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Aripiprazole may suppress prolactin in boys who develop gynecomasta while on risperidon, other atypical antipsychotics
NEW YORK – In adolescent boys who develop gynecomastia while taking an atypical antipsychotic that elevates prolactin, extra steps should be taken to confirm that it is drug related, according to a review of data presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“In 13- to 14-year-old boys who develop gynecomastia while taking risperidone, the odds of it being due to pubertal gynecomastia rather than risperidone are about 15:1,” reported Dr. Harold E. Carlson, division head of endocrinology, State University of New York at Stony Brook.
Hyperprolactinemia is associated with a variety of adverse effects on normal physiology, resulting in osteoporosis, decreased libido, erectile dysfunction in men, and amenorrhea and possibly hirsutism in women, Dr. Carlson said. However, he cautioned that clinicians should not assume that breast enlargement in peripubertal children is a result of elevated prolactin.
“Remember that nearly all boys who take drugs like risperidone will have an elevated serum prolactin at least early on, and then it will come down,” Dr. Carlson said. “But the data say that 3%-5% will get gynecomastia on risperidone, which means that 95%-97% of people taking risperidone don’t get gynecomastia,”
Most cases of gynecomastia in boys on risperidone are unrelated to the medication. “Pubertal gynecomastia has nothing to do with prolactin. It is a phenomenon that occurs in normal puberty,” Dr. Carlson emphasized. The pubertal breast enlargement was once considered most likely to be produced by a transient imbalance in the sex steroids, but Dr. Carlson said that recent studies have linked this phenomenon to insulinlike growth factor I (IGF-I). This is supported by several sets of data, said Dr. Carlson, who also noted, “teenage boys have the highest IGF-I levels of anybody.”
The data suggest that normal physiology is a more likely cause of breast enlargement in pubertal boys than an antipsychotic drug that raises prolactin, but Dr. Carlson said clinicians should educate patients and parents about the risk.
In a boy or a girl who reports breast tenderness that appears to be glandular rather than adipose on palpation, Dr. Carlson suggested measuring serum prolactin levels. If prolactin levels are greater than 30 ng/mL, an alternative, prolactin-neutral therapy, is “prudent,” he said. He showed data in which a switch from risperidone or ziprasidone to quetiapine produced large reductions in serum prolactin within 3 months.
Another strategy, which is useful when there is concern about discontinuing a prolactin-raising antipsychotic, is to add aripiprazole, which suppresses prolactin. “Aripiprazole doses of 5-15 mg per day are often effective in normalizing serum prolactin in patients receiving haloperidol, risperidone, paliperidone, or olanzapine,” Dr. Carlson said, However, he noted that it is “not as effective in lowering serum prolactin in patients receiving amisulpride or sulpiride.”
Prolonged periods of hyperprolactinemia can produce adverse effects in boys and girls, but those effects are “generally reversible if the underlying problem is corrected within 1-2 years,” Dr. Carlson said. In adolescents on prolactin-elevating drugs, however, it is important to demonstrate rather than assume that elevated prolactin is the cause of symptoms. It also is important to consider all causes of hyperprolactinemia, which can include impaired thyroid or kidney function.
“Inquire about menstruation, breast enlargement or tenderness, nipple discharge, sexual functioning, and pubertal development,” Dr. Carlson advised. “If normal, there is no need to measure serum prolactin.”
Dr. Carlson reported financial relationships with Lundbeck and Pfizer.
*This story was updated on Feb. 24, 2016.
NEW YORK – In adolescent boys who develop gynecomastia while taking an atypical antipsychotic that elevates prolactin, extra steps should be taken to confirm that it is drug related, according to a review of data presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“In 13- to 14-year-old boys who develop gynecomastia while taking risperidone, the odds of it being due to pubertal gynecomastia rather than risperidone are about 15:1,” reported Dr. Harold E. Carlson, division head of endocrinology, State University of New York at Stony Brook.
Hyperprolactinemia is associated with a variety of adverse effects on normal physiology, resulting in osteoporosis, decreased libido, erectile dysfunction in men, and amenorrhea and possibly hirsutism in women, Dr. Carlson said. However, he cautioned that clinicians should not assume that breast enlargement in peripubertal children is a result of elevated prolactin.
“Remember that nearly all boys who take drugs like risperidone will have an elevated serum prolactin at least early on, and then it will come down,” Dr. Carlson said. “But the data say that 3%-5% will get gynecomastia on risperidone, which means that 95%-97% of people taking risperidone don’t get gynecomastia,”
Most cases of gynecomastia in boys on risperidone are unrelated to the medication. “Pubertal gynecomastia has nothing to do with prolactin. It is a phenomenon that occurs in normal puberty,” Dr. Carlson emphasized. The pubertal breast enlargement was once considered most likely to be produced by a transient imbalance in the sex steroids, but Dr. Carlson said that recent studies have linked this phenomenon to insulinlike growth factor I (IGF-I). This is supported by several sets of data, said Dr. Carlson, who also noted, “teenage boys have the highest IGF-I levels of anybody.”
The data suggest that normal physiology is a more likely cause of breast enlargement in pubertal boys than an antipsychotic drug that raises prolactin, but Dr. Carlson said clinicians should educate patients and parents about the risk.
In a boy or a girl who reports breast tenderness that appears to be glandular rather than adipose on palpation, Dr. Carlson suggested measuring serum prolactin levels. If prolactin levels are greater than 30 ng/mL, an alternative, prolactin-neutral therapy, is “prudent,” he said. He showed data in which a switch from risperidone or ziprasidone to quetiapine produced large reductions in serum prolactin within 3 months.
Another strategy, which is useful when there is concern about discontinuing a prolactin-raising antipsychotic, is to add aripiprazole, which suppresses prolactin. “Aripiprazole doses of 5-15 mg per day are often effective in normalizing serum prolactin in patients receiving haloperidol, risperidone, paliperidone, or olanzapine,” Dr. Carlson said, However, he noted that it is “not as effective in lowering serum prolactin in patients receiving amisulpride or sulpiride.”
Prolonged periods of hyperprolactinemia can produce adverse effects in boys and girls, but those effects are “generally reversible if the underlying problem is corrected within 1-2 years,” Dr. Carlson said. In adolescents on prolactin-elevating drugs, however, it is important to demonstrate rather than assume that elevated prolactin is the cause of symptoms. It also is important to consider all causes of hyperprolactinemia, which can include impaired thyroid or kidney function.
“Inquire about menstruation, breast enlargement or tenderness, nipple discharge, sexual functioning, and pubertal development,” Dr. Carlson advised. “If normal, there is no need to measure serum prolactin.”
Dr. Carlson reported financial relationships with Lundbeck and Pfizer.
*This story was updated on Feb. 24, 2016.
NEW YORK – In adolescent boys who develop gynecomastia while taking an atypical antipsychotic that elevates prolactin, extra steps should be taken to confirm that it is drug related, according to a review of data presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“In 13- to 14-year-old boys who develop gynecomastia while taking risperidone, the odds of it being due to pubertal gynecomastia rather than risperidone are about 15:1,” reported Dr. Harold E. Carlson, division head of endocrinology, State University of New York at Stony Brook.
Hyperprolactinemia is associated with a variety of adverse effects on normal physiology, resulting in osteoporosis, decreased libido, erectile dysfunction in men, and amenorrhea and possibly hirsutism in women, Dr. Carlson said. However, he cautioned that clinicians should not assume that breast enlargement in peripubertal children is a result of elevated prolactin.
“Remember that nearly all boys who take drugs like risperidone will have an elevated serum prolactin at least early on, and then it will come down,” Dr. Carlson said. “But the data say that 3%-5% will get gynecomastia on risperidone, which means that 95%-97% of people taking risperidone don’t get gynecomastia,”
Most cases of gynecomastia in boys on risperidone are unrelated to the medication. “Pubertal gynecomastia has nothing to do with prolactin. It is a phenomenon that occurs in normal puberty,” Dr. Carlson emphasized. The pubertal breast enlargement was once considered most likely to be produced by a transient imbalance in the sex steroids, but Dr. Carlson said that recent studies have linked this phenomenon to insulinlike growth factor I (IGF-I). This is supported by several sets of data, said Dr. Carlson, who also noted, “teenage boys have the highest IGF-I levels of anybody.”
The data suggest that normal physiology is a more likely cause of breast enlargement in pubertal boys than an antipsychotic drug that raises prolactin, but Dr. Carlson said clinicians should educate patients and parents about the risk.
