Mental Health

Headache, including migraine, tension-type, trigeminal autonomic cephalalgia (TAC), and posttraumatic stress headache are significantly associated with both attempted and completed suicide, results of a large study suggested.

The risk for attempted and completed suicide was more than threefold higher for individuals with posttraumatic headache and about twofold higher for those with TAC than their counterparts without headache.

Even those with tension-type headache, one of the milder headache types, carried nearly a twofold increased risk for attempted suicide vs the comparison group with no headache.

First author Holly Elser, MD, MPH, PhD, a resident physician in the Department of Neurology at the University of Pennsylvania, Philadelphia, told Medscape Medical News that the findings were “quite striking” and underscore the importance of screening for suicide risk even in patients with mild headache.

The findings were published online on February 3 in JAMA Neurology.

Common, Disabling 

With an estimated global lifetime prevalence of 67%, headache disorders are a leading cause of productivity loss, work absences, and short-term disability.

The mechanisms linking headache disorders to suicide remain unclear for several reasons, the investigators noted.

First, the relationship between headache and psychiatric comorbidities may be complex and bidirectional, with psychiatric symptoms potentially exacerbating headache severity and frequency, the investigators noted.

Secondly, research has shown a consistent link between chronic pain and suicidality, even after adjusting for comorbid psychiatric conditions. Finally, disruptions in serotonergic pathways and increased production of inflammatory cytokines may contribute to both headache disorders and psychiatric symptoms, suggesting a shared biological basis.

The mechanisms linking headache disorders to suicide remain unclear for several reasons, the investigators noted.

First, the relationship between headache and psychiatric comorbidities may be complex and bidirectional, with psychiatric symptoms potentially exacerbating headache severity and frequency, the investigators noted.

Secondly, research has shown a consistent link between chronic pain and suicidality, even after adjusting for comorbid psychiatric conditions. Finally, disruptions in serotonergic pathways and increased production of inflammatory cytokines may contribute to both headache disorders and psychiatric symptoms, suggesting a shared biological basis.

“Patients diagnosed with headache with comorbid psychiatric symptoms may benefit in particular from comanagement with behavioral health specialists,” she added.

Not ‘Just Headaches’

In an interview with Medscape Medical News, Fred Cohen, MD, an assistant professor of medicine and neurology at the Icahn School of Medicine at Mount Sinai Hospital, New York City, shared his perspective on the findings. Cohen, who was not involved in the study agreed with Elser’s point and incorporated screening into his practice.

“As part of my routine at every new patient appointment, I conduct screenings for depression and suicide risk. If a patient responds affirmatively to any of these questions, I make sure they get connected to the mental health resources they need,” Cohen said.

At least one of his patients per week screens positive for depression, he noted.

“Primary headaches, including migraine and trigeminal autonomic cephalalgias, are a significant source of disability and suffering,” said Cohen, adding that migraine, in particular, is the leading cause of disability worldwide among women aged 18-50 years. “These conditions are often misunderstood and dismissed as ‘just headaches,’ when in reality, they are much more complex and debilitating.”

Given that depression and anxiety are common co-occurring conditions with primary headache disorders, he said, “depression screenings should be standard practice when evaluating patients with headaches.”

The study’s limitations include dependence on diagnosis codes, which are prone to misclassification, and lack of information about headache chronicity and severity, which could have affected the findings.

There was no information provided about study funding. Elser and Cohen reported no relevant financial relationships.

Headache, including migraine, tension-type, trigeminal autonomic cephalalgia (TAC), and posttraumatic stress headache are significantly associated with both attempted and completed suicide, results of a large study suggested.

The risk for attempted and completed suicide was more than threefold higher for individuals with posttraumatic headache and about twofold higher for those with TAC than their counterparts without headache.

Even those with tension-type headache, one of the milder headache types, carried nearly a twofold increased risk for attempted suicide vs the comparison group with no headache.

First author Holly Elser, MD, MPH, PhD, a resident physician in the Department of Neurology at the University of Pennsylvania, Philadelphia, told Medscape Medical News that the findings were “quite striking” and underscore the importance of screening for suicide risk even in patients with mild headache.

The findings were published online on February 3 in JAMA Neurology.

Common, Disabling 

With an estimated global lifetime prevalence of 67%, headache disorders are a leading cause of productivity loss, work absences, and short-term disability.

The mechanisms linking headache disorders to suicide remain unclear for several reasons, the investigators noted.

First, the relationship between headache and psychiatric comorbidities may be complex and bidirectional, with psychiatric symptoms potentially exacerbating headache severity and frequency, the investigators noted.

Secondly, research has shown a consistent link between chronic pain and suicidality, even after adjusting for comorbid psychiatric conditions. Finally, disruptions in serotonergic pathways and increased production of inflammatory cytokines may contribute to both headache disorders and psychiatric symptoms, suggesting a shared biological basis.

The mechanisms linking headache disorders to suicide remain unclear for several reasons, the investigators noted.

First, the relationship between headache and psychiatric comorbidities may be complex and bidirectional, with psychiatric symptoms potentially exacerbating headache severity and frequency, the investigators noted.

Secondly, research has shown a consistent link between chronic pain and suicidality, even after adjusting for comorbid psychiatric conditions. Finally, disruptions in serotonergic pathways and increased production of inflammatory cytokines may contribute to both headache disorders and psychiatric symptoms, suggesting a shared biological basis.

“Patients diagnosed with headache with comorbid psychiatric symptoms may benefit in particular from comanagement with behavioral health specialists,” she added.

Not ‘Just Headaches’

In an interview with Medscape Medical News, Fred Cohen, MD, an assistant professor of medicine and neurology at the Icahn School of Medicine at Mount Sinai Hospital, New York City, shared his perspective on the findings. Cohen, who was not involved in the study agreed with Elser’s point and incorporated screening into his practice.

“As part of my routine at every new patient appointment, I conduct screenings for depression and suicide risk. If a patient responds affirmatively to any of these questions, I make sure they get connected to the mental health resources they need,” Cohen said.

At least one of his patients per week screens positive for depression, he noted.

“Primary headaches, including migraine and trigeminal autonomic cephalalgias, are a significant source of disability and suffering,” said Cohen, adding that migraine, in particular, is the leading cause of disability worldwide among women aged 18-50 years. “These conditions are often misunderstood and dismissed as ‘just headaches,’ when in reality, they are much more complex and debilitating.”

Given that depression and anxiety are common co-occurring conditions with primary headache disorders, he said, “depression screenings should be standard practice when evaluating patients with headaches.”

The study’s limitations include dependence on diagnosis codes, which are prone to misclassification, and lack of information about headache chronicity and severity, which could have affected the findings.

There was no information provided about study funding. Elser and Cohen reported no relevant financial relationships.

Headache, including migraine, tension-type, trigeminal autonomic cephalalgia (TAC), and posttraumatic stress headache are significantly associated with both attempted and completed suicide, results of a large study suggested.

The risk for attempted and completed suicide was more than threefold higher for individuals with posttraumatic headache and about twofold higher for those with TAC than their counterparts without headache.

Even those with tension-type headache, one of the milder headache types, carried nearly a twofold increased risk for attempted suicide vs the comparison group with no headache.

First author Holly Elser, MD, MPH, PhD, a resident physician in the Department of Neurology at the University of Pennsylvania, Philadelphia, told Medscape Medical News that the findings were “quite striking” and underscore the importance of screening for suicide risk even in patients with mild headache.

The findings were published online on February 3 in JAMA Neurology.

Common, Disabling 

With an estimated global lifetime prevalence of 67%, headache disorders are a leading cause of productivity loss, work absences, and short-term disability.

The mechanisms linking headache disorders to suicide remain unclear for several reasons, the investigators noted.

First, the relationship between headache and psychiatric comorbidities may be complex and bidirectional, with psychiatric symptoms potentially exacerbating headache severity and frequency, the investigators noted.

Secondly, research has shown a consistent link between chronic pain and suicidality, even after adjusting for comorbid psychiatric conditions. Finally, disruptions in serotonergic pathways and increased production of inflammatory cytokines may contribute to both headache disorders and psychiatric symptoms, suggesting a shared biological basis.

The mechanisms linking headache disorders to suicide remain unclear for several reasons, the investigators noted.

First, the relationship between headache and psychiatric comorbidities may be complex and bidirectional, with psychiatric symptoms potentially exacerbating headache severity and frequency, the investigators noted.

Secondly, research has shown a consistent link between chronic pain and suicidality, even after adjusting for comorbid psychiatric conditions. Finally, disruptions in serotonergic pathways and increased production of inflammatory cytokines may contribute to both headache disorders and psychiatric symptoms, suggesting a shared biological basis.

“Patients diagnosed with headache with comorbid psychiatric symptoms may benefit in particular from comanagement with behavioral health specialists,” she added.

Not ‘Just Headaches’

In an interview with Medscape Medical News, Fred Cohen, MD, an assistant professor of medicine and neurology at the Icahn School of Medicine at Mount Sinai Hospital, New York City, shared his perspective on the findings. Cohen, who was not involved in the study agreed with Elser’s point and incorporated screening into his practice.

“As part of my routine at every new patient appointment, I conduct screenings for depression and suicide risk. If a patient responds affirmatively to any of these questions, I make sure they get connected to the mental health resources they need,” Cohen said.

At least one of his patients per week screens positive for depression, he noted.

“Primary headaches, including migraine and trigeminal autonomic cephalalgias, are a significant source of disability and suffering,” said Cohen, adding that migraine, in particular, is the leading cause of disability worldwide among women aged 18-50 years. “These conditions are often misunderstood and dismissed as ‘just headaches,’ when in reality, they are much more complex and debilitating.”

Given that depression and anxiety are common co-occurring conditions with primary headache disorders, he said, “depression screenings should be standard practice when evaluating patients with headaches.”

The study’s limitations include dependence on diagnosis codes, which are prone to misclassification, and lack of information about headache chronicity and severity, which could have affected the findings.

There was no information provided about study funding. Elser and Cohen reported no relevant financial relationships.

A study of more than 2 million veterans with diabetes builds on evidence of broad-ranging benefits and risks of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in the clinical setting, providing an “atlas” mapping extensive outcomes and some new insights to potentially explore in more rigorous clinical trials.

“This is the largest study on GLP-1 receptor agonists,” first author Ziyad Al-Aly, MD, chief of research and development at the US Department of Veterans Affairs (VA) St. Louis Healthcare System, in St. Louis, told this news organization regarding the research, published this week, in Nature Medicine.

“The [study] reflects the real experiences of people using GLP-1 RAs [in the VA] clinical setting,” he said.

“Altogether, our discovery approach confirms previous studies and clinical trials and also uncovers previously unreported benefits and risks of GLP-1 RAs,” the authors wrote.

For the comprehensive study, Al-Aly and his colleagues evaluated data from the US Department of Veterans Affairs on more than 2 million veterans treated for diabetes between October 2017 and December 2023, assessing GLP-1 RA treatment in comparison with other diabetes therapies regarding a striking 175 clinical outcomes.

Of the patients, 215,970 initiated treatment with GLP-1 RAs; 159,465 started sulfonylureas, 117,989 dipeptidyl peptidase 4 inhibitors, and 258,614 were initiated on sodium-glucose cotransporter-2 inhibitors.

The study also included a composite group of the latter three drug groups (n = 536,068), and a control group of 1,203,097 of patients receiving usual care, who were compared with usual care with the addition of GLP-1 RAs.

After inverse probability weighting, the groups were well-balanced in terms of their baseline characteristics. While the majority in the VA cohort overall were White men, the study adjusted for gender, age, race, comorbidities, and an extensive array of covariates.

With an average follow-up of 3.68 years, after the multivariate adjustment, GLP-1 RAs showed “effectiveness and risks that extended beyond those currently recognized,” in comparison with each of the treatment groups and with the main control group of usual care, the authors reported.

For the largest comparison with the main control group of usual care alone, the addition of GLP-1 RAs was associated with a decreased risk in 24% of the outcomes evaluated, and an increased risk in 10.86% of outcomes, with no significant difference for the remaining 65.14% of outcomes.

