Pediatrics

Physicians continue to prescribe off-label drugs for children, with rates increasing over a 10-year period from 2006 to 2015, according to findings from a new study.

The increase occurred despite recent legislation aimed at encouraging pediatric clinical trials, with the intention of improving the “quality of evidence and the number of drugs approved for children,” Divya Hoon of Rutgers University in New Brunswick, N.J., and colleagues wrote in Pediatrics.

“[Our] results can help inform ongoing education, research, and policies around efficacious, effective, and safe use of medications in children,” the researchers said.

To determine trends in, and categories of, drugs prescribed off label, the researchers used data from the National Ambulatory Medical Care Surveys for all pediatric visits and subsequent drug orders from 2006 to 2015. They focused on 141 drugs that are predominantly or exclusively used in systemic formulations and that had been ordered at least 30 times.

At least one off-label systemic drug order occurred at 18.5% of the 1.74 billion estimated ambulatory pediatric visits (95% confidence interval, 17.7%-19.3%), totaling 41.2 million off-label orders per year. The primary reason for a drug being considered off label was that it was for an unapproved condition (74.6%), followed by patient age (17.6%) and weight (0.6%). Absolute and relative rates of off-label ordering increased throughout the study, especially in regard to antihistamines and psychotropic drugs, the investigators said.

In an accompanying editorial, Katelyn Yackey, MD, of the University of Kentucky Children’s Hospital, Lexington, and Rachel Stanley, MD, of Nationwide Children’s Hospital, Columbus, Ohio, stated that “off label is not synonymous with off evidence” and emphasized the need for more clinical trials of medications for children (Pediatrics. 2019 Sep 16. doi: 10.1542/peds.2019-1571).

“Although drugs are often used off label, there may be sufficient preliminary research about a medical condition and particular drugs to support their use,” they wrote. While recognizing that evaluating medications in pediatric patients has been challenging, they added that “children continue to receive medications off label and for unapproved conditions,” so studies that evaluate “safety, efficacy, pharmacokinetics, and optimal dosing in pediatric patients” remain a necessity.

Though the research featured a long study period and large study population, the authors recognized its possible limitations, including the exclusion of less commonly ordered drugs, the inability to determine drug formulation or dosage, and the fact that the survey data captured only ordered medicines and not whether they were actually dispensed or consumed.

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Rutgers Robert Wood Johnson Medical School Summer Research Fellowship. The authors reported no conflicts of interest.

SOURCE: Hoon D et al. Pediatrics. 2019 Sep 16. doi: 10.1542/peds.2019-0896.

Physicians continue to prescribe off-label drugs for children, with rates increasing over a 10-year period from 2006 to 2015, according to findings from a new study.

The increase occurred despite recent legislation aimed at encouraging pediatric clinical trials, with the intention of improving the “quality of evidence and the number of drugs approved for children,” Divya Hoon of Rutgers University in New Brunswick, N.J., and colleagues wrote in Pediatrics.

“[Our] results can help inform ongoing education, research, and policies around efficacious, effective, and safe use of medications in children,” the researchers said.

To determine trends in, and categories of, drugs prescribed off label, the researchers used data from the National Ambulatory Medical Care Surveys for all pediatric visits and subsequent drug orders from 2006 to 2015. They focused on 141 drugs that are predominantly or exclusively used in systemic formulations and that had been ordered at least 30 times.

At least one off-label systemic drug order occurred at 18.5% of the 1.74 billion estimated ambulatory pediatric visits (95% confidence interval, 17.7%-19.3%), totaling 41.2 million off-label orders per year. The primary reason for a drug being considered off label was that it was for an unapproved condition (74.6%), followed by patient age (17.6%) and weight (0.6%). Absolute and relative rates of off-label ordering increased throughout the study, especially in regard to antihistamines and psychotropic drugs, the investigators said.

In an accompanying editorial, Katelyn Yackey, MD, of the University of Kentucky Children’s Hospital, Lexington, and Rachel Stanley, MD, of Nationwide Children’s Hospital, Columbus, Ohio, stated that “off label is not synonymous with off evidence” and emphasized the need for more clinical trials of medications for children (Pediatrics. 2019 Sep 16. doi: 10.1542/peds.2019-1571).

“Although drugs are often used off label, there may be sufficient preliminary research about a medical condition and particular drugs to support their use,” they wrote. While recognizing that evaluating medications in pediatric patients has been challenging, they added that “children continue to receive medications off label and for unapproved conditions,” so studies that evaluate “safety, efficacy, pharmacokinetics, and optimal dosing in pediatric patients” remain a necessity.

Though the research featured a long study period and large study population, the authors recognized its possible limitations, including the exclusion of less commonly ordered drugs, the inability to determine drug formulation or dosage, and the fact that the survey data captured only ordered medicines and not whether they were actually dispensed or consumed.

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Rutgers Robert Wood Johnson Medical School Summer Research Fellowship. The authors reported no conflicts of interest.

SOURCE: Hoon D et al. Pediatrics. 2019 Sep 16. doi: 10.1542/peds.2019-0896.

Physicians continue to prescribe off-label drugs for children, with rates increasing over a 10-year period from 2006 to 2015, according to findings from a new study.

The increase occurred despite recent legislation aimed at encouraging pediatric clinical trials, with the intention of improving the “quality of evidence and the number of drugs approved for children,” Divya Hoon of Rutgers University in New Brunswick, N.J., and colleagues wrote in Pediatrics.

“[Our] results can help inform ongoing education, research, and policies around efficacious, effective, and safe use of medications in children,” the researchers said.

To determine trends in, and categories of, drugs prescribed off label, the researchers used data from the National Ambulatory Medical Care Surveys for all pediatric visits and subsequent drug orders from 2006 to 2015. They focused on 141 drugs that are predominantly or exclusively used in systemic formulations and that had been ordered at least 30 times.

At least one off-label systemic drug order occurred at 18.5% of the 1.74 billion estimated ambulatory pediatric visits (95% confidence interval, 17.7%-19.3%), totaling 41.2 million off-label orders per year. The primary reason for a drug being considered off label was that it was for an unapproved condition (74.6%), followed by patient age (17.6%) and weight (0.6%). Absolute and relative rates of off-label ordering increased throughout the study, especially in regard to antihistamines and psychotropic drugs, the investigators said.

In an accompanying editorial, Katelyn Yackey, MD, of the University of Kentucky Children’s Hospital, Lexington, and Rachel Stanley, MD, of Nationwide Children’s Hospital, Columbus, Ohio, stated that “off label is not synonymous with off evidence” and emphasized the need for more clinical trials of medications for children (Pediatrics. 2019 Sep 16. doi: 10.1542/peds.2019-1571).

“Although drugs are often used off label, there may be sufficient preliminary research about a medical condition and particular drugs to support their use,” they wrote. While recognizing that evaluating medications in pediatric patients has been challenging, they added that “children continue to receive medications off label and for unapproved conditions,” so studies that evaluate “safety, efficacy, pharmacokinetics, and optimal dosing in pediatric patients” remain a necessity.

Though the research featured a long study period and large study population, the authors recognized its possible limitations, including the exclusion of less commonly ordered drugs, the inability to determine drug formulation or dosage, and the fact that the survey data captured only ordered medicines and not whether they were actually dispensed or consumed.

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Rutgers Robert Wood Johnson Medical School Summer Research Fellowship. The authors reported no conflicts of interest.

SOURCE: Hoon D et al. Pediatrics. 2019 Sep 16. doi: 10.1542/peds.2019-0896.

STOCKHOLM – Children with multiple sclerosis (MS) who are initially treated with one of the newer disease-modifying therapies experienced significantly better disease activity control in terms of clinical and radiologic outcomes, compared with those started on an injectable drug in a large, observational, cohort study conducted by the U.S. Network of Pediatric MS Centers.

This was the first-ever comparative effectiveness study of initial disease-modifying therapies (DMTs) in children with MS. The take-home message was clear: “This study supports the use of newer DMTs early in the course of pediatric MS,” Kristen M. Krysko, MD, said in presenting the results at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

The study was conducted because she and her coinvestigators in the network have noted increasing use of newer DMTs, even as first-line initial treatment, in the setting of pediatric MS. This represents a break with the traditional approach, which entails starting with one of the injectables – either an interferon-beta or glatiramer acetate – because of their more favorable safety profile, then escalating therapy by switching to a newer, more potent agent in the event of a disease breakthrough, explained Dr. Krysko, a clinical fellow in neurology at the University of California, San Francisco.

Until now, there has been only limited evidence on how the newer DMTs stack up in comparison with the injectables in a pediatric MS population. The chief supporting evidence for the harder-hitting initial approach, Dr. Krysko said, has come from a randomized clinical trial in 215 children showing that fingolimod had a lower relapse rate and better MRI outcomes, compared with interferon beta-1a, during 2 years of follow-up, but at the cost of a higher rate of serious adverse events (N Engl J Med. 2018;379[11]:1017-27).

Dr. Krysko presented a prospective study conducted at 12 sites participating in the network. It included 741 children, 85% of whom had MS, with clinically isolated syndrome in the remainder. For 197 patients, the first MS treatment was an injectable. The other 544 children were started on a newer DMT, most often dimethyl fumarate, rituximab, natalizumab, or fingolimod, with a smattering of patients on teriflunomide or ocrelizumab. Patients averaged roughly a 1-year disease history at the time they went on their first DMT and were then followed for a mean of 1.5-1.8 years on that drug.

The primary outcome was the propensity score–matched, annualized relapse rate during follow-up: The annualized rate was 0.2 in the group on newer DMTs, compared with 0.47 with the injectables. The propensity score matching was used because patients were not randomized by treatment. The propensity scores attempted to neutralize potential confounders, including differences in patient demographics, baseline disease activity, and severity of a first pretreatment relapse, she explained.

The between-group difference in adjusted annualized relapse rate was statistically significant. It translated to a 55% reduction in relative risk favoring children on a newer DMT. Moreover, the number needed to treat was impressively low, at 3.7.

“This can be interpreted as [needing] to treat 3.7 individuals with newer rather than injectable DMTs to prevent one relapse,” Dr. Krysko observed.

Secondary endpoints focused on brain MRI findings. The median time to development of new or enlarging T2 hyperintense lesions was 2.79 years with the newer DMTs, compared with 0.42 years with the injectables. The adjusted risk of developing such lesions was reduced by 49% with the newer DMTs.

Similarly, the median time to development of gadolinium-enhancing lesions was 2.25 years with the injectables and had not yet been reached in patients on newer DMTs when the study closed in January 2019.

“Many children on the newer DMTs never experienced a new gadolinium-positive lesion on follow-up,” she noted.

The adjusted risk of developing a new gadolinium-enhancing lesion was 62% lower in the newer-DMT group.

In terms of the safety of the newer DMTs, there were no surprises: The adverse-event profiles mirrored those that have been examined far more extensively in adults, according to Dr. Krysko.

The newer DMTs included oral agents as well as drugs given by intravenous infusion. The IV agents generally resulted in better disease control, compared with the oral agents, as one would expect, she said. The patient numbers were not sufficient to break down the results on an individual drug basis, however, even though this was a relatively large study.

Asked if these study results warranted a sweeping change in clinical practice – a move away from the conventional escalation treatment strategy in children in favor of upfront use of the newer, more effective DMTs – Dr. Krysko said that was tempting in light of a few recent studies in adults showing that even the first treatment can affect important long-term outcomes, including conversion to secondary progressive MS. However, she said she’d like to see additional studies in children that are focused on safety before making widespread changes in treatment strategy, especially because the pediatric MS network study did not include many very young children.

The study was sponsored by the Multiple Sclerosis Society. Dr. Kysko reported having no financial conflicts in regard to the study.

[email protected]

SOURCE: Krysko KM et al. ECTRIMS 2019, abstract 249.

STOCKHOLM – Children with multiple sclerosis (MS) who are initially treated with one of the newer disease-modifying therapies experienced significantly better disease activity control in terms of clinical and radiologic outcomes, compared with those started on an injectable drug in a large, observational, cohort study conducted by the U.S. Network of Pediatric MS Centers.

This was the first-ever comparative effectiveness study of initial disease-modifying therapies (DMTs) in children with MS. The take-home message was clear: “This study supports the use of newer DMTs early in the course of pediatric MS,” Kristen M. Krysko, MD, said in presenting the results at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

The study was conducted because she and her coinvestigators in the network have noted increasing use of newer DMTs, even as first-line initial treatment, in the setting of pediatric MS. This represents a break with the traditional approach, which entails starting with one of the injectables – either an interferon-beta or glatiramer acetate – because of their more favorable safety profile, then escalating therapy by switching to a newer, more potent agent in the event of a disease breakthrough, explained Dr. Krysko, a clinical fellow in neurology at the University of California, San Francisco.

Until now, there has been only limited evidence on how the newer DMTs stack up in comparison with the injectables in a pediatric MS population. The chief supporting evidence for the harder-hitting initial approach, Dr. Krysko said, has come from a randomized clinical trial in 215 children showing that fingolimod had a lower relapse rate and better MRI outcomes, compared with interferon beta-1a, during 2 years of follow-up, but at the cost of a higher rate of serious adverse events (N Engl J Med. 2018;379[11]:1017-27).

Dr. Krysko presented a prospective study conducted at 12 sites participating in the network. It included 741 children, 85% of whom had MS, with clinically isolated syndrome in the remainder. For 197 patients, the first MS treatment was an injectable. The other 544 children were started on a newer DMT, most often dimethyl fumarate, rituximab, natalizumab, or fingolimod, with a smattering of patients on teriflunomide or ocrelizumab. Patients averaged roughly a 1-year disease history at the time they went on their first DMT and were then followed for a mean of 1.5-1.8 years on that drug.

The primary outcome was the propensity score–matched, annualized relapse rate during follow-up: The annualized rate was 0.2 in the group on newer DMTs, compared with 0.47 with the injectables. The propensity score matching was used because patients were not randomized by treatment. The propensity scores attempted to neutralize potential confounders, including differences in patient demographics, baseline disease activity, and severity of a first pretreatment relapse, she explained.

The between-group difference in adjusted annualized relapse rate was statistically significant. It translated to a 55% reduction in relative risk favoring children on a newer DMT. Moreover, the number needed to treat was impressively low, at 3.7.

