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If you give a mouse a genetically engineered bitcoin wallet
The world’s most valuable mouse
You’ve heard of Mighty Mouse. Now say hello to the world’s newest mouse superhero, Crypto-Mouse! After being bitten by a radioactive cryptocurrency investor, Crypto-Mouse can tap directly into the power of the blockchain itself, allowing it to perform incredible, death-defying feats of strength!
We’re going to stop right there before Crypto-Mouse gains entry into the Marvel cinematic universe. Let’s rewind to the beginning, because that’s precisely where this crazy scheme is at. In late January, a new decentralized autonomous organization, BitMouseDAO, launched to enormous … -ly little fanfare, according to Vice. Two investors as of Jan. 31. But what they lack in money they make up for in sheer ambition.
BitMouseDAO’s $100 million dollar idea is to genetically engineer mice to carry bitcoin, the first cryptocurrency and one of the most valuable. This isn’t as crazy an idea as it sounds since DNA can be modified to store information, potentially even bitcoin information. Their plan is to create a private bitcoin wallet, which will be stored in the mouse DNA, and purchase online bitcoin to store in this wallet.
BitMouseDAO, being a “collection of artists,” plans to partner with a lab to translate its private key into a specific DNA sequence to be encoded into the mice during fertilization; or, if that doesn’t work, inject them with a harmless virus that carries the key.
Since these are artists, their ultimate plan is to use their bitcoin mice to make NFTs (scratch that off your cryptocurrency bingo card) and auction them off to people. Or, as Vice put it, BitMouseDAO essentially plans to send preserved dead mice to people. Artistic dead mice! Artistic dead mice worth millions! Maybe. Even BitMouseDAO admits bitcoin could be worthless by the time the project gets off the ground.
If this all sounds completely insane, that’s because it is. But it also sounds crazy enough to work. Now, if you’ll excuse us, we’re off to write a screenplay about a scrappy group of high-tech thieves who steal a group of genetically altered bitcoin mice to sell for millions, only to keep them as their adorable pets. Trust us Hollywood, it’ll make millions!
Alcoholic monkeys vs. the future of feces
Which is more important, the journey or the destination? Science is all about the destination, yes? Solving the problem, saving a life, expanding horizons. That’s science. Or is it? The scientific method is a process, so does that make it a journey?
For us, today’s journey begins at the University of Iowa, where investigators are trying to reduce alcohol consumption. A worthy goal, and they seem to have made some progress by targeting a liver hormone called fibroblast growth factor 21 (FGF21). But we’re more interested in the process right now, so bring on the alcoholic monkeys. And no, that’s not a death metal/reggae fusion band. Should be, though.
“The vervet monkey population is [composed] of alcohol avoiders, moderate alcohol drinkers, and a group of heavy drinkers,” Matthew Potthoff, PhD, and associates wrote in Cell Metabolism. When this particular bunch of heavy-drinking vervets were given FGF21, they consumed 50% less alcohol than did vehicle-treated controls, so mission accomplished.
Maybe it could be a breakfast cereal. Who wouldn’t enjoy a bowl of alcoholic monkeys in the morning?
And after breakfast, you might be ready for a digitized bowel movement, courtesy of researchers at University of California, San Diego. They’re studying ulcerative colitis (UC) by examining the gut microbiome, and their “most useful biological sample is patient stool,” according to a written statement from the university.
“Once we had all the technology to digitize the stool, the question was, is this going to tell us what’s happening in these patients? The answer turned out to be yes,” co-senior author Rob Knight, PhD, said in the statement. “Digitizing fecal material is the future.” The road to UC treatment, in other words, is paved with digital stool.
About 40% of the UC patients had elevated protease levels, and their high-protease feces were then transplanted into germ-free mice, which subsequently developed colitis and were successfully treated with protease inhibitors. And that is our final destination.
As our revered founder and mentor, Josephine Lotmevich, used to say, an alcoholic monkey in the hand is worth a number 2 in the bush.
Raise a glass to delinquency
You wouldn’t think that a glass of water could lead to a life of crime, but a recent study suggests just that.
Children exposed to lead in their drinking water during their early years had a 21% higher risk of delinquency after the age of 14 years and a 38% higher risk of having a record for a serious complaint, Jackie MacDonald Gibson and associates said in a statement on Eurekalert.
Data for the study came from Wake County, N.C., which includes rural areas, wealthy exurban developments, and predominantly Black communities. The investigators compared the blood lead levels for children tested between 1998 and 2011 with juvenile delinquency reports of the same children from the N.C. Department of Public Safety.
The main culprit, they found, was well water. Blood lead levels were 11% higher in the children whose water came from private wells, compared with children using community water. About 13% of U.S. households rely on private wells, which are not regulated under the Safe Drinking Water Act, for their water supply.
The researchers said there is an urgent need for better drinking-water solutions in communities that rely on well water, whether it be through subsidized home filtration or infrastructure redevelopment.
An earlier study had estimated that preventing just one child from entering the adult criminal justice system would save $1.3 to $1.5 million in 1997 dollars. That’s about $2.2 to $2.5 million dollars today!
If you do the math, it’s not hard to see what’s cheaper (and healthier) in the long run.
A ‘dirty’ scam
Another one? This is just getting sad. You’ve probably heard of muds and clays being good for the skin and maybe you’ve gone to a spa and sat in a mud bath, but would you believe it if someone told you that mud can cure all your ailments? No? Neither would we. Senatorial candidate Beto O’Rourke was definitely someone who brought this strange treatment to light, but it seems like this is something that has been going on for years, even before the pandemic.
A company called Black Oxygen Organics (BOO) was selling “magic dirt” for $110 per 4-ounce package. It claimed the dirt was high in fulvic acid and humic acid, which are good for many things. They were, however, literally getting this mud from bogs with landfills nearby, Mel magazine reported.
That doesn’t sound appealing at all, but wait, there’s more. People were eating, drinking, bathing, and feeding their families this sludge in hopes that they would be cured of their ailments. A lot of people jumped aboard the magic dirt train when the pandemic arose, but it quickly became clear that this mud was not as helpful as BOO claimed it to be.
