Clinical Psychiatry News

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

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

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

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

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

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

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Onyda XR (clonidine hydrochloride) for the treatment of attention-deficit/hyperactivity disorder (ADHD), drug manufacturer Tris Pharma announced in a statement.

The drug is the first approved liquid nonstimulant ADHD medication. The once-daily extended-release oral suspension, with nighttime dosing, can be used alone or as an adjunctive therapy to FDA-approved stimulant medications in pediatric patients 6 years of age or older.

“People with ADHD require a range of therapeutic options that are designed for their individual needs, because not every medication or type of therapy works for every patient,” Ann Childress, MD, a psychiatrist and president of the Las Vegas–based Center for Psychiatry and Behavioral Medicine, said in the release. 

“The approval of Onyda XR, the only liquid non-stimulant ADHD medication, with nighttime dosing that shifts the release profile, is a convenient option for patients needing better ADHD control,” she added.

The approval was based on “adequate and well-controlled studies” of the company’s extended-release tablets.

Onyda XR is contraindicated in patients with a history of a hypersensitivity reaction to clonidine. 

The medication can cause dose-related decreases in blood pressure and heart rate. Vital signs should be monitored frequently in at-risk patients. In studies with the extended-release tablets, somnolence and sedation were commonly reported adverse reactions. The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular block, especially in patients taking other sympatholytic drugs, the company noted.

Onyda XR should be available in pharmacies in the second half of 2024.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Onyda XR (clonidine hydrochloride) for the treatment of attention-deficit/hyperactivity disorder (ADHD), drug manufacturer Tris Pharma announced in a statement.

The drug is the first approved liquid nonstimulant ADHD medication. The once-daily extended-release oral suspension, with nighttime dosing, can be used alone or as an adjunctive therapy to FDA-approved stimulant medications in pediatric patients 6 years of age or older.

“People with ADHD require a range of therapeutic options that are designed for their individual needs, because not every medication or type of therapy works for every patient,” Ann Childress, MD, a psychiatrist and president of the Las Vegas–based Center for Psychiatry and Behavioral Medicine, said in the release. 

“The approval of Onyda XR, the only liquid non-stimulant ADHD medication, with nighttime dosing that shifts the release profile, is a convenient option for patients needing better ADHD control,” she added.

The approval was based on “adequate and well-controlled studies” of the company’s extended-release tablets.

Onyda XR is contraindicated in patients with a history of a hypersensitivity reaction to clonidine. 

The medication can cause dose-related decreases in blood pressure and heart rate. Vital signs should be monitored frequently in at-risk patients. In studies with the extended-release tablets, somnolence and sedation were commonly reported adverse reactions. The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular block, especially in patients taking other sympatholytic drugs, the company noted.

Onyda XR should be available in pharmacies in the second half of 2024.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Onyda XR (clonidine hydrochloride) for the treatment of attention-deficit/hyperactivity disorder (ADHD), drug manufacturer Tris Pharma announced in a statement.

The drug is the first approved liquid nonstimulant ADHD medication. The once-daily extended-release oral suspension, with nighttime dosing, can be used alone or as an adjunctive therapy to FDA-approved stimulant medications in pediatric patients 6 years of age or older.

“People with ADHD require a range of therapeutic options that are designed for their individual needs, because not every medication or type of therapy works for every patient,” Ann Childress, MD, a psychiatrist and president of the Las Vegas–based Center for Psychiatry and Behavioral Medicine, said in the release. 

“The approval of Onyda XR, the only liquid non-stimulant ADHD medication, with nighttime dosing that shifts the release profile, is a convenient option for patients needing better ADHD control,” she added.

The approval was based on “adequate and well-controlled studies” of the company’s extended-release tablets.

Onyda XR is contraindicated in patients with a history of a hypersensitivity reaction to clonidine. 

The medication can cause dose-related decreases in blood pressure and heart rate. Vital signs should be monitored frequently in at-risk patients. In studies with the extended-release tablets, somnolence and sedation were commonly reported adverse reactions. The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular block, especially in patients taking other sympatholytic drugs, the company noted.

Onyda XR should be available in pharmacies in the second half of 2024.
 

A version of this article appeared on Medscape.com.

Teens with classmates who have a mental illness have a significantly greater risk for a psychiatric diagnosis later in life, even after controlling for parents’ mental health history and other factors, a new study suggested.

The research provides new evidence that adolescents within a specific peer network may possibly “transmit” mental disorders such as depression and anxiety to each other, the investigators noted.

Having a classmate with a mental illness was associated with a 3% higher risk for subsequent psychiatric diagnosis, researchers found. The risk was highest — 13% — in the first year of follow-up and was strongest for mood, anxiety, and eating disorders.

The study is said to the be the largest to date on the topic, including data on more than 700,000 ninth graders in Finland who were followed for up to 18 years.

At least one expert noted that the numbers are higher than he would have expected, but the investigators were quick to caution the study doesn’t prove having a classmate with a mental illness leads to later psychiatric diagnosis among peers.

“The associations observed in the study are not necessarily causal,” lead investigator Jussi Alho, PhD, a postdoctoral researcher at the University of Helsinki, Finland, told this news organization. “The study did not investigate the mechanisms that explain the observed associations.”

The results were published online on May 22 in JAMA Psychiatry.
 

Few Data

Previous studies have reported a clustering of mood symptoms, eating disorders, and other psychiatric illnesses among adolescent and adult social networks. But most involve self-selected peer groups.

“Investigating the transmission of mental disorders is especially important in childhood and adolescence,” the authors noted. “Yet, despite a few survey studies reporting that adolescents may experience increased mental health symptoms when exposed to friends or peers with mental health problems, large-scale studies on the potential peer influences of mental disorders in youth are lacking,” the authors wrote.

Researchers used a database of 713,809 students in the ninth grade, about half boys and half girls. All were born between January 1, 1985, and December 31, 1997. About 47,000 were excluded as they had a mental disorder diagnosis before the study began.

Some 666,000 students in 860 schools were followed from ninth grade until the first diagnosed mental disorder, death, emigration, or the end of the study in 2019. Median follow-up was 11.4 years.

Diagnoses were gathered from Finnish registries for inpatient, outpatient, and primary care and included ICD-9 and ICD-10 diagnoses for substance misuse disorders, schizophrenia spectrum disorders, mood disorders, anxiety disorders, eating disorders, emotional and social-functioning disorders, and hyperkinetic and conduct disorders.

The authors adjusted for sex, birth year, school and ninth-grade class size, area-level urbanicity, area-level morbidity, area-level education, area-level employment rate, parental educational level, and parental mental health, with a random intercept per school.
 

Dose-Response Relationship

Overall, a quarter (167,227) of the students were diagnosed with a mental disorder.

The risk of being diagnosed with any mental disorder was 3% higher during the entire follow-up period (hazard ratio [HR], 1.03; 95% CI, 1.02-1.04). Risk was highest in the first year of follow-up (HR, 1.13; 95% CI, 1.08-1.18) and then rose again in years 4 and 5, when the risk was 5% higher with one diagnosed classmate and 10% higher with more than one diagnosed classmate.

The risk was significantly increased for mood, anxiety, and eating disorders in each follow-up time window. Investigators also noted a dose-response relationship: The more classmates with a psychiatric illness, the greater the risk for later mental illness.

“These findings suggest that mental disorders may be transmitted within adolescent peer networks,” the authors wrote.

The researchers chose to describe the spread of mental disorders among peer classmates as “transmission” in part because it has been previously used in the literature, Dr. Alho said.

Alho said the researchers also believe that transmission is an accurate term to describe the potential mechanisms by which mental disorders may spread.

The authors hypothesized that more students might be diagnosed when disorders are normalized, through increased awareness and receptivity to diagnosis and treatment.

Conversely, the rate of disorders might also have increased — especially in the first year of follow-up — if there were no students in the peer network who had been diagnosed, the authors added. Without an example, it might discourage a student to seek help.

The authors also noted that it’s “conceivable that long-term exposure to a depressive individual could lead to gradual development of depressive symptoms through the well-established neural mechanisms of emotional contagion.”
 

New Direction for Treatment?

Commenting on the findings, Madhukar H. Trivedi, MD, the Betty Jo Hay Distinguished Chair in Mental Health at UT Southwestern Medical School, Dallas, said that the theory that having classmates with psychiatric illness could normalize these conditions has merit.

Once someone is diagnosed or receives treatment, “their peers kind of get implicit permission to be able to then express their own symptoms or express their own problems, which they may have been hiding or not recognized,” he said.

However, Dr. Trivedi disagreed with the authors’ suggestion that the rate of disorders might also have increased if no classmates had received a psychiatric diagnosis, noting that it was unlikely that a student would not have been exposed to depression, anxiety, or another mood disorder — through a peer or family member — given how common those illnesses are.

“The numbers are slightly higher than I would have expected,” Dr. Trivedi said, adding that peer influence having that type of impact “is something that has not been shown before.”

The study is notable for its use of comprehensive registries, which helped solidify the data integrity, Trivedi said, and the results offer some potential new directions for treatment, such as adding peer support. That has been found useful in adult treatment but has been less utilized with adolescents, he said.

The study was funded by the European Union and the Academy of Finland. The authors reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Teens with classmates who have a mental illness have a significantly greater risk for a psychiatric diagnosis later in life, even after controlling for parents’ mental health history and other factors, a new study suggested.

The research provides new evidence that adolescents within a specific peer network may possibly “transmit” mental disorders such as depression and anxiety to each other, the investigators noted.

Having a classmate with a mental illness was associated with a 3% higher risk for subsequent psychiatric diagnosis, researchers found. The risk was highest — 13% — in the first year of follow-up and was strongest for mood, anxiety, and eating disorders.

The study is said to the be the largest to date on the topic, including data on more than 700,000 ninth graders in Finland who were followed for up to 18 years.

At least one expert noted that the numbers are higher than he would have expected, but the investigators were quick to caution the study doesn’t prove having a classmate with a mental illness leads to later psychiatric diagnosis among peers.

“The associations observed in the study are not necessarily causal,” lead investigator Jussi Alho, PhD, a postdoctoral researcher at the University of Helsinki, Finland, told this news organization. “The study did not investigate the mechanisms that explain the observed associations.”

The results were published online on May 22 in JAMA Psychiatry.
 

Few Data

Previous studies have reported a clustering of mood symptoms, eating disorders, and other psychiatric illnesses among adolescent and adult social networks. But most involve self-selected peer groups.

