not done a good job in separating relative effects on the two key forms of irritability, Dr. Carlson said.
“Irritability needs to be measured not only by how one feels but what one does,” said Dr. Carlson, explaining that the impact of therapy has not always been adequately described in therapy studies.
For the tonic form, irritability is likely to improve or resolve with control of the underlying psychiatric condition. Although this might also be true of the phasic form, this type of irritability often accompanies conditions that are less readily controlled even through the threat of self-harm, harm to others, or other destructive behaviors invites intervention specifically targeted at this symptom.
Unfortunately, the best approach to irritability is unclear for many underling pathologies.
“Clinicians should recognize that empirical evidence is still lacking as to aggression-targeted treatments with favorable benefit-risk profiles for children and adolescents with ADHD and severe aggression,” said Dr. Carlson, providing ADHD as one of several examples.
Psychological interventions, such as dialectical behavior therapy in children (DBT-C), have been associated with control of both tonic and phasic forms of irritability, but Dr. Carlson cautioned that few studies have adequately differentiated improvement in irritability as measured by behavior relative to mood. In addition, the baseline severity and the degree to which improvement meant adequate control have been unclear.
“Many psychological treatments are school based or group delivered, making it likely that patients are less impaired than explosive kids in psychiatry clinics and hospitals,” Dr. Carlson said.
Providing some practical tips for addressing the phasic form of irritability, She advised clinicians to “maximize the treatment of the base condition” but to add pharmacologic therapies to psychological interventions if symptoms persist.
“Our pendulum has swung from dishing out atypicals to eschewing them completely,” Dr. Carlson noted. Although she agreed these are no longer appropriate as first-line therapies, she suggested they might be employed judiciously if weight gain is monitored carefully.
“If they don’t work, stop them. If they do work, try to limit the duration of use,” Dr. Carlson said.
She reported having no relevant financial relationships to disclose.
BROOKLYN, N.Y. – As a target of therapy in children with a psychiatric disorder, irritability expressed as grumpy mood or anger should be uncoupled from irritability expressed as threatening behavior, according to an exploration of this common clinical issue at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“Irritability is like fever,” reported Gabrielle A. Carlson, MD, professor of psychiatry and pediatrics, State University of New York at Stony Brook. “It is a nonspecific symptom that only tells you that something is wrong.”
Irritability might be nothing more than a negative mood, but it also can be the source of explosive aggression, leading to tantrums and destructive behaviors, according to Dr. Carlson. She placed them into two different categories when considering treatment. Irritability leading to annoyance, grumpiness, withdrawal, or persistent anger is characterized as the “internalizing” or “tonic” form of the symptom. As opposed to the aggressive subtype, the tonic form is more closely associated with depression or anxiety. Irritability leading to extreme verbal outbursts or physical violence is characterized as the “externalizing” or “phasic” form, Dr. Carlson said. This type of irritability, defined by behavior more than mood, might signal disruptive mood dysregulation disorder (DMDD). But it is important to recognize that DMDD can overlap with other conditions, such as attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, oppositional defiant disorder (ODD), and autism spectrum disorders.
In defining the impact of treatments on tonic versus phasic symptoms of irritability within the context of the underlying diagnoses, studies have not done a good job in separating relative effects on the two key forms of irritability, Dr. Carlson said.
“Irritability needs to be measured not only by how one feels but what one does,” said Dr. Carlson, explaining that the impact of therapy has not always been adequately described in therapy studies.
For the tonic form, irritability is likely to improve or resolve with control of the underlying psychiatric condition. Although this might also be true of the phasic form, this type of irritability often accompanies conditions that are less readily controlled even through the threat of self-harm, harm to others, or other destructive behaviors invites intervention specifically targeted at this symptom.
Unfortunately, the best approach to irritability is unclear for many underling pathologies.
“Clinicians should recognize that empirical evidence is still lacking as to aggression-targeted treatments with favorable benefit-risk profiles for children and adolescents with ADHD and severe aggression,” said Dr. Carlson, providing ADHD as one of several examples.
Psychological interventions, such as dialectical behavior therapy in children (DBT-C), have been associated with control of both tonic and phasic forms of irritability, but Dr. Carlson cautioned that few studies have adequately differentiated improvement in irritability as measured by behavior relative to mood. In addition, the baseline severity and the degree to which improvement meant adequate control have been unclear.
“Many psychological treatments are school based or group delivered, making it likely that patients are less impaired than explosive kids in psychiatry clinics and hospitals,” Dr. Carlson said.
Providing some practical tips for addressing the phasic form of irritability, She advised clinicians to “maximize the treatment of the base condition” but to add pharmacologic therapies to psychological interventions if symptoms persist.
“Our pendulum has swung from dishing out atypicals to eschewing them completely,” Dr. Carlson noted. Although she agreed these are no longer appropriate as first-line therapies, she suggested they might be employed judiciously if weight gain is monitored carefully.
“If they don’t work, stop them. If they do work, try to limit the duration of use,” Dr. Carlson said.
She reported having no relevant financial relationships to disclose.
BROOKLYN, N.Y. – As a target of therapy in children with a psychiatric disorder, irritability expressed as grumpy mood or anger should be uncoupled from irritability expressed as threatening behavior, according to an exploration of this common clinical issue at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“Irritability is like fever,” reported Gabrielle A. Carlson, MD, professor of psychiatry and pediatrics, State University of New York at Stony Brook. “It is a nonspecific symptom that only tells you that something is wrong.”
Irritability might be nothing more than a negative mood, but it also can be the source of explosive aggression, leading to tantrums and destructive behaviors, according to Dr. Carlson. She placed them into two different categories when considering treatment. Irritability leading to annoyance, grumpiness, withdrawal, or persistent anger is characterized as the “internalizing” or “tonic” form of the symptom. As opposed to the aggressive subtype, the tonic form is more closely associated with depression or anxiety. Irritability leading to extreme verbal outbursts or physical violence is characterized as the “externalizing” or “phasic” form, Dr. Carlson said. This type of irritability, defined by behavior more than mood, might signal disruptive mood dysregulation disorder (DMDD). But it is important to recognize that DMDD can overlap with other conditions, such as attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, oppositional defiant disorder (ODD), and autism spectrum disorders.
In defining the impact of treatments on tonic versus phasic symptoms of irritability within the context of the underlying diagnoses, studies have not done a good job in separating relative effects on the two key forms of irritability, Dr. Carlson said.
“Irritability needs to be measured not only by how one feels but what one does,” said Dr. Carlson, explaining that the impact of therapy has not always been adequately described in therapy studies.
For the tonic form, irritability is likely to improve or resolve with control of the underlying psychiatric condition. Although this might also be true of the phasic form, this type of irritability often accompanies conditions that are less readily controlled even through the threat of self-harm, harm to others, or other destructive behaviors invites intervention specifically targeted at this symptom.
Unfortunately, the best approach to irritability is unclear for many underling pathologies.
“Clinicians should recognize that empirical evidence is still lacking as to aggression-targeted treatments with favorable benefit-risk profiles for children and adolescents with ADHD and severe aggression,” said Dr. Carlson, providing ADHD as one of several examples.
Psychological interventions, such as dialectical behavior therapy in children (DBT-C), have been associated with control of both tonic and phasic forms of irritability, but Dr. Carlson cautioned that few studies have adequately differentiated improvement in irritability as measured by behavior relative to mood. In addition, the baseline severity and the degree to which improvement meant adequate control have been unclear.
“Many psychological treatments are school based or group delivered, making it likely that patients are less impaired than explosive kids in psychiatry clinics and hospitals,” Dr. Carlson said.
Providing some practical tips for addressing the phasic form of irritability, She advised clinicians to “maximize the treatment of the base condition” but to add pharmacologic therapies to psychological interventions if symptoms persist.
“Our pendulum has swung from dishing out atypicals to eschewing them completely,” Dr. Carlson noted. Although she agreed these are no longer appropriate as first-line therapies, she suggested they might be employed judiciously if weight gain is monitored carefully.
“If they don’t work, stop them. If they do work, try to limit the duration of use,” Dr. Carlson said.
She reported having no relevant financial relationships to disclose.
REPORTING FROM The PSYCHOPHARMACOLOGY UPDATE INSTITUTE
Early lead exposure tied to greater psychopathology in adulthood
Lead exposure during childhood appears tied to a significant increase in the risk of psychopathology in adulthood, results of a multidecade, prospective cohort study show.
“These results suggest that early life lead exposure in the era of leaded gasoline experienced by individuals who are currently adults may have contributed to subtle, lifelong differences in emotion and behavior that are detectable at least up to 38 years of age,” Aaron Reuben and his coauthors wrote in JAMA Psychiatry.
The ongoing Dunedin longitudinal cohort study in New Zealand has followed 1,037 individuals born during 1972-1973. Of these individuals, 579 were tested for lead exposure at 11 years of age. The study assessed their mental health at 18, 21, 26, 32, and 38 years of age.
“Although follow-up studies of lead-tested children have reported the persistence of lead-related cognitive deficits well into adulthood, apart from antisocial outcomes, the long-term mental and behavioral health consequences of early life lead exposure have not been fully characterized,” wrote Mr. Reuben, a PhD student in the department of psychology and neuroscience at Duke University in Durham, N.C., and his coauthors.
Researchers saw that, for each 5-mcg/dL increase in childhood blood lead level, there was a significant 1.34-point increase in general psychopathology (P = 0.03), which was largely driven by a 1.41-point increase in internalizing (P = 0.02) and 1.30-point increase in thought-disorder symptoms (P = 0.04). Those associations were seen after adjustment for covariates, such as family socioeconomic status, maternal IQ, and family history of mental illness.
Adults who had higher lead exposure during childhood also were described by their informants – close friends or family members – as being significantly more neurotic, less agreeable, and less conscientious. However, they showed no significant differences in extroversion or in openness to experience, compared with those with less lead exposure.
“These results suggest that early-life lead exposure in the era of leaded gasoline experienced by individuals who are currently adults may have contributed to subtle, lifelong differences in emotion and behavior that are detectable at least up to 38 years of age,” the authors wrote.
They noted that the size of the effect was around one-third the size of the associations seen between psychopathology and other risk factors, such as family history of mental illness and childhood maltreatment. However, the effects of lead exposure on adult psychopathology were similar to its effects on IQ and stronger than the associations seen between lead exposure and criminal offending.
The researchers also examined how early these psychopathology symptoms could be detected with use of parent- and teacher-reported measures of antisocial behavior, hyperactivity, and internalizing from 11 years of age. This showed that individuals with higher lead exposure scored higher on these measures even at 11 years of age, “suggesting that
Mr. Reuben and his associates cited several limitations. One is that the study used a cohort that was predominantly white and born in the 1970s. Also, as an observational study, it does not establish causality between lead exposure and psychopathology.
Nevertheless, they wrote, the study results suggest that adult patients who were exposed to high levels of lead as children might benefit from increased screening and access to mental health services.
The Dunedin study is supported by the New Zealand Health Research Council and the New Zealand Ministry of Business, Innovation, and Employment. This study was supported by several entities, including the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Human Development, and the National Institute of Environmental Health Sciences. The authors reported no conflicts of interest.
SOURCE: Reuben A et al. JAMA Psychiatry. 2019 Jan 23. doi: 10.1001/jamapsychiatry.2018.4192.
Lead exposure during childhood appears tied to a significant increase in the risk of psychopathology in adulthood, results of a multidecade, prospective cohort study show.
“These results suggest that early life lead exposure in the era of leaded gasoline experienced by individuals who are currently adults may have contributed to subtle, lifelong differences in emotion and behavior that are detectable at least up to 38 years of age,” Aaron Reuben and his coauthors wrote in JAMA Psychiatry.
The ongoing Dunedin longitudinal cohort study in New Zealand has followed 1,037 individuals born during 1972-1973. Of these individuals, 579 were tested for lead exposure at 11 years of age. The study assessed their mental health at 18, 21, 26, 32, and 38 years of age.
“Although follow-up studies of lead-tested children have reported the persistence of lead-related cognitive deficits well into adulthood, apart from antisocial outcomes, the long-term mental and behavioral health consequences of early life lead exposure have not been fully characterized,” wrote Mr. Reuben, a PhD student in the department of psychology and neuroscience at Duke University in Durham, N.C., and his coauthors.