“We began to receive inquiries and calls on our website with people having problems and issues. Ultimately, we sent the products out for independent testing, and then when that came back and showed that there were toxic heavy metals [lead, arsenic, and cadmium among them] at an unsafe level, that’s when we knew we had to act,” Atlanta-based attorney Matt Wetherington, who filed a federal lawsuit against BOO, told Mel.
After a very complicated series of events involving an expose by NBC, product recalls, extortion claims, and grassroots activism, BOO was shut down by both the Canadian and U.S. governments.
As always, please listen only to health care professionals when you wish to use natural remedies for illnesses and ailments.
The world’s most valuable mouse
You’ve heard of Mighty Mouse. Now say hello to the world’s newest mouse superhero, Crypto-Mouse! After being bitten by a radioactive cryptocurrency investor, Crypto-Mouse can tap directly into the power of the blockchain itself, allowing it to perform incredible, death-defying feats of strength!
We’re going to stop right there before Crypto-Mouse gains entry into the Marvel cinematic universe. Let’s rewind to the beginning, because that’s precisely where this crazy scheme is at. In late January, a new decentralized autonomous organization, BitMouseDAO, launched to enormous … -ly little fanfare, according to Vice. Two investors as of Jan. 31. But what they lack in money they make up for in sheer ambition.
BitMouseDAO’s $100 million dollar idea is to genetically engineer mice to carry bitcoin, the first cryptocurrency and one of the most valuable. This isn’t as crazy an idea as it sounds since DNA can be modified to store information, potentially even bitcoin information. Their plan is to create a private bitcoin wallet, which will be stored in the mouse DNA, and purchase online bitcoin to store in this wallet.
BitMouseDAO, being a “collection of artists,” plans to partner with a lab to translate its private key into a specific DNA sequence to be encoded into the mice during fertilization; or, if that doesn’t work, inject them with a harmless virus that carries the key.
Since these are artists, their ultimate plan is to use their bitcoin mice to make NFTs (scratch that off your cryptocurrency bingo card) and auction them off to people. Or, as Vice put it, BitMouseDAO essentially plans to send preserved dead mice to people. Artistic dead mice! Artistic dead mice worth millions! Maybe. Even BitMouseDAO admits bitcoin could be worthless by the time the project gets off the ground.
If this all sounds completely insane, that’s because it is. But it also sounds crazy enough to work. Now, if you’ll excuse us, we’re off to write a screenplay about a scrappy group of high-tech thieves who steal a group of genetically altered bitcoin mice to sell for millions, only to keep them as their adorable pets. Trust us Hollywood, it’ll make millions!
Alcoholic monkeys vs. the future of feces
Which is more important, the journey or the destination? Science is all about the destination, yes? Solving the problem, saving a life, expanding horizons. That’s science. Or is it? The scientific method is a process, so does that make it a journey?
For us, today’s journey begins at the University of Iowa, where investigators are trying to reduce alcohol consumption. A worthy goal, and they seem to have made some progress by targeting a liver hormone called fibroblast growth factor 21 (FGF21). But we’re more interested in the process right now, so bring on the alcoholic monkeys. And no, that’s not a death metal/reggae fusion band. Should be, though.
“The vervet monkey population is [composed] of alcohol avoiders, moderate alcohol drinkers, and a group of heavy drinkers,” Matthew Potthoff, PhD, and associates wrote in Cell Metabolism. When this particular bunch of heavy-drinking vervets were given FGF21, they consumed 50% less alcohol than did vehicle-treated controls, so mission accomplished.
Maybe it could be a breakfast cereal. Who wouldn’t enjoy a bowl of alcoholic monkeys in the morning?
And after breakfast, you might be ready for a digitized bowel movement, courtesy of researchers at University of California, San Diego. They’re studying ulcerative colitis (UC) by examining the gut microbiome, and their “most useful biological sample is patient stool,” according to a written statement from the university.
“Once we had all the technology to digitize the stool, the question was, is this going to tell us what’s happening in these patients? The answer turned out to be yes,” co-senior author Rob Knight, PhD, said in the statement. “Digitizing fecal material is the future.” The road to UC treatment, in other words, is paved with digital stool.
About 40% of the UC patients had elevated protease levels, and their high-protease feces were then transplanted into germ-free mice, which subsequently developed colitis and were successfully treated with protease inhibitors. And that is our final destination.
As our revered founder and mentor, Josephine Lotmevich, used to say, an alcoholic monkey in the hand is worth a number 2 in the bush.
Raise a glass to delinquency
You wouldn’t think that a glass of water could lead to a life of crime, but a recent study suggests just that.
Children exposed to lead in their drinking water during their early years had a 21% higher risk of delinquency after the age of 14 years and a 38% higher risk of having a record for a serious complaint, Jackie MacDonald Gibson and associates said in a statement on Eurekalert.
Data for the study came from Wake County, N.C., which includes rural areas, wealthy exurban developments, and predominantly Black communities. The investigators compared the blood lead levels for children tested between 1998 and 2011 with juvenile delinquency reports of the same children from the N.C. Department of Public Safety.
The main culprit, they found, was well water. Blood lead levels were 11% higher in the children whose water came from private wells, compared with children using community water. About 13% of U.S. households rely on private wells, which are not regulated under the Safe Drinking Water Act, for their water supply.
The researchers said there is an urgent need for better drinking-water solutions in communities that rely on well water, whether it be through subsidized home filtration or infrastructure redevelopment.
An earlier study had estimated that preventing just one child from entering the adult criminal justice system would save $1.3 to $1.5 million in 1997 dollars. That’s about $2.2 to $2.5 million dollars today!
If you do the math, it’s not hard to see what’s cheaper (and healthier) in the long run.
A ‘dirty’ scam
Another one? This is just getting sad. You’ve probably heard of muds and clays being good for the skin and maybe you’ve gone to a spa and sat in a mud bath, but would you believe it if someone told you that mud can cure all your ailments? No? Neither would we. Senatorial candidate Beto O’Rourke was definitely someone who brought this strange treatment to light, but it seems like this is something that has been going on for years, even before the pandemic.
A company called Black Oxygen Organics (BOO) was selling “magic dirt” for $110 per 4-ounce package. It claimed the dirt was high in fulvic acid and humic acid, which are good for many things. They were, however, literally getting this mud from bogs with landfills nearby, Mel magazine reported.