“This can be interpreted as [needing] to treat 3.7 individuals with newer rather than injectable DMTs to prevent one relapse,” Dr. Krysko observed.

Secondary endpoints focused on brain MRI findings. The median time to development of new or enlarging T2 hyperintense lesions was 2.79 years with the newer DMTs, compared with 0.42 years with the injectables. The adjusted risk of developing such lesions was reduced by 49% with the newer DMTs.

Similarly, the median time to development of gadolinium-enhancing lesions was 2.25 years with the injectables and had not yet been reached in patients on newer DMTs when the study closed in January 2019.

“Many children on the newer DMTs never experienced a new gadolinium-positive lesion on follow-up,” she noted.

The adjusted risk of developing a new gadolinium-enhancing lesion was 62% lower in the newer-DMT group.

In terms of the safety of the newer DMTs, there were no surprises: The adverse-event profiles mirrored those that have been examined far more extensively in adults, according to Dr. Krysko.

The newer DMTs included oral agents as well as drugs given by intravenous infusion. The IV agents generally resulted in better disease control, compared with the oral agents, as one would expect, she said. The patient numbers were not sufficient to break down the results on an individual drug basis, however, even though this was a relatively large study.

Asked if these study results warranted a sweeping change in clinical practice – a move away from the conventional escalation treatment strategy in children in favor of upfront use of the newer, more effective DMTs – Dr. Krysko said that was tempting in light of a few recent studies in adults showing that even the first treatment can affect important long-term outcomes, including conversion to secondary progressive MS. However, she said she’d like to see additional studies in children that are focused on safety before making widespread changes in treatment strategy, especially because the pediatric MS network study did not include many very young children.

The study was sponsored by the Multiple Sclerosis Society. Dr. Kysko reported having no financial conflicts in regard to the study.

[email protected]

SOURCE: Krysko KM et al. ECTRIMS 2019, abstract 249.

STOCKHOLM – Children with multiple sclerosis (MS) who are initially treated with one of the newer disease-modifying therapies experienced significantly better disease activity control in terms of clinical and radiologic outcomes, compared with those started on an injectable drug in a large, observational, cohort study conducted by the U.S. Network of Pediatric MS Centers.

This was the first-ever comparative effectiveness study of initial disease-modifying therapies (DMTs) in children with MS. The take-home message was clear: “This study supports the use of newer DMTs early in the course of pediatric MS,” Kristen M. Krysko, MD, said in presenting the results at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

The study was conducted because she and her coinvestigators in the network have noted increasing use of newer DMTs, even as first-line initial treatment, in the setting of pediatric MS. This represents a break with the traditional approach, which entails starting with one of the injectables – either an interferon-beta or glatiramer acetate – because of their more favorable safety profile, then escalating therapy by switching to a newer, more potent agent in the event of a disease breakthrough, explained Dr. Krysko, a clinical fellow in neurology at the University of California, San Francisco.

Until now, there has been only limited evidence on how the newer DMTs stack up in comparison with the injectables in a pediatric MS population. The chief supporting evidence for the harder-hitting initial approach, Dr. Krysko said, has come from a randomized clinical trial in 215 children showing that fingolimod had a lower relapse rate and better MRI outcomes, compared with interferon beta-1a, during 2 years of follow-up, but at the cost of a higher rate of serious adverse events (N Engl J Med. 2018;379[11]:1017-27).

Dr. Krysko presented a prospective study conducted at 12 sites participating in the network. It included 741 children, 85% of whom had MS, with clinically isolated syndrome in the remainder. For 197 patients, the first MS treatment was an injectable. The other 544 children were started on a newer DMT, most often dimethyl fumarate, rituximab, natalizumab, or fingolimod, with a smattering of patients on teriflunomide or ocrelizumab. Patients averaged roughly a 1-year disease history at the time they went on their first DMT and were then followed for a mean of 1.5-1.8 years on that drug.

The primary outcome was the propensity score–matched, annualized relapse rate during follow-up: The annualized rate was 0.2 in the group on newer DMTs, compared with 0.47 with the injectables. The propensity score matching was used because patients were not randomized by treatment. The propensity scores attempted to neutralize potential confounders, including differences in patient demographics, baseline disease activity, and severity of a first pretreatment relapse, she explained.

The between-group difference in adjusted annualized relapse rate was statistically significant. It translated to a 55% reduction in relative risk favoring children on a newer DMT. Moreover, the number needed to treat was impressively low, at 3.7.

“This can be interpreted as [needing] to treat 3.7 individuals with newer rather than injectable DMTs to prevent one relapse,” Dr. Krysko observed.

Secondary endpoints focused on brain MRI findings. The median time to development of new or enlarging T2 hyperintense lesions was 2.79 years with the newer DMTs, compared with 0.42 years with the injectables. The adjusted risk of developing such lesions was reduced by 49% with the newer DMTs.

Similarly, the median time to development of gadolinium-enhancing lesions was 2.25 years with the injectables and had not yet been reached in patients on newer DMTs when the study closed in January 2019.

“Many children on the newer DMTs never experienced a new gadolinium-positive lesion on follow-up,” she noted.

The adjusted risk of developing a new gadolinium-enhancing lesion was 62% lower in the newer-DMT group.

In terms of the safety of the newer DMTs, there were no surprises: The adverse-event profiles mirrored those that have been examined far more extensively in adults, according to Dr. Krysko.

The newer DMTs included oral agents as well as drugs given by intravenous infusion. The IV agents generally resulted in better disease control, compared with the oral agents, as one would expect, she said. The patient numbers were not sufficient to break down the results on an individual drug basis, however, even though this was a relatively large study.

Asked if these study results warranted a sweeping change in clinical practice – a move away from the conventional escalation treatment strategy in children in favor of upfront use of the newer, more effective DMTs – Dr. Krysko said that was tempting in light of a few recent studies in adults showing that even the first treatment can affect important long-term outcomes, including conversion to secondary progressive MS. However, she said she’d like to see additional studies in children that are focused on safety before making widespread changes in treatment strategy, especially because the pediatric MS network study did not include many very young children.

The study was sponsored by the Multiple Sclerosis Society. Dr. Kysko reported having no financial conflicts in regard to the study.

[email protected]

SOURCE: Krysko KM et al. ECTRIMS 2019, abstract 249.

A pill designed to desensitize peanut-allergic children and teenagers may be on the way.

The Food and Drug Administration’s Allergenic Products Advisory Committee has voted to recommend approval of the AR101 peanut protein capsules (Palforzia) for use in oral immunotherapy in those aged 4-17 years old with a confirmed peanut allergy. Conditions for approval include stipulations that a black-box warning and medication use guide are included in the packaging, the panel said. The FDA usually follows the recommendations of its advisory panels. 

bankrx/Getty Images

The committee members voted 7-2 that the drug was effective and 8-1 that it was safe. 

John Kelso, MD, the sole dissenter on safety, voiced concerns about the dearth of long-term follow-up in Aimmune Therapeutic’s body of research and the finding that children who received the treatment during the dose-escalation and maintenance periods had twice the number of allergic reactions requiring epinephrine, compared with those who received placebo. There are no long-term safety data to rely on yet, he added.

“Efficacy has not been demonstrated, except on the day the peanut challenge is administered,” said Dr. Kelso, an allergist at the Scripps Clinic, San Diego, adding that only long-term follow-up data would fully convince him that the drug’s benefits outweigh the risks.

In the discussion, however, other committee members pointed out that new drugs are often approved without long-term efficacy and safety data. Those data are extrapolated from clinical trials, and only real-world experience will confirm the data, they noted.

Company representatives did not explicitly address the potential cost of the therapy, but a recent review by the Institute for Clinical and Economic Review estimated the cost to be $4,200 a year. Palforzia would have to be taken every day, for an unknown amount of time, to maintain peanut tolerance.

“Using prices from analysts for AR101 ($4,200 a year), we estimated that only 41% of eligible patients could be treated in a given year without exceeding ICER’s budget impact threshold,” the institute concluded in a publicly released analysis.

Palforzia comes in individual packs of capsules filled with peanut protein, not flour. The capsules come in doses of 0.5, 1, 10, 20, and 100, and 300 mg. A single-dose sachet contains 300 mg. Treatment begins with 0.5-6 mg over 1 day and escalates every 2 weeks until 300 mg is reached or there is a reaction requiring epinephrine. Passing at least a 300-mg dose was the requirement for exiting the escalation phase and moving on to the daily, year-long maintenance phase.

The four efficacy studies presented showed that 96% of patients tolerated 300 mg, 84% tolerated 600 mg, and 63% 1,000 mg – about 10 times the reactive dose observed in the placebo controls.

“Only 125 mg of peanut protein – the amount in about half a peanut kernel – can be enough to provoke a reaction,” said Daniel Adelman, MD, chief medical officer of Aimmune. If patients can tolerate 600 mg of protein – the equivalent of two kernels, accidental ingestion will result in a “predictable, manageable” reaction.

“This is truly a clinically significant result for patients and families who report lives dictated by the allergy,” Dr. Adelman said.

Consistent manufacturing processes and positive safety data should reassure clinicians and patients that they are receiving a safe, effective, and well-regulated treatment, he added.

The capsule, however, is not a panacea. The company advises that families continue with the peanut avoidance diet. “It’s important to remember that reactive episodes can occur with dosing, and accidental exposures can occur at unpredictable times, away from home, and despite the best efforts at avoidance,” Dr. Adelman said. “This is not a drug for everyone, but it is an effective desensitization tool and would clearly be the first therapy to treat a food allergy, providing statistically significant and clinically important improvement. Outcomes align with patients’ goals.”

Safety was assessed in 709 treated patients who received the medication and 292 who received placebo. Treatment-related adverse events were most common in initial dosing: 89% of the treatment group and 58% of the placebo group experienced at least one adverse event during that time. Adverse events were mostly mild to moderate and decreased in severity over the study period. They included abdominal pain (45% active vs. 18% placebo), throat irritation (40% vs. 17%), pruritus (33% vs. 20%), vomiting (37% vs. 16%), cough (32% vs. 24%), nausea (32% vs. 14%), urticaria (28% vs. 19%), and upper abdominal pain (30% vs. 14%).

Discontinuations caused by these adverse events were infrequent, with only 1.8% of participants who were taking the active capsule and 1% of those taking placebo discontinuing the study product during initial dose escalation. Only the severe systemic allergic reactions were considered to be anaphylaxis, and they had to affect at least two body systems.

Respiratory events were more common in those in the active group, especially in children with asthma. These events included cough, wheezing, dyspnea, dysphonia, throat irritation and tightness, and exercise-induced asthma. There was, however, no “concerning change” in asthma control.

Systemic allergic reactions and anaphylaxis were more common in the active-dose group. Systemic reactions during dose escalation occurred in 9.4% of active patients and 3.8% those taking placebo. During the maintenance phase, they occurred in 8.7% and 1.7% of patients, respectively. Three patients in the active group had a serious systemic reaction – two during up-dosing and one during maintenance.

• The first dose of each progressive dose must be administered in a facility that is equipped to treat systemic allergic reactions.
• Families must have a valid prescription for injectable epinephrine before treatment starts and must demonstrate that they know how to use it.
• There must be distribution controls in every pharmacy that dispenses the product.
• Packaging will be dose specific to ensure proper at-home administration.
• Pharmacologic questionnaires will be used as data collection instruments.
• Professional and patient-focused labeling will include a medication guide and educational material.

Palforzia is not the only peanut desensitization product in the works. DBC Technology has resubmitted its biologics license application to the FDA in the hope of getting approval for its peanut allergy treatment, the Viaskin Peanut patch.

The patch is designed to desensitize allergic children aged 4-11 years through a skin-patch method known as epicutaneous immunotherapy. Results from two controlled clinical trials were included in the submission. The company is also investigating the potential of this form of skin-patch therapy for milk and egg allergies.

Correction, 9/15/19: An earlier version of this article did not clearly state that the panel recommended approval rather than granted approval for the drug.

[email protected]

A pill designed to desensitize peanut-allergic children and teenagers may be on the way.

The Food and Drug Administration’s Allergenic Products Advisory Committee has voted to recommend approval of the AR101 peanut protein capsules (Palforzia) for use in oral immunotherapy in those aged 4-17 years old with a confirmed peanut allergy. Conditions for approval include stipulations that a black-box warning and medication use guide are included in the packaging, the panel said. The FDA usually follows the recommendations of its advisory panels. 

bankrx/Getty Images

The committee members voted 7-2 that the drug was effective and 8-1 that it was safe. 

John Kelso, MD, the sole dissenter on safety, voiced concerns about the dearth of long-term follow-up in Aimmune Therapeutic’s body of research and the finding that children who received the treatment during the dose-escalation and maintenance periods had twice the number of allergic reactions requiring epinephrine, compared with those who received placebo. There are no long-term safety data to rely on yet, he added.

“Efficacy has not been demonstrated, except on the day the peanut challenge is administered,” said Dr. Kelso, an allergist at the Scripps Clinic, San Diego, adding that only long-term follow-up data would fully convince him that the drug’s benefits outweigh the risks.

In the discussion, however, other committee members pointed out that new drugs are often approved without long-term efficacy and safety data. Those data are extrapolated from clinical trials, and only real-world experience will confirm the data, they noted.

Company representatives did not explicitly address the potential cost of the therapy, but a recent review by the Institute for Clinical and Economic Review estimated the cost to be $4,200 a year. Palforzia would have to be taken every day, for an unknown amount of time, to maintain peanut tolerance.

“Using prices from analysts for AR101 ($4,200 a year), we estimated that only 41% of eligible patients could be treated in a given year without exceeding ICER’s budget impact threshold,” the institute concluded in a publicly released analysis.

Palforzia comes in individual packs of capsules filled with peanut protein, not flour. The capsules come in doses of 0.5, 1, 10, 20, and 100, and 300 mg. A single-dose sachet contains 300 mg. Treatment begins with 0.5-6 mg over 1 day and escalates every 2 weeks until 300 mg is reached or there is a reaction requiring epinephrine. Passing at least a 300-mg dose was the requirement for exiting the escalation phase and moving on to the daily, year-long maintenance phase.

The four efficacy studies presented showed that 96% of patients tolerated 300 mg, 84% tolerated 600 mg, and 63% 1,000 mg – about 10 times the reactive dose observed in the placebo controls.

