Addiction Medicine

VIENNA – The production of estrogen in the thalamus appears to be curtailed by just one dose of nicotine, equivalent to that in a cigarette, reveals a whole brain analysis of healthy women in the first study of its kind.

The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.

The researchers performed both MRI and positron emission tomography (PET) scans in 10 healthy women using a tracer that binds to aromatase, also known as estrogen synthase.

They found that, following an intranasal spray delivering 1 mg of nicotine, there was a significant reduction in estrogen synthase in both the right and left thalamus.

“For the first time, we can see that nicotine works to shut down the estrogen production mechanism in the brains of women,” said lead researcher Erika Comasco, PhD, department of neuroscience, Uppsala University, Sweden, in a release.

“We were surprised to see that this effect could be seen even with a single dose of nicotine, equivalent to just one cigarette, showing how powerful the effects of smoking are on a woman’s brain.”

Emphasizing the preliminary nature of the study and the need for a larger sample, she added: “We’re still not sure what the behavioral or cognitive outcomes are, only that nicotine acts on this area of the brain.

“However, we note that the affected brain system is a target for addictive drugs, such as nicotine.”

Previous research has revealed that women are less successful at quitting smoking than men, and appear to be more resistant to nicotine replacement therapy, and experience more relapses.

There is evidence to suggest that there is a complex interaction between sex and steroid hormones and the reward effect of nicotine, modulated by the dopaminergic system.

Moreover, women who smoke enter menopause earlier than nonsmokers, and have lower plasma estrogen levels, Dr. Camasco told this news organization.

Dr. Comasco explained that “besides its role in reproductive function and sexual behavior, estrogen has an impact on the brain wherever there are receptors, which is basically regions that are related to emotional regulation, cognitive function, and so on.”

Estrogen, she continued, has two main mechanisms of action, via dopaminergic and serotonergic signaling. However, levels of the hormone cannot be measured directly in the brain.

The researchers therefore turned to estrogen synthase, which regulates the synthesis of estrogen, and is highly expressed in the limbic system, a brain region associated with addiction.

Moreover, estrogen synthase levels can be measured in vivo, and previous animal studies have indicated that nicotine inhibits estrogen synthase.

To investigate its impact in humans, the researchers performed structural MRI and two ¹¹C-cetrozole PET scans in 10 healthy women.

The assessments were performed before and after the nasal administration of 1 mg of nicotine, the dose contained in one cigarette, via two sprays of a nasal spray each containing 0.5 mg of nicotine.

A whole brain analysis was then used to determine changes in nondisplaceable binding potential of ¹¹C-cetrozole to estrogen synthase between the two scans to indicate the availability of the enzyme at the two time points.

The results showed that, at baseline, high availability of estrogen synthase was observed in the thalamus, hypothalamus, and amygdala, with the highest levels in the right and left thalamus.

However, nicotine exposure was associated with a significant reduction in estrogen binding bilaterally in the thalamus when averaged across the participants (P < .01).

Region-of-interest analysis using within-individual voxel-wise comparison confirmed reduced estrogen synthase levels in both the right and left thalamus (P < .05), as well as in the subthalamic area.

Next, Dr. Comasco would like to test the impact of nicotine on estrogen synthase in men.

While men have lower levels of estrogen then women, “the reaction will take place anyway,” she said, although the “impact would be different.”

She would also like to look at the behavioral effects of reductions in estrogen synthase, and look at the effect of nicotine from a functional point of view.

Wim van den Brink, MD, PhD, professor of psychiatry and addiction at the Academic Medical Center, University of Amsterdam, commented that this is an “important first finding.”

“Smoking has many adverse effects in men and in women, but this particular effect of nicotine on the reduction of estrogen production in women was not known before,” he added in the release.

However, he underlined that tobacco addition is a “complex disorder” and it is “unlikely that this specific effect of nicotine on the thalamus explains all the observed differences in the development, treatment, and outcomes between male and female smokers.”

“It is still a long way from a nicotine-induced reduction in estrogen production to a reduced risk of nicotine addiction and negative effects of treatment and relapse in female cigarette smokers, but this work merits further investigation,” Dr. van den Brink said.

The study was funded by the Science for Life Laboratory/Uppsala University.

No relevant financial relationships were declared.

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

VIENNA – The production of estrogen in the thalamus appears to be curtailed by just one dose of nicotine, equivalent to that in a cigarette, reveals a whole brain analysis of healthy women in the first study of its kind.

The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.

The researchers performed both MRI and positron emission tomography (PET) scans in 10 healthy women using a tracer that binds to aromatase, also known as estrogen synthase.

They found that, following an intranasal spray delivering 1 mg of nicotine, there was a significant reduction in estrogen synthase in both the right and left thalamus.

“For the first time, we can see that nicotine works to shut down the estrogen production mechanism in the brains of women,” said lead researcher Erika Comasco, PhD, department of neuroscience, Uppsala University, Sweden, in a release.

“We were surprised to see that this effect could be seen even with a single dose of nicotine, equivalent to just one cigarette, showing how powerful the effects of smoking are on a woman’s brain.”

Emphasizing the preliminary nature of the study and the need for a larger sample, she added: “We’re still not sure what the behavioral or cognitive outcomes are, only that nicotine acts on this area of the brain.

“However, we note that the affected brain system is a target for addictive drugs, such as nicotine.”

Previous research has revealed that women are less successful at quitting smoking than men, and appear to be more resistant to nicotine replacement therapy, and experience more relapses.

There is evidence to suggest that there is a complex interaction between sex and steroid hormones and the reward effect of nicotine, modulated by the dopaminergic system.

Moreover, women who smoke enter menopause earlier than nonsmokers, and have lower plasma estrogen levels, Dr. Camasco told this news organization.

Dr. Comasco explained that “besides its role in reproductive function and sexual behavior, estrogen has an impact on the brain wherever there are receptors, which is basically regions that are related to emotional regulation, cognitive function, and so on.”

Estrogen, she continued, has two main mechanisms of action, via dopaminergic and serotonergic signaling. However, levels of the hormone cannot be measured directly in the brain.

The researchers therefore turned to estrogen synthase, which regulates the synthesis of estrogen, and is highly expressed in the limbic system, a brain region associated with addiction.

Moreover, estrogen synthase levels can be measured in vivo, and previous animal studies have indicated that nicotine inhibits estrogen synthase.

To investigate its impact in humans, the researchers performed structural MRI and two ¹¹C-cetrozole PET scans in 10 healthy women.

The assessments were performed before and after the nasal administration of 1 mg of nicotine, the dose contained in one cigarette, via two sprays of a nasal spray each containing 0.5 mg of nicotine.

A whole brain analysis was then used to determine changes in nondisplaceable binding potential of ¹¹C-cetrozole to estrogen synthase between the two scans to indicate the availability of the enzyme at the two time points.

The results showed that, at baseline, high availability of estrogen synthase was observed in the thalamus, hypothalamus, and amygdala, with the highest levels in the right and left thalamus.

However, nicotine exposure was associated with a significant reduction in estrogen binding bilaterally in the thalamus when averaged across the participants (P < .01).

Region-of-interest analysis using within-individual voxel-wise comparison confirmed reduced estrogen synthase levels in both the right and left thalamus (P < .05), as well as in the subthalamic area.

Next, Dr. Comasco would like to test the impact of nicotine on estrogen synthase in men.

While men have lower levels of estrogen then women, “the reaction will take place anyway,” she said, although the “impact would be different.”

She would also like to look at the behavioral effects of reductions in estrogen synthase, and look at the effect of nicotine from a functional point of view.

Wim van den Brink, MD, PhD, professor of psychiatry and addiction at the Academic Medical Center, University of Amsterdam, commented that this is an “important first finding.”

“Smoking has many adverse effects in men and in women, but this particular effect of nicotine on the reduction of estrogen production in women was not known before,” he added in the release.

However, he underlined that tobacco addition is a “complex disorder” and it is “unlikely that this specific effect of nicotine on the thalamus explains all the observed differences in the development, treatment, and outcomes between male and female smokers.”

“It is still a long way from a nicotine-induced reduction in estrogen production to a reduced risk of nicotine addiction and negative effects of treatment and relapse in female cigarette smokers, but this work merits further investigation,” Dr. van den Brink said.

The study was funded by the Science for Life Laboratory/Uppsala University.

No relevant financial relationships were declared.

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

VIENNA – The production of estrogen in the thalamus appears to be curtailed by just one dose of nicotine, equivalent to that in a cigarette, reveals a whole brain analysis of healthy women in the first study of its kind.

The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.

The researchers performed both MRI and positron emission tomography (PET) scans in 10 healthy women using a tracer that binds to aromatase, also known as estrogen synthase.

They found that, following an intranasal spray delivering 1 mg of nicotine, there was a significant reduction in estrogen synthase in both the right and left thalamus.

“For the first time, we can see that nicotine works to shut down the estrogen production mechanism in the brains of women,” said lead researcher Erika Comasco, PhD, department of neuroscience, Uppsala University, Sweden, in a release.

“We were surprised to see that this effect could be seen even with a single dose of nicotine, equivalent to just one cigarette, showing how powerful the effects of smoking are on a woman’s brain.”

Emphasizing the preliminary nature of the study and the need for a larger sample, she added: “We’re still not sure what the behavioral or cognitive outcomes are, only that nicotine acts on this area of the brain.

“However, we note that the affected brain system is a target for addictive drugs, such as nicotine.”

Previous research has revealed that women are less successful at quitting smoking than men, and appear to be more resistant to nicotine replacement therapy, and experience more relapses.

There is evidence to suggest that there is a complex interaction between sex and steroid hormones and the reward effect of nicotine, modulated by the dopaminergic system.

Moreover, women who smoke enter menopause earlier than nonsmokers, and have lower plasma estrogen levels, Dr. Camasco told this news organization.

Dr. Comasco explained that “besides its role in reproductive function and sexual behavior, estrogen has an impact on the brain wherever there are receptors, which is basically regions that are related to emotional regulation, cognitive function, and so on.”

Estrogen, she continued, has two main mechanisms of action, via dopaminergic and serotonergic signaling. However, levels of the hormone cannot be measured directly in the brain.

The researchers therefore turned to estrogen synthase, which regulates the synthesis of estrogen, and is highly expressed in the limbic system, a brain region associated with addiction.

Moreover, estrogen synthase levels can be measured in vivo, and previous animal studies have indicated that nicotine inhibits estrogen synthase.

To investigate its impact in humans, the researchers performed structural MRI and two ¹¹C-cetrozole PET scans in 10 healthy women.

The assessments were performed before and after the nasal administration of 1 mg of nicotine, the dose contained in one cigarette, via two sprays of a nasal spray each containing 0.5 mg of nicotine.

A whole brain analysis was then used to determine changes in nondisplaceable binding potential of ¹¹C-cetrozole to estrogen synthase between the two scans to indicate the availability of the enzyme at the two time points.

The results showed that, at baseline, high availability of estrogen synthase was observed in the thalamus, hypothalamus, and amygdala, with the highest levels in the right and left thalamus.

However, nicotine exposure was associated with a significant reduction in estrogen binding bilaterally in the thalamus when averaged across the participants (P < .01).

Region-of-interest analysis using within-individual voxel-wise comparison confirmed reduced estrogen synthase levels in both the right and left thalamus (P < .05), as well as in the subthalamic area.

Next, Dr. Comasco would like to test the impact of nicotine on estrogen synthase in men.

While men have lower levels of estrogen then women, “the reaction will take place anyway,” she said, although the “impact would be different.”

She would also like to look at the behavioral effects of reductions in estrogen synthase, and look at the effect of nicotine from a functional point of view.

Wim van den Brink, MD, PhD, professor of psychiatry and addiction at the Academic Medical Center, University of Amsterdam, commented that this is an “important first finding.”

“Smoking has many adverse effects in men and in women, but this particular effect of nicotine on the reduction of estrogen production in women was not known before,” he added in the release.

However, he underlined that tobacco addition is a “complex disorder” and it is “unlikely that this specific effect of nicotine on the thalamus explains all the observed differences in the development, treatment, and outcomes between male and female smokers.”

“It is still a long way from a nicotine-induced reduction in estrogen production to a reduced risk of nicotine addiction and negative effects of treatment and relapse in female cigarette smokers, but this work merits further investigation,” Dr. van den Brink said.

The study was funded by the Science for Life Laboratory/Uppsala University.

No relevant financial relationships were declared.

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

Smokers who quit before age 35 showed a "substantial" reduction in risk, compared with people who never smoked, according to a new national study.

Researchers also quantified the benefit of quitting for those older than 35. The added risk of death associated with smoking was reduced by 90% for those who quit before age 45 and 66% for those who quit at ages 45 to 64.

“The distal nature of the health consequences for young smokers is a challenge for professionals trying to motivate quitting in younger age groups. Without a proximal goal, it is tempting for smokers to abandon a quit attempt with cognitions such as ‘I don’t really need to do it just now,’ ” John P. Pierce, PhD, director for Population Sciences at UC-San Diego’s Moores Cancer Center, wrote in a commentary. 

Current smokers were twice as likely to die from any cause during the study, compared with the group researchers called “never smokers,” who were defined as smoking fewer than 100 lifetime cigarettes. 

Published in JAMA Network Open, the study involved 551,388 U.S. participants using information collected by the CDC from 1997 to 2018. Researchers collected data for specific causes of death of participants through the end of 2019.

The results echo past findings but also established whether demographic factors such as a smoker’s race and gender impact the benefits of quitting. (In many areas of health research, a person’s race or gender is associated with varying risks.)

The researchers found that the benefits of quitting smoking in reducing risk of death are comparable across demographic groups.

“Among former smokers in each racial and ethnic group, whether male or female, quitting was associated with reductions of approximately 80% of the excess mortality associated with continued smoking,” the authors stated. “These associations were generally consistent for deaths from cancer, cardiovascular disease, and lower respiratory disease.”

The findings are also important for guiding stop-smoking efforts because while smoking nationwide has decreased, the reduction has varied across demographic groups.

“Monitoring the association of smoking with mortality by race, ethnicity, and sex is critical to understanding how the U.S. tobacco epidemic continues to evolve over time and who is most affected by the changes,” the authors stated. “Despite continued decreases in U.S. smoking prevalence in recent decades, progress has not been equal across demographic groups. Recent progress in raising the quit ratio among U.S. ever-smokers overall has been modest, and the quit ratio has been consistently lower among Black and Hispanic ever-smokers than among non-Hispanic White ever-smokers.”

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

This article was updated 10/27/22.

Smokers who quit before age 35 showed a "substantial" reduction in risk, compared with people who never smoked, according to a new national study.

Researchers also quantified the benefit of quitting for those older than 35. The added risk of death associated with smoking was reduced by 90% for those who quit before age 45 and 66% for those who quit at ages 45 to 64.

“The distal nature of the health consequences for young smokers is a challenge for professionals trying to motivate quitting in younger age groups. Without a proximal goal, it is tempting for smokers to abandon a quit attempt with cognitions such as ‘I don’t really need to do it just now,’ ” John P. Pierce, PhD, director for Population Sciences at UC-San Diego’s Moores Cancer Center, wrote in a commentary. 

Current smokers were twice as likely to die from any cause during the study, compared with the group researchers called “never smokers,” who were defined as smoking fewer than 100 lifetime cigarettes. 

Published in JAMA Network Open, the study involved 551,388 U.S. participants using information collected by the CDC from 1997 to 2018. Researchers collected data for specific causes of death of participants through the end of 2019.

The results echo past findings but also established whether demographic factors such as a smoker’s race and gender impact the benefits of quitting. (In many areas of health research, a person’s race or gender is associated with varying risks.)

The researchers found that the benefits of quitting smoking in reducing risk of death are comparable across demographic groups.

“Among former smokers in each racial and ethnic group, whether male or female, quitting was associated with reductions of approximately 80% of the excess mortality associated with continued smoking,” the authors stated. “These associations were generally consistent for deaths from cancer, cardiovascular disease, and lower respiratory disease.”

The findings are also important for guiding stop-smoking efforts because while smoking nationwide has decreased, the reduction has varied across demographic groups.

“Monitoring the association of smoking with mortality by race, ethnicity, and sex is critical to understanding how the U.S. tobacco epidemic continues to evolve over time and who is most affected by the changes,” the authors stated. “Despite continued decreases in U.S. smoking prevalence in recent decades, progress has not been equal across demographic groups. Recent progress in raising the quit ratio among U.S. ever-smokers overall has been modest, and the quit ratio has been consistently lower among Black and Hispanic ever-smokers than among non-Hispanic White ever-smokers.”

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

This article was updated 10/27/22.

Smokers who quit before age 35 showed a "substantial" reduction in risk, compared with people who never smoked, according to a new national study.

Researchers also quantified the benefit of quitting for those older than 35. The added risk of death associated with smoking was reduced by 90% for those who quit before age 45 and 66% for those who quit at ages 45 to 64.

“The distal nature of the health consequences for young smokers is a challenge for professionals trying to motivate quitting in younger age groups. Without a proximal goal, it is tempting for smokers to abandon a quit attempt with cognitions such as ‘I don’t really need to do it just now,’ ” John P. Pierce, PhD, director for Population Sciences at UC-San Diego’s Moores Cancer Center, wrote in a commentary. 

Current smokers were twice as likely to die from any cause during the study, compared with the group researchers called “never smokers,” who were defined as smoking fewer than 100 lifetime cigarettes. 

Published in JAMA Network Open, the study involved 551,388 U.S. participants using information collected by the CDC from 1997 to 2018. Researchers collected data for specific causes of death of participants through the end of 2019.

The results echo past findings but also established whether demographic factors such as a smoker’s race and gender impact the benefits of quitting. (In many areas of health research, a person’s race or gender is associated with varying risks.)

The researchers found that the benefits of quitting smoking in reducing risk of death are comparable across demographic groups.

“Among former smokers in each racial and ethnic group, whether male or female, quitting was associated with reductions of approximately 80% of the excess mortality associated with continued smoking,” the authors stated. “These associations were generally consistent for deaths from cancer, cardiovascular disease, and lower respiratory disease.”

The findings are also important for guiding stop-smoking efforts because while smoking nationwide has decreased, the reduction has varied across demographic groups.

“Monitoring the association of smoking with mortality by race, ethnicity, and sex is critical to understanding how the U.S. tobacco epidemic continues to evolve over time and who is most affected by the changes,” the authors stated. “Despite continued decreases in U.S. smoking prevalence in recent decades, progress has not been equal across demographic groups. Recent progress in raising the quit ratio among U.S. ever-smokers overall has been modest, and the quit ratio has been consistently lower among Black and Hispanic ever-smokers than among non-Hispanic White ever-smokers.”

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

This article was updated 10/27/22.

Cocaine, methamphetamine, opioids, and cannabis may independently increase risk of atrial fibrillation (AFib), based on data from almost 24 million people.

While more work is needed to uncover causal links, physicians should be aware that these commonly abused substances could be driving new cases of AFib, reported investigators from the University of California, San Francisco.

“Though alcohol and tobacco smoking have each been associated with a heightened risk of [AFib], relationships between other drug use and [AFib] are poorly understood,” they wrote in European Heart Journal.

Some previous studies have ventured into this terrain, but most focused on fatal arrhythmias, or offered anecdotal evidence. This knowledge gap is particularly concerning for cannabis, the researchers noted, as medical and recreational use are on the rise.

American Heart Association

The present analysis included data from 23.5 million adults in California who received care through a hospital, emergency department, or outpatient surgery center during 2005-2015. Based on ICD-9 diagnostic codes, 132,834 of these patients used cannabis, 98,271 used methamphetamines, 48,701 used cocaine, and 10,032 used opiates. Inclusion required lack of AFib at baseline.

Reliance on ICD-9 codes makes the data “quite specific,” but lacking sensitivity, according to principal author Gregory M. Marcus, MD, cardiologist and professor of medicine at UCSF.

“If they were designated as using these drugs, that is very likely true,” Dr. Marcus said in an interview. “But certainly, the absence of any mention of use of these drugs does not exclude the possibility that some people were still using them. That would not create spurious false-positive relationships; if anything, it attenuates existing relationships.”

In other words, using ICD-9 codes reduced the power to detect an association between each drug and AFib, meaning any relationship needed to be sufficiently strong enough to generate a significant result.

At the end of the decade-long study period, 998,747 patients (4.2%) had developed incident AFib. After adjusting for potential confounders and mediators, all four drugs showed significant, independent associations with AFib. Methamphetamines presented the greatest risk (hazard ratio, 1.86%), followed by opiates (HR, 1.74), cocaine (HR, 1.61), and cannabis (HR, 1.35).