In a boy or a girl who reports breast tenderness that appears to be glandular rather than adipose on palpation, Dr. Carlson suggested measuring serum prolactin levels. If prolactin levels are greater than 30 ng/mL, an alternative, prolactin-neutral therapy, is “prudent,” he said. He showed data in which a switch from risperidone or ziprasidone to quetiapine produced large reductions in serum prolactin within 3 months.
Another strategy, which is useful when there is concern about discontinuing a prolactin-raising antipsychotic, is to add aripiprazole, which suppresses prolactin. “Aripiprazole doses of 5-15 mg per day are often effective in normalizing serum prolactin in patients receiving haloperidol, risperidone, paliperidone, or olanzapine,” Dr. Carlson said, However, he noted that it is “not as effective in lowering serum prolactin in patients receiving amisulpride or sulpiride.”
Prolonged periods of hyperprolactinemia can produce adverse effects in boys and girls, but those effects are “generally reversible if the underlying problem is corrected within 1-2 years,” Dr. Carlson said. In adolescents on prolactin-elevating drugs, however, it is important to demonstrate rather than assume that elevated prolactin is the cause of symptoms. It also is important to consider all causes of hyperprolactinemia, which can include impaired thyroid or kidney function.
“Inquire about menstruation, breast enlargement or tenderness, nipple discharge, sexual functioning, and pubertal development,” Dr. Carlson advised. “If normal, there is no need to measure serum prolactin.”
Dr. Carlson reported financial relationships with Lundbeck and Pfizer.
*This story was updated on Feb. 24, 2016.
EXPERT ANALYSIS FROM THE PSYCHOPHARMACOLOGY UPDATE INSTITUTE
Psychotropics low on list of therapies for autism
NEW YORK – Some of the behavioral and psychiatric problems observed in children with autism spectrum disorder (ASD) may improve on atypical antipsychotics, but these drugs do not improve core symptoms and should be used sparingly in this population, according to an expert’s analysis at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“Most children with ASD either do not need or will not benefit from available psychotropic medications,” reported Dr. Jeremy M. Veenstra-VanderWeele of the Center for Autism and the Developing Brain, Columbia University, New York.
In a review of the evidence, he suggested that psychopharmacologic treatments for children with ASD, when indicated at all, are only relevant to behavioral issues and psychiatric comorbidities. On an evidence basis, behavioral modification and psychosocial support for the patient and family should come first or at least accompany psychotropic agents.
“These families are desperate and, oftentimes, they cannot get the services that would actually make things better for their child on a behavioral level,” Dr. Veenstra-VanderWeele said. He said that the “pressure to prescribe,” along with a desire to help, drive many clinicians to offer medications, “but we just should be honest and recognize that our evidence does not suggest that we are able to help the majority.”
Most children with ASD do receive one or more prescriptions for psychotropic agents, according to Dr. Veenstra-VanderWeele’s experience. In fact, he reported that he often is asked to consult on a child who has been prescribed two or three medications when it is unclear which, if any, are offering benefit. While he also finds that these agents often are prescribed at low doses, a better approach would be to use an evidence-based therapy at an adequate dose after carefully evaluating the risk-to-benefit ratio.
“I find that a lot of the kids I see in consultation have had, in desperation, more than one medicine started within the time window of response, and that’s really problematic. That is how kids end up on three or four medicines without a clear sense of what led to improvement,” Dr. Veenstra-VanderWeele noted. He suggested that the more appropriate strategy is to attempt to maximize benefit on one therapy, including behavioral therapies, before initiating another.
In his review of psychotropic medicines for ASD comorbidities, he suggested the evidence is “high” that the atypical antipsychotics risperidone and aripiprazole are effective in at least some children for irritability and agitation. He also reported that the evidence of lack of benefit from secretin also should now be labeled as high.
The evidence for benefit from long-acting stimulants for behavioral improvement was labeled as “moderate,” particularly when considered in the context of adverse events. Atomoxetine, a selective norepinephrine reuptake inhibitor also used for attention-deficit/hyperactivity disorder, is another drug placed by Dr. Veenstra-VanderWeele in the category for “moderate” evidence. Two controlled studies have demonstrated activity, but the overall response in each was relatively modest.
In a third group, labeled “insufficient evidence,” he placed both guanfacine, particularly for irritability, and selective serotonin reuptake inhibitors.
Although the strongest evidence for pharmacotherapy to control comorbidities in ASD is related to atypical antipsychotics, he emphasized that these are accompanied with adverse events. Some, such as weight gain, can be difficult to reverse after long-term therapy.
“Particularly in this population, I talk about stopping the medicine at the time that I start the medicine,” Dr. Veenstra-VanderWeele reported. Citing the frequency of rapid weight gain in patients on some atypical antipsychotics, he said that it is important to warn patients that a switch in therapy may be necessary.
“It is often hard to say we are going to switch when everyone feels that the patient is much better. You have to lay it out in advance and write it down, so the family knows what to expect,” Dr. Veenstra-VanderWeele said.
Management of pediatric ASD typically involves multiple coexisting clinical issues. Because “there is always something else going on” in the ASD patient, he emphasized the need for a systematic approach in which medical and behavioral issues and psychiatric comorbidities are addressed in the context of clear goals for each targeted symptom.
Dr. Veenstra-VanderWeele reported financial relationships with Forest Laboratories, Hoffmann-La Roche, Novartis, Seaside Therapeutics, Sunovion Pharmaceuticals, and SynapDx.
NEW YORK – Some of the behavioral and psychiatric problems observed in children with autism spectrum disorder (ASD) may improve on atypical antipsychotics, but these drugs do not improve core symptoms and should be used sparingly in this population, according to an expert’s analysis at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“Most children with ASD either do not need or will not benefit from available psychotropic medications,” reported Dr. Jeremy M. Veenstra-VanderWeele of the Center for Autism and the Developing Brain, Columbia University, New York.
In a review of the evidence, he suggested that psychopharmacologic treatments for children with ASD, when indicated at all, are only relevant to behavioral issues and psychiatric comorbidities. On an evidence basis, behavioral modification and psychosocial support for the patient and family should come first or at least accompany psychotropic agents.
“These families are desperate and, oftentimes, they cannot get the services that would actually make things better for their child on a behavioral level,” Dr. Veenstra-VanderWeele said. He said that the “pressure to prescribe,” along with a desire to help, drive many clinicians to offer medications, “but we just should be honest and recognize that our evidence does not suggest that we are able to help the majority.”
Most children with ASD do receive one or more prescriptions for psychotropic agents, according to Dr. Veenstra-VanderWeele’s experience. In fact, he reported that he often is asked to consult on a child who has been prescribed two or three medications when it is unclear which, if any, are offering benefit. While he also finds that these agents often are prescribed at low doses, a better approach would be to use an evidence-based therapy at an adequate dose after carefully evaluating the risk-to-benefit ratio.
“I find that a lot of the kids I see in consultation have had, in desperation, more than one medicine started within the time window of response, and that’s really problematic. That is how kids end up on three or four medicines without a clear sense of what led to improvement,” Dr. Veenstra-VanderWeele noted. He suggested that the more appropriate strategy is to attempt to maximize benefit on one therapy, including behavioral therapies, before initiating another.
In his review of psychotropic medicines for ASD comorbidities, he suggested the evidence is “high” that the atypical antipsychotics risperidone and aripiprazole are effective in at least some children for irritability and agitation. He also reported that the evidence of lack of benefit from secretin also should now be labeled as high.
The evidence for benefit from long-acting stimulants for behavioral improvement was labeled as “moderate,” particularly when considered in the context of adverse events. Atomoxetine, a selective norepinephrine reuptake inhibitor also used for attention-deficit/hyperactivity disorder, is another drug placed by Dr. Veenstra-VanderWeele in the category for “moderate” evidence. Two controlled studies have demonstrated activity, but the overall response in each was relatively modest.
In a third group, labeled “insufficient evidence,” he placed both guanfacine, particularly for irritability, and selective serotonin reuptake inhibitors.
Although the strongest evidence for pharmacotherapy to control comorbidities in ASD is related to atypical antipsychotics, he emphasized that these are accompanied with adverse events. Some, such as weight gain, can be difficult to reverse after long-term therapy.
“Particularly in this population, I talk about stopping the medicine at the time that I start the medicine,” Dr. Veenstra-VanderWeele reported. Citing the frequency of rapid weight gain in patients on some atypical antipsychotics, he said that it is important to warn patients that a switch in therapy may be necessary.
“It is often hard to say we are going to switch when everyone feels that the patient is much better. You have to lay it out in advance and write it down, so the family knows what to expect,” Dr. Veenstra-VanderWeele said.