“Only 125 mg of peanut protein – the amount in about half a peanut kernel – can be enough to provoke a reaction,” said Daniel Adelman, MD, chief medical officer of Aimmune. If patients can tolerate 600 mg of protein – the equivalent of two kernels, accidental ingestion will result in a “predictable, manageable” reaction.

“This is truly a clinically significant result for patients and families who report lives dictated by the allergy,” Dr. Adelman said.

Consistent manufacturing processes and positive safety data should reassure clinicians and patients that they are receiving a safe, effective, and well-regulated treatment, he added.

The capsule, however, is not a panacea. The company advises that families continue with the peanut avoidance diet. “It’s important to remember that reactive episodes can occur with dosing, and accidental exposures can occur at unpredictable times, away from home, and despite the best efforts at avoidance,” Dr. Adelman said. “This is not a drug for everyone, but it is an effective desensitization tool and would clearly be the first therapy to treat a food allergy, providing statistically significant and clinically important improvement. Outcomes align with patients’ goals.”

Safety was assessed in 709 treated patients who received the medication and 292 who received placebo. Treatment-related adverse events were most common in initial dosing: 89% of the treatment group and 58% of the placebo group experienced at least one adverse event during that time. Adverse events were mostly mild to moderate and decreased in severity over the study period. They included abdominal pain (45% active vs. 18% placebo), throat irritation (40% vs. 17%), pruritus (33% vs. 20%), vomiting (37% vs. 16%), cough (32% vs. 24%), nausea (32% vs. 14%), urticaria (28% vs. 19%), and upper abdominal pain (30% vs. 14%).

Discontinuations caused by these adverse events were infrequent, with only 1.8% of participants who were taking the active capsule and 1% of those taking placebo discontinuing the study product during initial dose escalation. Only the severe systemic allergic reactions were considered to be anaphylaxis, and they had to affect at least two body systems.

Respiratory events were more common in those in the active group, especially in children with asthma. These events included cough, wheezing, dyspnea, dysphonia, throat irritation and tightness, and exercise-induced asthma. There was, however, no “concerning change” in asthma control.

Systemic allergic reactions and anaphylaxis were more common in the active-dose group. Systemic reactions during dose escalation occurred in 9.4% of active patients and 3.8% those taking placebo. During the maintenance phase, they occurred in 8.7% and 1.7% of patients, respectively. Three patients in the active group had a serious systemic reaction – two during up-dosing and one during maintenance.

• The first dose of each progressive dose must be administered in a facility that is equipped to treat systemic allergic reactions.
• Families must have a valid prescription for injectable epinephrine before treatment starts and must demonstrate that they know how to use it.
• There must be distribution controls in every pharmacy that dispenses the product.
• Packaging will be dose specific to ensure proper at-home administration.
• Pharmacologic questionnaires will be used as data collection instruments.
• Professional and patient-focused labeling will include a medication guide and educational material.

Palforzia is not the only peanut desensitization product in the works. DBC Technology has resubmitted its biologics license application to the FDA in the hope of getting approval for its peanut allergy treatment, the Viaskin Peanut patch.

The patch is designed to desensitize allergic children aged 4-11 years through a skin-patch method known as epicutaneous immunotherapy. Results from two controlled clinical trials were included in the submission. The company is also investigating the potential of this form of skin-patch therapy for milk and egg allergies.

Correction, 9/15/19: An earlier version of this article did not clearly state that the panel recommended approval rather than granted approval for the drug.

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A pill designed to desensitize peanut-allergic children and teenagers may be on the way.

The Food and Drug Administration’s Allergenic Products Advisory Committee has voted to recommend approval of the AR101 peanut protein capsules (Palforzia) for use in oral immunotherapy in those aged 4-17 years old with a confirmed peanut allergy. Conditions for approval include stipulations that a black-box warning and medication use guide are included in the packaging, the panel said. The FDA usually follows the recommendations of its advisory panels. 

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The committee members voted 7-2 that the drug was effective and 8-1 that it was safe. 

John Kelso, MD, the sole dissenter on safety, voiced concerns about the dearth of long-term follow-up in Aimmune Therapeutic’s body of research and the finding that children who received the treatment during the dose-escalation and maintenance periods had twice the number of allergic reactions requiring epinephrine, compared with those who received placebo. There are no long-term safety data to rely on yet, he added.

“Efficacy has not been demonstrated, except on the day the peanut challenge is administered,” said Dr. Kelso, an allergist at the Scripps Clinic, San Diego, adding that only long-term follow-up data would fully convince him that the drug’s benefits outweigh the risks.

In the discussion, however, other committee members pointed out that new drugs are often approved without long-term efficacy and safety data. Those data are extrapolated from clinical trials, and only real-world experience will confirm the data, they noted.

Company representatives did not explicitly address the potential cost of the therapy, but a recent review by the Institute for Clinical and Economic Review estimated the cost to be $4,200 a year. Palforzia would have to be taken every day, for an unknown amount of time, to maintain peanut tolerance.

“Using prices from analysts for AR101 ($4,200 a year), we estimated that only 41% of eligible patients could be treated in a given year without exceeding ICER’s budget impact threshold,” the institute concluded in a publicly released analysis.

Palforzia comes in individual packs of capsules filled with peanut protein, not flour. The capsules come in doses of 0.5, 1, 10, 20, and 100, and 300 mg. A single-dose sachet contains 300 mg. Treatment begins with 0.5-6 mg over 1 day and escalates every 2 weeks until 300 mg is reached or there is a reaction requiring epinephrine. Passing at least a 300-mg dose was the requirement for exiting the escalation phase and moving on to the daily, year-long maintenance phase.

The four efficacy studies presented showed that 96% of patients tolerated 300 mg, 84% tolerated 600 mg, and 63% 1,000 mg – about 10 times the reactive dose observed in the placebo controls.

“Only 125 mg of peanut protein – the amount in about half a peanut kernel – can be enough to provoke a reaction,” said Daniel Adelman, MD, chief medical officer of Aimmune. If patients can tolerate 600 mg of protein – the equivalent of two kernels, accidental ingestion will result in a “predictable, manageable” reaction.

“This is truly a clinically significant result for patients and families who report lives dictated by the allergy,” Dr. Adelman said.

Consistent manufacturing processes and positive safety data should reassure clinicians and patients that they are receiving a safe, effective, and well-regulated treatment, he added.

The capsule, however, is not a panacea. The company advises that families continue with the peanut avoidance diet. “It’s important to remember that reactive episodes can occur with dosing, and accidental exposures can occur at unpredictable times, away from home, and despite the best efforts at avoidance,” Dr. Adelman said. “This is not a drug for everyone, but it is an effective desensitization tool and would clearly be the first therapy to treat a food allergy, providing statistically significant and clinically important improvement. Outcomes align with patients’ goals.”

Safety was assessed in 709 treated patients who received the medication and 292 who received placebo. Treatment-related adverse events were most common in initial dosing: 89% of the treatment group and 58% of the placebo group experienced at least one adverse event during that time. Adverse events were mostly mild to moderate and decreased in severity over the study period. They included abdominal pain (45% active vs. 18% placebo), throat irritation (40% vs. 17%), pruritus (33% vs. 20%), vomiting (37% vs. 16%), cough (32% vs. 24%), nausea (32% vs. 14%), urticaria (28% vs. 19%), and upper abdominal pain (30% vs. 14%).

Discontinuations caused by these adverse events were infrequent, with only 1.8% of participants who were taking the active capsule and 1% of those taking placebo discontinuing the study product during initial dose escalation. Only the severe systemic allergic reactions were considered to be anaphylaxis, and they had to affect at least two body systems.

Respiratory events were more common in those in the active group, especially in children with asthma. These events included cough, wheezing, dyspnea, dysphonia, throat irritation and tightness, and exercise-induced asthma. There was, however, no “concerning change” in asthma control.

Systemic allergic reactions and anaphylaxis were more common in the active-dose group. Systemic reactions during dose escalation occurred in 9.4% of active patients and 3.8% those taking placebo. During the maintenance phase, they occurred in 8.7% and 1.7% of patients, respectively. Three patients in the active group had a serious systemic reaction – two during up-dosing and one during maintenance.

• The first dose of each progressive dose must be administered in a facility that is equipped to treat systemic allergic reactions.
• Families must have a valid prescription for injectable epinephrine before treatment starts and must demonstrate that they know how to use it.
• There must be distribution controls in every pharmacy that dispenses the product.
• Packaging will be dose specific to ensure proper at-home administration.
• Pharmacologic questionnaires will be used as data collection instruments.
• Professional and patient-focused labeling will include a medication guide and educational material.

Palforzia is not the only peanut desensitization product in the works. DBC Technology has resubmitted its biologics license application to the FDA in the hope of getting approval for its peanut allergy treatment, the Viaskin Peanut patch.

The patch is designed to desensitize allergic children aged 4-11 years through a skin-patch method known as epicutaneous immunotherapy. Results from two controlled clinical trials were included in the submission. The company is also investigating the potential of this form of skin-patch therapy for milk and egg allergies.

Correction, 9/15/19: An earlier version of this article did not clearly state that the panel recommended approval rather than granted approval for the drug.

[email protected]

The Food and Drug Administration has approved mepolizumab (Nucala, 40 mg subcutaneous) for patients aged 6-11 years with severe eosinophilic asthma, according to a release from GlaxoSmithKline, which developed the drug. This is the first targeted biologic approved for this condition in this age group.

Olivier Le Moal/Getty Images

The approval is supported by both an open-label study in children aged 6-11 years and evidence from other trials conducted in adults and adolescents. The 52-week, long-term study in these younger patients investigated pharmacokinetics, pharmacodynamics, and safety, the last of which was shown to be similar to that seen in older patients.

Hypersensitivity reactions, such as anaphylaxis, rash, and bronchospasm, have been associated with mepolizumab. It should not be used to treat acute bronchospasm or status asthmaticus, nor should systemic or inhaled corticosteroids be stopped abruptly after initiating mepolizumab treatment. Common adverse events include headache, injection-site reactions, back pain, and fatigue. Injection site reactions (such as pain, erythema, and itching) occurred in 8% of mepolizumab patients treated with 100 mg of the drug versus 3% of placebo patients.

The monoclonal antibody targeting interleukin-5 was first approved for severe eosinophilic asthma in 2015 for ages 12 years and older and in ages 6 years and older in the European Union in August 2018. It inhibits IL-5 from binding to eosinophils, which reduces the presence of eosinophils in blood without completely eliminating them.

[email protected]

The Food and Drug Administration has approved mepolizumab (Nucala, 40 mg subcutaneous) for patients aged 6-11 years with severe eosinophilic asthma, according to a release from GlaxoSmithKline, which developed the drug. This is the first targeted biologic approved for this condition in this age group.

Olivier Le Moal/Getty Images

The approval is supported by both an open-label study in children aged 6-11 years and evidence from other trials conducted in adults and adolescents. The 52-week, long-term study in these younger patients investigated pharmacokinetics, pharmacodynamics, and safety, the last of which was shown to be similar to that seen in older patients.

Hypersensitivity reactions, such as anaphylaxis, rash, and bronchospasm, have been associated with mepolizumab. It should not be used to treat acute bronchospasm or status asthmaticus, nor should systemic or inhaled corticosteroids be stopped abruptly after initiating mepolizumab treatment. Common adverse events include headache, injection-site reactions, back pain, and fatigue. Injection site reactions (such as pain, erythema, and itching) occurred in 8% of mepolizumab patients treated with 100 mg of the drug versus 3% of placebo patients.

The monoclonal antibody targeting interleukin-5 was first approved for severe eosinophilic asthma in 2015 for ages 12 years and older and in ages 6 years and older in the European Union in August 2018. It inhibits IL-5 from binding to eosinophils, which reduces the presence of eosinophils in blood without completely eliminating them.

[email protected]

The Food and Drug Administration has approved mepolizumab (Nucala, 40 mg subcutaneous) for patients aged 6-11 years with severe eosinophilic asthma, according to a release from GlaxoSmithKline, which developed the drug. This is the first targeted biologic approved for this condition in this age group.

Olivier Le Moal/Getty Images

The approval is supported by both an open-label study in children aged 6-11 years and evidence from other trials conducted in adults and adolescents. The 52-week, long-term study in these younger patients investigated pharmacokinetics, pharmacodynamics, and safety, the last of which was shown to be similar to that seen in older patients.

Hypersensitivity reactions, such as anaphylaxis, rash, and bronchospasm, have been associated with mepolizumab. It should not be used to treat acute bronchospasm or status asthmaticus, nor should systemic or inhaled corticosteroids be stopped abruptly after initiating mepolizumab treatment. Common adverse events include headache, injection-site reactions, back pain, and fatigue. Injection site reactions (such as pain, erythema, and itching) occurred in 8% of mepolizumab patients treated with 100 mg of the drug versus 3% of placebo patients.

The monoclonal antibody targeting interleukin-5 was first approved for severe eosinophilic asthma in 2015 for ages 12 years and older and in ages 6 years and older in the European Union in August 2018. It inhibits IL-5 from binding to eosinophils, which reduces the presence of eosinophils in blood without completely eliminating them.

[email protected]

Participation in sports, competitive team sports in particular, is very good for the physical well-being and emotional development of children and adolescents. Specifically, there is growing evidence that sports promote healthy development socially and emotionally, protecting against drug use, poor body image, and against psychiatric illness in youth.

©photoaged/FOTOLIA

Sustaining academic productivity and team sports is demanding. By the middle of autumn, the amount of homework can begin to wear on teenagers, and the burden of getting them to practices and games can wear on parents. It can be very tempting for youth and their parents to drop team sports in high school, and turn their time and effort more completely to the serious work of school. But advocating for your patients and their parents to protect the time for team sports participation will pay dividends in the health and well-being of your patients and may even support rather than detract from academic performance.

The benefits of regular exercise for physical health are well established. Most teenagers do not get the recommended 60 minutes daily of moderate to vigorous physical activity. Participating in a team sport enforces this level of activity, in ways that parents typically don’t have to enforce. This level of physical activity typically promotes healthy eating and a healthy weight. Daily exercise promotes adequate, restful sleep, one of the most critical (and usually compromised) components of adolescent health. These exercise habits are easier to maintain into adulthood – when they protect against cardiovascular and inflammatory diseases – if they have been established early.