“Our findings provide the first evidence utilizing a longitudinal cohort to demonstrate that cannabis use predicts the future onset of AFib,” Dr. Marcus and colleagues wrote.

Dose-response relationships were not detected for any of the substances; however, usage levels were also derived from ICD-9 codes, which may have been insufficient for this purpose, according to the investigators.
 

Causal mechanisms deserve a closer look

Causal links between AFib and each of the drugs remain unclear. Citing prior research, Dr. Marcus and colleagues explained how methamphetamines are capable of “significant cardiac electrical remodeling,” while cocaine may cause sodium channel dysregulation, and opioids can render atrial myocytes more susceptible to oxidative damage. Although cannabis has previously been linked with hospitalization for arrhythmia, a pharmacologic driver of this phenomenon remains largely unexamined.

“We don’t know for sure precisely what the constituents are that are responsible for our findings,” Dr. Marcus said. “It’s possible that there are some effects that are much more generic, such as inhaling a burned substance. There is good evidence that if you inhale pretty much any sort of particulate matter, that increases inflammation in the body. Inflammation is known to be a trigger for atrial fibrillation.”

Alternatively, all four drugs – whether stimulants or depressants – cause “quite dramatic and often rapid effects on the autonomic nervous system,” Dr. Marcus said, noting that these rapid swings are a known trigger for AFib.

Brian Olshansky, MD, emeritus professor of internal medicine-cardiovascular medicine at the University of Iowa, Iowa City, suggested that nonpharmacologic factors are likely also playing a role.

“All these drugs have slightly different mechanisms of action, so there’s not one mechanism that would explain why all of them would cause atrial fibrillation,” Dr. Olshansky said in an interview. “That does suggest that there’s something else going on, besides just the drug itself. It would be potentially concerning if we were to lay the blame totally on these drugs.”

Dr. Olshansky, who recently coauthored a review of stimulant drugs and arrhythmias, suggested that lifestyle, comorbidities, and drug impurities may have added to the risk of AF.

“[The investigators] did try to correct for that kind of stuff, but it’s very hard to correct for a lot of the issues that may be ongoing with individuals who partake in these drugs,” Dr. Olshansky said in an interview. “They may not be a healthy lot, in general.”

Still, considering previous data linking drugs of abuse with arrhythmias, he said the detected risks were “intriguing,” and deserved a closer look.

“It’s a nice groundbreaking study, with regard to the fact that they showed unique relationships that we don’t completely understand,” Dr. Olshansky said. “It opens up a new opportunity for further investigation.”

The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Olshansky disclosed no relevant competing interests.

Cocaine, methamphetamine, opioids, and cannabis may independently increase risk of atrial fibrillation (AFib), based on data from almost 24 million people.

While more work is needed to uncover causal links, physicians should be aware that these commonly abused substances could be driving new cases of AFib, reported investigators from the University of California, San Francisco.

“Though alcohol and tobacco smoking have each been associated with a heightened risk of [AFib], relationships between other drug use and [AFib] are poorly understood,” they wrote in European Heart Journal.

Some previous studies have ventured into this terrain, but most focused on fatal arrhythmias, or offered anecdotal evidence. This knowledge gap is particularly concerning for cannabis, the researchers noted, as medical and recreational use are on the rise.

American Heart Association

The present analysis included data from 23.5 million adults in California who received care through a hospital, emergency department, or outpatient surgery center during 2005-2015. Based on ICD-9 diagnostic codes, 132,834 of these patients used cannabis, 98,271 used methamphetamines, 48,701 used cocaine, and 10,032 used opiates. Inclusion required lack of AFib at baseline.

Reliance on ICD-9 codes makes the data “quite specific,” but lacking sensitivity, according to principal author Gregory M. Marcus, MD, cardiologist and professor of medicine at UCSF.

“If they were designated as using these drugs, that is very likely true,” Dr. Marcus said in an interview. “But certainly, the absence of any mention of use of these drugs does not exclude the possibility that some people were still using them. That would not create spurious false-positive relationships; if anything, it attenuates existing relationships.”

In other words, using ICD-9 codes reduced the power to detect an association between each drug and AFib, meaning any relationship needed to be sufficiently strong enough to generate a significant result.

At the end of the decade-long study period, 998,747 patients (4.2%) had developed incident AFib. After adjusting for potential confounders and mediators, all four drugs showed significant, independent associations with AFib. Methamphetamines presented the greatest risk (hazard ratio, 1.86%), followed by opiates (HR, 1.74), cocaine (HR, 1.61), and cannabis (HR, 1.35).

“Our findings provide the first evidence utilizing a longitudinal cohort to demonstrate that cannabis use predicts the future onset of AFib,” Dr. Marcus and colleagues wrote.

Dose-response relationships were not detected for any of the substances; however, usage levels were also derived from ICD-9 codes, which may have been insufficient for this purpose, according to the investigators.
 

Causal mechanisms deserve a closer look

Causal links between AFib and each of the drugs remain unclear. Citing prior research, Dr. Marcus and colleagues explained how methamphetamines are capable of “significant cardiac electrical remodeling,” while cocaine may cause sodium channel dysregulation, and opioids can render atrial myocytes more susceptible to oxidative damage. Although cannabis has previously been linked with hospitalization for arrhythmia, a pharmacologic driver of this phenomenon remains largely unexamined.

“We don’t know for sure precisely what the constituents are that are responsible for our findings,” Dr. Marcus said. “It’s possible that there are some effects that are much more generic, such as inhaling a burned substance. There is good evidence that if you inhale pretty much any sort of particulate matter, that increases inflammation in the body. Inflammation is known to be a trigger for atrial fibrillation.”

Alternatively, all four drugs – whether stimulants or depressants – cause “quite dramatic and often rapid effects on the autonomic nervous system,” Dr. Marcus said, noting that these rapid swings are a known trigger for AFib.

Brian Olshansky, MD, emeritus professor of internal medicine-cardiovascular medicine at the University of Iowa, Iowa City, suggested that nonpharmacologic factors are likely also playing a role.

“All these drugs have slightly different mechanisms of action, so there’s not one mechanism that would explain why all of them would cause atrial fibrillation,” Dr. Olshansky said in an interview. “That does suggest that there’s something else going on, besides just the drug itself. It would be potentially concerning if we were to lay the blame totally on these drugs.”

Dr. Olshansky, who recently coauthored a review of stimulant drugs and arrhythmias, suggested that lifestyle, comorbidities, and drug impurities may have added to the risk of AF.

“[The investigators] did try to correct for that kind of stuff, but it’s very hard to correct for a lot of the issues that may be ongoing with individuals who partake in these drugs,” Dr. Olshansky said in an interview. “They may not be a healthy lot, in general.”

Still, considering previous data linking drugs of abuse with arrhythmias, he said the detected risks were “intriguing,” and deserved a closer look.

“It’s a nice groundbreaking study, with regard to the fact that they showed unique relationships that we don’t completely understand,” Dr. Olshansky said. “It opens up a new opportunity for further investigation.”

The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Olshansky disclosed no relevant competing interests.

Cocaine, methamphetamine, opioids, and cannabis may independently increase risk of atrial fibrillation (AFib), based on data from almost 24 million people.

While more work is needed to uncover causal links, physicians should be aware that these commonly abused substances could be driving new cases of AFib, reported investigators from the University of California, San Francisco.

“Though alcohol and tobacco smoking have each been associated with a heightened risk of [AFib], relationships between other drug use and [AFib] are poorly understood,” they wrote in European Heart Journal.

Some previous studies have ventured into this terrain, but most focused on fatal arrhythmias, or offered anecdotal evidence. This knowledge gap is particularly concerning for cannabis, the researchers noted, as medical and recreational use are on the rise.

American Heart Association

The present analysis included data from 23.5 million adults in California who received care through a hospital, emergency department, or outpatient surgery center during 2005-2015. Based on ICD-9 diagnostic codes, 132,834 of these patients used cannabis, 98,271 used methamphetamines, 48,701 used cocaine, and 10,032 used opiates. Inclusion required lack of AFib at baseline.

Reliance on ICD-9 codes makes the data “quite specific,” but lacking sensitivity, according to principal author Gregory M. Marcus, MD, cardiologist and professor of medicine at UCSF.

“If they were designated as using these drugs, that is very likely true,” Dr. Marcus said in an interview. “But certainly, the absence of any mention of use of these drugs does not exclude the possibility that some people were still using them. That would not create spurious false-positive relationships; if anything, it attenuates existing relationships.”

In other words, using ICD-9 codes reduced the power to detect an association between each drug and AFib, meaning any relationship needed to be sufficiently strong enough to generate a significant result.

At the end of the decade-long study period, 998,747 patients (4.2%) had developed incident AFib. After adjusting for potential confounders and mediators, all four drugs showed significant, independent associations with AFib. Methamphetamines presented the greatest risk (hazard ratio, 1.86%), followed by opiates (HR, 1.74), cocaine (HR, 1.61), and cannabis (HR, 1.35).

“Our findings provide the first evidence utilizing a longitudinal cohort to demonstrate that cannabis use predicts the future onset of AFib,” Dr. Marcus and colleagues wrote.

Dose-response relationships were not detected for any of the substances; however, usage levels were also derived from ICD-9 codes, which may have been insufficient for this purpose, according to the investigators.
 

Causal mechanisms deserve a closer look

Causal links between AFib and each of the drugs remain unclear. Citing prior research, Dr. Marcus and colleagues explained how methamphetamines are capable of “significant cardiac electrical remodeling,” while cocaine may cause sodium channel dysregulation, and opioids can render atrial myocytes more susceptible to oxidative damage. Although cannabis has previously been linked with hospitalization for arrhythmia, a pharmacologic driver of this phenomenon remains largely unexamined.

“We don’t know for sure precisely what the constituents are that are responsible for our findings,” Dr. Marcus said. “It’s possible that there are some effects that are much more generic, such as inhaling a burned substance. There is good evidence that if you inhale pretty much any sort of particulate matter, that increases inflammation in the body. Inflammation is known to be a trigger for atrial fibrillation.”

Alternatively, all four drugs – whether stimulants or depressants – cause “quite dramatic and often rapid effects on the autonomic nervous system,” Dr. Marcus said, noting that these rapid swings are a known trigger for AFib.

Brian Olshansky, MD, emeritus professor of internal medicine-cardiovascular medicine at the University of Iowa, Iowa City, suggested that nonpharmacologic factors are likely also playing a role.

“All these drugs have slightly different mechanisms of action, so there’s not one mechanism that would explain why all of them would cause atrial fibrillation,” Dr. Olshansky said in an interview. “That does suggest that there’s something else going on, besides just the drug itself. It would be potentially concerning if we were to lay the blame totally on these drugs.”

Dr. Olshansky, who recently coauthored a review of stimulant drugs and arrhythmias, suggested that lifestyle, comorbidities, and drug impurities may have added to the risk of AF.

“[The investigators] did try to correct for that kind of stuff, but it’s very hard to correct for a lot of the issues that may be ongoing with individuals who partake in these drugs,” Dr. Olshansky said in an interview. “They may not be a healthy lot, in general.”

Still, considering previous data linking drugs of abuse with arrhythmias, he said the detected risks were “intriguing,” and deserved a closer look.

“It’s a nice groundbreaking study, with regard to the fact that they showed unique relationships that we don’t completely understand,” Dr. Olshansky said. “It opens up a new opportunity for further investigation.”

The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Olshansky disclosed no relevant competing interests.

One quiet afternoon at a mobile outreach clinic, where I had been working on the West Side of Chicago, a young man without a home to go to, and clothes he kept as clean as he could, came to get a refill of buprenorphine. The drug, which works on the same opioid receptors as heroin, was helping him feel normal. It was also probably helping to keep him alive, as a study found that taking it after an overdose was associated with a one-third reduction in all-cause mortality.

He was still using drugs, but now only a few days a week instead of multiple times a day. He had put on some weight and looked visibly healthier.

I gave him his prescription and thanked him for coming back. As he got up to leave, he turned to our outreach team and said, “Thank you for being here and caring about us. Because a lot of people don’t. They don’t care if we live or die.”

But a lot of people do care and are still failing him and others who use drugs. When I first started treating addictions, I was taught to cut people like him off treatment. We could give patients a medication, but they had to follow the rules, first and foremost to stop using drugs. Keep using, even if you were using less and your health was improving, and I would have to dismiss you from the practice. This was the kind of “tough love” that many doctors have been taught, and are, in many cases, still being taught today. Even though we know that this approach does not work.

For too long, doctors, nurses, caregivers, and the broader American public have favored abstinence only treatment, criminalization, and prohibition. The proof that this approach does not work is in the spectacular overdose crisis we are experiencing in this country, as CDC data documents. While we continue to blame drugs like fentanyl and methamphetamine (and thirty years ago, crack and heroin), we fail to see how our approach contributes to these overdose deaths.

For instance, treating with buprenorphine or methadone was associated with reductions in overdose and serious opioid-related acute care use compared with detox alone. But only one in three centers offer these medications, the gold standard of care. We continue to imprison people who use drugs, even though we have known for 15 years that the risk of overdose is exponentially higher in the first few weeks after people leave prison.

Patients who use opioids safely for decades are also arbitrarily being forced off their prescriptions because too many clinicians equate opioid use with opioid addiction, despite the fact that opioid tapering was associated with increased rates of overdose. And prohibition has led to a change in the drug supply that is now dominated by methamphetamine and fentanyl, substances far more deadly than the ones we demonized and seized decades ago.

We have tried and failed to rid the country of many drugs. We never will. Human beings will seek mind-altering substances, from caffeine to alcohol to hallucinogens. But we can stop the grim massacre of people who use drugs. We have the tools. What we lack is moral clarity.

In lecture after lecture of physicians and medical students, I hear the refrain that patients are not often “ready” for treatment. There’s nothing that doctors can do, they say, if the patient doesn’t want help. Yet they do not examine why that may be. Are we offering the help that they need? Time and again I have seen that if we meet people where they are, we can help virtually anyone.
 

Tools for fighting the opioid crisis

The reason our policies have failed is because we have not confronted a simple truth: We must care more about saving and improving the lives of people who use drugs than stopping drug use. With that framework, the approach is clear and multifactorial. First, we must make methadone treatment less draconian. Methadone, like buprenorphine, has been associated with a large reduction in all-cause mortality for people who have a history of overdose.

In this country, to access it, however, you must go to a clinic daily for the first 90 days of treatment and jump through hoops that often make it impossible to have a job and accomplish other goals. Other countries have safely moved methadone to primary care offices, and so should we. The other main drug for opioid addiction, buprenorphine, requires a special license to prescribe, even though it is far safer than other opioids that any physician can prescribe. This requirement has been weakened, but it should be removed entirely.

Moreover, the DEA conducts regular audits of buprenorphine prescribers in an effort to prevent diversion, discouraging doctors from prescribing it. This despite the fact that it is almost impossible to overdose on buprenorphine alone, and a study suggests that diversion of buprenorphine is associated with a lower overdose risk in a community by making the medication available to more people who can benefit.

Treatment is not the only way we can help people using drugs. Naloxone, an overdose rescue drug, should be available in every first aid kit and free at pharmacies without a prescription. Clean needles and pipes for people who use can help prevent infections, potentially mitigating the severity of outbreaks. Overdose prevention sites, where people can safely use, should be opened across the country.

We need accessible drug testing so people do not accidentally overdose and so they can know what they are using. We should stop sending people to jail for drug use when we know that it is too often tantamount to a death sentence, and offer effective medical treatment to anyone who is incarcerated.

All these interventions remain controversial within medicine and in the larger culture. If our metric, however, is lives saved and harm avoided, these are sure-fire approaches.

Right now, I am focused on clinical care and changing the culture of medicine, where we have opportunities to help but too often do harm instead. The impact of a shift in mentality would be huge, because we would realize there is no one we cannot help, only millions of people we do not listen to. But this is a national crisis and requires a national response. Until we are clear that our goal should and must be to stem the mounting deaths and harms above all else, we will continue to fail.

Dr. Poorman is board certified in internal medicine and addiction medicine, assistant professor of medicine, University of Illinois at Chicago, and provides primary care and addiction services in Chicago. Her views do not necessarily reflect the views of her employer. She has reported no relevant disclosures.

One quiet afternoon at a mobile outreach clinic, where I had been working on the West Side of Chicago, a young man without a home to go to, and clothes he kept as clean as he could, came to get a refill of buprenorphine. The drug, which works on the same opioid receptors as heroin, was helping him feel normal. It was also probably helping to keep him alive, as a study found that taking it after an overdose was associated with a one-third reduction in all-cause mortality.

He was still using drugs, but now only a few days a week instead of multiple times a day. He had put on some weight and looked visibly healthier.

I gave him his prescription and thanked him for coming back. As he got up to leave, he turned to our outreach team and said, “Thank you for being here and caring about us. Because a lot of people don’t. They don’t care if we live or die.”

But a lot of people do care and are still failing him and others who use drugs. When I first started treating addictions, I was taught to cut people like him off treatment. We could give patients a medication, but they had to follow the rules, first and foremost to stop using drugs. Keep using, even if you were using less and your health was improving, and I would have to dismiss you from the practice. This was the kind of “tough love” that many doctors have been taught, and are, in many cases, still being taught today. Even though we know that this approach does not work.

For too long, doctors, nurses, caregivers, and the broader American public have favored abstinence only treatment, criminalization, and prohibition. The proof that this approach does not work is in the spectacular overdose crisis we are experiencing in this country, as CDC data documents. While we continue to blame drugs like fentanyl and methamphetamine (and thirty years ago, crack and heroin), we fail to see how our approach contributes to these overdose deaths.

For instance, treating with buprenorphine or methadone was associated with reductions in overdose and serious opioid-related acute care use compared with detox alone. But only one in three centers offer these medications, the gold standard of care. We continue to imprison people who use drugs, even though we have known for 15 years that the risk of overdose is exponentially higher in the first few weeks after people leave prison.

Patients who use opioids safely for decades are also arbitrarily being forced off their prescriptions because too many clinicians equate opioid use with opioid addiction, despite the fact that opioid tapering was associated with increased rates of overdose. And prohibition has led to a change in the drug supply that is now dominated by methamphetamine and fentanyl, substances far more deadly than the ones we demonized and seized decades ago.

We have tried and failed to rid the country of many drugs. We never will. Human beings will seek mind-altering substances, from caffeine to alcohol to hallucinogens. But we can stop the grim massacre of people who use drugs. We have the tools. What we lack is moral clarity.

In lecture after lecture of physicians and medical students, I hear the refrain that patients are not often “ready” for treatment. There’s nothing that doctors can do, they say, if the patient doesn’t want help. Yet they do not examine why that may be. Are we offering the help that they need? Time and again I have seen that if we meet people where they are, we can help virtually anyone.
 

Tools for fighting the opioid crisis

The reason our policies have failed is because we have not confronted a simple truth: We must care more about saving and improving the lives of people who use drugs than stopping drug use. With that framework, the approach is clear and multifactorial. First, we must make methadone treatment less draconian. Methadone, like buprenorphine, has been associated with a large reduction in all-cause mortality for people who have a history of overdose.

In this country, to access it, however, you must go to a clinic daily for the first 90 days of treatment and jump through hoops that often make it impossible to have a job and accomplish other goals. Other countries have safely moved methadone to primary care offices, and so should we. The other main drug for opioid addiction, buprenorphine, requires a special license to prescribe, even though it is far safer than other opioids that any physician can prescribe. This requirement has been weakened, but it should be removed entirely.

Moreover, the DEA conducts regular audits of buprenorphine prescribers in an effort to prevent diversion, discouraging doctors from prescribing it. This despite the fact that it is almost impossible to overdose on buprenorphine alone, and a study suggests that diversion of buprenorphine is associated with a lower overdose risk in a community by making the medication available to more people who can benefit.

Treatment is not the only way we can help people using drugs. Naloxone, an overdose rescue drug, should be available in every first aid kit and free at pharmacies without a prescription. Clean needles and pipes for people who use can help prevent infections, potentially mitigating the severity of outbreaks. Overdose prevention sites, where people can safely use, should be opened across the country.

We need accessible drug testing so people do not accidentally overdose and so they can know what they are using. We should stop sending people to jail for drug use when we know that it is too often tantamount to a death sentence, and offer effective medical treatment to anyone who is incarcerated.

All these interventions remain controversial within medicine and in the larger culture. If our metric, however, is lives saved and harm avoided, these are sure-fire approaches.

Right now, I am focused on clinical care and changing the culture of medicine, where we have opportunities to help but too often do harm instead. The impact of a shift in mentality would be huge, because we would realize there is no one we cannot help, only millions of people we do not listen to. But this is a national crisis and requires a national response. Until we are clear that our goal should and must be to stem the mounting deaths and harms above all else, we will continue to fail.