“Investigating the transmission of mental disorders is especially important in childhood and adolescence,” the authors noted. “Yet, despite a few survey studies reporting that adolescents may experience increased mental health symptoms when exposed to friends or peers with mental health problems, large-scale studies on the potential peer influences of mental disorders in youth are lacking,” the authors wrote.

Researchers used a database of 713,809 students in the ninth grade, about half boys and half girls. All were born between January 1, 1985, and December 31, 1997. About 47,000 were excluded as they had a mental disorder diagnosis before the study began.

Some 666,000 students in 860 schools were followed from ninth grade until the first diagnosed mental disorder, death, emigration, or the end of the study in 2019. Median follow-up was 11.4 years.

Diagnoses were gathered from Finnish registries for inpatient, outpatient, and primary care and included ICD-9 and ICD-10 diagnoses for substance misuse disorders, schizophrenia spectrum disorders, mood disorders, anxiety disorders, eating disorders, emotional and social-functioning disorders, and hyperkinetic and conduct disorders.

The authors adjusted for sex, birth year, school and ninth-grade class size, area-level urbanicity, area-level morbidity, area-level education, area-level employment rate, parental educational level, and parental mental health, with a random intercept per school.
 

Dose-Response Relationship

Overall, a quarter (167,227) of the students were diagnosed with a mental disorder.

The risk of being diagnosed with any mental disorder was 3% higher during the entire follow-up period (hazard ratio [HR], 1.03; 95% CI, 1.02-1.04). Risk was highest in the first year of follow-up (HR, 1.13; 95% CI, 1.08-1.18) and then rose again in years 4 and 5, when the risk was 5% higher with one diagnosed classmate and 10% higher with more than one diagnosed classmate.

The risk was significantly increased for mood, anxiety, and eating disorders in each follow-up time window. Investigators also noted a dose-response relationship: The more classmates with a psychiatric illness, the greater the risk for later mental illness.

“These findings suggest that mental disorders may be transmitted within adolescent peer networks,” the authors wrote.

The researchers chose to describe the spread of mental disorders among peer classmates as “transmission” in part because it has been previously used in the literature, Dr. Alho said.

Alho said the researchers also believe that transmission is an accurate term to describe the potential mechanisms by which mental disorders may spread.

The authors hypothesized that more students might be diagnosed when disorders are normalized, through increased awareness and receptivity to diagnosis and treatment.

Conversely, the rate of disorders might also have increased — especially in the first year of follow-up — if there were no students in the peer network who had been diagnosed, the authors added. Without an example, it might discourage a student to seek help.

The authors also noted that it’s “conceivable that long-term exposure to a depressive individual could lead to gradual development of depressive symptoms through the well-established neural mechanisms of emotional contagion.”
 

New Direction for Treatment?

Commenting on the findings, Madhukar H. Trivedi, MD, the Betty Jo Hay Distinguished Chair in Mental Health at UT Southwestern Medical School, Dallas, said that the theory that having classmates with psychiatric illness could normalize these conditions has merit.

Once someone is diagnosed or receives treatment, “their peers kind of get implicit permission to be able to then express their own symptoms or express their own problems, which they may have been hiding or not recognized,” he said.

However, Dr. Trivedi disagreed with the authors’ suggestion that the rate of disorders might also have increased if no classmates had received a psychiatric diagnosis, noting that it was unlikely that a student would not have been exposed to depression, anxiety, or another mood disorder — through a peer or family member — given how common those illnesses are.

“The numbers are slightly higher than I would have expected,” Dr. Trivedi said, adding that peer influence having that type of impact “is something that has not been shown before.”

The study is notable for its use of comprehensive registries, which helped solidify the data integrity, Trivedi said, and the results offer some potential new directions for treatment, such as adding peer support. That has been found useful in adult treatment but has been less utilized with adolescents, he said.

The study was funded by the European Union and the Academy of Finland. The authors reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Teens with classmates who have a mental illness have a significantly greater risk for a psychiatric diagnosis later in life, even after controlling for parents’ mental health history and other factors, a new study suggested.

The research provides new evidence that adolescents within a specific peer network may possibly “transmit” mental disorders such as depression and anxiety to each other, the investigators noted.

Having a classmate with a mental illness was associated with a 3% higher risk for subsequent psychiatric diagnosis, researchers found. The risk was highest — 13% — in the first year of follow-up and was strongest for mood, anxiety, and eating disorders.

The study is said to the be the largest to date on the topic, including data on more than 700,000 ninth graders in Finland who were followed for up to 18 years.

At least one expert noted that the numbers are higher than he would have expected, but the investigators were quick to caution the study doesn’t prove having a classmate with a mental illness leads to later psychiatric diagnosis among peers.

“The associations observed in the study are not necessarily causal,” lead investigator Jussi Alho, PhD, a postdoctoral researcher at the University of Helsinki, Finland, told this news organization. “The study did not investigate the mechanisms that explain the observed associations.”

The results were published online on May 22 in JAMA Psychiatry.
 

Few Data

Previous studies have reported a clustering of mood symptoms, eating disorders, and other psychiatric illnesses among adolescent and adult social networks. But most involve self-selected peer groups.

“Investigating the transmission of mental disorders is especially important in childhood and adolescence,” the authors noted. “Yet, despite a few survey studies reporting that adolescents may experience increased mental health symptoms when exposed to friends or peers with mental health problems, large-scale studies on the potential peer influences of mental disorders in youth are lacking,” the authors wrote.

Researchers used a database of 713,809 students in the ninth grade, about half boys and half girls. All were born between January 1, 1985, and December 31, 1997. About 47,000 were excluded as they had a mental disorder diagnosis before the study began.

Some 666,000 students in 860 schools were followed from ninth grade until the first diagnosed mental disorder, death, emigration, or the end of the study in 2019. Median follow-up was 11.4 years.

Diagnoses were gathered from Finnish registries for inpatient, outpatient, and primary care and included ICD-9 and ICD-10 diagnoses for substance misuse disorders, schizophrenia spectrum disorders, mood disorders, anxiety disorders, eating disorders, emotional and social-functioning disorders, and hyperkinetic and conduct disorders.

The authors adjusted for sex, birth year, school and ninth-grade class size, area-level urbanicity, area-level morbidity, area-level education, area-level employment rate, parental educational level, and parental mental health, with a random intercept per school.
 

Dose-Response Relationship

Overall, a quarter (167,227) of the students were diagnosed with a mental disorder.

The risk of being diagnosed with any mental disorder was 3% higher during the entire follow-up period (hazard ratio [HR], 1.03; 95% CI, 1.02-1.04). Risk was highest in the first year of follow-up (HR, 1.13; 95% CI, 1.08-1.18) and then rose again in years 4 and 5, when the risk was 5% higher with one diagnosed classmate and 10% higher with more than one diagnosed classmate.

The risk was significantly increased for mood, anxiety, and eating disorders in each follow-up time window. Investigators also noted a dose-response relationship: The more classmates with a psychiatric illness, the greater the risk for later mental illness.

“These findings suggest that mental disorders may be transmitted within adolescent peer networks,” the authors wrote.

The researchers chose to describe the spread of mental disorders among peer classmates as “transmission” in part because it has been previously used in the literature, Dr. Alho said.

Alho said the researchers also believe that transmission is an accurate term to describe the potential mechanisms by which mental disorders may spread.

The authors hypothesized that more students might be diagnosed when disorders are normalized, through increased awareness and receptivity to diagnosis and treatment.

Conversely, the rate of disorders might also have increased — especially in the first year of follow-up — if there were no students in the peer network who had been diagnosed, the authors added. Without an example, it might discourage a student to seek help.

The authors also noted that it’s “conceivable that long-term exposure to a depressive individual could lead to gradual development of depressive symptoms through the well-established neural mechanisms of emotional contagion.”
 

New Direction for Treatment?

Commenting on the findings, Madhukar H. Trivedi, MD, the Betty Jo Hay Distinguished Chair in Mental Health at UT Southwestern Medical School, Dallas, said that the theory that having classmates with psychiatric illness could normalize these conditions has merit.

Once someone is diagnosed or receives treatment, “their peers kind of get implicit permission to be able to then express their own symptoms or express their own problems, which they may have been hiding or not recognized,” he said.

However, Dr. Trivedi disagreed with the authors’ suggestion that the rate of disorders might also have increased if no classmates had received a psychiatric diagnosis, noting that it was unlikely that a student would not have been exposed to depression, anxiety, or another mood disorder — through a peer or family member — given how common those illnesses are.

“The numbers are slightly higher than I would have expected,” Dr. Trivedi said, adding that peer influence having that type of impact “is something that has not been shown before.”

The study is notable for its use of comprehensive registries, which helped solidify the data integrity, Trivedi said, and the results offer some potential new directions for treatment, such as adding peer support. That has been found useful in adult treatment but has been less utilized with adolescents, he said.

The study was funded by the European Union and the Academy of Finland. The authors reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.

An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.

The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.

“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.” 

The study was published online on May 10, 2024, in JAMA Network Open.

To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.

In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.

Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.

Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.

“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.

High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.

“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”

In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”

“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”

Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.

“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.

This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.

An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.

The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.

“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.” 

The study was published online on May 10, 2024, in JAMA Network Open.

To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.

In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.

Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.

Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.

“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.

High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.

“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”

In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”

“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”

Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.

“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.

This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.

An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.

The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.

“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.” 

The study was published online on May 10, 2024, in JAMA Network Open.

To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.

In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.

Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.

Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.

“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.

High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.

“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”

In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”

“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”

Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.

“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.

This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

Neuropsychiatric symptoms, including nightmares and hallucinatory “daymares,” may be a more important aspect of systemic lupus erythematosus (SLE) than formerly recognized, according to a qualitative mixed methods study published in The Lancet Discovery Science’s eClinicalMedicine. The findings suggested these neuropsychiatric symptoms can sometimes present as prodromal and other times act as an early warning system for a forthcoming flare.

“For clinicians, the key point is to be aware that neurological and psychiatric symptoms are much more common in patients with lupus and other autoimmune systemic rheumatic diseases than previously thought,” lead author Melanie Sloan, PhD, of the Department of Public Health and Primary Care at the University of Cambridge in England, told this news organization.

“If clinicians — and some do already — could all ask about and document these symptoms for each patient, the usual progression of symptoms in a flare can then be monitored, and patients could be supported and treated at an earlier stage,” Dr. Sloan said. “Another key point is to consider systemic autoimmune diseases at an early stage if a patient presents with multiple seemingly unconnected symptoms, which often include both physical and mental health symptoms.”

Alfred Kim, MD, PhD, associate professor of medicine in rheumatology at Washington University School of Medicine in St. Louis, Missouri, noted the difficulty of determining what neuropsychiatric symptoms may be linked to lupus vs those occurring independently or as part of a different condition.