Of the various benefits, key improvements included a reduced risk for several substance use disorders including alcohol (hazard ratio [HR], 0.89) and opioid (HR, 0.87) use, suicidal ideation, attempt or intentional self-harm (HR, 0.90), seizures (HR, 0.90), neurocognitive disorders including Alzheimer disease (HR, 0.88) and dementia (HR, 0.92), coagulation and clotting disorders (HR, 0.92), and cardiac arrest (HR, 0.78).

Further benefits vs usual care alone included a reduced risk for infectious illnesses (HR, 0.88), acute kidney injury (HR, 0.88), and chronic kidney disease (CKD) (HR, 0.97; P <.05 for all the outcomes).

In terms of risks associated with GLP-1 RAs, in addition to the well-known risks for nausea and vomiting, additional increased risks vs usual care included gastrointestinal disorders such as noninfectious gastroenteritis (HR, 1.12), hypotension (HR, 1.06), arthritis (HR, 1.11), tendinitis and synovitis (HR, 1.10), interstitial nephritis (HR, 1.06), nephrolithiasis (HR, 1.15), and the known risk for drug-induced acute pancreatitis (HR, 2.46).

 

Neuropsychiatric Effects

Among the various benefits in the study, Al-Aly said some of the most intriguing are those involving the brain.

“I am struck by the consistent effects on many neuropsychiatric disorders — this aligns with data showing the presence of GLP-1 receptors in the brain and evidence showing that GLP-1s permeates through the blood brain barrier and acts on the brain to reduce inflammation and oxidative stress, improve neuroplasticity, etc.,” he said.

“Clearly, there is a neurotropic effect. There is also the possibility of an effect on the immune system/fighting infection — with reduced risks of infections, sepsis, etc.”

The reductions in suicidal ideation are encouraging after earlier reports of suicidal thoughts and self-injury among young users of GLP-1 RAs prompted concerns, including a 2023 review of the drug use by the European Medicines Agency that ultimately found no causal association, the authors added. The US Food and Drug Administration also found no association with GLP-1s and suicide risk.

The reductions in addictive behaviors are also encouraging and are consistent with the role of GLP-1 receptors in the brain in terms of impulse control and reward signaling that can relate to addictive behaviors, Al-Aly explained.

The reduced risks for dementia and Alzheimer disease are likewise consistent with preclinical studies in animal models of Alzheimer disease, as well as clinical studies showing a reduced risk for dementia in patients with type 2 diabetes, the authors noted.

The observed reduced risk for seizures further “adds to an emerging body of knowledge, both mechanistic and early clinical data, indicative of the anticonvulsant properties of GLP-1 RA use,” they added.

“GLP-1 RAs should be further evaluated in future studies as potential adjuvant therapeutics for epilepsy and its associated comorbidities,” the authors suggested.

 

Kidneys

While the findings support evidence of protective effects of GLP-1 RAs on the kidneys and a reduction in CKD risk, notable risks observed, also involving the kidneys, include nephrolithiasis or kidney stones.

Al-Aly noted the mechanisms with kidney stone formation are very different from CKD, and he speculated that the risk for the former could in fact stem from potentially low hydration with GLP-1 RA use.

“When patients are on GLP-1 RAs, they definitely eat a lot less to lose weight, but they also hydrate themselves less,” he explained in a press briefing. “They drink less water because they feel full very quickly after eating, and I’m just theorizing, but perhaps chronic dehydration [is behind] the increased risk of kidney stones.”

 

Modest Effects?

While, overall, the benefits of GLP-1 RA drugs showed modest benefits ranging between a 10% and 20% reduction for most outcomes, Al-Aly said those effects are still important.

“The modest effect does not negate the potential value of these drugs, especially for conditions where few effective treatment options exist, for example, dementia,” he said in the press statement.

“This may also imply that these drugs are most beneficial when used in conjunction with other interventions, such as lifestyle changes or other medications.”

 

Potential Confounders A Concern

Commenting on the study, David M. Nathan, MD, founder of the MGH Diabetes Center and a professor of medicine at Harvard Medical School, in Boston, Massachusetts, noted that, while the study is hypothesis-generating, the key limitation is its observational nature.

“The authors did a perfectly respectable job of doing all you can do to adjust for [confounders], but with these kinds of studies, as much as you try to statistically account for differences in the populations before they were put on the drug, you can never truly adjust for all the potential confounders that may influence the results,” he told this news organization.

In addition, the 3.8-year follow-up time of the study, as the authors acknowledge, is especially short considering that GLP-1 RAs are generally recommended to be taken indefinitely.

“You have to take these drugs presumably for a lifetime and we have no idea what the longer-term benefits and risks are,” Nathan said.

Nathan, who was among the first investigators to evaluate GLP-1 RAs about 30 years ago, underscored that “I do think that these drugs are generally really spectacular; they’ve taken over the world and they are probably the single greatest pharmaceutical story of the 21st century.”

“But much more rigorous randomized trials would be needed to prove study results that haven’t already been established in previous clinical trials,” he said.

“The types of [randomized] trials that are necessary are very expensive and require a huge amount of work, but at the end of the day, they provide proof as to what does and doesn’t work, and what the true risks are,” he added. “Whether the GLP-RAs will cure all ills and bring about world peace needs to be proved.”

In further comments provided through the Science Media Center, Stephen O’Rahilly, FRS, a professor of clinical biochemistry and medicine and director of the Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, England, echoed Nathan’s concern that “studies such as these have to be interpreted very cautiously as the people studied have not been randomly allocated to GLP-1 RA treatment, so any difference between those taking and not taking the class of drug could potentially be attributable to factors other than the drug.”

He noted, however, that “the study provides useful reassurance about the safety of this class of drugs. The expected benefits on heart disease, stroke and other cardiovascular and most kidney diseases are clearly seen.”

Al-Aly reported being an uncompensated consultant for Pfizer. Nathan, who has previously conducted clinical trials on GLP-1 RAs, currently has no relationships to report. O’Rahilly reported receiving remuneration from several pharmaceutical companies for scientific advice relating to the development of drugs for metabolic diseases, but none involving GLP-1 RAs in the past 3 years.

A version of this article first appeared on Medscape.com.

A study of more than 2 million veterans with diabetes builds on evidence of broad-ranging benefits and risks of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in the clinical setting, providing an “atlas” mapping extensive outcomes and some new insights to potentially explore in more rigorous clinical trials.

“This is the largest study on GLP-1 receptor agonists,” first author Ziyad Al-Aly, MD, chief of research and development at the US Department of Veterans Affairs (VA) St. Louis Healthcare System, in St. Louis, told this news organization regarding the research, published this week, in Nature Medicine.

“The [study] reflects the real experiences of people using GLP-1 RAs [in the VA] clinical setting,” he said.

“Altogether, our discovery approach confirms previous studies and clinical trials and also uncovers previously unreported benefits and risks of GLP-1 RAs,” the authors wrote.

For the comprehensive study, Al-Aly and his colleagues evaluated data from the US Department of Veterans Affairs on more than 2 million veterans treated for diabetes between October 2017 and December 2023, assessing GLP-1 RA treatment in comparison with other diabetes therapies regarding a striking 175 clinical outcomes.

Of the patients, 215,970 initiated treatment with GLP-1 RAs; 159,465 started sulfonylureas, 117,989 dipeptidyl peptidase 4 inhibitors, and 258,614 were initiated on sodium-glucose cotransporter-2 inhibitors.

The study also included a composite group of the latter three drug groups (n = 536,068), and a control group of 1,203,097 of patients receiving usual care, who were compared with usual care with the addition of GLP-1 RAs.

After inverse probability weighting, the groups were well-balanced in terms of their baseline characteristics. While the majority in the VA cohort overall were White men, the study adjusted for gender, age, race, comorbidities, and an extensive array of covariates.

With an average follow-up of 3.68 years, after the multivariate adjustment, GLP-1 RAs showed “effectiveness and risks that extended beyond those currently recognized,” in comparison with each of the treatment groups and with the main control group of usual care, the authors reported.

For the largest comparison with the main control group of usual care alone, the addition of GLP-1 RAs was associated with a decreased risk in 24% of the outcomes evaluated, and an increased risk in 10.86% of outcomes, with no significant difference for the remaining 65.14% of outcomes.

Of the various benefits, key improvements included a reduced risk for several substance use disorders including alcohol (hazard ratio [HR], 0.89) and opioid (HR, 0.87) use, suicidal ideation, attempt or intentional self-harm (HR, 0.90), seizures (HR, 0.90), neurocognitive disorders including Alzheimer disease (HR, 0.88) and dementia (HR, 0.92), coagulation and clotting disorders (HR, 0.92), and cardiac arrest (HR, 0.78).

Further benefits vs usual care alone included a reduced risk for infectious illnesses (HR, 0.88), acute kidney injury (HR, 0.88), and chronic kidney disease (CKD) (HR, 0.97; P <.05 for all the outcomes).

In terms of risks associated with GLP-1 RAs, in addition to the well-known risks for nausea and vomiting, additional increased risks vs usual care included gastrointestinal disorders such as noninfectious gastroenteritis (HR, 1.12), hypotension (HR, 1.06), arthritis (HR, 1.11), tendinitis and synovitis (HR, 1.10), interstitial nephritis (HR, 1.06), nephrolithiasis (HR, 1.15), and the known risk for drug-induced acute pancreatitis (HR, 2.46).

 

Neuropsychiatric Effects

Among the various benefits in the study, Al-Aly said some of the most intriguing are those involving the brain.

“I am struck by the consistent effects on many neuropsychiatric disorders — this aligns with data showing the presence of GLP-1 receptors in the brain and evidence showing that GLP-1s permeates through the blood brain barrier and acts on the brain to reduce inflammation and oxidative stress, improve neuroplasticity, etc.,” he said.

“Clearly, there is a neurotropic effect. There is also the possibility of an effect on the immune system/fighting infection — with reduced risks of infections, sepsis, etc.”

The reductions in suicidal ideation are encouraging after earlier reports of suicidal thoughts and self-injury among young users of GLP-1 RAs prompted concerns, including a 2023 review of the drug use by the European Medicines Agency that ultimately found no causal association, the authors added. The US Food and Drug Administration also found no association with GLP-1s and suicide risk.

The reductions in addictive behaviors are also encouraging and are consistent with the role of GLP-1 receptors in the brain in terms of impulse control and reward signaling that can relate to addictive behaviors, Al-Aly explained.

The reduced risks for dementia and Alzheimer disease are likewise consistent with preclinical studies in animal models of Alzheimer disease, as well as clinical studies showing a reduced risk for dementia in patients with type 2 diabetes, the authors noted.

The observed reduced risk for seizures further “adds to an emerging body of knowledge, both mechanistic and early clinical data, indicative of the anticonvulsant properties of GLP-1 RA use,” they added.

“GLP-1 RAs should be further evaluated in future studies as potential adjuvant therapeutics for epilepsy and its associated comorbidities,” the authors suggested.

 

Kidneys

While the findings support evidence of protective effects of GLP-1 RAs on the kidneys and a reduction in CKD risk, notable risks observed, also involving the kidneys, include nephrolithiasis or kidney stones.

Al-Aly noted the mechanisms with kidney stone formation are very different from CKD, and he speculated that the risk for the former could in fact stem from potentially low hydration with GLP-1 RA use.

“When patients are on GLP-1 RAs, they definitely eat a lot less to lose weight, but they also hydrate themselves less,” he explained in a press briefing. “They drink less water because they feel full very quickly after eating, and I’m just theorizing, but perhaps chronic dehydration [is behind] the increased risk of kidney stones.”

 

Modest Effects?

While, overall, the benefits of GLP-1 RA drugs showed modest benefits ranging between a 10% and 20% reduction for most outcomes, Al-Aly said those effects are still important.

“The modest effect does not negate the potential value of these drugs, especially for conditions where few effective treatment options exist, for example, dementia,” he said in the press statement.

“This may also imply that these drugs are most beneficial when used in conjunction with other interventions, such as lifestyle changes or other medications.”

 

Potential Confounders A Concern

Commenting on the study, David M. Nathan, MD, founder of the MGH Diabetes Center and a professor of medicine at Harvard Medical School, in Boston, Massachusetts, noted that, while the study is hypothesis-generating, the key limitation is its observational nature.

“The authors did a perfectly respectable job of doing all you can do to adjust for [confounders], but with these kinds of studies, as much as you try to statistically account for differences in the populations before they were put on the drug, you can never truly adjust for all the potential confounders that may influence the results,” he told this news organization.