Dr. Poorman is board certified in internal medicine and addiction medicine, assistant professor of medicine, University of Illinois at Chicago, and provides primary care and addiction services in Chicago. Her views do not necessarily reflect the views of her employer. She has reported no relevant disclosures.

One quiet afternoon at a mobile outreach clinic, where I had been working on the West Side of Chicago, a young man without a home to go to, and clothes he kept as clean as he could, came to get a refill of buprenorphine. The drug, which works on the same opioid receptors as heroin, was helping him feel normal. It was also probably helping to keep him alive, as a study found that taking it after an overdose was associated with a one-third reduction in all-cause mortality.

He was still using drugs, but now only a few days a week instead of multiple times a day. He had put on some weight and looked visibly healthier.

I gave him his prescription and thanked him for coming back. As he got up to leave, he turned to our outreach team and said, “Thank you for being here and caring about us. Because a lot of people don’t. They don’t care if we live or die.”

But a lot of people do care and are still failing him and others who use drugs. When I first started treating addictions, I was taught to cut people like him off treatment. We could give patients a medication, but they had to follow the rules, first and foremost to stop using drugs. Keep using, even if you were using less and your health was improving, and I would have to dismiss you from the practice. This was the kind of “tough love” that many doctors have been taught, and are, in many cases, still being taught today. Even though we know that this approach does not work.

For too long, doctors, nurses, caregivers, and the broader American public have favored abstinence only treatment, criminalization, and prohibition. The proof that this approach does not work is in the spectacular overdose crisis we are experiencing in this country, as CDC data documents. While we continue to blame drugs like fentanyl and methamphetamine (and thirty years ago, crack and heroin), we fail to see how our approach contributes to these overdose deaths.

For instance, treating with buprenorphine or methadone was associated with reductions in overdose and serious opioid-related acute care use compared with detox alone. But only one in three centers offer these medications, the gold standard of care. We continue to imprison people who use drugs, even though we have known for 15 years that the risk of overdose is exponentially higher in the first few weeks after people leave prison.

Patients who use opioids safely for decades are also arbitrarily being forced off their prescriptions because too many clinicians equate opioid use with opioid addiction, despite the fact that opioid tapering was associated with increased rates of overdose. And prohibition has led to a change in the drug supply that is now dominated by methamphetamine and fentanyl, substances far more deadly than the ones we demonized and seized decades ago.

We have tried and failed to rid the country of many drugs. We never will. Human beings will seek mind-altering substances, from caffeine to alcohol to hallucinogens. But we can stop the grim massacre of people who use drugs. We have the tools. What we lack is moral clarity.

In lecture after lecture of physicians and medical students, I hear the refrain that patients are not often “ready” for treatment. There’s nothing that doctors can do, they say, if the patient doesn’t want help. Yet they do not examine why that may be. Are we offering the help that they need? Time and again I have seen that if we meet people where they are, we can help virtually anyone.
 

Tools for fighting the opioid crisis

The reason our policies have failed is because we have not confronted a simple truth: We must care more about saving and improving the lives of people who use drugs than stopping drug use. With that framework, the approach is clear and multifactorial. First, we must make methadone treatment less draconian. Methadone, like buprenorphine, has been associated with a large reduction in all-cause mortality for people who have a history of overdose.

In this country, to access it, however, you must go to a clinic daily for the first 90 days of treatment and jump through hoops that often make it impossible to have a job and accomplish other goals. Other countries have safely moved methadone to primary care offices, and so should we. The other main drug for opioid addiction, buprenorphine, requires a special license to prescribe, even though it is far safer than other opioids that any physician can prescribe. This requirement has been weakened, but it should be removed entirely.

Moreover, the DEA conducts regular audits of buprenorphine prescribers in an effort to prevent diversion, discouraging doctors from prescribing it. This despite the fact that it is almost impossible to overdose on buprenorphine alone, and a study suggests that diversion of buprenorphine is associated with a lower overdose risk in a community by making the medication available to more people who can benefit.

Treatment is not the only way we can help people using drugs. Naloxone, an overdose rescue drug, should be available in every first aid kit and free at pharmacies without a prescription. Clean needles and pipes for people who use can help prevent infections, potentially mitigating the severity of outbreaks. Overdose prevention sites, where people can safely use, should be opened across the country.

We need accessible drug testing so people do not accidentally overdose and so they can know what they are using. We should stop sending people to jail for drug use when we know that it is too often tantamount to a death sentence, and offer effective medical treatment to anyone who is incarcerated.

All these interventions remain controversial within medicine and in the larger culture. If our metric, however, is lives saved and harm avoided, these are sure-fire approaches.

Right now, I am focused on clinical care and changing the culture of medicine, where we have opportunities to help but too often do harm instead. The impact of a shift in mentality would be huge, because we would realize there is no one we cannot help, only millions of people we do not listen to. But this is a national crisis and requires a national response. Until we are clear that our goal should and must be to stem the mounting deaths and harms above all else, we will continue to fail.

Dr. Poorman is board certified in internal medicine and addiction medicine, assistant professor of medicine, University of Illinois at Chicago, and provides primary care and addiction services in Chicago. Her views do not necessarily reflect the views of her employer. She has reported no relevant disclosures.

Opioid use disorder (OUD) is a public health crisis significantly affecting veterans. A substantial increase in veterans diagnosed with OUD has occurred, nearly tripling from 25,031 in 2003 to 69,142 in 2017.¹ Furthermore, compared with civilians, veterans are twice as likely to die of an accidental overdose, most often from opioids.²

For patients with active OUD, medications for opioid use disorder (MOUD) reduce the risk of overdose and all-cause mortality.³ In 2009, the US Department of Veterans Affairs (VA) and Department of Defense (DoD) published clinical practice guidelines for substance use disorders that strongly recommended MOUD with either buprenorphine or methadone as a first-line treatment. In 2015 updated guidelines encouraged buprenorphine initiation in primary care settings.^4,5 This was followed by an academic detailing campaign designed to encourage VA clinicians to initiate MOUD.¹ Despite this institutional support, MOUD remains underutilized within the VA, with widely variable rates of prescribing among VA sites.¹

Efforts to further expand MOUD cultivated interest in administering buprenorphine in VA emergency departments (EDs). Patients with OUD often use the ED for same-day care, providing opportunities to initiate buprenorphine in the ED 24 hours, 7 days per week. This has been especially true during the COVID-19 pandemic during which reliable access to usual recovery services has been disrupted and EDs have served as a safety net.⁶

Buprenorphine’s safety profile and prolonged effect duration make it superior to other MOUD options for ED administration. As a partial opioid agonist, buprenorphine is unlikely to cause significant sedation or respiratory depression compared with full agonists like methadone. This is known as the ceiling effect. Additionally, at higher doses, buprenorphine’s effects can last for about 3 days, potentially obviating the need for repeat dosing. D’Onofrio and colleagues seminal 2015 paper conceptually proved the feasibility and value of initiating buprenorphine in the ED; patients who received ED initiation therapy were more likely to be engaged in addiction treatment 30 days after their visit and have reduced rates of illicit opioid drug use.⁷ Such ED harm-reduction strategies are increasingly recognized as essential, given that 1 in 20 patients treated for a nonfatal opioid overdose in an ED will die within 1 year of their visit, many within 2 days.⁸ Finally, a significant barrier faced by physicians wanting to administer or prescribe buprenorphine for patients with OUD has been the special licensing required by the Drug Enforcement Administration Drug Addiction Treatment Act of 2000, also known as an X-waiver. A notable exception to this X-waiver requirement is the 72-hour rule, which allows nonwaivered practitioners to administer (but not prescribe for home use) buprenorphine to a patient to relieve acute withdrawal symptoms for up to 72 hours while arranging for specialist referral.Under the 72-hour rule, ED clinicians have a unique opportunity to treat patients experiencing acute withdrawal symptoms and bridge them to specialty care, without the burden of an X-waiver requirement.

The VA Greater Los Angeles Healthcare System (VAGLAHS), therefore, developed and implemented a program to administer buprenorphine in the ED to bridge patients with OUD to an appointment with substance use disorder (SUD) services. We describe our development, implementation and evaluation of this program protocol as a model for other VA EDs. This project was determined to be quality improvement (nonresearch) by the VAGLAHS Institutional Review Board.

ED MOUD Program

We engaged in a 2-month (January-March 2019) preimplementation process during which we (1) obtained stakeholder buy-in; (2) developed a protocol and supporting resources and tools; (3) worked with stakeholders to enact local organizational policy and process modifications; and (4) educated practitioners. 

Appendix 1 provides an overview of MOUD terminology, pharmacology, and regulations. We developed an 8-step program implementation plan for the ED MOUD program (Figure 1).

Obtaining Stakeholder Buy-in

Two ED physician champions (MC, JH) organized all activities. Champions obtained stakeholder buy-in from clinical and administrative leaders as well as from frontline personnel in OUD specialty care, ED, and pharmacy services. ED social workers and clerks who schedule post-ED appointments also were engaged. These stakeholders emphasized the importance of fitting the developed protocol into the existing ED workflows as well as minimizing additional resources required to initiate and maintain the program.

We ascertained that in fiscal year 2018, VAGLAHS had 156 ED visits with International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes related to OUD for 108 unique patients. Based on these data and in consultation with OUD specialty care, we determined that the potential number of referrals to the SUD clinic would be manageable with existing resources. Additionally, there was consensus that most opioid withdrawal patients could be treated in the urgent care portion of our ED since these patients generally do not require special monitoring. This consideration was important for obtaining ED stakeholder buy-in and for planning protocol logistics.

Developing the Protocol

We customized resources created by CalBridge Behavioral Health Navigator Program (CA Bridge), formerly called ED Bridge, a program of the Public Health Institute in Oakland, California, funded through California Department of Health Care Services. CA Bridge offers technical assistance and support for hospitals as well as guidance and tools for establishing processes for EDs providing buprenorphine prescriptions for the management of acute opioid withdrawal and serving as a bridge to follow-up care in SUD clinics.⁹ We also reviewed protocols described by D’Onofrio and colleagues. With iterative input from stakeholders, we created a protocol concretely delineating each process and corresponding responsible party with the overall aim of removing potential barriers to MOUD initiation and follow-up (Appendix 2).

Identifying Appropriate Follow-up

To operationalize protocol implementation, we built on VA’s Emergency Department Rapid Access Clinic (ED-RAC) process, a mechanism for scheduling appointments for post-ED specialty follow-up care. This process facilitated veterans’ access to urgent specialty care follow-up after ED visits by scheduling appointments prior to ED discharge.¹⁰ For the ED MOUD program, we adapted the ED-RAC process to schedule appointments in SUD clinic prior to ED discharge. These appointments allowed patients to be seen by an SUD clinician within 72 hours of ED discharge. This step was critical to working within the 72-hour rule without relying on X-waiver licensing of ED clinicians. Alternatively, as was previous practice, per patient preference, patients were also referred to non-VA residential rehabilitation services if the facility had capacity and patients met criteria for admission.

Identification of Eligible Veterans

Target patients were those primarily presenting with a request for treatment of opioid dependence or withdrawal. Patients were not actively screened for OUD. Clinicians diagnosed and assessed for OUD as per their usual practice. Patients with OUD who presented to the ED for other reasons were assessed, at clinician discretion, for their interest in receiving MOUD. If patients presented in moderate-to-severe withdrawal (eg, Clinical Opiate Withdrawal Scale [COWS] ≥ 8), buprenorphine was initiated in the ED. These patients were subsequently referred to either the local SUD clinic or to a residential treatment center. Patients presenting with a COWS score < 8 were referred to the outpatient SUD clinic or residential treatment centers without initiating buprenorphine from the ED. The SUD clinic or residential treatment centers could offer buprenorphine or other MOUD options. From the ED, prescribing buprenorphine for patients to self-initiate at home was not available as this required an X-waivered prescriber, which were limited during the program time frame.

Support Tools and Resources

To facilitate ED clinicians using the protocol, we worked with a programmer experienced with the Computerized Patient Record System, the VA electronic health record (EHR), to create electronic order menu sets that directed clinicians to the protocol and educational materials (Appendix 3). These menus are readily accessible and embedded into the ED clinician workflow. The menus highlight key elements of the protocol, including indications for initiation, contraindications, recommended dosing with quick orders, and how to obtain follow-up for the patient. Links also are provided to the protocol and patient discharge handouts, including the CA Bridge website.

Organizational Policy and Processes

Before implementing the developed protocol, we worked with stakeholders to modify organizational policies and processes. Our pharmacy agreed to stock buprenorphine in the ED to make it readily available. EHR restrictions that historically prohibited ordering buprenorphine for ED administration by nonwaivered clinicians were modified. Additionally, our chief of staff, pharmacy, and credentialing department agreed that physicians did not need to apply for additional delineated privileges.

Clinician Education

The final preparation step was educating clinicians and other protocol users. The VAGLAHS SUD chief presented a lecture and answered questions about MOUD to core ED faculty about the rising prevalence of OUD and use of buprenorphine as a recommended treatment.

Evaluation

To assess adherence to the developed protocol, we conducted a retrospective health record review of all ED visits March 1 to October 25, 2019, in which the patient had OUD and may have qualified for MOUD. To do this, we identified (1) ED visits with an OUD ICD-10 code as a primary or secondary diagnoses; (2) ED referrals to outpatient SUD treatment; and/or (3) ED visits in which buprenorphine was given or prescribed. We included the latter 2 criteria as application of ICD-10 codes for OUD care was inconsistent. Visits were excluded if patients did not have OUD, had OUD in remission, were already maintained on a stable MOUD regimen and no longer using illicit drugs or craving additional opioids, or were presenting solely for a refill or administration of a missed dose. Patients who relapsed were categorized as unstable. Visits were excluded if the patient was admitted to the hospital or left against medical advice. Patients on MOUD who had relapsed or requested a change in MOUD treatment were included. For all included visits, 2 ED physicians (MC, JH) reviewed the ED clinician and nursing notes, pharmacy and referral records, diagnostic codes, and veteran demographics.

In the evaluation, there were 130 visits with 92 unique veterans meeting inclusion criteria. The final sample included 70 visits with 47 unique veterans (Table 1). Of note, 24 (53%) patients self-identified as homeless or were engaged with VA housing services. Twelve veterans had multiple ED visits (7 patients with 2 visits; 5 patients with ≥ 3 visits). In 30 (43%) visits the veteran’s primary reason for seeking ED care was to obtain treatment for opioid withdrawal or receive MOUD. Type of opiate used was specified in 58% of visits; of these, 69% indicated heroin use and 17% prescription medications. Buprenorphine was initiated in the ED in 18 (26%) visits for 10 veterans. Appendix 4 outlines the clinical course and follow-up after these visits. Some veterans returned to the ED for buprenorphine redosing per the 72-hour rule. SUD clinic appointments were provided in 11 visits, and direct transfer to an inpatient rehabilitation center was arranged in 4 visits. In 42 (60%) visits, across 32 unique veterans, buprenorphine was not given in the ED, but patients were referred for SUD treatment (Table 2). In 10 (14%) visits, patients were not referred for SUD treatment or given buprenorphine, primarily because the presenting reason was not definitively related to OUDs.

DISCUSSION

We developed the ED MOUD program as a bridge to SUD specialty care. Our 8 implementation steps can serve as a model for implementing programs at other VA EDs. We demonstrated feasibility, high follow-up rates, and high retention in treatment.

Patients who received ED buprenorphine initiation were more likely to follow up and had higher rates of ongoing engagement at 30 days than did those who received only a clinic referral. In a similar Canadian study, buprenorphine was initiated in the ED, and patients followed up as a walk-in for addiction services; however, only 54% of patients presented to this initial follow-up.¹¹ Our higher initial follow-up rate may be due to our ability to directly schedule clinic appointments. Our 70% 30-day follow-up rate is comparable, but slightly lower than the 2015 D’Onofrio and colleagues study in which 78% of patients remained engaged at 30 days.⁷ A possible reason is that in the D’Onofrio and colleagues study, all study physicians obtained X-waiver training and were able to prescribe buprenorphine after ED initiation or for self-initiation at home. X-waiver training was not required of our clinicians, and none of our patients were offered a prescription for self-initiation.

Our program demonstrates that it is feasible to develop a protocol without X-waiver licensing. This program provides a supportive framework for the use of MOUD and allows nonspecialists to gain experience and confidence in using buprenorphine. Any clinician could administer buprenorphine in the ED, and patients could be bridged at later ED visits until follow-up with a specialist. Of note, only a small percentage of the total visits for buprenorphine initiation required multiple daily visits for buprenorphine. Appointments with the specialist were assured to fall within a 72-hour window.

Our program has some limitations. First, the number of patients who were candidates for our ED MOUD program was small. In our 7-month review, only 47 patients were identified as potential candidates for MOUD treatment across 70 visits, and only 10 were initiated in the ED. Second, all patients were not actively screened for OUD. There was potential for missing eligible veterans as inclusion criteria relied on clinicians both recognizing OUD and manually entering a correct diagnostic code. We attempted to mitigate this by also reviewing all ED referrals to the SUD clinic and all patients who received buprenorphine in the ED. In addition, we do not have data on preimplementation rates of follow-up for comparison.

Future Directions

More than half of our patients did not receive ED buprenorphine initiation because they were not in moderate or severe withdrawal (COWS ≥ 8) similar to 57% of patients cited in the D’Onofrio and colleagues study.⁷ Teaching veterans how to start buprenorphine at home could greatly expand enrollment. However, this requires a prescription from an X-waiver licensed clinician. In 2021, the US Department of Health and Human Services removed the 8-hour training requirement for obtaining an X-waiver.¹² However, clinicians are still required to apply for licensing. Eliminating the X-waiver requirement, as proposed by D’Onofrio and colleagues in a 2021 editorial, would have allowed all clinicians to offer home initiation.¹³

Previous studies suggest that despite the ability to provide a prescription, clinicians may be reluctant to offer home initiation.^14–17 In a national VA 2019 survey, many emergency medicine physicians believe that SUD care is not in their scope of practice, as Dieujuste and colleagues described in Federal Practitioner.¹⁴ Although it is likely some attitudes have changed with the increased visibility of ED MOUD programs, there is still much work to be done to change perceptions.

Another area for improvement is screening for OUD in the ED to better reveal MOUD candidates. Missed opportunities (neither referral nor treatment offered) occurred in 21% of our visits. D’Onofrio and colleagues identified 66% of patients by screening all ED patients.⁷ Although universal screening for SUD in routine health care settings has been recommended, 2021 VA guidelines state that there is insufficient evidence to recommend universal screening.^18-20 There are also limited data on the best screening tool for OUD in the ED.²¹ Further research on how to effectively and efficiently identify OUD patients in the ED is needed.

Conclusions

With minimal resource allocation, we started the program to offer MOUD with buprenorphine for patients with OUD at a VA ED and provided addiction treatment follow-up. This program, the first of its kind within VA, can be modeled and expanded to other VA facilities. Given increasing numbers of fatal opioid overdose, and significant adverse impacts of the COVID-19 pandemic on the OUD crisis, developing local and national strategies to treat OUD is essential. Future steps include improved screening and expanding capacity to offer home initiation by increasing the number of X-waiver ED clinicians.⁶

Acknowledgments

Thank you to Jeffrey Balsam, PharmD, BCPS, Veterans Affairs Greater Los Angeles Clinical Applications Coordinator for his contributions in creating a Computerized Patient Record System opioid use disorder screening tool. Thank you to Gracielle Tan, MD, Veterans Affairs Greater Los Angeles Health Science Specialist for her administrative assistance in manuscript preparation.