Researchers saw that, for each 5-mcg/dL increase in childhood blood lead level, there was a significant 1.34-point increase in general psychopathology (P = 0.03), which was largely driven by a 1.41-point increase in internalizing (P = 0.02) and 1.30-point increase in thought-disorder symptoms (P = 0.04). Those associations were seen after adjustment for covariates, such as family socioeconomic status, maternal IQ, and family history of mental illness.
Adults who had higher lead exposure during childhood also were described by their informants – close friends or family members – as being significantly more neurotic, less agreeable, and less conscientious. However, they showed no significant differences in extroversion or in openness to experience, compared with those with less lead exposure.
“These results suggest that early-life lead exposure in the era of leaded gasoline experienced by individuals who are currently adults may have contributed to subtle, lifelong differences in emotion and behavior that are detectable at least up to 38 years of age,” the authors wrote.
They noted that the size of the effect was around one-third the size of the associations seen between psychopathology and other risk factors, such as family history of mental illness and childhood maltreatment. However, the effects of lead exposure on adult psychopathology were similar to its effects on IQ and stronger than the associations seen between lead exposure and criminal offending.
The researchers also examined how early these psychopathology symptoms could be detected with use of parent- and teacher-reported measures of antisocial behavior, hyperactivity, and internalizing from 11 years of age. This showed that individuals with higher lead exposure scored higher on these measures even at 11 years of age, “suggesting that
Mr. Reuben and his associates cited several limitations. One is that the study used a cohort that was predominantly white and born in the 1970s. Also, as an observational study, it does not establish causality between lead exposure and psychopathology.
Nevertheless, they wrote, the study results suggest that adult patients who were exposed to high levels of lead as children might benefit from increased screening and access to mental health services.
The Dunedin study is supported by the New Zealand Health Research Council and the New Zealand Ministry of Business, Innovation, and Employment. This study was supported by several entities, including the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Human Development, and the National Institute of Environmental Health Sciences. The authors reported no conflicts of interest.
SOURCE: Reuben A et al. JAMA Psychiatry. 2019 Jan 23. doi: 10.1001/jamapsychiatry.2018.4192.
Lead exposure during childhood appears tied to a significant increase in the risk of psychopathology in adulthood, results of a multidecade, prospective cohort study show.
“These results suggest that early life lead exposure in the era of leaded gasoline experienced by individuals who are currently adults may have contributed to subtle, lifelong differences in emotion and behavior that are detectable at least up to 38 years of age,” Aaron Reuben and his coauthors wrote in JAMA Psychiatry.
The ongoing Dunedin longitudinal cohort study in New Zealand has followed 1,037 individuals born during 1972-1973. Of these individuals, 579 were tested for lead exposure at 11 years of age. The study assessed their mental health at 18, 21, 26, 32, and 38 years of age.
“Although follow-up studies of lead-tested children have reported the persistence of lead-related cognitive deficits well into adulthood, apart from antisocial outcomes, the long-term mental and behavioral health consequences of early life lead exposure have not been fully characterized,” wrote Mr. Reuben, a PhD student in the department of psychology and neuroscience at Duke University in Durham, N.C., and his coauthors.
Researchers saw that, for each 5-mcg/dL increase in childhood blood lead level, there was a significant 1.34-point increase in general psychopathology (P = 0.03), which was largely driven by a 1.41-point increase in internalizing (P = 0.02) and 1.30-point increase in thought-disorder symptoms (P = 0.04). Those associations were seen after adjustment for covariates, such as family socioeconomic status, maternal IQ, and family history of mental illness.
Adults who had higher lead exposure during childhood also were described by their informants – close friends or family members – as being significantly more neurotic, less agreeable, and less conscientious. However, they showed no significant differences in extroversion or in openness to experience, compared with those with less lead exposure.
“These results suggest that early-life lead exposure in the era of leaded gasoline experienced by individuals who are currently adults may have contributed to subtle, lifelong differences in emotion and behavior that are detectable at least up to 38 years of age,” the authors wrote.
They noted that the size of the effect was around one-third the size of the associations seen between psychopathology and other risk factors, such as family history of mental illness and childhood maltreatment. However, the effects of lead exposure on adult psychopathology were similar to its effects on IQ and stronger than the associations seen between lead exposure and criminal offending.
The researchers also examined how early these psychopathology symptoms could be detected with use of parent- and teacher-reported measures of antisocial behavior, hyperactivity, and internalizing from 11 years of age. This showed that individuals with higher lead exposure scored higher on these measures even at 11 years of age, “suggesting that
Mr. Reuben and his associates cited several limitations. One is that the study used a cohort that was predominantly white and born in the 1970s. Also, as an observational study, it does not establish causality between lead exposure and psychopathology.
Nevertheless, they wrote, the study results suggest that adult patients who were exposed to high levels of lead as children might benefit from increased screening and access to mental health services.
The Dunedin study is supported by the New Zealand Health Research Council and the New Zealand Ministry of Business, Innovation, and Employment. This study was supported by several entities, including the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Human Development, and the National Institute of Environmental Health Sciences. The authors reported no conflicts of interest.
SOURCE: Reuben A et al. JAMA Psychiatry. 2019 Jan 23. doi: 10.1001/jamapsychiatry.2018.4192.
FROM JAMA PSYCHIATRY
Key clinical point: Higher lead exposure in childhood is linked to psychopathology in adulthood.
Major finding: Children who experienced more lead exposure in childhood show more internalizing and thought-disorder symptoms in adulthood.
Study details: Longitudinal cohort study of 579 individuals.
Disclosures: The Dunedin study is supported by the New Zealand Health Research Council and the New Zealand Ministry of Business, Innovation, and Employment. This study was supported by several entities, including the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Human Development, and the National Institute of Environmental Health Sciences. The authors reported no conflicts of interest.
Source: Reuben A et al. JAMA Psychiatry. 2019 Jan 23. doi: 10.1001/jamapsychiatry.2018.4192.
A prescription for ‘deprescribing’: A case report
In 2016, Swapnil Gupta, MD, and John Daniel Cahill, MD, PhD, challenged the field of psychiatry to reexamine our prescribing patterns. They warned against our use of polypharmacy when not attached to improvement in functioning for our patients.1 They were concerned about the lack of evidence for those treatment regimens and for our diagnostic criteria. In their inspiring article, they described how psychiatrists might proceed in the process of “deprescribing” – which they define as a process of pharmacologic regimen optimization through reducing or ending medications for which “benefits no longer outweigh risks.”1
In my practice, I routinely confront medication regimens that I have never encountered in the literature. The evidence for two psychotropics is limited but certainly available, in particular adjunct treatment of antidepressants2 and mood stabilizers.3 The evidence supporting the use of more than two psychotropics, however, is quite sparse. Yet, patients often enter my office on more than five psychotropics. I am also confronted with poorly defined diagnostic labels – which present more as means to justify polypharmacy than a thorough review of the patient’s current state.
Dr. Gupta and Dr. Cahill recommend a series of steps aimed at attempting the deprescription of psychotropics. Those steps include timeliness, knowledge of the patient’s current regimen, discussion about the risk of prescriptions, discussion about deprescribing, choosing the right medications to stop, a plan for describing, and monitoring. In the case presented below, I used some of those steps in an effort to provide the best care for the patient. Key details of the case have been changed, including the name, to protect the patient’s confidentiality.
Overview of the case
Rosalie Bertin is a 54-year-old female who has been treated for depression by a variety of primary care physicians for the better part of the last 30 years. She had tried an array of antidepressants, including sertraline, citalopram, duloxetine, and mirtazapine, over that time. Each seemed to provide some benefit when reviewing the notes, but there is no mention of why she was continued on those medications despite the absence of continuing symptoms. Occasionally, Rosalie would present to her clinician tearful and endorsing sadness, though the record did not comment on reports of energy, concentration, sleep, appetite, and interest.
In 2014, Rosalie’s husband passed away from lung cancer. His death was fairly quick, and initially, Rosalie did not mention any significant emotional complaints. However, when visiting her primary care physician 4 months later, she was noted to experience auditory hallucinations. “Sometimes I hear my husband when I am alone in my home,” she said. Rosalie was referred to a psychiatrist with a diagnosis of “psychosis not otherwise specified.”
When discussing her condition with the psychiatrist, Rosalie mentioned experiencing low mood, and having diminished interest in engaging in activities. “I miss Marc when I go places; I used to do everything with him.” She reported hearing him often but only when at her home. He would say things like, “I miss you,” or ask her about her day. She was diagnosed with “major depressive disorder with psychotic features.” Risperidone was added to the escitalopram, buspirone, and gabapentin that had been started by her primary care physician.
After several months of psychotropic management, the dose of risperidone was titrated to 8 mg per day. Her mood symptoms were unchanged, but she now was complaining of poor concentration and memory. The psychiatrist performed a Mini-Mental State Examination (MMSE). It was noted that taking the MMSE engendered significant anxiety for the patient. Rosalie received a score suggesting mild cognitive impairment. She was started on donepezil for the memory complaint, quetiapine for the continued voices, and recommended for disability.
Once on short-term disability, the patient relocated to live closer to her mother in San Diego and subsequently contacted me about continuing psychiatric care.
Initial visit
Rosalie is a petite white woman, raised in the Midwest, who married her high school sweetheart, and subsequently became an administrative assistant. Rosalie and Marc were unable to have children. Marc was an engineer, and a longtime smoker. She describes their lives as simple – “few friends, few vacations, few problems, few regrets.” She states she misses her husband and often cries when thinking about him.
When asked about psychiatric diagnoses, she answered: “I have psychosis. … My doctor said maybe schizophrenia, but he is not sure yet.” She described schizophrenia as hearing voices. Rosalie also mentioned having memory problems: “They cannot tell if it is Alzheimer’s disease until I die and they look at my brain, but the medication should delay the progression.”
She reported no significant effect from her prior antidepressant trials: “I am not sure if or how they helped.” Rosalie could not explain the role of the medication. “I take medications as prescribed by my doctor,” she said.
When discussing her antipsychotics, she mentioned: “Those are strong medications; it is hard for me to stay awake with them.” She declared having had no changes in the voices while on the risperidone but said they went away since also being on the quetiapine: “I wonder if the combination of the two really fixed my brain imbalance.”
Assessment
I admit that I have a critical bias against the overuse of psychotropics, and this might have painted how I interpreted Rosalie’s story. Nonetheless, I was honest with her and told her of my concerns. I informed her that her diagnosis was not consistent with my understanding of mood and thought disorders. Her initial reports of depression neither met the DSM criteria for depression nor felt consistent with my conceptualization of the illness. She had retained appropriate functioning and seemed to be responding with the sadness expected when facing difficult challenges like grief.
Her subsequent reports of auditory hallucinations were not associated with delusions or forms of disorganization that I would expect in someone with a thought disorder. Furthermore, the context of the onset gave me the impression that this was part of her process of grief. Her poor result in the dementia screen was most surprising and inconsistent with my evaluation. I told her that I suspected that she was not suffering from Alzheimer’s but from being overmedicated and from anxiety at the time of the testing.
She was excited and hesitant about my report. She was surprised by the length of our visit and interested in hearing more from me. Strangely, I wished she had challenged my different approach. I think that I was hoping she would question my conceptualization, the way I hoped she would have done with her prior clinicians. Nonetheless, she agreed to make a plan with me.
Treatment plan
We decided to review each of her medications and discuss their benefits and risks over a couple of visits. She was most eager to discontinue the donepezil, which had caused diarrhea. She was concerned when I informed her of the potential side effects of antipsychotics. “My doctor asked me if I had any side effects at each visit; I answered that I felt nothing wrong; I had not realized that side effects could appear later.”
She was adamant about staying on buspirone, as she felt it helped her the most with her anxiety at social events. She voiced concern about discontinuing the antipsychotics despite being unsettled by my review of their risks. She asked that we taper them slowly.
In regard to receiving psychosocial support throughout this period of deprescribing, Rosalie declined weekly psychotherapy. She reported having a good social network in San Diego that she wanted to rely on.
Outcome
I often worry about consequences of stopping a medication, especially when I was not present at the time of its initiation. I agonize that the patient might relapse from my need to carry out my agenda on deprescribing. I try to remind myself that the evidence supports my decision making. The risks of psychotropics often are slow to show up, making the benefit of deprescribing less tangible. However, this case was straightforward.