In addition, the 3.8-year follow-up time of the study, as the authors acknowledge, is especially short considering that GLP-1 RAs are generally recommended to be taken indefinitely.

“You have to take these drugs presumably for a lifetime and we have no idea what the longer-term benefits and risks are,” Nathan said.

Nathan, who was among the first investigators to evaluate GLP-1 RAs about 30 years ago, underscored that “I do think that these drugs are generally really spectacular; they’ve taken over the world and they are probably the single greatest pharmaceutical story of the 21st century.”

“But much more rigorous randomized trials would be needed to prove study results that haven’t already been established in previous clinical trials,” he said.

“The types of [randomized] trials that are necessary are very expensive and require a huge amount of work, but at the end of the day, they provide proof as to what does and doesn’t work, and what the true risks are,” he added. “Whether the GLP-RAs will cure all ills and bring about world peace needs to be proved.”

In further comments provided through the Science Media Center, Stephen O’Rahilly, FRS, a professor of clinical biochemistry and medicine and director of the Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, England, echoed Nathan’s concern that “studies such as these have to be interpreted very cautiously as the people studied have not been randomly allocated to GLP-1 RA treatment, so any difference between those taking and not taking the class of drug could potentially be attributable to factors other than the drug.”

He noted, however, that “the study provides useful reassurance about the safety of this class of drugs. The expected benefits on heart disease, stroke and other cardiovascular and most kidney diseases are clearly seen.”

Al-Aly reported being an uncompensated consultant for Pfizer. Nathan, who has previously conducted clinical trials on GLP-1 RAs, currently has no relationships to report. O’Rahilly reported receiving remuneration from several pharmaceutical companies for scientific advice relating to the development of drugs for metabolic diseases, but none involving GLP-1 RAs in the past 3 years.

A version of this article first appeared on Medscape.com.

A study of more than 2 million veterans with diabetes builds on evidence of broad-ranging benefits and risks of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in the clinical setting, providing an “atlas” mapping extensive outcomes and some new insights to potentially explore in more rigorous clinical trials.

“This is the largest study on GLP-1 receptor agonists,” first author Ziyad Al-Aly, MD, chief of research and development at the US Department of Veterans Affairs (VA) St. Louis Healthcare System, in St. Louis, told this news organization regarding the research, published this week, in Nature Medicine.

“The [study] reflects the real experiences of people using GLP-1 RAs [in the VA] clinical setting,” he said.

“Altogether, our discovery approach confirms previous studies and clinical trials and also uncovers previously unreported benefits and risks of GLP-1 RAs,” the authors wrote.

For the comprehensive study, Al-Aly and his colleagues evaluated data from the US Department of Veterans Affairs on more than 2 million veterans treated for diabetes between October 2017 and December 2023, assessing GLP-1 RA treatment in comparison with other diabetes therapies regarding a striking 175 clinical outcomes.

Of the patients, 215,970 initiated treatment with GLP-1 RAs; 159,465 started sulfonylureas, 117,989 dipeptidyl peptidase 4 inhibitors, and 258,614 were initiated on sodium-glucose cotransporter-2 inhibitors.

The study also included a composite group of the latter three drug groups (n = 536,068), and a control group of 1,203,097 of patients receiving usual care, who were compared with usual care with the addition of GLP-1 RAs.

After inverse probability weighting, the groups were well-balanced in terms of their baseline characteristics. While the majority in the VA cohort overall were White men, the study adjusted for gender, age, race, comorbidities, and an extensive array of covariates.

With an average follow-up of 3.68 years, after the multivariate adjustment, GLP-1 RAs showed “effectiveness and risks that extended beyond those currently recognized,” in comparison with each of the treatment groups and with the main control group of usual care, the authors reported.

For the largest comparison with the main control group of usual care alone, the addition of GLP-1 RAs was associated with a decreased risk in 24% of the outcomes evaluated, and an increased risk in 10.86% of outcomes, with no significant difference for the remaining 65.14% of outcomes.

Of the various benefits, key improvements included a reduced risk for several substance use disorders including alcohol (hazard ratio [HR], 0.89) and opioid (HR, 0.87) use, suicidal ideation, attempt or intentional self-harm (HR, 0.90), seizures (HR, 0.90), neurocognitive disorders including Alzheimer disease (HR, 0.88) and dementia (HR, 0.92), coagulation and clotting disorders (HR, 0.92), and cardiac arrest (HR, 0.78).

Further benefits vs usual care alone included a reduced risk for infectious illnesses (HR, 0.88), acute kidney injury (HR, 0.88), and chronic kidney disease (CKD) (HR, 0.97; P <.05 for all the outcomes).

In terms of risks associated with GLP-1 RAs, in addition to the well-known risks for nausea and vomiting, additional increased risks vs usual care included gastrointestinal disorders such as noninfectious gastroenteritis (HR, 1.12), hypotension (HR, 1.06), arthritis (HR, 1.11), tendinitis and synovitis (HR, 1.10), interstitial nephritis (HR, 1.06), nephrolithiasis (HR, 1.15), and the known risk for drug-induced acute pancreatitis (HR, 2.46).

 

Neuropsychiatric Effects

Among the various benefits in the study, Al-Aly said some of the most intriguing are those involving the brain.

“I am struck by the consistent effects on many neuropsychiatric disorders — this aligns with data showing the presence of GLP-1 receptors in the brain and evidence showing that GLP-1s permeates through the blood brain barrier and acts on the brain to reduce inflammation and oxidative stress, improve neuroplasticity, etc.,” he said.

“Clearly, there is a neurotropic effect. There is also the possibility of an effect on the immune system/fighting infection — with reduced risks of infections, sepsis, etc.”

The reductions in suicidal ideation are encouraging after earlier reports of suicidal thoughts and self-injury among young users of GLP-1 RAs prompted concerns, including a 2023 review of the drug use by the European Medicines Agency that ultimately found no causal association, the authors added. The US Food and Drug Administration also found no association with GLP-1s and suicide risk.

The reductions in addictive behaviors are also encouraging and are consistent with the role of GLP-1 receptors in the brain in terms of impulse control and reward signaling that can relate to addictive behaviors, Al-Aly explained.

The reduced risks for dementia and Alzheimer disease are likewise consistent with preclinical studies in animal models of Alzheimer disease, as well as clinical studies showing a reduced risk for dementia in patients with type 2 diabetes, the authors noted.

The observed reduced risk for seizures further “adds to an emerging body of knowledge, both mechanistic and early clinical data, indicative of the anticonvulsant properties of GLP-1 RA use,” they added.

“GLP-1 RAs should be further evaluated in future studies as potential adjuvant therapeutics for epilepsy and its associated comorbidities,” the authors suggested.

 

Kidneys

While the findings support evidence of protective effects of GLP-1 RAs on the kidneys and a reduction in CKD risk, notable risks observed, also involving the kidneys, include nephrolithiasis or kidney stones.

Al-Aly noted the mechanisms with kidney stone formation are very different from CKD, and he speculated that the risk for the former could in fact stem from potentially low hydration with GLP-1 RA use.

“When patients are on GLP-1 RAs, they definitely eat a lot less to lose weight, but they also hydrate themselves less,” he explained in a press briefing. “They drink less water because they feel full very quickly after eating, and I’m just theorizing, but perhaps chronic dehydration [is behind] the increased risk of kidney stones.”

 

Modest Effects?

While, overall, the benefits of GLP-1 RA drugs showed modest benefits ranging between a 10% and 20% reduction for most outcomes, Al-Aly said those effects are still important.

“The modest effect does not negate the potential value of these drugs, especially for conditions where few effective treatment options exist, for example, dementia,” he said in the press statement.

“This may also imply that these drugs are most beneficial when used in conjunction with other interventions, such as lifestyle changes or other medications.”

 

Potential Confounders A Concern

Commenting on the study, David M. Nathan, MD, founder of the MGH Diabetes Center and a professor of medicine at Harvard Medical School, in Boston, Massachusetts, noted that, while the study is hypothesis-generating, the key limitation is its observational nature.

“The authors did a perfectly respectable job of doing all you can do to adjust for [confounders], but with these kinds of studies, as much as you try to statistically account for differences in the populations before they were put on the drug, you can never truly adjust for all the potential confounders that may influence the results,” he told this news organization.

In addition, the 3.8-year follow-up time of the study, as the authors acknowledge, is especially short considering that GLP-1 RAs are generally recommended to be taken indefinitely.

“You have to take these drugs presumably for a lifetime and we have no idea what the longer-term benefits and risks are,” Nathan said.

Nathan, who was among the first investigators to evaluate GLP-1 RAs about 30 years ago, underscored that “I do think that these drugs are generally really spectacular; they’ve taken over the world and they are probably the single greatest pharmaceutical story of the 21st century.”

“But much more rigorous randomized trials would be needed to prove study results that haven’t already been established in previous clinical trials,” he said.

“The types of [randomized] trials that are necessary are very expensive and require a huge amount of work, but at the end of the day, they provide proof as to what does and doesn’t work, and what the true risks are,” he added. “Whether the GLP-RAs will cure all ills and bring about world peace needs to be proved.”

In further comments provided through the Science Media Center, Stephen O’Rahilly, FRS, a professor of clinical biochemistry and medicine and director of the Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, England, echoed Nathan’s concern that “studies such as these have to be interpreted very cautiously as the people studied have not been randomly allocated to GLP-1 RA treatment, so any difference between those taking and not taking the class of drug could potentially be attributable to factors other than the drug.”

He noted, however, that “the study provides useful reassurance about the safety of this class of drugs. The expected benefits on heart disease, stroke and other cardiovascular and most kidney diseases are clearly seen.”

Al-Aly reported being an uncompensated consultant for Pfizer. Nathan, who has previously conducted clinical trials on GLP-1 RAs, currently has no relationships to report. O’Rahilly reported receiving remuneration from several pharmaceutical companies for scientific advice relating to the development of drugs for metabolic diseases, but none involving GLP-1 RAs in the past 3 years.

A version of this article first appeared on Medscape.com.

A young boy with a habit of screaming when he didn’t get his way is among the patients Joannie Yeh, MD, a primary care physician at Nemours Children’s Health in Media, Pennsylvania, has helped in her practice.

Yeh taught the boy to stretch out his hands into the shape of a starfish, then trace around the edges of his fingers while breathing slowly and deeply. His parents later reported that after using the strategy at home, their son was no longer taking his rage out on his younger siblings.

Interventions like breathing exercises are just a few techniques Yeh hopes more primary care clinicians will teach young patients as mental health issues among this population soar to a national state of emergency, major medical groups say. But many children go without treatment because of shortages of mental health clinicians and long wait-lists for appointments.

“Knowledge of different types of interventions allows pediatricians to offer more options to families — more than just medication alone,” Yeh said. “There are some strategies, like cognitive behavioral therapy, that a therapist is equipped to deliver, but we can help explain them or teach simple skills that borrow from principles of higher-level techniques and can help patients and families while they wait to see a therapist.”

The use of techniques that are based on mindfulness, cognitive behavioral therapy, and psychotherapy are especially helpful to pediatricians after a child’s answers on a screener indicate they may be struggling with anxiety, depression, or attention-deficit/hyperactivity disorder (ADHD), said Theresa Nguyen, MD, chair of pediatrics at Greater Baltimore Medical Center, Baltimore.

“It kind of sucks if you come in worried and then your doctor says, ‘Okay, let me send you to a psychiatrist who you can’t see for 6 months; let me send you to a therapist who’s going to take a couple of weeks to get in with,’” Nguyen said.

Yeh said over the past few years she has cared for more youth coming in as follow-ups after an emergency department visit for a mental health episode.

“Oftentimes, this is the first time we become aware that the child is struggling,” Yeh said. “We are seeing issues like intentional medication overdose, referrals after other self-harm actions, or even the discovery of a note indicating the intention to do harm to self.”

Suicide deaths among 10- to 14-year-olds tripled between 2007 and 2018 and held steady through 2021, with rates climbing even among children as young as 8 years, according to a research in JAMA Network Open. Meanwhile, one in five high school students seriously contemplated suicide in 2023 (27% girls, 14% boys).

 

Mental Health Strategies for Kids in Primary Care

While pediatricians cannot replace a mental health professional, they have the unique advantage of maintaining a long-term relationship with patients. Experts said clinicians should take an active role in supporting the mental health of patients through a variety of evidence-based strategies.