Opioid use disorder (OUD) is a public health crisis significantly affecting veterans. A substantial increase in veterans diagnosed with OUD has occurred, nearly tripling from 25,031 in 2003 to 69,142 in 2017.¹ Furthermore, compared with civilians, veterans are twice as likely to die of an accidental overdose, most often from opioids.²

For patients with active OUD, medications for opioid use disorder (MOUD) reduce the risk of overdose and all-cause mortality.³ In 2009, the US Department of Veterans Affairs (VA) and Department of Defense (DoD) published clinical practice guidelines for substance use disorders that strongly recommended MOUD with either buprenorphine or methadone as a first-line treatment. In 2015 updated guidelines encouraged buprenorphine initiation in primary care settings.^4,5 This was followed by an academic detailing campaign designed to encourage VA clinicians to initiate MOUD.¹ Despite this institutional support, MOUD remains underutilized within the VA, with widely variable rates of prescribing among VA sites.¹

Efforts to further expand MOUD cultivated interest in administering buprenorphine in VA emergency departments (EDs). Patients with OUD often use the ED for same-day care, providing opportunities to initiate buprenorphine in the ED 24 hours, 7 days per week. This has been especially true during the COVID-19 pandemic during which reliable access to usual recovery services has been disrupted and EDs have served as a safety net.⁶

Buprenorphine’s safety profile and prolonged effect duration make it superior to other MOUD options for ED administration. As a partial opioid agonist, buprenorphine is unlikely to cause significant sedation or respiratory depression compared with full agonists like methadone. This is known as the ceiling effect. Additionally, at higher doses, buprenorphine’s effects can last for about 3 days, potentially obviating the need for repeat dosing. D’Onofrio and colleagues seminal 2015 paper conceptually proved the feasibility and value of initiating buprenorphine in the ED; patients who received ED initiation therapy were more likely to be engaged in addiction treatment 30 days after their visit and have reduced rates of illicit opioid drug use.⁷ Such ED harm-reduction strategies are increasingly recognized as essential, given that 1 in 20 patients treated for a nonfatal opioid overdose in an ED will die within 1 year of their visit, many within 2 days.⁸ Finally, a significant barrier faced by physicians wanting to administer or prescribe buprenorphine for patients with OUD has been the special licensing required by the Drug Enforcement Administration Drug Addiction Treatment Act of 2000, also known as an X-waiver. A notable exception to this X-waiver requirement is the 72-hour rule, which allows nonwaivered practitioners to administer (but not prescribe for home use) buprenorphine to a patient to relieve acute withdrawal symptoms for up to 72 hours while arranging for specialist referral.Under the 72-hour rule, ED clinicians have a unique opportunity to treat patients experiencing acute withdrawal symptoms and bridge them to specialty care, without the burden of an X-waiver requirement.

The VA Greater Los Angeles Healthcare System (VAGLAHS), therefore, developed and implemented a program to administer buprenorphine in the ED to bridge patients with OUD to an appointment with substance use disorder (SUD) services. We describe our development, implementation and evaluation of this program protocol as a model for other VA EDs. This project was determined to be quality improvement (nonresearch) by the VAGLAHS Institutional Review Board.

ED MOUD Program

We engaged in a 2-month (January-March 2019) preimplementation process during which we (1) obtained stakeholder buy-in; (2) developed a protocol and supporting resources and tools; (3) worked with stakeholders to enact local organizational policy and process modifications; and (4) educated practitioners. 

Appendix 1 provides an overview of MOUD terminology, pharmacology, and regulations. We developed an 8-step program implementation plan for the ED MOUD program (Figure 1).

Obtaining Stakeholder Buy-in

Two ED physician champions (MC, JH) organized all activities. Champions obtained stakeholder buy-in from clinical and administrative leaders as well as from frontline personnel in OUD specialty care, ED, and pharmacy services. ED social workers and clerks who schedule post-ED appointments also were engaged. These stakeholders emphasized the importance of fitting the developed protocol into the existing ED workflows as well as minimizing additional resources required to initiate and maintain the program.

We ascertained that in fiscal year 2018, VAGLAHS had 156 ED visits with International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes related to OUD for 108 unique patients. Based on these data and in consultation with OUD specialty care, we determined that the potential number of referrals to the SUD clinic would be manageable with existing resources. Additionally, there was consensus that most opioid withdrawal patients could be treated in the urgent care portion of our ED since these patients generally do not require special monitoring. This consideration was important for obtaining ED stakeholder buy-in and for planning protocol logistics.

Developing the Protocol

We customized resources created by CalBridge Behavioral Health Navigator Program (CA Bridge), formerly called ED Bridge, a program of the Public Health Institute in Oakland, California, funded through California Department of Health Care Services. CA Bridge offers technical assistance and support for hospitals as well as guidance and tools for establishing processes for EDs providing buprenorphine prescriptions for the management of acute opioid withdrawal and serving as a bridge to follow-up care in SUD clinics.⁹ We also reviewed protocols described by D’Onofrio and colleagues. With iterative input from stakeholders, we created a protocol concretely delineating each process and corresponding responsible party with the overall aim of removing potential barriers to MOUD initiation and follow-up (Appendix 2).

Identifying Appropriate Follow-up

To operationalize protocol implementation, we built on VA’s Emergency Department Rapid Access Clinic (ED-RAC) process, a mechanism for scheduling appointments for post-ED specialty follow-up care. This process facilitated veterans’ access to urgent specialty care follow-up after ED visits by scheduling appointments prior to ED discharge.¹⁰ For the ED MOUD program, we adapted the ED-RAC process to schedule appointments in SUD clinic prior to ED discharge. These appointments allowed patients to be seen by an SUD clinician within 72 hours of ED discharge. This step was critical to working within the 72-hour rule without relying on X-waiver licensing of ED clinicians. Alternatively, as was previous practice, per patient preference, patients were also referred to non-VA residential rehabilitation services if the facility had capacity and patients met criteria for admission.

Identification of Eligible Veterans

Target patients were those primarily presenting with a request for treatment of opioid dependence or withdrawal. Patients were not actively screened for OUD. Clinicians diagnosed and assessed for OUD as per their usual practice. Patients with OUD who presented to the ED for other reasons were assessed, at clinician discretion, for their interest in receiving MOUD. If patients presented in moderate-to-severe withdrawal (eg, Clinical Opiate Withdrawal Scale [COWS] ≥ 8), buprenorphine was initiated in the ED. These patients were subsequently referred to either the local SUD clinic or to a residential treatment center. Patients presenting with a COWS score < 8 were referred to the outpatient SUD clinic or residential treatment centers without initiating buprenorphine from the ED. The SUD clinic or residential treatment centers could offer buprenorphine or other MOUD options. From the ED, prescribing buprenorphine for patients to self-initiate at home was not available as this required an X-waivered prescriber, which were limited during the program time frame.

Support Tools and Resources

To facilitate ED clinicians using the protocol, we worked with a programmer experienced with the Computerized Patient Record System, the VA electronic health record (EHR), to create electronic order menu sets that directed clinicians to the protocol and educational materials (Appendix 3). These menus are readily accessible and embedded into the ED clinician workflow. The menus highlight key elements of the protocol, including indications for initiation, contraindications, recommended dosing with quick orders, and how to obtain follow-up for the patient. Links also are provided to the protocol and patient discharge handouts, including the CA Bridge website.

Organizational Policy and Processes

Before implementing the developed protocol, we worked with stakeholders to modify organizational policies and processes. Our pharmacy agreed to stock buprenorphine in the ED to make it readily available. EHR restrictions that historically prohibited ordering buprenorphine for ED administration by nonwaivered clinicians were modified. Additionally, our chief of staff, pharmacy, and credentialing department agreed that physicians did not need to apply for additional delineated privileges.

Clinician Education

The final preparation step was educating clinicians and other protocol users. The VAGLAHS SUD chief presented a lecture and answered questions about MOUD to core ED faculty about the rising prevalence of OUD and use of buprenorphine as a recommended treatment.

Evaluation

To assess adherence to the developed protocol, we conducted a retrospective health record review of all ED visits March 1 to October 25, 2019, in which the patient had OUD and may have qualified for MOUD. To do this, we identified (1) ED visits with an OUD ICD-10 code as a primary or secondary diagnoses; (2) ED referrals to outpatient SUD treatment; and/or (3) ED visits in which buprenorphine was given or prescribed. We included the latter 2 criteria as application of ICD-10 codes for OUD care was inconsistent. Visits were excluded if patients did not have OUD, had OUD in remission, were already maintained on a stable MOUD regimen and no longer using illicit drugs or craving additional opioids, or were presenting solely for a refill or administration of a missed dose. Patients who relapsed were categorized as unstable. Visits were excluded if the patient was admitted to the hospital or left against medical advice. Patients on MOUD who had relapsed or requested a change in MOUD treatment were included. For all included visits, 2 ED physicians (MC, JH) reviewed the ED clinician and nursing notes, pharmacy and referral records, diagnostic codes, and veteran demographics.

In the evaluation, there were 130 visits with 92 unique veterans meeting inclusion criteria. The final sample included 70 visits with 47 unique veterans (Table 1). Of note, 24 (53%) patients self-identified as homeless or were engaged with VA housing services. Twelve veterans had multiple ED visits (7 patients with 2 visits; 5 patients with ≥ 3 visits). In 30 (43%) visits the veteran’s primary reason for seeking ED care was to obtain treatment for opioid withdrawal or receive MOUD. Type of opiate used was specified in 58% of visits; of these, 69% indicated heroin use and 17% prescription medications. Buprenorphine was initiated in the ED in 18 (26%) visits for 10 veterans. Appendix 4 outlines the clinical course and follow-up after these visits. Some veterans returned to the ED for buprenorphine redosing per the 72-hour rule. SUD clinic appointments were provided in 11 visits, and direct transfer to an inpatient rehabilitation center was arranged in 4 visits. In 42 (60%) visits, across 32 unique veterans, buprenorphine was not given in the ED, but patients were referred for SUD treatment (Table 2). In 10 (14%) visits, patients were not referred for SUD treatment or given buprenorphine, primarily because the presenting reason was not definitively related to OUDs.

DISCUSSION

We developed the ED MOUD program as a bridge to SUD specialty care. Our 8 implementation steps can serve as a model for implementing programs at other VA EDs. We demonstrated feasibility, high follow-up rates, and high retention in treatment.

Patients who received ED buprenorphine initiation were more likely to follow up and had higher rates of ongoing engagement at 30 days than did those who received only a clinic referral. In a similar Canadian study, buprenorphine was initiated in the ED, and patients followed up as a walk-in for addiction services; however, only 54% of patients presented to this initial follow-up.¹¹ Our higher initial follow-up rate may be due to our ability to directly schedule clinic appointments. Our 70% 30-day follow-up rate is comparable, but slightly lower than the 2015 D’Onofrio and colleagues study in which 78% of patients remained engaged at 30 days.⁷ A possible reason is that in the D’Onofrio and colleagues study, all study physicians obtained X-waiver training and were able to prescribe buprenorphine after ED initiation or for self-initiation at home. X-waiver training was not required of our clinicians, and none of our patients were offered a prescription for self-initiation.

Our program demonstrates that it is feasible to develop a protocol without X-waiver licensing. This program provides a supportive framework for the use of MOUD and allows nonspecialists to gain experience and confidence in using buprenorphine. Any clinician could administer buprenorphine in the ED, and patients could be bridged at later ED visits until follow-up with a specialist. Of note, only a small percentage of the total visits for buprenorphine initiation required multiple daily visits for buprenorphine. Appointments with the specialist were assured to fall within a 72-hour window.

Our program has some limitations. First, the number of patients who were candidates for our ED MOUD program was small. In our 7-month review, only 47 patients were identified as potential candidates for MOUD treatment across 70 visits, and only 10 were initiated in the ED. Second, all patients were not actively screened for OUD. There was potential for missing eligible veterans as inclusion criteria relied on clinicians both recognizing OUD and manually entering a correct diagnostic code. We attempted to mitigate this by also reviewing all ED referrals to the SUD clinic and all patients who received buprenorphine in the ED. In addition, we do not have data on preimplementation rates of follow-up for comparison.

Future Directions

More than half of our patients did not receive ED buprenorphine initiation because they were not in moderate or severe withdrawal (COWS ≥ 8) similar to 57% of patients cited in the D’Onofrio and colleagues study.⁷ Teaching veterans how to start buprenorphine at home could greatly expand enrollment. However, this requires a prescription from an X-waiver licensed clinician. In 2021, the US Department of Health and Human Services removed the 8-hour training requirement for obtaining an X-waiver.¹² However, clinicians are still required to apply for licensing. Eliminating the X-waiver requirement, as proposed by D’Onofrio and colleagues in a 2021 editorial, would have allowed all clinicians to offer home initiation.¹³

Previous studies suggest that despite the ability to provide a prescription, clinicians may be reluctant to offer home initiation.^14–17 In a national VA 2019 survey, many emergency medicine physicians believe that SUD care is not in their scope of practice, as Dieujuste and colleagues described in Federal Practitioner.¹⁴ Although it is likely some attitudes have changed with the increased visibility of ED MOUD programs, there is still much work to be done to change perceptions.

Another area for improvement is screening for OUD in the ED to better reveal MOUD candidates. Missed opportunities (neither referral nor treatment offered) occurred in 21% of our visits. D’Onofrio and colleagues identified 66% of patients by screening all ED patients.⁷ Although universal screening for SUD in routine health care settings has been recommended, 2021 VA guidelines state that there is insufficient evidence to recommend universal screening.^18-20 There are also limited data on the best screening tool for OUD in the ED.²¹ Further research on how to effectively and efficiently identify OUD patients in the ED is needed.

Conclusions

With minimal resource allocation, we started the program to offer MOUD with buprenorphine for patients with OUD at a VA ED and provided addiction treatment follow-up. This program, the first of its kind within VA, can be modeled and expanded to other VA facilities. Given increasing numbers of fatal opioid overdose, and significant adverse impacts of the COVID-19 pandemic on the OUD crisis, developing local and national strategies to treat OUD is essential. Future steps include improved screening and expanding capacity to offer home initiation by increasing the number of X-waiver ED clinicians.⁶

Acknowledgments

Thank you to Jeffrey Balsam, PharmD, BCPS, Veterans Affairs Greater Los Angeles Clinical Applications Coordinator for his contributions in creating a Computerized Patient Record System opioid use disorder screening tool. Thank you to Gracielle Tan, MD, Veterans Affairs Greater Los Angeles Health Science Specialist for her administrative assistance in manuscript preparation.

Opioid use disorder (OUD) is a public health crisis significantly affecting veterans. A substantial increase in veterans diagnosed with OUD has occurred, nearly tripling from 25,031 in 2003 to 69,142 in 2017.¹ Furthermore, compared with civilians, veterans are twice as likely to die of an accidental overdose, most often from opioids.²

For patients with active OUD, medications for opioid use disorder (MOUD) reduce the risk of overdose and all-cause mortality.³ In 2009, the US Department of Veterans Affairs (VA) and Department of Defense (DoD) published clinical practice guidelines for substance use disorders that strongly recommended MOUD with either buprenorphine or methadone as a first-line treatment. In 2015 updated guidelines encouraged buprenorphine initiation in primary care settings.^4,5 This was followed by an academic detailing campaign designed to encourage VA clinicians to initiate MOUD.¹ Despite this institutional support, MOUD remains underutilized within the VA, with widely variable rates of prescribing among VA sites.¹

Efforts to further expand MOUD cultivated interest in administering buprenorphine in VA emergency departments (EDs). Patients with OUD often use the ED for same-day care, providing opportunities to initiate buprenorphine in the ED 24 hours, 7 days per week. This has been especially true during the COVID-19 pandemic during which reliable access to usual recovery services has been disrupted and EDs have served as a safety net.⁶

Buprenorphine’s safety profile and prolonged effect duration make it superior to other MOUD options for ED administration. As a partial opioid agonist, buprenorphine is unlikely to cause significant sedation or respiratory depression compared with full agonists like methadone. This is known as the ceiling effect. Additionally, at higher doses, buprenorphine’s effects can last for about 3 days, potentially obviating the need for repeat dosing. D’Onofrio and colleagues seminal 2015 paper conceptually proved the feasibility and value of initiating buprenorphine in the ED; patients who received ED initiation therapy were more likely to be engaged in addiction treatment 30 days after their visit and have reduced rates of illicit opioid drug use.⁷ Such ED harm-reduction strategies are increasingly recognized as essential, given that 1 in 20 patients treated for a nonfatal opioid overdose in an ED will die within 1 year of their visit, many within 2 days.⁸ Finally, a significant barrier faced by physicians wanting to administer or prescribe buprenorphine for patients with OUD has been the special licensing required by the Drug Enforcement Administration Drug Addiction Treatment Act of 2000, also known as an X-waiver. A notable exception to this X-waiver requirement is the 72-hour rule, which allows nonwaivered practitioners to administer (but not prescribe for home use) buprenorphine to a patient to relieve acute withdrawal symptoms for up to 72 hours while arranging for specialist referral.Under the 72-hour rule, ED clinicians have a unique opportunity to treat patients experiencing acute withdrawal symptoms and bridge them to specialty care, without the burden of an X-waiver requirement.

The VA Greater Los Angeles Healthcare System (VAGLAHS), therefore, developed and implemented a program to administer buprenorphine in the ED to bridge patients with OUD to an appointment with substance use disorder (SUD) services. We describe our development, implementation and evaluation of this program protocol as a model for other VA EDs. This project was determined to be quality improvement (nonresearch) by the VAGLAHS Institutional Review Board.

ED MOUD Program

We engaged in a 2-month (January-March 2019) preimplementation process during which we (1) obtained stakeholder buy-in; (2) developed a protocol and supporting resources and tools; (3) worked with stakeholders to enact local organizational policy and process modifications; and (4) educated practitioners. 

Appendix 1 provides an overview of MOUD terminology, pharmacology, and regulations. We developed an 8-step program implementation plan for the ED MOUD program (Figure 1).

Obtaining Stakeholder Buy-in

Two ED physician champions (MC, JH) organized all activities. Champions obtained stakeholder buy-in from clinical and administrative leaders as well as from frontline personnel in OUD specialty care, ED, and pharmacy services. ED social workers and clerks who schedule post-ED appointments also were engaged. These stakeholders emphasized the importance of fitting the developed protocol into the existing ED workflows as well as minimizing additional resources required to initiate and maintain the program.

We ascertained that in fiscal year 2018, VAGLAHS had 156 ED visits with International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes related to OUD for 108 unique patients. Based on these data and in consultation with OUD specialty care, we determined that the potential number of referrals to the SUD clinic would be manageable with existing resources. Additionally, there was consensus that most opioid withdrawal patients could be treated in the urgent care portion of our ED since these patients generally do not require special monitoring. This consideration was important for obtaining ED stakeholder buy-in and for planning protocol logistics.

Developing the Protocol

We customized resources created by CalBridge Behavioral Health Navigator Program (CA Bridge), formerly called ED Bridge, a program of the Public Health Institute in Oakland, California, funded through California Department of Health Care Services. CA Bridge offers technical assistance and support for hospitals as well as guidance and tools for establishing processes for EDs providing buprenorphine prescriptions for the management of acute opioid withdrawal and serving as a bridge to follow-up care in SUD clinics.⁹ We also reviewed protocols described by D’Onofrio and colleagues. With iterative input from stakeholders, we created a protocol concretely delineating each process and corresponding responsible party with the overall aim of removing potential barriers to MOUD initiation and follow-up (Appendix 2).

Identifying Appropriate Follow-up

To operationalize protocol implementation, we built on VA’s Emergency Department Rapid Access Clinic (ED-RAC) process, a mechanism for scheduling appointments for post-ED specialty follow-up care. This process facilitated veterans’ access to urgent specialty care follow-up after ED visits by scheduling appointments prior to ED discharge.¹⁰ For the ED MOUD program, we adapted the ED-RAC process to schedule appointments in SUD clinic prior to ED discharge. These appointments allowed patients to be seen by an SUD clinician within 72 hours of ED discharge. This step was critical to working within the 72-hour rule without relying on X-waiver licensing of ED clinicians. Alternatively, as was previous practice, per patient preference, patients were also referred to non-VA residential rehabilitation services if the facility had capacity and patients met criteria for admission.

Identification of Eligible Veterans

Target patients were those primarily presenting with a request for treatment of opioid dependence or withdrawal. Patients were not actively screened for OUD. Clinicians diagnosed and assessed for OUD as per their usual practice. Patients with OUD who presented to the ED for other reasons were assessed, at clinician discretion, for their interest in receiving MOUD. If patients presented in moderate-to-severe withdrawal (eg, Clinical Opiate Withdrawal Scale [COWS] ≥ 8), buprenorphine was initiated in the ED. These patients were subsequently referred to either the local SUD clinic or to a residential treatment center. Patients presenting with a COWS score < 8 were referred to the outpatient SUD clinic or residential treatment centers without initiating buprenorphine from the ED. The SUD clinic or residential treatment centers could offer buprenorphine or other MOUD options. From the ED, prescribing buprenorphine for patients to self-initiate at home was not available as this required an X-waivered prescriber, which were limited during the program time frame.

Support Tools and Resources

To facilitate ED clinicians using the protocol, we worked with a programmer experienced with the Computerized Patient Record System, the VA electronic health record (EHR), to create electronic order menu sets that directed clinicians to the protocol and educational materials (Appendix 3). These menus are readily accessible and embedded into the ED clinician workflow. The menus highlight key elements of the protocol, including indications for initiation, contraindications, recommended dosing with quick orders, and how to obtain follow-up for the patient. Links also are provided to the protocol and patient discharge handouts, including the CA Bridge website.