Management of pediatric ASD typically involves multiple coexisting clinical issues. Because “there is always something else going on” in the ASD patient, he emphasized the need for a systematic approach in which medical and behavioral issues and psychiatric comorbidities are addressed in the context of clear goals for each targeted symptom.
Dr. Veenstra-VanderWeele reported financial relationships with Forest Laboratories, Hoffmann-La Roche, Novartis, Seaside Therapeutics, Sunovion Pharmaceuticals, and SynapDx.
NEW YORK – Some of the behavioral and psychiatric problems observed in children with autism spectrum disorder (ASD) may improve on atypical antipsychotics, but these drugs do not improve core symptoms and should be used sparingly in this population, according to an expert’s analysis at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“Most children with ASD either do not need or will not benefit from available psychotropic medications,” reported Dr. Jeremy M. Veenstra-VanderWeele of the Center for Autism and the Developing Brain, Columbia University, New York.
In a review of the evidence, he suggested that psychopharmacologic treatments for children with ASD, when indicated at all, are only relevant to behavioral issues and psychiatric comorbidities. On an evidence basis, behavioral modification and psychosocial support for the patient and family should come first or at least accompany psychotropic agents.
“These families are desperate and, oftentimes, they cannot get the services that would actually make things better for their child on a behavioral level,” Dr. Veenstra-VanderWeele said. He said that the “pressure to prescribe,” along with a desire to help, drive many clinicians to offer medications, “but we just should be honest and recognize that our evidence does not suggest that we are able to help the majority.”
Most children with ASD do receive one or more prescriptions for psychotropic agents, according to Dr. Veenstra-VanderWeele’s experience. In fact, he reported that he often is asked to consult on a child who has been prescribed two or three medications when it is unclear which, if any, are offering benefit. While he also finds that these agents often are prescribed at low doses, a better approach would be to use an evidence-based therapy at an adequate dose after carefully evaluating the risk-to-benefit ratio.
“I find that a lot of the kids I see in consultation have had, in desperation, more than one medicine started within the time window of response, and that’s really problematic. That is how kids end up on three or four medicines without a clear sense of what led to improvement,” Dr. Veenstra-VanderWeele noted. He suggested that the more appropriate strategy is to attempt to maximize benefit on one therapy, including behavioral therapies, before initiating another.
In his review of psychotropic medicines for ASD comorbidities, he suggested the evidence is “high” that the atypical antipsychotics risperidone and aripiprazole are effective in at least some children for irritability and agitation. He also reported that the evidence of lack of benefit from secretin also should now be labeled as high.
The evidence for benefit from long-acting stimulants for behavioral improvement was labeled as “moderate,” particularly when considered in the context of adverse events. Atomoxetine, a selective norepinephrine reuptake inhibitor also used for attention-deficit/hyperactivity disorder, is another drug placed by Dr. Veenstra-VanderWeele in the category for “moderate” evidence. Two controlled studies have demonstrated activity, but the overall response in each was relatively modest.
In a third group, labeled “insufficient evidence,” he placed both guanfacine, particularly for irritability, and selective serotonin reuptake inhibitors.
Although the strongest evidence for pharmacotherapy to control comorbidities in ASD is related to atypical antipsychotics, he emphasized that these are accompanied with adverse events. Some, such as weight gain, can be difficult to reverse after long-term therapy.
“Particularly in this population, I talk about stopping the medicine at the time that I start the medicine,” Dr. Veenstra-VanderWeele reported. Citing the frequency of rapid weight gain in patients on some atypical antipsychotics, he said that it is important to warn patients that a switch in therapy may be necessary.
“It is often hard to say we are going to switch when everyone feels that the patient is much better. You have to lay it out in advance and write it down, so the family knows what to expect,” Dr. Veenstra-VanderWeele said.
Management of pediatric ASD typically involves multiple coexisting clinical issues. Because “there is always something else going on” in the ASD patient, he emphasized the need for a systematic approach in which medical and behavioral issues and psychiatric comorbidities are addressed in the context of clear goals for each targeted symptom.
Dr. Veenstra-VanderWeele reported financial relationships with Forest Laboratories, Hoffmann-La Roche, Novartis, Seaside Therapeutics, Sunovion Pharmaceuticals, and SynapDx.
EXPERT ANALYSIS FROM THE PSYCHOPHARMACOLOGY UPDATE INSTITUTE
Try behavioral therapies first, then melatonin for pediatric insomnia
NEW YORK – In children with insomnia, melatonin is the appropriate first-line drug therapy, but pharmacologic treatments come after behavioral interventions, according to an evidence-based summary presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“Medication should rarely be our first choice. We should always be trying to combine it with behavioral therapies, because they work just as well and last longer,” reported Dr. Jess P. Shatkin, a professor in the department of child and adolescent psychiatry, New York University.
The number of randomized trials for sleep medications in children is limited, and there is no pharmacotherapy approved by the Food and Drug Administration for this indication, Dr. Shatkin said. Clinicians often extrapolate from adult studies, but Dr. Shatkin said these data are not necessarily transferable. He noted, for example, that a study of zolpidem in children, which is approved for adults, was negative.
The antihistamine diphenhydramine also has been studied in children, and results were mixed. In one of two double-blind, placebo-controlled pediatric studies, parents reported improvement in getting children to sleep. In the other, conducted in children aged 6 months to 15 months, no significant advantage was found for this agent over placebo.
“[Diphenhydramine] Benadryl may make your kids sleep, it may make your patients sleep, it may make you sleep, which is fine, but the data do not convince us that [diphenhydramine] Benadryl is a great treatment for sleep in children,” Dr. Shatkin reported.
Rather, the best data are with melatonin, an endogenous hormone produced on a circadian rhythm correlating with the end-of-day phenomenon known as dim-light melatonin onset (DLMO). In one study conducted in otherwise healthy children aged 6 to 12 years with chronic sleep-onset insomnia, the administration of exogenous melatonin decreased sleep-onset latency by 35 minutes as measured with actigraphy, according to Dr. Shatkin. Similar benefit has been observed in studies conducted in children with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD).
“Melatonin is efficacious in typically developing children and those with neurodevelopmental disorders. It imposes minimal effects on sleep architecture, it is associated with a low risk of side effects, the cost is low, and it is widely available,” Dr. Shatkin said. However, he advised against using this drug in children younger than 6 months old.
“The timing of the dosing is critical and should be based on DLMO,” Dr. Shatkin said. Specifically, he recommended a starting dose of 0.2 to 0.5 mg administered 2-3 hours before sleep time. The dose can be increased as needed by 0.2-0.5 mg per week to a maximum of 3.0 mg. Dr. Shatkin reported that there is “little evidence” to support extended-release formulations, but he did warn that over-the-counter preparations may vary in quality.
As an alternative, clonidine was listed as a second choice for treating insomnia in children. Although this therapy is not supported by controlled data, several open-label studies and chart reviews suggest benefit, and this therapy is less likely than diphenhydramine to produce next-day drowsiness.
Yet, he reiterated that the best evidence-based treatment of sleep problems in children is cognitive-behavioral therapy. He called the techniques – such as regular bedtimes, avoidance of stimuli, and creating a relaxing bedtime ritual – as easy to learn and teach to parents. Obvious problems in the sleep routine, such as irregular bedtimes, typically can be identified with a sleep history. There are numerous strategies to wean children from requiring the presence of a parent to fall asleep, such as “graduated extinction,” which involves incrementally distancing the parent from the child’s bedside.
Empathetic to the frequency of sleep disturbances in children, Dr. Shatkin cited data suggesting that 50% of preschool children, 30% of school-age children, and 40% of adolescents report sleep problems. A survey of child psychiatrists found that most acknowledged prescribing a sleep medication within the past month for pediatric insomnia, but Dr. Shatkin emphasized that behavioral therapies often may produce a longer-lasting result.
For treating pediatric sleep disturbances, “our educational and behavioral efforts really should trump our medications,” Dr. Shatkin said. “We should be using any medication sparingly.”
Dr. Shatkin reported financial relationships with Assurex Health, Edgemont Pharmaceuticals, Eli Lilly, Forest Laboratories, and Lundbeck.
NEW YORK – In children with insomnia, melatonin is the appropriate first-line drug therapy, but pharmacologic treatments come after behavioral interventions, according to an evidence-based summary presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“Medication should rarely be our first choice. We should always be trying to combine it with behavioral therapies, because they work just as well and last longer,” reported Dr. Jess P. Shatkin, a professor in the department of child and adolescent psychiatry, New York University.