That doesn’t sound appealing at all, but wait, there’s more. People were eating, drinking, bathing, and feeding their families this sludge in hopes that they would be cured of their ailments. A lot of people jumped aboard the magic dirt train when the pandemic arose, but it quickly became clear that this mud was not as helpful as BOO claimed it to be.
“We began to receive inquiries and calls on our website with people having problems and issues. Ultimately, we sent the products out for independent testing, and then when that came back and showed that there were toxic heavy metals [lead, arsenic, and cadmium among them] at an unsafe level, that’s when we knew we had to act,” Atlanta-based attorney Matt Wetherington, who filed a federal lawsuit against BOO, told Mel.
After a very complicated series of events involving an expose by NBC, product recalls, extortion claims, and grassroots activism, BOO was shut down by both the Canadian and U.S. governments.
As always, please listen only to health care professionals when you wish to use natural remedies for illnesses and ailments.
The world’s most valuable mouse
You’ve heard of Mighty Mouse. Now say hello to the world’s newest mouse superhero, Crypto-Mouse! After being bitten by a radioactive cryptocurrency investor, Crypto-Mouse can tap directly into the power of the blockchain itself, allowing it to perform incredible, death-defying feats of strength!
We’re going to stop right there before Crypto-Mouse gains entry into the Marvel cinematic universe. Let’s rewind to the beginning, because that’s precisely where this crazy scheme is at. In late January, a new decentralized autonomous organization, BitMouseDAO, launched to enormous … -ly little fanfare, according to Vice. Two investors as of Jan. 31. But what they lack in money they make up for in sheer ambition.
BitMouseDAO’s $100 million dollar idea is to genetically engineer mice to carry bitcoin, the first cryptocurrency and one of the most valuable. This isn’t as crazy an idea as it sounds since DNA can be modified to store information, potentially even bitcoin information. Their plan is to create a private bitcoin wallet, which will be stored in the mouse DNA, and purchase online bitcoin to store in this wallet.
BitMouseDAO, being a “collection of artists,” plans to partner with a lab to translate its private key into a specific DNA sequence to be encoded into the mice during fertilization; or, if that doesn’t work, inject them with a harmless virus that carries the key.
Since these are artists, their ultimate plan is to use their bitcoin mice to make NFTs (scratch that off your cryptocurrency bingo card) and auction them off to people. Or, as Vice put it, BitMouseDAO essentially plans to send preserved dead mice to people. Artistic dead mice! Artistic dead mice worth millions! Maybe. Even BitMouseDAO admits bitcoin could be worthless by the time the project gets off the ground.
If this all sounds completely insane, that’s because it is. But it also sounds crazy enough to work. Now, if you’ll excuse us, we’re off to write a screenplay about a scrappy group of high-tech thieves who steal a group of genetically altered bitcoin mice to sell for millions, only to keep them as their adorable pets. Trust us Hollywood, it’ll make millions!
Alcoholic monkeys vs. the future of feces
Which is more important, the journey or the destination? Science is all about the destination, yes? Solving the problem, saving a life, expanding horizons. That’s science. Or is it? The scientific method is a process, so does that make it a journey?
For us, today’s journey begins at the University of Iowa, where investigators are trying to reduce alcohol consumption. A worthy goal, and they seem to have made some progress by targeting a liver hormone called fibroblast growth factor 21 (FGF21). But we’re more interested in the process right now, so bring on the alcoholic monkeys. And no, that’s not a death metal/reggae fusion band. Should be, though.
“The vervet monkey population is [composed] of alcohol avoiders, moderate alcohol drinkers, and a group of heavy drinkers,” Matthew Potthoff, PhD, and associates wrote in Cell Metabolism. When this particular bunch of heavy-drinking vervets were given FGF21, they consumed 50% less alcohol than did vehicle-treated controls, so mission accomplished.
Maybe it could be a breakfast cereal. Who wouldn’t enjoy a bowl of alcoholic monkeys in the morning?
And after breakfast, you might be ready for a digitized bowel movement, courtesy of researchers at University of California, San Diego. They’re studying ulcerative colitis (UC) by examining the gut microbiome, and their “most useful biological sample is patient stool,” according to a written statement from the university.
“Once we had all the technology to digitize the stool, the question was, is this going to tell us what’s happening in these patients? The answer turned out to be yes,” co-senior author Rob Knight, PhD, said in the statement. “Digitizing fecal material is the future.” The road to UC treatment, in other words, is paved with digital stool.
About 40% of the UC patients had elevated protease levels, and their high-protease feces were then transplanted into germ-free mice, which subsequently developed colitis and were successfully treated with protease inhibitors. And that is our final destination.
As our revered founder and mentor, Josephine Lotmevich, used to say, an alcoholic monkey in the hand is worth a number 2 in the bush.
Raise a glass to delinquency
You wouldn’t think that a glass of water could lead to a life of crime, but a recent study suggests just that.
Children exposed to lead in their drinking water during their early years had a 21% higher risk of delinquency after the age of 14 years and a 38% higher risk of having a record for a serious complaint, Jackie MacDonald Gibson and associates said in a statement on Eurekalert.
Data for the study came from Wake County, N.C., which includes rural areas, wealthy exurban developments, and predominantly Black communities. The investigators compared the blood lead levels for children tested between 1998 and 2011 with juvenile delinquency reports of the same children from the N.C. Department of Public Safety.
The main culprit, they found, was well water. Blood lead levels were 11% higher in the children whose water came from private wells, compared with children using community water. About 13% of U.S. households rely on private wells, which are not regulated under the Safe Drinking Water Act, for their water supply.
The researchers said there is an urgent need for better drinking-water solutions in communities that rely on well water, whether it be through subsidized home filtration or infrastructure redevelopment.
An earlier study had estimated that preventing just one child from entering the adult criminal justice system would save $1.3 to $1.5 million in 1997 dollars. That’s about $2.2 to $2.5 million dollars today!
If you do the math, it’s not hard to see what’s cheaper (and healthier) in the long run.