Dr. Kim

Study Details

In planning for the study, the researchers first searched the existing literature for studies involving neuropsychiatric symptoms in patients with systemic autoimmune rheumatic diseases (SARDs). “The literature indicated frequent underreporting and misattributions of neuropsychiatric symptoms in SLE and other SARD patients, and clinician-patient discordance in neuropsychiatric symptom attribution,” the authors reported.

During 2022-2023, the researchers conducted two surveys, one with 676 adult patients with SLE and one with 400 clinicians, recruited through social media, online patient support groups, and professional networks. All patients self-reported an SLE diagnosis that the researchers did not independently confirm. The patients were predominantly White (80%) and female (94%), ranging in age from 18 to over 70, with most falling between ages 40 and 69. Most patients lived in the United Kingdom (76%) or Europe (15%).

The clinicians included 51% rheumatologists, 24% psychiatrists, 13% neurologists, 5% rheumatology nurses, 3% primary care physicians, and 7% other clinicians. Nearly half of the clinicians (45%) were from the United Kingdom, with others from the United States or Canada (16%), Europe (17%), Asia (9%), Latin America (8%), Australia or New Zealand (3%), or elsewhere (3%).

The patient surveys asked whether they had experienced any of the 29 neuropsychiatric symptoms. For the symptoms that patients had experienced at least three times in their lives, the survey asked when they first experienced the symptom in relation to their SLE onset or other SLE symptoms: Over a year before, within a year of (on either side), 1-4 years after, or more than 5 years after onset/other symptoms. “Other quantitative data included timings of disrupted dreaming sleep in relation to hallucinations for those patients reporting experiencing these,” the authors wrote.

The researchers also conducted video conference interviews with 50 clinicians, including 20 rheumatologists, and 69 interviews with patients who had a systemic autoimmune rheumatic disease, including 27 patients with SLE. Other conditions among those interviewed included inflammatory arthritis, vasculitis, Sjögren disease, systemic sclerosis, myositis, undifferentiated and mixed connective tissue diseases, and polymyalgia rheumatica. During interviews, the term “daymare” was used to discuss possible hallucinations.
 

Linking Neuropsychiatric Symptoms and Disease

Four themes emerged from the analysis of the surveys and interviews. First, despite many rheumatologists stating that it was an “established theory” that most neuropsychiatric symptoms related to SLE would initially present around the time of diagnosis or disease onset, the findings from patients and interviews with psychiatrists did not align with this theory. The first presentation of each neuropsychiatric symptom only occurred around the onset of other SLE symptoms, about one fifth to one third of the time. In fact, more than half of the patients with SLE who had experienced hallucinations or delusions/paranoia said they occurred more than a year after they first experienced their other SLE symptoms.

Patient experiences differed in terms of whether they believed their neuropsychiatric symptoms were directly related to their SLE or other rheumatic disease. Some did attribute the symptoms, such as hypomania, to their rheumatic illness, while others, such as a patient with major depression, did not see the two as linked.

A second theme focused on pattern recognition of neuropsychiatric symptoms and the onset of a disease flare. “For example, several patients described how they felt that some types of depressive symptoms were directly attributable to active inflammation due to its time of onset and differences in type and intensity compared to their more ‘reactive’ low mood that could be more attributable to a consequence of psychological distress,” the authors wrote. Another common report from patients was experiencing a sudden, intense fatigue that coincided with a flare and differed from other types of fatigue.

Some patients could recognize that a flare was coming because of familiar neuropsychiatric symptoms that acted like an “early warning system.” Often, however, these symptoms “were absent from current diagnostic guidelines and only rarely identified by clinician interviewees as related to SLE/NPSLE,” the authors found. “These neuropsychiatric prodromal symptoms were reported as sometimes preceding the more widely recognized SLE and other SARD symptoms such as joint pain, rashes, and other organ involvement.” These symptoms included sudden changes in mood (usually a lowering but sometimes mania), increased nightmares, a “feeling of unreality,” or increased sensory symptoms.

Other patients, on the other hand, had not considered a link between neuropsychiatric symptoms and their rheumatic disease until the interview, and many of the clinicians, aside from psychiatrists and nurses, said they had little time in clinic to gather information about symptom progression.
 

Nightmares and Daymares

A third theme centered on disrupted dreaming sleep, nightmares, and “daymares” as a prodromal symptom in particular. Some patients had already drawn a connection between an oncoming flare of their disease and these dreaming-related symptoms, while others had not considered a link until the interviews.

“Several SLE patients recounted flares consistently involving the segueing of increasingly vivid and distressing nightmares into distorted reality and daytime hallucinations,” the authors reported. Flare-related nightmares in particular “often involved being attacked, trapped, crushed, or falling.” Patients tended to be more forthcoming about hallucinatory experiences when the term “daymare” was used to describe them, and they often related to the idea of feeling “in-between asleep and awake.”

Only one of the rheumatologists interviewed had considered nightmares as potentially related to SLE flares, and several appeared skeptical about a link but planned to ask their patients about it. Most of the specialists interviewed, meanwhile, said they often discussed sleep disruption with patients.

“There was agreement that recognizing and eliciting these early flare symptoms may improve care and even reduce clinic times by averting flares at any earlier stage, although some rheumatologists were clear that limited appointment times meant that these symptoms would not be prioritized for discussion,” the authors wrote.

Though Dr. Kim acknowledged the possibility of nightmares as prodromal, he noted other ways in which nightmares may be indirectly linked to lupus. “Trauma is a major risk factor for lupus,” Dr. Kim said, with multiple studies showing childhood traumatic experiences and even posttraumatic stress disorder to be risk factors for lupus. “Whether nightmares represent a traumatic event or prior traumatic events is not clear to me, but one could hypothesize that this may be a manifestation of trauma,” Dr. Kim said.

In addition, nightmares represent a sleep disorder that can substantially reduce sleep quality, Dr. Kim said, and poor sleep is also associated with lupus. “One has to wonder whether disruptive dreaming sleep is one of several specific manifestations of poor sleep quality, which then increases the risk of lupus in those patients,” Dr. Kim said.
 

Misattribution of Neuropsychiatric Symptoms

The final theme to emerge from the findings was patients had been misdiagnosed with psychiatric or psychosomatic conditions shortly before getting their rheumatic disease diagnosis. One patient, for example, reported being diagnosed with borderline personality disorder just 6 months before the lupus diagnosis at age 19 and noticed that the symptoms of one “got under control” when the symptoms of the other did.

“Early misattributions of SARD symptoms to primary psychiatric or psychosomatic conditions were frequently reported to have delayed SARD diagnosis and led to future misattributions,” the authors reported. “Whilst some of these misdiagnoses likely reflect the widespread lack of knowledge and limited definitive tests for SLE, it is plausible that some early SLE neurological and/or psychiatric symptoms may represent a neuropsychiatric prodrome for SLE itself.”

Dr. Kim agreed that misattribution of symptoms to other diagnoses is common with lupus and a common reason for delays in diagnosis, even with symptoms that are not neuropsychiatric. The findings in this study broaden “the type of symptoms we need to put on our radar pre-diagnosis,” Dr. Kim said. “We just also have to be aware that these prodromal symptoms are not diagnostic for lupus, though.”

Dr. Sloan cited earlier work in recommending an “ABC” approach to improving clinician-patient relationships: “Availability is being accessible when patients need them, Belief is demonstrating belief and validating patient self-reports of symptoms, and Continuity is when the same clinician sees the same patient each clinic visit to build up a trusting relationship.” She noted the importance of asking about and normalizing the existence of these symptoms with rheumatic diseases.

The research was funded by The Lupus Trust. Three authors reported consultancy, speaker, or advisory fees from Alumis, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, MGP, Novartis, Pfizer, Sanofi, UCB, Vifor, and/or Werfen Group. The other authors, including Dr. Sloan, had no industry-related disclosures. Dr. Kim reported research support from AstraZeneca, GlaxoSmithKline, and Novartis; speaking fees from Exagen Diagnostics and GlaxoSmithKline; and consulting fees from AbbVie, Amgen, ANI Pharmaceuticals, AstraZeneca, Atara Bio, Aurinia Pharmaceuticals, Cargo Therapeutics, Exagen Diagnostics, Hinge Bio, GlaxoSmithKline, Kypha, Miltenyi Biotec, Synthekine, and Tectonic Therapeutic.
 

A version of this article appeared on Medscape.com.

Neuropsychiatric symptoms, including nightmares and hallucinatory “daymares,” may be a more important aspect of systemic lupus erythematosus (SLE) than formerly recognized, according to a qualitative mixed methods study published in The Lancet Discovery Science’s eClinicalMedicine. The findings suggested these neuropsychiatric symptoms can sometimes present as prodromal and other times act as an early warning system for a forthcoming flare.

“For clinicians, the key point is to be aware that neurological and psychiatric symptoms are much more common in patients with lupus and other autoimmune systemic rheumatic diseases than previously thought,” lead author Melanie Sloan, PhD, of the Department of Public Health and Primary Care at the University of Cambridge in England, told this news organization.

“If clinicians — and some do already — could all ask about and document these symptoms for each patient, the usual progression of symptoms in a flare can then be monitored, and patients could be supported and treated at an earlier stage,” Dr. Sloan said. “Another key point is to consider systemic autoimmune diseases at an early stage if a patient presents with multiple seemingly unconnected symptoms, which often include both physical and mental health symptoms.”

Alfred Kim, MD, PhD, associate professor of medicine in rheumatology at Washington University School of Medicine in St. Louis, Missouri, noted the difficulty of determining what neuropsychiatric symptoms may be linked to lupus vs those occurring independently or as part of a different condition.

Dr. Kim

Study Details

In planning for the study, the researchers first searched the existing literature for studies involving neuropsychiatric symptoms in patients with systemic autoimmune rheumatic diseases (SARDs). “The literature indicated frequent underreporting and misattributions of neuropsychiatric symptoms in SLE and other SARD patients, and clinician-patient discordance in neuropsychiatric symptom attribution,” the authors reported.

During 2022-2023, the researchers conducted two surveys, one with 676 adult patients with SLE and one with 400 clinicians, recruited through social media, online patient support groups, and professional networks. All patients self-reported an SLE diagnosis that the researchers did not independently confirm. The patients were predominantly White (80%) and female (94%), ranging in age from 18 to over 70, with most falling between ages 40 and 69. Most patients lived in the United Kingdom (76%) or Europe (15%).