Rosalie quickly improved. Tapering the antipsychotics was astonishing to her: “I can think clearly again.” Within 6 months, she was on buspirone only – though willing to discuss its discontinuation. She had a lead for a job and was hoping to return to work soon. Rosalie continued to miss her husband but had not heard him in some time. She has not had symptoms of psychosis or depression. Her cognition and mood were intact on my clinical assessment.
Discussion
Sadly and shockingly, cases like that of Rosalie are common. In my practice, I routinely see patients on multiple psychotropics – often on more than one antipsychotic. Their diagnoses are vague and dubious, and include diagnoses such as “unspecified psychosis” and “cognitive impairments.” Clinicians occasionally worry about relapse and promote a narrative that treatment must be not only long term but lifelong.4 There is some evidence for this perspective in a research context, but the clinical world also is filled with patients like Rosalie.
Her reports of auditory hallucinations were better explained by her grief than by a psychotic process.5 Her memory complaints were better explained by anxiety at the time of her testing while suffering from the side effects from her numerous psychotropics.6 Her depressive complaints were better explained by appropriate sadness in response to stressors. Several months later with fewer diagnoses and far fewer psychotropics, she is functioning better.
Take-home points
- Polypharmacy can lead to psychiatric symptoms and functional impairment.
- Patients often are unaware of the complete risks of psychotropics.
- Psychiatric symptoms are not always associated with a psychiatric disorder.
- Deprescribing can be performed safely and effectively.
- Deprescribing can be performed with the patient’s informed consent and agreement.
References
1. Psychiatr Serv. 2016 Aug 1;67(8):904-7.
2. Focus. 2016 Apr 13; doi: 10.1176/appi.focus.20150041.
3. Bipolar Disord. 2016 Dec;18(8):684-91.
4. Am J Psychiatry. 2017 Sep 1;174(9):840-9.
5. World Psychiatry. 2009 Jun;8(2):67-74.
6. Hosp Community Psychiatry. 1983 Sep;34(9):830-5.
Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Springer, 2019).
*This column was updated 1/11/2019.
In 2016, Swapnil Gupta, MD, and John Daniel Cahill, MD, PhD, challenged the field of psychiatry to reexamine our prescribing patterns. They warned against our use of polypharmacy when not attached to improvement in functioning for our patients.1 They were concerned about the lack of evidence for those treatment regimens and for our diagnostic criteria. In their inspiring article, they described how psychiatrists might proceed in the process of “deprescribing” – which they define as a process of pharmacologic regimen optimization through reducing or ending medications for which “benefits no longer outweigh risks.”1
In my practice, I routinely confront medication regimens that I have never encountered in the literature. The evidence for two psychotropics is limited but certainly available, in particular adjunct treatment of antidepressants2 and mood stabilizers.3 The evidence supporting the use of more than two psychotropics, however, is quite sparse. Yet, patients often enter my office on more than five psychotropics. I am also confronted with poorly defined diagnostic labels – which present more as means to justify polypharmacy than a thorough review of the patient’s current state.
Dr. Gupta and Dr. Cahill recommend a series of steps aimed at attempting the deprescription of psychotropics. Those steps include timeliness, knowledge of the patient’s current regimen, discussion about the risk of prescriptions, discussion about deprescribing, choosing the right medications to stop, a plan for describing, and monitoring. In the case presented below, I used some of those steps in an effort to provide the best care for the patient. Key details of the case have been changed, including the name, to protect the patient’s confidentiality.
Overview of the case
Rosalie Bertin is a 54-year-old female who has been treated for depression by a variety of primary care physicians for the better part of the last 30 years. She had tried an array of antidepressants, including sertraline, citalopram, duloxetine, and mirtazapine, over that time. Each seemed to provide some benefit when reviewing the notes, but there is no mention of why she was continued on those medications despite the absence of continuing symptoms. Occasionally, Rosalie would present to her clinician tearful and endorsing sadness, though the record did not comment on reports of energy, concentration, sleep, appetite, and interest.
In 2014, Rosalie’s husband passed away from lung cancer. His death was fairly quick, and initially, Rosalie did not mention any significant emotional complaints. However, when visiting her primary care physician 4 months later, she was noted to experience auditory hallucinations. “Sometimes I hear my husband when I am alone in my home,” she said. Rosalie was referred to a psychiatrist with a diagnosis of “psychosis not otherwise specified.”
When discussing her condition with the psychiatrist, Rosalie mentioned experiencing low mood, and having diminished interest in engaging in activities. “I miss Marc when I go places; I used to do everything with him.” She reported hearing him often but only when at her home. He would say things like, “I miss you,” or ask her about her day. She was diagnosed with “major depressive disorder with psychotic features.” Risperidone was added to the escitalopram, buspirone, and gabapentin that had been started by her primary care physician.
After several months of psychotropic management, the dose of risperidone was titrated to 8 mg per day. Her mood symptoms were unchanged, but she now was complaining of poor concentration and memory. The psychiatrist performed a Mini-Mental State Examination (MMSE). It was noted that taking the MMSE engendered significant anxiety for the patient. Rosalie received a score suggesting mild cognitive impairment. She was started on donepezil for the memory complaint, quetiapine for the continued voices, and recommended for disability.
Once on short-term disability, the patient relocated to live closer to her mother in San Diego and subsequently contacted me about continuing psychiatric care.
Initial visit
Rosalie is a petite white woman, raised in the Midwest, who married her high school sweetheart, and subsequently became an administrative assistant. Rosalie and Marc were unable to have children. Marc was an engineer, and a longtime smoker. She describes their lives as simple – “few friends, few vacations, few problems, few regrets.” She states she misses her husband and often cries when thinking about him.
When asked about psychiatric diagnoses, she answered: “I have psychosis. … My doctor said maybe schizophrenia, but he is not sure yet.” She described schizophrenia as hearing voices. Rosalie also mentioned having memory problems: “They cannot tell if it is Alzheimer’s disease until I die and they look at my brain, but the medication should delay the progression.”
She reported no significant effect from her prior antidepressant trials: “I am not sure if or how they helped.” Rosalie could not explain the role of the medication. “I take medications as prescribed by my doctor,” she said.
When discussing her antipsychotics, she mentioned: “Those are strong medications; it is hard for me to stay awake with them.” She declared having had no changes in the voices while on the risperidone but said they went away since also being on the quetiapine: “I wonder if the combination of the two really fixed my brain imbalance.”
Assessment
I admit that I have a critical bias against the overuse of psychotropics, and this might have painted how I interpreted Rosalie’s story. Nonetheless, I was honest with her and told her of my concerns. I informed her that her diagnosis was not consistent with my understanding of mood and thought disorders. Her initial reports of depression neither met the DSM criteria for depression nor felt consistent with my conceptualization of the illness. She had retained appropriate functioning and seemed to be responding with the sadness expected when facing difficult challenges like grief.
Her subsequent reports of auditory hallucinations were not associated with delusions or forms of disorganization that I would expect in someone with a thought disorder. Furthermore, the context of the onset gave me the impression that this was part of her process of grief. Her poor result in the dementia screen was most surprising and inconsistent with my evaluation. I told her that I suspected that she was not suffering from Alzheimer’s but from being overmedicated and from anxiety at the time of the testing.
She was excited and hesitant about my report. She was surprised by the length of our visit and interested in hearing more from me. Strangely, I wished she had challenged my different approach. I think that I was hoping she would question my conceptualization, the way I hoped she would have done with her prior clinicians. Nonetheless, she agreed to make a plan with me.
Treatment plan
We decided to review each of her medications and discuss their benefits and risks over a couple of visits. She was most eager to discontinue the donepezil, which had caused diarrhea. She was concerned when I informed her of the potential side effects of antipsychotics. “My doctor asked me if I had any side effects at each visit; I answered that I felt nothing wrong; I had not realized that side effects could appear later.”
She was adamant about staying on buspirone, as she felt it helped her the most with her anxiety at social events. She voiced concern about discontinuing the antipsychotics despite being unsettled by my review of their risks. She asked that we taper them slowly.
In regard to receiving psychosocial support throughout this period of deprescribing, Rosalie declined weekly psychotherapy. She reported having a good social network in San Diego that she wanted to rely on.
Outcome
I often worry about consequences of stopping a medication, especially when I was not present at the time of its initiation. I agonize that the patient might relapse from my need to carry out my agenda on deprescribing. I try to remind myself that the evidence supports my decision making. The risks of psychotropics often are slow to show up, making the benefit of deprescribing less tangible. However, this case was straightforward.
Rosalie quickly improved. Tapering the antipsychotics was astonishing to her: “I can think clearly again.” Within 6 months, she was on buspirone only – though willing to discuss its discontinuation. She had a lead for a job and was hoping to return to work soon. Rosalie continued to miss her husband but had not heard him in some time. She has not had symptoms of psychosis or depression. Her cognition and mood were intact on my clinical assessment.
Discussion
Sadly and shockingly, cases like that of Rosalie are common. In my practice, I routinely see patients on multiple psychotropics – often on more than one antipsychotic. Their diagnoses are vague and dubious, and include diagnoses such as “unspecified psychosis” and “cognitive impairments.” Clinicians occasionally worry about relapse and promote a narrative that treatment must be not only long term but lifelong.4 There is some evidence for this perspective in a research context, but the clinical world also is filled with patients like Rosalie.
Her reports of auditory hallucinations were better explained by her grief than by a psychotic process.5 Her memory complaints were better explained by anxiety at the time of her testing while suffering from the side effects from her numerous psychotropics.6 Her depressive complaints were better explained by appropriate sadness in response to stressors. Several months later with fewer diagnoses and far fewer psychotropics, she is functioning better.
Take-home points
- Polypharmacy can lead to psychiatric symptoms and functional impairment.
- Patients often are unaware of the complete risks of psychotropics.
- Psychiatric symptoms are not always associated with a psychiatric disorder.
- Deprescribing can be performed safely and effectively.
- Deprescribing can be performed with the patient’s informed consent and agreement.
References
1. Psychiatr Serv. 2016 Aug 1;67(8):904-7.
2. Focus. 2016 Apr 13; doi: 10.1176/appi.focus.20150041.
3. Bipolar Disord. 2016 Dec;18(8):684-91.
4. Am J Psychiatry. 2017 Sep 1;174(9):840-9.
5. World Psychiatry. 2009 Jun;8(2):67-74.
6. Hosp Community Psychiatry. 1983 Sep;34(9):830-5.
Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Springer, 2019).
*This column was updated 1/11/2019.
In 2016, Swapnil Gupta, MD, and John Daniel Cahill, MD, PhD, challenged the field of psychiatry to reexamine our prescribing patterns. They warned against our use of polypharmacy when not attached to improvement in functioning for our patients.1 They were concerned about the lack of evidence for those treatment regimens and for our diagnostic criteria. In their inspiring article, they described how psychiatrists might proceed in the process of “deprescribing” – which they define as a process of pharmacologic regimen optimization through reducing or ending medications for which “benefits no longer outweigh risks.”1
In my practice, I routinely confront medication regimens that I have never encountered in the literature. The evidence for two psychotropics is limited but certainly available, in particular adjunct treatment of antidepressants2 and mood stabilizers.3 The evidence supporting the use of more than two psychotropics, however, is quite sparse. Yet, patients often enter my office on more than five psychotropics. I am also confronted with poorly defined diagnostic labels – which present more as means to justify polypharmacy than a thorough review of the patient’s current state.
Dr. Gupta and Dr. Cahill recommend a series of steps aimed at attempting the deprescription of psychotropics. Those steps include timeliness, knowledge of the patient’s current regimen, discussion about the risk of prescriptions, discussion about deprescribing, choosing the right medications to stop, a plan for describing, and monitoring. In the case presented below, I used some of those steps in an effort to provide the best care for the patient. Key details of the case have been changed, including the name, to protect the patient’s confidentiality.
Overview of the case
Rosalie Bertin is a 54-year-old female who has been treated for depression by a variety of primary care physicians for the better part of the last 30 years. She had tried an array of antidepressants, including sertraline, citalopram, duloxetine, and mirtazapine, over that time. Each seemed to provide some benefit when reviewing the notes, but there is no mention of why she was continued on those medications despite the absence of continuing symptoms. Occasionally, Rosalie would present to her clinician tearful and endorsing sadness, though the record did not comment on reports of energy, concentration, sleep, appetite, and interest.