Organizational Policy and Processes

Before implementing the developed protocol, we worked with stakeholders to modify organizational policies and processes. Our pharmacy agreed to stock buprenorphine in the ED to make it readily available. EHR restrictions that historically prohibited ordering buprenorphine for ED administration by nonwaivered clinicians were modified. Additionally, our chief of staff, pharmacy, and credentialing department agreed that physicians did not need to apply for additional delineated privileges.

Clinician Education

The final preparation step was educating clinicians and other protocol users. The VAGLAHS SUD chief presented a lecture and answered questions about MOUD to core ED faculty about the rising prevalence of OUD and use of buprenorphine as a recommended treatment.

Evaluation

To assess adherence to the developed protocol, we conducted a retrospective health record review of all ED visits March 1 to October 25, 2019, in which the patient had OUD and may have qualified for MOUD. To do this, we identified (1) ED visits with an OUD ICD-10 code as a primary or secondary diagnoses; (2) ED referrals to outpatient SUD treatment; and/or (3) ED visits in which buprenorphine was given or prescribed. We included the latter 2 criteria as application of ICD-10 codes for OUD care was inconsistent. Visits were excluded if patients did not have OUD, had OUD in remission, were already maintained on a stable MOUD regimen and no longer using illicit drugs or craving additional opioids, or were presenting solely for a refill or administration of a missed dose. Patients who relapsed were categorized as unstable. Visits were excluded if the patient was admitted to the hospital or left against medical advice. Patients on MOUD who had relapsed or requested a change in MOUD treatment were included. For all included visits, 2 ED physicians (MC, JH) reviewed the ED clinician and nursing notes, pharmacy and referral records, diagnostic codes, and veteran demographics.

In the evaluation, there were 130 visits with 92 unique veterans meeting inclusion criteria. The final sample included 70 visits with 47 unique veterans (Table 1). Of note, 24 (53%) patients self-identified as homeless or were engaged with VA housing services. Twelve veterans had multiple ED visits (7 patients with 2 visits; 5 patients with ≥ 3 visits). In 30 (43%) visits the veteran’s primary reason for seeking ED care was to obtain treatment for opioid withdrawal or receive MOUD. Type of opiate used was specified in 58% of visits; of these, 69% indicated heroin use and 17% prescription medications. Buprenorphine was initiated in the ED in 18 (26%) visits for 10 veterans. Appendix 4 outlines the clinical course and follow-up after these visits. Some veterans returned to the ED for buprenorphine redosing per the 72-hour rule. SUD clinic appointments were provided in 11 visits, and direct transfer to an inpatient rehabilitation center was arranged in 4 visits. In 42 (60%) visits, across 32 unique veterans, buprenorphine was not given in the ED, but patients were referred for SUD treatment (Table 2). In 10 (14%) visits, patients were not referred for SUD treatment or given buprenorphine, primarily because the presenting reason was not definitively related to OUDs.

DISCUSSION

We developed the ED MOUD program as a bridge to SUD specialty care. Our 8 implementation steps can serve as a model for implementing programs at other VA EDs. We demonstrated feasibility, high follow-up rates, and high retention in treatment.

Patients who received ED buprenorphine initiation were more likely to follow up and had higher rates of ongoing engagement at 30 days than did those who received only a clinic referral. In a similar Canadian study, buprenorphine was initiated in the ED, and patients followed up as a walk-in for addiction services; however, only 54% of patients presented to this initial follow-up.¹¹ Our higher initial follow-up rate may be due to our ability to directly schedule clinic appointments. Our 70% 30-day follow-up rate is comparable, but slightly lower than the 2015 D’Onofrio and colleagues study in which 78% of patients remained engaged at 30 days.⁷ A possible reason is that in the D’Onofrio and colleagues study, all study physicians obtained X-waiver training and were able to prescribe buprenorphine after ED initiation or for self-initiation at home. X-waiver training was not required of our clinicians, and none of our patients were offered a prescription for self-initiation.

Our program demonstrates that it is feasible to develop a protocol without X-waiver licensing. This program provides a supportive framework for the use of MOUD and allows nonspecialists to gain experience and confidence in using buprenorphine. Any clinician could administer buprenorphine in the ED, and patients could be bridged at later ED visits until follow-up with a specialist. Of note, only a small percentage of the total visits for buprenorphine initiation required multiple daily visits for buprenorphine. Appointments with the specialist were assured to fall within a 72-hour window.

Our program has some limitations. First, the number of patients who were candidates for our ED MOUD program was small. In our 7-month review, only 47 patients were identified as potential candidates for MOUD treatment across 70 visits, and only 10 were initiated in the ED. Second, all patients were not actively screened for OUD. There was potential for missing eligible veterans as inclusion criteria relied on clinicians both recognizing OUD and manually entering a correct diagnostic code. We attempted to mitigate this by also reviewing all ED referrals to the SUD clinic and all patients who received buprenorphine in the ED. In addition, we do not have data on preimplementation rates of follow-up for comparison.

Future Directions

More than half of our patients did not receive ED buprenorphine initiation because they were not in moderate or severe withdrawal (COWS ≥ 8) similar to 57% of patients cited in the D’Onofrio and colleagues study.⁷ Teaching veterans how to start buprenorphine at home could greatly expand enrollment. However, this requires a prescription from an X-waiver licensed clinician. In 2021, the US Department of Health and Human Services removed the 8-hour training requirement for obtaining an X-waiver.¹² However, clinicians are still required to apply for licensing. Eliminating the X-waiver requirement, as proposed by D’Onofrio and colleagues in a 2021 editorial, would have allowed all clinicians to offer home initiation.¹³

Previous studies suggest that despite the ability to provide a prescription, clinicians may be reluctant to offer home initiation.^14–17 In a national VA 2019 survey, many emergency medicine physicians believe that SUD care is not in their scope of practice, as Dieujuste and colleagues described in Federal Practitioner.¹⁴ Although it is likely some attitudes have changed with the increased visibility of ED MOUD programs, there is still much work to be done to change perceptions.

Another area for improvement is screening for OUD in the ED to better reveal MOUD candidates. Missed opportunities (neither referral nor treatment offered) occurred in 21% of our visits. D’Onofrio and colleagues identified 66% of patients by screening all ED patients.⁷ Although universal screening for SUD in routine health care settings has been recommended, 2021 VA guidelines state that there is insufficient evidence to recommend universal screening.^18-20 There are also limited data on the best screening tool for OUD in the ED.²¹ Further research on how to effectively and efficiently identify OUD patients in the ED is needed.

Conclusions

With minimal resource allocation, we started the program to offer MOUD with buprenorphine for patients with OUD at a VA ED and provided addiction treatment follow-up. This program, the first of its kind within VA, can be modeled and expanded to other VA facilities. Given increasing numbers of fatal opioid overdose, and significant adverse impacts of the COVID-19 pandemic on the OUD crisis, developing local and national strategies to treat OUD is essential. Future steps include improved screening and expanding capacity to offer home initiation by increasing the number of X-waiver ED clinicians.⁶

Acknowledgments

Thank you to Jeffrey Balsam, PharmD, BCPS, Veterans Affairs Greater Los Angeles Clinical Applications Coordinator for his contributions in creating a Computerized Patient Record System opioid use disorder screening tool. Thank you to Gracielle Tan, MD, Veterans Affairs Greater Los Angeles Health Science Specialist for her administrative assistance in manuscript preparation.

There is a concerning lack of follow-up care for young people who experience a mental health crisis, new research suggests.

Results from a large database study showed less than half of youth and young adults hospitalized for a psychiatric event received follow-up care within 7 days. The follow-up rate was less than 30% for those who had visited an ED.

The strongest predictor of follow-up was having received both primary and mental health care during the 6 months prior to using the acute service.

“For people discharging folks after a psychiatric crisis, whether it be in a hospital or emergency room setting, connecting them with their outpatient provider to ensure the transfer of care and continuity of care is vitally important to reduce risks for this population,” coinvestigator Brian Skehan, MD, PhD, assistant professor and psychiatrist, University of Massachusetts, Worcester, said during a press briefing.

If these discharged patients do not have a provider, “make sure they get one,” Lisa Dixon, MD, editor-in-chief of Psychiatric Services, added during the same briefing. “That’s the gift of life potentially for these young people.”

The findings were published online  in Psychiatric Services.
 

Alarming trends

The alarming suicide trends among youths were exacerbated by the COVID-19 pandemic, Dr. Skehan noted.

He cited a 2021 study that showed more than 44% of high school students experienced persistent sadness or hopelessness over the previous year, 1 in 5 seriously considered suicide, and almost 1 in 10 actually attempted suicide.

“When we look at the number of young adults and adolescents struggling with behavioral health issues, the data trend is disturbing nationwide,” Dr. Skehan said.

The current study included participants aged 12-27 years who had private insurance. Many youth in this age category are experiencing significant changes, such as moving from high school to college and from pediatric providers to adult providers – and some “get lost in this transition,” said Dr. Skehan.

He noted many inpatient psychiatric units are not geared to young adults. “They may miss out on some aspects of inpatient care because it’s not geared to their developmental stage,” he said.

Assessing U.S. patient data in the IBM MarketScan commercial database (2013-2018), the researchers created two study samples: 95,153 inpatients and 108,576 patients who used the ED. All had an acute event stemming from a mental health condition.

The investigators explored the role of “established” outpatient care, defined as having had at least one visit with a provider of primary or mental health care in the 6 months prior to the acute psychiatric event.

Covariates included age at time of service (aged 12-17 years or 18-27 years), gender, health care plan type, psychiatric diagnosis, whether the acute event was self-harm or suicide related, and medical complexity.
 

Low follow-up rates

In the inpatient group, the average age was 18.9 years, the most common length of hospital stay was 4-6 days, and 1.5% left against medical advice. The most common primary diagnosis was major depression (53.7%), followed by bipolar disorder (22.3%). The least common disorders were PTSD, comorbid eating disorders, and disruptive disorders.

About one-third of participants had used both primary and mental health care during the 6 months before hospitalization, whereas 22.8% had no established outpatient care. Established care was most common among those with comorbid eating disorders and least common among those with psychotic disorders.

Results showed 42.7% of the hospitalized patients received follow up within 7 days and 67.4% received follow up within 30 days.

The strongest predictor of mental health follow-up care was established outpatient care. Compared with those who had no such care, those who had received both primary care and mental health care before the acute event had the highest odds of receiving follow-up (within 7 days, adjusted odds ratio, 2.81; 95% confidence interval, 2.68-2.94).

Older age and leaving against medical advice were associated with decreased likelihood of follow-up. Female sex, hospitalizations related to self-harm or suicidality, and longer length of stay were associated with increased likelihood of mental health follow-up care.

Compared with those hospitalized for major depression, those hospitalized for schizophrenia, bipolar disorder, PTSD, disruptive disorders, or comorbid substance use disorder were less likely to receive mental health follow-up. For example, only 23.7% of youth with comorbid substance use discharged from the hospital had follow-up within 7 days.

Similar patterns were observed for 30-day follow-up care.
 

‘Accessible and appealing’ options needed

In the ED-visit group, the average age was 19.5 years (58% female). Most (70.4%) had no chronic health conditions other than a psychiatric disorder. The primary diagnoses were anxiety disorders or phobias (44.1%) and major depression (23%).

One in four visits included a code for self-harm, suicidal ideation, or suicide attempt. And almost one third lacked established outpatient care before the ED visit.

Results showed 28.6% of the ED group received mental health care follow-up within 7 days and 46.4% received it within 30 days.

Again, the strongest predictor of mental health follow-up was prior outpatient care. For example, compared with participants with no established outpatient care, those with both primary care and mental health care were the most likely to receive follow-up within 7 days (aOR, 4.06; 95% CI, 3.72-4.42).

These numbers “are far from the goal of making sure everybody is getting follow-up care within 7 days of an acute psychiatric event,” Dr. Skehan said.

He stressed the need for “accessible and appealing options for youth.” These could include telehealth services, improved communication among health care providers in the ED, and reducing barriers to access follow-up care.

“This probably highlights the need to have more case management and referral services, and maybe make sure patients have a follow-up appointment before they leave the emergency room,” said Dr. Skehan. “This doesn’t necessarily guarantee they’ll get there but hopefully it makes it more likely they will have that access should they need it.”

The study was funded by grants from the National Institute of General Medical Sciences and the National Center for Advancing Translational Sciences, from the National Institutes of Health. The investigators reported no relevant financial relationships.

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

There is a concerning lack of follow-up care for young people who experience a mental health crisis, new research suggests.

Results from a large database study showed less than half of youth and young adults hospitalized for a psychiatric event received follow-up care within 7 days. The follow-up rate was less than 30% for those who had visited an ED.

The strongest predictor of follow-up was having received both primary and mental health care during the 6 months prior to using the acute service.

“For people discharging folks after a psychiatric crisis, whether it be in a hospital or emergency room setting, connecting them with their outpatient provider to ensure the transfer of care and continuity of care is vitally important to reduce risks for this population,” coinvestigator Brian Skehan, MD, PhD, assistant professor and psychiatrist, University of Massachusetts, Worcester, said during a press briefing.

If these discharged patients do not have a provider, “make sure they get one,” Lisa Dixon, MD, editor-in-chief of Psychiatric Services, added during the same briefing. “That’s the gift of life potentially for these young people.”

The findings were published online  in Psychiatric Services.
 

Alarming trends

The alarming suicide trends among youths were exacerbated by the COVID-19 pandemic, Dr. Skehan noted.

He cited a 2021 study that showed more than 44% of high school students experienced persistent sadness or hopelessness over the previous year, 1 in 5 seriously considered suicide, and almost 1 in 10 actually attempted suicide.

“When we look at the number of young adults and adolescents struggling with behavioral health issues, the data trend is disturbing nationwide,” Dr. Skehan said.

The current study included participants aged 12-27 years who had private insurance. Many youth in this age category are experiencing significant changes, such as moving from high school to college and from pediatric providers to adult providers – and some “get lost in this transition,” said Dr. Skehan.

He noted many inpatient psychiatric units are not geared to young adults. “They may miss out on some aspects of inpatient care because it’s not geared to their developmental stage,” he said.

Assessing U.S. patient data in the IBM MarketScan commercial database (2013-2018), the researchers created two study samples: 95,153 inpatients and 108,576 patients who used the ED. All had an acute event stemming from a mental health condition.

The investigators explored the role of “established” outpatient care, defined as having had at least one visit with a provider of primary or mental health care in the 6 months prior to the acute psychiatric event.

Covariates included age at time of service (aged 12-17 years or 18-27 years), gender, health care plan type, psychiatric diagnosis, whether the acute event was self-harm or suicide related, and medical complexity.
 

Low follow-up rates

In the inpatient group, the average age was 18.9 years, the most common length of hospital stay was 4-6 days, and 1.5% left against medical advice. The most common primary diagnosis was major depression (53.7%), followed by bipolar disorder (22.3%). The least common disorders were PTSD, comorbid eating disorders, and disruptive disorders.

About one-third of participants had used both primary and mental health care during the 6 months before hospitalization, whereas 22.8% had no established outpatient care. Established care was most common among those with comorbid eating disorders and least common among those with psychotic disorders.

Results showed 42.7% of the hospitalized patients received follow up within 7 days and 67.4% received follow up within 30 days.

The strongest predictor of mental health follow-up care was established outpatient care. Compared with those who had no such care, those who had received both primary care and mental health care before the acute event had the highest odds of receiving follow-up (within 7 days, adjusted odds ratio, 2.81; 95% confidence interval, 2.68-2.94).

Older age and leaving against medical advice were associated with decreased likelihood of follow-up. Female sex, hospitalizations related to self-harm or suicidality, and longer length of stay were associated with increased likelihood of mental health follow-up care.

Compared with those hospitalized for major depression, those hospitalized for schizophrenia, bipolar disorder, PTSD, disruptive disorders, or comorbid substance use disorder were less likely to receive mental health follow-up. For example, only 23.7% of youth with comorbid substance use discharged from the hospital had follow-up within 7 days.

Similar patterns were observed for 30-day follow-up care.
 

‘Accessible and appealing’ options needed

In the ED-visit group, the average age was 19.5 years (58% female). Most (70.4%) had no chronic health conditions other than a psychiatric disorder. The primary diagnoses were anxiety disorders or phobias (44.1%) and major depression (23%).

One in four visits included a code for self-harm, suicidal ideation, or suicide attempt. And almost one third lacked established outpatient care before the ED visit.

Results showed 28.6% of the ED group received mental health care follow-up within 7 days and 46.4% received it within 30 days.

Again, the strongest predictor of mental health follow-up was prior outpatient care. For example, compared with participants with no established outpatient care, those with both primary care and mental health care were the most likely to receive follow-up within 7 days (aOR, 4.06; 95% CI, 3.72-4.42).

These numbers “are far from the goal of making sure everybody is getting follow-up care within 7 days of an acute psychiatric event,” Dr. Skehan said.

He stressed the need for “accessible and appealing options for youth.” These could include telehealth services, improved communication among health care providers in the ED, and reducing barriers to access follow-up care.

“This probably highlights the need to have more case management and referral services, and maybe make sure patients have a follow-up appointment before they leave the emergency room,” said Dr. Skehan. “This doesn’t necessarily guarantee they’ll get there but hopefully it makes it more likely they will have that access should they need it.”

The study was funded by grants from the National Institute of General Medical Sciences and the National Center for Advancing Translational Sciences, from the National Institutes of Health. The investigators reported no relevant financial relationships.

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

There is a concerning lack of follow-up care for young people who experience a mental health crisis, new research suggests.

Results from a large database study showed less than half of youth and young adults hospitalized for a psychiatric event received follow-up care within 7 days. The follow-up rate was less than 30% for those who had visited an ED.

The strongest predictor of follow-up was having received both primary and mental health care during the 6 months prior to using the acute service.

“For people discharging folks after a psychiatric crisis, whether it be in a hospital or emergency room setting, connecting them with their outpatient provider to ensure the transfer of care and continuity of care is vitally important to reduce risks for this population,” coinvestigator Brian Skehan, MD, PhD, assistant professor and psychiatrist, University of Massachusetts, Worcester, said during a press briefing.

If these discharged patients do not have a provider, “make sure they get one,” Lisa Dixon, MD, editor-in-chief of Psychiatric Services, added during the same briefing. “That’s the gift of life potentially for these young people.”

The findings were published online  in Psychiatric Services.
 

Alarming trends

The alarming suicide trends among youths were exacerbated by the COVID-19 pandemic, Dr. Skehan noted.

He cited a 2021 study that showed more than 44% of high school students experienced persistent sadness or hopelessness over the previous year, 1 in 5 seriously considered suicide, and almost 1 in 10 actually attempted suicide.

“When we look at the number of young adults and adolescents struggling with behavioral health issues, the data trend is disturbing nationwide,” Dr. Skehan said.

The current study included participants aged 12-27 years who had private insurance. Many youth in this age category are experiencing significant changes, such as moving from high school to college and from pediatric providers to adult providers – and some “get lost in this transition,” said Dr. Skehan.

He noted many inpatient psychiatric units are not geared to young adults. “They may miss out on some aspects of inpatient care because it’s not geared to their developmental stage,” he said.

Assessing U.S. patient data in the IBM MarketScan commercial database (2013-2018), the researchers created two study samples: 95,153 inpatients and 108,576 patients who used the ED. All had an acute event stemming from a mental health condition.

The investigators explored the role of “established” outpatient care, defined as having had at least one visit with a provider of primary or mental health care in the 6 months prior to the acute psychiatric event.

Covariates included age at time of service (aged 12-17 years or 18-27 years), gender, health care plan type, psychiatric diagnosis, whether the acute event was self-harm or suicide related, and medical complexity.
 

Low follow-up rates

In the inpatient group, the average age was 18.9 years, the most common length of hospital stay was 4-6 days, and 1.5% left against medical advice. The most common primary diagnosis was major depression (53.7%), followed by bipolar disorder (22.3%). The least common disorders were PTSD, comorbid eating disorders, and disruptive disorders.

About one-third of participants had used both primary and mental health care during the 6 months before hospitalization, whereas 22.8% had no established outpatient care. Established care was most common among those with comorbid eating disorders and least common among those with psychotic disorders.

Results showed 42.7% of the hospitalized patients received follow up within 7 days and 67.4% received follow up within 30 days.

The strongest predictor of mental health follow-up care was established outpatient care. Compared with those who had no such care, those who had received both primary care and mental health care before the acute event had the highest odds of receiving follow-up (within 7 days, adjusted odds ratio, 2.81; 95% confidence interval, 2.68-2.94).

Older age and leaving against medical advice were associated with decreased likelihood of follow-up. Female sex, hospitalizations related to self-harm or suicidality, and longer length of stay were associated with increased likelihood of mental health follow-up care.