Changing Thought Patterns 

Cognitive-behavioral therapy (CBT) involves identifying and challenging automatic negative thoughts, which can affect a child’s emotional state and lead to behaviors like withdrawal or lashing out.

Yeh recommended asking a child about what is bothering them, pointing out unhelpful and negative thoughts, and then offering a different, positive one instead.

She also often draws a picture of the CBT chart, which is a visual representation of how feelings lead to thoughts, and then behaviors.

“I draw this diagram because it helps give the patients a visual understanding of how their feelings and emotions are connected,” Yeh said.

 

Tools to Tolerate Stressful Situations

Simple tools like breathing exercises, body scanning, and physical exercise can help children better tolerate distress.

Pediatricians can also recommend families use guided meditations, which have been shown to lower anxiety and increase positive social behavior, said Mollie Grow, MD, an associate professor of pediatrics at the University of Washington Medicine and Seattle Children’s Hospital, both in Seattle.

But a child might first need to get negative energy out before they can become calm.

“So I’m like, ‘okay, let’s do actual physical exercise. Give me 10 jumping jacks.’ No one’s nervous after those jumping jacks,” Nguyen said. “When you’ve already been triggered, your nerves have gotten going, and you’re starting to spiral, you can’t slow yourself down enough to do a breathing exercise.”

Nguyen also said that cold water quickly calms the nervous system.

“I’ll run cold water in the office and have them put their hand in it until it’s almost frozen,” and the child or teen is able to think more clearly, Nguyen said. “It’s a real physiological response. It works.”

 

The Origin of a Feeling 

Explaining how symptoms of anxiety, depression, or ADHD work can help children and teens better understand that what they are experiencing is normal and better cope, Yeh said.

Clinicians might teach patients about how shallow breathing — a symptom of anxiety — is a result of the brain scanning for danger, and how slowing breathing tricks the brain into feeling safe again.

 

Barriers Abound

The use of these interventions in pediatric settings is not yet widespread, Grow said.

But starting in July 2025, the Accreditation Council for Graduate Medical Education will require pediatric residencies to include 4 weeks of mental health training. How that requirement is fulfilled will be up to residencies, said Brian Alverson, MD, pediatric program director and vice-chair of education at Nemours Children’s Hospital in Wilmington, Delaware.

Even with training, many pediatricians lack the time to address mental health issues during an office visit, said Carlos Lerner, MD, a professor of clinical pediatrics at University of California, Los Angeles Health. And despite low or sometimes no reimbursement for discussing these issues with patients, “the reality is we end up doing it anyway.”

Treating issues like anxiety and depression “is a daily, constant part of the care that I provide for my patients,” said Lerner. “Whether the pandemic or social media exacerbated it, we are absolutely seeing a rise in mental health issues.”

A version of this article first appeared on Medscape.com.

A young boy with a habit of screaming when he didn’t get his way is among the patients Joannie Yeh, MD, a primary care physician at Nemours Children’s Health in Media, Pennsylvania, has helped in her practice.

Yeh taught the boy to stretch out his hands into the shape of a starfish, then trace around the edges of his fingers while breathing slowly and deeply. His parents later reported that after using the strategy at home, their son was no longer taking his rage out on his younger siblings.

Interventions like breathing exercises are just a few techniques Yeh hopes more primary care clinicians will teach young patients as mental health issues among this population soar to a national state of emergency, major medical groups say. But many children go without treatment because of shortages of mental health clinicians and long wait-lists for appointments.

“Knowledge of different types of interventions allows pediatricians to offer more options to families — more than just medication alone,” Yeh said. “There are some strategies, like cognitive behavioral therapy, that a therapist is equipped to deliver, but we can help explain them or teach simple skills that borrow from principles of higher-level techniques and can help patients and families while they wait to see a therapist.”

The use of techniques that are based on mindfulness, cognitive behavioral therapy, and psychotherapy are especially helpful to pediatricians after a child’s answers on a screener indicate they may be struggling with anxiety, depression, or attention-deficit/hyperactivity disorder (ADHD), said Theresa Nguyen, MD, chair of pediatrics at Greater Baltimore Medical Center, Baltimore.

“It kind of sucks if you come in worried and then your doctor says, ‘Okay, let me send you to a psychiatrist who you can’t see for 6 months; let me send you to a therapist who’s going to take a couple of weeks to get in with,’” Nguyen said.

Yeh said over the past few years she has cared for more youth coming in as follow-ups after an emergency department visit for a mental health episode.

“Oftentimes, this is the first time we become aware that the child is struggling,” Yeh said. “We are seeing issues like intentional medication overdose, referrals after other self-harm actions, or even the discovery of a note indicating the intention to do harm to self.”

Suicide deaths among 10- to 14-year-olds tripled between 2007 and 2018 and held steady through 2021, with rates climbing even among children as young as 8 years, according to a research in JAMA Network Open. Meanwhile, one in five high school students seriously contemplated suicide in 2023 (27% girls, 14% boys).

 

Mental Health Strategies for Kids in Primary Care

While pediatricians cannot replace a mental health professional, they have the unique advantage of maintaining a long-term relationship with patients. Experts said clinicians should take an active role in supporting the mental health of patients through a variety of evidence-based strategies.

Changing Thought Patterns 

Cognitive-behavioral therapy (CBT) involves identifying and challenging automatic negative thoughts, which can affect a child’s emotional state and lead to behaviors like withdrawal or lashing out.

Yeh recommended asking a child about what is bothering them, pointing out unhelpful and negative thoughts, and then offering a different, positive one instead.

She also often draws a picture of the CBT chart, which is a visual representation of how feelings lead to thoughts, and then behaviors.

“I draw this diagram because it helps give the patients a visual understanding of how their feelings and emotions are connected,” Yeh said.

 

Tools to Tolerate Stressful Situations

Simple tools like breathing exercises, body scanning, and physical exercise can help children better tolerate distress.

Pediatricians can also recommend families use guided meditations, which have been shown to lower anxiety and increase positive social behavior, said Mollie Grow, MD, an associate professor of pediatrics at the University of Washington Medicine and Seattle Children’s Hospital, both in Seattle.

But a child might first need to get negative energy out before they can become calm.

“So I’m like, ‘okay, let’s do actual physical exercise. Give me 10 jumping jacks.’ No one’s nervous after those jumping jacks,” Nguyen said. “When you’ve already been triggered, your nerves have gotten going, and you’re starting to spiral, you can’t slow yourself down enough to do a breathing exercise.”

Nguyen also said that cold water quickly calms the nervous system.

“I’ll run cold water in the office and have them put their hand in it until it’s almost frozen,” and the child or teen is able to think more clearly, Nguyen said. “It’s a real physiological response. It works.”

 

The Origin of a Feeling 

Explaining how symptoms of anxiety, depression, or ADHD work can help children and teens better understand that what they are experiencing is normal and better cope, Yeh said.

Clinicians might teach patients about how shallow breathing — a symptom of anxiety — is a result of the brain scanning for danger, and how slowing breathing tricks the brain into feeling safe again.

 

Barriers Abound

The use of these interventions in pediatric settings is not yet widespread, Grow said.

But starting in July 2025, the Accreditation Council for Graduate Medical Education will require pediatric residencies to include 4 weeks of mental health training. How that requirement is fulfilled will be up to residencies, said Brian Alverson, MD, pediatric program director and vice-chair of education at Nemours Children’s Hospital in Wilmington, Delaware.

Even with training, many pediatricians lack the time to address mental health issues during an office visit, said Carlos Lerner, MD, a professor of clinical pediatrics at University of California, Los Angeles Health. And despite low or sometimes no reimbursement for discussing these issues with patients, “the reality is we end up doing it anyway.”

Treating issues like anxiety and depression “is a daily, constant part of the care that I provide for my patients,” said Lerner. “Whether the pandemic or social media exacerbated it, we are absolutely seeing a rise in mental health issues.”

A version of this article first appeared on Medscape.com.

A young boy with a habit of screaming when he didn’t get his way is among the patients Joannie Yeh, MD, a primary care physician at Nemours Children’s Health in Media, Pennsylvania, has helped in her practice.

Yeh taught the boy to stretch out his hands into the shape of a starfish, then trace around the edges of his fingers while breathing slowly and deeply. His parents later reported that after using the strategy at home, their son was no longer taking his rage out on his younger siblings.

Interventions like breathing exercises are just a few techniques Yeh hopes more primary care clinicians will teach young patients as mental health issues among this population soar to a national state of emergency, major medical groups say. But many children go without treatment because of shortages of mental health clinicians and long wait-lists for appointments.

“Knowledge of different types of interventions allows pediatricians to offer more options to families — more than just medication alone,” Yeh said. “There are some strategies, like cognitive behavioral therapy, that a therapist is equipped to deliver, but we can help explain them or teach simple skills that borrow from principles of higher-level techniques and can help patients and families while they wait to see a therapist.”

The use of techniques that are based on mindfulness, cognitive behavioral therapy, and psychotherapy are especially helpful to pediatricians after a child’s answers on a screener indicate they may be struggling with anxiety, depression, or attention-deficit/hyperactivity disorder (ADHD), said Theresa Nguyen, MD, chair of pediatrics at Greater Baltimore Medical Center, Baltimore.

“It kind of sucks if you come in worried and then your doctor says, ‘Okay, let me send you to a psychiatrist who you can’t see for 6 months; let me send you to a therapist who’s going to take a couple of weeks to get in with,’” Nguyen said.

Yeh said over the past few years she has cared for more youth coming in as follow-ups after an emergency department visit for a mental health episode.

“Oftentimes, this is the first time we become aware that the child is struggling,” Yeh said. “We are seeing issues like intentional medication overdose, referrals after other self-harm actions, or even the discovery of a note indicating the intention to do harm to self.”

Suicide deaths among 10- to 14-year-olds tripled between 2007 and 2018 and held steady through 2021, with rates climbing even among children as young as 8 years, according to a research in JAMA Network Open. Meanwhile, one in five high school students seriously contemplated suicide in 2023 (27% girls, 14% boys).

 

Mental Health Strategies for Kids in Primary Care

While pediatricians cannot replace a mental health professional, they have the unique advantage of maintaining a long-term relationship with patients. Experts said clinicians should take an active role in supporting the mental health of patients through a variety of evidence-based strategies.

Changing Thought Patterns 

Cognitive-behavioral therapy (CBT) involves identifying and challenging automatic negative thoughts, which can affect a child’s emotional state and lead to behaviors like withdrawal or lashing out.

Yeh recommended asking a child about what is bothering them, pointing out unhelpful and negative thoughts, and then offering a different, positive one instead.

She also often draws a picture of the CBT chart, which is a visual representation of how feelings lead to thoughts, and then behaviors.

“I draw this diagram because it helps give the patients a visual understanding of how their feelings and emotions are connected,” Yeh said.

 

Tools to Tolerate Stressful Situations

Simple tools like breathing exercises, body scanning, and physical exercise can help children better tolerate distress.

Pediatricians can also recommend families use guided meditations, which have been shown to lower anxiety and increase positive social behavior, said Mollie Grow, MD, an associate professor of pediatrics at the University of Washington Medicine and Seattle Children’s Hospital, both in Seattle.

But a child might first need to get negative energy out before they can become calm.

“So I’m like, ‘okay, let’s do actual physical exercise. Give me 10 jumping jacks.’ No one’s nervous after those jumping jacks,” Nguyen said. “When you’ve already been triggered, your nerves have gotten going, and you’re starting to spiral, you can’t slow yourself down enough to do a breathing exercise.”

Nguyen also said that cold water quickly calms the nervous system.

“I’ll run cold water in the office and have them put their hand in it until it’s almost frozen,” and the child or teen is able to think more clearly, Nguyen said. “It’s a real physiological response. It works.”

 

The Origin of a Feeling 

Explaining how symptoms of anxiety, depression, or ADHD work can help children and teens better understand that what they are experiencing is normal and better cope, Yeh said.

Clinicians might teach patients about how shallow breathing — a symptom of anxiety — is a result of the brain scanning for danger, and how slowing breathing tricks the brain into feeling safe again.

 

Barriers Abound

The use of these interventions in pediatric settings is not yet widespread, Grow said.

