This month’s column comes directly by request from a pediatric colleague. She asked about a common diagnostic dilemma for pediatricians that involves what at least on the surface appears like disruptive or oppositional behavior at the home, school, or both, but is complicated by the possibility that the primary engine of this behavior is anxiety. This is an important challenge to try and get right because the treatment plan will take different paths, depending on the final call that is made.

Case summary

Devin is a 6-year-old boy who comes in with his parents for concerns about his behavior. His parents note that he has always been “high strung” but not disruptive or aggressive. When he was younger, Devin was quite sensitive to sounds, textures, and tactile sensations, but this has improved on its own. Thunderstorms continue to bother him quite a bit, though, and he often will ask his parents repeated questions when it is cloudy about the possibility of a thunderstorm. With some extra teacher and parent support, Devin made the transition to kindergarten fairly well. Now, however, he is struggling in a larger 1st grade class. His teacher states that he often seems distracted, fidgety, and easily frustrated, causing him to “shut down” and refuse to do his work. This past week, during a more challenging assignment, he crawled under his desk and would not come out. The teacher is now recommending an evaluation for attention-deficit/hyperactivity disorder (ADHD).

Discussion

1. Are there other times in the child’s life when clearly he is very anxious? The presence of developmentally elevated levels of anxiety in areas outside the particular situations in question can provide a clue that anxiety is contributing to what otherwise might be seen as more oppositional behavior. In this case, the high levels of anxiety about thunderstorms show that anxiety is present in the child and could be playing a role in his disruptive behavior at school.

2. When he’s not focusing on the task at hand, what is he thinking about? Nonanxious children with or without ADHD can frequently daydream and go “off task,” but the content of those thoughts frequently involves anticipation for more preferred activities, reminisces of positive events from the past, or attention to other stimuli in the environment (for example, the bird in a tree outside). More anxious children, by contrast, may have more worried and ruminating thoughts about poor performance, possible bad events that might happen in the future, or “what if?” kinds of concerns.

3. Is there a family history of anxiety? While one should not over-rely on family history, the presence of one or more family members with clinically significant anxiety does raise the possibility of anxiety in the identified patient. Research indicates that the heritability of anxiety is about 50%,^1,2 but that a significant amount of the transmission of anxiety from parent to child comes from environmental mechanisms.³

4. Is there a consistent trigger to his outbursts? For anxious children, meltdowns are frequently provoked by situations in which a child feels uncomfortable, overstimulated, or overwhelmed, and the outburst is a reflection of those intense feelings that are difficult to manage. An outburst like that above, which occurs when a child is pushed to finish difficult work, might be a good example of one that is triggered by anxiety.

5. What does the rating scale show? A broad-based rating scale that assesses multiple domains of symptoms can be a big help for diagnostic dilemmas such as this one. Our clinic uses the Child Behavior Checklist⁴ which has subscales for both anxiety and attention problems. Evidence of a spike in either of those domains, or both, really can help guide our thinking.

Of course, it is very possible that the answer to the ADHD versus anxiety question is that both are present. This is a common conclusion when it comes to mental health assessment, and it is different from the traditional “this or that” thinking present in more classic differential diagnosis decision making. Research indicates that the ADHD and anxiety disorders frequently co-occur.⁵ When that happens, concurrent evidence-based psychotherapy for anxiety in conjunction with multimodal treatment for ADHD has been recommended as a first step.⁶

Case follow-up

Based on all the information, the pediatrician judges that Devin’s disruptive behavior is in large part being driven by his level of anxiety. She makes a referral to a child psychologist to begin evidence-based psychotherapy and recommends that the school consider some modifications and accommodations that may help his behavior at school. At a follow-up appointment, Devin’s difficulties have improved, and there is little evidence of ADHD now that the anxiety has been fully addressed.

References

1. Genes Brain Behav. 2005;4(8):466-81.

2. J Am Acad Child Adolesc Psychiatry. 2010;49(3):248-55.

3. Am J Psychiatry. 2015;172(7):630-7.

4. Manual for the ASEBA School-Age Forms & Profiles (Burlington, Vt.: University of Vermont, Research Center for Children, Youth, and Families, 2001).

5. J Anxiety Disord. 1997;11(4):377-94.

6. J Abnorm Child Psychol. 2000;28(6):527-41.
 

Dr. Rettew is a child and adolescent psychiatrist and assistant professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine, Burlington. Follow him on Twitter @PediPsych. Email him at [email protected].

This month’s column comes directly by request from a pediatric colleague. She asked about a common diagnostic dilemma for pediatricians that involves what at least on the surface appears like disruptive or oppositional behavior at the home, school, or both, but is complicated by the possibility that the primary engine of this behavior is anxiety. This is an important challenge to try and get right because the treatment plan will take different paths, depending on the final call that is made.

Case summary

Devin is a 6-year-old boy who comes in with his parents for concerns about his behavior. His parents note that he has always been “high strung” but not disruptive or aggressive. When he was younger, Devin was quite sensitive to sounds, textures, and tactile sensations, but this has improved on its own. Thunderstorms continue to bother him quite a bit, though, and he often will ask his parents repeated questions when it is cloudy about the possibility of a thunderstorm. With some extra teacher and parent support, Devin made the transition to kindergarten fairly well. Now, however, he is struggling in a larger 1st grade class. His teacher states that he often seems distracted, fidgety, and easily frustrated, causing him to “shut down” and refuse to do his work. This past week, during a more challenging assignment, he crawled under his desk and would not come out. The teacher is now recommending an evaluation for attention-deficit/hyperactivity disorder (ADHD).

Discussion

1. Are there other times in the child’s life when clearly he is very anxious? The presence of developmentally elevated levels of anxiety in areas outside the particular situations in question can provide a clue that anxiety is contributing to what otherwise might be seen as more oppositional behavior. In this case, the high levels of anxiety about thunderstorms show that anxiety is present in the child and could be playing a role in his disruptive behavior at school.

2. When he’s not focusing on the task at hand, what is he thinking about? Nonanxious children with or without ADHD can frequently daydream and go “off task,” but the content of those thoughts frequently involves anticipation for more preferred activities, reminisces of positive events from the past, or attention to other stimuli in the environment (for example, the bird in a tree outside). More anxious children, by contrast, may have more worried and ruminating thoughts about poor performance, possible bad events that might happen in the future, or “what if?” kinds of concerns.

3. Is there a family history of anxiety? While one should not over-rely on family history, the presence of one or more family members with clinically significant anxiety does raise the possibility of anxiety in the identified patient. Research indicates that the heritability of anxiety is about 50%,^1,2 but that a significant amount of the transmission of anxiety from parent to child comes from environmental mechanisms.³

4. Is there a consistent trigger to his outbursts? For anxious children, meltdowns are frequently provoked by situations in which a child feels uncomfortable, overstimulated, or overwhelmed, and the outburst is a reflection of those intense feelings that are difficult to manage. An outburst like that above, which occurs when a child is pushed to finish difficult work, might be a good example of one that is triggered by anxiety.

5. What does the rating scale show? A broad-based rating scale that assesses multiple domains of symptoms can be a big help for diagnostic dilemmas such as this one. Our clinic uses the Child Behavior Checklist⁴ which has subscales for both anxiety and attention problems. Evidence of a spike in either of those domains, or both, really can help guide our thinking.

Of course, it is very possible that the answer to the ADHD versus anxiety question is that both are present. This is a common conclusion when it comes to mental health assessment, and it is different from the traditional “this or that” thinking present in more classic differential diagnosis decision making. Research indicates that the ADHD and anxiety disorders frequently co-occur.⁵ When that happens, concurrent evidence-based psychotherapy for anxiety in conjunction with multimodal treatment for ADHD has been recommended as a first step.⁶

Case follow-up

Based on all the information, the pediatrician judges that Devin’s disruptive behavior is in large part being driven by his level of anxiety. She makes a referral to a child psychologist to begin evidence-based psychotherapy and recommends that the school consider some modifications and accommodations that may help his behavior at school. At a follow-up appointment, Devin’s difficulties have improved, and there is little evidence of ADHD now that the anxiety has been fully addressed.

References

1. Genes Brain Behav. 2005;4(8):466-81.

2. J Am Acad Child Adolesc Psychiatry. 2010;49(3):248-55.

3. Am J Psychiatry. 2015;172(7):630-7.

4. Manual for the ASEBA School-Age Forms & Profiles (Burlington, Vt.: University of Vermont, Research Center for Children, Youth, and Families, 2001).