The number of randomized trials for sleep medications in children is limited, and there is no pharmacotherapy approved by the Food and Drug Administration for this indication, Dr. Shatkin said. Clinicians often extrapolate from adult studies, but Dr. Shatkin said these data are not necessarily transferable. He noted, for example, that a study of zolpidem in children, which is approved for adults, was negative.
The antihistamine diphenhydramine also has been studied in children, and results were mixed. In one of two double-blind, placebo-controlled pediatric studies, parents reported improvement in getting children to sleep. In the other, conducted in children aged 6 months to 15 months, no significant advantage was found for this agent over placebo.
“[Diphenhydramine] Benadryl may make your kids sleep, it may make your patients sleep, it may make you sleep, which is fine, but the data do not convince us that [diphenhydramine] Benadryl is a great treatment for sleep in children,” Dr. Shatkin reported.
Rather, the best data are with melatonin, an endogenous hormone produced on a circadian rhythm correlating with the end-of-day phenomenon known as dim-light melatonin onset (DLMO). In one study conducted in otherwise healthy children aged 6 to 12 years with chronic sleep-onset insomnia, the administration of exogenous melatonin decreased sleep-onset latency by 35 minutes as measured with actigraphy, according to Dr. Shatkin. Similar benefit has been observed in studies conducted in children with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD).
“Melatonin is efficacious in typically developing children and those with neurodevelopmental disorders. It imposes minimal effects on sleep architecture, it is associated with a low risk of side effects, the cost is low, and it is widely available,” Dr. Shatkin said. However, he advised against using this drug in children younger than 6 months old.
“The timing of the dosing is critical and should be based on DLMO,” Dr. Shatkin said. Specifically, he recommended a starting dose of 0.2 to 0.5 mg administered 2-3 hours before sleep time. The dose can be increased as needed by 0.2-0.5 mg per week to a maximum of 3.0 mg. Dr. Shatkin reported that there is “little evidence” to support extended-release formulations, but he did warn that over-the-counter preparations may vary in quality.
As an alternative, clonidine was listed as a second choice for treating insomnia in children. Although this therapy is not supported by controlled data, several open-label studies and chart reviews suggest benefit, and this therapy is less likely than diphenhydramine to produce next-day drowsiness.
Yet, he reiterated that the best evidence-based treatment of sleep problems in children is cognitive-behavioral therapy. He called the techniques – such as regular bedtimes, avoidance of stimuli, and creating a relaxing bedtime ritual – as easy to learn and teach to parents. Obvious problems in the sleep routine, such as irregular bedtimes, typically can be identified with a sleep history. There are numerous strategies to wean children from requiring the presence of a parent to fall asleep, such as “graduated extinction,” which involves incrementally distancing the parent from the child’s bedside.
Empathetic to the frequency of sleep disturbances in children, Dr. Shatkin cited data suggesting that 50% of preschool children, 30% of school-age children, and 40% of adolescents report sleep problems. A survey of child psychiatrists found that most acknowledged prescribing a sleep medication within the past month for pediatric insomnia, but Dr. Shatkin emphasized that behavioral therapies often may produce a longer-lasting result.
For treating pediatric sleep disturbances, “our educational and behavioral efforts really should trump our medications,” Dr. Shatkin said. “We should be using any medication sparingly.”
Dr. Shatkin reported financial relationships with Assurex Health, Edgemont Pharmaceuticals, Eli Lilly, Forest Laboratories, and Lundbeck.
NEW YORK – In children with insomnia, melatonin is the appropriate first-line drug therapy, but pharmacologic treatments come after behavioral interventions, according to an evidence-based summary presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“Medication should rarely be our first choice. We should always be trying to combine it with behavioral therapies, because they work just as well and last longer,” reported Dr. Jess P. Shatkin, a professor in the department of child and adolescent psychiatry, New York University.
The number of randomized trials for sleep medications in children is limited, and there is no pharmacotherapy approved by the Food and Drug Administration for this indication, Dr. Shatkin said. Clinicians often extrapolate from adult studies, but Dr. Shatkin said these data are not necessarily transferable. He noted, for example, that a study of zolpidem in children, which is approved for adults, was negative.
The antihistamine diphenhydramine also has been studied in children, and results were mixed. In one of two double-blind, placebo-controlled pediatric studies, parents reported improvement in getting children to sleep. In the other, conducted in children aged 6 months to 15 months, no significant advantage was found for this agent over placebo.
“[Diphenhydramine] Benadryl may make your kids sleep, it may make your patients sleep, it may make you sleep, which is fine, but the data do not convince us that [diphenhydramine] Benadryl is a great treatment for sleep in children,” Dr. Shatkin reported.
Rather, the best data are with melatonin, an endogenous hormone produced on a circadian rhythm correlating with the end-of-day phenomenon known as dim-light melatonin onset (DLMO). In one study conducted in otherwise healthy children aged 6 to 12 years with chronic sleep-onset insomnia, the administration of exogenous melatonin decreased sleep-onset latency by 35 minutes as measured with actigraphy, according to Dr. Shatkin. Similar benefit has been observed in studies conducted in children with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD).
“Melatonin is efficacious in typically developing children and those with neurodevelopmental disorders. It imposes minimal effects on sleep architecture, it is associated with a low risk of side effects, the cost is low, and it is widely available,” Dr. Shatkin said. However, he advised against using this drug in children younger than 6 months old.
“The timing of the dosing is critical and should be based on DLMO,” Dr. Shatkin said. Specifically, he recommended a starting dose of 0.2 to 0.5 mg administered 2-3 hours before sleep time. The dose can be increased as needed by 0.2-0.5 mg per week to a maximum of 3.0 mg. Dr. Shatkin reported that there is “little evidence” to support extended-release formulations, but he did warn that over-the-counter preparations may vary in quality.
As an alternative, clonidine was listed as a second choice for treating insomnia in children. Although this therapy is not supported by controlled data, several open-label studies and chart reviews suggest benefit, and this therapy is less likely than diphenhydramine to produce next-day drowsiness.
Yet, he reiterated that the best evidence-based treatment of sleep problems in children is cognitive-behavioral therapy. He called the techniques – such as regular bedtimes, avoidance of stimuli, and creating a relaxing bedtime ritual – as easy to learn and teach to parents. Obvious problems in the sleep routine, such as irregular bedtimes, typically can be identified with a sleep history. There are numerous strategies to wean children from requiring the presence of a parent to fall asleep, such as “graduated extinction,” which involves incrementally distancing the parent from the child’s bedside.
Empathetic to the frequency of sleep disturbances in children, Dr. Shatkin cited data suggesting that 50% of preschool children, 30% of school-age children, and 40% of adolescents report sleep problems. A survey of child psychiatrists found that most acknowledged prescribing a sleep medication within the past month for pediatric insomnia, but Dr. Shatkin emphasized that behavioral therapies often may produce a longer-lasting result.
For treating pediatric sleep disturbances, “our educational and behavioral efforts really should trump our medications,” Dr. Shatkin said. “We should be using any medication sparingly.”
Dr. Shatkin reported financial relationships with Assurex Health, Edgemont Pharmaceuticals, Eli Lilly, Forest Laboratories, and Lundbeck.
EXPERT ANALYSIS FROM THE PSYCHOPHARMACOLOGY UPDATE INSTITUTE
Anxiety is poorly recognized, treated in children
NEW YORK – Of psychiatric issues affecting child development, generalized anxiety is not getting the attention it deserves and is frequently mistaken for attention-deficit/hyperactivity disorder (ADHD), according to a review of key diagnostic signs and evidence-based therapies presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“Pediatricians have an ASD [autism spectrum disorder] toolkit, they have an ADHD toolkit, and they now have a postpartum depression toolkit for moms, but they do not have an anxiety tool kit,” reported Dr. John T. Walkup, director of the division of child and adolescent psychiatry, Cornell University, New York. “So if a kid is 7 or 8 and is inattentive, they have two choices: Either he has ASD or he has ADHD.”
Confusion with ASD is less likely, because there is less symptom crossover, but the differential diagnosis with ADHD is more challenging. For anxiety, symptoms typically peak between the ages of 6 and 12 years. Although the onset of ADHD symptoms, like symptoms of ASD, generally occurs earlier, children with anxiety and ADHD often are brought to the attention of a physician within the same general window of time.
From the point of view of the complaints that initiated an evaluation, “generalized anxiety disorder and the inattentive subtype of ADHD are almost indistinguishable,” Dr. Walkup asserted. He suggested that children who are anxious have difficulty concentrating in class because their minds are “full of ideas, worries, and concerns.” Children with ADHD have difficulty concentrating in class because their minds are “susceptible to distraction,” but the result is the same.