A ‘dirty’ scam
Another one? This is just getting sad. You’ve probably heard of muds and clays being good for the skin and maybe you’ve gone to a spa and sat in a mud bath, but would you believe it if someone told you that mud can cure all your ailments? No? Neither would we. Senatorial candidate Beto O’Rourke was definitely someone who brought this strange treatment to light, but it seems like this is something that has been going on for years, even before the pandemic.
A company called Black Oxygen Organics (BOO) was selling “magic dirt” for $110 per 4-ounce package. It claimed the dirt was high in fulvic acid and humic acid, which are good for many things. They were, however, literally getting this mud from bogs with landfills nearby, Mel magazine reported.
That doesn’t sound appealing at all, but wait, there’s more. People were eating, drinking, bathing, and feeding their families this sludge in hopes that they would be cured of their ailments. A lot of people jumped aboard the magic dirt train when the pandemic arose, but it quickly became clear that this mud was not as helpful as BOO claimed it to be.
“We began to receive inquiries and calls on our website with people having problems and issues. Ultimately, we sent the products out for independent testing, and then when that came back and showed that there were toxic heavy metals [lead, arsenic, and cadmium among them] at an unsafe level, that’s when we knew we had to act,” Atlanta-based attorney Matt Wetherington, who filed a federal lawsuit against BOO, told Mel.
After a very complicated series of events involving an expose by NBC, product recalls, extortion claims, and grassroots activism, BOO was shut down by both the Canadian and U.S. governments.
As always, please listen only to health care professionals when you wish to use natural remedies for illnesses and ailments.
Buprenorphine may curb opioid-induced respiratory depression
High plasma concentrations of buprenorphine may reduce fentanyl-induced respiratory depression, new research suggests.
The primary endpoint measure in a small “proof of principal” pharmacology study was effect of escalating fentanyl dosing on respiratory depression by way of decreased isohypercapnic minute ventilation (VE) – or volume of gas inhaled or exhaled per minute from the lungs.
Results showed the maximum decrease in highest-dose fentanyl-induced VE was almost 50% less for opioid-tolerant patients receiving a 2.0 ng/mL concentration of steady-state plasma buprenorphine than when receiving matching placebo.
Risk for apnea requiring stimulation after fentanyl dosing was also significantly lower with buprenorphine.
“Even though the study is small, a lot of data were collected which will allow us to very accurately predict which plasma concentrations, and therefore drug doses, are needed to protect people adequately in practice,” study coinvestigator Geert Jan Groeneveld, MD, PhD, neurologist and clinical pharmacologist at the Centre for Human Drug Research, Leiden, the Netherlands, and professor of clinical neuropharmacology at Leiden University Medical Center, told this news organization.
He added the “beautiful results” were in line with what the researchers expected and although further research is needed, the study provides a lot of useful information for clinicians.
“I think this is an approach that works, and this study makes that clear,” Dr. Groeneveld added.
The findings were published online Jan. 27, 2022, in PLoS One.
High death rate from synthetic opioids
A recent report from the Centers for Disease Control and Prevention noted that, between June 2020 and June 2021, there were more than 100,000 drug overdose deaths in the United States. Of these, more than 73,000 were attributed to opioids and more than 60,000 to synthetic opioids such as fentanyl.
Most opioid-related overdose deaths in the United States are attributable to synthetic opioids “that can unexpectedly cause respiratory depression by being ingested as a substitute for heroin or with [other] drugs,” Indivior noted in a press release.
Buprenorphine is a partial agonist that “binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects,” the investigators wrote.
As reported by this news organization, the Food and Drug Administration approved buprenorphine extended release (Sublocade, Indivior) in 2017 as the first once-monthly injection for the treatment of opioid use disorder.
In the current study, which was conducted in Leiden, the Netherlands, the investigators used continuous intravenous buprenorphine in order to “mimic” the sustained plasma concentrations of the drug that can be delivered with the long-acting injectable, noted Christian Heidbreder, PhD, chief scientific officer at Indivior.
“This was an experimental medicine study, whereby we used intravenous buprenorphine to really understand the interaction with escalating doses of fentanyl” on respiratory depression, he told this news organization.
Two-part, two-period study
In part A, period one of the two-period crossover study, 14 healthy volunteers were randomly assigned to receive for 360 minutes continuous infusion of 0.02 or 0.05 mg/70 kg per hour of buprenorphine to target plasma concentrations of 0.2 or 0.5 ng/mL, respectively, or matching placebo. In the second period, participants received the alternative infusion – either placebo or the active drug.
In part B, eight opioid-tolerant patients who had used high-dose opioids for at least 3 months prior received a higher infusion rate of 0.1, 0.2, or 0.5 mg/70 kg per hour to target plasma concentrations of 1, 2, or 5 ng/mL, respectively.
The 2 ng/mL “is a very important threshold for us” and the result from several previous experiments, Dr. Heidbreder noted. So the investigators targeted that concentration as well as one below and one “much higher” in the current study.
“Because tolerance to opioid effects is poorly characterized in patients receiving long-term opioids, opioid-tolerant participants in part B had a fixed treatment sequence, receiving placebo infusion plus fentanyl challenges in period 1 to optimize the fentanyl dose escalation before buprenorphine and fentanyl were coadministered in period 2,” the investigators reported.
All participants received up to four escalating doses of intravenous fentanyl after reaching target buprenorphine plasma concentrations.
For healthy volunteers, the planned fentanyl doses were 0.075, 0.15, 0.25, and 0.35 mg/70 kg. For the opioid-tolerant patients, the doses were 0.25, 0.35, 0.5, and 0.7 mg/70 kg.
The infusions began after baseline VE had stabilized at 20 plus or minus 2 L/min, which is about four times above normal resting VE.
First clinical evidence?
Results showed fentanyl-induced adverse changes in VE were less at higher concentrations of buprenorphine plasma.
Opioid-tolerant patients receiving the 2.0 ng/mL concentration of buprenorphine had a 33.7% decrease in highest dose fentanyl-induced VE versus an 82.3% decrease when receiving placebo.
In addition, fentanyl reduced VE up to 49% (95% confidence interval, 21%-76%) in opioid-tolerant patients in all buprenorphine concentration groups combined versus reducing VE up to 100% (95% CI, 68%-132%) during placebo infusion (P = .006).