The clinicians included 51% rheumatologists, 24% psychiatrists, 13% neurologists, 5% rheumatology nurses, 3% primary care physicians, and 7% other clinicians. Nearly half of the clinicians (45%) were from the United Kingdom, with others from the United States or Canada (16%), Europe (17%), Asia (9%), Latin America (8%), Australia or New Zealand (3%), or elsewhere (3%).

The patient surveys asked whether they had experienced any of the 29 neuropsychiatric symptoms. For the symptoms that patients had experienced at least three times in their lives, the survey asked when they first experienced the symptom in relation to their SLE onset or other SLE symptoms: Over a year before, within a year of (on either side), 1-4 years after, or more than 5 years after onset/other symptoms. “Other quantitative data included timings of disrupted dreaming sleep in relation to hallucinations for those patients reporting experiencing these,” the authors wrote.

The researchers also conducted video conference interviews with 50 clinicians, including 20 rheumatologists, and 69 interviews with patients who had a systemic autoimmune rheumatic disease, including 27 patients with SLE. Other conditions among those interviewed included inflammatory arthritis, vasculitis, Sjögren disease, systemic sclerosis, myositis, undifferentiated and mixed connective tissue diseases, and polymyalgia rheumatica. During interviews, the term “daymare” was used to discuss possible hallucinations.
 

Linking Neuropsychiatric Symptoms and Disease

Four themes emerged from the analysis of the surveys and interviews. First, despite many rheumatologists stating that it was an “established theory” that most neuropsychiatric symptoms related to SLE would initially present around the time of diagnosis or disease onset, the findings from patients and interviews with psychiatrists did not align with this theory. The first presentation of each neuropsychiatric symptom only occurred around the onset of other SLE symptoms, about one fifth to one third of the time. In fact, more than half of the patients with SLE who had experienced hallucinations or delusions/paranoia said they occurred more than a year after they first experienced their other SLE symptoms.

Patient experiences differed in terms of whether they believed their neuropsychiatric symptoms were directly related to their SLE or other rheumatic disease. Some did attribute the symptoms, such as hypomania, to their rheumatic illness, while others, such as a patient with major depression, did not see the two as linked.

A second theme focused on pattern recognition of neuropsychiatric symptoms and the onset of a disease flare. “For example, several patients described how they felt that some types of depressive symptoms were directly attributable to active inflammation due to its time of onset and differences in type and intensity compared to their more ‘reactive’ low mood that could be more attributable to a consequence of psychological distress,” the authors wrote. Another common report from patients was experiencing a sudden, intense fatigue that coincided with a flare and differed from other types of fatigue.

Some patients could recognize that a flare was coming because of familiar neuropsychiatric symptoms that acted like an “early warning system.” Often, however, these symptoms “were absent from current diagnostic guidelines and only rarely identified by clinician interviewees as related to SLE/NPSLE,” the authors found. “These neuropsychiatric prodromal symptoms were reported as sometimes preceding the more widely recognized SLE and other SARD symptoms such as joint pain, rashes, and other organ involvement.” These symptoms included sudden changes in mood (usually a lowering but sometimes mania), increased nightmares, a “feeling of unreality,” or increased sensory symptoms.

Other patients, on the other hand, had not considered a link between neuropsychiatric symptoms and their rheumatic disease until the interview, and many of the clinicians, aside from psychiatrists and nurses, said they had little time in clinic to gather information about symptom progression.
 

Nightmares and Daymares

A third theme centered on disrupted dreaming sleep, nightmares, and “daymares” as a prodromal symptom in particular. Some patients had already drawn a connection between an oncoming flare of their disease and these dreaming-related symptoms, while others had not considered a link until the interviews.

“Several SLE patients recounted flares consistently involving the segueing of increasingly vivid and distressing nightmares into distorted reality and daytime hallucinations,” the authors reported. Flare-related nightmares in particular “often involved being attacked, trapped, crushed, or falling.” Patients tended to be more forthcoming about hallucinatory experiences when the term “daymare” was used to describe them, and they often related to the idea of feeling “in-between asleep and awake.”

Only one of the rheumatologists interviewed had considered nightmares as potentially related to SLE flares, and several appeared skeptical about a link but planned to ask their patients about it. Most of the specialists interviewed, meanwhile, said they often discussed sleep disruption with patients.

“There was agreement that recognizing and eliciting these early flare symptoms may improve care and even reduce clinic times by averting flares at any earlier stage, although some rheumatologists were clear that limited appointment times meant that these symptoms would not be prioritized for discussion,” the authors wrote.

Though Dr. Kim acknowledged the possibility of nightmares as prodromal, he noted other ways in which nightmares may be indirectly linked to lupus. “Trauma is a major risk factor for lupus,” Dr. Kim said, with multiple studies showing childhood traumatic experiences and even posttraumatic stress disorder to be risk factors for lupus. “Whether nightmares represent a traumatic event or prior traumatic events is not clear to me, but one could hypothesize that this may be a manifestation of trauma,” Dr. Kim said.

In addition, nightmares represent a sleep disorder that can substantially reduce sleep quality, Dr. Kim said, and poor sleep is also associated with lupus. “One has to wonder whether disruptive dreaming sleep is one of several specific manifestations of poor sleep quality, which then increases the risk of lupus in those patients,” Dr. Kim said.
 

Misattribution of Neuropsychiatric Symptoms

The final theme to emerge from the findings was patients had been misdiagnosed with psychiatric or psychosomatic conditions shortly before getting their rheumatic disease diagnosis. One patient, for example, reported being diagnosed with borderline personality disorder just 6 months before the lupus diagnosis at age 19 and noticed that the symptoms of one “got under control” when the symptoms of the other did.

“Early misattributions of SARD symptoms to primary psychiatric or psychosomatic conditions were frequently reported to have delayed SARD diagnosis and led to future misattributions,” the authors reported. “Whilst some of these misdiagnoses likely reflect the widespread lack of knowledge and limited definitive tests for SLE, it is plausible that some early SLE neurological and/or psychiatric symptoms may represent a neuropsychiatric prodrome for SLE itself.”

Dr. Kim agreed that misattribution of symptoms to other diagnoses is common with lupus and a common reason for delays in diagnosis, even with symptoms that are not neuropsychiatric. The findings in this study broaden “the type of symptoms we need to put on our radar pre-diagnosis,” Dr. Kim said. “We just also have to be aware that these prodromal symptoms are not diagnostic for lupus, though.”

Dr. Sloan cited earlier work in recommending an “ABC” approach to improving clinician-patient relationships: “Availability is being accessible when patients need them, Belief is demonstrating belief and validating patient self-reports of symptoms, and Continuity is when the same clinician sees the same patient each clinic visit to build up a trusting relationship.” She noted the importance of asking about and normalizing the existence of these symptoms with rheumatic diseases.

The research was funded by The Lupus Trust. Three authors reported consultancy, speaker, or advisory fees from Alumis, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, MGP, Novartis, Pfizer, Sanofi, UCB, Vifor, and/or Werfen Group. The other authors, including Dr. Sloan, had no industry-related disclosures. Dr. Kim reported research support from AstraZeneca, GlaxoSmithKline, and Novartis; speaking fees from Exagen Diagnostics and GlaxoSmithKline; and consulting fees from AbbVie, Amgen, ANI Pharmaceuticals, AstraZeneca, Atara Bio, Aurinia Pharmaceuticals, Cargo Therapeutics, Exagen Diagnostics, Hinge Bio, GlaxoSmithKline, Kypha, Miltenyi Biotec, Synthekine, and Tectonic Therapeutic.
 

A version of this article appeared on Medscape.com.

Neuropsychiatric symptoms, including nightmares and hallucinatory “daymares,” may be a more important aspect of systemic lupus erythematosus (SLE) than formerly recognized, according to a qualitative mixed methods study published in The Lancet Discovery Science’s eClinicalMedicine. The findings suggested these neuropsychiatric symptoms can sometimes present as prodromal and other times act as an early warning system for a forthcoming flare.

“For clinicians, the key point is to be aware that neurological and psychiatric symptoms are much more common in patients with lupus and other autoimmune systemic rheumatic diseases than previously thought,” lead author Melanie Sloan, PhD, of the Department of Public Health and Primary Care at the University of Cambridge in England, told this news organization.

“If clinicians — and some do already — could all ask about and document these symptoms for each patient, the usual progression of symptoms in a flare can then be monitored, and patients could be supported and treated at an earlier stage,” Dr. Sloan said. “Another key point is to consider systemic autoimmune diseases at an early stage if a patient presents with multiple seemingly unconnected symptoms, which often include both physical and mental health symptoms.”

Alfred Kim, MD, PhD, associate professor of medicine in rheumatology at Washington University School of Medicine in St. Louis, Missouri, noted the difficulty of determining what neuropsychiatric symptoms may be linked to lupus vs those occurring independently or as part of a different condition.

Dr. Kim

Study Details

In planning for the study, the researchers first searched the existing literature for studies involving neuropsychiatric symptoms in patients with systemic autoimmune rheumatic diseases (SARDs). “The literature indicated frequent underreporting and misattributions of neuropsychiatric symptoms in SLE and other SARD patients, and clinician-patient discordance in neuropsychiatric symptom attribution,” the authors reported.

During 2022-2023, the researchers conducted two surveys, one with 676 adult patients with SLE and one with 400 clinicians, recruited through social media, online patient support groups, and professional networks. All patients self-reported an SLE diagnosis that the researchers did not independently confirm. The patients were predominantly White (80%) and female (94%), ranging in age from 18 to over 70, with most falling between ages 40 and 69. Most patients lived in the United Kingdom (76%) or Europe (15%).

The clinicians included 51% rheumatologists, 24% psychiatrists, 13% neurologists, 5% rheumatology nurses, 3% primary care physicians, and 7% other clinicians. Nearly half of the clinicians (45%) were from the United Kingdom, with others from the United States or Canada (16%), Europe (17%), Asia (9%), Latin America (8%), Australia or New Zealand (3%), or elsewhere (3%).

The patient surveys asked whether they had experienced any of the 29 neuropsychiatric symptoms. For the symptoms that patients had experienced at least three times in their lives, the survey asked when they first experienced the symptom in relation to their SLE onset or other SLE symptoms: Over a year before, within a year of (on either side), 1-4 years after, or more than 5 years after onset/other symptoms. “Other quantitative data included timings of disrupted dreaming sleep in relation to hallucinations for those patients reporting experiencing these,” the authors wrote.