But starting in July 2025, the Accreditation Council for Graduate Medical Education will require pediatric residencies to include 4 weeks of mental health training. How that requirement is fulfilled will be up to residencies, said Brian Alverson, MD, pediatric program director and vice-chair of education at Nemours Children’s Hospital in Wilmington, Delaware.

Even with training, many pediatricians lack the time to address mental health issues during an office visit, said Carlos Lerner, MD, a professor of clinical pediatrics at University of California, Los Angeles Health. And despite low or sometimes no reimbursement for discussing these issues with patients, “the reality is we end up doing it anyway.”

Treating issues like anxiety and depression “is a daily, constant part of the care that I provide for my patients,” said Lerner. “Whether the pandemic or social media exacerbated it, we are absolutely seeing a rise in mental health issues.”

A version of this article first appeared on Medscape.com.

In his parting words as US Surgeon General, Vivek Murthy, MD, MBA, urges togetherness as it works through current and future issues, as opposed to continuing down the path of divisiveness.

“Today, we are faced with a profound choice: do we continue with the status quo, marked by pain, disconnection, and division? Or do we choose a different path—one of joy, health, and fulfillment where we turn toward each other instead of away from each other, where we choose love over fear; where we recognize community as the irreplaceable foundation for our well-being?” Murthy writes in his Jan. 7 valedictory essay. “As I finish my tenure as Surgeon General, this is my parting prescription, my final wish for all of us: choose community.”

Murthy based his essay on personal and professional experiences from his tenures as the 19th and 21st US Surgeon General. He outlines his individual perspective on the root causes of widespread pain and unhappiness he has seen across America and offers a prescription for how we can “cultivate health and fulfillment.”

The core pillars of community—relationships, service, and purpose—are powerful drivers of fulfillment, Murthy writes, because “community is a powerful source of life satisfaction and life expectancy.” In his essay, he describes how these elements affect our health.

Relationships can be a powerful source of joy and support. They can act as buffers to stress and break down the barriers of loneliness and improve your overall health. According to Murthy, one-third of adults and one-half of young people experience loneliness; and social disconnectedness increases the risk of heart disease, dementia, depression, anxiety, and premature death.

Service comprises the actions we take that benefit others. Research shows that sustained service efforts can reduce the risk of hypertension, stroke, early death, depression, and cognitive decline.

And purpose is the feeling of having an overarching life aim to guide our decisions and actions. Simply, it is the “why” we do something, and according to Murthy, a high sense of individual purpose may reduce the risk of early death as well as stroke, lung disease, and dementia.

Building community isn’t always easy, Murthy wrote. It requires “rethinking and, in some cases, rejecting the conventional wisdom that tells us what defines success and a good life.” At the conclusion of his essay, Murthy notes how choices we make now must be made with an eye toward the future.

“The choice we make to build community has the power to change lives and transform society,” he writes. “Let us never forget that good people with hearts full of love can change the world.”

In his parting words as US Surgeon General, Vivek Murthy, MD, MBA, urges togetherness as it works through current and future issues, as opposed to continuing down the path of divisiveness.

“Today, we are faced with a profound choice: do we continue with the status quo, marked by pain, disconnection, and division? Or do we choose a different path—one of joy, health, and fulfillment where we turn toward each other instead of away from each other, where we choose love over fear; where we recognize community as the irreplaceable foundation for our well-being?” Murthy writes in his Jan. 7 valedictory essay. “As I finish my tenure as Surgeon General, this is my parting prescription, my final wish for all of us: choose community.”

Murthy based his essay on personal and professional experiences from his tenures as the 19th and 21st US Surgeon General. He outlines his individual perspective on the root causes of widespread pain and unhappiness he has seen across America and offers a prescription for how we can “cultivate health and fulfillment.”

The core pillars of community—relationships, service, and purpose—are powerful drivers of fulfillment, Murthy writes, because “community is a powerful source of life satisfaction and life expectancy.” In his essay, he describes how these elements affect our health.

Relationships can be a powerful source of joy and support. They can act as buffers to stress and break down the barriers of loneliness and improve your overall health. According to Murthy, one-third of adults and one-half of young people experience loneliness; and social disconnectedness increases the risk of heart disease, dementia, depression, anxiety, and premature death.

Service comprises the actions we take that benefit others. Research shows that sustained service efforts can reduce the risk of hypertension, stroke, early death, depression, and cognitive decline.

And purpose is the feeling of having an overarching life aim to guide our decisions and actions. Simply, it is the “why” we do something, and according to Murthy, a high sense of individual purpose may reduce the risk of early death as well as stroke, lung disease, and dementia.

Building community isn’t always easy, Murthy wrote. It requires “rethinking and, in some cases, rejecting the conventional wisdom that tells us what defines success and a good life.” At the conclusion of his essay, Murthy notes how choices we make now must be made with an eye toward the future.

“The choice we make to build community has the power to change lives and transform society,” he writes. “Let us never forget that good people with hearts full of love can change the world.”

In his parting words as US Surgeon General, Vivek Murthy, MD, MBA, urges togetherness as it works through current and future issues, as opposed to continuing down the path of divisiveness.

“Today, we are faced with a profound choice: do we continue with the status quo, marked by pain, disconnection, and division? Or do we choose a different path—one of joy, health, and fulfillment where we turn toward each other instead of away from each other, where we choose love over fear; where we recognize community as the irreplaceable foundation for our well-being?” Murthy writes in his Jan. 7 valedictory essay. “As I finish my tenure as Surgeon General, this is my parting prescription, my final wish for all of us: choose community.”

Murthy based his essay on personal and professional experiences from his tenures as the 19th and 21st US Surgeon General. He outlines his individual perspective on the root causes of widespread pain and unhappiness he has seen across America and offers a prescription for how we can “cultivate health and fulfillment.”

The core pillars of community—relationships, service, and purpose—are powerful drivers of fulfillment, Murthy writes, because “community is a powerful source of life satisfaction and life expectancy.” In his essay, he describes how these elements affect our health.

Relationships can be a powerful source of joy and support. They can act as buffers to stress and break down the barriers of loneliness and improve your overall health. According to Murthy, one-third of adults and one-half of young people experience loneliness; and social disconnectedness increases the risk of heart disease, dementia, depression, anxiety, and premature death.

Service comprises the actions we take that benefit others. Research shows that sustained service efforts can reduce the risk of hypertension, stroke, early death, depression, and cognitive decline.

And purpose is the feeling of having an overarching life aim to guide our decisions and actions. Simply, it is the “why” we do something, and according to Murthy, a high sense of individual purpose may reduce the risk of early death as well as stroke, lung disease, and dementia.

Building community isn’t always easy, Murthy wrote. It requires “rethinking and, in some cases, rejecting the conventional wisdom that tells us what defines success and a good life.” At the conclusion of his essay, Murthy notes how choices we make now must be made with an eye toward the future.

“The choice we make to build community has the power to change lives and transform society,” he writes. “Let us never forget that good people with hearts full of love can change the world.”

In the second half of the school year, you may find that there is a surge of families coming to appointments with concerns about school performance, wondering if their child has ADHD. We expect you are very familiar with this condition, both diagnosing and treating it. So this month we will offer “mythbusters” for ADHD: Responding to common misperceptions about ADHD with a summary of what the research has demonstrated as emerging facts, what is clearly fiction and what falls into the gray space between.

Demographics

A CDC survey of parents from 2022 indicates that 11.4% of children aged 3-17 have ever been diagnosed with ADHD in the United States. This is more than double the ADHD global prevalence of 5%, suggesting that there is overdiagnosis of this condition in this country. Boys are almost twice as likely to be diagnosed (14.5%) as girls (8%), and White children were more likely to be diagnosed than were Black and Hispanic children. The prevalence of ADHD diagnosis decreases as family income increases, and the condition is more frequently diagnosed in 12- to 17-year-olds than in children 11 and younger. The great majority of youth with an ADHD diagnosis (78%) have at least one co-occurring psychiatric condition. Of the children diagnosed with ADHD, slightly over half receive medication treatment (53.6%) whereas nearly a third (30.1%) receive no ADHD-specific treatment.

The Multimodal Treatment of ADHD Study (MTA), a large (600 children, aged 7-9 years), multicenter, longitudinal study of treatment outcomes for medication as well as behavioral and combination therapies demonstrated in every site that medication alone and combination therapy were significantly superior to intensive behavioral treatment alone and to routine community care in the reduction of ADHD symptoms. Of note, problems commonly associated with ADHD (parent-child conflict, anxiety symptoms, poor academic performance, and limited social skills) improved only with the combination treatment. This suggests that while core ADHD symptoms require medication, associated problems will also require behavioral treatment.

The American Academy of Pediatrics has a useful resource guide (healthychildren.org) highlighting the possible symptoms of inattention, hyperactivity, and impulsivity that should be investigated when considering this diagnosis. It is a clinical diagnosis, but screening instruments (such as the Vanderbilt) can be very helpful to identifying symptoms that should be present in more than one setting (home and school). While a child with ADHD can appear calm and focused when receiving direct one-to-one attention (as during a pediatrician’s appointment), symptoms may flourish in less structured or supervised settings. Sometimes parents are keen reporters of a child’s behaviors, but some loving (and exhausted) parents may overreact to a normal degree of inattention or disobedience. This can be especially true when a parent has a more detail-oriented temperament than the child, or with younger children and first-time parents. It is important to consider ADHD when you hear about social difficulties as well as academic ones, where there is a family history of ADHD or when a child is more impulsive, hyperactive, or inattentive than you would expect given their age and developmental stage. Confirm your clinical exam with teacher and parent reports. If the reports don’t line up or there are persistent learning problems in school, consider neuropsychological testing to root out a learning disability.

 

Myth 1: “ADHD never starts in adolescence; you can’t diagnose it after elementary school.”

Diagnostic criteria used to require that symptoms were present before the age of 7 (DSM 3). But current criteria allow for diagnosis before 12 years of age or after. While the consensus is that ADHD is present in childhood, its symptoms are often not apparent. This is because normal development in much younger children is marked by higher levels of activity, distractibility, and impulsivity. Also, children with inattentive-type ADHD may not be apparent to adults if they are performing adequately in school. These youth often do not present for assessment until the challenges of a busy course load make their inattention and consequent inefficiency apparent, in high school or even college. Certainly, when a teenager presents complaining of trouble performing at school, it is critical to rule out an overburdened schedule, anxiety or mood disorder, poor sleep habits or sleep disorder, and substance use disorders, all of which are more common in adolescence. But inattentive-type ADHD that was previously missed is also a possibility worth investigating.

Myth 2: “Most children outgrow ADHD; it’s best to find natural solutions and wait it out.”

Early epidemiological studies suggested that as many as 30% of ADHD cases remitted by adulthood, but more recent data has adjusted that number down substantially, closer to 9%. Interestingly, it appears that 10% of patients will experience sustained symptoms, 9% will experience recovery (sustained remission without treatment), and a large majority will have a remitting and relapsing course into adulthood.¹

This emerging evidence suggests that ADHD is almost always a lifelong condition. Untreated, it can threaten healthy development (including social skills and self-esteem) and day-to-day function (academic, social and athletic performance and even vulnerability to accidents) in ways that can be profound. The MTA Study has powerfully demonstrated the efficacy of pharmacological treatment and of specific behavioral treatments for ADHD and associated problems.

 

Myth 3: “You should exhaust natural cures first before trying medications.”

There has been a large amount of research into a variety of “natural” treatments for ADHD: special diets, supplements, increased exercise, and interventions like neurofeedback. While high-dose omega 3 fatty acid supplementation has demonstrated mild improvement in ADHD symptoms, no “natural” treatment has come close to the efficacy of stimulant medications. Interventions such as neurofeedback are expensive and time-consuming without any demonstrated efficacy. That said, improving a child’s routines around sleep, nutrition, and regular exercise are broadly useful strategies to improve any child’s (or adult’s) energy, impulse control, attention, motivation, and capacity to manage adversity and stress. Start any treatment by addressing sleep and exercise, including moderating time spent on screens, to support healthy function. But only medication will achieve symptom remission if your patient has underlying ADHD.

Myth 4: “All medications are equally effective in ADHD.”