In addition, buprenorphine was associated with a lower risk versus placebo for apnea requiring verbal stimulation after fentanyl dosing (odds ratio, 0.07; P = .001).
For the healthy volunteers, the first fentanyl bolus reduced VE by 26% for those at target buprenorphine concentration of 0.5 ng/mL versus 51% when receiving placebo (P = .001). The second bolus reduced VE by 47% versus 79%, respectively (P < .001).
“Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection,” the investigators reported.
Overall, the findings “provide the first clinical evidence that high sustained plasma concentrations of buprenorphine may protect against respiratory depression induced by potent opioids,” they added.
Additional research is now “warranted to assess the competitive interaction of buprenorphine and fentanyl (as well as other illicitly manufactured fentanyl analogs) as we continue to deepen our understanding of buprenorphine as an evidence-based treatment for patients struggling with opioid use disorder,” Dr. Heidbreder said in a press release.
It’s unclear whether the study’s findings are generalizable to other populations, said Dr. Heidbreder.
“So and for that we’ll be using [the injectable] Sublocade as the medication of choice,” said Dr. Heidbreder.
“Conceptually, we feel confident about these data, but now we need to demonstrate what is happening in the real world,” he added.
The study was funded by Indivior. Dr. Groeneveld has reported no relevant financial relationships. Dr. Heidbreder is an employee of Indivior.
A version of this article first appeared on Medscape.com.
High plasma concentrations of buprenorphine may reduce fentanyl-induced respiratory depression, new research suggests.
The primary endpoint measure in a small “proof of principal” pharmacology study was effect of escalating fentanyl dosing on respiratory depression by way of decreased isohypercapnic minute ventilation (VE) – or volume of gas inhaled or exhaled per minute from the lungs.
Results showed the maximum decrease in highest-dose fentanyl-induced VE was almost 50% less for opioid-tolerant patients receiving a 2.0 ng/mL concentration of steady-state plasma buprenorphine than when receiving matching placebo.
Risk for apnea requiring stimulation after fentanyl dosing was also significantly lower with buprenorphine.
“Even though the study is small, a lot of data were collected which will allow us to very accurately predict which plasma concentrations, and therefore drug doses, are needed to protect people adequately in practice,” study coinvestigator Geert Jan Groeneveld, MD, PhD, neurologist and clinical pharmacologist at the Centre for Human Drug Research, Leiden, the Netherlands, and professor of clinical neuropharmacology at Leiden University Medical Center, told this news organization.
He added the “beautiful results” were in line with what the researchers expected and although further research is needed, the study provides a lot of useful information for clinicians.
“I think this is an approach that works, and this study makes that clear,” Dr. Groeneveld added.
The findings were published online Jan. 27, 2022, in PLoS One.
High death rate from synthetic opioids
A recent report from the Centers for Disease Control and Prevention noted that, between June 2020 and June 2021, there were more than 100,000 drug overdose deaths in the United States. Of these, more than 73,000 were attributed to opioids and more than 60,000 to synthetic opioids such as fentanyl.
Most opioid-related overdose deaths in the United States are attributable to synthetic opioids “that can unexpectedly cause respiratory depression by being ingested as a substitute for heroin or with [other] drugs,” Indivior noted in a press release.
Buprenorphine is a partial agonist that “binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects,” the investigators wrote.
As reported by this news organization, the Food and Drug Administration approved buprenorphine extended release (Sublocade, Indivior) in 2017 as the first once-monthly injection for the treatment of opioid use disorder.
In the current study, which was conducted in Leiden, the Netherlands, the investigators used continuous intravenous buprenorphine in order to “mimic” the sustained plasma concentrations of the drug that can be delivered with the long-acting injectable, noted Christian Heidbreder, PhD, chief scientific officer at Indivior.
“This was an experimental medicine study, whereby we used intravenous buprenorphine to really understand the interaction with escalating doses of fentanyl” on respiratory depression, he told this news organization.
Two-part, two-period study
In part A, period one of the two-period crossover study, 14 healthy volunteers were randomly assigned to receive for 360 minutes continuous infusion of 0.02 or 0.05 mg/70 kg per hour of buprenorphine to target plasma concentrations of 0.2 or 0.5 ng/mL, respectively, or matching placebo. In the second period, participants received the alternative infusion – either placebo or the active drug.
In part B, eight opioid-tolerant patients who had used high-dose opioids for at least 3 months prior received a higher infusion rate of 0.1, 0.2, or 0.5 mg/70 kg per hour to target plasma concentrations of 1, 2, or 5 ng/mL, respectively.
The 2 ng/mL “is a very important threshold for us” and the result from several previous experiments, Dr. Heidbreder noted. So the investigators targeted that concentration as well as one below and one “much higher” in the current study.
“Because tolerance to opioid effects is poorly characterized in patients receiving long-term opioids, opioid-tolerant participants in part B had a fixed treatment sequence, receiving placebo infusion plus fentanyl challenges in period 1 to optimize the fentanyl dose escalation before buprenorphine and fentanyl were coadministered in period 2,” the investigators reported.
All participants received up to four escalating doses of intravenous fentanyl after reaching target buprenorphine plasma concentrations.
For healthy volunteers, the planned fentanyl doses were 0.075, 0.15, 0.25, and 0.35 mg/70 kg. For the opioid-tolerant patients, the doses were 0.25, 0.35, 0.5, and 0.7 mg/70 kg.
The infusions began after baseline VE had stabilized at 20 plus or minus 2 L/min, which is about four times above normal resting VE.
First clinical evidence?
Results showed fentanyl-induced adverse changes in VE were less at higher concentrations of buprenorphine plasma.
Opioid-tolerant patients receiving the 2.0 ng/mL concentration of buprenorphine had a 33.7% decrease in highest dose fentanyl-induced VE versus an 82.3% decrease when receiving placebo.
In addition, fentanyl reduced VE up to 49% (95% confidence interval, 21%-76%) in opioid-tolerant patients in all buprenorphine concentration groups combined versus reducing VE up to 100% (95% CI, 68%-132%) during placebo infusion (P = .006).
In addition, buprenorphine was associated with a lower risk versus placebo for apnea requiring verbal stimulation after fentanyl dosing (odds ratio, 0.07; P = .001).