Beyond physical health, participation in team sports has been shown to promote good mental health and protect against psychiatric illnesses. High school athletes have lower rates of anxiety and depression than those of their peers. They generally are less likely to use drugs and more likely to have a healthy body image than are their nonathlete peers. It is worth noting that the mental health benefits of team sports are even more robust than the benefits of solitary exercise in teenagers,¹ possibly because of the social connections to peers and adults that grow out of them.

While student athletes benefit from the opportunity to develop deep social connections – ones forged in the intense setting of competition, collaboration, and sustained teamwork – they also benefit from strong mentorship connections with adults, including coaches, trainers, and even the parents of teammates who participate in all of the efforts that go into team sports in youth. While it might seem that all of the mental and physical benefits must be offset by lower academic performance, it turns out that is not the case. It is well established that regular exercise promotes healthy cognitive function, including processing speed, working memory, and even creativity. According to data from the Monitoring the Future survey, adolescents who participated in team sports were more likely to have As and to plan on attending a 4-year college than were their nonathlete peers.

Beyond the physiologic and social benefits of exercise, team sports provide adolescents with a powerful opportunity to get comfortable with failure. Even the best athletes cannot win all the time, and sports are unique in building failure into the work. Practice is almost entirely about failure, gradually getting better at something that is difficult. While everyone aims to win, they also prepare to struggle and lose. Athletes must learn how to persevere through a match that they are losing, and then pick themselves up and prepare again for the next match. When young people get comfortable with facing and managing challenges, managing setbacks and failure, they are ready to face the larger challenges, setbacks, and failures of adult life.

Team sports enable young people to learn what they are actually capable of managing – they build resilience. This promotion of resilience is illustrated in recent research that demonstrated that team sports may be especially protective for young people who have experienced trauma (adverse childhood experiences, or “ACEs”). Researchers at the University of California, Los Angeles, followed teenagers with and without high ACE scores into their mid 20s. They found that those with high ACE scores who participated in team sports as adolescents were 24% less likely to have depression and 30% less likely to have anxiety diagnoses as adults, compared with their peers who did not participate in team sports.²

Of course, the details matter in team sports. If your patients are participating and they or their parents are worried about spending so much time on something other than homework, talk to them about all of these exceptional benefits of team sports. But the culture of the team matters also. Some teams may be focused on winning at all costs, or have a practice culture that is humiliating or bullying. Some teams may have a culture of partying after games, with binge drinking and drug use. Ask your patients about whether they feel they are respected members of the team, and if effort and sportsmanship are valued as well as performance. Do they trust their coaches? Do they believe their coaches know and care about them? If your patients are not participating in a team sport, encourage them to find one (or more) that engage their interests. The benefits of track and field, crew, and tennis can be just as robust as the benefits of football or soccer. Speak with your patients and their parents about the payoff for their physical, mental, and developmental health the time and effort they are putting into a team sport can provide.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Int J Nutr Phys Act. 2013 Aug 15. doi: 10.1186/1479-5868-10-98.

2. JAMA Pediatr. 2019 Jul 1;173(7):681-8.

Participation in sports, competitive team sports in particular, is very good for the physical well-being and emotional development of children and adolescents. Specifically, there is growing evidence that sports promote healthy development socially and emotionally, protecting against drug use, poor body image, and against psychiatric illness in youth.

©photoaged/FOTOLIA

Sustaining academic productivity and team sports is demanding. By the middle of autumn, the amount of homework can begin to wear on teenagers, and the burden of getting them to practices and games can wear on parents. It can be very tempting for youth and their parents to drop team sports in high school, and turn their time and effort more completely to the serious work of school. But advocating for your patients and their parents to protect the time for team sports participation will pay dividends in the health and well-being of your patients and may even support rather than detract from academic performance.

The benefits of regular exercise for physical health are well established. Most teenagers do not get the recommended 60 minutes daily of moderate to vigorous physical activity. Participating in a team sport enforces this level of activity, in ways that parents typically don’t have to enforce. This level of physical activity typically promotes healthy eating and a healthy weight. Daily exercise promotes adequate, restful sleep, one of the most critical (and usually compromised) components of adolescent health. These exercise habits are easier to maintain into adulthood – when they protect against cardiovascular and inflammatory diseases – if they have been established early.

Beyond physical health, participation in team sports has been shown to promote good mental health and protect against psychiatric illnesses. High school athletes have lower rates of anxiety and depression than those of their peers. They generally are less likely to use drugs and more likely to have a healthy body image than are their nonathlete peers. It is worth noting that the mental health benefits of team sports are even more robust than the benefits of solitary exercise in teenagers,¹ possibly because of the social connections to peers and adults that grow out of them.

While student athletes benefit from the opportunity to develop deep social connections – ones forged in the intense setting of competition, collaboration, and sustained teamwork – they also benefit from strong mentorship connections with adults, including coaches, trainers, and even the parents of teammates who participate in all of the efforts that go into team sports in youth. While it might seem that all of the mental and physical benefits must be offset by lower academic performance, it turns out that is not the case. It is well established that regular exercise promotes healthy cognitive function, including processing speed, working memory, and even creativity. According to data from the Monitoring the Future survey, adolescents who participated in team sports were more likely to have As and to plan on attending a 4-year college than were their nonathlete peers.

Beyond the physiologic and social benefits of exercise, team sports provide adolescents with a powerful opportunity to get comfortable with failure. Even the best athletes cannot win all the time, and sports are unique in building failure into the work. Practice is almost entirely about failure, gradually getting better at something that is difficult. While everyone aims to win, they also prepare to struggle and lose. Athletes must learn how to persevere through a match that they are losing, and then pick themselves up and prepare again for the next match. When young people get comfortable with facing and managing challenges, managing setbacks and failure, they are ready to face the larger challenges, setbacks, and failures of adult life.

Team sports enable young people to learn what they are actually capable of managing – they build resilience. This promotion of resilience is illustrated in recent research that demonstrated that team sports may be especially protective for young people who have experienced trauma (adverse childhood experiences, or “ACEs”). Researchers at the University of California, Los Angeles, followed teenagers with and without high ACE scores into their mid 20s. They found that those with high ACE scores who participated in team sports as adolescents were 24% less likely to have depression and 30% less likely to have anxiety diagnoses as adults, compared with their peers who did not participate in team sports.²

Of course, the details matter in team sports. If your patients are participating and they or their parents are worried about spending so much time on something other than homework, talk to them about all of these exceptional benefits of team sports. But the culture of the team matters also. Some teams may be focused on winning at all costs, or have a practice culture that is humiliating or bullying. Some teams may have a culture of partying after games, with binge drinking and drug use. Ask your patients about whether they feel they are respected members of the team, and if effort and sportsmanship are valued as well as performance. Do they trust their coaches? Do they believe their coaches know and care about them? If your patients are not participating in a team sport, encourage them to find one (or more) that engage their interests. The benefits of track and field, crew, and tennis can be just as robust as the benefits of football or soccer. Speak with your patients and their parents about the payoff for their physical, mental, and developmental health the time and effort they are putting into a team sport can provide.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Int J Nutr Phys Act. 2013 Aug 15. doi: 10.1186/1479-5868-10-98.

2. JAMA Pediatr. 2019 Jul 1;173(7):681-8.

Participation in sports, competitive team sports in particular, is very good for the physical well-being and emotional development of children and adolescents. Specifically, there is growing evidence that sports promote healthy development socially and emotionally, protecting against drug use, poor body image, and against psychiatric illness in youth.

©photoaged/FOTOLIA

Sustaining academic productivity and team sports is demanding. By the middle of autumn, the amount of homework can begin to wear on teenagers, and the burden of getting them to practices and games can wear on parents. It can be very tempting for youth and their parents to drop team sports in high school, and turn their time and effort more completely to the serious work of school. But advocating for your patients and their parents to protect the time for team sports participation will pay dividends in the health and well-being of your patients and may even support rather than detract from academic performance.

The benefits of regular exercise for physical health are well established. Most teenagers do not get the recommended 60 minutes daily of moderate to vigorous physical activity. Participating in a team sport enforces this level of activity, in ways that parents typically don’t have to enforce. This level of physical activity typically promotes healthy eating and a healthy weight. Daily exercise promotes adequate, restful sleep, one of the most critical (and usually compromised) components of adolescent health. These exercise habits are easier to maintain into adulthood – when they protect against cardiovascular and inflammatory diseases – if they have been established early.

Beyond physical health, participation in team sports has been shown to promote good mental health and protect against psychiatric illnesses. High school athletes have lower rates of anxiety and depression than those of their peers. They generally are less likely to use drugs and more likely to have a healthy body image than are their nonathlete peers. It is worth noting that the mental health benefits of team sports are even more robust than the benefits of solitary exercise in teenagers,¹ possibly because of the social connections to peers and adults that grow out of them.

While student athletes benefit from the opportunity to develop deep social connections – ones forged in the intense setting of competition, collaboration, and sustained teamwork – they also benefit from strong mentorship connections with adults, including coaches, trainers, and even the parents of teammates who participate in all of the efforts that go into team sports in youth. While it might seem that all of the mental and physical benefits must be offset by lower academic performance, it turns out that is not the case. It is well established that regular exercise promotes healthy cognitive function, including processing speed, working memory, and even creativity. According to data from the Monitoring the Future survey, adolescents who participated in team sports were more likely to have As and to plan on attending a 4-year college than were their nonathlete peers.

Beyond the physiologic and social benefits of exercise, team sports provide adolescents with a powerful opportunity to get comfortable with failure. Even the best athletes cannot win all the time, and sports are unique in building failure into the work. Practice is almost entirely about failure, gradually getting better at something that is difficult. While everyone aims to win, they also prepare to struggle and lose. Athletes must learn how to persevere through a match that they are losing, and then pick themselves up and prepare again for the next match. When young people get comfortable with facing and managing challenges, managing setbacks and failure, they are ready to face the larger challenges, setbacks, and failures of adult life.

Team sports enable young people to learn what they are actually capable of managing – they build resilience. This promotion of resilience is illustrated in recent research that demonstrated that team sports may be especially protective for young people who have experienced trauma (adverse childhood experiences, or “ACEs”). Researchers at the University of California, Los Angeles, followed teenagers with and without high ACE scores into their mid 20s. They found that those with high ACE scores who participated in team sports as adolescents were 24% less likely to have depression and 30% less likely to have anxiety diagnoses as adults, compared with their peers who did not participate in team sports.²

Of course, the details matter in team sports. If your patients are participating and they or their parents are worried about spending so much time on something other than homework, talk to them about all of these exceptional benefits of team sports. But the culture of the team matters also. Some teams may be focused on winning at all costs, or have a practice culture that is humiliating or bullying. Some teams may have a culture of partying after games, with binge drinking and drug use. Ask your patients about whether they feel they are respected members of the team, and if effort and sportsmanship are valued as well as performance. Do they trust their coaches? Do they believe their coaches know and care about them? If your patients are not participating in a team sport, encourage them to find one (or more) that engage their interests. The benefits of track and field, crew, and tennis can be just as robust as the benefits of football or soccer. Speak with your patients and their parents about the payoff for their physical, mental, and developmental health the time and effort they are putting into a team sport can provide.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Int J Nutr Phys Act. 2013 Aug 15. doi: 10.1186/1479-5868-10-98.

2. JAMA Pediatr. 2019 Jul 1;173(7):681-8.

NEW ORLEANS – In children, ambulatory systolic daytime blood pressure load – the amount of time spent above the 95^th blood pressure percentile for age and height – predicts cardiovascular target-organ damage, specifically diastolic dysfunction and arterial stiffness, according to an investigation from the American Heart Association Strategically Focused Research Network.

M. Alexander Otto/MDedge News

Blood pressure load is considered in the 2017 American Academy of Pediatrics BP guideline, but the new findings add granularity on how to use it in practice. It’s part of an effort “to supply data to guide future guidelines, rather than arbitrarily picking a number – the 95th percentile – out of the sky,” said lead investigator and pediatric cardiologist Elaine Urbina, MD, director of preventative cardiology at the Cincinnati Children’s Hospital Medical Center, and senior author on the 2017 guideline.

In the absence of data linking specific BP levels to hard cardiovascular outcomes, as in adults, “we feel that load is helpful in determining risk categories for kids as we make decisions about who should get lifestyle counseling and who should get medication. It gets a little bit at blood pressure variability” and supplements the arbitrary 95th-percentile threshold, she said.

“If I saw a child with only a mild elevation of mean ambulatory blood pressure but they had increased load, it would prompt me to order an echocardiogram to look for target organ damage, which may then change my therapy from lifestyle to medication,” Dr. Urbina said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

These conclusions come from an investigation of 339 healthy adolescents with a mean age of 15.6 years at six sites across the United States. Office BP was averaged over six readings during two visits, and ambulatory pressure was taken every 20 minutes over 26 hours. BP load was correlated with measures of left ventricular mass index (LVMI), systolic and diastolic function (E/e’ ratio), and pulse wave velocity (PWV), a gauge of arterial stiffness.

Overall, 215 subjects spent less than 25% of their time above the 95th percentile and were classified as the low-load group, 62 were above that mark 25%-49% of the time (mid-load group), and 62 were over it at least half of the time (high-load group).

Both load category and load as a continuous variable were significant predictors of arterial stiffness and diastolic dysfunction even after adjustment for age, sex, body mass index, and mean daytime ambulatory systolic blood pressure (P less than 0.0001).

Subjects in the high-load group, for instance, had a PWV above 5.5 m/sec, versus about 5.2 m/sec and less than 5 m/sec in the mid- and low-load groups, respectively. The high-load group had an E/e’ ratio above 7, versus 6 or less in the other groups. There was a trend for higher LVMI and reduced strain as well in the low- versus high-load groups.

Although the findings don’t indicate clinically relevant cardiovascular damage, children with higher loads seem to be “on the road to getting it,” Dr. Urbina said. Greater arterial stiffness means that high pulsatile pressures are transmitted to the microvasculature. Meanwhile, “the strength of the relationship with diastolic dysfunction worries me. It’s a precursor of heart failure with preserved ejection fraction, for which there are no effective therapies. We have to identify the precursors early and treat them so these kids don’t get heart failure later in life.”

Almost two-thirds of the subjects were white, most of the remainder were black, and 58% were boys. There were no statistically significant differences in age, race, sex, or body mass index across the groups, but overall, the children were overweight, and those with high BP load were more insulin resistant and had higher clinic and ambulatory BPs.