5. J Anxiety Disord. 1997;11(4):377-94.

6. J Abnorm Child Psychol. 2000;28(6):527-41.
 

Dr. Rettew is a child and adolescent psychiatrist and assistant professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine, Burlington. Follow him on Twitter @PediPsych. Email him at [email protected].

This month’s column comes directly by request from a pediatric colleague. She asked about a common diagnostic dilemma for pediatricians that involves what at least on the surface appears like disruptive or oppositional behavior at the home, school, or both, but is complicated by the possibility that the primary engine of this behavior is anxiety. This is an important challenge to try and get right because the treatment plan will take different paths, depending on the final call that is made.

Case summary

Devin is a 6-year-old boy who comes in with his parents for concerns about his behavior. His parents note that he has always been “high strung” but not disruptive or aggressive. When he was younger, Devin was quite sensitive to sounds, textures, and tactile sensations, but this has improved on its own. Thunderstorms continue to bother him quite a bit, though, and he often will ask his parents repeated questions when it is cloudy about the possibility of a thunderstorm. With some extra teacher and parent support, Devin made the transition to kindergarten fairly well. Now, however, he is struggling in a larger 1st grade class. His teacher states that he often seems distracted, fidgety, and easily frustrated, causing him to “shut down” and refuse to do his work. This past week, during a more challenging assignment, he crawled under his desk and would not come out. The teacher is now recommending an evaluation for attention-deficit/hyperactivity disorder (ADHD).

Discussion

1. Are there other times in the child’s life when clearly he is very anxious? The presence of developmentally elevated levels of anxiety in areas outside the particular situations in question can provide a clue that anxiety is contributing to what otherwise might be seen as more oppositional behavior. In this case, the high levels of anxiety about thunderstorms show that anxiety is present in the child and could be playing a role in his disruptive behavior at school.

2. When he’s not focusing on the task at hand, what is he thinking about? Nonanxious children with or without ADHD can frequently daydream and go “off task,” but the content of those thoughts frequently involves anticipation for more preferred activities, reminisces of positive events from the past, or attention to other stimuli in the environment (for example, the bird in a tree outside). More anxious children, by contrast, may have more worried and ruminating thoughts about poor performance, possible bad events that might happen in the future, or “what if?” kinds of concerns.

3. Is there a family history of anxiety? While one should not over-rely on family history, the presence of one or more family members with clinically significant anxiety does raise the possibility of anxiety in the identified patient. Research indicates that the heritability of anxiety is about 50%,^1,2 but that a significant amount of the transmission of anxiety from parent to child comes from environmental mechanisms.³

4. Is there a consistent trigger to his outbursts? For anxious children, meltdowns are frequently provoked by situations in which a child feels uncomfortable, overstimulated, or overwhelmed, and the outburst is a reflection of those intense feelings that are difficult to manage. An outburst like that above, which occurs when a child is pushed to finish difficult work, might be a good example of one that is triggered by anxiety.

5. What does the rating scale show? A broad-based rating scale that assesses multiple domains of symptoms can be a big help for diagnostic dilemmas such as this one. Our clinic uses the Child Behavior Checklist⁴ which has subscales for both anxiety and attention problems. Evidence of a spike in either of those domains, or both, really can help guide our thinking.

Of course, it is very possible that the answer to the ADHD versus anxiety question is that both are present. This is a common conclusion when it comes to mental health assessment, and it is different from the traditional “this or that” thinking present in more classic differential diagnosis decision making. Research indicates that the ADHD and anxiety disorders frequently co-occur.⁵ When that happens, concurrent evidence-based psychotherapy for anxiety in conjunction with multimodal treatment for ADHD has been recommended as a first step.⁶

Case follow-up

Based on all the information, the pediatrician judges that Devin’s disruptive behavior is in large part being driven by his level of anxiety. She makes a referral to a child psychologist to begin evidence-based psychotherapy and recommends that the school consider some modifications and accommodations that may help his behavior at school. At a follow-up appointment, Devin’s difficulties have improved, and there is little evidence of ADHD now that the anxiety has been fully addressed.

References

1. Genes Brain Behav. 2005;4(8):466-81.

2. J Am Acad Child Adolesc Psychiatry. 2010;49(3):248-55.

3. Am J Psychiatry. 2015;172(7):630-7.

4. Manual for the ASEBA School-Age Forms & Profiles (Burlington, Vt.: University of Vermont, Research Center for Children, Youth, and Families, 2001).

5. J Anxiety Disord. 1997;11(4):377-94.

6. J Abnorm Child Psychol. 2000;28(6):527-41.
 

Dr. Rettew is a child and adolescent psychiatrist and assistant professor of psychiatry and pediatrics at the University of Vermont Larner College of Medicine, Burlington. Follow him on Twitter @PediPsych. Email him at [email protected].

SAN DIEGO – Ladostigil, a drug that combines molecular characteristics of rivastigmine and rasagiline, was associated with some modest memory improvement and – perhaps more interestingly – a signal of brain volume preservation in a phase IIb study of patients with mild cognitive impairment.

Both whole brain and hippocampal volume after 3 years were about 1% higher in the trial’s active group than in the placebo group.

The volumetric data are potentially of more interest than the cognitive results, which didn’t meet the study’s primary endpoint of delaying or preventing conversion from mild cognitive impairment (MCI) to Alzheimer’s disease, Lon Schneider, MD, said at the Clinical Trials on Alzheimer’s Disease conference.

“The whole brain and hippocampal volume started to separate after 1 year and maximized at 2 years,” said Dr. Schneider of the University of Southern California, Los Angeles. “With hippocampal volume, we lose the significance of the effect by year 3, but when we continue on to the end there is a nominal significance in whole brain volume favoring the drug.”

He said the trial was plagued by a 35% dropout rate, probably because of perceived ineffectiveness of the drug. “Those numbers got in the way of looking at this outcome, particularly with 12 drops between years 2 and 3.”

Nevertheless, the drug will continue along its developmental pathway. The Israeli company developing it, Avraham Pharma, is seeking a larger pharmaceutical company with which to partner, according to its website.

Ladostigil pieces together molecular structures from both the monoamine oxidase-B inhibitor rasagiline and the anticholinesterase inhibitor rivastigmine (Exelon).

Avraham suggests that ladostigil could modify Alzheimer’s by neuroprotection, immune modulation, and reducing oxidative stress that leads the release of proinflammatory cytokines and microglial activation.

In 2012, the drug failed a phase II trial focusing on cognition in patients with Alzheimer’s. Afterward, Avraham lowered the dose from 80 mg to 20 mg and launched the current trial, with a refocus on MCI conversion.

It comprised 210 patients with MCI. The mean age was 71 years; mean Mini-Mental State Examination score was 28. About one-third were carriers of the high-risk apolipoprotein E4 allele. Patients were randomized to placebo or 20 mg ladostigil daily for 36 months. Brain MRI was performed at baseline and every 6 months throughout the trial.

The study failed to meet its primary endpoint of MCI conversion to Alzheimer’s. Fourteen patients in the active group and 20 in the placebo group progressed to Alzheimer’s. In year 3, there was a separation of curves with 4 vs. 10 patients progressing to Alzheimer’s, but overall the endpoint was not statistically significant (P = .16).

The two groups began to separate in the decline of brain volume around 1 year into the trial. For hippocampal volume, the difference was statistically significant only at 24 months. By 36 months, volume in the active and placebo groups overlapped slightly with a P value of .31.

The changes in whole-brain volume were somewhat more pronounced. The declining slopes in whole-brain volume began to separate at 12 months. At both 24 and 36 months, the differences were statistically significant (P = .033 and .036, respectively), with curves continuing to diverge at the study’s end.

Adverse events occurred in about 80% of patients (82% with active treatment vs. 79% with placebo); about 25% of both arms experienced serious adverse events.

Common adverse events were atrial fibrillation (8% vs. 3%), chest pain (5% vs. 3%), and benign prostatic hyperplasia (6% vs. 3%). Other events included dizziness, arthralgia, depression, and confusion.

None of the 35% who dropped out of the trial did so for an adverse event, Dr. Schneider noted.

The Neuropsychological Test Battery (NTB) and the Rey Auditory Verbal Learning Test (RAVLT) were secondary measures of behavior and cognition. Both showed positive trends for ladostigil, but neither was statistically significant.

Dr. Schneider has disclosed financial relationships with numerous pharmaceutical companies, but has no financial ties with Avraham.

[email protected]

On Twitter @alz_gal

SAN DIEGO – Ladostigil, a drug that combines molecular characteristics of rivastigmine and rasagiline, was associated with some modest memory improvement and – perhaps more interestingly – a signal of brain volume preservation in a phase IIb study of patients with mild cognitive impairment.