Some children, even those who are only 7 or 8 years old, “can really describe to you that difference,” Dr. Walkup observed, although he said other features can be useful for distinguishing anxiety from other psychiatric disorders, including depression. In taking the history of a child with potential anxiety, key signs include difficulty coping with novel situations, excessive sensitivity to perceived threats, and shyness. These features are less likely to be in children with ADHD or depression.
Once children reach adolescence, social insecurity is more ubiquitous, making this complaint less useful for identifying a child with pathologic anxiety, but here there is also room for confusion without a careful history.
“We see a lot of kids who have social anxiety who get mislabeled as depressed. Socially anxious kids become demoralized, but they do not become anhedonic,” Dr. Walkup reported. In patients who are inhibited with their peers but who do not otherwise report disturbances in mood, generalized anxiety rather than depression may be driving the psychopathology, according to Dr. Walkup, who said this set of circumstances is common.
Once the diagnosis of anxiety is made, both SSRIs and cognitive-behavioral therapy are effective, with response rates of about 55%-60%, Dr. Walkup said. The response rates can climb as high as 80% when the two are combined, particularly when CBT is performed at experienced centers.
With SSRIs, one of the biggest concerns is activation, an adverse event that occurs in up to 10% of patients, Dr. Walkup said. If activation occurs, he advised switching patients to a nonactivating antidepressant, such as duloxetine, nefazodone, or a tricyclic agent, rather than rechallenging them with another SSRI. In his experience, activation on one agent predicts activation on another, but he cautioned against confusing activation with SSRI-induced mania.
“We do see so many kids who get activated on an SSRI and never see another antidepressant again, simply because the doc is afraid of precipitating mania,” Dr. Walkup said. He said mania is a very uncommon adverse event not typically observed, like activation, relatively quickly after initiating therapy. Because of the efficacy of SSRIs for pediatric anxiety, Dr. Walkup advised being slow in abandoning this drug class.
“Antidepressants work extremely well, and SSRIs are the medications of choice,” emphasized Dr. Walkup, who identified atypical antidepressants as a second-line choice in children and benzodiazepines, for which pediatric data are “limited,” as an option further down the list.
However, therapy first requires a diagnosis.
“Identifying anxiety is key,” Dr. Walkup said. “With evidence-based treatments available, there is a need to enhance public awareness and advocacy.”
Dr. Walkup reported no financial relationships.
NEW YORK – Of psychiatric issues affecting child development, generalized anxiety is not getting the attention it deserves and is frequently mistaken for attention-deficit/hyperactivity disorder (ADHD), according to a review of key diagnostic signs and evidence-based therapies presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“Pediatricians have an ASD [autism spectrum disorder] toolkit, they have an ADHD toolkit, and they now have a postpartum depression toolkit for moms, but they do not have an anxiety tool kit,” reported Dr. John T. Walkup, director of the division of child and adolescent psychiatry, Cornell University, New York. “So if a kid is 7 or 8 and is inattentive, they have two choices: Either he has ASD or he has ADHD.”
Confusion with ASD is less likely, because there is less symptom crossover, but the differential diagnosis with ADHD is more challenging. For anxiety, symptoms typically peak between the ages of 6 and 12 years. Although the onset of ADHD symptoms, like symptoms of ASD, generally occurs earlier, children with anxiety and ADHD often are brought to the attention of a physician within the same general window of time.
From the point of view of the complaints that initiated an evaluation, “generalized anxiety disorder and the inattentive subtype of ADHD are almost indistinguishable,” Dr. Walkup asserted. He suggested that children who are anxious have difficulty concentrating in class because their minds are “full of ideas, worries, and concerns.” Children with ADHD have difficulty concentrating in class because their minds are “susceptible to distraction,” but the result is the same.
Some children, even those who are only 7 or 8 years old, “can really describe to you that difference,” Dr. Walkup observed, although he said other features can be useful for distinguishing anxiety from other psychiatric disorders, including depression. In taking the history of a child with potential anxiety, key signs include difficulty coping with novel situations, excessive sensitivity to perceived threats, and shyness. These features are less likely to be in children with ADHD or depression.
Once children reach adolescence, social insecurity is more ubiquitous, making this complaint less useful for identifying a child with pathologic anxiety, but here there is also room for confusion without a careful history.
“We see a lot of kids who have social anxiety who get mislabeled as depressed. Socially anxious kids become demoralized, but they do not become anhedonic,” Dr. Walkup reported. In patients who are inhibited with their peers but who do not otherwise report disturbances in mood, generalized anxiety rather than depression may be driving the psychopathology, according to Dr. Walkup, who said this set of circumstances is common.
Once the diagnosis of anxiety is made, both SSRIs and cognitive-behavioral therapy are effective, with response rates of about 55%-60%, Dr. Walkup said. The response rates can climb as high as 80% when the two are combined, particularly when CBT is performed at experienced centers.
With SSRIs, one of the biggest concerns is activation, an adverse event that occurs in up to 10% of patients, Dr. Walkup said. If activation occurs, he advised switching patients to a nonactivating antidepressant, such as duloxetine, nefazodone, or a tricyclic agent, rather than rechallenging them with another SSRI. In his experience, activation on one agent predicts activation on another, but he cautioned against confusing activation with SSRI-induced mania.
“We do see so many kids who get activated on an SSRI and never see another antidepressant again, simply because the doc is afraid of precipitating mania,” Dr. Walkup said. He said mania is a very uncommon adverse event not typically observed, like activation, relatively quickly after initiating therapy. Because of the efficacy of SSRIs for pediatric anxiety, Dr. Walkup advised being slow in abandoning this drug class.
“Antidepressants work extremely well, and SSRIs are the medications of choice,” emphasized Dr. Walkup, who identified atypical antidepressants as a second-line choice in children and benzodiazepines, for which pediatric data are “limited,” as an option further down the list.
However, therapy first requires a diagnosis.
“Identifying anxiety is key,” Dr. Walkup said. “With evidence-based treatments available, there is a need to enhance public awareness and advocacy.”
Dr. Walkup reported no financial relationships.
NEW YORK – Of psychiatric issues affecting child development, generalized anxiety is not getting the attention it deserves and is frequently mistaken for attention-deficit/hyperactivity disorder (ADHD), according to a review of key diagnostic signs and evidence-based therapies presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“Pediatricians have an ASD [autism spectrum disorder] toolkit, they have an ADHD toolkit, and they now have a postpartum depression toolkit for moms, but they do not have an anxiety tool kit,” reported Dr. John T. Walkup, director of the division of child and adolescent psychiatry, Cornell University, New York. “So if a kid is 7 or 8 and is inattentive, they have two choices: Either he has ASD or he has ADHD.”
Confusion with ASD is less likely, because there is less symptom crossover, but the differential diagnosis with ADHD is more challenging. For anxiety, symptoms typically peak between the ages of 6 and 12 years. Although the onset of ADHD symptoms, like symptoms of ASD, generally occurs earlier, children with anxiety and ADHD often are brought to the attention of a physician within the same general window of time.
From the point of view of the complaints that initiated an evaluation, “generalized anxiety disorder and the inattentive subtype of ADHD are almost indistinguishable,” Dr. Walkup asserted. He suggested that children who are anxious have difficulty concentrating in class because their minds are “full of ideas, worries, and concerns.” Children with ADHD have difficulty concentrating in class because their minds are “susceptible to distraction,” but the result is the same.
Some children, even those who are only 7 or 8 years old, “can really describe to you that difference,” Dr. Walkup observed, although he said other features can be useful for distinguishing anxiety from other psychiatric disorders, including depression. In taking the history of a child with potential anxiety, key signs include difficulty coping with novel situations, excessive sensitivity to perceived threats, and shyness. These features are less likely to be in children with ADHD or depression.
Once children reach adolescence, social insecurity is more ubiquitous, making this complaint less useful for identifying a child with pathologic anxiety, but here there is also room for confusion without a careful history.
“We see a lot of kids who have social anxiety who get mislabeled as depressed. Socially anxious kids become demoralized, but they do not become anhedonic,” Dr. Walkup reported. In patients who are inhibited with their peers but who do not otherwise report disturbances in mood, generalized anxiety rather than depression may be driving the psychopathology, according to Dr. Walkup, who said this set of circumstances is common.
Once the diagnosis of anxiety is made, both SSRIs and cognitive-behavioral therapy are effective, with response rates of about 55%-60%, Dr. Walkup said. The response rates can climb as high as 80% when the two are combined, particularly when CBT is performed at experienced centers.