The researchers also conducted video conference interviews with 50 clinicians, including 20 rheumatologists, and 69 interviews with patients who had a systemic autoimmune rheumatic disease, including 27 patients with SLE. Other conditions among those interviewed included inflammatory arthritis, vasculitis, Sjögren disease, systemic sclerosis, myositis, undifferentiated and mixed connective tissue diseases, and polymyalgia rheumatica. During interviews, the term “daymare” was used to discuss possible hallucinations.
 

Linking Neuropsychiatric Symptoms and Disease

Four themes emerged from the analysis of the surveys and interviews. First, despite many rheumatologists stating that it was an “established theory” that most neuropsychiatric symptoms related to SLE would initially present around the time of diagnosis or disease onset, the findings from patients and interviews with psychiatrists did not align with this theory. The first presentation of each neuropsychiatric symptom only occurred around the onset of other SLE symptoms, about one fifth to one third of the time. In fact, more than half of the patients with SLE who had experienced hallucinations or delusions/paranoia said they occurred more than a year after they first experienced their other SLE symptoms.

Patient experiences differed in terms of whether they believed their neuropsychiatric symptoms were directly related to their SLE or other rheumatic disease. Some did attribute the symptoms, such as hypomania, to their rheumatic illness, while others, such as a patient with major depression, did not see the two as linked.

A second theme focused on pattern recognition of neuropsychiatric symptoms and the onset of a disease flare. “For example, several patients described how they felt that some types of depressive symptoms were directly attributable to active inflammation due to its time of onset and differences in type and intensity compared to their more ‘reactive’ low mood that could be more attributable to a consequence of psychological distress,” the authors wrote. Another common report from patients was experiencing a sudden, intense fatigue that coincided with a flare and differed from other types of fatigue.

Some patients could recognize that a flare was coming because of familiar neuropsychiatric symptoms that acted like an “early warning system.” Often, however, these symptoms “were absent from current diagnostic guidelines and only rarely identified by clinician interviewees as related to SLE/NPSLE,” the authors found. “These neuropsychiatric prodromal symptoms were reported as sometimes preceding the more widely recognized SLE and other SARD symptoms such as joint pain, rashes, and other organ involvement.” These symptoms included sudden changes in mood (usually a lowering but sometimes mania), increased nightmares, a “feeling of unreality,” or increased sensory symptoms.

Other patients, on the other hand, had not considered a link between neuropsychiatric symptoms and their rheumatic disease until the interview, and many of the clinicians, aside from psychiatrists and nurses, said they had little time in clinic to gather information about symptom progression.
 

Nightmares and Daymares

A third theme centered on disrupted dreaming sleep, nightmares, and “daymares” as a prodromal symptom in particular. Some patients had already drawn a connection between an oncoming flare of their disease and these dreaming-related symptoms, while others had not considered a link until the interviews.

“Several SLE patients recounted flares consistently involving the segueing of increasingly vivid and distressing nightmares into distorted reality and daytime hallucinations,” the authors reported. Flare-related nightmares in particular “often involved being attacked, trapped, crushed, or falling.” Patients tended to be more forthcoming about hallucinatory experiences when the term “daymare” was used to describe them, and they often related to the idea of feeling “in-between asleep and awake.”

Only one of the rheumatologists interviewed had considered nightmares as potentially related to SLE flares, and several appeared skeptical about a link but planned to ask their patients about it. Most of the specialists interviewed, meanwhile, said they often discussed sleep disruption with patients.

“There was agreement that recognizing and eliciting these early flare symptoms may improve care and even reduce clinic times by averting flares at any earlier stage, although some rheumatologists were clear that limited appointment times meant that these symptoms would not be prioritized for discussion,” the authors wrote.

Though Dr. Kim acknowledged the possibility of nightmares as prodromal, he noted other ways in which nightmares may be indirectly linked to lupus. “Trauma is a major risk factor for lupus,” Dr. Kim said, with multiple studies showing childhood traumatic experiences and even posttraumatic stress disorder to be risk factors for lupus. “Whether nightmares represent a traumatic event or prior traumatic events is not clear to me, but one could hypothesize that this may be a manifestation of trauma,” Dr. Kim said.

In addition, nightmares represent a sleep disorder that can substantially reduce sleep quality, Dr. Kim said, and poor sleep is also associated with lupus. “One has to wonder whether disruptive dreaming sleep is one of several specific manifestations of poor sleep quality, which then increases the risk of lupus in those patients,” Dr. Kim said.
 

Misattribution of Neuropsychiatric Symptoms

The final theme to emerge from the findings was patients had been misdiagnosed with psychiatric or psychosomatic conditions shortly before getting their rheumatic disease diagnosis. One patient, for example, reported being diagnosed with borderline personality disorder just 6 months before the lupus diagnosis at age 19 and noticed that the symptoms of one “got under control” when the symptoms of the other did.

“Early misattributions of SARD symptoms to primary psychiatric or psychosomatic conditions were frequently reported to have delayed SARD diagnosis and led to future misattributions,” the authors reported. “Whilst some of these misdiagnoses likely reflect the widespread lack of knowledge and limited definitive tests for SLE, it is plausible that some early SLE neurological and/or psychiatric symptoms may represent a neuropsychiatric prodrome for SLE itself.”

Dr. Kim agreed that misattribution of symptoms to other diagnoses is common with lupus and a common reason for delays in diagnosis, even with symptoms that are not neuropsychiatric. The findings in this study broaden “the type of symptoms we need to put on our radar pre-diagnosis,” Dr. Kim said. “We just also have to be aware that these prodromal symptoms are not diagnostic for lupus, though.”

Dr. Sloan cited earlier work in recommending an “ABC” approach to improving clinician-patient relationships: “Availability is being accessible when patients need them, Belief is demonstrating belief and validating patient self-reports of symptoms, and Continuity is when the same clinician sees the same patient each clinic visit to build up a trusting relationship.” She noted the importance of asking about and normalizing the existence of these symptoms with rheumatic diseases.

The research was funded by The Lupus Trust. Three authors reported consultancy, speaker, or advisory fees from Alumis, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, MGP, Novartis, Pfizer, Sanofi, UCB, Vifor, and/or Werfen Group. The other authors, including Dr. Sloan, had no industry-related disclosures. Dr. Kim reported research support from AstraZeneca, GlaxoSmithKline, and Novartis; speaking fees from Exagen Diagnostics and GlaxoSmithKline; and consulting fees from AbbVie, Amgen, ANI Pharmaceuticals, AstraZeneca, Atara Bio, Aurinia Pharmaceuticals, Cargo Therapeutics, Exagen Diagnostics, Hinge Bio, GlaxoSmithKline, Kypha, Miltenyi Biotec, Synthekine, and Tectonic Therapeutic.
 

A version of this article appeared on Medscape.com.

About one in six children (17%) between 3 and 17 years have a disability, which may affect their ability to make decisions when they transition to adulthood.

Typically, at age 18, a young adult assumes rights such as the legal right to make medical decisions (including reproductive decisions), and mental health, financial, and education decisions.

The American Academy of Pediatrics (AAP) recently issued a policy statement in Pediatrics to help pediatricians help young people with Intellectual and/or Developmental Disabilities (IDD) and their families with alternative ways to make those decisions if necessary .
 

Several Options in the Continuum

The AAP describes a continuum of decision-making for youth with IDD from fully autonomous decisions to decisions made by an appointed guardian.

Highlighting an array of options is one way this paper is helpful, said Matthew Siegel, MD, chief of clinical enterprise with the Department of Psychiatry & Behavioral Sciences at Boston Children’s Hospital in Massachusetts. “I suspect that for a lot of practitioners what they’re aware of is guardianship or no guardianship.” These authors highlight that the options are more nuanced, he said.

Pediatricians have widely different ideas about what their role should be in facilitating decision-making in the transition period, he said, so this paper helps clarify what advocacy and discussion are needed.

The paper, written by first author Renee M. Turchi, MD, MPH, and colleagues on behalf of the Council on Children with Disabilities’ Committee on Medical Liability and Risk Management, states that, “The goal should always be the least restrictive decision-making that balances autonomy with safety and supports.”
 

One Alternative Is Supported Decision-Making

Supported decision-making is one alternative to guardianship. Authors explain that under that framework, a patient can choose a trusted support person and create an agreement with that person on what kinds of decisions the person needs help with and how much assistance is needed. The individual makes the final decision, not the support person.

Authors explain the benefits of that approach: “Individuals with IDD who use supported decision-making report increased confidence in themselves and their decision-making, improved decision-making skills, increased engagement with their community, and perceived more control of their lives,” the authors wrote.

Another option for people with IDD might be, rather than formally naming a substitute decision-maker, allowing a parent or caregiver access to their electronic health record or allowing that person to have independent discussions with their physician.

With guardianship, also called conservatorship in some states, a court requires clear and convincing evidence that the youth is not competent to make his or her own decisions. The court may order evaluations by many professionals, including pediatricians.
 

State-Specific Legal Information Is Available

Many states have recently enacted laws surrounding supported decision-making and guardianship. The authors reference a national resource center website that details the legislation for each state and points to resources and tools for pediatricians, families, and patients.

“Historically, pediatricians have rarely discussed the legal aspects of transition to adult-oriented services with the youth with IDD and subsequently, their families,” the authors wrote.
 

Discussions Should Start Early

Ideally, the authors wrote, the discussions about what level of supports might be necessary in the transition to adulthood should start at age 12-14 and include the youth, teachers, parents, and the medical team.

That’s earlier than some of the previous guidance, Dr. Siegel said, and it will be important to evaluate future evidence on the best age to start planning “both from a cognitive development standpoint and from a practicality standpoint.”

The authors point out that the needs for level of support may change and “pediatricians can reevaluate the decision-making arrangement as part of the annual physical/mental examinations to align with the youth’s desires, needs, and decision-making abilities over time.”

The authors and Dr. Siegel report no relevant financial relationships.

About one in six children (17%) between 3 and 17 years have a disability, which may affect their ability to make decisions when they transition to adulthood.

Typically, at age 18, a young adult assumes rights such as the legal right to make medical decisions (including reproductive decisions), and mental health, financial, and education decisions.

The American Academy of Pediatrics (AAP) recently issued a policy statement in Pediatrics to help pediatricians help young people with Intellectual and/or Developmental Disabilities (IDD) and their families with alternative ways to make those decisions if necessary .
 

Several Options in the Continuum

The AAP describes a continuum of decision-making for youth with IDD from fully autonomous decisions to decisions made by an appointed guardian.

Highlighting an array of options is one way this paper is helpful, said Matthew Siegel, MD, chief of clinical enterprise with the Department of Psychiatry & Behavioral Sciences at Boston Children’s Hospital in Massachusetts. “I suspect that for a lot of practitioners what they’re aware of is guardianship or no guardianship.” These authors highlight that the options are more nuanced, he said.