Compared with those hospitalized for major depression, those hospitalized for schizophrenia, bipolar disorder, PTSD, disruptive disorders, or comorbid substance use disorder were less likely to receive mental health follow-up. For example, only 23.7% of youth with comorbid substance use discharged from the hospital had follow-up within 7 days.

Similar patterns were observed for 30-day follow-up care.
 

‘Accessible and appealing’ options needed

In the ED-visit group, the average age was 19.5 years (58% female). Most (70.4%) had no chronic health conditions other than a psychiatric disorder. The primary diagnoses were anxiety disorders or phobias (44.1%) and major depression (23%).

One in four visits included a code for self-harm, suicidal ideation, or suicide attempt. And almost one third lacked established outpatient care before the ED visit.

Results showed 28.6% of the ED group received mental health care follow-up within 7 days and 46.4% received it within 30 days.

Again, the strongest predictor of mental health follow-up was prior outpatient care. For example, compared with participants with no established outpatient care, those with both primary care and mental health care were the most likely to receive follow-up within 7 days (aOR, 4.06; 95% CI, 3.72-4.42).

These numbers “are far from the goal of making sure everybody is getting follow-up care within 7 days of an acute psychiatric event,” Dr. Skehan said.

He stressed the need for “accessible and appealing options for youth.” These could include telehealth services, improved communication among health care providers in the ED, and reducing barriers to access follow-up care.

“This probably highlights the need to have more case management and referral services, and maybe make sure patients have a follow-up appointment before they leave the emergency room,” said Dr. Skehan. “This doesn’t necessarily guarantee they’ll get there but hopefully it makes it more likely they will have that access should they need it.”

The study was funded by grants from the National Institute of General Medical Sciences and the National Center for Advancing Translational Sciences, from the National Institutes of Health. The investigators reported no relevant financial relationships.

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

Google the word “dopamine” and you will learn that its nicknames are the “happy hormone” and the “pleasure molecule” and that it is among the most important chemicals in our brains. With The Guardian branding it “the Kim Kardashian of neurotransmitters,” dopamine has become a true pop-science darling – people across the globe have attempted to boost their mood with dopamine fasts and dopamine dressing.

A century ago, however, newly discovered dopamine was seen as an uninspiring chemical, nothing more than a precursor of noradrenaline. It took several stubborn and hardworking scientists to change that view.
 

Levodopa: An indifferent precursor

When Casimir Funk, PhD, a Polish biochemist and the discoverer of vitamins, first synthesized the dopamine precursor levodopa in 1911, he had no idea how important the molecule would prove to be in pharmacology and neurobiology. Nor did Markus Guggenheim, PhD, a Swiss biochemist, who isolated levodopa in 1913 from the seeds of a broad bean, Vicia faba. Dr. Guggenheim administered 1 g of levodopa to a rabbit, with no apparent negative consequences. He then prepared a larger dose (2.5 g) and tested it on himself. “Ten minutes after taking it, I felt very nauseous, I had to vomit twice,” he wrote in his paper. In the body, levodopa is converted into dopamine, which may act as an emetic – an effect Dr. Guggenheim didn’t understand. He simply abandoned his human study, erroneously concluding, on the basis of his animal research, that levodopa is “pharmacologically fairly indifferent.”

Around the same time, several scientists across Europe successfully synthesized dopamine, but those discoveries were shelved without much fanfare. For the next 3 decades, dopamine and levodopa were pushed into academic obscurity. Just before World War II, a group of German scientists showed that levodopa is metabolized to dopamine in the body, while another German researcher, Hermann Blaschko, MD, discovered that dopamine is an intermediary in the synthesis of noradrenaline. Even these findings, however, were not immediately accepted.

The dopamine story picked up pace in the post-war years with the observation that the hormone was present in various tissues and body fluids, although nowhere as abundantly as in the central nervous system. Intrigued, Dr. Blaschko, who (after escaping Nazi Germany, changing his name to Hugh, and starting work at Oxford [England] University) hypothesized that dopamine couldn’t be an unremarkable precursor of noradrenaline – it had to have some physiologic functions of its own. He asked his postdoctoral fellow, Oheh Hornykiewicz, MD, to test a few ideas. Dr. Hornykiewicz soon confirmed that dopamine lowered blood pressure in guinea pigs, proving that dopamine indeed had physiologic activity that was independent of other catecholamines.
 

Reserpine and rabbit ears

While Dr. Blaschko and Dr. Hornykiewicz were puzzling over dopamine’s physiologic role in the body, across the ocean at the National Heart Institute in Maryland, pharmacologist Bernard Brodie, PhD and colleagues were laying the groundwork for the discovery of dopamine’s starring role in the brain.

Spoiler alert: Dr. Brodie’s work showed that a new psychiatric drug known as reserpine was capable of fully depleting the brain’s stores of serotonin and – of greatest significance, as it turned out – mimicking the neuromuscular symptoms typical of Parkinson’s disease. The connection to dopamine would be made by new lab colleague Arvid Carlsson, MD, PhD, who would go on to win a Nobel Prize.

Derived from Rauwolfia serpentina (a plant that for centuries has been used in India for the treatment of mental illness, insomnia, and snake bites), reserpine was introduced in the West as a treatment for schizophrenia.

It worked marvels. In 1954, the press lauded the “dramatic” and seemingly “incredible”: results in treating “hopelessly insane patients.” Reserpine had a downside, however. Reports soon changed in tone regarding the drug’s severe side effects, including headaches, dizziness, vomiting, and, far more disturbingly, symptoms mimicking Parkinson’s disease, from muscular rigidity to tremors.

Dr. Brodie observed that, when reserpine was injected, animals became completely immobile. Serotonin nearly vanished from their brains, but bizarrely, drugs that spur serotonin production did not reverse the rabbits’ immobility.

Dr. Carlsson realized that other catecholamines must be involved in reserpine’s side effects, and he began to search for the culprits. He moved back to his native Sweden and ordered a spectrophotofluorimeter. In one of his experiments, Carlsson injected a pair of rabbits with reserpine, which caused the animals to become catatonic with flattened ears. After the researchers injected the animals with levodopa, within 15 minutes, the rabbits were hopping around, ears proudly vertical. “We were just as excited as the rabbits,” Dr. Carlsson later recalled in a 2016 interview. Dr. Carlsson realized that, because there was no noradrenaline in the rabbits’ brains, dopamine depletion must have been directly responsible for producing reserpine’s motor inhibitory effects.
 

Skeptics are silenced

In 1960, however, the medical community was not yet ready to accept that dopamine was anything but a boring intermediate between levodopa and noradrenaline. At a prestigious London symposium, Dr. Carlsson and his two colleagues presented their hypothesis that dopamine may be a neurotransmitter, thus implicating it in Parkinson’s disease. They were met with harsh criticism. Some of the experts said levodopa was nothing more than a poison. Dr. Carlsson later recalled facing “a profound and nearly unanimous skepticism regarding our points of view.”

That would soon change. Dr. Hornykiewicz, the biochemist who had earlier discovered dopamine’s BP-lowering effects, tested Dr. Carlsson’s ideas using the postmortem brains of Parkinson’s disease patients. It appeared Dr. Carlsson was right: Unlike in healthy brains, the striatum of patients with Parkinson’s disease contained almost no dopamine whatsoever. Beginning in 1961, in collaboration with neurologist Walther Birkmayer, MD, Hornykiewicz injected levodopa into 20 patients with Parkinson’s disease and observed a “miraculous” (albeit temporary) amelioration of rigidity, motionlessness, and speechlessness.

By the late 1960s, levodopa and dopamine were making headlines. A 1969 New York Times article described similar stunning improvements in patients with Parkinson’s disease who were treated with levodopa. A patient who had arrived at a hospital unable to speak, with hands clenched and rigid expression, was suddenly able to stride into his doctor’s office and even jog around. “I might say I’m a human being,” he told reporters. Although the treatment was expensive – equivalent to $210 in 2022 – physicians were deluged with requests for “dopa.” To this day, levodopa remains a gold standard in the treatment of Parkinson’s disease.
 

Still misunderstood

The history of dopamine, however, is not only about Parkinson’s disease but extends to the treatment of schizophrenia and addiction. When in the1940s a French military surgeon started giving a new antihistamine drug, promethazine, to prevent shock in soldiers undergoing surgery, he noticed a bizarre side effect: the soldiers would become euphoric yet oddly calm at the same time.

After the drug was modified by adding a chlorine atom and renamed chlorpromazine, it fast became a go-to treatment for psychosis. At the time, no one made the connection to dopamine. Contemporary doctors believed that it calmed people by lowering body temperature (common treatments for mental illness back in the day included swaddling patients in cold, wet sheets). Yet just like reserpine, chlorpromazine produced range of nasty side effects that closely mimicked Parkinson’s disease. This led a Dutch pharmacologist, Jacques van Rossum, to hypothesize that dopamine receptor blockade could explain chlorpromazine’s antipsychotic effects – an idea that remains widely accepted today.

In the 1970s, dopamine was linked with addiction through research on rodents, and this novel idea caught people’s imagination over the coming decades. A story on dopamine titled, “How We Get Addicted,” made the cover of Time in 1997.

Yet as the dopamine/addiction connection became widespread, it also became oversimplified. According to a 2015 article in Nature Reviews Neuroscience, a wave of low-quality research followed – nonreplicated, insufficient – which led the authors to conclude that we are “addicted to the dopamine theory of addiction.” Just about every pleasure under the sun was being attributed to dopamine, from eating delicious foods and playing computer games to sex, music, and hot showers. As recent science shows, however, dopamine is not simply about pleasure – it’s about reward prediction, response to stress, memory, learning, and even the functioning of the immune system. Since its first synthesis in the early 20th century, dopamine has often been misunderstood and oversimplified – and it seems the story is repeating itself now.

In one of his final interviews, Dr. Carlsson, who passed away in 2018 at the age of 95, warned about playing around with dopamine and, in particular, prescribing drugs that have an inhibitory action on this neurotransmitter. “Dopamine is involved in everything that happens in our brains – all its important functions,” he said.

We should be careful how we handle such a delicate and still little-known system.

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

Google the word “dopamine” and you will learn that its nicknames are the “happy hormone” and the “pleasure molecule” and that it is among the most important chemicals in our brains. With The Guardian branding it “the Kim Kardashian of neurotransmitters,” dopamine has become a true pop-science darling – people across the globe have attempted to boost their mood with dopamine fasts and dopamine dressing.

A century ago, however, newly discovered dopamine was seen as an uninspiring chemical, nothing more than a precursor of noradrenaline. It took several stubborn and hardworking scientists to change that view.
 

Levodopa: An indifferent precursor

When Casimir Funk, PhD, a Polish biochemist and the discoverer of vitamins, first synthesized the dopamine precursor levodopa in 1911, he had no idea how important the molecule would prove to be in pharmacology and neurobiology. Nor did Markus Guggenheim, PhD, a Swiss biochemist, who isolated levodopa in 1913 from the seeds of a broad bean, Vicia faba. Dr. Guggenheim administered 1 g of levodopa to a rabbit, with no apparent negative consequences. He then prepared a larger dose (2.5 g) and tested it on himself. “Ten minutes after taking it, I felt very nauseous, I had to vomit twice,” he wrote in his paper. In the body, levodopa is converted into dopamine, which may act as an emetic – an effect Dr. Guggenheim didn’t understand. He simply abandoned his human study, erroneously concluding, on the basis of his animal research, that levodopa is “pharmacologically fairly indifferent.”

Around the same time, several scientists across Europe successfully synthesized dopamine, but those discoveries were shelved without much fanfare. For the next 3 decades, dopamine and levodopa were pushed into academic obscurity. Just before World War II, a group of German scientists showed that levodopa is metabolized to dopamine in the body, while another German researcher, Hermann Blaschko, MD, discovered that dopamine is an intermediary in the synthesis of noradrenaline. Even these findings, however, were not immediately accepted.

The dopamine story picked up pace in the post-war years with the observation that the hormone was present in various tissues and body fluids, although nowhere as abundantly as in the central nervous system. Intrigued, Dr. Blaschko, who (after escaping Nazi Germany, changing his name to Hugh, and starting work at Oxford [England] University) hypothesized that dopamine couldn’t be an unremarkable precursor of noradrenaline – it had to have some physiologic functions of its own. He asked his postdoctoral fellow, Oheh Hornykiewicz, MD, to test a few ideas. Dr. Hornykiewicz soon confirmed that dopamine lowered blood pressure in guinea pigs, proving that dopamine indeed had physiologic activity that was independent of other catecholamines.
 

Reserpine and rabbit ears

While Dr. Blaschko and Dr. Hornykiewicz were puzzling over dopamine’s physiologic role in the body, across the ocean at the National Heart Institute in Maryland, pharmacologist Bernard Brodie, PhD and colleagues were laying the groundwork for the discovery of dopamine’s starring role in the brain.

Spoiler alert: Dr. Brodie’s work showed that a new psychiatric drug known as reserpine was capable of fully depleting the brain’s stores of serotonin and – of greatest significance, as it turned out – mimicking the neuromuscular symptoms typical of Parkinson’s disease. The connection to dopamine would be made by new lab colleague Arvid Carlsson, MD, PhD, who would go on to win a Nobel Prize.

Derived from Rauwolfia serpentina (a plant that for centuries has been used in India for the treatment of mental illness, insomnia, and snake bites), reserpine was introduced in the West as a treatment for schizophrenia.

It worked marvels. In 1954, the press lauded the “dramatic” and seemingly “incredible”: results in treating “hopelessly insane patients.” Reserpine had a downside, however. Reports soon changed in tone regarding the drug’s severe side effects, including headaches, dizziness, vomiting, and, far more disturbingly, symptoms mimicking Parkinson’s disease, from muscular rigidity to tremors.

Dr. Brodie observed that, when reserpine was injected, animals became completely immobile. Serotonin nearly vanished from their brains, but bizarrely, drugs that spur serotonin production did not reverse the rabbits’ immobility.

Dr. Carlsson realized that other catecholamines must be involved in reserpine’s side effects, and he began to search for the culprits. He moved back to his native Sweden and ordered a spectrophotofluorimeter. In one of his experiments, Carlsson injected a pair of rabbits with reserpine, which caused the animals to become catatonic with flattened ears. After the researchers injected the animals with levodopa, within 15 minutes, the rabbits were hopping around, ears proudly vertical. “We were just as excited as the rabbits,” Dr. Carlsson later recalled in a 2016 interview. Dr. Carlsson realized that, because there was no noradrenaline in the rabbits’ brains, dopamine depletion must have been directly responsible for producing reserpine’s motor inhibitory effects.
 

Skeptics are silenced

In 1960, however, the medical community was not yet ready to accept that dopamine was anything but a boring intermediate between levodopa and noradrenaline. At a prestigious London symposium, Dr. Carlsson and his two colleagues presented their hypothesis that dopamine may be a neurotransmitter, thus implicating it in Parkinson’s disease. They were met with harsh criticism. Some of the experts said levodopa was nothing more than a poison. Dr. Carlsson later recalled facing “a profound and nearly unanimous skepticism regarding our points of view.”

That would soon change. Dr. Hornykiewicz, the biochemist who had earlier discovered dopamine’s BP-lowering effects, tested Dr. Carlsson’s ideas using the postmortem brains of Parkinson’s disease patients. It appeared Dr. Carlsson was right: Unlike in healthy brains, the striatum of patients with Parkinson’s disease contained almost no dopamine whatsoever. Beginning in 1961, in collaboration with neurologist Walther Birkmayer, MD, Hornykiewicz injected levodopa into 20 patients with Parkinson’s disease and observed a “miraculous” (albeit temporary) amelioration of rigidity, motionlessness, and speechlessness.

By the late 1960s, levodopa and dopamine were making headlines. A 1969 New York Times article described similar stunning improvements in patients with Parkinson’s disease who were treated with levodopa. A patient who had arrived at a hospital unable to speak, with hands clenched and rigid expression, was suddenly able to stride into his doctor’s office and even jog around. “I might say I’m a human being,” he told reporters. Although the treatment was expensive – equivalent to $210 in 2022 – physicians were deluged with requests for “dopa.” To this day, levodopa remains a gold standard in the treatment of Parkinson’s disease.
 

Still misunderstood

The history of dopamine, however, is not only about Parkinson’s disease but extends to the treatment of schizophrenia and addiction. When in the1940s a French military surgeon started giving a new antihistamine drug, promethazine, to prevent shock in soldiers undergoing surgery, he noticed a bizarre side effect: the soldiers would become euphoric yet oddly calm at the same time.

After the drug was modified by adding a chlorine atom and renamed chlorpromazine, it fast became a go-to treatment for psychosis. At the time, no one made the connection to dopamine. Contemporary doctors believed that it calmed people by lowering body temperature (common treatments for mental illness back in the day included swaddling patients in cold, wet sheets). Yet just like reserpine, chlorpromazine produced range of nasty side effects that closely mimicked Parkinson’s disease. This led a Dutch pharmacologist, Jacques van Rossum, to hypothesize that dopamine receptor blockade could explain chlorpromazine’s antipsychotic effects – an idea that remains widely accepted today.

In the 1970s, dopamine was linked with addiction through research on rodents, and this novel idea caught people’s imagination over the coming decades. A story on dopamine titled, “How We Get Addicted,” made the cover of Time in 1997.

Yet as the dopamine/addiction connection became widespread, it also became oversimplified. According to a 2015 article in Nature Reviews Neuroscience, a wave of low-quality research followed – nonreplicated, insufficient – which led the authors to conclude that we are “addicted to the dopamine theory of addiction.” Just about every pleasure under the sun was being attributed to dopamine, from eating delicious foods and playing computer games to sex, music, and hot showers. As recent science shows, however, dopamine is not simply about pleasure – it’s about reward prediction, response to stress, memory, learning, and even the functioning of the immune system. Since its first synthesis in the early 20th century, dopamine has often been misunderstood and oversimplified – and it seems the story is repeating itself now.

In one of his final interviews, Dr. Carlsson, who passed away in 2018 at the age of 95, warned about playing around with dopamine and, in particular, prescribing drugs that have an inhibitory action on this neurotransmitter. “Dopamine is involved in everything that happens in our brains – all its important functions,” he said.

We should be careful how we handle such a delicate and still little-known system.

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

Google the word “dopamine” and you will learn that its nicknames are the “happy hormone” and the “pleasure molecule” and that it is among the most important chemicals in our brains. With The Guardian branding it “the Kim Kardashian of neurotransmitters,” dopamine has become a true pop-science darling – people across the globe have attempted to boost their mood with dopamine fasts and dopamine dressing.

A century ago, however, newly discovered dopamine was seen as an uninspiring chemical, nothing more than a precursor of noradrenaline. It took several stubborn and hardworking scientists to change that view.
 

Levodopa: An indifferent precursor

When Casimir Funk, PhD, a Polish biochemist and the discoverer of vitamins, first synthesized the dopamine precursor levodopa in 1911, he had no idea how important the molecule would prove to be in pharmacology and neurobiology. Nor did Markus Guggenheim, PhD, a Swiss biochemist, who isolated levodopa in 1913 from the seeds of a broad bean, Vicia faba. Dr. Guggenheim administered 1 g of levodopa to a rabbit, with no apparent negative consequences. He then prepared a larger dose (2.5 g) and tested it on himself. “Ten minutes after taking it, I felt very nauseous, I had to vomit twice,” he wrote in his paper. In the body, levodopa is converted into dopamine, which may act as an emetic – an effect Dr. Guggenheim didn’t understand. He simply abandoned his human study, erroneously concluding, on the basis of his animal research, that levodopa is “pharmacologically fairly indifferent.”

Around the same time, several scientists across Europe successfully synthesized dopamine, but those discoveries were shelved without much fanfare. For the next 3 decades, dopamine and levodopa were pushed into academic obscurity. Just before World War II, a group of German scientists showed that levodopa is metabolized to dopamine in the body, while another German researcher, Hermann Blaschko, MD, discovered that dopamine is an intermediary in the synthesis of noradrenaline. Even these findings, however, were not immediately accepted.

The dopamine story picked up pace in the post-war years with the observation that the hormone was present in various tissues and body fluids, although nowhere as abundantly as in the central nervous system. Intrigued, Dr. Blaschko, who (after escaping Nazi Germany, changing his name to Hugh, and starting work at Oxford [England] University) hypothesized that dopamine couldn’t be an unremarkable precursor of noradrenaline – it had to have some physiologic functions of its own. He asked his postdoctoral fellow, Oheh Hornykiewicz, MD, to test a few ideas. Dr. Hornykiewicz soon confirmed that dopamine lowered blood pressure in guinea pigs, proving that dopamine indeed had physiologic activity that was independent of other catecholamines.
 