Both whole brain and hippocampal volume after 3 years were about 1% higher in the trial’s active group than in the placebo group.

The volumetric data are potentially of more interest than the cognitive results, which didn’t meet the study’s primary endpoint of delaying or preventing conversion from mild cognitive impairment (MCI) to Alzheimer’s disease, Lon Schneider, MD, said at the Clinical Trials on Alzheimer’s Disease conference.

“The whole brain and hippocampal volume started to separate after 1 year and maximized at 2 years,” said Dr. Schneider of the University of Southern California, Los Angeles. “With hippocampal volume, we lose the significance of the effect by year 3, but when we continue on to the end there is a nominal significance in whole brain volume favoring the drug.”

He said the trial was plagued by a 35% dropout rate, probably because of perceived ineffectiveness of the drug. “Those numbers got in the way of looking at this outcome, particularly with 12 drops between years 2 and 3.”

Nevertheless, the drug will continue along its developmental pathway. The Israeli company developing it, Avraham Pharma, is seeking a larger pharmaceutical company with which to partner, according to its website.

Ladostigil pieces together molecular structures from both the monoamine oxidase-B inhibitor rasagiline and the anticholinesterase inhibitor rivastigmine (Exelon).

Avraham suggests that ladostigil could modify Alzheimer’s by neuroprotection, immune modulation, and reducing oxidative stress that leads the release of proinflammatory cytokines and microglial activation.

In 2012, the drug failed a phase II trial focusing on cognition in patients with Alzheimer’s. Afterward, Avraham lowered the dose from 80 mg to 20 mg and launched the current trial, with a refocus on MCI conversion.

It comprised 210 patients with MCI. The mean age was 71 years; mean Mini-Mental State Examination score was 28. About one-third were carriers of the high-risk apolipoprotein E4 allele. Patients were randomized to placebo or 20 mg ladostigil daily for 36 months. Brain MRI was performed at baseline and every 6 months throughout the trial.

The study failed to meet its primary endpoint of MCI conversion to Alzheimer’s. Fourteen patients in the active group and 20 in the placebo group progressed to Alzheimer’s. In year 3, there was a separation of curves with 4 vs. 10 patients progressing to Alzheimer’s, but overall the endpoint was not statistically significant (P = .16).

The two groups began to separate in the decline of brain volume around 1 year into the trial. For hippocampal volume, the difference was statistically significant only at 24 months. By 36 months, volume in the active and placebo groups overlapped slightly with a P value of .31.

The changes in whole-brain volume were somewhat more pronounced. The declining slopes in whole-brain volume began to separate at 12 months. At both 24 and 36 months, the differences were statistically significant (P = .033 and .036, respectively), with curves continuing to diverge at the study’s end.

Adverse events occurred in about 80% of patients (82% with active treatment vs. 79% with placebo); about 25% of both arms experienced serious adverse events.

Common adverse events were atrial fibrillation (8% vs. 3%), chest pain (5% vs. 3%), and benign prostatic hyperplasia (6% vs. 3%). Other events included dizziness, arthralgia, depression, and confusion.

None of the 35% who dropped out of the trial did so for an adverse event, Dr. Schneider noted.

The Neuropsychological Test Battery (NTB) and the Rey Auditory Verbal Learning Test (RAVLT) were secondary measures of behavior and cognition. Both showed positive trends for ladostigil, but neither was statistically significant.

Dr. Schneider has disclosed financial relationships with numerous pharmaceutical companies, but has no financial ties with Avraham.

[email protected]

On Twitter @alz_gal

SAN DIEGO – Ladostigil, a drug that combines molecular characteristics of rivastigmine and rasagiline, was associated with some modest memory improvement and – perhaps more interestingly – a signal of brain volume preservation in a phase IIb study of patients with mild cognitive impairment.

Both whole brain and hippocampal volume after 3 years were about 1% higher in the trial’s active group than in the placebo group.

The volumetric data are potentially of more interest than the cognitive results, which didn’t meet the study’s primary endpoint of delaying or preventing conversion from mild cognitive impairment (MCI) to Alzheimer’s disease, Lon Schneider, MD, said at the Clinical Trials on Alzheimer’s Disease conference.

“The whole brain and hippocampal volume started to separate after 1 year and maximized at 2 years,” said Dr. Schneider of the University of Southern California, Los Angeles. “With hippocampal volume, we lose the significance of the effect by year 3, but when we continue on to the end there is a nominal significance in whole brain volume favoring the drug.”

He said the trial was plagued by a 35% dropout rate, probably because of perceived ineffectiveness of the drug. “Those numbers got in the way of looking at this outcome, particularly with 12 drops between years 2 and 3.”

Nevertheless, the drug will continue along its developmental pathway. The Israeli company developing it, Avraham Pharma, is seeking a larger pharmaceutical company with which to partner, according to its website.

Ladostigil pieces together molecular structures from both the monoamine oxidase-B inhibitor rasagiline and the anticholinesterase inhibitor rivastigmine (Exelon).

Avraham suggests that ladostigil could modify Alzheimer’s by neuroprotection, immune modulation, and reducing oxidative stress that leads the release of proinflammatory cytokines and microglial activation.

In 2012, the drug failed a phase II trial focusing on cognition in patients with Alzheimer’s. Afterward, Avraham lowered the dose from 80 mg to 20 mg and launched the current trial, with a refocus on MCI conversion.

It comprised 210 patients with MCI. The mean age was 71 years; mean Mini-Mental State Examination score was 28. About one-third were carriers of the high-risk apolipoprotein E4 allele. Patients were randomized to placebo or 20 mg ladostigil daily for 36 months. Brain MRI was performed at baseline and every 6 months throughout the trial.

The study failed to meet its primary endpoint of MCI conversion to Alzheimer’s. Fourteen patients in the active group and 20 in the placebo group progressed to Alzheimer’s. In year 3, there was a separation of curves with 4 vs. 10 patients progressing to Alzheimer’s, but overall the endpoint was not statistically significant (P = .16).

The two groups began to separate in the decline of brain volume around 1 year into the trial. For hippocampal volume, the difference was statistically significant only at 24 months. By 36 months, volume in the active and placebo groups overlapped slightly with a P value of .31.

The changes in whole-brain volume were somewhat more pronounced. The declining slopes in whole-brain volume began to separate at 12 months. At both 24 and 36 months, the differences were statistically significant (P = .033 and .036, respectively), with curves continuing to diverge at the study’s end.

Adverse events occurred in about 80% of patients (82% with active treatment vs. 79% with placebo); about 25% of both arms experienced serious adverse events.

Common adverse events were atrial fibrillation (8% vs. 3%), chest pain (5% vs. 3%), and benign prostatic hyperplasia (6% vs. 3%). Other events included dizziness, arthralgia, depression, and confusion.

None of the 35% who dropped out of the trial did so for an adverse event, Dr. Schneider noted.

The Neuropsychological Test Battery (NTB) and the Rey Auditory Verbal Learning Test (RAVLT) were secondary measures of behavior and cognition. Both showed positive trends for ladostigil, but neither was statistically significant.

Dr. Schneider has disclosed financial relationships with numerous pharmaceutical companies, but has no financial ties with Avraham.

[email protected]

On Twitter @alz_gal

A few years before the launch of Pediatric News in 1967, Dr. Henry Kempe and his colleagues at the University of Colorado, Denver, published a groundbreaking report on child abuse, “The Battered Child Syndrome,” in JAMA.

It had a major impact on Calvin C.J. Sia, MD, a now-retired pediatrician in Hawaii, not only because it was pioneering work and one of the milestones of 20th century pediatrics, but also because Dr. Kempe was a close friend and mentor of Dr. Sia, going back to when Dr. Sia was a resident in the 1950s.

Dr. Kempe “alerted me to the battered child syndrome and taught me the importance of looking at the whole child within the context of the family, and he repeatedly reminded me of the importance of preventive care. He taught me how to make preventive change, with the emphasis on the first 3 years” of life, Dr. Sia said in an interview from his home in Honolulu.

To celebrate the 50th anniversary of Pediatric News, it seemed appropriate to turn to Dr. Sia. His practice, launched in 1958, not only spanned our 50 years, but also illustrated one of the major themes in pediatrics over the past half-century. With the old scourges of infectious disease, malnutrition, and infant mortality largely brought under control, pediatrics turned to the broader struggles of childhood, including learning, poverty, and abusive parenting.