Pediatricians have widely different ideas about what their role should be in facilitating decision-making in the transition period, he said, so this paper helps clarify what advocacy and discussion are needed.

The paper, written by first author Renee M. Turchi, MD, MPH, and colleagues on behalf of the Council on Children with Disabilities’ Committee on Medical Liability and Risk Management, states that, “The goal should always be the least restrictive decision-making that balances autonomy with safety and supports.”
 

One Alternative Is Supported Decision-Making

Supported decision-making is one alternative to guardianship. Authors explain that under that framework, a patient can choose a trusted support person and create an agreement with that person on what kinds of decisions the person needs help with and how much assistance is needed. The individual makes the final decision, not the support person.

Authors explain the benefits of that approach: “Individuals with IDD who use supported decision-making report increased confidence in themselves and their decision-making, improved decision-making skills, increased engagement with their community, and perceived more control of their lives,” the authors wrote.

Another option for people with IDD might be, rather than formally naming a substitute decision-maker, allowing a parent or caregiver access to their electronic health record or allowing that person to have independent discussions with their physician.

With guardianship, also called conservatorship in some states, a court requires clear and convincing evidence that the youth is not competent to make his or her own decisions. The court may order evaluations by many professionals, including pediatricians.
 

State-Specific Legal Information Is Available

Many states have recently enacted laws surrounding supported decision-making and guardianship. The authors reference a national resource center website that details the legislation for each state and points to resources and tools for pediatricians, families, and patients.

“Historically, pediatricians have rarely discussed the legal aspects of transition to adult-oriented services with the youth with IDD and subsequently, their families,” the authors wrote.
 

Discussions Should Start Early

Ideally, the authors wrote, the discussions about what level of supports might be necessary in the transition to adulthood should start at age 12-14 and include the youth, teachers, parents, and the medical team.

That’s earlier than some of the previous guidance, Dr. Siegel said, and it will be important to evaluate future evidence on the best age to start planning “both from a cognitive development standpoint and from a practicality standpoint.”

The authors point out that the needs for level of support may change and “pediatricians can reevaluate the decision-making arrangement as part of the annual physical/mental examinations to align with the youth’s desires, needs, and decision-making abilities over time.”

The authors and Dr. Siegel report no relevant financial relationships.

About one in six children (17%) between 3 and 17 years have a disability, which may affect their ability to make decisions when they transition to adulthood.

Typically, at age 18, a young adult assumes rights such as the legal right to make medical decisions (including reproductive decisions), and mental health, financial, and education decisions.

The American Academy of Pediatrics (AAP) recently issued a policy statement in Pediatrics to help pediatricians help young people with Intellectual and/or Developmental Disabilities (IDD) and their families with alternative ways to make those decisions if necessary .
 

Several Options in the Continuum

The AAP describes a continuum of decision-making for youth with IDD from fully autonomous decisions to decisions made by an appointed guardian.

Highlighting an array of options is one way this paper is helpful, said Matthew Siegel, MD, chief of clinical enterprise with the Department of Psychiatry & Behavioral Sciences at Boston Children’s Hospital in Massachusetts. “I suspect that for a lot of practitioners what they’re aware of is guardianship or no guardianship.” These authors highlight that the options are more nuanced, he said.

Pediatricians have widely different ideas about what their role should be in facilitating decision-making in the transition period, he said, so this paper helps clarify what advocacy and discussion are needed.

The paper, written by first author Renee M. Turchi, MD, MPH, and colleagues on behalf of the Council on Children with Disabilities’ Committee on Medical Liability and Risk Management, states that, “The goal should always be the least restrictive decision-making that balances autonomy with safety and supports.”
 

One Alternative Is Supported Decision-Making

Supported decision-making is one alternative to guardianship. Authors explain that under that framework, a patient can choose a trusted support person and create an agreement with that person on what kinds of decisions the person needs help with and how much assistance is needed. The individual makes the final decision, not the support person.

Authors explain the benefits of that approach: “Individuals with IDD who use supported decision-making report increased confidence in themselves and their decision-making, improved decision-making skills, increased engagement with their community, and perceived more control of their lives,” the authors wrote.

Another option for people with IDD might be, rather than formally naming a substitute decision-maker, allowing a parent or caregiver access to their electronic health record or allowing that person to have independent discussions with their physician.

With guardianship, also called conservatorship in some states, a court requires clear and convincing evidence that the youth is not competent to make his or her own decisions. The court may order evaluations by many professionals, including pediatricians.
 

State-Specific Legal Information Is Available

Many states have recently enacted laws surrounding supported decision-making and guardianship. The authors reference a national resource center website that details the legislation for each state and points to resources and tools for pediatricians, families, and patients.

“Historically, pediatricians have rarely discussed the legal aspects of transition to adult-oriented services with the youth with IDD and subsequently, their families,” the authors wrote.
 

Discussions Should Start Early

Ideally, the authors wrote, the discussions about what level of supports might be necessary in the transition to adulthood should start at age 12-14 and include the youth, teachers, parents, and the medical team.

That’s earlier than some of the previous guidance, Dr. Siegel said, and it will be important to evaluate future evidence on the best age to start planning “both from a cognitive development standpoint and from a practicality standpoint.”

The authors point out that the needs for level of support may change and “pediatricians can reevaluate the decision-making arrangement as part of the annual physical/mental examinations to align with the youth’s desires, needs, and decision-making abilities over time.”

The authors and Dr. Siegel report no relevant financial relationships.

For those outside the medical profession, it took a global pandemic to finally understand how pervasive distress and suicide are among medical professionals, particularly surgeons.

For James Harrop, MD, it was made real years earlier by a colleague he’d trained alongside and worked with for decades — “one of the best surgeons I’ve ever seen” who, one day, just wasn’t there.

Lost in his own work, it wasn’t until Dr. Harrop, a professor of neurological and orthopedic surgery at Thomas Jefferson University, Philadelphia, read an article in The New England Journal of Medicine and realized his friend Michael Weinstein, MD, MPH, had been profoundly depressed for years and was hospitalized for his own safety.

Dr. Weinstein recovered and later gave grand rounds at Thomas Jefferson University, where he is an associate professor of surgery in the Acute Care Surgery Division. But the story stuck with Dr. Harrop.

“I said to Mike afterward, I’ve known you for 20 years and, retrospectively, going back, I never saw a single sign that you were depressed, sad, or had any issues, and he said to me ‘that’s because I did everything I could to make sure no one knew I had a problem,’ ” Dr. Harrop said during a talk on physician suicide on May 4 at the American Association of Neurological Surgeons (AANS) 2024 Annual Meeting.

“And that scared me because we need to help these people, we need to identify who they are.”

Surgeons at Greater Risk

Studies have reported that suicide and suicidal ideation are nearly twice as common among physicians, compared with among the general population. Among 9175 physicians surveyed in the 2023 Medscape Physician Suicide Report, 9% had considered suicide, and 1% had attempted it. The average for US adults is 4.9% and 0.5%, respectively.

Surgeons are at particularly high risk. A 2011 survey of 7905 US surgeons found that 1 in 16 (6.3%) had considered suicide in the previous year. A post-pandemic survey of more than 600 surgeons and surgical trainees reported that one in seven had suicidal ideation.

It’s often estimated that between 300 and 400 physicians die by suicide each year in the United States, but exact numbers are not known. Recent updated estimates from the National Violent Death Reporting System put the number at 119 physician suicides annually.

Notably, that’s no better than data reported more than 50 years ago in the landmark policy paper The Sick Physician: Impairment by Psychiatric Disorders, Including Alcoholism and Drug Dependence. It sounded the alarm on poor mental health in physicians and reported that 100 doctors died by suicide annually — the equivalent of the average medical school graduating class at the time.

“If I take my med school class and double it, that’s how many physicians die each year,” Dr. Harrop said. “And here’s the bad news, it starts in medical school.”

Research shows higher rates of depression and suicidal ideation in medical students and residents than in other graduates, with rates varying by stage of training, he noted.

In a multischool study, 12% of medical students and residents had probable major depression, 9.2% mild/moderate depression, and suicidal ideation jumped from 6.6% in the first year of medical school to 9.4% in year 4.

A recent AANS survey of 346 neurosurgery residents revealed 67% had burnout, and 41% seriously considered quitting. Burnout rose to a high of 76% in the second year and decreased to 49% and 54% in years 3 and 4, respectively.

Inadequate operating room exposure, hostile faculty, and stressors outside work were tied to burnout, whereas mentorship was linked to a threefold lower likelihood of burnout.

Notably, a 2019 study conservatively estimated that the annual cost of burnout-related physician turnover and reduced clinical hours was $4.6 billion nationally and $7600 per employed physician for an organization.

“We need to be kinder to each other, to look out for each other, and to talk to each other,” Dr. Harrop told conference attendees.

‘Death by a 1000 Cuts’

A host of factors are associated with physician suicide including long work hours, delayed gratification, difficulty balancing work and home life, changing healthcare systems, lawsuits, and the unique ability to prescribe medications, said Dr. Harrop.

“In my life, I think of it as death by 1000 cuts. Every day I come in, you’ve got another person attacking you,” he said, referencing Death by 1000 Cuts: Medscape National Physician Burnout & Suicide Report 2021.

Dr. Harrop told this news organization that talking with numerous experts in this field has made him appreciate that anyone is at a risk for suicide.

“The problem is an overload of external resources crushing your existence to the point that you become paralyzed and make the irrational thought that the best solution is to end your life,” he said.

Ann Stroink, MD, immediate past president of the AANS, said in an interview that one potential trigger for burnout is the current shortage of neurosurgeons in the United States, which has led to increased workloads and potential sleep deprivation among existing neurosurgeons.

“To address this critical issue, we’ve been advocating through legislative channels for additional Medicare[-funded] slots” to train more neurosurgeons, she said. “It’s imperative that we take proactive steps to ensure that our healthcare system can sustainably meet the needs of patients, while also supporting the well-being of our neurosurgical professionals.”

The AANS is also advocating for decreased regulatory burdens associated with Medicare and insurance coverage, such as prior authorization, to help alleviate the administrative burdens that often contribute to burnout among its members, Dr. Stroink said.

A Model for Suicide Prevention

Dr. Harrop emphasized that suicide is preventable and that there is “some good news.” Turning to another high-risk profession, he noted that the US Air Force was able to reduce its suicide rate by 42.7% between 1994 and 1998 by doing three basic things.

The agency established a central surveillance database, restructured prevention services, and, more importantly, began conducting annual suicide prevention and awareness training, using gatekeepers to channel at-risk personnel to appropriate agencies and performing mental health questionnaires at enrollment and annually.