For the healthy volunteers, the first fentanyl bolus reduced VE by 26% for those at target buprenorphine concentration of 0.5 ng/mL versus 51% when receiving placebo (P = .001). The second bolus reduced VE by 47% versus 79%, respectively (P < .001).
“Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection,” the investigators reported.
Overall, the findings “provide the first clinical evidence that high sustained plasma concentrations of buprenorphine may protect against respiratory depression induced by potent opioids,” they added.
Additional research is now “warranted to assess the competitive interaction of buprenorphine and fentanyl (as well as other illicitly manufactured fentanyl analogs) as we continue to deepen our understanding of buprenorphine as an evidence-based treatment for patients struggling with opioid use disorder,” Dr. Heidbreder said in a press release.
It’s unclear whether the study’s findings are generalizable to other populations, said Dr. Heidbreder.
“So and for that we’ll be using [the injectable] Sublocade as the medication of choice,” said Dr. Heidbreder.
“Conceptually, we feel confident about these data, but now we need to demonstrate what is happening in the real world,” he added.
The study was funded by Indivior. Dr. Groeneveld has reported no relevant financial relationships. Dr. Heidbreder is an employee of Indivior.
A version of this article first appeared on Medscape.com.
High plasma concentrations of buprenorphine may reduce fentanyl-induced respiratory depression, new research suggests.
The primary endpoint measure in a small “proof of principal” pharmacology study was effect of escalating fentanyl dosing on respiratory depression by way of decreased isohypercapnic minute ventilation (VE) – or volume of gas inhaled or exhaled per minute from the lungs.
Results showed the maximum decrease in highest-dose fentanyl-induced VE was almost 50% less for opioid-tolerant patients receiving a 2.0 ng/mL concentration of steady-state plasma buprenorphine than when receiving matching placebo.
Risk for apnea requiring stimulation after fentanyl dosing was also significantly lower with buprenorphine.
“Even though the study is small, a lot of data were collected which will allow us to very accurately predict which plasma concentrations, and therefore drug doses, are needed to protect people adequately in practice,” study coinvestigator Geert Jan Groeneveld, MD, PhD, neurologist and clinical pharmacologist at the Centre for Human Drug Research, Leiden, the Netherlands, and professor of clinical neuropharmacology at Leiden University Medical Center, told this news organization.
He added the “beautiful results” were in line with what the researchers expected and although further research is needed, the study provides a lot of useful information for clinicians.
“I think this is an approach that works, and this study makes that clear,” Dr. Groeneveld added.
The findings were published online Jan. 27, 2022, in PLoS One.
High death rate from synthetic opioids
A recent report from the Centers for Disease Control and Prevention noted that, between June 2020 and June 2021, there were more than 100,000 drug overdose deaths in the United States. Of these, more than 73,000 were attributed to opioids and more than 60,000 to synthetic opioids such as fentanyl.
Most opioid-related overdose deaths in the United States are attributable to synthetic opioids “that can unexpectedly cause respiratory depression by being ingested as a substitute for heroin or with [other] drugs,” Indivior noted in a press release.
Buprenorphine is a partial agonist that “binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects,” the investigators wrote.
As reported by this news organization, the Food and Drug Administration approved buprenorphine extended release (Sublocade, Indivior) in 2017 as the first once-monthly injection for the treatment of opioid use disorder.
In the current study, which was conducted in Leiden, the Netherlands, the investigators used continuous intravenous buprenorphine in order to “mimic” the sustained plasma concentrations of the drug that can be delivered with the long-acting injectable, noted Christian Heidbreder, PhD, chief scientific officer at Indivior.
“This was an experimental medicine study, whereby we used intravenous buprenorphine to really understand the interaction with escalating doses of fentanyl” on respiratory depression, he told this news organization.
Two-part, two-period study
In part A, period one of the two-period crossover study, 14 healthy volunteers were randomly assigned to receive for 360 minutes continuous infusion of 0.02 or 0.05 mg/70 kg per hour of buprenorphine to target plasma concentrations of 0.2 or 0.5 ng/mL, respectively, or matching placebo. In the second period, participants received the alternative infusion – either placebo or the active drug.
In part B, eight opioid-tolerant patients who had used high-dose opioids for at least 3 months prior received a higher infusion rate of 0.1, 0.2, or 0.5 mg/70 kg per hour to target plasma concentrations of 1, 2, or 5 ng/mL, respectively.
The 2 ng/mL “is a very important threshold for us” and the result from several previous experiments, Dr. Heidbreder noted. So the investigators targeted that concentration as well as one below and one “much higher” in the current study.
“Because tolerance to opioid effects is poorly characterized in patients receiving long-term opioids, opioid-tolerant participants in part B had a fixed treatment sequence, receiving placebo infusion plus fentanyl challenges in period 1 to optimize the fentanyl dose escalation before buprenorphine and fentanyl were coadministered in period 2,” the investigators reported.
All participants received up to four escalating doses of intravenous fentanyl after reaching target buprenorphine plasma concentrations.
For healthy volunteers, the planned fentanyl doses were 0.075, 0.15, 0.25, and 0.35 mg/70 kg. For the opioid-tolerant patients, the doses were 0.25, 0.35, 0.5, and 0.7 mg/70 kg.
The infusions began after baseline VE had stabilized at 20 plus or minus 2 L/min, which is about four times above normal resting VE.
First clinical evidence?
Results showed fentanyl-induced adverse changes in VE were less at higher concentrations of buprenorphine plasma.
Opioid-tolerant patients receiving the 2.0 ng/mL concentration of buprenorphine had a 33.7% decrease in highest dose fentanyl-induced VE versus an 82.3% decrease when receiving placebo.
In addition, fentanyl reduced VE up to 49% (95% confidence interval, 21%-76%) in opioid-tolerant patients in all buprenorphine concentration groups combined versus reducing VE up to 100% (95% CI, 68%-132%) during placebo infusion (P = .006).
In addition, buprenorphine was associated with a lower risk versus placebo for apnea requiring verbal stimulation after fentanyl dosing (odds ratio, 0.07; P = .001).