Photo by Nicole Y. Lee

[email protected]

A few years before the launch of Pediatric News in 1967, Dr. Henry Kempe and his colleagues at the University of Colorado, Denver, published a groundbreaking report on child abuse, “The Battered Child Syndrome,” in JAMA.

It had a major impact on Calvin C.J. Sia, MD, a now-retired pediatrician in Hawaii, not only because it was pioneering work and one of the milestones of 20th century pediatrics, but also because Dr. Kempe was a close friend and mentor of Dr. Sia, going back to when Dr. Sia was a resident in the 1950s.

Dr. Kempe “alerted me to the battered child syndrome and taught me the importance of looking at the whole child within the context of the family, and he repeatedly reminded me of the importance of preventive care. He taught me how to make preventive change, with the emphasis on the first 3 years” of life, Dr. Sia said in an interview from his home in Honolulu.

To celebrate the 50th anniversary of Pediatric News, it seemed appropriate to turn to Dr. Sia. His practice, launched in 1958, not only spanned our 50 years, but also illustrated one of the major themes in pediatrics over the past half-century. With the old scourges of infectious disease, malnutrition, and infant mortality largely brought under control, pediatrics turned to the broader struggles of childhood, including learning, poverty, and abusive parenting.

Photo by Nicole Y. Lee

[email protected]

A few years before the launch of Pediatric News in 1967, Dr. Henry Kempe and his colleagues at the University of Colorado, Denver, published a groundbreaking report on child abuse, “The Battered Child Syndrome,” in JAMA.

It had a major impact on Calvin C.J. Sia, MD, a now-retired pediatrician in Hawaii, not only because it was pioneering work and one of the milestones of 20th century pediatrics, but also because Dr. Kempe was a close friend and mentor of Dr. Sia, going back to when Dr. Sia was a resident in the 1950s.

Dr. Kempe “alerted me to the battered child syndrome and taught me the importance of looking at the whole child within the context of the family, and he repeatedly reminded me of the importance of preventive care. He taught me how to make preventive change, with the emphasis on the first 3 years” of life, Dr. Sia said in an interview from his home in Honolulu.

To celebrate the 50th anniversary of Pediatric News, it seemed appropriate to turn to Dr. Sia. His practice, launched in 1958, not only spanned our 50 years, but also illustrated one of the major themes in pediatrics over the past half-century. With the old scourges of infectious disease, malnutrition, and infant mortality largely brought under control, pediatrics turned to the broader struggles of childhood, including learning, poverty, and abusive parenting.

Photo by Nicole Y. Lee

[email protected]

ORLANDO – In a study of 644 people with moderate to severe inflammatory bowel disease treated with vedolizumab (Entyvio, Takeda Pharmaceuticals), 346 achieved remission or a significant response. This 54% response rate includes 192 people with Crohn’s disease and 154 others with ulcerative colitis.

However, after a median of 143 days, some of the initial responders experienced a loss of response to vedolizumab therapy.
 

“In our real-world study of vedolizumab use in patients with IBD predominantly refractory to anti-TNF [tumor necrosis factor] therapy, loss of response was observed in about 40% of patients at 12 months,” said Eugenia Shmidt, MD, a gastroenterology fellow at the Icahn School of Medicine at Mount Sinai hospital in New York City.

To counter the loss of response, Dr. Shmidt and her colleagues shortened the dosing interval of vedolizumab to either 4 or 6 weeks in a subgroup of 36 patients who lost response. They also shortened the dosing interval to try to attempt an initial response in a subgroup of 47 people who did not respond  to initial induction therapy in the first place. “Dose intensification led to a successful recapture of response in 32% of patients who had initial response and in 19% of patients who did not have an initial response,” Dr. Shmidt said at the Advances in Inflammatory Bowel Diseases meeting.

“We find it interesting that there was greater success in recapturing significant response in patients who responded to vedolizumab initially compared to those who did not initially respond,” she said when asked if she found any of her findings surprising. “This emphasizes a likely need for different management strategies for initial vedolizumab responders and nonresponders, as well as early recognition of the need for dose optimization,” she added.

varaphoto/Thinkstock

ORLANDO – In a study of 644 people with moderate to severe inflammatory bowel disease treated with vedolizumab (Entyvio, Takeda Pharmaceuticals), 346 achieved remission or a significant response. This 54% response rate includes 192 people with Crohn’s disease and 154 others with ulcerative colitis.

However, after a median of 143 days, some of the initial responders experienced a loss of response to vedolizumab therapy.
 

“In our real-world study of vedolizumab use in patients with IBD predominantly refractory to anti-TNF [tumor necrosis factor] therapy, loss of response was observed in about 40% of patients at 12 months,” said Eugenia Shmidt, MD, a gastroenterology fellow at the Icahn School of Medicine at Mount Sinai hospital in New York City.

To counter the loss of response, Dr. Shmidt and her colleagues shortened the dosing interval of vedolizumab to either 4 or 6 weeks in a subgroup of 36 patients who lost response. They also shortened the dosing interval to try to attempt an initial response in a subgroup of 47 people who did not respond  to initial induction therapy in the first place. “Dose intensification led to a successful recapture of response in 32% of patients who had initial response and in 19% of patients who did not have an initial response,” Dr. Shmidt said at the Advances in Inflammatory Bowel Diseases meeting.

“We find it interesting that there was greater success in recapturing significant response in patients who responded to vedolizumab initially compared to those who did not initially respond,” she said when asked if she found any of her findings surprising. “This emphasizes a likely need for different management strategies for initial vedolizumab responders and nonresponders, as well as early recognition of the need for dose optimization,” she added.

varaphoto/Thinkstock

ORLANDO – In a study of 644 people with moderate to severe inflammatory bowel disease treated with vedolizumab (Entyvio, Takeda Pharmaceuticals), 346 achieved remission or a significant response. This 54% response rate includes 192 people with Crohn’s disease and 154 others with ulcerative colitis.

However, after a median of 143 days, some of the initial responders experienced a loss of response to vedolizumab therapy.
 

“In our real-world study of vedolizumab use in patients with IBD predominantly refractory to anti-TNF [tumor necrosis factor] therapy, loss of response was observed in about 40% of patients at 12 months,” said Eugenia Shmidt, MD, a gastroenterology fellow at the Icahn School of Medicine at Mount Sinai hospital in New York City.

To counter the loss of response, Dr. Shmidt and her colleagues shortened the dosing interval of vedolizumab to either 4 or 6 weeks in a subgroup of 36 patients who lost response. They also shortened the dosing interval to try to attempt an initial response in a subgroup of 47 people who did not respond  to initial induction therapy in the first place. “Dose intensification led to a successful recapture of response in 32% of patients who had initial response and in 19% of patients who did not have an initial response,” Dr. Shmidt said at the Advances in Inflammatory Bowel Diseases meeting.

“We find it interesting that there was greater success in recapturing significant response in patients who responded to vedolizumab initially compared to those who did not initially respond,” she said when asked if she found any of her findings surprising. “This emphasizes a likely need for different management strategies for initial vedolizumab responders and nonresponders, as well as early recognition of the need for dose optimization,” she added.

varaphoto/Thinkstock

Hospitals that aim to offer women long-acting reversible contraception immediately after giving birth require up-front coordination across departments, including early recruitment of nonclinical staff, researchers have found.

One of the advantages to offering LARC postpartum in the hospital, instead of an outpatient clinic, is that patients are not required to present for repeat visits. The American College of Obstetricians and Gynecologists has called the immediate postpartum period an optimal time for LARC placement.

flocu/ThinkStock.com

[email protected]

Hospitals that aim to offer women long-acting reversible contraception immediately after giving birth require up-front coordination across departments, including early recruitment of nonclinical staff, researchers have found.

One of the advantages to offering LARC postpartum in the hospital, instead of an outpatient clinic, is that patients are not required to present for repeat visits. The American College of Obstetricians and Gynecologists has called the immediate postpartum period an optimal time for LARC placement.

flocu/ThinkStock.com

[email protected]

Hospitals that aim to offer women long-acting reversible contraception immediately after giving birth require up-front coordination across departments, including early recruitment of nonclinical staff, researchers have found.

One of the advantages to offering LARC postpartum in the hospital, instead of an outpatient clinic, is that patients are not required to present for repeat visits. The American College of Obstetricians and Gynecologists has called the immediate postpartum period an optimal time for LARC placement.

flocu/ThinkStock.com

[email protected]

VIENNA – The prospect on the horizon of two new effective therapies for chronic cocaine dependence – sustained-release dextroamphetamine and subanesthetic ketamine infusions – was among the top developments of the year in addiction medicine, Wim van den Brink, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

Other highlights on his list included:

• Studies establishing that comorbid attention-deficit/hyperactivity disorder (ADHD) and substance use disorder now can be treated effectively with either extended-release mixed amphetamine salts or high-dose methylphenidate.