Reserpine and rabbit ears

While Dr. Blaschko and Dr. Hornykiewicz were puzzling over dopamine’s physiologic role in the body, across the ocean at the National Heart Institute in Maryland, pharmacologist Bernard Brodie, PhD and colleagues were laying the groundwork for the discovery of dopamine’s starring role in the brain.

Spoiler alert: Dr. Brodie’s work showed that a new psychiatric drug known as reserpine was capable of fully depleting the brain’s stores of serotonin and – of greatest significance, as it turned out – mimicking the neuromuscular symptoms typical of Parkinson’s disease. The connection to dopamine would be made by new lab colleague Arvid Carlsson, MD, PhD, who would go on to win a Nobel Prize.

Derived from Rauwolfia serpentina (a plant that for centuries has been used in India for the treatment of mental illness, insomnia, and snake bites), reserpine was introduced in the West as a treatment for schizophrenia.

It worked marvels. In 1954, the press lauded the “dramatic” and seemingly “incredible”: results in treating “hopelessly insane patients.” Reserpine had a downside, however. Reports soon changed in tone regarding the drug’s severe side effects, including headaches, dizziness, vomiting, and, far more disturbingly, symptoms mimicking Parkinson’s disease, from muscular rigidity to tremors.

Dr. Brodie observed that, when reserpine was injected, animals became completely immobile. Serotonin nearly vanished from their brains, but bizarrely, drugs that spur serotonin production did not reverse the rabbits’ immobility.

Dr. Carlsson realized that other catecholamines must be involved in reserpine’s side effects, and he began to search for the culprits. He moved back to his native Sweden and ordered a spectrophotofluorimeter. In one of his experiments, Carlsson injected a pair of rabbits with reserpine, which caused the animals to become catatonic with flattened ears. After the researchers injected the animals with levodopa, within 15 minutes, the rabbits were hopping around, ears proudly vertical. “We were just as excited as the rabbits,” Dr. Carlsson later recalled in a 2016 interview. Dr. Carlsson realized that, because there was no noradrenaline in the rabbits’ brains, dopamine depletion must have been directly responsible for producing reserpine’s motor inhibitory effects.
 

Skeptics are silenced

In 1960, however, the medical community was not yet ready to accept that dopamine was anything but a boring intermediate between levodopa and noradrenaline. At a prestigious London symposium, Dr. Carlsson and his two colleagues presented their hypothesis that dopamine may be a neurotransmitter, thus implicating it in Parkinson’s disease. They were met with harsh criticism. Some of the experts said levodopa was nothing more than a poison. Dr. Carlsson later recalled facing “a profound and nearly unanimous skepticism regarding our points of view.”

That would soon change. Dr. Hornykiewicz, the biochemist who had earlier discovered dopamine’s BP-lowering effects, tested Dr. Carlsson’s ideas using the postmortem brains of Parkinson’s disease patients. It appeared Dr. Carlsson was right: Unlike in healthy brains, the striatum of patients with Parkinson’s disease contained almost no dopamine whatsoever. Beginning in 1961, in collaboration with neurologist Walther Birkmayer, MD, Hornykiewicz injected levodopa into 20 patients with Parkinson’s disease and observed a “miraculous” (albeit temporary) amelioration of rigidity, motionlessness, and speechlessness.

By the late 1960s, levodopa and dopamine were making headlines. A 1969 New York Times article described similar stunning improvements in patients with Parkinson’s disease who were treated with levodopa. A patient who had arrived at a hospital unable to speak, with hands clenched and rigid expression, was suddenly able to stride into his doctor’s office and even jog around. “I might say I’m a human being,” he told reporters. Although the treatment was expensive – equivalent to $210 in 2022 – physicians were deluged with requests for “dopa.” To this day, levodopa remains a gold standard in the treatment of Parkinson’s disease.
 

Still misunderstood

The history of dopamine, however, is not only about Parkinson’s disease but extends to the treatment of schizophrenia and addiction. When in the1940s a French military surgeon started giving a new antihistamine drug, promethazine, to prevent shock in soldiers undergoing surgery, he noticed a bizarre side effect: the soldiers would become euphoric yet oddly calm at the same time.

After the drug was modified by adding a chlorine atom and renamed chlorpromazine, it fast became a go-to treatment for psychosis. At the time, no one made the connection to dopamine. Contemporary doctors believed that it calmed people by lowering body temperature (common treatments for mental illness back in the day included swaddling patients in cold, wet sheets). Yet just like reserpine, chlorpromazine produced range of nasty side effects that closely mimicked Parkinson’s disease. This led a Dutch pharmacologist, Jacques van Rossum, to hypothesize that dopamine receptor blockade could explain chlorpromazine’s antipsychotic effects – an idea that remains widely accepted today.

In the 1970s, dopamine was linked with addiction through research on rodents, and this novel idea caught people’s imagination over the coming decades. A story on dopamine titled, “How We Get Addicted,” made the cover of Time in 1997.

Yet as the dopamine/addiction connection became widespread, it also became oversimplified. According to a 2015 article in Nature Reviews Neuroscience, a wave of low-quality research followed – nonreplicated, insufficient – which led the authors to conclude that we are “addicted to the dopamine theory of addiction.” Just about every pleasure under the sun was being attributed to dopamine, from eating delicious foods and playing computer games to sex, music, and hot showers. As recent science shows, however, dopamine is not simply about pleasure – it’s about reward prediction, response to stress, memory, learning, and even the functioning of the immune system. Since its first synthesis in the early 20th century, dopamine has often been misunderstood and oversimplified – and it seems the story is repeating itself now.

In one of his final interviews, Dr. Carlsson, who passed away in 2018 at the age of 95, warned about playing around with dopamine and, in particular, prescribing drugs that have an inhibitory action on this neurotransmitter. “Dopamine is involved in everything that happens in our brains – all its important functions,” he said.

We should be careful how we handle such a delicate and still little-known system.

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

Despite money’s central role in our psychic lives, many trainees – and some seasoned practitioners – skirt around financial issues. Some clinicians confess that inquiring about patients’ finances feels “too personal.” They fear that asking about money could suggest that the clinician is primarily concerned with getting paid. Some clinicians feel that looking into patients’ finances might be unprofessional, outside one’s scope of practice. But it is not.

Trainees often receive little guidance concerning money matters in patients’ lives and treatments, considerations we have labeled clinical psychoeconomics. Considerable evidence suggests that financial concerns often provoke emotional distress and dysfunctional behaviors, and directly influence patient’s health care decisions. Financial issues also influence how clinicians view and react to patients.

We have recently reviewed (and illustrated through case vignettes) how money matters might impact psychiatric assessment, case formulation, treatment planning, and ongoing psychiatric treatments including psychotherapies.¹ Consider how money affects people’s lives: Money helps people meet multiple practical, psychological, and social needs by enabling them to obtain food, clothing, shelter, other material goods, services, discretionary time, and opportunities. And money strongly influences relationships. Regardless of poverty or wealth, thoughts and behaviors connected to acquiring, possessing, and disposing of money, and feelings accompanying these processes such as greed, neediness, envy, pride, shame, guilt, and self-satisfaction often underly intrapsychic and interpersonal conflicts.

Individuals constantly engage in numerous simultaneous conscious, preconscious, and unconscious neuro-economic trade-offs that determine goals, efforts, and timing. Many are financially influenced. Money influences how virtually all patients seek, receive, and sustain their mental health care including psychotherapy.

Money problems can be associated with insecurity, impotence, feeling unloved, and lack of freedom or subjugation. Individuals may resent how they’re forced to acquire money, and feel shamed or morally injured by their jobs, financial dependence on other family members, public assistance, or their questionable ways of obtaining money.

Impoverished individuals may face choosing between food, housing, medications, and medical care. Domestically abused individuals may reluctantly remain with their abusers, risking physical harm or death rather than face destitution. Some families tolerate severely disabled individuals at home because they rely on their disability checks and caregiver payments. Suicides may turn on how individuals forecast financial repercussions affecting their families. Desires to avoid debt may lead to treatment avoidance.

Individuals with enough money to get by face daily financially related choices involving competing needs, desires, values, and loyalties. They may experience conflicts concerning spending on necessities vs. indulgences or spending on oneself vs. significant others.

Whereas some wealthy individuals may assume unwarranted airs of superiority and entitlement, others may feel guilty about wealth, or fearful that others like them only for their money. Individuals on the receiving end of wealth may feel emotionally and behaviorally manipulated by their benefactors.
 

Assessment

Assessments should consider how financial matters have shaped patients’ early psychological development as well their current lives. How do patients’ emotions, thoughts, and behaviors reflect money matters? What money-related pathologies are evident? What aspects of the patient’s “financial world” seem modifiable?

Financial questions should be posed colloquially. Screeners include: “Where do you live?”, “Who’s in the home?”, “How do you (all) manage financially?”, “What do you all do for a living?”, “How do you make ends meet?”, and “What financial problems are you facing?” Clinicians can quickly learn about patients’ financial self-sufficiencies, individuals for whom they bear financial responsibility, and others they rely on for support, for example, relatives. If patients avoid answering such questions forthrightly, particularly when financial arrangements are “complicated,” clinicians will want to revisit these issues later after establishing a firmer alliance but continue to wonder about the meaning of the patient’s reluctance.

Clinically, money matters manifest intrapsychically or interpersonally in three ways: as explicit conflicts, implicit issues, and unequivocal money-related pathologies. When explicit, patients, families, and couples are fully aware of the conflicts but have difficulty resolving financial disputes. When conflicts are implicit, money problems may be unacknowledged, avoided, denied, or minimized. Conflicts concerning money are often transmitted trans-generationally.

Psychopathological conditions unequivocally linked to money include compulsive shopping, gambling disorders, miserly hoarding, impulse buying, and spending sprees during hypomanic and manic states. Mounting debts may create progressively insurmountable sources of distress. Money can be weaponized to sadistically create enticement, envy, or deprivation. Some monetarily antisocial individuals compromise interpersonal relationships as well as treatments. Individuals with alcohol/substance use disorders may spend so much on substances that little is left for necessities. Financially needy individuals may engage in morally questionable behaviors they might otherwise shun.
 

Case formulation and treatment planning

Incorporating money matters into case formulations entails demonstrating how financial concerns influenced maladaptive development and distort current attitudes, perceptions, and behaviors.

Concurrently, clinicians should acknowledge patients’ reality-based fiscal decisions, appreciating cultural and family value differences concerning how money should be acquired and spent. Since money often determines frequency and duration of treatment visits, clinicians are ethically obligated to discuss with patients what they might expect from different medications and psychotherapies, and their comparative costs.
 

Money matters’ impact on psychotherapies

Money matters often affect transference and countertransference reactions. Some reactions stem from how patients and clinicians compare their own financial situations with those of the other.

To help identify and ameliorate money-related countertransference responses, clinicians can reflect on questions such as: “How comfortable are you with people who are much poorer or richer than you are?” “How comfortable are you with impoverished individuals or with multimillionaires or their children?” And “why?” For trainees, all these reactions should be discussed in supervision.
 

Conclusions

To summarize, four clinical psychoeconomic issues should be routinely assessed and factored into psychiatric case formulations and treatment plans: how financial issues 1) have impacted patients’ psychological development; 2) impact patients’ current lives; 3) are likely to impact access, type, intensity, and duration of treatment visits; and 4) might provoke money-related transference and countertransference concerns.

In advising patients about treatment options, clinicians should discuss each treatment’s relative effectiveness and estimated costs of care. Patients’ decisions will likely be heavily influenced by financial considerations.

Dr. Yager is based in the department of psychiatry, University of Colorado at Denver, Aurora. Dr. Kay is based in the department of psychiatry, Wright State University, Dayton, Ohio. No external funds were received for this project, and the authors have no conflicts to disclose.

Reference

1. Yager J and Kay J. Money matters in psychiatric assessment, case formulation, treatment planning, and ongoing psychotherapy: Clinical psychoeconomics. J Nerv Ment Dis. 2022 Jun 10. doi: 10.1097/NMD.0000000000001552.

Despite money’s central role in our psychic lives, many trainees – and some seasoned practitioners – skirt around financial issues. Some clinicians confess that inquiring about patients’ finances feels “too personal.” They fear that asking about money could suggest that the clinician is primarily concerned with getting paid. Some clinicians feel that looking into patients’ finances might be unprofessional, outside one’s scope of practice. But it is not.

Trainees often receive little guidance concerning money matters in patients’ lives and treatments, considerations we have labeled clinical psychoeconomics. Considerable evidence suggests that financial concerns often provoke emotional distress and dysfunctional behaviors, and directly influence patient’s health care decisions. Financial issues also influence how clinicians view and react to patients.

We have recently reviewed (and illustrated through case vignettes) how money matters might impact psychiatric assessment, case formulation, treatment planning, and ongoing psychiatric treatments including psychotherapies.¹ Consider how money affects people’s lives: Money helps people meet multiple practical, psychological, and social needs by enabling them to obtain food, clothing, shelter, other material goods, services, discretionary time, and opportunities. And money strongly influences relationships. Regardless of poverty or wealth, thoughts and behaviors connected to acquiring, possessing, and disposing of money, and feelings accompanying these processes such as greed, neediness, envy, pride, shame, guilt, and self-satisfaction often underly intrapsychic and interpersonal conflicts.

Individuals constantly engage in numerous simultaneous conscious, preconscious, and unconscious neuro-economic trade-offs that determine goals, efforts, and timing. Many are financially influenced. Money influences how virtually all patients seek, receive, and sustain their mental health care including psychotherapy.

Money problems can be associated with insecurity, impotence, feeling unloved, and lack of freedom or subjugation. Individuals may resent how they’re forced to acquire money, and feel shamed or morally injured by their jobs, financial dependence on other family members, public assistance, or their questionable ways of obtaining money.

Impoverished individuals may face choosing between food, housing, medications, and medical care. Domestically abused individuals may reluctantly remain with their abusers, risking physical harm or death rather than face destitution. Some families tolerate severely disabled individuals at home because they rely on their disability checks and caregiver payments. Suicides may turn on how individuals forecast financial repercussions affecting their families. Desires to avoid debt may lead to treatment avoidance.

Individuals with enough money to get by face daily financially related choices involving competing needs, desires, values, and loyalties. They may experience conflicts concerning spending on necessities vs. indulgences or spending on oneself vs. significant others.

Whereas some wealthy individuals may assume unwarranted airs of superiority and entitlement, others may feel guilty about wealth, or fearful that others like them only for their money. Individuals on the receiving end of wealth may feel emotionally and behaviorally manipulated by their benefactors.
 

Assessment

Assessments should consider how financial matters have shaped patients’ early psychological development as well their current lives. How do patients’ emotions, thoughts, and behaviors reflect money matters? What money-related pathologies are evident? What aspects of the patient’s “financial world” seem modifiable?

Financial questions should be posed colloquially. Screeners include: “Where do you live?”, “Who’s in the home?”, “How do you (all) manage financially?”, “What do you all do for a living?”, “How do you make ends meet?”, and “What financial problems are you facing?” Clinicians can quickly learn about patients’ financial self-sufficiencies, individuals for whom they bear financial responsibility, and others they rely on for support, for example, relatives. If patients avoid answering such questions forthrightly, particularly when financial arrangements are “complicated,” clinicians will want to revisit these issues later after establishing a firmer alliance but continue to wonder about the meaning of the patient’s reluctance.

Clinically, money matters manifest intrapsychically or interpersonally in three ways: as explicit conflicts, implicit issues, and unequivocal money-related pathologies. When explicit, patients, families, and couples are fully aware of the conflicts but have difficulty resolving financial disputes. When conflicts are implicit, money problems may be unacknowledged, avoided, denied, or minimized. Conflicts concerning money are often transmitted trans-generationally.

Psychopathological conditions unequivocally linked to money include compulsive shopping, gambling disorders, miserly hoarding, impulse buying, and spending sprees during hypomanic and manic states. Mounting debts may create progressively insurmountable sources of distress. Money can be weaponized to sadistically create enticement, envy, or deprivation. Some monetarily antisocial individuals compromise interpersonal relationships as well as treatments. Individuals with alcohol/substance use disorders may spend so much on substances that little is left for necessities. Financially needy individuals may engage in morally questionable behaviors they might otherwise shun.
 

Case formulation and treatment planning

Incorporating money matters into case formulations entails demonstrating how financial concerns influenced maladaptive development and distort current attitudes, perceptions, and behaviors.

Concurrently, clinicians should acknowledge patients’ reality-based fiscal decisions, appreciating cultural and family value differences concerning how money should be acquired and spent. Since money often determines frequency and duration of treatment visits, clinicians are ethically obligated to discuss with patients what they might expect from different medications and psychotherapies, and their comparative costs.
 

Money matters’ impact on psychotherapies

Money matters often affect transference and countertransference reactions. Some reactions stem from how patients and clinicians compare their own financial situations with those of the other.

To help identify and ameliorate money-related countertransference responses, clinicians can reflect on questions such as: “How comfortable are you with people who are much poorer or richer than you are?” “How comfortable are you with impoverished individuals or with multimillionaires or their children?” And “why?” For trainees, all these reactions should be discussed in supervision.
 

Conclusions

To summarize, four clinical psychoeconomic issues should be routinely assessed and factored into psychiatric case formulations and treatment plans: how financial issues 1) have impacted patients’ psychological development; 2) impact patients’ current lives; 3) are likely to impact access, type, intensity, and duration of treatment visits; and 4) might provoke money-related transference and countertransference concerns.

In advising patients about treatment options, clinicians should discuss each treatment’s relative effectiveness and estimated costs of care. Patients’ decisions will likely be heavily influenced by financial considerations.

Dr. Yager is based in the department of psychiatry, University of Colorado at Denver, Aurora. Dr. Kay is based in the department of psychiatry, Wright State University, Dayton, Ohio. No external funds were received for this project, and the authors have no conflicts to disclose.

Reference

1. Yager J and Kay J. Money matters in psychiatric assessment, case formulation, treatment planning, and ongoing psychotherapy: Clinical psychoeconomics. J Nerv Ment Dis. 2022 Jun 10. doi: 10.1097/NMD.0000000000001552.

Despite money’s central role in our psychic lives, many trainees – and some seasoned practitioners – skirt around financial issues. Some clinicians confess that inquiring about patients’ finances feels “too personal.” They fear that asking about money could suggest that the clinician is primarily concerned with getting paid. Some clinicians feel that looking into patients’ finances might be unprofessional, outside one’s scope of practice. But it is not.

Trainees often receive little guidance concerning money matters in patients’ lives and treatments, considerations we have labeled clinical psychoeconomics. Considerable evidence suggests that financial concerns often provoke emotional distress and dysfunctional behaviors, and directly influence patient’s health care decisions. Financial issues also influence how clinicians view and react to patients.

We have recently reviewed (and illustrated through case vignettes) how money matters might impact psychiatric assessment, case formulation, treatment planning, and ongoing psychiatric treatments including psychotherapies.¹ Consider how money affects people’s lives: Money helps people meet multiple practical, psychological, and social needs by enabling them to obtain food, clothing, shelter, other material goods, services, discretionary time, and opportunities. And money strongly influences relationships. Regardless of poverty or wealth, thoughts and behaviors connected to acquiring, possessing, and disposing of money, and feelings accompanying these processes such as greed, neediness, envy, pride, shame, guilt, and self-satisfaction often underly intrapsychic and interpersonal conflicts.

Individuals constantly engage in numerous simultaneous conscious, preconscious, and unconscious neuro-economic trade-offs that determine goals, efforts, and timing. Many are financially influenced. Money influences how virtually all patients seek, receive, and sustain their mental health care including psychotherapy.

Money problems can be associated with insecurity, impotence, feeling unloved, and lack of freedom or subjugation. Individuals may resent how they’re forced to acquire money, and feel shamed or morally injured by their jobs, financial dependence on other family members, public assistance, or their questionable ways of obtaining money.

Impoverished individuals may face choosing between food, housing, medications, and medical care. Domestically abused individuals may reluctantly remain with their abusers, risking physical harm or death rather than face destitution. Some families tolerate severely disabled individuals at home because they rely on their disability checks and caregiver payments. Suicides may turn on how individuals forecast financial repercussions affecting their families. Desires to avoid debt may lead to treatment avoidance.

Individuals with enough money to get by face daily financially related choices involving competing needs, desires, values, and loyalties. They may experience conflicts concerning spending on necessities vs. indulgences or spending on oneself vs. significant others.

Whereas some wealthy individuals may assume unwarranted airs of superiority and entitlement, others may feel guilty about wealth, or fearful that others like them only for their money. Individuals on the receiving end of wealth may feel emotionally and behaviorally manipulated by their benefactors.
 