In 2014, Rosalie’s husband passed away from lung cancer. His death was fairly quick, and initially, Rosalie did not mention any significant emotional complaints. However, when visiting her primary care physician 4 months later, she was noted to experience auditory hallucinations. “Sometimes I hear my husband when I am alone in my home,” she said. Rosalie was referred to a psychiatrist with a diagnosis of “psychosis not otherwise specified.”
When discussing her condition with the psychiatrist, Rosalie mentioned experiencing low mood, and having diminished interest in engaging in activities. “I miss Marc when I go places; I used to do everything with him.” She reported hearing him often but only when at her home. He would say things like, “I miss you,” or ask her about her day. She was diagnosed with “major depressive disorder with psychotic features.” Risperidone was added to the escitalopram, buspirone, and gabapentin that had been started by her primary care physician.
After several months of psychotropic management, the dose of risperidone was titrated to 8 mg per day. Her mood symptoms were unchanged, but she now was complaining of poor concentration and memory. The psychiatrist performed a Mini-Mental State Examination (MMSE). It was noted that taking the MMSE engendered significant anxiety for the patient. Rosalie received a score suggesting mild cognitive impairment. She was started on donepezil for the memory complaint, quetiapine for the continued voices, and recommended for disability.
Once on short-term disability, the patient relocated to live closer to her mother in San Diego and subsequently contacted me about continuing psychiatric care.
Initial visit
Rosalie is a petite white woman, raised in the Midwest, who married her high school sweetheart, and subsequently became an administrative assistant. Rosalie and Marc were unable to have children. Marc was an engineer, and a longtime smoker. She describes their lives as simple – “few friends, few vacations, few problems, few regrets.” She states she misses her husband and often cries when thinking about him.
When asked about psychiatric diagnoses, she answered: “I have psychosis. … My doctor said maybe schizophrenia, but he is not sure yet.” She described schizophrenia as hearing voices. Rosalie also mentioned having memory problems: “They cannot tell if it is Alzheimer’s disease until I die and they look at my brain, but the medication should delay the progression.”
She reported no significant effect from her prior antidepressant trials: “I am not sure if or how they helped.” Rosalie could not explain the role of the medication. “I take medications as prescribed by my doctor,” she said.
When discussing her antipsychotics, she mentioned: “Those are strong medications; it is hard for me to stay awake with them.” She declared having had no changes in the voices while on the risperidone but said they went away since also being on the quetiapine: “I wonder if the combination of the two really fixed my brain imbalance.”
Assessment
I admit that I have a critical bias against the overuse of psychotropics, and this might have painted how I interpreted Rosalie’s story. Nonetheless, I was honest with her and told her of my concerns. I informed her that her diagnosis was not consistent with my understanding of mood and thought disorders. Her initial reports of depression neither met the DSM criteria for depression nor felt consistent with my conceptualization of the illness. She had retained appropriate functioning and seemed to be responding with the sadness expected when facing difficult challenges like grief.
Her subsequent reports of auditory hallucinations were not associated with delusions or forms of disorganization that I would expect in someone with a thought disorder. Furthermore, the context of the onset gave me the impression that this was part of her process of grief. Her poor result in the dementia screen was most surprising and inconsistent with my evaluation. I told her that I suspected that she was not suffering from Alzheimer’s but from being overmedicated and from anxiety at the time of the testing.
She was excited and hesitant about my report. She was surprised by the length of our visit and interested in hearing more from me. Strangely, I wished she had challenged my different approach. I think that I was hoping she would question my conceptualization, the way I hoped she would have done with her prior clinicians. Nonetheless, she agreed to make a plan with me.
Treatment plan
We decided to review each of her medications and discuss their benefits and risks over a couple of visits. She was most eager to discontinue the donepezil, which had caused diarrhea. She was concerned when I informed her of the potential side effects of antipsychotics. “My doctor asked me if I had any side effects at each visit; I answered that I felt nothing wrong; I had not realized that side effects could appear later.”
She was adamant about staying on buspirone, as she felt it helped her the most with her anxiety at social events. She voiced concern about discontinuing the antipsychotics despite being unsettled by my review of their risks. She asked that we taper them slowly.
In regard to receiving psychosocial support throughout this period of deprescribing, Rosalie declined weekly psychotherapy. She reported having a good social network in San Diego that she wanted to rely on.
Outcome
I often worry about consequences of stopping a medication, especially when I was not present at the time of its initiation. I agonize that the patient might relapse from my need to carry out my agenda on deprescribing. I try to remind myself that the evidence supports my decision making. The risks of psychotropics often are slow to show up, making the benefit of deprescribing less tangible. However, this case was straightforward.
Rosalie quickly improved. Tapering the antipsychotics was astonishing to her: “I can think clearly again.” Within 6 months, she was on buspirone only – though willing to discuss its discontinuation. She had a lead for a job and was hoping to return to work soon. Rosalie continued to miss her husband but had not heard him in some time. She has not had symptoms of psychosis or depression. Her cognition and mood were intact on my clinical assessment.
Discussion
Sadly and shockingly, cases like that of Rosalie are common. In my practice, I routinely see patients on multiple psychotropics – often on more than one antipsychotic. Their diagnoses are vague and dubious, and include diagnoses such as “unspecified psychosis” and “cognitive impairments.” Clinicians occasionally worry about relapse and promote a narrative that treatment must be not only long term but lifelong.4 There is some evidence for this perspective in a research context, but the clinical world also is filled with patients like Rosalie.
Her reports of auditory hallucinations were better explained by her grief than by a psychotic process.5 Her memory complaints were better explained by anxiety at the time of her testing while suffering from the side effects from her numerous psychotropics.6 Her depressive complaints were better explained by appropriate sadness in response to stressors. Several months later with fewer diagnoses and far fewer psychotropics, she is functioning better.
Take-home points
- Polypharmacy can lead to psychiatric symptoms and functional impairment.
- Patients often are unaware of the complete risks of psychotropics.
- Psychiatric symptoms are not always associated with a psychiatric disorder.
- Deprescribing can be performed safely and effectively.
- Deprescribing can be performed with the patient’s informed consent and agreement.
References
1. Psychiatr Serv. 2016 Aug 1;67(8):904-7.
2. Focus. 2016 Apr 13; doi: 10.1176/appi.focus.20150041.
3. Bipolar Disord. 2016 Dec;18(8):684-91.
4. Am J Psychiatry. 2017 Sep 1;174(9):840-9.
5. World Psychiatry. 2009 Jun;8(2):67-74.
6. Hosp Community Psychiatry. 1983 Sep;34(9):830-5.
Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Springer, 2019).
*This column was updated 1/11/2019.
Prenatal valproate exposure raises ADHD risk
Children exposed to valproate in utero were 48% more likely to be diagnosed with ADHD when compared with unexposed children in a population-based cohort study of more than 900,000 children in Denmark.
Antiepileptic drug exposure is associated with an increased risk of various congenital malformations, but its role in the development of ADHD in children has not been well documented, first author Jakob Christensen, MD, PhD, DrMedSci, of Aarhus (Denmark) University Hospital, and his colleagues wrote in their paper, published online Jan. 4 in JAMA Network Open.
The researchers identified 913,302 singleton births in Denmark from 1997 through 2011, with children followed through 2015.
Overall, children who were prenatally exposed to valproate had a 48% increased risk of ADHD. Antiepileptic drug exposure was defined as 30 days before the estimated day of conception to the day of birth, and included valproate, clobazam, and other antiepileptic drugs. The average age of the children at the study’s end was 10 years, and approximately half were male.
A total of 580 children were exposed to valproate in utero; of these, 8.4% were later diagnosed with ADHD, compared with 3.2% of 912,722 children who were not exposed to valproate. In addition, the absolute 15-year risk of ADHD was 11% in valproate-exposed children vs. 4.6% in unexposed children. No significant associations appeared between ADHD and other antiepileptic drugs.
The study findings were limited by several factors, including the contraindication of valproate for use in pregnancy, which may mean that the women taking valproate had more severe disease, the researchers noted.
“Due to the observational nature of this study, we cannot rule out that the observed risk increase for ADHD is at least in part explained by the mother’s health condition that triggered the prescription of valproate during pregnancy,” they said. Other limitations included a lack of data on the exact amounts of valproate taken during pregnancy and the potential impact of nonepilepsy medications, they noted.
However, the results were strengthened by the large size and population-based cohort, and support warnings by professional medical organizations against valproate use in pregnancy, the researchers said. “As randomized clinical trials of valproate use during pregnancy are neither feasible nor ethical, our study provides clinical information on the risk of ADHD associated with valproate use during pregnancy,” they concluded.
The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.
SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.
The data from the current study differ from a recent meta-analysis of five studies that did not find a statistically significant increase in ADHD risk in children associated with prenatal valproate exposure, Kimford J. Meador, MD, wrote in an accompanying editorial (JAMA Network Open. 2019;2[1]:e186603. doi: 10.1001/jamanetworkopen.2018.6603). 
“The discrepancy between the present study and the prior meta-analysis might be due to the meta-analysis using different analytical approaches and examining studies with smaller sample sizes, higher attrition rates, shorter follow-ups, and cohort differences,” Dr. Meador said. “Nevertheless, the findings by Christensen et al. are consistent with multiple studies demonstrating adverse neurodevelopmental effects associated with fetal valproate exposure.”
Given the potential risks associated with valproate exposure not only for behavior problems such as ADHD but also for congenital malformations and other cognitive and behavioral issues in children, women of childbearing age who are using valproate or considering a prescription should be counseled for informed consent, Dr. Meador said.
Dr. Meador advocated additional research on the impact of antiepileptic drugs during pregnancy and risk assessment strategies, including “a national reporting system for congenital malformations, routine preclinical testing of all new antiseizure medications for neurodevelopmental effects, monitoring of antiseizure medication prescription practices for women of childbearing age to determine whether emerging knowledge is being appropriately applied, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms of anatomical and behavioral teratogenesis from antiseizure medications.”
Dr. Meador is affiliated with the department of neurology and neurological sciences at Stanford (Calif.) University. He disclosed research support from the National Institutes of Health and Sunovion, and travel support from UCB. The Epilepsy Study Consortium pays Stanford University for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB, and Vivus.
The data from the current study differ from a recent meta-analysis of five studies that did not find a statistically significant increase in ADHD risk in children associated with prenatal valproate exposure, Kimford J. Meador, MD, wrote in an accompanying editorial (JAMA Network Open. 2019;2[1]:e186603. doi: 10.1001/jamanetworkopen.2018.6603).
“The discrepancy between the present study and the prior meta-analysis might be due to the meta-analysis using different analytical approaches and examining studies with smaller sample sizes, higher attrition rates, shorter follow-ups, and cohort differences,” Dr. Meador said. “Nevertheless, the findings by Christensen et al. are consistent with multiple studies demonstrating adverse neurodevelopmental effects associated with fetal valproate exposure.”
Given the potential risks associated with valproate exposure not only for behavior problems such as ADHD but also for congenital malformations and other cognitive and behavioral issues in children, women of childbearing age who are using valproate or considering a prescription should be counseled for informed consent, Dr. Meador said.
Dr. Meador advocated additional research on the impact of antiepileptic drugs during pregnancy and risk assessment strategies, including “a national reporting system for congenital malformations, routine preclinical testing of all new antiseizure medications for neurodevelopmental effects, monitoring of antiseizure medication prescription practices for women of childbearing age to determine whether emerging knowledge is being appropriately applied, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms of anatomical and behavioral teratogenesis from antiseizure medications.”
Dr. Meador is affiliated with the department of neurology and neurological sciences at Stanford (Calif.) University. He disclosed research support from the National Institutes of Health and Sunovion, and travel support from UCB. The Epilepsy Study Consortium pays Stanford University for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB, and Vivus.
The data from the current study differ from a recent meta-analysis of five studies that did not find a statistically significant increase in ADHD risk in children associated with prenatal valproate exposure, Kimford J. Meador, MD, wrote in an accompanying editorial (JAMA Network Open. 2019;2[1]:e186603. doi: 10.1001/jamanetworkopen.2018.6603).
“The discrepancy between the present study and the prior meta-analysis might be due to the meta-analysis using different analytical approaches and examining studies with smaller sample sizes, higher attrition rates, shorter follow-ups, and cohort differences,” Dr. Meador said. “Nevertheless, the findings by Christensen et al. are consistent with multiple studies demonstrating adverse neurodevelopmental effects associated with fetal valproate exposure.”