The team is assessing cognitive performance as a function of BP load.

Ambulatory pressures were taken by the Spacelabs OnTrak monitor.

The work was funded by the AHA and the National Institutes of Health. The investigators had no commercial disclosures.

[email protected]

SOURCE: Urbina E. Joint Hypertension 2019, Abstract P2056.

NEW ORLEANS – In children, ambulatory systolic daytime blood pressure load – the amount of time spent above the 95^th blood pressure percentile for age and height – predicts cardiovascular target-organ damage, specifically diastolic dysfunction and arterial stiffness, according to an investigation from the American Heart Association Strategically Focused Research Network.

M. Alexander Otto/MDedge News

Blood pressure load is considered in the 2017 American Academy of Pediatrics BP guideline, but the new findings add granularity on how to use it in practice. It’s part of an effort “to supply data to guide future guidelines, rather than arbitrarily picking a number – the 95th percentile – out of the sky,” said lead investigator and pediatric cardiologist Elaine Urbina, MD, director of preventative cardiology at the Cincinnati Children’s Hospital Medical Center, and senior author on the 2017 guideline.

In the absence of data linking specific BP levels to hard cardiovascular outcomes, as in adults, “we feel that load is helpful in determining risk categories for kids as we make decisions about who should get lifestyle counseling and who should get medication. It gets a little bit at blood pressure variability” and supplements the arbitrary 95th-percentile threshold, she said.

“If I saw a child with only a mild elevation of mean ambulatory blood pressure but they had increased load, it would prompt me to order an echocardiogram to look for target organ damage, which may then change my therapy from lifestyle to medication,” Dr. Urbina said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

These conclusions come from an investigation of 339 healthy adolescents with a mean age of 15.6 years at six sites across the United States. Office BP was averaged over six readings during two visits, and ambulatory pressure was taken every 20 minutes over 26 hours. BP load was correlated with measures of left ventricular mass index (LVMI), systolic and diastolic function (E/e’ ratio), and pulse wave velocity (PWV), a gauge of arterial stiffness.

Overall, 215 subjects spent less than 25% of their time above the 95th percentile and were classified as the low-load group, 62 were above that mark 25%-49% of the time (mid-load group), and 62 were over it at least half of the time (high-load group).

Both load category and load as a continuous variable were significant predictors of arterial stiffness and diastolic dysfunction even after adjustment for age, sex, body mass index, and mean daytime ambulatory systolic blood pressure (P less than 0.0001).

Subjects in the high-load group, for instance, had a PWV above 5.5 m/sec, versus about 5.2 m/sec and less than 5 m/sec in the mid- and low-load groups, respectively. The high-load group had an E/e’ ratio above 7, versus 6 or less in the other groups. There was a trend for higher LVMI and reduced strain as well in the low- versus high-load groups.

Although the findings don’t indicate clinically relevant cardiovascular damage, children with higher loads seem to be “on the road to getting it,” Dr. Urbina said. Greater arterial stiffness means that high pulsatile pressures are transmitted to the microvasculature. Meanwhile, “the strength of the relationship with diastolic dysfunction worries me. It’s a precursor of heart failure with preserved ejection fraction, for which there are no effective therapies. We have to identify the precursors early and treat them so these kids don’t get heart failure later in life.”

Almost two-thirds of the subjects were white, most of the remainder were black, and 58% were boys. There were no statistically significant differences in age, race, sex, or body mass index across the groups, but overall, the children were overweight, and those with high BP load were more insulin resistant and had higher clinic and ambulatory BPs.

The team is assessing cognitive performance as a function of BP load.

Ambulatory pressures were taken by the Spacelabs OnTrak monitor.

The work was funded by the AHA and the National Institutes of Health. The investigators had no commercial disclosures.

[email protected]

SOURCE: Urbina E. Joint Hypertension 2019, Abstract P2056.

NEW ORLEANS – In children, ambulatory systolic daytime blood pressure load – the amount of time spent above the 95^th blood pressure percentile for age and height – predicts cardiovascular target-organ damage, specifically diastolic dysfunction and arterial stiffness, according to an investigation from the American Heart Association Strategically Focused Research Network.

M. Alexander Otto/MDedge News

Blood pressure load is considered in the 2017 American Academy of Pediatrics BP guideline, but the new findings add granularity on how to use it in practice. It’s part of an effort “to supply data to guide future guidelines, rather than arbitrarily picking a number – the 95th percentile – out of the sky,” said lead investigator and pediatric cardiologist Elaine Urbina, MD, director of preventative cardiology at the Cincinnati Children’s Hospital Medical Center, and senior author on the 2017 guideline.

In the absence of data linking specific BP levels to hard cardiovascular outcomes, as in adults, “we feel that load is helpful in determining risk categories for kids as we make decisions about who should get lifestyle counseling and who should get medication. It gets a little bit at blood pressure variability” and supplements the arbitrary 95th-percentile threshold, she said.

“If I saw a child with only a mild elevation of mean ambulatory blood pressure but they had increased load, it would prompt me to order an echocardiogram to look for target organ damage, which may then change my therapy from lifestyle to medication,” Dr. Urbina said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

These conclusions come from an investigation of 339 healthy adolescents with a mean age of 15.6 years at six sites across the United States. Office BP was averaged over six readings during two visits, and ambulatory pressure was taken every 20 minutes over 26 hours. BP load was correlated with measures of left ventricular mass index (LVMI), systolic and diastolic function (E/e’ ratio), and pulse wave velocity (PWV), a gauge of arterial stiffness.

Overall, 215 subjects spent less than 25% of their time above the 95th percentile and were classified as the low-load group, 62 were above that mark 25%-49% of the time (mid-load group), and 62 were over it at least half of the time (high-load group).

Both load category and load as a continuous variable were significant predictors of arterial stiffness and diastolic dysfunction even after adjustment for age, sex, body mass index, and mean daytime ambulatory systolic blood pressure (P less than 0.0001).

Subjects in the high-load group, for instance, had a PWV above 5.5 m/sec, versus about 5.2 m/sec and less than 5 m/sec in the mid- and low-load groups, respectively. The high-load group had an E/e’ ratio above 7, versus 6 or less in the other groups. There was a trend for higher LVMI and reduced strain as well in the low- versus high-load groups.

Although the findings don’t indicate clinically relevant cardiovascular damage, children with higher loads seem to be “on the road to getting it,” Dr. Urbina said. Greater arterial stiffness means that high pulsatile pressures are transmitted to the microvasculature. Meanwhile, “the strength of the relationship with diastolic dysfunction worries me. It’s a precursor of heart failure with preserved ejection fraction, for which there are no effective therapies. We have to identify the precursors early and treat them so these kids don’t get heart failure later in life.”

Almost two-thirds of the subjects were white, most of the remainder were black, and 58% were boys. There were no statistically significant differences in age, race, sex, or body mass index across the groups, but overall, the children were overweight, and those with high BP load were more insulin resistant and had higher clinic and ambulatory BPs.

The team is assessing cognitive performance as a function of BP load.

Ambulatory pressures were taken by the Spacelabs OnTrak monitor.

The work was funded by the AHA and the National Institutes of Health. The investigators had no commercial disclosures.

[email protected]

SOURCE: Urbina E. Joint Hypertension 2019, Abstract P2056.

Grace is a 15-year-old girl in the 10th grade whom you have been treating for anxiety. Family history also is notable for her father having an anxiety disorder. She has been taking an SSRI and is engaged in therapy, which has resulted in some improvement in symptoms. She can become overwhelmed when taking tests, and she has breakthrough anxiety in social situations and occasional difficulties with sleep. She denies using any substances. Her parents, who have come to her appointment with her, noted that while they see some progress, they would like to try more natural interventions. They had done some research on cannabidiol (CBD), and Grace’s father said that using it has tremendously helped his sleep. They inquired about Grace using it as well.

Bhupi/Getty Images

Discussion

CBD use has dramatically increased over the past few years, and in many places can be found in gummies, chocolate, tinctures, and other forms at grocery and convenience stores, in addition to being widely available online. It is a nonpsychoactive compound (versus tetrahydrocannabinol or THC) found in the Cannabis sativa plant. The Farm Bill, which was passed in 2018, legalized production of hemp or the cannabis plant with a THC concentration less than 0.3%. This bill additionally maintained the Food and Drug Administration’s oversight with CBD. States may have laws that are more restrictive about use. CBD was approved in 2018 by the FDA for treatment of Lennox-Gastaut syndrome and Dravet syndrome in individuals 2 years of age and older, and is categorized as a schedule I substance due to its being derived from the cannabis plant.

In randomized, double-blind, placebo-controlled trials leading to CBD’s approval, the most common side effects were drowsiness, insomnia, disrupted sleep, sedation, malaise, weakness, decreased appetite, diarrhea, elevated liver enzymes, rash, and infections. CBD also carries a warning about the potential for suicidal ideation, agitation, new or worsening depression, aggression, and panic attacks.¹ In in vitro and animal studies, CBD has been found to affect growth of tumor cell lines, to have no effects on embryonic development, and to potentially cause some drug-drug interactions through inhibition of CYP2C9, CYP2C19, and CYP3A4. However, the clinical relevance currently is unknown. Animal studies also indicate potential efficacy in decreasing anxiety.²

CBD has been promoted as being effective in treating a number of ailments including migraines, chronic pain, insomnia, ADHD, and anxiety. Multiple anecdotal reports tout the benefits. In a study exploring abuse potential, there were no significant findings, and CBD was generally well tolerated in open trials exploring potential clinical benefits. A retrospective feasibility study – conducted in Israel – exploring use of CBD to decrease problematic behaviors in youth with autism spectrum disorder demonstrated improvement in communication, anxiety, disruptive behaviors, and parental stress.³

• There is potential lack of clarity regarding legality of use in some states. Based on federal law, it is legal to possess CBD derived from hemp, but state laws may differ.
• There is lack of oversight regarding monitoring what is in each supplement. Lab testing for CBD to determine contents is not mandatory in every state. The amount of active compound as well as other ingredients may not be consistent or accurate. According to the FDA, CBD-containing products cannot claim to have health benefits, treat disease, or be sold as dietary supplements without its approval.
• Clear information about appropriate dosing for children is limited.
• Varying delivery systems could affect absorption and bioavailability of CBD.
• Information is lacking regarding potential drug-drug interactions.
• There is a lack of information regarding effects of long-term use.

Use of CBD is an area with significant interest and potential for growth. Although risks are thought to be low overall, there likely is insufficient evidence at this time to actively recommend its use. Additional research in human subjects exploring effective and safe dosing, tolerability, as well as use in special populations (including children, pregnant women, elderly) is needed.
 

Dr. Strange is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and University of Vermont Robert Larner College of Medicine, both in Burlington. She works with children and adolescents. She has no relevant financial disclosures. Email her at [email protected].

References

1. “FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy,” FDA news release, June 25, 2018.

2. Cannabidiol (CBD) Critical Review Report. Expert Committee on Drug Dependence Fortieth Meeting. World Health Organization. Geneva June 4-7, 2018.

3. J Autism Dev Disord. 2019 Mar;49(3):1284-8.

Grace is a 15-year-old girl in the 10th grade whom you have been treating for anxiety. Family history also is notable for her father having an anxiety disorder. She has been taking an SSRI and is engaged in therapy, which has resulted in some improvement in symptoms. She can become overwhelmed when taking tests, and she has breakthrough anxiety in social situations and occasional difficulties with sleep. She denies using any substances. Her parents, who have come to her appointment with her, noted that while they see some progress, they would like to try more natural interventions. They had done some research on cannabidiol (CBD), and Grace’s father said that using it has tremendously helped his sleep. They inquired about Grace using it as well.

Bhupi/Getty Images

Discussion

CBD use has dramatically increased over the past few years, and in many places can be found in gummies, chocolate, tinctures, and other forms at grocery and convenience stores, in addition to being widely available online. It is a nonpsychoactive compound (versus tetrahydrocannabinol or THC) found in the Cannabis sativa plant. The Farm Bill, which was passed in 2018, legalized production of hemp or the cannabis plant with a THC concentration less than 0.3%. This bill additionally maintained the Food and Drug Administration’s oversight with CBD. States may have laws that are more restrictive about use. CBD was approved in 2018 by the FDA for treatment of Lennox-Gastaut syndrome and Dravet syndrome in individuals 2 years of age and older, and is categorized as a schedule I substance due to its being derived from the cannabis plant.

In randomized, double-blind, placebo-controlled trials leading to CBD’s approval, the most common side effects were drowsiness, insomnia, disrupted sleep, sedation, malaise, weakness, decreased appetite, diarrhea, elevated liver enzymes, rash, and infections. CBD also carries a warning about the potential for suicidal ideation, agitation, new or worsening depression, aggression, and panic attacks.¹ In in vitro and animal studies, CBD has been found to affect growth of tumor cell lines, to have no effects on embryonic development, and to potentially cause some drug-drug interactions through inhibition of CYP2C9, CYP2C19, and CYP3A4. However, the clinical relevance currently is unknown. Animal studies also indicate potential efficacy in decreasing anxiety.²

CBD has been promoted as being effective in treating a number of ailments including migraines, chronic pain, insomnia, ADHD, and anxiety. Multiple anecdotal reports tout the benefits. In a study exploring abuse potential, there were no significant findings, and CBD was generally well tolerated in open trials exploring potential clinical benefits. A retrospective feasibility study – conducted in Israel – exploring use of CBD to decrease problematic behaviors in youth with autism spectrum disorder demonstrated improvement in communication, anxiety, disruptive behaviors, and parental stress.³

• There is potential lack of clarity regarding legality of use in some states. Based on federal law, it is legal to possess CBD derived from hemp, but state laws may differ.
• There is lack of oversight regarding monitoring what is in each supplement. Lab testing for CBD to determine contents is not mandatory in every state. The amount of active compound as well as other ingredients may not be consistent or accurate. According to the FDA, CBD-containing products cannot claim to have health benefits, treat disease, or be sold as dietary supplements without its approval.
• Clear information about appropriate dosing for children is limited.
• Varying delivery systems could affect absorption and bioavailability of CBD.
• Information is lacking regarding potential drug-drug interactions.
• There is a lack of information regarding effects of long-term use.