Similarly, education, screening, and access to mental health treatment are core recommendations for a national response to depression and suicide in physician trainees, said Dr. Harrop, who noted that his own hospital has started using the Patient Health Questionnaire 9-item for its staff.

Asked by this news organization how much progress has been made since The Sick Physician report, Dr. Harrop said, “we are probably doing worse” in terms of the number of physician suicides, but “on a positive note, we are better with resources and acknowledgment that a problem exists.”

He noted that the AANS, which has published a physician burnout series on its Neurosurgery Blog, has shown great interest in this topic and is working to spread the word to help neurosurgeons. “My simple talk has led to me being approached by numerous people and healthcare organizations on how to further focus resources and prevention of this problem.”

Asked the one thing he would tell his friend, Michael Weinstein, a fellow surgeon, or trainee who’s struggling, Dr. Harrop said, “I am here for you, and we will get over these temporary problems, which are not significant in the big picture of what you mean to the world.”

Dr. Harrop reported serving as an adviser for Ethicon and Spiderwort.

A version of this article appeared on Medscape.com.

For those outside the medical profession, it took a global pandemic to finally understand how pervasive distress and suicide are among medical professionals, particularly surgeons.

For James Harrop, MD, it was made real years earlier by a colleague he’d trained alongside and worked with for decades — “one of the best surgeons I’ve ever seen” who, one day, just wasn’t there.

Lost in his own work, it wasn’t until Dr. Harrop, a professor of neurological and orthopedic surgery at Thomas Jefferson University, Philadelphia, read an article in The New England Journal of Medicine and realized his friend Michael Weinstein, MD, MPH, had been profoundly depressed for years and was hospitalized for his own safety.

Dr. Weinstein recovered and later gave grand rounds at Thomas Jefferson University, where he is an associate professor of surgery in the Acute Care Surgery Division. But the story stuck with Dr. Harrop.

“I said to Mike afterward, I’ve known you for 20 years and, retrospectively, going back, I never saw a single sign that you were depressed, sad, or had any issues, and he said to me ‘that’s because I did everything I could to make sure no one knew I had a problem,’ ” Dr. Harrop said during a talk on physician suicide on May 4 at the American Association of Neurological Surgeons (AANS) 2024 Annual Meeting.

“And that scared me because we need to help these people, we need to identify who they are.”

Surgeons at Greater Risk

Studies have reported that suicide and suicidal ideation are nearly twice as common among physicians, compared with among the general population. Among 9175 physicians surveyed in the 2023 Medscape Physician Suicide Report, 9% had considered suicide, and 1% had attempted it. The average for US adults is 4.9% and 0.5%, respectively.

Surgeons are at particularly high risk. A 2011 survey of 7905 US surgeons found that 1 in 16 (6.3%) had considered suicide in the previous year. A post-pandemic survey of more than 600 surgeons and surgical trainees reported that one in seven had suicidal ideation.

It’s often estimated that between 300 and 400 physicians die by suicide each year in the United States, but exact numbers are not known. Recent updated estimates from the National Violent Death Reporting System put the number at 119 physician suicides annually.

Notably, that’s no better than data reported more than 50 years ago in the landmark policy paper The Sick Physician: Impairment by Psychiatric Disorders, Including Alcoholism and Drug Dependence. It sounded the alarm on poor mental health in physicians and reported that 100 doctors died by suicide annually — the equivalent of the average medical school graduating class at the time.

“If I take my med school class and double it, that’s how many physicians die each year,” Dr. Harrop said. “And here’s the bad news, it starts in medical school.”

Research shows higher rates of depression and suicidal ideation in medical students and residents than in other graduates, with rates varying by stage of training, he noted.

In a multischool study, 12% of medical students and residents had probable major depression, 9.2% mild/moderate depression, and suicidal ideation jumped from 6.6% in the first year of medical school to 9.4% in year 4.

A recent AANS survey of 346 neurosurgery residents revealed 67% had burnout, and 41% seriously considered quitting. Burnout rose to a high of 76% in the second year and decreased to 49% and 54% in years 3 and 4, respectively.

Inadequate operating room exposure, hostile faculty, and stressors outside work were tied to burnout, whereas mentorship was linked to a threefold lower likelihood of burnout.

Notably, a 2019 study conservatively estimated that the annual cost of burnout-related physician turnover and reduced clinical hours was $4.6 billion nationally and $7600 per employed physician for an organization.

“We need to be kinder to each other, to look out for each other, and to talk to each other,” Dr. Harrop told conference attendees.

‘Death by a 1000 Cuts’

A host of factors are associated with physician suicide including long work hours, delayed gratification, difficulty balancing work and home life, changing healthcare systems, lawsuits, and the unique ability to prescribe medications, said Dr. Harrop.

“In my life, I think of it as death by 1000 cuts. Every day I come in, you’ve got another person attacking you,” he said, referencing Death by 1000 Cuts: Medscape National Physician Burnout & Suicide Report 2021.

Dr. Harrop told this news organization that talking with numerous experts in this field has made him appreciate that anyone is at a risk for suicide.

“The problem is an overload of external resources crushing your existence to the point that you become paralyzed and make the irrational thought that the best solution is to end your life,” he said.

Ann Stroink, MD, immediate past president of the AANS, said in an interview that one potential trigger for burnout is the current shortage of neurosurgeons in the United States, which has led to increased workloads and potential sleep deprivation among existing neurosurgeons.

“To address this critical issue, we’ve been advocating through legislative channels for additional Medicare[-funded] slots” to train more neurosurgeons, she said. “It’s imperative that we take proactive steps to ensure that our healthcare system can sustainably meet the needs of patients, while also supporting the well-being of our neurosurgical professionals.”

The AANS is also advocating for decreased regulatory burdens associated with Medicare and insurance coverage, such as prior authorization, to help alleviate the administrative burdens that often contribute to burnout among its members, Dr. Stroink said.

A Model for Suicide Prevention

Dr. Harrop emphasized that suicide is preventable and that there is “some good news.” Turning to another high-risk profession, he noted that the US Air Force was able to reduce its suicide rate by 42.7% between 1994 and 1998 by doing three basic things.

The agency established a central surveillance database, restructured prevention services, and, more importantly, began conducting annual suicide prevention and awareness training, using gatekeepers to channel at-risk personnel to appropriate agencies and performing mental health questionnaires at enrollment and annually.

Similarly, education, screening, and access to mental health treatment are core recommendations for a national response to depression and suicide in physician trainees, said Dr. Harrop, who noted that his own hospital has started using the Patient Health Questionnaire 9-item for its staff.

Asked by this news organization how much progress has been made since The Sick Physician report, Dr. Harrop said, “we are probably doing worse” in terms of the number of physician suicides, but “on a positive note, we are better with resources and acknowledgment that a problem exists.”

He noted that the AANS, which has published a physician burnout series on its Neurosurgery Blog, has shown great interest in this topic and is working to spread the word to help neurosurgeons. “My simple talk has led to me being approached by numerous people and healthcare organizations on how to further focus resources and prevention of this problem.”

Asked the one thing he would tell his friend, Michael Weinstein, a fellow surgeon, or trainee who’s struggling, Dr. Harrop said, “I am here for you, and we will get over these temporary problems, which are not significant in the big picture of what you mean to the world.”

Dr. Harrop reported serving as an adviser for Ethicon and Spiderwort.

A version of this article appeared on Medscape.com.

For those outside the medical profession, it took a global pandemic to finally understand how pervasive distress and suicide are among medical professionals, particularly surgeons.

For James Harrop, MD, it was made real years earlier by a colleague he’d trained alongside and worked with for decades — “one of the best surgeons I’ve ever seen” who, one day, just wasn’t there.

Lost in his own work, it wasn’t until Dr. Harrop, a professor of neurological and orthopedic surgery at Thomas Jefferson University, Philadelphia, read an article in The New England Journal of Medicine and realized his friend Michael Weinstein, MD, MPH, had been profoundly depressed for years and was hospitalized for his own safety.

Dr. Weinstein recovered and later gave grand rounds at Thomas Jefferson University, where he is an associate professor of surgery in the Acute Care Surgery Division. But the story stuck with Dr. Harrop.

“I said to Mike afterward, I’ve known you for 20 years and, retrospectively, going back, I never saw a single sign that you were depressed, sad, or had any issues, and he said to me ‘that’s because I did everything I could to make sure no one knew I had a problem,’ ” Dr. Harrop said during a talk on physician suicide on May 4 at the American Association of Neurological Surgeons (AANS) 2024 Annual Meeting.

“And that scared me because we need to help these people, we need to identify who they are.”

Surgeons at Greater Risk

Studies have reported that suicide and suicidal ideation are nearly twice as common among physicians, compared with among the general population. Among 9175 physicians surveyed in the 2023 Medscape Physician Suicide Report, 9% had considered suicide, and 1% had attempted it. The average for US adults is 4.9% and 0.5%, respectively.

Surgeons are at particularly high risk. A 2011 survey of 7905 US surgeons found that 1 in 16 (6.3%) had considered suicide in the previous year. A post-pandemic survey of more than 600 surgeons and surgical trainees reported that one in seven had suicidal ideation.

It’s often estimated that between 300 and 400 physicians die by suicide each year in the United States, but exact numbers are not known. Recent updated estimates from the National Violent Death Reporting System put the number at 119 physician suicides annually.

Notably, that’s no better than data reported more than 50 years ago in the landmark policy paper The Sick Physician: Impairment by Psychiatric Disorders, Including Alcoholism and Drug Dependence. It sounded the alarm on poor mental health in physicians and reported that 100 doctors died by suicide annually — the equivalent of the average medical school graduating class at the time.

“If I take my med school class and double it, that’s how many physicians die each year,” Dr. Harrop said. “And here’s the bad news, it starts in medical school.”

Research shows higher rates of depression and suicidal ideation in medical students and residents than in other graduates, with rates varying by stage of training, he noted.

In a multischool study, 12% of medical students and residents had probable major depression, 9.2% mild/moderate depression, and suicidal ideation jumped from 6.6% in the first year of medical school to 9.4% in year 4.

A recent AANS survey of 346 neurosurgery residents revealed 67% had burnout, and 41% seriously considered quitting. Burnout rose to a high of 76% in the second year and decreased to 49% and 54% in years 3 and 4, respectively.

Inadequate operating room exposure, hostile faculty, and stressors outside work were tied to burnout, whereas mentorship was linked to a threefold lower likelihood of burnout.