“It’s too strange that we have such conflicting evidence out there. Too many people are prescribing crazy-high doses of baclofen with no strong supporting evidence,” Dr. van den Brink said.
 

Cocaine dependence

Dr. van den Brink was a coinvestigator in a Dutch multicenter randomized, double-blind, placebo-controlled trial of multitreatment-refractory comorbid cocaine dependence in 73 heroin-dependent patients in heroin-assisted treatment. Patients assigned to 60 mg/day of sustained-release dextroamphetamine, in addition to the background methadone and diacetylmorphine all participants were on for their heroin dependence, had significantly fewer days of cocaine use in the 12-week study: a mean of 44.9 days, compared with 60.6 days in placebo-treated controls. Adverse events were transient and well tolerated (Lancet. 2016 May 28;387[10034]:2226-34).

“A lot of medications have been tried for treatment of cocaine dependence, but actually none of them has been shown to be effective with the exception of substitution treatment with stimulants. Ours is one of the most successful trials. These patients were using cocaine an average of 24 days per month along with a lot of other drugs, despite being in heroin treatment for 4 years,” Dr. van den Brink said. “Patients were very willing to take the sustained-release dextroamphetamine. In the last 4 weeks, 84% of them used at least 80% of their medication. And they were blinded to what they were using.

“We saw good effect sizes: 0.6-0.7 for self-report measures and 0.31 for negative urine samples. So this is a very promising approach. But it also means that, like with tobacco dependence or alcohol dependence, we have to start thinking about substitution therapy in stimulant-dependent patients,” he said.

Dr. van den Brink said subanesthetic ketamine as a novel treatment for cocaine dependence is not yet ready for prime time use in clinical practice, because it’s just not practical to bring patients in for a roughly hour-long intravenous infusion on a daily basis, as was done in a highly impressive proof-of-concept study. But new formulations of ketamine are under development that should better lend themselves to use in clinical practice.

In the proof-of-concept study, investigators at the New York State Psychiatric Institute brought into the laboratory cocaine-dependent volunteers not seeking treatment or abstinence and administered 52-minute infusions of ketamine at 0.41 or 71 mg/kg or lorazepam at 2 mg (Biol Psychiatry. 2014 Jul 1;76[1]:40-6). Lorazepam had absolutely no effect on motivation to change, but ketamine was a different story.

“As soon as you give a low dose of ketamine, you see a wonderful effect on motivation to change and on craving ratings in assessments at 24 hours post infusion. This looks like another promising way of treating cocaine dependence,” he said.
 

Doxazosin for alcoholism

Investigators at the National Institute on Alcohol Abuse and Alcoholism and several U.S. universities hypothesized that the norepinephrine system could be an important treatment target in alcohol dependence. They conducted a double-blind, placebo-controlled randomized trial in which alcohol-dependent patients seeking outpatient treatment were assigned to the alpha₁-adrenergic blocker doxazosin (Cardura) titrated to a maximum of 16 mg/day or placebo. They found doxazosin significantly reduced drinks per week and the number of heavy drinking days per week, but only in the subgroup of patients with a strong family history of alcoholism. In patients without such a family history, doxazosin paradoxically increased drinking (Addict Biol. 2016 Jul;21[4]:904-14).

One of the reasons adult ADHD is greatly underrecognized is that it tends to occur in combination with flashier substance use disorders. “Addiction is very comorbid with all kinds of disorders, but especially with externalizing childhood disorders like conduct disorder and ADHD,” Dr. van den Brink said.

It was shown half-a-decade ago that normal doses of methylphenidate have no effect on ADHD symptoms or substance use in comorbid adults. Then Swedish investigators reported that treating criminal offenders with high-dose methylphenidate – roughly three times greater than standard dosing – was effective in reducing both ADHD symptoms and comorbid substance use in criminal offenders. Those findings prompted investigators at the New York State Psychiatric Institute and the University of Minnesota to examine whether prescribing extended-release mixed amphetamine salts in adults with comorbid cocaine use disorder and ADHD would achieve improvement in both conditions. Indeed, it did, Dr. van den Brink said.

One hundred twenty-six affected patients were randomized to 60 or 80 mg/day of extended-release mixed amphetamine salts or placebo for 13 weeks coupled with weekly individual cognitive-behavioral therapy for all in this double-blind, three-arm clinical trial.

“They showed a number-needed-to-treat of about 2.5 in order to achieve a significant reduction in cocaine use and a very nice reduction in ADHD symptoms with a number-needed-to-treat of 3,” Dr. van den Brink said.

The rate of continuous cocaine abstinence in the last 3 weeks of the trial was 30% in the 80-mg group and 17.5% with 60 mg of extended-release mixed amphetamine salts, compared with just 7% with placebo (JAMA Psychiatry. 2015 Jun;72[6]:593-602).
 

Interpreting baclofen studies

The first high-quality multicenter, randomized, placebo-controlled, double-blind clinical trial, conducted in Germany, showed baclofen (Lioresal) at a mean dose of 180 mg/day was effective in maintaining alcohol abstinence (Eur Neuropsychopharmacol. 2015 Aug;25[8]:1167-77).

“They got wonderful results, with a number-needed-to-treat of 2.3. That is something we’re not used to seeing in the treatment of alcoholism. But there was no dose-response effect, which is a little unusual,” the psychiatrist observed.

Then a multicenter group of Dutch investigators, including Dr. van den Brink, carried out what they believed would be a confirmatory randomized, double-blind, placebo-controlled trial. However, it showed no difference between high- or low-dose baclofen and placebo in time to relapse (Eur Neuropsychopharmacol. 2016 Dec;26[12]:1950-9).

Little further light was shed by the two large French randomized, placebo-controlled clinical trials presented at the 2016 World Congress for Alcohol and Alcoholism in Berlin. One, the BACLOVILLE trial, included 320 patients treated in 60 family practice clinics; it showed strongly positive results for high-dose baclofen. In contrast, the 316-patient ALPADIR study proved negative. These conflicting results were particularly disappointing because France has been at the forefront of using high-dose baclofen to treat alcoholism, Dr. van den Brink said.

“Maybe some 100,000 people have been treated with high-dose baclofen for alcoholism in France,” he said. “What is the conclusion from all these baclofen studies? You can interpret them in many ways. Maybe there are two positive trials and two negative trials, or maybe there are two positive trials and two failed trials. The debate is not closed, even after four randomized trials.”

Dr. van den Brink reported receiving research funding from and/or serving as a consultant to more than half a dozen pharmaceutical companies.

[email protected]


 

VIENNA – The prospect on the horizon of two new effective therapies for chronic cocaine dependence – sustained-release dextroamphetamine and subanesthetic ketamine infusions – was among the top developments of the year in addiction medicine, Wim van den Brink, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

Other highlights on his list included:

• Studies establishing that comorbid attention-deficit/hyperactivity disorder (ADHD) and substance use disorder now can be treated effectively with either extended-release mixed amphetamine salts or high-dose methylphenidate.

“It’s too strange that we have such conflicting evidence out there. Too many people are prescribing crazy-high doses of baclofen with no strong supporting evidence,” Dr. van den Brink said.
 

Cocaine dependence

Dr. van den Brink was a coinvestigator in a Dutch multicenter randomized, double-blind, placebo-controlled trial of multitreatment-refractory comorbid cocaine dependence in 73 heroin-dependent patients in heroin-assisted treatment. Patients assigned to 60 mg/day of sustained-release dextroamphetamine, in addition to the background methadone and diacetylmorphine all participants were on for their heroin dependence, had significantly fewer days of cocaine use in the 12-week study: a mean of 44.9 days, compared with 60.6 days in placebo-treated controls. Adverse events were transient and well tolerated (Lancet. 2016 May 28;387[10034]:2226-34).

“A lot of medications have been tried for treatment of cocaine dependence, but actually none of them has been shown to be effective with the exception of substitution treatment with stimulants. Ours is one of the most successful trials. These patients were using cocaine an average of 24 days per month along with a lot of other drugs, despite being in heroin treatment for 4 years,” Dr. van den Brink said. “Patients were very willing to take the sustained-release dextroamphetamine. In the last 4 weeks, 84% of them used at least 80% of their medication. And they were blinded to what they were using.

“We saw good effect sizes: 0.6-0.7 for self-report measures and 0.31 for negative urine samples. So this is a very promising approach. But it also means that, like with tobacco dependence or alcohol dependence, we have to start thinking about substitution therapy in stimulant-dependent patients,” he said.