Use of CBD is an area with significant interest and potential for growth. Although risks are thought to be low overall, there likely is insufficient evidence at this time to actively recommend its use. Additional research in human subjects exploring effective and safe dosing, tolerability, as well as use in special populations (including children, pregnant women, elderly) is needed.
 

Dr. Strange is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and University of Vermont Robert Larner College of Medicine, both in Burlington. She works with children and adolescents. She has no relevant financial disclosures. Email her at [email protected].

References

1. “FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy,” FDA news release, June 25, 2018.

2. Cannabidiol (CBD) Critical Review Report. Expert Committee on Drug Dependence Fortieth Meeting. World Health Organization. Geneva June 4-7, 2018.

3. J Autism Dev Disord. 2019 Mar;49(3):1284-8.

Grace is a 15-year-old girl in the 10th grade whom you have been treating for anxiety. Family history also is notable for her father having an anxiety disorder. She has been taking an SSRI and is engaged in therapy, which has resulted in some improvement in symptoms. She can become overwhelmed when taking tests, and she has breakthrough anxiety in social situations and occasional difficulties with sleep. She denies using any substances. Her parents, who have come to her appointment with her, noted that while they see some progress, they would like to try more natural interventions. They had done some research on cannabidiol (CBD), and Grace’s father said that using it has tremendously helped his sleep. They inquired about Grace using it as well.

Bhupi/Getty Images

Discussion

CBD use has dramatically increased over the past few years, and in many places can be found in gummies, chocolate, tinctures, and other forms at grocery and convenience stores, in addition to being widely available online. It is a nonpsychoactive compound (versus tetrahydrocannabinol or THC) found in the Cannabis sativa plant. The Farm Bill, which was passed in 2018, legalized production of hemp or the cannabis plant with a THC concentration less than 0.3%. This bill additionally maintained the Food and Drug Administration’s oversight with CBD. States may have laws that are more restrictive about use. CBD was approved in 2018 by the FDA for treatment of Lennox-Gastaut syndrome and Dravet syndrome in individuals 2 years of age and older, and is categorized as a schedule I substance due to its being derived from the cannabis plant.

In randomized, double-blind, placebo-controlled trials leading to CBD’s approval, the most common side effects were drowsiness, insomnia, disrupted sleep, sedation, malaise, weakness, decreased appetite, diarrhea, elevated liver enzymes, rash, and infections. CBD also carries a warning about the potential for suicidal ideation, agitation, new or worsening depression, aggression, and panic attacks.¹ In in vitro and animal studies, CBD has been found to affect growth of tumor cell lines, to have no effects on embryonic development, and to potentially cause some drug-drug interactions through inhibition of CYP2C9, CYP2C19, and CYP3A4. However, the clinical relevance currently is unknown. Animal studies also indicate potential efficacy in decreasing anxiety.²

CBD has been promoted as being effective in treating a number of ailments including migraines, chronic pain, insomnia, ADHD, and anxiety. Multiple anecdotal reports tout the benefits. In a study exploring abuse potential, there were no significant findings, and CBD was generally well tolerated in open trials exploring potential clinical benefits. A retrospective feasibility study – conducted in Israel – exploring use of CBD to decrease problematic behaviors in youth with autism spectrum disorder demonstrated improvement in communication, anxiety, disruptive behaviors, and parental stress.³

• There is potential lack of clarity regarding legality of use in some states. Based on federal law, it is legal to possess CBD derived from hemp, but state laws may differ.
• There is lack of oversight regarding monitoring what is in each supplement. Lab testing for CBD to determine contents is not mandatory in every state. The amount of active compound as well as other ingredients may not be consistent or accurate. According to the FDA, CBD-containing products cannot claim to have health benefits, treat disease, or be sold as dietary supplements without its approval.
• Clear information about appropriate dosing for children is limited.
• Varying delivery systems could affect absorption and bioavailability of CBD.
• Information is lacking regarding potential drug-drug interactions.
• There is a lack of information regarding effects of long-term use.

Use of CBD is an area with significant interest and potential for growth. Although risks are thought to be low overall, there likely is insufficient evidence at this time to actively recommend its use. Additional research in human subjects exploring effective and safe dosing, tolerability, as well as use in special populations (including children, pregnant women, elderly) is needed.
 

Dr. Strange is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and University of Vermont Robert Larner College of Medicine, both in Burlington. She works with children and adolescents. She has no relevant financial disclosures. Email her at [email protected].

References

1. “FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy,” FDA news release, June 25, 2018.

2. Cannabidiol (CBD) Critical Review Report. Expert Committee on Drug Dependence Fortieth Meeting. World Health Organization. Geneva June 4-7, 2018.

3. J Autism Dev Disord. 2019 Mar;49(3):1284-8.

Physicians have been alarmed about the vaping craze for quite some time. This alarm has grown louder in the wake of news that electronic cigarettes have been associated with a mysterious lung disease.

LiudmylaSupynska/Thinkstock

Public health officials have reported that there have been 530 cases of vaping-related respiratory disease,¹ and as of press time at least seven deaths had been attributed to vaping*. On Sept. 6, 2019, the Food and Drug Administration, Centers for Disease Control and Prevention, and other health officials issued an investigation notice on vaping and e-cigarettes,² cautioning teenagers, young adults, and pregnant women to avoid e-cigarettes completely and cautioning all users to never buy e-cigarettes off the street or from social sources.

A few days later, on Sept. 9, the FDA’s Center for Tobacco Products issued a warning letter to JUUL Labs, makers of a popular e-cigarette, for illegal marketing of modified-risk tobacco products.³ Then on Sept. 10, health officials in Kansas reported that a sixth person has died of a lung illness related to vaping.⁴

Researchers have found that 80% of those diagnosed with the vaping illness used products that contained THC, the psychoactive ingredient in marijuana, 61% had used nicotine products, and 7% used cannabidiol (CBD) products. Vitamin E acetate is another substance identified in press reports as tied to the severe lung disease.

Most of the patients affected are adolescents and young adults, with the average age of 19 years.⁵ This comes as vaping among high school students rose 78% between 2017 and 2018.6 According the U.S. surgeon general, one in five teens vapes. Other data show that teen use of e-cigarettes comes with most users having never smoked a traditional cigarette.⁷ Teens and young adults frequently borrow buy* e-cigarette “pods” from gas stations but borrow and purchase from friends or peers. In addition, young people are known to alter the pods to insert other liquids, such as CBD and other marijuana products.

Teens and young adults are at higher risk for vaping complications. Their respiratory and immune systems are still developing. In addition to concerns about the recent surge of respiratory illnesses, nicotine is known to also suppress the immune system, which makes people who use it more susceptible to viral and bacterial infections – and also making it harder for them to recover.

In addition nicotine hyperactivates the reward centers of the brain, which can trigger addictive behaviors. Because the brains of young adults are not yet fully developed until at or after age 26, nicotine use before this can “prime the pump” of a still-developing brain, thereby increasing the likelihood for addiction to harder drugs. Nicotine has been shown to disrupt sleep patterns, which are critical for mental and physical health. Lastly, research shows that smoking increases the risks of various psychiatric disorders, such as depression and anxiety. My teen and young adult patients have endlessly debated with me the idea that smoking – either nicotine or marijuana – eases their anxiety or helps them get to sleep. I tell them that, in the long run, the data show that smoking makes those problems worse.^8-11

Nationally, we are seeing an explosion of multistate legislation pushing marijuana as a health food. E-cigarettes have followed as the “healthy” alternative to traditional tobacco. Unfortunately for our patients, the market has found a new way to promote e-cigarettes as the “cleaner, harmless” substitute to smoking. As clinicians, we must counter those messages.

Finally, our world is now filled with smartphones, sexting, and social media overuse. An entire peer group exists that knows life only with constant electronic stimulation. It is not without irony that our national nicotine obsessions have morphed from paper cigarettes to electronic versions. This raises questions: Are teens and young adults using e-cigarettes because of boredom? Are we witnessing a generational ADHD borne from restlessness that stems from lives with fewer meaningful face-to-face human interactions?

In addition to educating our teens and young adults about the physical risks tied to vaping, we need to teach them to build meaning into their lives that exists outside of this digital age.

Dr. Jorandby is chief medical officer of Lakeview Health in Jacksonville, Fla. She trained in addiction psychiatry at Yale University, New Haven, Conn.
 

References

1. CDC. Outbreak of lung injury associated with e-cigarette use, or vaping. 2019 Sep 19. 

2. CDC. Outbreak of lung illness associated with using e-cigarette products. Investigation notice. 2019 Sep 6.

3. FDA. Warning letter, JUUL Labs. 2019 Sep 9.

4. Sixth person dies of vaping-related illness. The Hill. 2019 Sep 10.

5. Layden JE. Pulmonary illness related to cigarette use in Illinois and Wisconsin – preliminary report. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMoa1911614.

6. Cullen KA et al. CDC. MMWR. 2018 Nov 16;67(45):1276-7.

7. National Academies of Sciences, Engineering, and Medicine. Public health consequences of e-cigarettes. 2018.

8. Patton GC et al. Am J Public Health. 1996 Feb;86(2):225-30.

9. Leventhal AM et al. J Psychiatr Res. 2016 Feb;73:71-8.

10. Levine A et al. J Am Acad Child Adolesc Psychiatry. 2017 Mar;56(3):214-2.

11. Leadbeater BJ et al. Addiction. 2019 Feb;114(2):278-93.

* This column was updated 9/24/2019.

Physicians have been alarmed about the vaping craze for quite some time. This alarm has grown louder in the wake of news that electronic cigarettes have been associated with a mysterious lung disease.

LiudmylaSupynska/Thinkstock

Public health officials have reported that there have been 530 cases of vaping-related respiratory disease,¹ and as of press time at least seven deaths had been attributed to vaping*. On Sept. 6, 2019, the Food and Drug Administration, Centers for Disease Control and Prevention, and other health officials issued an investigation notice on vaping and e-cigarettes,² cautioning teenagers, young adults, and pregnant women to avoid e-cigarettes completely and cautioning all users to never buy e-cigarettes off the street or from social sources.

A few days later, on Sept. 9, the FDA’s Center for Tobacco Products issued a warning letter to JUUL Labs, makers of a popular e-cigarette, for illegal marketing of modified-risk tobacco products.³ Then on Sept. 10, health officials in Kansas reported that a sixth person has died of a lung illness related to vaping.⁴

Researchers have found that 80% of those diagnosed with the vaping illness used products that contained THC, the psychoactive ingredient in marijuana, 61% had used nicotine products, and 7% used cannabidiol (CBD) products. Vitamin E acetate is another substance identified in press reports as tied to the severe lung disease.

Most of the patients affected are adolescents and young adults, with the average age of 19 years.⁵ This comes as vaping among high school students rose 78% between 2017 and 2018.6 According the U.S. surgeon general, one in five teens vapes. Other data show that teen use of e-cigarettes comes with most users having never smoked a traditional cigarette.⁷ Teens and young adults frequently borrow buy* e-cigarette “pods” from gas stations but borrow and purchase from friends or peers. In addition, young people are known to alter the pods to insert other liquids, such as CBD and other marijuana products.

Teens and young adults are at higher risk for vaping complications. Their respiratory and immune systems are still developing. In addition to concerns about the recent surge of respiratory illnesses, nicotine is known to also suppress the immune system, which makes people who use it more susceptible to viral and bacterial infections – and also making it harder for them to recover.

In addition nicotine hyperactivates the reward centers of the brain, which can trigger addictive behaviors. Because the brains of young adults are not yet fully developed until at or after age 26, nicotine use before this can “prime the pump” of a still-developing brain, thereby increasing the likelihood for addiction to harder drugs. Nicotine has been shown to disrupt sleep patterns, which are critical for mental and physical health. Lastly, research shows that smoking increases the risks of various psychiatric disorders, such as depression and anxiety. My teen and young adult patients have endlessly debated with me the idea that smoking – either nicotine or marijuana – eases their anxiety or helps them get to sleep. I tell them that, in the long run, the data show that smoking makes those problems worse.^8-11

Nationally, we are seeing an explosion of multistate legislation pushing marijuana as a health food. E-cigarettes have followed as the “healthy” alternative to traditional tobacco. Unfortunately for our patients, the market has found a new way to promote e-cigarettes as the “cleaner, harmless” substitute to smoking. As clinicians, we must counter those messages.

Finally, our world is now filled with smartphones, sexting, and social media overuse. An entire peer group exists that knows life only with constant electronic stimulation. It is not without irony that our national nicotine obsessions have morphed from paper cigarettes to electronic versions. This raises questions: Are teens and young adults using e-cigarettes because of boredom? Are we witnessing a generational ADHD borne from restlessness that stems from lives with fewer meaningful face-to-face human interactions?

In addition to educating our teens and young adults about the physical risks tied to vaping, we need to teach them to build meaning into their lives that exists outside of this digital age.

Dr. Jorandby is chief medical officer of Lakeview Health in Jacksonville, Fla. She trained in addiction psychiatry at Yale University, New Haven, Conn.
 

References

1. CDC. Outbreak of lung injury associated with e-cigarette use, or vaping. 2019 Sep 19. 

2. CDC. Outbreak of lung illness associated with using e-cigarette products. Investigation notice. 2019 Sep 6.

3. FDA. Warning letter, JUUL Labs. 2019 Sep 9.

4. Sixth person dies of vaping-related illness. The Hill. 2019 Sep 10.

5. Layden JE. Pulmonary illness related to cigarette use in Illinois and Wisconsin – preliminary report. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMoa1911614.

6. Cullen KA et al. CDC. MMWR. 2018 Nov 16;67(45):1276-7.

7. National Academies of Sciences, Engineering, and Medicine. Public health consequences of e-cigarettes. 2018.

8. Patton GC et al. Am J Public Health. 1996 Feb;86(2):225-30.

9. Leventhal AM et al. J Psychiatr Res. 2016 Feb;73:71-8.

10. Levine A et al. J Am Acad Child Adolesc Psychiatry. 2017 Mar;56(3):214-2.

11. Leadbeater BJ et al. Addiction. 2019 Feb;114(2):278-93.

* This column was updated 9/24/2019.

Physicians have been alarmed about the vaping craze for quite some time. This alarm has grown louder in the wake of news that electronic cigarettes have been associated with a mysterious lung disease.