Notably, a 2019 study conservatively estimated that the annual cost of burnout-related physician turnover and reduced clinical hours was $4.6 billion nationally and $7600 per employed physician for an organization.

“We need to be kinder to each other, to look out for each other, and to talk to each other,” Dr. Harrop told conference attendees.

‘Death by a 1000 Cuts’

A host of factors are associated with physician suicide including long work hours, delayed gratification, difficulty balancing work and home life, changing healthcare systems, lawsuits, and the unique ability to prescribe medications, said Dr. Harrop.

“In my life, I think of it as death by 1000 cuts. Every day I come in, you’ve got another person attacking you,” he said, referencing Death by 1000 Cuts: Medscape National Physician Burnout & Suicide Report 2021.

Dr. Harrop told this news organization that talking with numerous experts in this field has made him appreciate that anyone is at a risk for suicide.

“The problem is an overload of external resources crushing your existence to the point that you become paralyzed and make the irrational thought that the best solution is to end your life,” he said.

Ann Stroink, MD, immediate past president of the AANS, said in an interview that one potential trigger for burnout is the current shortage of neurosurgeons in the United States, which has led to increased workloads and potential sleep deprivation among existing neurosurgeons.

“To address this critical issue, we’ve been advocating through legislative channels for additional Medicare[-funded] slots” to train more neurosurgeons, she said. “It’s imperative that we take proactive steps to ensure that our healthcare system can sustainably meet the needs of patients, while also supporting the well-being of our neurosurgical professionals.”

The AANS is also advocating for decreased regulatory burdens associated with Medicare and insurance coverage, such as prior authorization, to help alleviate the administrative burdens that often contribute to burnout among its members, Dr. Stroink said.

A Model for Suicide Prevention

Dr. Harrop emphasized that suicide is preventable and that there is “some good news.” Turning to another high-risk profession, he noted that the US Air Force was able to reduce its suicide rate by 42.7% between 1994 and 1998 by doing three basic things.

The agency established a central surveillance database, restructured prevention services, and, more importantly, began conducting annual suicide prevention and awareness training, using gatekeepers to channel at-risk personnel to appropriate agencies and performing mental health questionnaires at enrollment and annually.

Similarly, education, screening, and access to mental health treatment are core recommendations for a national response to depression and suicide in physician trainees, said Dr. Harrop, who noted that his own hospital has started using the Patient Health Questionnaire 9-item for its staff.

Asked by this news organization how much progress has been made since The Sick Physician report, Dr. Harrop said, “we are probably doing worse” in terms of the number of physician suicides, but “on a positive note, we are better with resources and acknowledgment that a problem exists.”

He noted that the AANS, which has published a physician burnout series on its Neurosurgery Blog, has shown great interest in this topic and is working to spread the word to help neurosurgeons. “My simple talk has led to me being approached by numerous people and healthcare organizations on how to further focus resources and prevention of this problem.”

Asked the one thing he would tell his friend, Michael Weinstein, a fellow surgeon, or trainee who’s struggling, Dr. Harrop said, “I am here for you, and we will get over these temporary problems, which are not significant in the big picture of what you mean to the world.”

Dr. Harrop reported serving as an adviser for Ethicon and Spiderwort.

A version of this article appeared on Medscape.com.

TOPLINE:

US fentanyl seizures increased by more than 1700% between 2017 and 2023, new data showed. 

METHODOLOGY:

• Investigators analyzed data from the High Intensity Drug Trafficking Areas (HIDTA) program from 2017 through 2023.
• To assess trends in illicit fentanyl availability, investigators used eight indicators of potential shifts in illicit fentanyl supply, including total seizures, powder seizures, pill seizures, and the total weight of seizures.

TAKEAWAY:

• A total of 66,303 fentanyl seizures were identified. Of the total number of seizures, 67% were in powder form and 33% were pills.
• The total number of seizures during the study period increased by > 1700% — from 74,663 in 2017 to 115,221 in 2023.
• In 2023, the greatest number of fentanyl seizures was in Florida (n = 2,089), followed by Arizona (n = 1783) and California (n = 1440).Western United States experienced the greatest increase in seizures, particularly in pill form, suggesting a significant regional shift in fentanyl distribution. California had the greatest number of pills seized (n = 38.6 million) and also the greatest weight of powder seized (4315 kg).
• The findings highlight the rapidly changing nature of the illicit fentanyl market, with an increasing prevalence of fentanyl pills.
• Western United States experienced the greatest increase in seizures, particularly in pill form, suggesting a significant regional shift in fentanyl distribution. California had the greatest number of pills seized (n = 38.6 million) and also the greatest weight of powder seized (4315 kg).

The findings highlight the rapidly changing nature of the illicit fentanyl market, with an increasing prevalence of fentanyl pills.

IN PRACTICE:

“About half of seized fentanyl is now in pill form, suggesting that the illicit drug landscape has rapidly changed,” Joseph J. Palamar, PhD, MPH, of NYU Langone Health, New York, said in a press release. “The study’s findings underscore the evolving challenge of fentanyl in the illicit drug market, emphasizing the need for healthcare professionals to be vigilant in recognizing and responding to the risks associated with fentanyl, especially in pill form,” he added.

SOURCE:

Dr. Palamar led the study, which was published online on May 13, 2024, in the International Journal of Drug Policy. 

LIMITATIONS:

One limitation of the study is the inability to differentiate whether seizures were solely fentanyl, fentanyl combined with other drugs, or fentanyl analogs. Additionally, the reliance on HIDTA data may not fully represent the extent of illicit fentanyl availability.

DISCLOSURES:

Dr. Palamar reports a consulting or advisory relationship with the Washington Baltimore High Intensity Drug Trafficking Area. The study was supported by the National Institute on Drug Abuse.

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:

US fentanyl seizures increased by more than 1700% between 2017 and 2023, new data showed. 

METHODOLOGY:

• Investigators analyzed data from the High Intensity Drug Trafficking Areas (HIDTA) program from 2017 through 2023.
• To assess trends in illicit fentanyl availability, investigators used eight indicators of potential shifts in illicit fentanyl supply, including total seizures, powder seizures, pill seizures, and the total weight of seizures.

TAKEAWAY:

• A total of 66,303 fentanyl seizures were identified. Of the total number of seizures, 67% were in powder form and 33% were pills.
• The total number of seizures during the study period increased by > 1700% — from 74,663 in 2017 to 115,221 in 2023.
• In 2023, the greatest number of fentanyl seizures was in Florida (n = 2,089), followed by Arizona (n = 1783) and California (n = 1440).Western United States experienced the greatest increase in seizures, particularly in pill form, suggesting a significant regional shift in fentanyl distribution. California had the greatest number of pills seized (n = 38.6 million) and also the greatest weight of powder seized (4315 kg).
• The findings highlight the rapidly changing nature of the illicit fentanyl market, with an increasing prevalence of fentanyl pills.
• Western United States experienced the greatest increase in seizures, particularly in pill form, suggesting a significant regional shift in fentanyl distribution. California had the greatest number of pills seized (n = 38.6 million) and also the greatest weight of powder seized (4315 kg).

The findings highlight the rapidly changing nature of the illicit fentanyl market, with an increasing prevalence of fentanyl pills.

IN PRACTICE:

“About half of seized fentanyl is now in pill form, suggesting that the illicit drug landscape has rapidly changed,” Joseph J. Palamar, PhD, MPH, of NYU Langone Health, New York, said in a press release. “The study’s findings underscore the evolving challenge of fentanyl in the illicit drug market, emphasizing the need for healthcare professionals to be vigilant in recognizing and responding to the risks associated with fentanyl, especially in pill form,” he added.

SOURCE:

Dr. Palamar led the study, which was published online on May 13, 2024, in the International Journal of Drug Policy. 

LIMITATIONS:

One limitation of the study is the inability to differentiate whether seizures were solely fentanyl, fentanyl combined with other drugs, or fentanyl analogs. Additionally, the reliance on HIDTA data may not fully represent the extent of illicit fentanyl availability.

DISCLOSURES:

Dr. Palamar reports a consulting or advisory relationship with the Washington Baltimore High Intensity Drug Trafficking Area. The study was supported by the National Institute on Drug Abuse.

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:

US fentanyl seizures increased by more than 1700% between 2017 and 2023, new data showed. 

METHODOLOGY:

• Investigators analyzed data from the High Intensity Drug Trafficking Areas (HIDTA) program from 2017 through 2023.
• To assess trends in illicit fentanyl availability, investigators used eight indicators of potential shifts in illicit fentanyl supply, including total seizures, powder seizures, pill seizures, and the total weight of seizures.

TAKEAWAY:

• A total of 66,303 fentanyl seizures were identified. Of the total number of seizures, 67% were in powder form and 33% were pills.
• The total number of seizures during the study period increased by > 1700% — from 74,663 in 2017 to 115,221 in 2023.
• In 2023, the greatest number of fentanyl seizures was in Florida (n = 2,089), followed by Arizona (n = 1783) and California (n = 1440).Western United States experienced the greatest increase in seizures, particularly in pill form, suggesting a significant regional shift in fentanyl distribution. California had the greatest number of pills seized (n = 38.6 million) and also the greatest weight of powder seized (4315 kg).
• The findings highlight the rapidly changing nature of the illicit fentanyl market, with an increasing prevalence of fentanyl pills.
• Western United States experienced the greatest increase in seizures, particularly in pill form, suggesting a significant regional shift in fentanyl distribution. California had the greatest number of pills seized (n = 38.6 million) and also the greatest weight of powder seized (4315 kg).

The findings highlight the rapidly changing nature of the illicit fentanyl market, with an increasing prevalence of fentanyl pills.

IN PRACTICE:

“About half of seized fentanyl is now in pill form, suggesting that the illicit drug landscape has rapidly changed,” Joseph J. Palamar, PhD, MPH, of NYU Langone Health, New York, said in a press release. “The study’s findings underscore the evolving challenge of fentanyl in the illicit drug market, emphasizing the need for healthcare professionals to be vigilant in recognizing and responding to the risks associated with fentanyl, especially in pill form,” he added.

SOURCE:

Dr. Palamar led the study, which was published online on May 13, 2024, in the International Journal of Drug Policy. 

LIMITATIONS:

One limitation of the study is the inability to differentiate whether seizures were solely fentanyl, fentanyl combined with other drugs, or fentanyl analogs. Additionally, the reliance on HIDTA data may not fully represent the extent of illicit fentanyl availability.

DISCLOSURES:

Dr. Palamar reports a consulting or advisory relationship with the Washington Baltimore High Intensity Drug Trafficking Area. The study was supported by the National Institute on Drug Abuse.

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.