For the healthy volunteers, the first fentanyl bolus reduced VE by 26% for those at target buprenorphine concentration of 0.5 ng/mL versus 51% when receiving placebo (P = .001). The second bolus reduced VE by 47% versus 79%, respectively (P < .001).
“Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection,” the investigators reported.
Overall, the findings “provide the first clinical evidence that high sustained plasma concentrations of buprenorphine may protect against respiratory depression induced by potent opioids,” they added.
Additional research is now “warranted to assess the competitive interaction of buprenorphine and fentanyl (as well as other illicitly manufactured fentanyl analogs) as we continue to deepen our understanding of buprenorphine as an evidence-based treatment for patients struggling with opioid use disorder,” Dr. Heidbreder said in a press release.
It’s unclear whether the study’s findings are generalizable to other populations, said Dr. Heidbreder.
“So and for that we’ll be using [the injectable] Sublocade as the medication of choice,” said Dr. Heidbreder.
“Conceptually, we feel confident about these data, but now we need to demonstrate what is happening in the real world,” he added.
The study was funded by Indivior. Dr. Groeneveld has reported no relevant financial relationships. Dr. Heidbreder is an employee of Indivior.
A version of this article first appeared on Medscape.com.
FROM PLOS ONE
Marijuana use during pregnancy raised risk of adverse neonatal outcomes
Women who used marijuana during pregnancy were at increased risk for adverse neonatal outcomes, based on data from a meta-analysis of nearly 60,000 individuals.
Marijuana misuse remains a top substance use disorder and studies of prenatal use show a prevalence as high as 22% worldwide, wrote Greg J. Marchand, MD, of the Marchand Institute for Minimally Invasive Surgery, Mesa, Ariz., and colleagues.
“The prevalence of marijuana use during pregnancy may continue to increase, given that there is a suggested association between legalized recreational marijuana and increased use in prenatal and postpartum periods,” they wrote. “Remarkably, 34%-60% of individuals who use marijuana keep using it during pregnancy,” and many women cite a belief that marijuana is safe to use while pregnant, they noted.
Cannabinoid receptors are present in the developing fetus by the start of the second trimester, and exposure to exogenous cannabinoids may be associated with changes in the prefrontal cortex, including development and function, the researchers said. However, previous studies of an association between maternal marijuana use and poor neonatal outcomes have been inconsistent, they added.
In a study published in JAMA Network Open, the researchers identified 16 interventional and observational studies including 59,138 patients; each study included pregnant women who were exposed to marijuana, compared with those not exposed to marijuana, along with neonatal outcomes. The data selection included studies published until Aug. 16, 2021, and 10 studies were published in 2015 or later.
Overall, the risk for seven adverse neonatal outcomes was significantly increased among women who were exposed to marijuana during pregnancy, compared with those not exposed. The researchers identified increased risk for birth weight less than 2,500 g (relative risk, 2.06; P = .005), small for gestational age (RR, 1.61; P < .001), preterm delivery (RR, 1.28; P < .001), and NICU admission (RR, 1.38; P < .001). In addition, they found significant differences in mean birth weight (mean difference, −112.30 g; P < .001), Apgar score at 1 minute (mean difference, −0.26; P = .002), and infant head circumference (mean difference, −0.34cm; P = .02) between women who used marijuana during pregnancy and those who did not.
The study findings were limited by several factors, including the assessment of only cohort studies, which might suffer from bias given their retrospective designs, the researchers noted. Other limitations included the reliance on self-reports, the inability to adjust for tobacco/marijuana coexposure, and the lack of differentiation between levels of use and between different types of marijuana ingestion, they added.
However, the results support an association between marijuana use and adverse neonatal outcomes, and the researchers recommended additional studies of both maternal and neonatal outcomes associated with marijuana exposure. “Given increasing marijuana legalization and use worldwide, raising awareness and educating patients about these adverse outcomes may help to improve neonatal health,” they concluded.
New research prompted new review
The motivation to conduct this analysis at this time was prompted by the publication of several new, high-quality studies on the use of marijuana in pregnancy, according to Dr. Marchand. “It’s been a few years since a full analysis of all of the available data had been done, so we decided it was time to see if the old conclusions still held,” he said in an interview.
Dr. Marchand said he was surprised to see such a clear connection to preterm deliveries and lower birth weights. “When we perform a meta-analysis, we use all of the available data, and some important studies performed as recently as the past few years provided the depth of evidence behind these connections,” he said. “We didn’t have that level of evidence the last time this topic was studied only a few years ago,” he added.
The study is the largest meta-analysis on this topic to date, so the message to clinicians is highly significant, Dr. Marchand said. That message is “that we now have a very high level of evidence to say that smoking marijuana during pregnancy is harmful, and we (physicians especially) can no longer state that we just don’t know,” he said. “This is going to mean that deciding to smoke marijuana during your pregnancy is also deciding to do something that can harm your baby,” he emphasized. “This paper also will force some difficult decisions for mothers who use marijuana to treat medical problems, and there may not be good substitute treatments for some of these conditions, especially chronic pain and anxiety,” Dr. Marchand noted. “This will set up a difficult risk-versus-benefits situation, where these mothers, ideally with the help of their physicians, will have to decide if the risks of stopping marijuana outweigh the possible harm to the unborn baby,” he said.
As for additional research, long-term studies to assess behavioral changes as exposed children grow up would be beneficial, Dr. Marchand said. Such studies “could really help us balance the risk of marijuana exposure in pregnancy, especially if it is being used to treat serious medical conditions,” he noted.
Findings are a call to action
The view among many women that prenatal cannabis use is safe and without consequence “is a false narrative perpetuated by a combination of outdated evidence and recent changes to state-level cannabis policies,” wrote Kara R. Skelton, PhD, of Towson (Md.) University, and Sara E. Benjamin-Neelon, PhD, of Johns Hopkins University, Baltimore, in an accompanying editorial.
The findings from the current study add to the growing evidence that prenatal cannabis use is associated with adverse birth outcomes, they wrote. “Clinician-directed communication about cannabis has been criticized by pregnant women, with recent findings supporting a need for increased cannabis communication by clinicians,” and not only clinicians, but all health professionals who encounter women who are pregnant or attempting pregnancy should not miss the opportunity to communicate the risks of prenatal cannabis use, they emphasized.