Assessment

Assessments should consider how financial matters have shaped patients’ early psychological development as well their current lives. How do patients’ emotions, thoughts, and behaviors reflect money matters? What money-related pathologies are evident? What aspects of the patient’s “financial world” seem modifiable?

Financial questions should be posed colloquially. Screeners include: “Where do you live?”, “Who’s in the home?”, “How do you (all) manage financially?”, “What do you all do for a living?”, “How do you make ends meet?”, and “What financial problems are you facing?” Clinicians can quickly learn about patients’ financial self-sufficiencies, individuals for whom they bear financial responsibility, and others they rely on for support, for example, relatives. If patients avoid answering such questions forthrightly, particularly when financial arrangements are “complicated,” clinicians will want to revisit these issues later after establishing a firmer alliance but continue to wonder about the meaning of the patient’s reluctance.

Clinically, money matters manifest intrapsychically or interpersonally in three ways: as explicit conflicts, implicit issues, and unequivocal money-related pathologies. When explicit, patients, families, and couples are fully aware of the conflicts but have difficulty resolving financial disputes. When conflicts are implicit, money problems may be unacknowledged, avoided, denied, or minimized. Conflicts concerning money are often transmitted trans-generationally.

Psychopathological conditions unequivocally linked to money include compulsive shopping, gambling disorders, miserly hoarding, impulse buying, and spending sprees during hypomanic and manic states. Mounting debts may create progressively insurmountable sources of distress. Money can be weaponized to sadistically create enticement, envy, or deprivation. Some monetarily antisocial individuals compromise interpersonal relationships as well as treatments. Individuals with alcohol/substance use disorders may spend so much on substances that little is left for necessities. Financially needy individuals may engage in morally questionable behaviors they might otherwise shun.
 

Case formulation and treatment planning

Incorporating money matters into case formulations entails demonstrating how financial concerns influenced maladaptive development and distort current attitudes, perceptions, and behaviors.

Concurrently, clinicians should acknowledge patients’ reality-based fiscal decisions, appreciating cultural and family value differences concerning how money should be acquired and spent. Since money often determines frequency and duration of treatment visits, clinicians are ethically obligated to discuss with patients what they might expect from different medications and psychotherapies, and their comparative costs.
 

Money matters’ impact on psychotherapies

Money matters often affect transference and countertransference reactions. Some reactions stem from how patients and clinicians compare their own financial situations with those of the other.

To help identify and ameliorate money-related countertransference responses, clinicians can reflect on questions such as: “How comfortable are you with people who are much poorer or richer than you are?” “How comfortable are you with impoverished individuals or with multimillionaires or their children?” And “why?” For trainees, all these reactions should be discussed in supervision.
 

Conclusions

To summarize, four clinical psychoeconomic issues should be routinely assessed and factored into psychiatric case formulations and treatment plans: how financial issues 1) have impacted patients’ psychological development; 2) impact patients’ current lives; 3) are likely to impact access, type, intensity, and duration of treatment visits; and 4) might provoke money-related transference and countertransference concerns.

In advising patients about treatment options, clinicians should discuss each treatment’s relative effectiveness and estimated costs of care. Patients’ decisions will likely be heavily influenced by financial considerations.

Dr. Yager is based in the department of psychiatry, University of Colorado at Denver, Aurora. Dr. Kay is based in the department of psychiatry, Wright State University, Dayton, Ohio. No external funds were received for this project, and the authors have no conflicts to disclose.

Reference

1. Yager J and Kay J. Money matters in psychiatric assessment, case formulation, treatment planning, and ongoing psychotherapy: Clinical psychoeconomics. J Nerv Ment Dis. 2022 Jun 10. doi: 10.1097/NMD.0000000000001552.

Starting treatment for alcohol use disorder (AUD) with extended-release naltrexone injections in the emergency department produced a dramatic reduction in alcohol consumption, according to findings presented at the annual meeting of the American College of Emergency Physicians.

The results show the feasibility of such a program and underscore the importance of the ED in combating AUD, said the researchers, from the University of California, San Francisco.

“According to the National Institute on Alcohol Abuse and Alcoholism, 18% of ED visits had alcohol as a contributing factor – the volume of alcohol-related ED visits has been climbing every year, and it is a significant public health problem,” said Maria Raven, MD, MPH, professor of emergency medicine at UCSF. “Right now, we do very little for people who come to the ED with AUD, so it is a missed opportunity to intervene, especially given the volume of visits we see and that our patient population is one that often has significant barriers to accessing outpatient treatment.”

The findings come from a 12-week, prospective, single-arm study of ED patients who were actively drinking adults with known or suspected AUD and who had positive scores on a screening test. Of 179 patients who were approached, 32 agreed to enroll; the enrollment yield was 18%. Participants were given monthly extended-release naltrexone and case management services.

Of the 32 participants, 25 completed all their study visits and 22 (69%) continued taking naltrexone after the 12 weeks.

The researchers said the results surprised them. The average daily alcohol consumption at baseline was 7.6 drinks a day, and it fell by 7.5 drinks a day – in other words, to almost no consumption.

“The median alcohol consumption when measured over the last 2 weeks of the study was zero,” Dr. Raven said. “This doesn’t mean everyone was at zero, but this was the median and reflects that many participants stopped drinking altogether. We were pleasantly surprised by this. I don’t know that we thought so many people who participated would actually fully abstain.”

On the Kemp Quality of Life Scale – with scores from 1 to 7, with 1 being “life is very distressing,” 4 being “life is so-so,” and 7 being “life is great” – the average baseline score was 3.6. That score rose by 1.2 points by the study’s end.

Dr. Raven said she hoped more would enroll but that “a number of people actually did not want the injection or were not ready to think about stopping.” Still, the 18% enrollment is “a major improvement,” considering that no attempt was made to initiate treatment with naltrexone prior to the study. Oral naltrexone, rather than the injection, could be offered to improve participation, but oral naltrexone has to be taken daily.

She said a larger study is planned at UCSF and that other institutions are interested in starting a similar program.

“When someone is in the ED for an AUD-related issue, it can serve as a turning point for them in some cases,” she said.

Erik S. Anderson, MD, associate research director at Oakland, Calif.–based Alameda Health System, who has studied naltrexone in the ED, said the findings dovetail with what his team has found at his center. He added that psychosocial support is important as well and that his team has found that navigation services are the most important factor in connecting patients with follow-up care – even more so than providing medications.

“In my mind, this is a situation where we have treatment options and approaches that work, and it’s really about implementing these services in a novel care setting,” he said. “ED patients are at higher risk of complications for AUD simply because they are in the ED in the first place – initiating AUD treatment in this setting is the right thing to do.”

Dr. Raven and Dr. Anderson disclosed no relevant financial relationships.

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

Starting treatment for alcohol use disorder (AUD) with extended-release naltrexone injections in the emergency department produced a dramatic reduction in alcohol consumption, according to findings presented at the annual meeting of the American College of Emergency Physicians.

The results show the feasibility of such a program and underscore the importance of the ED in combating AUD, said the researchers, from the University of California, San Francisco.

“According to the National Institute on Alcohol Abuse and Alcoholism, 18% of ED visits had alcohol as a contributing factor – the volume of alcohol-related ED visits has been climbing every year, and it is a significant public health problem,” said Maria Raven, MD, MPH, professor of emergency medicine at UCSF. “Right now, we do very little for people who come to the ED with AUD, so it is a missed opportunity to intervene, especially given the volume of visits we see and that our patient population is one that often has significant barriers to accessing outpatient treatment.”

The findings come from a 12-week, prospective, single-arm study of ED patients who were actively drinking adults with known or suspected AUD and who had positive scores on a screening test. Of 179 patients who were approached, 32 agreed to enroll; the enrollment yield was 18%. Participants were given monthly extended-release naltrexone and case management services.

Of the 32 participants, 25 completed all their study visits and 22 (69%) continued taking naltrexone after the 12 weeks.

The researchers said the results surprised them. The average daily alcohol consumption at baseline was 7.6 drinks a day, and it fell by 7.5 drinks a day – in other words, to almost no consumption.

“The median alcohol consumption when measured over the last 2 weeks of the study was zero,” Dr. Raven said. “This doesn’t mean everyone was at zero, but this was the median and reflects that many participants stopped drinking altogether. We were pleasantly surprised by this. I don’t know that we thought so many people who participated would actually fully abstain.”

On the Kemp Quality of Life Scale – with scores from 1 to 7, with 1 being “life is very distressing,” 4 being “life is so-so,” and 7 being “life is great” – the average baseline score was 3.6. That score rose by 1.2 points by the study’s end.

Dr. Raven said she hoped more would enroll but that “a number of people actually did not want the injection or were not ready to think about stopping.” Still, the 18% enrollment is “a major improvement,” considering that no attempt was made to initiate treatment with naltrexone prior to the study. Oral naltrexone, rather than the injection, could be offered to improve participation, but oral naltrexone has to be taken daily.

She said a larger study is planned at UCSF and that other institutions are interested in starting a similar program.

“When someone is in the ED for an AUD-related issue, it can serve as a turning point for them in some cases,” she said.

Erik S. Anderson, MD, associate research director at Oakland, Calif.–based Alameda Health System, who has studied naltrexone in the ED, said the findings dovetail with what his team has found at his center. He added that psychosocial support is important as well and that his team has found that navigation services are the most important factor in connecting patients with follow-up care – even more so than providing medications.

“In my mind, this is a situation where we have treatment options and approaches that work, and it’s really about implementing these services in a novel care setting,” he said. “ED patients are at higher risk of complications for AUD simply because they are in the ED in the first place – initiating AUD treatment in this setting is the right thing to do.”

Dr. Raven and Dr. Anderson disclosed no relevant financial relationships.

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

Starting treatment for alcohol use disorder (AUD) with extended-release naltrexone injections in the emergency department produced a dramatic reduction in alcohol consumption, according to findings presented at the annual meeting of the American College of Emergency Physicians.

The results show the feasibility of such a program and underscore the importance of the ED in combating AUD, said the researchers, from the University of California, San Francisco.

“According to the National Institute on Alcohol Abuse and Alcoholism, 18% of ED visits had alcohol as a contributing factor – the volume of alcohol-related ED visits has been climbing every year, and it is a significant public health problem,” said Maria Raven, MD, MPH, professor of emergency medicine at UCSF. “Right now, we do very little for people who come to the ED with AUD, so it is a missed opportunity to intervene, especially given the volume of visits we see and that our patient population is one that often has significant barriers to accessing outpatient treatment.”

The findings come from a 12-week, prospective, single-arm study of ED patients who were actively drinking adults with known or suspected AUD and who had positive scores on a screening test. Of 179 patients who were approached, 32 agreed to enroll; the enrollment yield was 18%. Participants were given monthly extended-release naltrexone and case management services.

Of the 32 participants, 25 completed all their study visits and 22 (69%) continued taking naltrexone after the 12 weeks.

The researchers said the results surprised them. The average daily alcohol consumption at baseline was 7.6 drinks a day, and it fell by 7.5 drinks a day – in other words, to almost no consumption.

“The median alcohol consumption when measured over the last 2 weeks of the study was zero,” Dr. Raven said. “This doesn’t mean everyone was at zero, but this was the median and reflects that many participants stopped drinking altogether. We were pleasantly surprised by this. I don’t know that we thought so many people who participated would actually fully abstain.”

On the Kemp Quality of Life Scale – with scores from 1 to 7, with 1 being “life is very distressing,” 4 being “life is so-so,” and 7 being “life is great” – the average baseline score was 3.6. That score rose by 1.2 points by the study’s end.

Dr. Raven said she hoped more would enroll but that “a number of people actually did not want the injection or were not ready to think about stopping.” Still, the 18% enrollment is “a major improvement,” considering that no attempt was made to initiate treatment with naltrexone prior to the study. Oral naltrexone, rather than the injection, could be offered to improve participation, but oral naltrexone has to be taken daily.

She said a larger study is planned at UCSF and that other institutions are interested in starting a similar program.

“When someone is in the ED for an AUD-related issue, it can serve as a turning point for them in some cases,” she said.

Erik S. Anderson, MD, associate research director at Oakland, Calif.–based Alameda Health System, who has studied naltrexone in the ED, said the findings dovetail with what his team has found at his center. He added that psychosocial support is important as well and that his team has found that navigation services are the most important factor in connecting patients with follow-up care – even more so than providing medications.

“In my mind, this is a situation where we have treatment options and approaches that work, and it’s really about implementing these services in a novel care setting,” he said. “ED patients are at higher risk of complications for AUD simply because they are in the ED in the first place – initiating AUD treatment in this setting is the right thing to do.”

Dr. Raven and Dr. Anderson disclosed no relevant financial relationships.

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

Murray et al have written a timely, thoughtful, and useful article (“Smoking cessation: Varenicline and the risk of neuropsychiatric adverse events,” Current Psychiatry, July 2022, p. 41-45) about the role of the nicotinic acetylcholine receptor partial agonist varenicline for helping patients stop smoking, which is still the main preventable cause of morbidity and premature death. Smoking remains a major problem among patients who are chronically mentally ill and those with substance use disorders, as well as “recovering” populations such as Alcoholic Anonymous participants.¹ Reviews of the EAGLES trial and other research analyses have gone a long way to allaying anxiety about interventions for smoking cessation.²

Just a few caveats regarding Murray et al’s excellent summary:

• The article did not address that nicotine is consumed in multiple ways, such as vaping, snuff, chewing tobacco, and hookah

• The safety of varenicline appears fair when psychiatric illness is well controlled but can be problematic (and even severely detrimental) when mental illness is not well controlled. This should not be glossed over, especially since it was the reason for the original black-box warning (for risks including behavioral impulsivity, suicidality, severe insomnia, and nightmares) that was removed in 2016

• Patients with severe mental illness may not fully understand the risks, benefits, and priorities of the treatment intervention. The importance of psychiatric and internal medicine in addition to pharmacy follow-up is critical and needs to be documented.

Varenicline has been contextualized in its current role as a first-line treatment for smoking cessation. By bypassing a sizeable population of patients who have unstable psychiatric illness (especially bipolar I disorder), the path has been opened for risky “off-label” varenicline prescribing to this population by internists, who should be very cautious and prudent about prescribing for such patients. This alone is probably a good reason to reinstate the black-box warning.

Interestingly, one review found that only 1 of 11 patients receiving varenicline stopped smoking.¹ Not dramatically beneficial for a first-line treatment! Decreasing smoking occurs as well and is more robust with combinational use with bupropion, nicotine replacement therapy, and cognitive-behavioral therapy.

If we are focusing on patients with unstable mental illness—who are seen primarily by psychiatrists—adherence, urgency of intervention, and context regarding acute safety for this population must be seen as top priorities.

So-called “second-line” treatment options must also be considered. Sandiego et al³ make excellent points regarding the role of alpha-adrenergic agonists such as guanfacine, which have been shown to be helpful in smoking cessation. They work by decreasing cortical dopamine release and their calming effects on the noradrenergic system, which may decrease smoking precipitated by stress. For the particularly challenging subpopulation of unstable smokers, the combination of varenicline plus guanfacine ER may turn out to be a game-changer.

Varenicline has not proven itself to be useful in patients who are severely mentally ill, and due to its low success rate, expectations should remain tempered, pragmatically realistic, and safety-based.^4,5 The bottom line is that in an unstable psychiatrically ill patient, interventions other than varenicline should be first-line.

Murray et al have written a timely, thoughtful, and useful article (“Smoking cessation: Varenicline and the risk of neuropsychiatric adverse events,” Current Psychiatry, July 2022, p. 41-45) about the role of the nicotinic acetylcholine receptor partial agonist varenicline for helping patients stop smoking, which is still the main preventable cause of morbidity and premature death. Smoking remains a major problem among patients who are chronically mentally ill and those with substance use disorders, as well as “recovering” populations such as Alcoholic Anonymous participants.¹ Reviews of the EAGLES trial and other research analyses have gone a long way to allaying anxiety about interventions for smoking cessation.²

Just a few caveats regarding Murray et al’s excellent summary:

• The article did not address that nicotine is consumed in multiple ways, such as vaping, snuff, chewing tobacco, and hookah

• The safety of varenicline appears fair when psychiatric illness is well controlled but can be problematic (and even severely detrimental) when mental illness is not well controlled. This should not be glossed over, especially since it was the reason for the original black-box warning (for risks including behavioral impulsivity, suicidality, severe insomnia, and nightmares) that was removed in 2016

• Patients with severe mental illness may not fully understand the risks, benefits, and priorities of the treatment intervention. The importance of psychiatric and internal medicine in addition to pharmacy follow-up is critical and needs to be documented.

Varenicline has been contextualized in its current role as a first-line treatment for smoking cessation. By bypassing a sizeable population of patients who have unstable psychiatric illness (especially bipolar I disorder), the path has been opened for risky “off-label” varenicline prescribing to this population by internists, who should be very cautious and prudent about prescribing for such patients. This alone is probably a good reason to reinstate the black-box warning.

Interestingly, one review found that only 1 of 11 patients receiving varenicline stopped smoking.¹ Not dramatically beneficial for a first-line treatment! Decreasing smoking occurs as well and is more robust with combinational use with bupropion, nicotine replacement therapy, and cognitive-behavioral therapy.

If we are focusing on patients with unstable mental illness—who are seen primarily by psychiatrists—adherence, urgency of intervention, and context regarding acute safety for this population must be seen as top priorities.

So-called “second-line” treatment options must also be considered. Sandiego et al³ make excellent points regarding the role of alpha-adrenergic agonists such as guanfacine, which have been shown to be helpful in smoking cessation. They work by decreasing cortical dopamine release and their calming effects on the noradrenergic system, which may decrease smoking precipitated by stress. For the particularly challenging subpopulation of unstable smokers, the combination of varenicline plus guanfacine ER may turn out to be a game-changer.

Varenicline has not proven itself to be useful in patients who are severely mentally ill, and due to its low success rate, expectations should remain tempered, pragmatically realistic, and safety-based.^4,5 The bottom line is that in an unstable psychiatrically ill patient, interventions other than varenicline should be first-line.

Murray et al have written a timely, thoughtful, and useful article (“Smoking cessation: Varenicline and the risk of neuropsychiatric adverse events,” Current Psychiatry, July 2022, p. 41-45) about the role of the nicotinic acetylcholine receptor partial agonist varenicline for helping patients stop smoking, which is still the main preventable cause of morbidity and premature death. Smoking remains a major problem among patients who are chronically mentally ill and those with substance use disorders, as well as “recovering” populations such as Alcoholic Anonymous participants.¹ Reviews of the EAGLES trial and other research analyses have gone a long way to allaying anxiety about interventions for smoking cessation.²

Just a few caveats regarding Murray et al’s excellent summary:

• The article did not address that nicotine is consumed in multiple ways, such as vaping, snuff, chewing tobacco, and hookah

• The safety of varenicline appears fair when psychiatric illness is well controlled but can be problematic (and even severely detrimental) when mental illness is not well controlled. This should not be glossed over, especially since it was the reason for the original black-box warning (for risks including behavioral impulsivity, suicidality, severe insomnia, and nightmares) that was removed in 2016

• Patients with severe mental illness may not fully understand the risks, benefits, and priorities of the treatment intervention. The importance of psychiatric and internal medicine in addition to pharmacy follow-up is critical and needs to be documented.

Varenicline has been contextualized in its current role as a first-line treatment for smoking cessation. By bypassing a sizeable population of patients who have unstable psychiatric illness (especially bipolar I disorder), the path has been opened for risky “off-label” varenicline prescribing to this population by internists, who should be very cautious and prudent about prescribing for such patients. This alone is probably a good reason to reinstate the black-box warning.

Interestingly, one review found that only 1 of 11 patients receiving varenicline stopped smoking.¹ Not dramatically beneficial for a first-line treatment! Decreasing smoking occurs as well and is more robust with combinational use with bupropion, nicotine replacement therapy, and cognitive-behavioral therapy.

If we are focusing on patients with unstable mental illness—who are seen primarily by psychiatrists—adherence, urgency of intervention, and context regarding acute safety for this population must be seen as top priorities.

So-called “second-line” treatment options must also be considered. Sandiego et al³ make excellent points regarding the role of alpha-adrenergic agonists such as guanfacine, which have been shown to be helpful in smoking cessation. They work by decreasing cortical dopamine release and their calming effects on the noradrenergic system, which may decrease smoking precipitated by stress. For the particularly challenging subpopulation of unstable smokers, the combination of varenicline plus guanfacine ER may turn out to be a game-changer.

Varenicline has not proven itself to be useful in patients who are severely mentally ill, and due to its low success rate, expectations should remain tempered, pragmatically realistic, and safety-based.^4,5 The bottom line is that in an unstable psychiatrically ill patient, interventions other than varenicline should be first-line.