Dr. van den Brink said subanesthetic ketamine as a novel treatment for cocaine dependence is not yet ready for prime time use in clinical practice, because it’s just not practical to bring patients in for a roughly hour-long intravenous infusion on a daily basis, as was done in a highly impressive proof-of-concept study. But new formulations of ketamine are under development that should better lend themselves to use in clinical practice.

In the proof-of-concept study, investigators at the New York State Psychiatric Institute brought into the laboratory cocaine-dependent volunteers not seeking treatment or abstinence and administered 52-minute infusions of ketamine at 0.41 or 71 mg/kg or lorazepam at 2 mg (Biol Psychiatry. 2014 Jul 1;76[1]:40-6). Lorazepam had absolutely no effect on motivation to change, but ketamine was a different story.

“As soon as you give a low dose of ketamine, you see a wonderful effect on motivation to change and on craving ratings in assessments at 24 hours post infusion. This looks like another promising way of treating cocaine dependence,” he said.
 

Doxazosin for alcoholism

Investigators at the National Institute on Alcohol Abuse and Alcoholism and several U.S. universities hypothesized that the norepinephrine system could be an important treatment target in alcohol dependence. They conducted a double-blind, placebo-controlled randomized trial in which alcohol-dependent patients seeking outpatient treatment were assigned to the alpha₁-adrenergic blocker doxazosin (Cardura) titrated to a maximum of 16 mg/day or placebo. They found doxazosin significantly reduced drinks per week and the number of heavy drinking days per week, but only in the subgroup of patients with a strong family history of alcoholism. In patients without such a family history, doxazosin paradoxically increased drinking (Addict Biol. 2016 Jul;21[4]:904-14).

One of the reasons adult ADHD is greatly underrecognized is that it tends to occur in combination with flashier substance use disorders. “Addiction is very comorbid with all kinds of disorders, but especially with externalizing childhood disorders like conduct disorder and ADHD,” Dr. van den Brink said.

It was shown half-a-decade ago that normal doses of methylphenidate have no effect on ADHD symptoms or substance use in comorbid adults. Then Swedish investigators reported that treating criminal offenders with high-dose methylphenidate – roughly three times greater than standard dosing – was effective in reducing both ADHD symptoms and comorbid substance use in criminal offenders. Those findings prompted investigators at the New York State Psychiatric Institute and the University of Minnesota to examine whether prescribing extended-release mixed amphetamine salts in adults with comorbid cocaine use disorder and ADHD would achieve improvement in both conditions. Indeed, it did, Dr. van den Brink said.

One hundred twenty-six affected patients were randomized to 60 or 80 mg/day of extended-release mixed amphetamine salts or placebo for 13 weeks coupled with weekly individual cognitive-behavioral therapy for all in this double-blind, three-arm clinical trial.

“They showed a number-needed-to-treat of about 2.5 in order to achieve a significant reduction in cocaine use and a very nice reduction in ADHD symptoms with a number-needed-to-treat of 3,” Dr. van den Brink said.

The rate of continuous cocaine abstinence in the last 3 weeks of the trial was 30% in the 80-mg group and 17.5% with 60 mg of extended-release mixed amphetamine salts, compared with just 7% with placebo (JAMA Psychiatry. 2015 Jun;72[6]:593-602).
 

Interpreting baclofen studies

The first high-quality multicenter, randomized, placebo-controlled, double-blind clinical trial, conducted in Germany, showed baclofen (Lioresal) at a mean dose of 180 mg/day was effective in maintaining alcohol abstinence (Eur Neuropsychopharmacol. 2015 Aug;25[8]:1167-77).

“They got wonderful results, with a number-needed-to-treat of 2.3. That is something we’re not used to seeing in the treatment of alcoholism. But there was no dose-response effect, which is a little unusual,” the psychiatrist observed.

Then a multicenter group of Dutch investigators, including Dr. van den Brink, carried out what they believed would be a confirmatory randomized, double-blind, placebo-controlled trial. However, it showed no difference between high- or low-dose baclofen and placebo in time to relapse (Eur Neuropsychopharmacol. 2016 Dec;26[12]:1950-9).

Little further light was shed by the two large French randomized, placebo-controlled clinical trials presented at the 2016 World Congress for Alcohol and Alcoholism in Berlin. One, the BACLOVILLE trial, included 320 patients treated in 60 family practice clinics; it showed strongly positive results for high-dose baclofen. In contrast, the 316-patient ALPADIR study proved negative. These conflicting results were particularly disappointing because France has been at the forefront of using high-dose baclofen to treat alcoholism, Dr. van den Brink said.

“Maybe some 100,000 people have been treated with high-dose baclofen for alcoholism in France,” he said. “What is the conclusion from all these baclofen studies? You can interpret them in many ways. Maybe there are two positive trials and two negative trials, or maybe there are two positive trials and two failed trials. The debate is not closed, even after four randomized trials.”

Dr. van den Brink reported receiving research funding from and/or serving as a consultant to more than half a dozen pharmaceutical companies.

[email protected]


 

VIENNA – The prospect on the horizon of two new effective therapies for chronic cocaine dependence – sustained-release dextroamphetamine and subanesthetic ketamine infusions – was among the top developments of the year in addiction medicine, Wim van den Brink, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

Other highlights on his list included:

• Studies establishing that comorbid attention-deficit/hyperactivity disorder (ADHD) and substance use disorder now can be treated effectively with either extended-release mixed amphetamine salts or high-dose methylphenidate.

“It’s too strange that we have such conflicting evidence out there. Too many people are prescribing crazy-high doses of baclofen with no strong supporting evidence,” Dr. van den Brink said.
 

Cocaine dependence

Dr. van den Brink was a coinvestigator in a Dutch multicenter randomized, double-blind, placebo-controlled trial of multitreatment-refractory comorbid cocaine dependence in 73 heroin-dependent patients in heroin-assisted treatment. Patients assigned to 60 mg/day of sustained-release dextroamphetamine, in addition to the background methadone and diacetylmorphine all participants were on for their heroin dependence, had significantly fewer days of cocaine use in the 12-week study: a mean of 44.9 days, compared with 60.6 days in placebo-treated controls. Adverse events were transient and well tolerated (Lancet. 2016 May 28;387[10034]:2226-34).

“A lot of medications have been tried for treatment of cocaine dependence, but actually none of them has been shown to be effective with the exception of substitution treatment with stimulants. Ours is one of the most successful trials. These patients were using cocaine an average of 24 days per month along with a lot of other drugs, despite being in heroin treatment for 4 years,” Dr. van den Brink said. “Patients were very willing to take the sustained-release dextroamphetamine. In the last 4 weeks, 84% of them used at least 80% of their medication. And they were blinded to what they were using.

“We saw good effect sizes: 0.6-0.7 for self-report measures and 0.31 for negative urine samples. So this is a very promising approach. But it also means that, like with tobacco dependence or alcohol dependence, we have to start thinking about substitution therapy in stimulant-dependent patients,” he said.

Dr. van den Brink said subanesthetic ketamine as a novel treatment for cocaine dependence is not yet ready for prime time use in clinical practice, because it’s just not practical to bring patients in for a roughly hour-long intravenous infusion on a daily basis, as was done in a highly impressive proof-of-concept study. But new formulations of ketamine are under development that should better lend themselves to use in clinical practice.

In the proof-of-concept study, investigators at the New York State Psychiatric Institute brought into the laboratory cocaine-dependent volunteers not seeking treatment or abstinence and administered 52-minute infusions of ketamine at 0.41 or 71 mg/kg or lorazepam at 2 mg (Biol Psychiatry. 2014 Jul 1;76[1]:40-6). Lorazepam had absolutely no effect on motivation to change, but ketamine was a different story.

“As soon as you give a low dose of ketamine, you see a wonderful effect on motivation to change and on craving ratings in assessments at 24 hours post infusion. This looks like another promising way of treating cocaine dependence,” he said.
 

Doxazosin for alcoholism

Investigators at the National Institute on Alcohol Abuse and Alcoholism and several U.S. universities hypothesized that the norepinephrine system could be an important treatment target in alcohol dependence. They conducted a double-blind, placebo-controlled randomized trial in which alcohol-dependent patients seeking outpatient treatment were assigned to the alpha₁-adrenergic blocker doxazosin (Cardura) titrated to a maximum of 16 mg/day or placebo. They found doxazosin significantly reduced drinks per week and the number of heavy drinking days per week, but only in the subgroup of patients with a strong family history of alcoholism. In patients without such a family history, doxazosin paradoxically increased drinking (Addict Biol. 2016 Jul;21[4]:904-14).