With SSRIs, one of the biggest concerns is activation, an adverse event that occurs in up to 10% of patients, Dr. Walkup said. If activation occurs, he advised switching patients to a nonactivating antidepressant, such as duloxetine, nefazodone, or a tricyclic agent, rather than rechallenging them with another SSRI. In his experience, activation on one agent predicts activation on another, but he cautioned against confusing activation with SSRI-induced mania.
“We do see so many kids who get activated on an SSRI and never see another antidepressant again, simply because the doc is afraid of precipitating mania,” Dr. Walkup said. He said mania is a very uncommon adverse event not typically observed, like activation, relatively quickly after initiating therapy. Because of the efficacy of SSRIs for pediatric anxiety, Dr. Walkup advised being slow in abandoning this drug class.
“Antidepressants work extremely well, and SSRIs are the medications of choice,” emphasized Dr. Walkup, who identified atypical antidepressants as a second-line choice in children and benzodiazepines, for which pediatric data are “limited,” as an option further down the list.
However, therapy first requires a diagnosis.
“Identifying anxiety is key,” Dr. Walkup said. “With evidence-based treatments available, there is a need to enhance public awareness and advocacy.”
Dr. Walkup reported no financial relationships.
EXPERT ANALYSIS FROM THE PSYCHOPHARMACOLOGY UPDATE INSTITUTE
Growing ADHD drug selection aids individualized therapy
NEW YORK – One way to individualize selection from the growing list of long-acting stimulants for attention-deficit/hyperactivity disorder is to consider when each provides peak activity, according to an update on these medications at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
If the immediate-release component of a given long-acting stimulant formation is relatively high, “that is a particularly good medication for early-morning problems, such as a math class in the first period,” said Dr. Laurence L. Greenhill, professor in the division of child and adolescent psychiatry at Columbia University in New York. “On the other hand, if the math class is in the eighth period and there are a lot of behavioral problems, then those agents with less immediate release may be a better choice.”
The list of long-acting stimulants, each with a unique formulation and pattern of stimulant release, has grown substantially over the last 2 years with two new agents released within the last 4 months, according to Dr. Greenhill. The latest regulatory approval in this class was for Adzenys XR-ODT (amphetamine), which is being marketed as the first extended-release orally disintegrating tablet for ADHD. FDA approval was granted on Jan. 28, which was the day before Dr. Greenhill spoke and just 3 months after approval of Dynavel XR, a long-acting amphetamine oral suspension.
All of the long-acting stimulants employ amphetamine, methylphenidate, or dexmethylphenidate as their active agent, but they employ different strategies to provide active drug over the 8-12 hours most claim as their duration of activity. Oral therapies, which can now be delivered in capsule, chewable, and liquid formulations, employ a large array of technologies to slow release of the active ingredient over each dosing interval. Skin patches provide yet another option for drug delivery.
By themselves, the differences in formulations may have their own relevance to drug selection. For example, liquid drugs can be sprinkled on food, while a patch may be the best option for children with difficulty swallowing pills. But Dr. Greenhill suggested that patterns of drug release could be important for individualizing drug selection according to the time of day that symptoms peak. For some, such as dexmethylphenidate XR (Focalin XR), up to 50% of the active ingredient is available in the immediate-release component with the remaining drug provided in delayed release. For others, such as methylphenidate XR (Concerta), only 20% is immediate release. These have obvious implications if timing of symptom control is important.
Because of the potential complications from stimulant drugs, Dr. Greenhill advocated employing these agents within the framework of published guidelines, including one from the AACAP, specific to the management of ADHD in children. Of specific risks, cardiac events are widely considered the most worrisome. According to Dr. Greenhill, a baseline history should include a focus on any cardiac abnormalities or syncope episodes. Although he said that routine electrocardiograms are not necessary, the patient’s pulse and blood pressure should be rechecked at least every 6 months. Referral to a cardiologist is appropriate for persistent abnormalities in elevated blood pressure or in patients with tachycardia.
New evidence, however, has refuted the previously reported association between long-acting stimulants and tics, Dr. Greenhill said. He cited a recently published meta-analysis of 22 randomized, placebo-controlled trials that found no significant no association between psychostimulant use and either new onset or worsening of tics (J Am Acad Child Adolesc Psychiatry. 2015 Sep;54[9]:728-36).
“The rate of worsening of new-onset tics in the stimulant group was, in fact, less than the rate of tics in the placebo group,” reported Dr. Greenhill, who characterized this as a take-home clinical pearl. “The bottom line is that practitioners can tell parents that there is no evidence that these medications will worsen tics.”
Nevertheless, to avoid the appearance of a temporal association between stimulants and tics, Dr. Greenhill suggested that children who discontinued stimulant therapy because of a tic should be rechallenged at a time of low stress.
Overall, ADHD patients without an adequate response to one stimulant should be tried on another, and these therapies can be combined with adjunctive drugs and behavioral treatments. But Dr. Greenhill suggested matching drug release patterns to the timing of ADHD symptoms is one way to guide the initial choice of long-acting agent.
Dr. Greenhill reported financial relationship with Hoffmann-LaRoche and Shire.
NEW YORK – One way to individualize selection from the growing list of long-acting stimulants for attention-deficit/hyperactivity disorder is to consider when each provides peak activity, according to an update on these medications at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
If the immediate-release component of a given long-acting stimulant formation is relatively high, “that is a particularly good medication for early-morning problems, such as a math class in the first period,” said Dr. Laurence L. Greenhill, professor in the division of child and adolescent psychiatry at Columbia University in New York. “On the other hand, if the math class is in the eighth period and there are a lot of behavioral problems, then those agents with less immediate release may be a better choice.”
The list of long-acting stimulants, each with a unique formulation and pattern of stimulant release, has grown substantially over the last 2 years with two new agents released within the last 4 months, according to Dr. Greenhill. The latest regulatory approval in this class was for Adzenys XR-ODT (amphetamine), which is being marketed as the first extended-release orally disintegrating tablet for ADHD. FDA approval was granted on Jan. 28, which was the day before Dr. Greenhill spoke and just 3 months after approval of Dynavel XR, a long-acting amphetamine oral suspension.
All of the long-acting stimulants employ amphetamine, methylphenidate, or dexmethylphenidate as their active agent, but they employ different strategies to provide active drug over the 8-12 hours most claim as their duration of activity. Oral therapies, which can now be delivered in capsule, chewable, and liquid formulations, employ a large array of technologies to slow release of the active ingredient over each dosing interval. Skin patches provide yet another option for drug delivery.
By themselves, the differences in formulations may have their own relevance to drug selection. For example, liquid drugs can be sprinkled on food, while a patch may be the best option for children with difficulty swallowing pills. But Dr. Greenhill suggested that patterns of drug release could be important for individualizing drug selection according to the time of day that symptoms peak. For some, such as dexmethylphenidate XR (Focalin XR), up to 50% of the active ingredient is available in the immediate-release component with the remaining drug provided in delayed release. For others, such as methylphenidate XR (Concerta), only 20% is immediate release. These have obvious implications if timing of symptom control is important.
Because of the potential complications from stimulant drugs, Dr. Greenhill advocated employing these agents within the framework of published guidelines, including one from the AACAP, specific to the management of ADHD in children. Of specific risks, cardiac events are widely considered the most worrisome. According to Dr. Greenhill, a baseline history should include a focus on any cardiac abnormalities or syncope episodes. Although he said that routine electrocardiograms are not necessary, the patient’s pulse and blood pressure should be rechecked at least every 6 months. Referral to a cardiologist is appropriate for persistent abnormalities in elevated blood pressure or in patients with tachycardia.
New evidence, however, has refuted the previously reported association between long-acting stimulants and tics, Dr. Greenhill said. He cited a recently published meta-analysis of 22 randomized, placebo-controlled trials that found no significant no association between psychostimulant use and either new onset or worsening of tics (J Am Acad Child Adolesc Psychiatry. 2015 Sep;54[9]:728-36).
“The rate of worsening of new-onset tics in the stimulant group was, in fact, less than the rate of tics in the placebo group,” reported Dr. Greenhill, who characterized this as a take-home clinical pearl. “The bottom line is that practitioners can tell parents that there is no evidence that these medications will worsen tics.”
Nevertheless, to avoid the appearance of a temporal association between stimulants and tics, Dr. Greenhill suggested that children who discontinued stimulant therapy because of a tic should be rechallenged at a time of low stress.