Given the potential risks associated with valproate exposure not only for behavior problems such as ADHD but also for congenital malformations and other cognitive and behavioral issues in children, women of childbearing age who are using valproate or considering a prescription should be counseled for informed consent, Dr. Meador said.
Dr. Meador advocated additional research on the impact of antiepileptic drugs during pregnancy and risk assessment strategies, including “a national reporting system for congenital malformations, routine preclinical testing of all new antiseizure medications for neurodevelopmental effects, monitoring of antiseizure medication prescription practices for women of childbearing age to determine whether emerging knowledge is being appropriately applied, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms of anatomical and behavioral teratogenesis from antiseizure medications.”
Dr. Meador is affiliated with the department of neurology and neurological sciences at Stanford (Calif.) University. He disclosed research support from the National Institutes of Health and Sunovion, and travel support from UCB. The Epilepsy Study Consortium pays Stanford University for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB, and Vivus.
Children exposed to valproate in utero were 48% more likely to be diagnosed with ADHD when compared with unexposed children in a population-based cohort study of more than 900,000 children in Denmark.
Antiepileptic drug exposure is associated with an increased risk of various congenital malformations, but its role in the development of ADHD in children has not been well documented, first author Jakob Christensen, MD, PhD, DrMedSci, of Aarhus (Denmark) University Hospital, and his colleagues wrote in their paper, published online Jan. 4 in JAMA Network Open.
The researchers identified 913,302 singleton births in Denmark from 1997 through 2011, with children followed through 2015.
Overall, children who were prenatally exposed to valproate had a 48% increased risk of ADHD. Antiepileptic drug exposure was defined as 30 days before the estimated day of conception to the day of birth, and included valproate, clobazam, and other antiepileptic drugs. The average age of the children at the study’s end was 10 years, and approximately half were male.
A total of 580 children were exposed to valproate in utero; of these, 8.4% were later diagnosed with ADHD, compared with 3.2% of 912,722 children who were not exposed to valproate. In addition, the absolute 15-year risk of ADHD was 11% in valproate-exposed children vs. 4.6% in unexposed children. No significant associations appeared between ADHD and other antiepileptic drugs.
The study findings were limited by several factors, including the contraindication of valproate for use in pregnancy, which may mean that the women taking valproate had more severe disease, the researchers noted.
“Due to the observational nature of this study, we cannot rule out that the observed risk increase for ADHD is at least in part explained by the mother’s health condition that triggered the prescription of valproate during pregnancy,” they said. Other limitations included a lack of data on the exact amounts of valproate taken during pregnancy and the potential impact of nonepilepsy medications, they noted.
However, the results were strengthened by the large size and population-based cohort, and support warnings by professional medical organizations against valproate use in pregnancy, the researchers said. “As randomized clinical trials of valproate use during pregnancy are neither feasible nor ethical, our study provides clinical information on the risk of ADHD associated with valproate use during pregnancy,” they concluded.
The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.
SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.
Children exposed to valproate in utero were 48% more likely to be diagnosed with ADHD when compared with unexposed children in a population-based cohort study of more than 900,000 children in Denmark.
Antiepileptic drug exposure is associated with an increased risk of various congenital malformations, but its role in the development of ADHD in children has not been well documented, first author Jakob Christensen, MD, PhD, DrMedSci, of Aarhus (Denmark) University Hospital, and his colleagues wrote in their paper, published online Jan. 4 in JAMA Network Open.
The researchers identified 913,302 singleton births in Denmark from 1997 through 2011, with children followed through 2015.
Overall, children who were prenatally exposed to valproate had a 48% increased risk of ADHD. Antiepileptic drug exposure was defined as 30 days before the estimated day of conception to the day of birth, and included valproate, clobazam, and other antiepileptic drugs. The average age of the children at the study’s end was 10 years, and approximately half were male.
A total of 580 children were exposed to valproate in utero; of these, 8.4% were later diagnosed with ADHD, compared with 3.2% of 912,722 children who were not exposed to valproate. In addition, the absolute 15-year risk of ADHD was 11% in valproate-exposed children vs. 4.6% in unexposed children. No significant associations appeared between ADHD and other antiepileptic drugs.
The study findings were limited by several factors, including the contraindication of valproate for use in pregnancy, which may mean that the women taking valproate had more severe disease, the researchers noted.
“Due to the observational nature of this study, we cannot rule out that the observed risk increase for ADHD is at least in part explained by the mother’s health condition that triggered the prescription of valproate during pregnancy,” they said. Other limitations included a lack of data on the exact amounts of valproate taken during pregnancy and the potential impact of nonepilepsy medications, they noted.
However, the results were strengthened by the large size and population-based cohort, and support warnings by professional medical organizations against valproate use in pregnancy, the researchers said. “As randomized clinical trials of valproate use during pregnancy are neither feasible nor ethical, our study provides clinical information on the risk of ADHD associated with valproate use during pregnancy,” they concluded.
The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.
SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.
FROM JAMA NETWORK OPEN
Key clinical point:
Major finding: The children whose mothers used valproate between 90 days before conception and birth had a 48% increased risk of ADHD compared with children whose mothers did not use valproate.
Study details: The data come from a population-based cohort study of 913,302 children in Denmark.
Disclosures: The study was supported by grants to various authors from the Danish Epilepsy Association Central Denmark Region, the Aarhus University Research Foundation, the Lundbeck Foundation, the National Institutes of Health, the Novo Nordisk Foundation, and the European Commission.
Source: SOURCE: Christensen J et al. JAMA Network Open. 2019;2(1):e186606. doi: 10.1001/jamanetworkopen.2018.6606.
ADHD more likely, causes worse outcomes in patients with BD
ADHD is significantly more common and is associated with worse outcomes in patients with bipolar disorder, according to Ross J. Baldessarini, MD, of McLean Hospital and Harvard Medical School, Boston, and his associates.
In a study of 703 patients diagnosed with bipolar disorder (BD) type I or II who were evaluated, treated, and followed at the Lucio Bini Mood Disorder Centers in Rome and Cagliari, Italy, 173 patients had co-occurring lifetime ADHD. Co-occurring conditions were more likely in men and in those with BD-I. The lifetime ADHD prevalence rate of 24.6% in patients with bipolar disorder is significantly higher than the incidence in the general population, the investigators wrote in the Journal of Affective Disorders.
Patients with co-occurring ADHD and BD were more likely to have performed worse in school, have higher Adult ADHD Self-Report Scale scores, be unemployed, have lower socioeconomic status, be married, have separated, have substance abuse, have attempted suicide, and have hypomania, compared with patients with only BD. However, they were less likely to have an anxiety disorder or a family history of mood disorders.
“The association of ADHD with a less successful and stable educational history, more unemployment, lack of or failed marriages, and greater risk of suicide attempts and substance abuse indicates unfavorable effects of having ADHD with BD. Such effects may arise by the impact of ADHD early during development,” the investigators concluded.
The study was partly supported by a research award from the Aretaeus Association of Rome and grants from the Bruce J. Anderson Foundation and the McLean Private Donors Research Fund. No conflicts of interest were reported.
SOURCE: Baldessarini RJ et al. J Affect Disord. 2018 Sep 17. doi: 10.1016/j.jad.2018.09.038.
ADHD is significantly more common and is associated with worse outcomes in patients with bipolar disorder, according to Ross J. Baldessarini, MD, of McLean Hospital and Harvard Medical School, Boston, and his associates.
In a study of 703 patients diagnosed with bipolar disorder (BD) type I or II who were evaluated, treated, and followed at the Lucio Bini Mood Disorder Centers in Rome and Cagliari, Italy, 173 patients had co-occurring lifetime ADHD. Co-occurring conditions were more likely in men and in those with BD-I. The lifetime ADHD prevalence rate of 24.6% in patients with bipolar disorder is significantly higher than the incidence in the general population, the investigators wrote in the Journal of Affective Disorders.
Patients with co-occurring ADHD and BD were more likely to have performed worse in school, have higher Adult ADHD Self-Report Scale scores, be unemployed, have lower socioeconomic status, be married, have separated, have substance abuse, have attempted suicide, and have hypomania, compared with patients with only BD. However, they were less likely to have an anxiety disorder or a family history of mood disorders.
“The association of ADHD with a less successful and stable educational history, more unemployment, lack of or failed marriages, and greater risk of suicide attempts and substance abuse indicates unfavorable effects of having ADHD with BD. Such effects may arise by the impact of ADHD early during development,” the investigators concluded.
The study was partly supported by a research award from the Aretaeus Association of Rome and grants from the Bruce J. Anderson Foundation and the McLean Private Donors Research Fund. No conflicts of interest were reported.
SOURCE: Baldessarini RJ et al. J Affect Disord. 2018 Sep 17. doi: 10.1016/j.jad.2018.09.038.
ADHD is significantly more common and is associated with worse outcomes in patients with bipolar disorder, according to Ross J. Baldessarini, MD, of McLean Hospital and Harvard Medical School, Boston, and his associates.
In a study of 703 patients diagnosed with bipolar disorder (BD) type I or II who were evaluated, treated, and followed at the Lucio Bini Mood Disorder Centers in Rome and Cagliari, Italy, 173 patients had co-occurring lifetime ADHD. Co-occurring conditions were more likely in men and in those with BD-I. The lifetime ADHD prevalence rate of 24.6% in patients with bipolar disorder is significantly higher than the incidence in the general population, the investigators wrote in the Journal of Affective Disorders.
Patients with co-occurring ADHD and BD were more likely to have performed worse in school, have higher Adult ADHD Self-Report Scale scores, be unemployed, have lower socioeconomic status, be married, have separated, have substance abuse, have attempted suicide, and have hypomania, compared with patients with only BD. However, they were less likely to have an anxiety disorder or a family history of mood disorders.
“The association of ADHD with a less successful and stable educational history, more unemployment, lack of or failed marriages, and greater risk of suicide attempts and substance abuse indicates unfavorable effects of having ADHD with BD. Such effects may arise by the impact of ADHD early during development,” the investigators concluded.
The study was partly supported by a research award from the Aretaeus Association of Rome and grants from the Bruce J. Anderson Foundation and the McLean Private Donors Research Fund. No conflicts of interest were reported.
SOURCE: Baldessarini RJ et al. J Affect Disord. 2018 Sep 17. doi: 10.1016/j.jad.2018.09.038.
FROM THE JOURNAL OF AFFECTIVE DISORDERS
Best of Psychopharmacology: Stimulants, ketamine, benzodiazapines
In this episode we go back to the summer for two master classes on ketamine and stimulants, respectively and we drop in on two conversations between Lorenzo Norris, MD on anxiety and comorbid ADHD as well as a conversation on benzodiazapines. The Psychcast will be back with new content in 2019.
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In this episode we go back to the summer for two master classes on ketamine and stimulants, respectively and we drop in on two conversations between Lorenzo Norris, MD on anxiety and comorbid ADHD as well as a conversation on benzodiazapines. The Psychcast will be back with new content in 2019.
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Apple
Google
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In this episode we go back to the summer for two master classes on ketamine and stimulants, respectively and we drop in on two conversations between Lorenzo Norris, MD on anxiety and comorbid ADHD as well as a conversation on benzodiazapines. The Psychcast will be back with new content in 2019.
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Apple
Google
Spotify
Overshadowed by opioids, meth is back and hospitalizations surge
The number of people hospitalized because of amphetamine use is skyrocketing in the United States, but the resurgence of the drug largely has been overshadowed by the nation’s intense focus on opioids.
Amphetamine-related hospitalizations jumped by about 245% during 2008-2015, according to a recent study in the Journal of the American Medical Association. That dwarfs the rise in hospitalizations from other drugs, such as opioids, which were up by about 46%. The most significant increases were in Western states.
The surge in hospitalizations and deaths from amphetamines “is just totally off the radar,” said Jane Maxwell, PhD, an researcher at the Addiction Research Institute at the University of Texas at Austin. “Nobody is paying attention.”
Doctors see evidence of the drug’s comeback in emergency departments, where patients arrive agitated, paranoid, and aggressive. Paramedics and police officers see it on the streets, where suspects’ heart rates are so high that they need to be taken to the hospital for medical clearance before being booked into jail. And medical examiners see it in the morgue, where in a few states, such as Texas and Colorado, overdoses from meth have surpassed those from the opioid heroin.