One of the reasons adult ADHD is greatly underrecognized is that it tends to occur in combination with flashier substance use disorders. “Addiction is very comorbid with all kinds of disorders, but especially with externalizing childhood disorders like conduct disorder and ADHD,” Dr. van den Brink said.

It was shown half-a-decade ago that normal doses of methylphenidate have no effect on ADHD symptoms or substance use in comorbid adults. Then Swedish investigators reported that treating criminal offenders with high-dose methylphenidate – roughly three times greater than standard dosing – was effective in reducing both ADHD symptoms and comorbid substance use in criminal offenders. Those findings prompted investigators at the New York State Psychiatric Institute and the University of Minnesota to examine whether prescribing extended-release mixed amphetamine salts in adults with comorbid cocaine use disorder and ADHD would achieve improvement in both conditions. Indeed, it did, Dr. van den Brink said.

One hundred twenty-six affected patients were randomized to 60 or 80 mg/day of extended-release mixed amphetamine salts or placebo for 13 weeks coupled with weekly individual cognitive-behavioral therapy for all in this double-blind, three-arm clinical trial.

“They showed a number-needed-to-treat of about 2.5 in order to achieve a significant reduction in cocaine use and a very nice reduction in ADHD symptoms with a number-needed-to-treat of 3,” Dr. van den Brink said.

The rate of continuous cocaine abstinence in the last 3 weeks of the trial was 30% in the 80-mg group and 17.5% with 60 mg of extended-release mixed amphetamine salts, compared with just 7% with placebo (JAMA Psychiatry. 2015 Jun;72[6]:593-602).
 

Interpreting baclofen studies

The first high-quality multicenter, randomized, placebo-controlled, double-blind clinical trial, conducted in Germany, showed baclofen (Lioresal) at a mean dose of 180 mg/day was effective in maintaining alcohol abstinence (Eur Neuropsychopharmacol. 2015 Aug;25[8]:1167-77).

“They got wonderful results, with a number-needed-to-treat of 2.3. That is something we’re not used to seeing in the treatment of alcoholism. But there was no dose-response effect, which is a little unusual,” the psychiatrist observed.

Then a multicenter group of Dutch investigators, including Dr. van den Brink, carried out what they believed would be a confirmatory randomized, double-blind, placebo-controlled trial. However, it showed no difference between high- or low-dose baclofen and placebo in time to relapse (Eur Neuropsychopharmacol. 2016 Dec;26[12]:1950-9).

Little further light was shed by the two large French randomized, placebo-controlled clinical trials presented at the 2016 World Congress for Alcohol and Alcoholism in Berlin. One, the BACLOVILLE trial, included 320 patients treated in 60 family practice clinics; it showed strongly positive results for high-dose baclofen. In contrast, the 316-patient ALPADIR study proved negative. These conflicting results were particularly disappointing because France has been at the forefront of using high-dose baclofen to treat alcoholism, Dr. van den Brink said.

“Maybe some 100,000 people have been treated with high-dose baclofen for alcoholism in France,” he said. “What is the conclusion from all these baclofen studies? You can interpret them in many ways. Maybe there are two positive trials and two negative trials, or maybe there are two positive trials and two failed trials. The debate is not closed, even after four randomized trials.”

Dr. van den Brink reported receiving research funding from and/or serving as a consultant to more than half a dozen pharmaceutical companies.

[email protected]


 

VIENNA – Newly enhanced appreciation of the profound burden of comorbidities associated with adult atopic dermatitis (AD) is provided by the Liberty AD-AWARE study, investigators said at a joint program of the International Eczema Council and the International Psoriasis Council held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

“I think the only reason we thought psoriasis is a systemic disease and atopic dermatitis is not is because people were researching it much more in psoriasis. I think atopic dermatitis will emerge as potentially more systemic than psoriasis, including the comorbidities. It’s just a matter of time before the evidence is put forth for atopic dermatitis,” predicted Emma Guttman-Yassky, MD, PhD, professor and vice chair of the department of dermatology at Mount Sinai School of Medicine in New York.

[email protected]

VIENNA – Newly enhanced appreciation of the profound burden of comorbidities associated with adult atopic dermatitis (AD) is provided by the Liberty AD-AWARE study, investigators said at a joint program of the International Eczema Council and the International Psoriasis Council held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

“I think the only reason we thought psoriasis is a systemic disease and atopic dermatitis is not is because people were researching it much more in psoriasis. I think atopic dermatitis will emerge as potentially more systemic than psoriasis, including the comorbidities. It’s just a matter of time before the evidence is put forth for atopic dermatitis,” predicted Emma Guttman-Yassky, MD, PhD, professor and vice chair of the department of dermatology at Mount Sinai School of Medicine in New York.

[email protected]

VIENNA – Newly enhanced appreciation of the profound burden of comorbidities associated with adult atopic dermatitis (AD) is provided by the Liberty AD-AWARE study, investigators said at a joint program of the International Eczema Council and the International Psoriasis Council held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

“I think the only reason we thought psoriasis is a systemic disease and atopic dermatitis is not is because people were researching it much more in psoriasis. I think atopic dermatitis will emerge as potentially more systemic than psoriasis, including the comorbidities. It’s just a matter of time before the evidence is put forth for atopic dermatitis,” predicted Emma Guttman-Yassky, MD, PhD, professor and vice chair of the department of dermatology at Mount Sinai School of Medicine in New York.

[email protected]

HOUSTON – More than one-third of children discontinued the ketogenic diet prior to completion of a 3-month trial because of reported difficulty, a single-center study showed.

The findings underscore the importance of carefully screening patients and their families prior to initiating the ketogenic diet, lead author Gogi Kumar, MD, said in an interview at the annual meeting of the American Epilepsy Society. “We always talk about how and when the ketogenic diet should be used, but we don’t talk about the barriers to continuing the diet, like the socioeconomic aspects that determine the feasibility of continuing the diet,” said Dr. Kumar, a pediatric neurologist at Dayton (Ohio) Children’s Hospital. “If it’s a single mom who has two jobs and has a kid with intractable epilepsy, she cannot do it because ketogenic diets are complex and very intense. If the child has a gastrostomy tube and you can feed them a formula it might work, but then you have to bring them in for multiple lab tests. The family has to be very committed. They have to have resources.”

Doug Brunk/Frontline Medical News

[email protected]

HOUSTON – More than one-third of children discontinued the ketogenic diet prior to completion of a 3-month trial because of reported difficulty, a single-center study showed.

The findings underscore the importance of carefully screening patients and their families prior to initiating the ketogenic diet, lead author Gogi Kumar, MD, said in an interview at the annual meeting of the American Epilepsy Society. “We always talk about how and when the ketogenic diet should be used, but we don’t talk about the barriers to continuing the diet, like the socioeconomic aspects that determine the feasibility of continuing the diet,” said Dr. Kumar, a pediatric neurologist at Dayton (Ohio) Children’s Hospital. “If it’s a single mom who has two jobs and has a kid with intractable epilepsy, she cannot do it because ketogenic diets are complex and very intense. If the child has a gastrostomy tube and you can feed them a formula it might work, but then you have to bring them in for multiple lab tests. The family has to be very committed. They have to have resources.”

Doug Brunk/Frontline Medical News

[email protected]

HOUSTON – More than one-third of children discontinued the ketogenic diet prior to completion of a 3-month trial because of reported difficulty, a single-center study showed.

The findings underscore the importance of carefully screening patients and their families prior to initiating the ketogenic diet, lead author Gogi Kumar, MD, said in an interview at the annual meeting of the American Epilepsy Society. “We always talk about how and when the ketogenic diet should be used, but we don’t talk about the barriers to continuing the diet, like the socioeconomic aspects that determine the feasibility of continuing the diet,” said Dr. Kumar, a pediatric neurologist at Dayton (Ohio) Children’s Hospital. “If it’s a single mom who has two jobs and has a kid with intractable epilepsy, she cannot do it because ketogenic diets are complex and very intense. If the child has a gastrostomy tube and you can feed them a formula it might work, but then you have to bring them in for multiple lab tests. The family has to be very committed. They have to have resources.”

Doug Brunk/Frontline Medical News

[email protected]

HOUSTON – Many patients who eventually receive a diagnosis of tuberous sclerosis complex present with related complaints for months, or even years, before their condition is recognized and correctly diagnosed, according to a retrospective study.