LiudmylaSupynska/Thinkstock

Public health officials have reported that there have been 530 cases of vaping-related respiratory disease,¹ and as of press time at least seven deaths had been attributed to vaping*. On Sept. 6, 2019, the Food and Drug Administration, Centers for Disease Control and Prevention, and other health officials issued an investigation notice on vaping and e-cigarettes,² cautioning teenagers, young adults, and pregnant women to avoid e-cigarettes completely and cautioning all users to never buy e-cigarettes off the street or from social sources.

A few days later, on Sept. 9, the FDA’s Center for Tobacco Products issued a warning letter to JUUL Labs, makers of a popular e-cigarette, for illegal marketing of modified-risk tobacco products.³ Then on Sept. 10, health officials in Kansas reported that a sixth person has died of a lung illness related to vaping.⁴

Researchers have found that 80% of those diagnosed with the vaping illness used products that contained THC, the psychoactive ingredient in marijuana, 61% had used nicotine products, and 7% used cannabidiol (CBD) products. Vitamin E acetate is another substance identified in press reports as tied to the severe lung disease.

Most of the patients affected are adolescents and young adults, with the average age of 19 years.⁵ This comes as vaping among high school students rose 78% between 2017 and 2018.6 According the U.S. surgeon general, one in five teens vapes. Other data show that teen use of e-cigarettes comes with most users having never smoked a traditional cigarette.⁷ Teens and young adults frequently borrow buy* e-cigarette “pods” from gas stations but borrow and purchase from friends or peers. In addition, young people are known to alter the pods to insert other liquids, such as CBD and other marijuana products.

Teens and young adults are at higher risk for vaping complications. Their respiratory and immune systems are still developing. In addition to concerns about the recent surge of respiratory illnesses, nicotine is known to also suppress the immune system, which makes people who use it more susceptible to viral and bacterial infections – and also making it harder for them to recover.

In addition nicotine hyperactivates the reward centers of the brain, which can trigger addictive behaviors. Because the brains of young adults are not yet fully developed until at or after age 26, nicotine use before this can “prime the pump” of a still-developing brain, thereby increasing the likelihood for addiction to harder drugs. Nicotine has been shown to disrupt sleep patterns, which are critical for mental and physical health. Lastly, research shows that smoking increases the risks of various psychiatric disorders, such as depression and anxiety. My teen and young adult patients have endlessly debated with me the idea that smoking – either nicotine or marijuana – eases their anxiety or helps them get to sleep. I tell them that, in the long run, the data show that smoking makes those problems worse.^8-11

Nationally, we are seeing an explosion of multistate legislation pushing marijuana as a health food. E-cigarettes have followed as the “healthy” alternative to traditional tobacco. Unfortunately for our patients, the market has found a new way to promote e-cigarettes as the “cleaner, harmless” substitute to smoking. As clinicians, we must counter those messages.

Finally, our world is now filled with smartphones, sexting, and social media overuse. An entire peer group exists that knows life only with constant electronic stimulation. It is not without irony that our national nicotine obsessions have morphed from paper cigarettes to electronic versions. This raises questions: Are teens and young adults using e-cigarettes because of boredom? Are we witnessing a generational ADHD borne from restlessness that stems from lives with fewer meaningful face-to-face human interactions?

In addition to educating our teens and young adults about the physical risks tied to vaping, we need to teach them to build meaning into their lives that exists outside of this digital age.

Dr. Jorandby is chief medical officer of Lakeview Health in Jacksonville, Fla. She trained in addiction psychiatry at Yale University, New Haven, Conn.
 

References

1. CDC. Outbreak of lung injury associated with e-cigarette use, or vaping. 2019 Sep 19. 

2. CDC. Outbreak of lung illness associated with using e-cigarette products. Investigation notice. 2019 Sep 6.

3. FDA. Warning letter, JUUL Labs. 2019 Sep 9.

4. Sixth person dies of vaping-related illness. The Hill. 2019 Sep 10.

5. Layden JE. Pulmonary illness related to cigarette use in Illinois and Wisconsin – preliminary report. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMoa1911614.

6. Cullen KA et al. CDC. MMWR. 2018 Nov 16;67(45):1276-7.

7. National Academies of Sciences, Engineering, and Medicine. Public health consequences of e-cigarettes. 2018.

8. Patton GC et al. Am J Public Health. 1996 Feb;86(2):225-30.

9. Leventhal AM et al. J Psychiatr Res. 2016 Feb;73:71-8.

10. Levine A et al. J Am Acad Child Adolesc Psychiatry. 2017 Mar;56(3):214-2.

11. Leadbeater BJ et al. Addiction. 2019 Feb;114(2):278-93.

* This column was updated 9/24/2019.

Adolescent suicides can be prevented, and clinicians have a key role to play, Joan Asarnow, PhD, said in a webinar presented on World Suicide Prevention Day, Sept. 10, 2019, to raise awareness of the latest research in suicide prevention and risk factors.

AlexRaths/Thinkstock

“Primary care doctors are the most trusted doctors for our teenagers,” Dr. Asarnow said during a question-and-answer session. Primary care can be the first-line screening to identify risk factors for suicide, and a close link with primary care “can make a very big difference in helping kids get through tough times.”

Other studies have shown that when doctors and nurses are able to recognize suicidality and link to behavioral health when needed, suicide attempts and ideation are reduced. Strategies including dialectical behavioral therapy and cognitive-behavior therapy have demonstrated success in reducing self -harm, she noted.

Schools have a role in suicide prevention as well, said Dr. Asarnow of the University of California, Los Angeles, and editor of a special issue of the Journal of Child Psychology and Psychiatry on suicide and self-harm.

She cited data from the Saving and Empowering Young Lives in Europe (SEYLE) study, a longitudinal study of school-based suicide prevention interventions, in which suicide attempts were significantly lower among teens who were exposed to a school-based program (Youth Aware of Mental Health) than they were among controls.

Additional findings from the SEYLE study recently were published in the Journal of Child Psychology and Psychiatry (2019. doi: 10.1111/jcpp.13119).

The authors investigated the interaction of three interventions with a certain model of suicide risk. The three interventions were Youth Aware of Mental Health (YAM); Question, Persuade and Refer (QPR); and ProfScreen. The latter two are established interventions for use by teachers. In the study, 11,110 high school students from 10 countries in the European Union completed questionnaires to assess baseline feelings of being a burden to others and feelings of loneliness and isolation from family and peers. The questionnaires also assessed health risk behaviors, self-injury, suicide ideation, and suicide attempts (SA), which were factors in the model being investigated. The participants were randomized to one of the interventions or to a control group that received educational posters with information about mental health resources.

In a reassessment of 8,972 adolescents 12 months later, the interventions all significantly reduced the association between repeated suicide attempts and the baseline interaction of self-injury and suicide ideation, compared with the control group.

“Among each of the three intervention groups, [suicide ideation] at baseline did not increase the risk of self-injury to be associated with repeated [suicide attempt]” at follow-up, Shira Barzilay, PhD, of Tel Aviv University, and coauthors said.

In addition, the researchers’ model found that “belongingness to parents” predicted lower odds of SI after controlling for depression, anxiety, and internalizing symptoms, and this prediction was similar across the intervention and control groups, although good relations with peers and lack of feeling like a burden on others were not significantly associated with lower odds of SI.

The study findings were limited by several factors including the limits of the model to fully capture the measures of belongingness or burdensomeness, and the use of a 12-month follow-up, which was too long to examine certain patterns of SA, the researchers noted. However, the results suggest that interventions can help reduce risk behaviors or self-harm that could lead to suicide. Areas for further study include examining spikes in risk variables that might have preceded suicide attempts, elevated stress, or interpersonal conflicts.

“The implications for suicide prevention, in both community and clinical settings, are to monitor youth who may be engaged in risky behaviors regardless of [suicide ideation] presentation and provide them with mental health education,” Dr. Barzilay and coauthors concluded.

The ongoing mission, Dr. Asarnow said, is “to send messages of hope, and that there is help out there.”

This is particularly important in the United States and the United Kingdom because, while suicide rates in adolescents have declined in some countries, they have increased in others, notably the two countries aforementioned, Dennis Ougrin, MD, said at the webinar.

Males are more likely to commit suicide than females by a ratio of 3 or 4 to 1 in most Western countries, said Dr. Ougrin, a child and adolescent psychiatrist at South London and Maudsley National Health Service Foundation Trust, leading the Child and Adolescent Mental Health Services Enhanced Treatment Service.

Although hanging is the most common method for suicides in most countries, followed by poisoning, more than 50% of suicides in the United States are caused by firearms, he noted.

Risk factors for completed suicide include male sex, low social status, restricted educational achievement, parental mental disorder, individual mental disorder, family history of suicidal behavior, problems with interpersonal relationships, drug and alcohol misuse, and feelings of hopelessness, said Dr. Ougrin, citing data from a 2012 study published in the Lancet (2012 Jun 23. doi: 10.1016/S0140-6736[12]60322-5).

The webinar was sponsored by Wiley partnership with the World Federation of Science Journalists and the Association of Health Care Journalists. Dr. Asarnow and Dr. Ougrin had no financial conflicts to disclose. The SEYLE project is supported by the European Union through the Seventh Framework Program. Dr. Barzilay and coauthors of the SEYLE study had no financial conflicts to disclose.

Adolescent suicides can be prevented, and clinicians have a key role to play, Joan Asarnow, PhD, said in a webinar presented on World Suicide Prevention Day, Sept. 10, 2019, to raise awareness of the latest research in suicide prevention and risk factors.

AlexRaths/Thinkstock

“Primary care doctors are the most trusted doctors for our teenagers,” Dr. Asarnow said during a question-and-answer session. Primary care can be the first-line screening to identify risk factors for suicide, and a close link with primary care “can make a very big difference in helping kids get through tough times.”

Other studies have shown that when doctors and nurses are able to recognize suicidality and link to behavioral health when needed, suicide attempts and ideation are reduced. Strategies including dialectical behavioral therapy and cognitive-behavior therapy have demonstrated success in reducing self -harm, she noted.

Schools have a role in suicide prevention as well, said Dr. Asarnow of the University of California, Los Angeles, and editor of a special issue of the Journal of Child Psychology and Psychiatry on suicide and self-harm.

She cited data from the Saving and Empowering Young Lives in Europe (SEYLE) study, a longitudinal study of school-based suicide prevention interventions, in which suicide attempts were significantly lower among teens who were exposed to a school-based program (Youth Aware of Mental Health) than they were among controls.

Additional findings from the SEYLE study recently were published in the Journal of Child Psychology and Psychiatry (2019. doi: 10.1111/jcpp.13119).

The authors investigated the interaction of three interventions with a certain model of suicide risk. The three interventions were Youth Aware of Mental Health (YAM); Question, Persuade and Refer (QPR); and ProfScreen. The latter two are established interventions for use by teachers. In the study, 11,110 high school students from 10 countries in the European Union completed questionnaires to assess baseline feelings of being a burden to others and feelings of loneliness and isolation from family and peers. The questionnaires also assessed health risk behaviors, self-injury, suicide ideation, and suicide attempts (SA), which were factors in the model being investigated. The participants were randomized to one of the interventions or to a control group that received educational posters with information about mental health resources.

In a reassessment of 8,972 adolescents 12 months later, the interventions all significantly reduced the association between repeated suicide attempts and the baseline interaction of self-injury and suicide ideation, compared with the control group.

“Among each of the three intervention groups, [suicide ideation] at baseline did not increase the risk of self-injury to be associated with repeated [suicide attempt]” at follow-up, Shira Barzilay, PhD, of Tel Aviv University, and coauthors said.

In addition, the researchers’ model found that “belongingness to parents” predicted lower odds of SI after controlling for depression, anxiety, and internalizing symptoms, and this prediction was similar across the intervention and control groups, although good relations with peers and lack of feeling like a burden on others were not significantly associated with lower odds of SI.

The study findings were limited by several factors including the limits of the model to fully capture the measures of belongingness or burdensomeness, and the use of a 12-month follow-up, which was too long to examine certain patterns of SA, the researchers noted. However, the results suggest that interventions can help reduce risk behaviors or self-harm that could lead to suicide. Areas for further study include examining spikes in risk variables that might have preceded suicide attempts, elevated stress, or interpersonal conflicts.

“The implications for suicide prevention, in both community and clinical settings, are to monitor youth who may be engaged in risky behaviors regardless of [suicide ideation] presentation and provide them with mental health education,” Dr. Barzilay and coauthors concluded.

The ongoing mission, Dr. Asarnow said, is “to send messages of hope, and that there is help out there.”

This is particularly important in the United States and the United Kingdom because, while suicide rates in adolescents have declined in some countries, they have increased in others, notably the two countries aforementioned, Dennis Ougrin, MD, said at the webinar.

Males are more likely to commit suicide than females by a ratio of 3 or 4 to 1 in most Western countries, said Dr. Ougrin, a child and adolescent psychiatrist at South London and Maudsley National Health Service Foundation Trust, leading the Child and Adolescent Mental Health Services Enhanced Treatment Service.

Although hanging is the most common method for suicides in most countries, followed by poisoning, more than 50% of suicides in the United States are caused by firearms, he noted.

Risk factors for completed suicide include male sex, low social status, restricted educational achievement, parental mental disorder, individual mental disorder, family history of suicidal behavior, problems with interpersonal relationships, drug and alcohol misuse, and feelings of hopelessness, said Dr. Ougrin, citing data from a 2012 study published in the Lancet (2012 Jun 23. doi: 10.1016/S0140-6736[12]60322-5).

The webinar was sponsored by Wiley partnership with the World Federation of Science Journalists and the Association of Health Care Journalists. Dr. Asarnow and Dr. Ougrin had no financial conflicts to disclose. The SEYLE project is supported by the European Union through the Seventh Framework Program. Dr. Barzilay and coauthors of the SEYLE study had no financial conflicts to disclose.

Adolescent suicides can be prevented, and clinicians have a key role to play, Joan Asarnow, PhD, said in a webinar presented on World Suicide Prevention Day, Sept. 10, 2019, to raise awareness of the latest research in suicide prevention and risk factors.

AlexRaths/Thinkstock

“Primary care doctors are the most trusted doctors for our teenagers,” Dr. Asarnow said during a question-and-answer session. Primary care can be the first-line screening to identify risk factors for suicide, and a close link with primary care “can make a very big difference in helping kids get through tough times.”