Amphetamines are stimulant drugs, which are legally prescribed to treat ADHD and produced illegally as methamphetamine. Most of the hospitalizations in the study are believed to be from methamphetamine use.
Commonly known as crystal meth, methamphetamine was popular in the 1990s before laws made it more difficult to access the pseudoephedrine, a common cold medicine, needed to produce it. In recent years, law enforcement officials said, there are fewer domestic meth labs and more meth is smuggled in from south of the border.
As opioids become harder to get, police said, more people have turned to meth, which is inexpensive and readily available.
Lupita Ruiz, 25, started using methamphetamine in her late teens but said she has been clean for about 2 years. When she was using, she said, her heart beat fast, she would stay up all night, and she would forget to eat.
Ms. Ruiz, who lives in Spokane, Wash., said she was taken to the hospital twice after having mental breakdowns related to methamphetamine use, including a month-long stay in the psychiatric ward in 2016. One time, Ms. Ruiz said, she yelled at and kicked police officers after they responded to a call to her apartment. Another time, she started walking on the freeway but doesn’t remember why.
“It just made me go crazy,” she said. “I was all messed up in my head.”
The federal government estimates that more than 10,000 people died of meth-related drug overdoses last year. Deaths from meth overdose generally result from multiple organ failure or heart attacks and strokes, caused by extraordinary pulse rates and skyrocketing blood pressure.
In California, the number of amphetamine-related overdose deaths rose by 127% from 456 in 2008 to 1,036 in 2013. During that same time, the number of opioid-related overdose deaths rose by 8.4% from 1,784 to 1,934, according to the most recent data from the state Department of Public Health.
“It taxes your first responders, your emergency rooms, your coroners,” said Robert Pennal, a retired supervisor with the California Department of Justice. “It’s an incredible burden on the health system.”
Costs also are rising. The JAMA study, based on hospital discharge data, found that the cost of amphetamine-related hospitalizations had jumped from $436 million in 2003 to nearly $2.2 billion by 2015. Medicaid was the primary payer.
“There is not a day that goes by that I don’t see someone acutely intoxicated on methamphetamine,” said Tarak Trivedi, MD,, an emergency room physician in Los Angeles and Santa Clara counties. “It’s a huge problem, and it is 100% spilling over into the emergency room.”
Dr. Trivedi said many psychiatric patients also are meth users. Some act so dangerously that they require sedation or restraints. He often sees people who have been using the drug for a long time and are dealing with the downstream consequences.
In the short term, the drug can cause a rapid heart rate and dangerously high blood pressure. In the long term, it can cause anxiety, dental problems and weight loss.
“You see people as young as their 30s with congestive heart failure as if they were in their 70s,” he said.
Jon E. Lopey, the sheriff-coroner of Siskiyou County in rural Northern California, said his officers frequently encounter meth users who are prone to violence and in the midst of what appear to be psychotic episodes. Many are emaciated and have missing teeth, dilated pupils, and a tendency to pick at their skin because of a sensation of something beneath it.
“Meth is very, very destructive,” said Sheriff Lopey, who also sits on the executive board of the California Peace Officers Association. “It is just so debilitating the way it ruins lives and health.”
Nationwide, amphetamine-related hospitalizations were primarily from mental health or cardiovascular complications of the drug use, the JAMA study found. About half of the amphetamine hospitalizations also involved at least one other drug.
Because there has been so much attention on opioids, “we have not been properly keeping tabs on other substance use trends as robustly as we should,” said study author Tyler Winkelman, MD, a physician at Hennepin Healthcare in Minneapolis.
Sometimes doctors have trouble distinguishing symptoms of methamphetamine intoxication and underlying mental health conditions, said Erik Anderson, MD, an ED physician at Highland Hospital in Oakland, Calif. Patients also may be homeless and using other drugs alongside the methamphetamine.
Unlike opioid addiction, meth addiction cannot be treated with medication. Rather, people addicted to the drug rely on counseling through outpatient and residential treatment centers.
The opioid epidemic, which resulted in about 49,000 overdose deaths last year, recently prompted bipartisan federal legislation to improve access to recovery, expand coverage to treatment, and combat drugs coming across the border.
There hasn’t been a similar recent legislative focus on methamphetamine or other drugs. And there simply aren’t enough resources devoted to amphetamine addiction to reduce the hospitalizations and deaths, said Dr. Maxwell. The number of residential treatment facilities, for example, has continued to decline, she said.
“We have really undercut treatment for methamphetamine,” Dr. Maxwell said. “Meth has been completely overshadowed by opioids.”
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente. KHN’s coverage in California is supported in part by Blue Shield of California Foundation.
The number of people hospitalized because of amphetamine use is skyrocketing in the United States, but the resurgence of the drug largely has been overshadowed by the nation’s intense focus on opioids.
Amphetamine-related hospitalizations jumped by about 245% during 2008-2015, according to a recent study in the Journal of the American Medical Association. That dwarfs the rise in hospitalizations from other drugs, such as opioids, which were up by about 46%. The most significant increases were in Western states.
The surge in hospitalizations and deaths from amphetamines “is just totally off the radar,” said Jane Maxwell, PhD, an researcher at the Addiction Research Institute at the University of Texas at Austin. “Nobody is paying attention.”
Doctors see evidence of the drug’s comeback in emergency departments, where patients arrive agitated, paranoid, and aggressive. Paramedics and police officers see it on the streets, where suspects’ heart rates are so high that they need to be taken to the hospital for medical clearance before being booked into jail. And medical examiners see it in the morgue, where in a few states, such as Texas and Colorado, overdoses from meth have surpassed those from the opioid heroin.
Amphetamines are stimulant drugs, which are legally prescribed to treat ADHD and produced illegally as methamphetamine. Most of the hospitalizations in the study are believed to be from methamphetamine use.
Commonly known as crystal meth, methamphetamine was popular in the 1990s before laws made it more difficult to access the pseudoephedrine, a common cold medicine, needed to produce it. In recent years, law enforcement officials said, there are fewer domestic meth labs and more meth is smuggled in from south of the border.
As opioids become harder to get, police said, more people have turned to meth, which is inexpensive and readily available.
Lupita Ruiz, 25, started using methamphetamine in her late teens but said she has been clean for about 2 years. When she was using, she said, her heart beat fast, she would stay up all night, and she would forget to eat.
Ms. Ruiz, who lives in Spokane, Wash., said she was taken to the hospital twice after having mental breakdowns related to methamphetamine use, including a month-long stay in the psychiatric ward in 2016. One time, Ms. Ruiz said, she yelled at and kicked police officers after they responded to a call to her apartment. Another time, she started walking on the freeway but doesn’t remember why.
“It just made me go crazy,” she said. “I was all messed up in my head.”
The federal government estimates that more than 10,000 people died of meth-related drug overdoses last year. Deaths from meth overdose generally result from multiple organ failure or heart attacks and strokes, caused by extraordinary pulse rates and skyrocketing blood pressure.
In California, the number of amphetamine-related overdose deaths rose by 127% from 456 in 2008 to 1,036 in 2013. During that same time, the number of opioid-related overdose deaths rose by 8.4% from 1,784 to 1,934, according to the most recent data from the state Department of Public Health.
“It taxes your first responders, your emergency rooms, your coroners,” said Robert Pennal, a retired supervisor with the California Department of Justice. “It’s an incredible burden on the health system.”
Costs also are rising. The JAMA study, based on hospital discharge data, found that the cost of amphetamine-related hospitalizations had jumped from $436 million in 2003 to nearly $2.2 billion by 2015. Medicaid was the primary payer.
“There is not a day that goes by that I don’t see someone acutely intoxicated on methamphetamine,” said Tarak Trivedi, MD,, an emergency room physician in Los Angeles and Santa Clara counties. “It’s a huge problem, and it is 100% spilling over into the emergency room.”
Dr. Trivedi said many psychiatric patients also are meth users. Some act so dangerously that they require sedation or restraints. He often sees people who have been using the drug for a long time and are dealing with the downstream consequences.
In the short term, the drug can cause a rapid heart rate and dangerously high blood pressure. In the long term, it can cause anxiety, dental problems and weight loss.
“You see people as young as their 30s with congestive heart failure as if they were in their 70s,” he said.
Jon E. Lopey, the sheriff-coroner of Siskiyou County in rural Northern California, said his officers frequently encounter meth users who are prone to violence and in the midst of what appear to be psychotic episodes. Many are emaciated and have missing teeth, dilated pupils, and a tendency to pick at their skin because of a sensation of something beneath it.
“Meth is very, very destructive,” said Sheriff Lopey, who also sits on the executive board of the California Peace Officers Association. “It is just so debilitating the way it ruins lives and health.”
Nationwide, amphetamine-related hospitalizations were primarily from mental health or cardiovascular complications of the drug use, the JAMA study found. About half of the amphetamine hospitalizations also involved at least one other drug.
Because there has been so much attention on opioids, “we have not been properly keeping tabs on other substance use trends as robustly as we should,” said study author Tyler Winkelman, MD, a physician at Hennepin Healthcare in Minneapolis.
Sometimes doctors have trouble distinguishing symptoms of methamphetamine intoxication and underlying mental health conditions, said Erik Anderson, MD, an ED physician at Highland Hospital in Oakland, Calif. Patients also may be homeless and using other drugs alongside the methamphetamine.
Unlike opioid addiction, meth addiction cannot be treated with medication. Rather, people addicted to the drug rely on counseling through outpatient and residential treatment centers.
The opioid epidemic, which resulted in about 49,000 overdose deaths last year, recently prompted bipartisan federal legislation to improve access to recovery, expand coverage to treatment, and combat drugs coming across the border.
There hasn’t been a similar recent legislative focus on methamphetamine or other drugs. And there simply aren’t enough resources devoted to amphetamine addiction to reduce the hospitalizations and deaths, said Dr. Maxwell. The number of residential treatment facilities, for example, has continued to decline, she said.
“We have really undercut treatment for methamphetamine,” Dr. Maxwell said. “Meth has been completely overshadowed by opioids.”
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente. KHN’s coverage in California is supported in part by Blue Shield of California Foundation.
The number of people hospitalized because of amphetamine use is skyrocketing in the United States, but the resurgence of the drug largely has been overshadowed by the nation’s intense focus on opioids.
Amphetamine-related hospitalizations jumped by about 245% during 2008-2015, according to a recent study in the Journal of the American Medical Association. That dwarfs the rise in hospitalizations from other drugs, such as opioids, which were up by about 46%. The most significant increases were in Western states.
The surge in hospitalizations and deaths from amphetamines “is just totally off the radar,” said Jane Maxwell, PhD, an researcher at the Addiction Research Institute at the University of Texas at Austin. “Nobody is paying attention.”
Doctors see evidence of the drug’s comeback in emergency departments, where patients arrive agitated, paranoid, and aggressive. Paramedics and police officers see it on the streets, where suspects’ heart rates are so high that they need to be taken to the hospital for medical clearance before being booked into jail. And medical examiners see it in the morgue, where in a few states, such as Texas and Colorado, overdoses from meth have surpassed those from the opioid heroin.
Amphetamines are stimulant drugs, which are legally prescribed to treat ADHD and produced illegally as methamphetamine. Most of the hospitalizations in the study are believed to be from methamphetamine use.
Commonly known as crystal meth, methamphetamine was popular in the 1990s before laws made it more difficult to access the pseudoephedrine, a common cold medicine, needed to produce it. In recent years, law enforcement officials said, there are fewer domestic meth labs and more meth is smuggled in from south of the border.
As opioids become harder to get, police said, more people have turned to meth, which is inexpensive and readily available.
Lupita Ruiz, 25, started using methamphetamine in her late teens but said she has been clean for about 2 years. When she was using, she said, her heart beat fast, she would stay up all night, and she would forget to eat.
Ms. Ruiz, who lives in Spokane, Wash., said she was taken to the hospital twice after having mental breakdowns related to methamphetamine use, including a month-long stay in the psychiatric ward in 2016. One time, Ms. Ruiz said, she yelled at and kicked police officers after they responded to a call to her apartment. Another time, she started walking on the freeway but doesn’t remember why.
“It just made me go crazy,” she said. “I was all messed up in my head.”
The federal government estimates that more than 10,000 people died of meth-related drug overdoses last year. Deaths from meth overdose generally result from multiple organ failure or heart attacks and strokes, caused by extraordinary pulse rates and skyrocketing blood pressure.