It is well-established that stimulants are more effective than non-stimulants in the treatment of ADHD symptoms, with an effect size that is almost double that of non-stimulants.²

Amphetamine-based medications are slightly more effective than methylphenidate-based medications, but they are also generally less well-tolerated. Individual patients commonly have a better response to one class than the other, but you will need a trial to determine which one. It is reasonable to start a patient with an extended formulation of one class, based on your assessment of their vulnerability to side effects or a family history of medication response. Non-stimulants are of use when stimulants are not tolerated (ie, use of atomoxetine with patients who have comorbid anxiety), or to target specific symptoms, such as guanfacine or clonidine for hyperactivity.

 

Myth 5: “You can’t treat ADHD in substance abusing teens, stimulant medications are addictive.”

ADHD itself (not medications) increases the risk for addiction; those with ADHD are almost twice as likely to develop a substance use disorder, with highest risk for marijuana, alcohol, and nicotine abuse.³

This may be a function of limited impulse control or increased sensitivity in the ADHD brain to a drug’s addictive potential. Importantly, there is growing evidence that youth whose ADHD is treated pharmacologically are at lower risk for addiction than their peers with untreated ADHD.⁴

Those youth who have both ADHD and addiction are more likely to stay engaged in treatment for addiction when their ADHD is effectively treated, and there are medication formulations (lisdexamfetamine) that are safe in addiction (cannot be absorbed nasally or intravenously). It is important for you to talk about the heightened vulnerability to addiction with your ADHD patients and their parents, and the value of effective treatment in preventing this complication.

 

Myth 6: “ADHD is usually behavioral. Help parents to set rules, expectations, and limits instead of medicating the problem.”

Bad parenting does not cause ADHD. ADHD is marked by difficulties with impulse control, hyperactivity, and sustaining attention with matters that are not intrinsically engaging. “Behavioral issues” are patterns of behavior children learn to seek rewards or avoid negative consequences. Youth with ADHD can develop behavioral problems, but these are usually driven by negative feedback about their activity level, forgetfulness, or impulse control, which they are not able to change. This can lead to frustration and irritability, poor self-esteem, and even hopelessness — in parents and children both!

While parents are not the source of ADHD symptoms, there is a great deal of parent education and support that can be powerfully effective for these families. Parents benefit from learning strategies that can help their children to shift their attention, plan ahead, and manage frustration, especially for times when their children are unmedicated (vacations and bedtime). It is worth noting that ADHD is among the most heritable of youth psychiatric illnesses, so it is not uncommon for a parent of a child with ADHD to have similar symptoms. If the parents’ ADHD is untreated, they may be more impulsive themselves. They may also be extra sensitive to the qualities they dislike in themselves, inadvertently adding to their children’s sense of shame. ADHD is very treatable, and those with it can learn executive function skills and organizational strategies that can equip them to manage residual symptoms. Parents will benefit from strategies to understand their children and to help them learn adaptive skills in a realistic way. Your discussions with parents could help the families in your practice make adjustments that can translate into big differences in their child’s healthiest development.

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

References

1. Sibley MH et al. MTA Cooperative Group. Variable Patterns of Remission From ADHD in the Multimodal Treatment Study of ADHD. Am J Psychiatry. 2022 Feb;179(2):142-151. doi: 10.1176/appi.ajp.2021.21010032.

2. Cortese S et al. Comparative Efficacy and Tolerability of Medications for Attention-Deficit Hyperactivity Disorder in Children, Adolescents, and Adults: A Systematic Review and Network Meta-Analysis. Lancet Psychiatry. 2018 Sep;5(9):727-738. doi: 10.1016/S2215-0366(18)30269-4.

3. Lee SS et al. Prospective Association of Childhood Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use and Abuse/Dependence: A Meta-Analytic Review. Clin Psychol Rev. 2011 Apr;31(3):328-41. doi: 10.1016/j.cpr.2011.01.006. 

4. Chorniy A, Kitashima L. Sex, Drugs, and ADHD: The Effects of ADHD Pharmacological Treatment on Teens’ Risky Behaviors. Labour Economics. 2016;43:87-105. doi.org/10.1016/j.labeco.2016.06.014.

In the second half of the school year, you may find that there is a surge of families coming to appointments with concerns about school performance, wondering if their child has ADHD. We expect you are very familiar with this condition, both diagnosing and treating it. So this month we will offer “mythbusters” for ADHD: Responding to common misperceptions about ADHD with a summary of what the research has demonstrated as emerging facts, what is clearly fiction and what falls into the gray space between.

Demographics

A CDC survey of parents from 2022 indicates that 11.4% of children aged 3-17 have ever been diagnosed with ADHD in the United States. This is more than double the ADHD global prevalence of 5%, suggesting that there is overdiagnosis of this condition in this country. Boys are almost twice as likely to be diagnosed (14.5%) as girls (8%), and White children were more likely to be diagnosed than were Black and Hispanic children. The prevalence of ADHD diagnosis decreases as family income increases, and the condition is more frequently diagnosed in 12- to 17-year-olds than in children 11 and younger. The great majority of youth with an ADHD diagnosis (78%) have at least one co-occurring psychiatric condition. Of the children diagnosed with ADHD, slightly over half receive medication treatment (53.6%) whereas nearly a third (30.1%) receive no ADHD-specific treatment.

The Multimodal Treatment of ADHD Study (MTA), a large (600 children, aged 7-9 years), multicenter, longitudinal study of treatment outcomes for medication as well as behavioral and combination therapies demonstrated in every site that medication alone and combination therapy were significantly superior to intensive behavioral treatment alone and to routine community care in the reduction of ADHD symptoms. Of note, problems commonly associated with ADHD (parent-child conflict, anxiety symptoms, poor academic performance, and limited social skills) improved only with the combination treatment. This suggests that while core ADHD symptoms require medication, associated problems will also require behavioral treatment.

The American Academy of Pediatrics has a useful resource guide (healthychildren.org) highlighting the possible symptoms of inattention, hyperactivity, and impulsivity that should be investigated when considering this diagnosis. It is a clinical diagnosis, but screening instruments (such as the Vanderbilt) can be very helpful to identifying symptoms that should be present in more than one setting (home and school). While a child with ADHD can appear calm and focused when receiving direct one-to-one attention (as during a pediatrician’s appointment), symptoms may flourish in less structured or supervised settings. Sometimes parents are keen reporters of a child’s behaviors, but some loving (and exhausted) parents may overreact to a normal degree of inattention or disobedience. This can be especially true when a parent has a more detail-oriented temperament than the child, or with younger children and first-time parents. It is important to consider ADHD when you hear about social difficulties as well as academic ones, where there is a family history of ADHD or when a child is more impulsive, hyperactive, or inattentive than you would expect given their age and developmental stage. Confirm your clinical exam with teacher and parent reports. If the reports don’t line up or there are persistent learning problems in school, consider neuropsychological testing to root out a learning disability.

 

Myth 1: “ADHD never starts in adolescence; you can’t diagnose it after elementary school.”

Diagnostic criteria used to require that symptoms were present before the age of 7 (DSM 3). But current criteria allow for diagnosis before 12 years of age or after. While the consensus is that ADHD is present in childhood, its symptoms are often not apparent. This is because normal development in much younger children is marked by higher levels of activity, distractibility, and impulsivity. Also, children with inattentive-type ADHD may not be apparent to adults if they are performing adequately in school. These youth often do not present for assessment until the challenges of a busy course load make their inattention and consequent inefficiency apparent, in high school or even college. Certainly, when a teenager presents complaining of trouble performing at school, it is critical to rule out an overburdened schedule, anxiety or mood disorder, poor sleep habits or sleep disorder, and substance use disorders, all of which are more common in adolescence. But inattentive-type ADHD that was previously missed is also a possibility worth investigating.

Myth 2: “Most children outgrow ADHD; it’s best to find natural solutions and wait it out.”

Early epidemiological studies suggested that as many as 30% of ADHD cases remitted by adulthood, but more recent data has adjusted that number down substantially, closer to 9%. Interestingly, it appears that 10% of patients will experience sustained symptoms, 9% will experience recovery (sustained remission without treatment), and a large majority will have a remitting and relapsing course into adulthood.¹

This emerging evidence suggests that ADHD is almost always a lifelong condition. Untreated, it can threaten healthy development (including social skills and self-esteem) and day-to-day function (academic, social and athletic performance and even vulnerability to accidents) in ways that can be profound. The MTA Study has powerfully demonstrated the efficacy of pharmacological treatment and of specific behavioral treatments for ADHD and associated problems.

 

Myth 3: “You should exhaust natural cures first before trying medications.”

There has been a large amount of research into a variety of “natural” treatments for ADHD: special diets, supplements, increased exercise, and interventions like neurofeedback. While high-dose omega 3 fatty acid supplementation has demonstrated mild improvement in ADHD symptoms, no “natural” treatment has come close to the efficacy of stimulant medications. Interventions such as neurofeedback are expensive and time-consuming without any demonstrated efficacy. That said, improving a child’s routines around sleep, nutrition, and regular exercise are broadly useful strategies to improve any child’s (or adult’s) energy, impulse control, attention, motivation, and capacity to manage adversity and stress. Start any treatment by addressing sleep and exercise, including moderating time spent on screens, to support healthy function. But only medication will achieve symptom remission if your patient has underlying ADHD.

Myth 4: “All medications are equally effective in ADHD.”

It is well-established that stimulants are more effective than non-stimulants in the treatment of ADHD symptoms, with an effect size that is almost double that of non-stimulants.²

Amphetamine-based medications are slightly more effective than methylphenidate-based medications, but they are also generally less well-tolerated. Individual patients commonly have a better response to one class than the other, but you will need a trial to determine which one. It is reasonable to start a patient with an extended formulation of one class, based on your assessment of their vulnerability to side effects or a family history of medication response. Non-stimulants are of use when stimulants are not tolerated (ie, use of atomoxetine with patients who have comorbid anxiety), or to target specific symptoms, such as guanfacine or clonidine for hyperactivity.

 

Myth 5: “You can’t treat ADHD in substance abusing teens, stimulant medications are addictive.”

ADHD itself (not medications) increases the risk for addiction; those with ADHD are almost twice as likely to develop a substance use disorder, with highest risk for marijuana, alcohol, and nicotine abuse.³

This may be a function of limited impulse control or increased sensitivity in the ADHD brain to a drug’s addictive potential. Importantly, there is growing evidence that youth whose ADHD is treated pharmacologically are at lower risk for addiction than their peers with untreated ADHD.⁴

Those youth who have both ADHD and addiction are more likely to stay engaged in treatment for addiction when their ADHD is effectively treated, and there are medication formulations (lisdexamfetamine) that are safe in addiction (cannot be absorbed nasally or intravenously). It is important for you to talk about the heightened vulnerability to addiction with your ADHD patients and their parents, and the value of effective treatment in preventing this complication.

 

Myth 6: “ADHD is usually behavioral. Help parents to set rules, expectations, and limits instead of medicating the problem.”

Bad parenting does not cause ADHD. ADHD is marked by difficulties with impulse control, hyperactivity, and sustaining attention with matters that are not intrinsically engaging. “Behavioral issues” are patterns of behavior children learn to seek rewards or avoid negative consequences. Youth with ADHD can develop behavioral problems, but these are usually driven by negative feedback about their activity level, forgetfulness, or impulse control, which they are not able to change. This can lead to frustration and irritability, poor self-esteem, and even hopelessness — in parents and children both!

While parents are not the source of ADHD symptoms, there is a great deal of parent education and support that can be powerfully effective for these families. Parents benefit from learning strategies that can help their children to shift their attention, plan ahead, and manage frustration, especially for times when their children are unmedicated (vacations and bedtime). It is worth noting that ADHD is among the most heritable of youth psychiatric illnesses, so it is not uncommon for a parent of a child with ADHD to have similar symptoms. If the parents’ ADHD is untreated, they may be more impulsive themselves. They may also be extra sensitive to the qualities they dislike in themselves, inadvertently adding to their children’s sense of shame. ADHD is very treatable, and those with it can learn executive function skills and organizational strategies that can equip them to manage residual symptoms. Parents will benefit from strategies to understand their children and to help them learn adaptive skills in a realistic way. Your discussions with parents could help the families in your practice make adjustments that can translate into big differences in their child’s healthiest development.

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

References

1. Sibley MH et al. MTA Cooperative Group. Variable Patterns of Remission From ADHD in the Multimodal Treatment Study of ADHD. Am J Psychiatry. 2022 Feb;179(2):142-151. doi: 10.1176/appi.ajp.2021.21010032.