Other studies have shown that when doctors and nurses are able to recognize suicidality and link to behavioral health when needed, suicide attempts and ideation are reduced. Strategies including dialectical behavioral therapy and cognitive-behavior therapy have demonstrated success in reducing self -harm, she noted.

Schools have a role in suicide prevention as well, said Dr. Asarnow of the University of California, Los Angeles, and editor of a special issue of the Journal of Child Psychology and Psychiatry on suicide and self-harm.

She cited data from the Saving and Empowering Young Lives in Europe (SEYLE) study, a longitudinal study of school-based suicide prevention interventions, in which suicide attempts were significantly lower among teens who were exposed to a school-based program (Youth Aware of Mental Health) than they were among controls.

Additional findings from the SEYLE study recently were published in the Journal of Child Psychology and Psychiatry (2019. doi: 10.1111/jcpp.13119).

The authors investigated the interaction of three interventions with a certain model of suicide risk. The three interventions were Youth Aware of Mental Health (YAM); Question, Persuade and Refer (QPR); and ProfScreen. The latter two are established interventions for use by teachers. In the study, 11,110 high school students from 10 countries in the European Union completed questionnaires to assess baseline feelings of being a burden to others and feelings of loneliness and isolation from family and peers. The questionnaires also assessed health risk behaviors, self-injury, suicide ideation, and suicide attempts (SA), which were factors in the model being investigated. The participants were randomized to one of the interventions or to a control group that received educational posters with information about mental health resources.

In a reassessment of 8,972 adolescents 12 months later, the interventions all significantly reduced the association between repeated suicide attempts and the baseline interaction of self-injury and suicide ideation, compared with the control group.

“Among each of the three intervention groups, [suicide ideation] at baseline did not increase the risk of self-injury to be associated with repeated [suicide attempt]” at follow-up, Shira Barzilay, PhD, of Tel Aviv University, and coauthors said.

In addition, the researchers’ model found that “belongingness to parents” predicted lower odds of SI after controlling for depression, anxiety, and internalizing symptoms, and this prediction was similar across the intervention and control groups, although good relations with peers and lack of feeling like a burden on others were not significantly associated with lower odds of SI.

The study findings were limited by several factors including the limits of the model to fully capture the measures of belongingness or burdensomeness, and the use of a 12-month follow-up, which was too long to examine certain patterns of SA, the researchers noted. However, the results suggest that interventions can help reduce risk behaviors or self-harm that could lead to suicide. Areas for further study include examining spikes in risk variables that might have preceded suicide attempts, elevated stress, or interpersonal conflicts.

“The implications for suicide prevention, in both community and clinical settings, are to monitor youth who may be engaged in risky behaviors regardless of [suicide ideation] presentation and provide them with mental health education,” Dr. Barzilay and coauthors concluded.

The ongoing mission, Dr. Asarnow said, is “to send messages of hope, and that there is help out there.”

This is particularly important in the United States and the United Kingdom because, while suicide rates in adolescents have declined in some countries, they have increased in others, notably the two countries aforementioned, Dennis Ougrin, MD, said at the webinar.

Males are more likely to commit suicide than females by a ratio of 3 or 4 to 1 in most Western countries, said Dr. Ougrin, a child and adolescent psychiatrist at South London and Maudsley National Health Service Foundation Trust, leading the Child and Adolescent Mental Health Services Enhanced Treatment Service.

Although hanging is the most common method for suicides in most countries, followed by poisoning, more than 50% of suicides in the United States are caused by firearms, he noted.

Risk factors for completed suicide include male sex, low social status, restricted educational achievement, parental mental disorder, individual mental disorder, family history of suicidal behavior, problems with interpersonal relationships, drug and alcohol misuse, and feelings of hopelessness, said Dr. Ougrin, citing data from a 2012 study published in the Lancet (2012 Jun 23. doi: 10.1016/S0140-6736[12]60322-5).

The webinar was sponsored by Wiley partnership with the World Federation of Science Journalists and the Association of Health Care Journalists. Dr. Asarnow and Dr. Ougrin had no financial conflicts to disclose. The SEYLE project is supported by the European Union through the Seventh Framework Program. Dr. Barzilay and coauthors of the SEYLE study had no financial conflicts to disclose.

Gender identity conversion efforts during early childhood quadruple lifetime risk of suicidal behavior for transgender people, a study of almost 28,000 adults has determined.

The findings prompted the authors to issue a blanket warning against the controversial treatment, which already has been decried by several medical associations.

“Our results support policy positions … which state that gender identity–conversion therapy should not be conducted for transgender patients at any age, Jack L. Turban, MD, and colleagues wrote in JAMA Psychiatry.

The American Academy of Child and Adolescent Psychiatry, the American Psychiatric Association, the American Academy of Pediatrics, and the American Medical Association all strongly warn against any kind of gender conversion efforts.

The significantly increased risk of suicidal behavior was similar whether the gender identity–conversion effort (GICE) was administered by a clinician or a cleric. “This suggests that any process of intervening to alter gender identity is associated with poorer mental health regardless of whether the intervention occurred within a secular or religious framework,” wrote Dr. Turban of Massachusetts General Hospital, Boston, and coauthors.

The study – the largest of its kind thus far – comprised 27,715 transgender adults included in the 2015 U.S. Transgender Survey, conducted by the National Center for Transgender Equality.

In the current study, investigators focused on the question: “Did any professional (such as a psychologist, counselor, or religious advisor) try to make you identify only with your sex assigned at birth (in other words, try to stop you being trans)?”

They compared responses among subjects who reported exposure to GICE before age 10 years with those who did not.

Subjects were aged a mean of 31 years when they participated in the survey. Slightly less than half (42.8%) were assigned male sex at birth. Most (19,751) had discussed their gender identity with a professional. Nearly 20% (3,869) reported some exposure to GICE; 35% said a religious adviser had conducted the effort.

In this group, exposure had significant negative lifetime effects on mental health. These subjects were at a 56% increased risk of psychological distress within the month before taking the survey (odds ratio, 1.56), and more than twice as likely to have tried at least once to end their lives by suicide (OR, 2.27).

But the negative effects were even more pronounced among the small group of 206 who reported exposure to GICE before they were 10 years old. In a multivariate analysis adjusted for demographics, GICE before age 10 more than quadrupled the risk of lifetime suicide attempts (OR, 4.15). Again, it didn’t matter whether a medical or religious professional administered GICE.

“A plausible association of these practices with poor mental health outcomes can be conceptualized through the minority stress framework; that is, elevated stigma-related stress from exposure to GICE may increase general emotion dysregulation, interpersonal dysfunction, and maladaptive cognitions,” the investigators wrote. “Although this study suggests that exposure to GICE is associated with increased odds of suicide attempts, GICE are not the only way in which minority group stress manifests, and thus, other factors are also likely to be associated with suicidality among gender-diverse people.”

The rate at which transgender people are exposed to GICE appears to be higher than that experienced by cisgender nonheterosexual people, the authors noted. “One potential explanation for this is that, compared with persons in the sexual-minority group, many persons in the gender-minority group must interact with clinical professionals to be medically and surgically affirmed in their identities. This higher prevalence of interactions with clinical professionals among people in the gender minority group may lead to greater risk of experiencing conversion effort.”

The authors cited the sample size of the study as one of its many strengths. One limitation includes the study’s cross-sectional design.

Dr. Turban reported collecting royalties from Springer for an upcoming textbook about pediatric gender identity. The other coauthors reported no disclosures.

[email protected]

SOURCE: Turban JL et al. JAMA Psychiatry. 2019 Sep 11. doi: 10.1001/jamapsychiatry.2019.2285.
 

Gender identity conversion efforts during early childhood quadruple lifetime risk of suicidal behavior for transgender people, a study of almost 28,000 adults has determined.

The findings prompted the authors to issue a blanket warning against the controversial treatment, which already has been decried by several medical associations.

“Our results support policy positions … which state that gender identity–conversion therapy should not be conducted for transgender patients at any age, Jack L. Turban, MD, and colleagues wrote in JAMA Psychiatry.

The American Academy of Child and Adolescent Psychiatry, the American Psychiatric Association, the American Academy of Pediatrics, and the American Medical Association all strongly warn against any kind of gender conversion efforts.

The significantly increased risk of suicidal behavior was similar whether the gender identity–conversion effort (GICE) was administered by a clinician or a cleric. “This suggests that any process of intervening to alter gender identity is associated with poorer mental health regardless of whether the intervention occurred within a secular or religious framework,” wrote Dr. Turban of Massachusetts General Hospital, Boston, and coauthors.

The study – the largest of its kind thus far – comprised 27,715 transgender adults included in the 2015 U.S. Transgender Survey, conducted by the National Center for Transgender Equality.

In the current study, investigators focused on the question: “Did any professional (such as a psychologist, counselor, or religious advisor) try to make you identify only with your sex assigned at birth (in other words, try to stop you being trans)?”

They compared responses among subjects who reported exposure to GICE before age 10 years with those who did not.

Subjects were aged a mean of 31 years when they participated in the survey. Slightly less than half (42.8%) were assigned male sex at birth. Most (19,751) had discussed their gender identity with a professional. Nearly 20% (3,869) reported some exposure to GICE; 35% said a religious adviser had conducted the effort.

In this group, exposure had significant negative lifetime effects on mental health. These subjects were at a 56% increased risk of psychological distress within the month before taking the survey (odds ratio, 1.56), and more than twice as likely to have tried at least once to end their lives by suicide (OR, 2.27).

But the negative effects were even more pronounced among the small group of 206 who reported exposure to GICE before they were 10 years old. In a multivariate analysis adjusted for demographics, GICE before age 10 more than quadrupled the risk of lifetime suicide attempts (OR, 4.15). Again, it didn’t matter whether a medical or religious professional administered GICE.

“A plausible association of these practices with poor mental health outcomes can be conceptualized through the minority stress framework; that is, elevated stigma-related stress from exposure to GICE may increase general emotion dysregulation, interpersonal dysfunction, and maladaptive cognitions,” the investigators wrote. “Although this study suggests that exposure to GICE is associated with increased odds of suicide attempts, GICE are not the only way in which minority group stress manifests, and thus, other factors are also likely to be associated with suicidality among gender-diverse people.”

The rate at which transgender people are exposed to GICE appears to be higher than that experienced by cisgender nonheterosexual people, the authors noted. “One potential explanation for this is that, compared with persons in the sexual-minority group, many persons in the gender-minority group must interact with clinical professionals to be medically and surgically affirmed in their identities. This higher prevalence of interactions with clinical professionals among people in the gender minority group may lead to greater risk of experiencing conversion effort.”

The authors cited the sample size of the study as one of its many strengths. One limitation includes the study’s cross-sectional design.

Dr. Turban reported collecting royalties from Springer for an upcoming textbook about pediatric gender identity. The other coauthors reported no disclosures.

[email protected]

SOURCE: Turban JL et al. JAMA Psychiatry. 2019 Sep 11. doi: 10.1001/jamapsychiatry.2019.2285.
 

Gender identity conversion efforts during early childhood quadruple lifetime risk of suicidal behavior for transgender people, a study of almost 28,000 adults has determined.

The findings prompted the authors to issue a blanket warning against the controversial treatment, which already has been decried by several medical associations.

“Our results support policy positions … which state that gender identity–conversion therapy should not be conducted for transgender patients at any age, Jack L. Turban, MD, and colleagues wrote in JAMA Psychiatry.

The American Academy of Child and Adolescent Psychiatry, the American Psychiatric Association, the American Academy of Pediatrics, and the American Medical Association all strongly warn against any kind of gender conversion efforts.

The significantly increased risk of suicidal behavior was similar whether the gender identity–conversion effort (GICE) was administered by a clinician or a cleric. “This suggests that any process of intervening to alter gender identity is associated with poorer mental health regardless of whether the intervention occurred within a secular or religious framework,” wrote Dr. Turban of Massachusetts General Hospital, Boston, and coauthors.

The study – the largest of its kind thus far – comprised 27,715 transgender adults included in the 2015 U.S. Transgender Survey, conducted by the National Center for Transgender Equality.

In the current study, investigators focused on the question: “Did any professional (such as a psychologist, counselor, or religious advisor) try to make you identify only with your sex assigned at birth (in other words, try to stop you being trans)?”

They compared responses among subjects who reported exposure to GICE before age 10 years with those who did not.

Subjects were aged a mean of 31 years when they participated in the survey. Slightly less than half (42.8%) were assigned male sex at birth. Most (19,751) had discussed their gender identity with a professional. Nearly 20% (3,869) reported some exposure to GICE; 35% said a religious adviser had conducted the effort.

In this group, exposure had significant negative lifetime effects on mental health. These subjects were at a 56% increased risk of psychological distress within the month before taking the survey (odds ratio, 1.56), and more than twice as likely to have tried at least once to end their lives by suicide (OR, 2.27).

But the negative effects were even more pronounced among the small group of 206 who reported exposure to GICE before they were 10 years old. In a multivariate analysis adjusted for demographics, GICE before age 10 more than quadrupled the risk of lifetime suicide attempts (OR, 4.15). Again, it didn’t matter whether a medical or religious professional administered GICE.

“A plausible association of these practices with poor mental health outcomes can be conceptualized through the minority stress framework; that is, elevated stigma-related stress from exposure to GICE may increase general emotion dysregulation, interpersonal dysfunction, and maladaptive cognitions,” the investigators wrote. “Although this study suggests that exposure to GICE is associated with increased odds of suicide attempts, GICE are not the only way in which minority group stress manifests, and thus, other factors are also likely to be associated with suicidality among gender-diverse people.”

The rate at which transgender people are exposed to GICE appears to be higher than that experienced by cisgender nonheterosexual people, the authors noted. “One potential explanation for this is that, compared with persons in the sexual-minority group, many persons in the gender-minority group must interact with clinical professionals to be medically and surgically affirmed in their identities. This higher prevalence of interactions with clinical professionals among people in the gender minority group may lead to greater risk of experiencing conversion effort.”

The authors cited the sample size of the study as one of its many strengths. One limitation includes the study’s cross-sectional design.

Dr. Turban reported collecting royalties from Springer for an upcoming textbook about pediatric gender identity. The other coauthors reported no disclosures.

[email protected]

SOURCE: Turban JL et al. JAMA Psychiatry. 2019 Sep 11. doi: 10.1001/jamapsychiatry.2019.2285.