In California, the number of amphetamine-related overdose deaths rose by 127% from 456 in 2008 to 1,036 in 2013. During that same time, the number of opioid-related overdose deaths rose by 8.4% from 1,784 to 1,934, according to the most recent data from the state Department of Public Health.
“It taxes your first responders, your emergency rooms, your coroners,” said Robert Pennal, a retired supervisor with the California Department of Justice. “It’s an incredible burden on the health system.”
Costs also are rising. The JAMA study, based on hospital discharge data, found that the cost of amphetamine-related hospitalizations had jumped from $436 million in 2003 to nearly $2.2 billion by 2015. Medicaid was the primary payer.
“There is not a day that goes by that I don’t see someone acutely intoxicated on methamphetamine,” said Tarak Trivedi, MD,, an emergency room physician in Los Angeles and Santa Clara counties. “It’s a huge problem, and it is 100% spilling over into the emergency room.”
Dr. Trivedi said many psychiatric patients also are meth users. Some act so dangerously that they require sedation or restraints. He often sees people who have been using the drug for a long time and are dealing with the downstream consequences.
In the short term, the drug can cause a rapid heart rate and dangerously high blood pressure. In the long term, it can cause anxiety, dental problems and weight loss.
“You see people as young as their 30s with congestive heart failure as if they were in their 70s,” he said.
Jon E. Lopey, the sheriff-coroner of Siskiyou County in rural Northern California, said his officers frequently encounter meth users who are prone to violence and in the midst of what appear to be psychotic episodes. Many are emaciated and have missing teeth, dilated pupils, and a tendency to pick at their skin because of a sensation of something beneath it.
“Meth is very, very destructive,” said Sheriff Lopey, who also sits on the executive board of the California Peace Officers Association. “It is just so debilitating the way it ruins lives and health.”
Nationwide, amphetamine-related hospitalizations were primarily from mental health or cardiovascular complications of the drug use, the JAMA study found. About half of the amphetamine hospitalizations also involved at least one other drug.
Because there has been so much attention on opioids, “we have not been properly keeping tabs on other substance use trends as robustly as we should,” said study author Tyler Winkelman, MD, a physician at Hennepin Healthcare in Minneapolis.
Sometimes doctors have trouble distinguishing symptoms of methamphetamine intoxication and underlying mental health conditions, said Erik Anderson, MD, an ED physician at Highland Hospital in Oakland, Calif. Patients also may be homeless and using other drugs alongside the methamphetamine.
Unlike opioid addiction, meth addiction cannot be treated with medication. Rather, people addicted to the drug rely on counseling through outpatient and residential treatment centers.
The opioid epidemic, which resulted in about 49,000 overdose deaths last year, recently prompted bipartisan federal legislation to improve access to recovery, expand coverage to treatment, and combat drugs coming across the border.
There hasn’t been a similar recent legislative focus on methamphetamine or other drugs. And there simply aren’t enough resources devoted to amphetamine addiction to reduce the hospitalizations and deaths, said Dr. Maxwell. The number of residential treatment facilities, for example, has continued to decline, she said.
“We have really undercut treatment for methamphetamine,” Dr. Maxwell said. “Meth has been completely overshadowed by opioids.”
Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente. KHN’s coverage in California is supported in part by Blue Shield of California Foundation.
Jornay PM improves classroom functioning in ADHD
SEATTLE – A novel formulation of methylphenidate could provide morning relief to pediatric patients with attention-deficit/hyperactivity disorder, according to results of a pivotal phase 3 classroom trial.
In the study, delayed release/extended release methylphenidate (DR/ER MPH), when taken the night before, improved ADHD symptoms throughout a 12-hour laboratory classroom period – including in the late afternoons and early mornings.
The formulation, also known as Jornay PM, received Food and Drug Administration approval for ADHD in August for patients aged 6 and older. “For kids who have a horrendous time in the morning, getting up out of bed, and getting ready for school, they get up and they’re ready to rock and roll. [The drug] makes the mornings go better,” Ann Childress, MD, said in an interview at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
In a previous phase 3 trial, DR/ER MPH proved beneficial in late afternoon and early morning symptoms in a naturalistic sample over a 3- week treatment course (J Child Adolesc Pharmacol. 2017 Aug 1;27[6]:474-82). The current work sought to show its value in a classroom setting. And in yet another earlier survey, 77% of parents rated early morning functional impairment in children with ADHD as moderate to severe (J Child Adolesc Pharmacol. 2017 Oct 1;27[8]:715-22).
“,” said Dr. Childress, president of the Center for Psychiatry and Behavioral Medicine in Las Vegas.
In the current study, presented by Dr. Childress at the meeting, 117 children aged 6-12 years with ADHD and morning behavioral problems, after a 5-day washout period, were started on an evening DR/ER MPH dose of 20 mg or 40 mg. They were then seen for up to 4 more weeks, and doses optimized (maximum 100 mg/day).
Adjustments also were made in the evening dose schedule to determine an optimal dosing time, which had to range from 6:30 pm to 9:30 pm, at least 1 hour after dinner. Clinicians optimized the dose and timing to achieve maximum symptom control throughout the day (minimum 30% improvement in total symptom score from baseline), while remaining safe and well-tolerated.The participants were then randomized to maintain the current drug dose, or to switch to placebo for 1 week. The primary endpoint was the average of all post-dose SKAMP-CS (Swanson, Kotkin, Agler, M-Flynn, and Pelham combined scale) measurements, as recorded by a trained, independent observer during the 12-hour period on the last classroom day.
There was a significant improvement in the primary measure, with the treatment group averaging 14.8 on the SKAMP-CS, compared with 20.7 for the placebo group (P less than .001). The improved outcomes were steady throughout the day, failing to achieve statistical significance at 8 a.m., but achieving significance in measurements taken at 9 a.m.,10 a.m., 12 p.m., 2 pm, 4 p.m., 6 p.m., and 7 p.m.
The formulation also achieved significant difference in morning and late afternoon measurements of the Parent Rating of Evening and Morning Behavior Scale, Revised (PREMB-R AM and PREMB-R PM). The treatment group scored a mean of 0.9 on PREMB-R AM, compared with 2.7 for placebo (P less than .001), and 6.1 vs. 9.3 in the PREMB-R PM scale (P = .003).
Most treatment emergent adverse events were considered mild or moderate, and occurred in 36.9% of the treatment group and 40.7% of placebo subjects.
The study was funded by Ironshore Pharmaceuticals, which said in a press statement that it plans to launch the drug early next year. In addition to Ironshore, Dr. Childress has served on the advisory board for, consulted for, or received research support from Aevi Genomic Medicine, Akili Interactive, Alcobra, Arbor Pharmaceuticals, Eli Lilly, Forest Laboratories, Lundbeck, KemPharm, Neos Therapeutics, Noven Pharmaceuticals, Otsuka America Pharmaceutical, Pearson, Pfizer, Purdue Pharma, Rhodes Pharmaceuticals, Shire, Sunovion, and Tris Pharma.
SEATTLE – A novel formulation of methylphenidate could provide morning relief to pediatric patients with attention-deficit/hyperactivity disorder, according to results of a pivotal phase 3 classroom trial.
In the study, delayed release/extended release methylphenidate (DR/ER MPH), when taken the night before, improved ADHD symptoms throughout a 12-hour laboratory classroom period – including in the late afternoons and early mornings.
The formulation, also known as Jornay PM, received Food and Drug Administration approval for ADHD in August for patients aged 6 and older. “For kids who have a horrendous time in the morning, getting up out of bed, and getting ready for school, they get up and they’re ready to rock and roll. [The drug] makes the mornings go better,” Ann Childress, MD, said in an interview at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
In a previous phase 3 trial, DR/ER MPH proved beneficial in late afternoon and early morning symptoms in a naturalistic sample over a 3- week treatment course (J Child Adolesc Pharmacol. 2017 Aug 1;27[6]:474-82). The current work sought to show its value in a classroom setting. And in yet another earlier survey, 77% of parents rated early morning functional impairment in children with ADHD as moderate to severe (J Child Adolesc Pharmacol. 2017 Oct 1;27[8]:715-22).
“,” said Dr. Childress, president of the Center for Psychiatry and Behavioral Medicine in Las Vegas.
In the current study, presented by Dr. Childress at the meeting, 117 children aged 6-12 years with ADHD and morning behavioral problems, after a 5-day washout period, were started on an evening DR/ER MPH dose of 20 mg or 40 mg. They were then seen for up to 4 more weeks, and doses optimized (maximum 100 mg/day).
Adjustments also were made in the evening dose schedule to determine an optimal dosing time, which had to range from 6:30 pm to 9:30 pm, at least 1 hour after dinner. Clinicians optimized the dose and timing to achieve maximum symptom control throughout the day (minimum 30% improvement in total symptom score from baseline), while remaining safe and well-tolerated.The participants were then randomized to maintain the current drug dose, or to switch to placebo for 1 week. The primary endpoint was the average of all post-dose SKAMP-CS (Swanson, Kotkin, Agler, M-Flynn, and Pelham combined scale) measurements, as recorded by a trained, independent observer during the 12-hour period on the last classroom day.
There was a significant improvement in the primary measure, with the treatment group averaging 14.8 on the SKAMP-CS, compared with 20.7 for the placebo group (P less than .001). The improved outcomes were steady throughout the day, failing to achieve statistical significance at 8 a.m., but achieving significance in measurements taken at 9 a.m.,10 a.m., 12 p.m., 2 pm, 4 p.m., 6 p.m., and 7 p.m.
The formulation also achieved significant difference in morning and late afternoon measurements of the Parent Rating of Evening and Morning Behavior Scale, Revised (PREMB-R AM and PREMB-R PM). The treatment group scored a mean of 0.9 on PREMB-R AM, compared with 2.7 for placebo (P less than .001), and 6.1 vs. 9.3 in the PREMB-R PM scale (P = .003).
Most treatment emergent adverse events were considered mild or moderate, and occurred in 36.9% of the treatment group and 40.7% of placebo subjects.
The study was funded by Ironshore Pharmaceuticals, which said in a press statement that it plans to launch the drug early next year. In addition to Ironshore, Dr. Childress has served on the advisory board for, consulted for, or received research support from Aevi Genomic Medicine, Akili Interactive, Alcobra, Arbor Pharmaceuticals, Eli Lilly, Forest Laboratories, Lundbeck, KemPharm, Neos Therapeutics, Noven Pharmaceuticals, Otsuka America Pharmaceutical, Pearson, Pfizer, Purdue Pharma, Rhodes Pharmaceuticals, Shire, Sunovion, and Tris Pharma.
SEATTLE – A novel formulation of methylphenidate could provide morning relief to pediatric patients with attention-deficit/hyperactivity disorder, according to results of a pivotal phase 3 classroom trial.
In the study, delayed release/extended release methylphenidate (DR/ER MPH), when taken the night before, improved ADHD symptoms throughout a 12-hour laboratory classroom period – including in the late afternoons and early mornings.
The formulation, also known as Jornay PM, received Food and Drug Administration approval for ADHD in August for patients aged 6 and older. “For kids who have a horrendous time in the morning, getting up out of bed, and getting ready for school, they get up and they’re ready to rock and roll. [The drug] makes the mornings go better,” Ann Childress, MD, said in an interview at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
In a previous phase 3 trial, DR/ER MPH proved beneficial in late afternoon and early morning symptoms in a naturalistic sample over a 3- week treatment course (J Child Adolesc Pharmacol. 2017 Aug 1;27[6]:474-82). The current work sought to show its value in a classroom setting. And in yet another earlier survey, 77% of parents rated early morning functional impairment in children with ADHD as moderate to severe (J Child Adolesc Pharmacol. 2017 Oct 1;27[8]:715-22).
“,” said Dr. Childress, president of the Center for Psychiatry and Behavioral Medicine in Las Vegas.
In the current study, presented by Dr. Childress at the meeting, 117 children aged 6-12 years with ADHD and morning behavioral problems, after a 5-day washout period, were started on an evening DR/ER MPH dose of 20 mg or 40 mg. They were then seen for up to 4 more weeks, and doses optimized (maximum 100 mg/day).