2. Cortese S et al. Comparative Efficacy and Tolerability of Medications for Attention-Deficit Hyperactivity Disorder in Children, Adolescents, and Adults: A Systematic Review and Network Meta-Analysis. Lancet Psychiatry. 2018 Sep;5(9):727-738. doi: 10.1016/S2215-0366(18)30269-4.

3. Lee SS et al. Prospective Association of Childhood Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use and Abuse/Dependence: A Meta-Analytic Review. Clin Psychol Rev. 2011 Apr;31(3):328-41. doi: 10.1016/j.cpr.2011.01.006. 

4. Chorniy A, Kitashima L. Sex, Drugs, and ADHD: The Effects of ADHD Pharmacological Treatment on Teens’ Risky Behaviors. Labour Economics. 2016;43:87-105. doi.org/10.1016/j.labeco.2016.06.014.

In the second half of the school year, you may find that there is a surge of families coming to appointments with concerns about school performance, wondering if their child has ADHD. We expect you are very familiar with this condition, both diagnosing and treating it. So this month we will offer “mythbusters” for ADHD: Responding to common misperceptions about ADHD with a summary of what the research has demonstrated as emerging facts, what is clearly fiction and what falls into the gray space between.

Demographics

A CDC survey of parents from 2022 indicates that 11.4% of children aged 3-17 have ever been diagnosed with ADHD in the United States. This is more than double the ADHD global prevalence of 5%, suggesting that there is overdiagnosis of this condition in this country. Boys are almost twice as likely to be diagnosed (14.5%) as girls (8%), and White children were more likely to be diagnosed than were Black and Hispanic children. The prevalence of ADHD diagnosis decreases as family income increases, and the condition is more frequently diagnosed in 12- to 17-year-olds than in children 11 and younger. The great majority of youth with an ADHD diagnosis (78%) have at least one co-occurring psychiatric condition. Of the children diagnosed with ADHD, slightly over half receive medication treatment (53.6%) whereas nearly a third (30.1%) receive no ADHD-specific treatment.

The Multimodal Treatment of ADHD Study (MTA), a large (600 children, aged 7-9 years), multicenter, longitudinal study of treatment outcomes for medication as well as behavioral and combination therapies demonstrated in every site that medication alone and combination therapy were significantly superior to intensive behavioral treatment alone and to routine community care in the reduction of ADHD symptoms. Of note, problems commonly associated with ADHD (parent-child conflict, anxiety symptoms, poor academic performance, and limited social skills) improved only with the combination treatment. This suggests that while core ADHD symptoms require medication, associated problems will also require behavioral treatment.

The American Academy of Pediatrics has a useful resource guide (healthychildren.org) highlighting the possible symptoms of inattention, hyperactivity, and impulsivity that should be investigated when considering this diagnosis. It is a clinical diagnosis, but screening instruments (such as the Vanderbilt) can be very helpful to identifying symptoms that should be present in more than one setting (home and school). While a child with ADHD can appear calm and focused when receiving direct one-to-one attention (as during a pediatrician’s appointment), symptoms may flourish in less structured or supervised settings. Sometimes parents are keen reporters of a child’s behaviors, but some loving (and exhausted) parents may overreact to a normal degree of inattention or disobedience. This can be especially true when a parent has a more detail-oriented temperament than the child, or with younger children and first-time parents. It is important to consider ADHD when you hear about social difficulties as well as academic ones, where there is a family history of ADHD or when a child is more impulsive, hyperactive, or inattentive than you would expect given their age and developmental stage. Confirm your clinical exam with teacher and parent reports. If the reports don’t line up or there are persistent learning problems in school, consider neuropsychological testing to root out a learning disability.

 

Myth 1: “ADHD never starts in adolescence; you can’t diagnose it after elementary school.”

Diagnostic criteria used to require that symptoms were present before the age of 7 (DSM 3). But current criteria allow for diagnosis before 12 years of age or after. While the consensus is that ADHD is present in childhood, its symptoms are often not apparent. This is because normal development in much younger children is marked by higher levels of activity, distractibility, and impulsivity. Also, children with inattentive-type ADHD may not be apparent to adults if they are performing adequately in school. These youth often do not present for assessment until the challenges of a busy course load make their inattention and consequent inefficiency apparent, in high school or even college. Certainly, when a teenager presents complaining of trouble performing at school, it is critical to rule out an overburdened schedule, anxiety or mood disorder, poor sleep habits or sleep disorder, and substance use disorders, all of which are more common in adolescence. But inattentive-type ADHD that was previously missed is also a possibility worth investigating.

Myth 2: “Most children outgrow ADHD; it’s best to find natural solutions and wait it out.”

Early epidemiological studies suggested that as many as 30% of ADHD cases remitted by adulthood, but more recent data has adjusted that number down substantially, closer to 9%. Interestingly, it appears that 10% of patients will experience sustained symptoms, 9% will experience recovery (sustained remission without treatment), and a large majority will have a remitting and relapsing course into adulthood.¹

This emerging evidence suggests that ADHD is almost always a lifelong condition. Untreated, it can threaten healthy development (including social skills and self-esteem) and day-to-day function (academic, social and athletic performance and even vulnerability to accidents) in ways that can be profound. The MTA Study has powerfully demonstrated the efficacy of pharmacological treatment and of specific behavioral treatments for ADHD and associated problems.

 

Myth 3: “You should exhaust natural cures first before trying medications.”

There has been a large amount of research into a variety of “natural” treatments for ADHD: special diets, supplements, increased exercise, and interventions like neurofeedback. While high-dose omega 3 fatty acid supplementation has demonstrated mild improvement in ADHD symptoms, no “natural” treatment has come close to the efficacy of stimulant medications. Interventions such as neurofeedback are expensive and time-consuming without any demonstrated efficacy. That said, improving a child’s routines around sleep, nutrition, and regular exercise are broadly useful strategies to improve any child’s (or adult’s) energy, impulse control, attention, motivation, and capacity to manage adversity and stress. Start any treatment by addressing sleep and exercise, including moderating time spent on screens, to support healthy function. But only medication will achieve symptom remission if your patient has underlying ADHD.

Myth 4: “All medications are equally effective in ADHD.”

It is well-established that stimulants are more effective than non-stimulants in the treatment of ADHD symptoms, with an effect size that is almost double that of non-stimulants.²

Amphetamine-based medications are slightly more effective than methylphenidate-based medications, but they are also generally less well-tolerated. Individual patients commonly have a better response to one class than the other, but you will need a trial to determine which one. It is reasonable to start a patient with an extended formulation of one class, based on your assessment of their vulnerability to side effects or a family history of medication response. Non-stimulants are of use when stimulants are not tolerated (ie, use of atomoxetine with patients who have comorbid anxiety), or to target specific symptoms, such as guanfacine or clonidine for hyperactivity.

 

Myth 5: “You can’t treat ADHD in substance abusing teens, stimulant medications are addictive.”

ADHD itself (not medications) increases the risk for addiction; those with ADHD are almost twice as likely to develop a substance use disorder, with highest risk for marijuana, alcohol, and nicotine abuse.³

This may be a function of limited impulse control or increased sensitivity in the ADHD brain to a drug’s addictive potential. Importantly, there is growing evidence that youth whose ADHD is treated pharmacologically are at lower risk for addiction than their peers with untreated ADHD.⁴

Those youth who have both ADHD and addiction are more likely to stay engaged in treatment for addiction when their ADHD is effectively treated, and there are medication formulations (lisdexamfetamine) that are safe in addiction (cannot be absorbed nasally or intravenously). It is important for you to talk about the heightened vulnerability to addiction with your ADHD patients and their parents, and the value of effective treatment in preventing this complication.

 

Myth 6: “ADHD is usually behavioral. Help parents to set rules, expectations, and limits instead of medicating the problem.”

Bad parenting does not cause ADHD. ADHD is marked by difficulties with impulse control, hyperactivity, and sustaining attention with matters that are not intrinsically engaging. “Behavioral issues” are patterns of behavior children learn to seek rewards or avoid negative consequences. Youth with ADHD can develop behavioral problems, but these are usually driven by negative feedback about their activity level, forgetfulness, or impulse control, which they are not able to change. This can lead to frustration and irritability, poor self-esteem, and even hopelessness — in parents and children both!

While parents are not the source of ADHD symptoms, there is a great deal of parent education and support that can be powerfully effective for these families. Parents benefit from learning strategies that can help their children to shift their attention, plan ahead, and manage frustration, especially for times when their children are unmedicated (vacations and bedtime). It is worth noting that ADHD is among the most heritable of youth psychiatric illnesses, so it is not uncommon for a parent of a child with ADHD to have similar symptoms. If the parents’ ADHD is untreated, they may be more impulsive themselves. They may also be extra sensitive to the qualities they dislike in themselves, inadvertently adding to their children’s sense of shame. ADHD is very treatable, and those with it can learn executive function skills and organizational strategies that can equip them to manage residual symptoms. Parents will benefit from strategies to understand their children and to help them learn adaptive skills in a realistic way. Your discussions with parents could help the families in your practice make adjustments that can translate into big differences in their child’s healthiest development.

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

References

1. Sibley MH et al. MTA Cooperative Group. Variable Patterns of Remission From ADHD in the Multimodal Treatment Study of ADHD. Am J Psychiatry. 2022 Feb;179(2):142-151. doi: 10.1176/appi.ajp.2021.21010032.

2. Cortese S et al. Comparative Efficacy and Tolerability of Medications for Attention-Deficit Hyperactivity Disorder in Children, Adolescents, and Adults: A Systematic Review and Network Meta-Analysis. Lancet Psychiatry. 2018 Sep;5(9):727-738. doi: 10.1016/S2215-0366(18)30269-4.

3. Lee SS et al. Prospective Association of Childhood Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use and Abuse/Dependence: A Meta-Analytic Review. Clin Psychol Rev. 2011 Apr;31(3):328-41. doi: 10.1016/j.cpr.2011.01.006. 

4. Chorniy A, Kitashima L. Sex, Drugs, and ADHD: The Effects of ADHD Pharmacological Treatment on Teens’ Risky Behaviors. Labour Economics. 2016;43:87-105. doi.org/10.1016/j.labeco.2016.06.014.

TOPLINE:

About one third of US adults aged 50-80 years report feeling lonely and socially isolated, a new study of data from 2018-2024 shows. While the levels have returned to the prepandemic range, investigators say the findings suggest clinicians should screen for loneliness and isolation.

METHODOLOGY:

• Researchers conducted a nationally representative survey of US adults aged 50-80 years through the University of Michigan National Poll on Healthy Aging at six timepoints between 2018 and 2024.
• Data collection involved online surveys conducted using the Ipsos KnowledgePanel from 2018 to 2021, transitioning to online and phone surveys conducted using the National Opinion Research Center AmeriSpeak panel from 2022 to 2024.
• Sample sizes ranged between 2051 and 2576 respondents, with completion rates ranging from 61% to 78% across the survey periods.

TAKEAWAY:

• Loneliness rates among adults aged 50-80 years showed notable fluctuation, starting at 34% (95% CI, 31.7%-36.2%) in 2018, rising to 41% (95% CI, 39.1%-43.7%) in 2020, and returning to 33% (95% CI, 31.7%-35.1%) by 2024.
• Social isolation showed a similar pattern in the study group, starting at 27% (95% CI, 24.5%-28.8%) in 2018, peaking at 56% (95% CI, 53.4%-58.1%) in 2020, and declining to 29% (95% CI, 27.5%-30.9%) by 2024.
• Higher loneliness and social isolation rates were frequently reported among individuals who did not work, lived alone, had lower household incomes, and had self-reported fair and poor physical and mental health than those who reported excellent, very good, or good health.

IN PRACTICE:

The findings suggest that “much like routinely asking about diet and exercise, clinicians should consider screening older adults for loneliness and social isolation and connect them with appropriate resources,” the investigators wrote.

SOURCE:

The study was led by Preeti N. Malani, MD, MSJ, University of Michigan Medical School, Ann Arbor. It was published online on December 9 in JAMA.

LIMITATIONS:

The study was limited by possible recall bias, reliance on self-reported data, lack of longitudinal results, and differences in survey timing, panels, and question framing across years. The findings may not have been applicable to excluded groups such as nursing home residents or individuals aged > 80 years, which limited their generalizability.