Overall, ADHD patients without an adequate response to one stimulant should be tried on another, and these therapies can be combined with adjunctive drugs and behavioral treatments. But Dr. Greenhill suggested matching drug release patterns to the timing of ADHD symptoms is one way to guide the initial choice of long-acting agent.
Dr. Greenhill reported financial relationship with Hoffmann-LaRoche and Shire.
NEW YORK – One way to individualize selection from the growing list of long-acting stimulants for attention-deficit/hyperactivity disorder is to consider when each provides peak activity, according to an update on these medications at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
If the immediate-release component of a given long-acting stimulant formation is relatively high, “that is a particularly good medication for early-morning problems, such as a math class in the first period,” said Dr. Laurence L. Greenhill, professor in the division of child and adolescent psychiatry at Columbia University in New York. “On the other hand, if the math class is in the eighth period and there are a lot of behavioral problems, then those agents with less immediate release may be a better choice.”
The list of long-acting stimulants, each with a unique formulation and pattern of stimulant release, has grown substantially over the last 2 years with two new agents released within the last 4 months, according to Dr. Greenhill. The latest regulatory approval in this class was for Adzenys XR-ODT (amphetamine), which is being marketed as the first extended-release orally disintegrating tablet for ADHD. FDA approval was granted on Jan. 28, which was the day before Dr. Greenhill spoke and just 3 months after approval of Dynavel XR, a long-acting amphetamine oral suspension.
All of the long-acting stimulants employ amphetamine, methylphenidate, or dexmethylphenidate as their active agent, but they employ different strategies to provide active drug over the 8-12 hours most claim as their duration of activity. Oral therapies, which can now be delivered in capsule, chewable, and liquid formulations, employ a large array of technologies to slow release of the active ingredient over each dosing interval. Skin patches provide yet another option for drug delivery.
By themselves, the differences in formulations may have their own relevance to drug selection. For example, liquid drugs can be sprinkled on food, while a patch may be the best option for children with difficulty swallowing pills. But Dr. Greenhill suggested that patterns of drug release could be important for individualizing drug selection according to the time of day that symptoms peak. For some, such as dexmethylphenidate XR (Focalin XR), up to 50% of the active ingredient is available in the immediate-release component with the remaining drug provided in delayed release. For others, such as methylphenidate XR (Concerta), only 20% is immediate release. These have obvious implications if timing of symptom control is important.
Because of the potential complications from stimulant drugs, Dr. Greenhill advocated employing these agents within the framework of published guidelines, including one from the AACAP, specific to the management of ADHD in children. Of specific risks, cardiac events are widely considered the most worrisome. According to Dr. Greenhill, a baseline history should include a focus on any cardiac abnormalities or syncope episodes. Although he said that routine electrocardiograms are not necessary, the patient’s pulse and blood pressure should be rechecked at least every 6 months. Referral to a cardiologist is appropriate for persistent abnormalities in elevated blood pressure or in patients with tachycardia.
New evidence, however, has refuted the previously reported association between long-acting stimulants and tics, Dr. Greenhill said. He cited a recently published meta-analysis of 22 randomized, placebo-controlled trials that found no significant no association between psychostimulant use and either new onset or worsening of tics (J Am Acad Child Adolesc Psychiatry. 2015 Sep;54[9]:728-36).
“The rate of worsening of new-onset tics in the stimulant group was, in fact, less than the rate of tics in the placebo group,” reported Dr. Greenhill, who characterized this as a take-home clinical pearl. “The bottom line is that practitioners can tell parents that there is no evidence that these medications will worsen tics.”
Nevertheless, to avoid the appearance of a temporal association between stimulants and tics, Dr. Greenhill suggested that children who discontinued stimulant therapy because of a tic should be rechallenged at a time of low stress.
Overall, ADHD patients without an adequate response to one stimulant should be tried on another, and these therapies can be combined with adjunctive drugs and behavioral treatments. But Dr. Greenhill suggested matching drug release patterns to the timing of ADHD symptoms is one way to guide the initial choice of long-acting agent.
Dr. Greenhill reported financial relationship with Hoffmann-LaRoche and Shire.
EXPERT ANALYSIS FROM THE PSYCHOPHARMACOLOGY UPDATE INSTITUTE
In adolescents, treat substance use disorder before ADHD
NEW YORK – When evaluating adolescents with substance use disorder (SUD), paying attention to frequently occurring comorbid conditions, such as attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder, is essential for developing a successful treatment plan, according to an expert summary of current strategies that was presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“If you see SUD in a juvenile, think psychopathogy,” reported Dr. Timothy Wilens, chief of the division of child and adolescent psychiatry, Massachusetts General Hospital, Boston. Citing a series of studies published over the past 20 years, he said that the proportion of patients with SUD and overlapping psychopathology “is approaching 90%.”
The most significant predictor of SUD is conduct disorder whether or not it is linked to ADHD, according to Dr. Wilens. He emphasized the risk of SUD, which can range from a mild form consisting of intermittent use of alcohol or drugs to a severe form consisting of functional impairment and substance dependence, exceeds 80% in children and adolescents with a history of conduct disorder. ADHD specifically can be diagnosed in about 50% of children with SUD.
Overall, the presence of ADHD, mood disorders such as depression or anxiety, posttraumatic stress disorder (PTSD), and bipolar disorder all double the risk of SUD in children and adolescents. In most but not all cases, SUD should be treated first. According to Dr. Wilens, SUD can complicate efforts to treat comorbid psychopathology, particularly if pharmacologic agents such as stimulants are part of the therapy. One exception is bipolar disorder.
Bipolar disorder “is a different story. When I have bipolar kids who are using, I blast through the substance use,” said Dr. Wilens, referring to his strategy of treating this condition either first or in conjunction with treatment of SUD. While he indicated that control of bipolar disorder might be more important for achieving control of SUD than the other way around, he also cited data demonstrating a favorable influence of lithium relative to placebo on alcohol- or marijuana-associated SUD in adolescents. In another study of adolescents with SUD, quetiapine plus topiramate was associated with a significant reduction in marijuana use when compared with quetiapine and placebo.
In adolescents, marijuana is the most common form of SUD. Although alcohol is involved in about 70% of cases of SUD in adults, marijuana is also the most common type of SUD in the pediatric population, according to Dr. Wilens. Although the use of opioids has been trending upwards over the last 10 years in all age groups, use remains relatively low in children and adolescents. Still, 40% of adolescents reported narcotics to be fairly easy or very easy to obtain in a recent survey cited by Dr. Wilens.
“Most are getting the narcotics from family or friends,” reported Dr. Wilens, noting that these are too often found in the bathroom medicine cabinet. He suggested that parents could reduce risk of adolescent use of narcotics by either throwing away spare pills or putting them in a place where they are less likely to be found.
In a treatment plan for adolescents, harm reduction is the first concern, but Dr. Wilens also counseled that reasonable goals and a collaborative approach to treatment should be introduced long before a “tough love” strategy that includes total abstinence. In children with moderate to severe SUD, Dr. Wilens suggested that clinicians should work to define triggers and then negotiate reasonable strategies to change behavior.
In motivated children, one strategy is “sobriety sampling.” In this approach, the patient is challenged to abstain from substance use for a finite period, such as a month. According to Dr. Wilens, “kids often realize that they feel better,” which is a critical step toward success in avoiding triggers.
There are a number of psychotherapies, such as cognitive behavioral modification, and psychopharmacologic strategies, such as N-acetyl cysteine (NAC) and buspirone, associated with success in treating SUD, but dedicated treatment facilities may be the right answer when clinicians do not have the time or experience to provide care. Dr. Wilens suggested that a national treatment facility locator developed by the Substance Abuse and Mental Health Services Administration may be helpful. The locator tool can be found online (www.findtreatment.samhsa.gov).
One reason to treat SUD in adolescents is that the problem, if untreated, is likely to persist. Data suggest that 50% of adults with SUD developed this condition before the age of 18. For many patients, success in treatment will depend on strategies that ultimately addresses both SUD and the frequently occurring comorbid conditions. Overall, Dr. Wilens recommended a systematic but not a rigid approach.
“The ultimate goal of harm reduction is abstinence, but we are not saying you are a failure if you did not just stop,” Dr. Wilens said. Although a “tough love” approach may have value in some patients “it is not an first, second, third, fourth, or fifth intervention. It may be one, but it’s down the line.”
NEW YORK – When evaluating adolescents with substance use disorder (SUD), paying attention to frequently occurring comorbid conditions, such as attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder, is essential for developing a successful treatment plan, according to an expert summary of current strategies that was presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“If you see SUD in a juvenile, think psychopathogy,” reported Dr. Timothy Wilens, chief of the division of child and adolescent psychiatry, Massachusetts General Hospital, Boston. Citing a series of studies published over the past 20 years, he said that the proportion of patients with SUD and overlapping psychopathology “is approaching 90%.”