Adjustments also were made in the evening dose schedule to determine an optimal dosing time, which had to range from 6:30 pm to 9:30 pm, at least 1 hour after dinner. Clinicians optimized the dose and timing to achieve maximum symptom control throughout the day (minimum 30% improvement in total symptom score from baseline), while remaining safe and well-tolerated.The participants were then randomized to maintain the current drug dose, or to switch to placebo for 1 week. The primary endpoint was the average of all post-dose SKAMP-CS (Swanson, Kotkin, Agler, M-Flynn, and Pelham combined scale) measurements, as recorded by a trained, independent observer during the 12-hour period on the last classroom day.
There was a significant improvement in the primary measure, with the treatment group averaging 14.8 on the SKAMP-CS, compared with 20.7 for the placebo group (P less than .001). The improved outcomes were steady throughout the day, failing to achieve statistical significance at 8 a.m., but achieving significance in measurements taken at 9 a.m.,10 a.m., 12 p.m., 2 pm, 4 p.m., 6 p.m., and 7 p.m.
The formulation also achieved significant difference in morning and late afternoon measurements of the Parent Rating of Evening and Morning Behavior Scale, Revised (PREMB-R AM and PREMB-R PM). The treatment group scored a mean of 0.9 on PREMB-R AM, compared with 2.7 for placebo (P less than .001), and 6.1 vs. 9.3 in the PREMB-R PM scale (P = .003).
Most treatment emergent adverse events were considered mild or moderate, and occurred in 36.9% of the treatment group and 40.7% of placebo subjects.
The study was funded by Ironshore Pharmaceuticals, which said in a press statement that it plans to launch the drug early next year. In addition to Ironshore, Dr. Childress has served on the advisory board for, consulted for, or received research support from Aevi Genomic Medicine, Akili Interactive, Alcobra, Arbor Pharmaceuticals, Eli Lilly, Forest Laboratories, Lundbeck, KemPharm, Neos Therapeutics, Noven Pharmaceuticals, Otsuka America Pharmaceutical, Pearson, Pfizer, Purdue Pharma, Rhodes Pharmaceuticals, Shire, Sunovion, and Tris Pharma.
REPORTING FROM AACAP 2018
Key clinical point: Children who took the formulation experienced improved, steady outcomes throughout the day.
Major finding: The treatment group scored an average of 0.9 on the PREMB-R morning test, compared with 2.7 in the placebo group.
Study details: Randomized, controlled trial involving 117 patients.
Disclosures: The study was funded by Ironshore Pharmaceuticals, which said in a press statement that it plans to launch the drug early next year. In addition to Ironshore, Dr. Childress has served on the advisory board for, consulted for, or received research support from Aevi Genomic Medicine, Akili Interactive, Alcobra, Arbor Pharmaceuticals, Eli Lilly, Forest Laboratories, Lundbeck, KemPharm, Neos Therapeutics, Noven Pharmaceuticals, Otsuka America Pharmaceutical, Pearson, Pfizer, Purdue Pharma, Rhodes Pharmaceuticals, Shire, Sunovion, and Tris Pharma.
Adult ADHD? Screen for hoarding symptoms
BARCELONA – Clinically meaningful hoarding symptoms are present in roughly one in four adults with attention-deficit/hyperactivity disorder, Sharon Morein-Zamir, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.
Her message to her fellow clinicians: “Nobody tends to ask about hoarding problems in adult ADHD clinics. Ask your ADHD patients carefully and routinely about hoarding symptoms. Screen them for it, ask their family members about it, and see whether it could be a problem contributing to daily impairment,” urged Dr. Morein-Zamir, a senior lecturer in clinical psychology at Anglia Ruskin University in Cambridge, England.
The clinician must broach the subject, because hoarding often is characterized by lack of insight.
“Patients don’t complain about it. You’ll have family members complain about it, neighbors complain about it, maybe social services, but the individuals themselves often don’t think they have a problem. And if they acknowledge it, they don’t seek treatment for it. So you really need to actively ask about the issue. They won’t raise it themselves,” she said.
Hoarding disorder and ADHD are considered two separate entities. But her study demonstrated that they share a common link: inattention symptoms.
the psychologist continued.
Indeed, one of the reasons why hoarding disorder is no longer grouped with obsessive-compulsive disorder in diagnostic schema is that inattention symptoms are not characteristic of OCD.
Dr. Morein-Zamir presented a cross-sectional study of 50 patients in an adult ADHD clinic and 46 age- and sex-matched controls. A total of 22 of the ADHD patients were on methylphenidate, 15 on selective serotonin reuptake inhibitors, 6 on amphetamine, and 7 were unmedicated.
Participants were assessed for hoarding using two validated measures well-suited for screening in daily practice: the Saving Inventory–Revised (SIR) and the Clutter Image Rating (CIR). Clinically meaningful hoarding symptoms – a designation requiring both a score of at least 42 on the SIR and 12 on the CIR – were present in 11 of 50 adult ADHD patients and none of the controls.
The group with clinically meaningful hoarding symptoms differed from the 39 ADHD patients without hoarding most noticeably in their more pronounced inattention symptoms as scored on the Adult ADHD Self-Report Scale (ASRS): a mean score of 32.8, compared with 28.8 in ADHD patients without clinically important hoarding. In contrast, the two groups scored similarly for hyperactivity/impulsivity on the patient-completed 18-item ASRS, as well as for depression and anxiety on the Depression Anxiety Stress Scales (DASS).
Within the ADHD group, only inattention as measured on the ASRS predicted hoarding severity on the SIR. In a multivariate regression analysis controlling for age, sex, hyperactivity/impulsivity on the ASRS, and DASS scores, inattention correlated strongly with all of the key hoarding dimensions: clutter, excessive acquisition, and difficulty discarding. Hyperactivity/impulsivity showed a modest correlation with clutter but not with the other hoarding dimensions.
Dr. Morein-Zamir observed that, while the last 3 or so years have seen booming interest in the development of manualized cognitive-behavioral therapy strategies for hoarding disorder, it’s not yet known whether those tools will be effective for treating high-level hoarding symptoms in patients with ADHD.
She reported having no financial conflicts regarding her study, which was funded by the British Academy.
BARCELONA – Clinically meaningful hoarding symptoms are present in roughly one in four adults with attention-deficit/hyperactivity disorder, Sharon Morein-Zamir, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.
Her message to her fellow clinicians: “Nobody tends to ask about hoarding problems in adult ADHD clinics. Ask your ADHD patients carefully and routinely about hoarding symptoms. Screen them for it, ask their family members about it, and see whether it could be a problem contributing to daily impairment,” urged Dr. Morein-Zamir, a senior lecturer in clinical psychology at Anglia Ruskin University in Cambridge, England.
The clinician must broach the subject, because hoarding often is characterized by lack of insight.
“Patients don’t complain about it. You’ll have family members complain about it, neighbors complain about it, maybe social services, but the individuals themselves often don’t think they have a problem. And if they acknowledge it, they don’t seek treatment for it. So you really need to actively ask about the issue. They won’t raise it themselves,” she said.
Hoarding disorder and ADHD are considered two separate entities. But her study demonstrated that they share a common link: inattention symptoms.
the psychologist continued.
Indeed, one of the reasons why hoarding disorder is no longer grouped with obsessive-compulsive disorder in diagnostic schema is that inattention symptoms are not characteristic of OCD.
Dr. Morein-Zamir presented a cross-sectional study of 50 patients in an adult ADHD clinic and 46 age- and sex-matched controls. A total of 22 of the ADHD patients were on methylphenidate, 15 on selective serotonin reuptake inhibitors, 6 on amphetamine, and 7 were unmedicated.
Participants were assessed for hoarding using two validated measures well-suited for screening in daily practice: the Saving Inventory–Revised (SIR) and the Clutter Image Rating (CIR). Clinically meaningful hoarding symptoms – a designation requiring both a score of at least 42 on the SIR and 12 on the CIR – were present in 11 of 50 adult ADHD patients and none of the controls.
The group with clinically meaningful hoarding symptoms differed from the 39 ADHD patients without hoarding most noticeably in their more pronounced inattention symptoms as scored on the Adult ADHD Self-Report Scale (ASRS): a mean score of 32.8, compared with 28.8 in ADHD patients without clinically important hoarding. In contrast, the two groups scored similarly for hyperactivity/impulsivity on the patient-completed 18-item ASRS, as well as for depression and anxiety on the Depression Anxiety Stress Scales (DASS).
Within the ADHD group, only inattention as measured on the ASRS predicted hoarding severity on the SIR. In a multivariate regression analysis controlling for age, sex, hyperactivity/impulsivity on the ASRS, and DASS scores, inattention correlated strongly with all of the key hoarding dimensions: clutter, excessive acquisition, and difficulty discarding. Hyperactivity/impulsivity showed a modest correlation with clutter but not with the other hoarding dimensions.
Dr. Morein-Zamir observed that, while the last 3 or so years have seen booming interest in the development of manualized cognitive-behavioral therapy strategies for hoarding disorder, it’s not yet known whether those tools will be effective for treating high-level hoarding symptoms in patients with ADHD.
She reported having no financial conflicts regarding her study, which was funded by the British Academy.
BARCELONA – Clinically meaningful hoarding symptoms are present in roughly one in four adults with attention-deficit/hyperactivity disorder, Sharon Morein-Zamir, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.
Her message to her fellow clinicians: “Nobody tends to ask about hoarding problems in adult ADHD clinics. Ask your ADHD patients carefully and routinely about hoarding symptoms. Screen them for it, ask their family members about it, and see whether it could be a problem contributing to daily impairment,” urged Dr. Morein-Zamir, a senior lecturer in clinical psychology at Anglia Ruskin University in Cambridge, England.
The clinician must broach the subject, because hoarding often is characterized by lack of insight.
“Patients don’t complain about it. You’ll have family members complain about it, neighbors complain about it, maybe social services, but the individuals themselves often don’t think they have a problem. And if they acknowledge it, they don’t seek treatment for it. So you really need to actively ask about the issue. They won’t raise it themselves,” she said.
Hoarding disorder and ADHD are considered two separate entities. But her study demonstrated that they share a common link: inattention symptoms.
the psychologist continued.
Indeed, one of the reasons why hoarding disorder is no longer grouped with obsessive-compulsive disorder in diagnostic schema is that inattention symptoms are not characteristic of OCD.
Dr. Morein-Zamir presented a cross-sectional study of 50 patients in an adult ADHD clinic and 46 age- and sex-matched controls. A total of 22 of the ADHD patients were on methylphenidate, 15 on selective serotonin reuptake inhibitors, 6 on amphetamine, and 7 were unmedicated.
Participants were assessed for hoarding using two validated measures well-suited for screening in daily practice: the Saving Inventory–Revised (SIR) and the Clutter Image Rating (CIR). Clinically meaningful hoarding symptoms – a designation requiring both a score of at least 42 on the SIR and 12 on the CIR – were present in 11 of 50 adult ADHD patients and none of the controls.
The group with clinically meaningful hoarding symptoms differed from the 39 ADHD patients without hoarding most noticeably in their more pronounced inattention symptoms as scored on the Adult ADHD Self-Report Scale (ASRS): a mean score of 32.8, compared with 28.8 in ADHD patients without clinically important hoarding. In contrast, the two groups scored similarly for hyperactivity/impulsivity on the patient-completed 18-item ASRS, as well as for depression and anxiety on the Depression Anxiety Stress Scales (DASS).
Within the ADHD group, only inattention as measured on the ASRS predicted hoarding severity on the SIR. In a multivariate regression analysis controlling for age, sex, hyperactivity/impulsivity on the ASRS, and DASS scores, inattention correlated strongly with all of the key hoarding dimensions: clutter, excessive acquisition, and difficulty discarding. Hyperactivity/impulsivity showed a modest correlation with clutter but not with the other hoarding dimensions.
Dr. Morein-Zamir observed that, while the last 3 or so years have seen booming interest in the development of manualized cognitive-behavioral therapy strategies for hoarding disorder, it’s not yet known whether those tools will be effective for treating high-level hoarding symptoms in patients with ADHD.
She reported having no financial conflicts regarding her study, which was funded by the British Academy.
REPORTING FROM THE ECNP CONGRESS
Key clinical point: Routinely screen adults with ADHD for hoarding disorder.
Major finding: Eleven of 50 (22%) unselected adults with ADHD displayed clinically meaningful hoarding symptoms.
Study details: This cross-sectional study included 50 adult ADHD patients and 46 matched controls who were assessed for hoarding symptoms and inattention.
Disclosures: The presenter reported having no financial conflicts regarding this study, which was funded by the British Academy.