DISCLOSURES:

The study was supported by AARP and Michigan Medicine and the Department of Veterans Affairs, Veterans Health Administration, and Health Systems Research. One author reported receiving consulting fees and honoraria from various organizations. Details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About one third of US adults aged 50-80 years report feeling lonely and socially isolated, a new study of data from 2018-2024 shows. While the levels have returned to the prepandemic range, investigators say the findings suggest clinicians should screen for loneliness and isolation.

METHODOLOGY:

• Researchers conducted a nationally representative survey of US adults aged 50-80 years through the University of Michigan National Poll on Healthy Aging at six timepoints between 2018 and 2024.
• Data collection involved online surveys conducted using the Ipsos KnowledgePanel from 2018 to 2021, transitioning to online and phone surveys conducted using the National Opinion Research Center AmeriSpeak panel from 2022 to 2024.
• Sample sizes ranged between 2051 and 2576 respondents, with completion rates ranging from 61% to 78% across the survey periods.

TAKEAWAY:

• Loneliness rates among adults aged 50-80 years showed notable fluctuation, starting at 34% (95% CI, 31.7%-36.2%) in 2018, rising to 41% (95% CI, 39.1%-43.7%) in 2020, and returning to 33% (95% CI, 31.7%-35.1%) by 2024.
• Social isolation showed a similar pattern in the study group, starting at 27% (95% CI, 24.5%-28.8%) in 2018, peaking at 56% (95% CI, 53.4%-58.1%) in 2020, and declining to 29% (95% CI, 27.5%-30.9%) by 2024.
• Higher loneliness and social isolation rates were frequently reported among individuals who did not work, lived alone, had lower household incomes, and had self-reported fair and poor physical and mental health than those who reported excellent, very good, or good health.

IN PRACTICE:

The findings suggest that “much like routinely asking about diet and exercise, clinicians should consider screening older adults for loneliness and social isolation and connect them with appropriate resources,” the investigators wrote.

SOURCE:

The study was led by Preeti N. Malani, MD, MSJ, University of Michigan Medical School, Ann Arbor. It was published online on December 9 in JAMA.

LIMITATIONS:

The study was limited by possible recall bias, reliance on self-reported data, lack of longitudinal results, and differences in survey timing, panels, and question framing across years. The findings may not have been applicable to excluded groups such as nursing home residents or individuals aged > 80 years, which limited their generalizability.

DISCLOSURES:

The study was supported by AARP and Michigan Medicine and the Department of Veterans Affairs, Veterans Health Administration, and Health Systems Research. One author reported receiving consulting fees and honoraria from various organizations. Details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About one third of US adults aged 50-80 years report feeling lonely and socially isolated, a new study of data from 2018-2024 shows. While the levels have returned to the prepandemic range, investigators say the findings suggest clinicians should screen for loneliness and isolation.

METHODOLOGY:

• Researchers conducted a nationally representative survey of US adults aged 50-80 years through the University of Michigan National Poll on Healthy Aging at six timepoints between 2018 and 2024.
• Data collection involved online surveys conducted using the Ipsos KnowledgePanel from 2018 to 2021, transitioning to online and phone surveys conducted using the National Opinion Research Center AmeriSpeak panel from 2022 to 2024.
• Sample sizes ranged between 2051 and 2576 respondents, with completion rates ranging from 61% to 78% across the survey periods.

TAKEAWAY:

• Loneliness rates among adults aged 50-80 years showed notable fluctuation, starting at 34% (95% CI, 31.7%-36.2%) in 2018, rising to 41% (95% CI, 39.1%-43.7%) in 2020, and returning to 33% (95% CI, 31.7%-35.1%) by 2024.
• Social isolation showed a similar pattern in the study group, starting at 27% (95% CI, 24.5%-28.8%) in 2018, peaking at 56% (95% CI, 53.4%-58.1%) in 2020, and declining to 29% (95% CI, 27.5%-30.9%) by 2024.
• Higher loneliness and social isolation rates were frequently reported among individuals who did not work, lived alone, had lower household incomes, and had self-reported fair and poor physical and mental health than those who reported excellent, very good, or good health.

IN PRACTICE:

The findings suggest that “much like routinely asking about diet and exercise, clinicians should consider screening older adults for loneliness and social isolation and connect them with appropriate resources,” the investigators wrote.

SOURCE:

The study was led by Preeti N. Malani, MD, MSJ, University of Michigan Medical School, Ann Arbor. It was published online on December 9 in JAMA.

LIMITATIONS:

The study was limited by possible recall bias, reliance on self-reported data, lack of longitudinal results, and differences in survey timing, panels, and question framing across years. The findings may not have been applicable to excluded groups such as nursing home residents or individuals aged > 80 years, which limited their generalizability.

DISCLOSURES:

The study was supported by AARP and Michigan Medicine and the Department of Veterans Affairs, Veterans Health Administration, and Health Systems Research. One author reported receiving consulting fees and honoraria from various organizations. Details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A brief self-guided online cognitive-behavioral therapy (CBT) intervention was noninferior to comprehensive clinician-guided CBT in reducing symptoms in patients with atopic dermatitis (AD), with both groups showing similar improvements on the Patient-Oriented Eczema Measure (POEM).

METHODOLOGY:

• Researchers conducted a single-blind randomized clinical noninferiority trial at Karolinska Institutet in Stockholm, Sweden, enrolling 168 adults with AD (mean age, 39 years; 84.5% women) from November 2022 to April 2023.
• Participants were randomly assigned to either a 12-week self-guided online CBT intervention (n = 86) without clinician support or a comprehensive 12-week clinician-guided online CBT program (n = 82).
• The primary outcome was the change in POEM score from baseline; reduction of 4 or more points was considered a response, and the predefined noninferiority margin was 3 points.

TAKEAWAY:

• The clinician-guided group improved by 4.20 points on POEM, while the self-guided group improved by 4.60 points, with an estimated mean difference in change of 0.36 points, which was below noninferiority margin.
• Clinicians spent a mean of 36 minutes on treatment guidance and an additional 14 minutes on assessments in the clinician-guided group, whereas they spent only 15.8 minutes on assessments in the self-guided group.
• Both groups demonstrated significant improvements in quality of life, sleep, depressive mood, pruritus, and stress, with no serious adverse events being reported.
• Completion rates were higher in the self-guided group with 81% of participants completing five or more modules, compared with 67% in the clinician-guided group.

IN PRACTICE:

“Overall, the findings support a self-guided intervention as a noninferior and cost-effective alternative to a previously evaluated clinician-guided treatment,” the authors wrote. “Because psychological interventions are rare in dermatological care, this study is an important step toward implementation of CBT for people with AD. The effectiveness of CBT interventions in primary and dermatological specialist care should be investigated.”

SOURCE:

The study was led by Dorian Kern, PhD, Division of Psychology, Karolinska Institutet, and was published online in JAMA Dermatology.

LIMITATIONS: 

High data loss for secondary measurements could affect interpretation of these results. The study relied solely on self-reported measures. The predominance of women participants and the Swedish-language requirement may have limited participation from migrant populations, which could hinder the broader implementation of the study’s findings.

DISCLOSURES:

The study was supported by the Swedish Ministry of Health and Social Affairs. Kern reported receiving grants from the Swedish Ministry of Health and Social Affairs during the conduct of the study. Other authors also reported authorships and royalties, personal fees, grants, or held stocks in DahliaQomit.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A brief self-guided online cognitive-behavioral therapy (CBT) intervention was noninferior to comprehensive clinician-guided CBT in reducing symptoms in patients with atopic dermatitis (AD), with both groups showing similar improvements on the Patient-Oriented Eczema Measure (POEM).

METHODOLOGY:

• Researchers conducted a single-blind randomized clinical noninferiority trial at Karolinska Institutet in Stockholm, Sweden, enrolling 168 adults with AD (mean age, 39 years; 84.5% women) from November 2022 to April 2023.
• Participants were randomly assigned to either a 12-week self-guided online CBT intervention (n = 86) without clinician support or a comprehensive 12-week clinician-guided online CBT program (n = 82).
• The primary outcome was the change in POEM score from baseline; reduction of 4 or more points was considered a response, and the predefined noninferiority margin was 3 points.

TAKEAWAY:

• The clinician-guided group improved by 4.20 points on POEM, while the self-guided group improved by 4.60 points, with an estimated mean difference in change of 0.36 points, which was below noninferiority margin.
• Clinicians spent a mean of 36 minutes on treatment guidance and an additional 14 minutes on assessments in the clinician-guided group, whereas they spent only 15.8 minutes on assessments in the self-guided group.
• Both groups demonstrated significant improvements in quality of life, sleep, depressive mood, pruritus, and stress, with no serious adverse events being reported.
• Completion rates were higher in the self-guided group with 81% of participants completing five or more modules, compared with 67% in the clinician-guided group.

IN PRACTICE:

“Overall, the findings support a self-guided intervention as a noninferior and cost-effective alternative to a previously evaluated clinician-guided treatment,” the authors wrote. “Because psychological interventions are rare in dermatological care, this study is an important step toward implementation of CBT for people with AD. The effectiveness of CBT interventions in primary and dermatological specialist care should be investigated.”

SOURCE:

The study was led by Dorian Kern, PhD, Division of Psychology, Karolinska Institutet, and was published online in JAMA Dermatology.

LIMITATIONS: 

High data loss for secondary measurements could affect interpretation of these results. The study relied solely on self-reported measures. The predominance of women participants and the Swedish-language requirement may have limited participation from migrant populations, which could hinder the broader implementation of the study’s findings.

DISCLOSURES:

The study was supported by the Swedish Ministry of Health and Social Affairs. Kern reported receiving grants from the Swedish Ministry of Health and Social Affairs during the conduct of the study. Other authors also reported authorships and royalties, personal fees, grants, or held stocks in DahliaQomit.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A brief self-guided online cognitive-behavioral therapy (CBT) intervention was noninferior to comprehensive clinician-guided CBT in reducing symptoms in patients with atopic dermatitis (AD), with both groups showing similar improvements on the Patient-Oriented Eczema Measure (POEM).

METHODOLOGY:

• Researchers conducted a single-blind randomized clinical noninferiority trial at Karolinska Institutet in Stockholm, Sweden, enrolling 168 adults with AD (mean age, 39 years; 84.5% women) from November 2022 to April 2023.
• Participants were randomly assigned to either a 12-week self-guided online CBT intervention (n = 86) without clinician support or a comprehensive 12-week clinician-guided online CBT program (n = 82).
• The primary outcome was the change in POEM score from baseline; reduction of 4 or more points was considered a response, and the predefined noninferiority margin was 3 points.

TAKEAWAY:

• The clinician-guided group improved by 4.20 points on POEM, while the self-guided group improved by 4.60 points, with an estimated mean difference in change of 0.36 points, which was below noninferiority margin.
• Clinicians spent a mean of 36 minutes on treatment guidance and an additional 14 minutes on assessments in the clinician-guided group, whereas they spent only 15.8 minutes on assessments in the self-guided group.
• Both groups demonstrated significant improvements in quality of life, sleep, depressive mood, pruritus, and stress, with no serious adverse events being reported.
• Completion rates were higher in the self-guided group with 81% of participants completing five or more modules, compared with 67% in the clinician-guided group.

IN PRACTICE:

“Overall, the findings support a self-guided intervention as a noninferior and cost-effective alternative to a previously evaluated clinician-guided treatment,” the authors wrote. “Because psychological interventions are rare in dermatological care, this study is an important step toward implementation of CBT for people with AD. The effectiveness of CBT interventions in primary and dermatological specialist care should be investigated.”

SOURCE:

The study was led by Dorian Kern, PhD, Division of Psychology, Karolinska Institutet, and was published online in JAMA Dermatology.

LIMITATIONS: 

High data loss for secondary measurements could affect interpretation of these results. The study relied solely on self-reported measures. The predominance of women participants and the Swedish-language requirement may have limited participation from migrant populations, which could hinder the broader implementation of the study’s findings.

DISCLOSURES:

The study was supported by the Swedish Ministry of Health and Social Affairs. Kern reported receiving grants from the Swedish Ministry of Health and Social Affairs during the conduct of the study. Other authors also reported authorships and royalties, personal fees, grants, or held stocks in DahliaQomit.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.