The study, presented at the annual meeting of the American Epilepsy Society, found that patients with tuberous sclerosis complex (TSC) first sought care for TSC-related conditions an average of 7 months before they were diagnosed with the condition. Younger patients received the correct diagnosis sooner than did older patients: Treatment for TSC-related conditions preceded the diagnosis for 3.4 months for those aged 4 years or younger, compared with 5.5 months for those aged 25-29 years, and 21 months for those aged 80 years or older.

Seizures and skin conditions were common initial diagnoses among TSC patients, with 27% of patients aged 0-4 years being diagnosed with seizures prior to receiving their TSC diagnosis. The likelihood of prediagnosis visits for seizures decreased to less than 6% for older age groups. Seizures remained common post-TSC diagnosis among younger patients, with 38% of patients aged 0-4 years having any seizure diagnosis, while the rate fell through the lifespan to zero for those aged 80 or older.

James Wheless, MD, and his associates examined claims and enrollment data records from 2,163 patients diagnosed with TSC between January 2000 and December 2011. In addition to the frequently-diagnosed seizures seen in many TSC patients, skin conditions were diagnosed in 16.3% of patients before their eventual TSC diagnosis.

Other early conditions associated with TSC, according to the study’s multivariable analysis, included bone cysts, anxiety, and ADHD. However, wrote Dr. Wheless, chief of the department of pediatric neurology at the University of Tennessee Health Science Center, Memphis, and his coauthors, “at any point in time, patients with seizures were 2.9 times more likely to receive a TSC diagnosis than patients without seizures.”

The study was drawn from U.S. health plan databases that included both commercial and Medicare Advantage enrollees, and included patients through the lifespan. The date of the first recorded TSC diagnosis was the index date, and patients had to have at least 12 months of prediagnosis health plan enrollment to be included, or 6 months for those aged 2 years or younger. Data were collected for all pre-index visits (some of which stretched back to 1993), and for visits in the 12 months after the index visit.

The proportion of female patients ranged from fewer than half for those under 15 years (0-4 years, 46%; 5-9 years, 43%; 10-14 years, 48%) to 64% for those aged 80 years or older (P less than .001).

Dr. Wheless and his coauthors noted that the claims data used for the analysis “may not adequately capture clinical characteristics such as disease severity,” and that some patient data may have been lost if patients were disenrolled for periods of time during the study period.

The findings of the poster may prompt clinicians to consider TSC as a diagnosis; though rare, occurring in 1-2 per 6,000 live births, it’s thought to be an underrecognized disease entity. “Understanding the initial diagnoses experienced by TSC patients may help lead to earlier diagnosis and treatment of TSC,” Dr. Wheless and his coauthors wrote.

Novartis funded the study. Four study authors are employed by Optum, and one is employed by Novartis.

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HOUSTON – Many patients who eventually receive a diagnosis of tuberous sclerosis complex present with related complaints for months, or even years, before their condition is recognized and correctly diagnosed, according to a retrospective study.

The study, presented at the annual meeting of the American Epilepsy Society, found that patients with tuberous sclerosis complex (TSC) first sought care for TSC-related conditions an average of 7 months before they were diagnosed with the condition. Younger patients received the correct diagnosis sooner than did older patients: Treatment for TSC-related conditions preceded the diagnosis for 3.4 months for those aged 4 years or younger, compared with 5.5 months for those aged 25-29 years, and 21 months for those aged 80 years or older.

Seizures and skin conditions were common initial diagnoses among TSC patients, with 27% of patients aged 0-4 years being diagnosed with seizures prior to receiving their TSC diagnosis. The likelihood of prediagnosis visits for seizures decreased to less than 6% for older age groups. Seizures remained common post-TSC diagnosis among younger patients, with 38% of patients aged 0-4 years having any seizure diagnosis, while the rate fell through the lifespan to zero for those aged 80 or older.

James Wheless, MD, and his associates examined claims and enrollment data records from 2,163 patients diagnosed with TSC between January 2000 and December 2011. In addition to the frequently-diagnosed seizures seen in many TSC patients, skin conditions were diagnosed in 16.3% of patients before their eventual TSC diagnosis.

Other early conditions associated with TSC, according to the study’s multivariable analysis, included bone cysts, anxiety, and ADHD. However, wrote Dr. Wheless, chief of the department of pediatric neurology at the University of Tennessee Health Science Center, Memphis, and his coauthors, “at any point in time, patients with seizures were 2.9 times more likely to receive a TSC diagnosis than patients without seizures.”

The study was drawn from U.S. health plan databases that included both commercial and Medicare Advantage enrollees, and included patients through the lifespan. The date of the first recorded TSC diagnosis was the index date, and patients had to have at least 12 months of prediagnosis health plan enrollment to be included, or 6 months for those aged 2 years or younger. Data were collected for all pre-index visits (some of which stretched back to 1993), and for visits in the 12 months after the index visit.

The proportion of female patients ranged from fewer than half for those under 15 years (0-4 years, 46%; 5-9 years, 43%; 10-14 years, 48%) to 64% for those aged 80 years or older (P less than .001).

Dr. Wheless and his coauthors noted that the claims data used for the analysis “may not adequately capture clinical characteristics such as disease severity,” and that some patient data may have been lost if patients were disenrolled for periods of time during the study period.

The findings of the poster may prompt clinicians to consider TSC as a diagnosis; though rare, occurring in 1-2 per 6,000 live births, it’s thought to be an underrecognized disease entity. “Understanding the initial diagnoses experienced by TSC patients may help lead to earlier diagnosis and treatment of TSC,” Dr. Wheless and his coauthors wrote.

Novartis funded the study. Four study authors are employed by Optum, and one is employed by Novartis.

[email protected]

On Twitter @karioakes

HOUSTON – Many patients who eventually receive a diagnosis of tuberous sclerosis complex present with related complaints for months, or even years, before their condition is recognized and correctly diagnosed, according to a retrospective study.

The study, presented at the annual meeting of the American Epilepsy Society, found that patients with tuberous sclerosis complex (TSC) first sought care for TSC-related conditions an average of 7 months before they were diagnosed with the condition. Younger patients received the correct diagnosis sooner than did older patients: Treatment for TSC-related conditions preceded the diagnosis for 3.4 months for those aged 4 years or younger, compared with 5.5 months for those aged 25-29 years, and 21 months for those aged 80 years or older.

Seizures and skin conditions were common initial diagnoses among TSC patients, with 27% of patients aged 0-4 years being diagnosed with seizures prior to receiving their TSC diagnosis. The likelihood of prediagnosis visits for seizures decreased to less than 6% for older age groups. Seizures remained common post-TSC diagnosis among younger patients, with 38% of patients aged 0-4 years having any seizure diagnosis, while the rate fell through the lifespan to zero for those aged 80 or older.

James Wheless, MD, and his associates examined claims and enrollment data records from 2,163 patients diagnosed with TSC between January 2000 and December 2011. In addition to the frequently-diagnosed seizures seen in many TSC patients, skin conditions were diagnosed in 16.3% of patients before their eventual TSC diagnosis.

Other early conditions associated with TSC, according to the study’s multivariable analysis, included bone cysts, anxiety, and ADHD. However, wrote Dr. Wheless, chief of the department of pediatric neurology at the University of Tennessee Health Science Center, Memphis, and his coauthors, “at any point in time, patients with seizures were 2.9 times more likely to receive a TSC diagnosis than patients without seizures.”

The study was drawn from U.S. health plan databases that included both commercial and Medicare Advantage enrollees, and included patients through the lifespan. The date of the first recorded TSC diagnosis was the index date, and patients had to have at least 12 months of prediagnosis health plan enrollment to be included, or 6 months for those aged 2 years or younger. Data were collected for all pre-index visits (some of which stretched back to 1993), and for visits in the 12 months after the index visit.

The proportion of female patients ranged from fewer than half for those under 15 years (0-4 years, 46%; 5-9 years, 43%; 10-14 years, 48%) to 64% for those aged 80 years or older (P less than .001).

Dr. Wheless and his coauthors noted that the claims data used for the analysis “may not adequately capture clinical characteristics such as disease severity,” and that some patient data may have been lost if patients were disenrolled for periods of time during the study period.

The findings of the poster may prompt clinicians to consider TSC as a diagnosis; though rare, occurring in 1-2 per 6,000 live births, it’s thought to be an underrecognized disease entity. “Understanding the initial diagnoses experienced by TSC patients may help lead to earlier diagnosis and treatment of TSC,” Dr. Wheless and his coauthors wrote.

Novartis funded the study. Four study authors are employed by Optum, and one is employed by Novartis.

[email protected]

On Twitter @karioakes