The most significant predictor of SUD is conduct disorder whether or not it is linked to ADHD, according to Dr. Wilens. He emphasized the risk of SUD, which can range from a mild form consisting of intermittent use of alcohol or drugs to a severe form consisting of functional impairment and substance dependence, exceeds 80% in children and adolescents with a history of conduct disorder. ADHD specifically can be diagnosed in about 50% of children with SUD.
Overall, the presence of ADHD, mood disorders such as depression or anxiety, posttraumatic stress disorder (PTSD), and bipolar disorder all double the risk of SUD in children and adolescents. In most but not all cases, SUD should be treated first. According to Dr. Wilens, SUD can complicate efforts to treat comorbid psychopathology, particularly if pharmacologic agents such as stimulants are part of the therapy. One exception is bipolar disorder.
Bipolar disorder “is a different story. When I have bipolar kids who are using, I blast through the substance use,” said Dr. Wilens, referring to his strategy of treating this condition either first or in conjunction with treatment of SUD. While he indicated that control of bipolar disorder might be more important for achieving control of SUD than the other way around, he also cited data demonstrating a favorable influence of lithium relative to placebo on alcohol- or marijuana-associated SUD in adolescents. In another study of adolescents with SUD, quetiapine plus topiramate was associated with a significant reduction in marijuana use when compared with quetiapine and placebo.
In adolescents, marijuana is the most common form of SUD. Although alcohol is involved in about 70% of cases of SUD in adults, marijuana is also the most common type of SUD in the pediatric population, according to Dr. Wilens. Although the use of opioids has been trending upwards over the last 10 years in all age groups, use remains relatively low in children and adolescents. Still, 40% of adolescents reported narcotics to be fairly easy or very easy to obtain in a recent survey cited by Dr. Wilens.
“Most are getting the narcotics from family or friends,” reported Dr. Wilens, noting that these are too often found in the bathroom medicine cabinet. He suggested that parents could reduce risk of adolescent use of narcotics by either throwing away spare pills or putting them in a place where they are less likely to be found.
In a treatment plan for adolescents, harm reduction is the first concern, but Dr. Wilens also counseled that reasonable goals and a collaborative approach to treatment should be introduced long before a “tough love” strategy that includes total abstinence. In children with moderate to severe SUD, Dr. Wilens suggested that clinicians should work to define triggers and then negotiate reasonable strategies to change behavior.
In motivated children, one strategy is “sobriety sampling.” In this approach, the patient is challenged to abstain from substance use for a finite period, such as a month. According to Dr. Wilens, “kids often realize that they feel better,” which is a critical step toward success in avoiding triggers.
There are a number of psychotherapies, such as cognitive behavioral modification, and psychopharmacologic strategies, such as N-acetyl cysteine (NAC) and buspirone, associated with success in treating SUD, but dedicated treatment facilities may be the right answer when clinicians do not have the time or experience to provide care. Dr. Wilens suggested that a national treatment facility locator developed by the Substance Abuse and Mental Health Services Administration may be helpful. The locator tool can be found online (www.findtreatment.samhsa.gov).
One reason to treat SUD in adolescents is that the problem, if untreated, is likely to persist. Data suggest that 50% of adults with SUD developed this condition before the age of 18. For many patients, success in treatment will depend on strategies that ultimately addresses both SUD and the frequently occurring comorbid conditions. Overall, Dr. Wilens recommended a systematic but not a rigid approach.
“The ultimate goal of harm reduction is abstinence, but we are not saying you are a failure if you did not just stop,” Dr. Wilens said. Although a “tough love” approach may have value in some patients “it is not an first, second, third, fourth, or fifth intervention. It may be one, but it’s down the line.”
NEW YORK – When evaluating adolescents with substance use disorder (SUD), paying attention to frequently occurring comorbid conditions, such as attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder, is essential for developing a successful treatment plan, according to an expert summary of current strategies that was presented at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
“If you see SUD in a juvenile, think psychopathogy,” reported Dr. Timothy Wilens, chief of the division of child and adolescent psychiatry, Massachusetts General Hospital, Boston. Citing a series of studies published over the past 20 years, he said that the proportion of patients with SUD and overlapping psychopathology “is approaching 90%.”
The most significant predictor of SUD is conduct disorder whether or not it is linked to ADHD, according to Dr. Wilens. He emphasized the risk of SUD, which can range from a mild form consisting of intermittent use of alcohol or drugs to a severe form consisting of functional impairment and substance dependence, exceeds 80% in children and adolescents with a history of conduct disorder. ADHD specifically can be diagnosed in about 50% of children with SUD.
Overall, the presence of ADHD, mood disorders such as depression or anxiety, posttraumatic stress disorder (PTSD), and bipolar disorder all double the risk of SUD in children and adolescents. In most but not all cases, SUD should be treated first. According to Dr. Wilens, SUD can complicate efforts to treat comorbid psychopathology, particularly if pharmacologic agents such as stimulants are part of the therapy. One exception is bipolar disorder.
Bipolar disorder “is a different story. When I have bipolar kids who are using, I blast through the substance use,” said Dr. Wilens, referring to his strategy of treating this condition either first or in conjunction with treatment of SUD. While he indicated that control of bipolar disorder might be more important for achieving control of SUD than the other way around, he also cited data demonstrating a favorable influence of lithium relative to placebo on alcohol- or marijuana-associated SUD in adolescents. In another study of adolescents with SUD, quetiapine plus topiramate was associated with a significant reduction in marijuana use when compared with quetiapine and placebo.
In adolescents, marijuana is the most common form of SUD. Although alcohol is involved in about 70% of cases of SUD in adults, marijuana is also the most common type of SUD in the pediatric population, according to Dr. Wilens. Although the use of opioids has been trending upwards over the last 10 years in all age groups, use remains relatively low in children and adolescents. Still, 40% of adolescents reported narcotics to be fairly easy or very easy to obtain in a recent survey cited by Dr. Wilens.
“Most are getting the narcotics from family or friends,” reported Dr. Wilens, noting that these are too often found in the bathroom medicine cabinet. He suggested that parents could reduce risk of adolescent use of narcotics by either throwing away spare pills or putting them in a place where they are less likely to be found.
In a treatment plan for adolescents, harm reduction is the first concern, but Dr. Wilens also counseled that reasonable goals and a collaborative approach to treatment should be introduced long before a “tough love” strategy that includes total abstinence. In children with moderate to severe SUD, Dr. Wilens suggested that clinicians should work to define triggers and then negotiate reasonable strategies to change behavior.
In motivated children, one strategy is “sobriety sampling.” In this approach, the patient is challenged to abstain from substance use for a finite period, such as a month. According to Dr. Wilens, “kids often realize that they feel better,” which is a critical step toward success in avoiding triggers.
There are a number of psychotherapies, such as cognitive behavioral modification, and psychopharmacologic strategies, such as N-acetyl cysteine (NAC) and buspirone, associated with success in treating SUD, but dedicated treatment facilities may be the right answer when clinicians do not have the time or experience to provide care. Dr. Wilens suggested that a national treatment facility locator developed by the Substance Abuse and Mental Health Services Administration may be helpful. The locator tool can be found online (www.findtreatment.samhsa.gov).
One reason to treat SUD in adolescents is that the problem, if untreated, is likely to persist. Data suggest that 50% of adults with SUD developed this condition before the age of 18. For many patients, success in treatment will depend on strategies that ultimately addresses both SUD and the frequently occurring comorbid conditions. Overall, Dr. Wilens recommended a systematic but not a rigid approach.
“The ultimate goal of harm reduction is abstinence, but we are not saying you are a failure if you did not just stop,” Dr. Wilens said. Although a “tough love” approach may have value in some patients “it is not an first, second, third, fourth, or fifth intervention. It may be one, but it’s down the line.”
AT THE PSYCHOPHARMACOLOGY UPDATE INSTITUTE
Key clinical point: In adolescents with both attention-deficit/hyperactivity disorder and substance use disorder, control of substance use comes first.
Major finding: Nearly 90% of adolescents with substance use disorder have a comorbid psychopathology for which the order of treatment may affect likelihood of treatment success.
Data source: Clinical expert opinion.
Disclosures: Dr. Wilens reports financial relationship with Euthymics Bioscience, Ironshore Inc., Sunovion Pharmaceuticals, Theravance Biopharma, and Tris Pharma.