The authors highlighted some of the current study’s limitations, including the inability to determine a dose-response association, the reliance on self-reports, and the lack of adjustment for tobacco/marijuana coexposure. However, they noted that the inclusion of recent studies (10 published in 2015 or later) strengthens the results because of the significant increase in the potency of Δ-9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, in recent decades.
“We urge clinicians, public health professionals, and policy makers to carefully consider the consequences of in utero cannabis exposure identified by Marchand et al. and partner to ensure prioritization of infant and child health during this time of precipitous cannabis legalization and commercialization,” the authors emphasized. “Without necessary safeguards to protect neonatal health, prenatal cannabis use poses a substantial threat to current and future generations of children,” they wrote.
The study received no outside funding. The researchers had no financial conflicts to disclose. The editorialists had no financial conflicts to disclose.
Women who used marijuana during pregnancy were at increased risk for adverse neonatal outcomes, based on data from a meta-analysis of nearly 60,000 individuals.
Marijuana misuse remains a top substance use disorder and studies of prenatal use show a prevalence as high as 22% worldwide, wrote Greg J. Marchand, MD, of the Marchand Institute for Minimally Invasive Surgery, Mesa, Ariz., and colleagues.
“The prevalence of marijuana use during pregnancy may continue to increase, given that there is a suggested association between legalized recreational marijuana and increased use in prenatal and postpartum periods,” they wrote. “Remarkably, 34%-60% of individuals who use marijuana keep using it during pregnancy,” and many women cite a belief that marijuana is safe to use while pregnant, they noted.
Cannabinoid receptors are present in the developing fetus by the start of the second trimester, and exposure to exogenous cannabinoids may be associated with changes in the prefrontal cortex, including development and function, the researchers said. However, previous studies of an association between maternal marijuana use and poor neonatal outcomes have been inconsistent, they added.
In a study published in JAMA Network Open, the researchers identified 16 interventional and observational studies including 59,138 patients; each study included pregnant women who were exposed to marijuana, compared with those not exposed to marijuana, along with neonatal outcomes. The data selection included studies published until Aug. 16, 2021, and 10 studies were published in 2015 or later.
Overall, the risk for seven adverse neonatal outcomes was significantly increased among women who were exposed to marijuana during pregnancy, compared with those not exposed. The researchers identified increased risk for birth weight less than 2,500 g (relative risk, 2.06; P = .005), small for gestational age (RR, 1.61; P < .001), preterm delivery (RR, 1.28; P < .001), and NICU admission (RR, 1.38; P < .001). In addition, they found significant differences in mean birth weight (mean difference, −112.30 g; P < .001), Apgar score at 1 minute (mean difference, −0.26; P = .002), and infant head circumference (mean difference, −0.34cm; P = .02) between women who used marijuana during pregnancy and those who did not.
The study findings were limited by several factors, including the assessment of only cohort studies, which might suffer from bias given their retrospective designs, the researchers noted. Other limitations included the reliance on self-reports, the inability to adjust for tobacco/marijuana coexposure, and the lack of differentiation between levels of use and between different types of marijuana ingestion, they added.
However, the results support an association between marijuana use and adverse neonatal outcomes, and the researchers recommended additional studies of both maternal and neonatal outcomes associated with marijuana exposure. “Given increasing marijuana legalization and use worldwide, raising awareness and educating patients about these adverse outcomes may help to improve neonatal health,” they concluded.
New research prompted new review
The motivation to conduct this analysis at this time was prompted by the publication of several new, high-quality studies on the use of marijuana in pregnancy, according to Dr. Marchand. “It’s been a few years since a full analysis of all of the available data had been done, so we decided it was time to see if the old conclusions still held,” he said in an interview.
Dr. Marchand said he was surprised to see such a clear connection to preterm deliveries and lower birth weights. “When we perform a meta-analysis, we use all of the available data, and some important studies performed as recently as the past few years provided the depth of evidence behind these connections,” he said. “We didn’t have that level of evidence the last time this topic was studied only a few years ago,” he added.
The study is the largest meta-analysis on this topic to date, so the message to clinicians is highly significant, Dr. Marchand said. That message is “that we now have a very high level of evidence to say that smoking marijuana during pregnancy is harmful, and we (physicians especially) can no longer state that we just don’t know,” he said. “This is going to mean that deciding to smoke marijuana during your pregnancy is also deciding to do something that can harm your baby,” he emphasized. “This paper also will force some difficult decisions for mothers who use marijuana to treat medical problems, and there may not be good substitute treatments for some of these conditions, especially chronic pain and anxiety,” Dr. Marchand noted. “This will set up a difficult risk-versus-benefits situation, where these mothers, ideally with the help of their physicians, will have to decide if the risks of stopping marijuana outweigh the possible harm to the unborn baby,” he said.
As for additional research, long-term studies to assess behavioral changes as exposed children grow up would be beneficial, Dr. Marchand said. Such studies “could really help us balance the risk of marijuana exposure in pregnancy, especially if it is being used to treat serious medical conditions,” he noted.
Findings are a call to action
The view among many women that prenatal cannabis use is safe and without consequence “is a false narrative perpetuated by a combination of outdated evidence and recent changes to state-level cannabis policies,” wrote Kara R. Skelton, PhD, of Towson (Md.) University, and Sara E. Benjamin-Neelon, PhD, of Johns Hopkins University, Baltimore, in an accompanying editorial.
The findings from the current study add to the growing evidence that prenatal cannabis use is associated with adverse birth outcomes, they wrote. “Clinician-directed communication about cannabis has been criticized by pregnant women, with recent findings supporting a need for increased cannabis communication by clinicians,” and not only clinicians, but all health professionals who encounter women who are pregnant or attempting pregnancy should not miss the opportunity to communicate the risks of prenatal cannabis use, they emphasized.
The authors highlighted some of the current study’s limitations, including the inability to determine a dose-response association, the reliance on self-reports, and the lack of adjustment for tobacco/marijuana coexposure. However, they noted that the inclusion of recent studies (10 published in 2015 or later) strengthens the results because of the significant increase in the potency of Δ-9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, in recent decades.
“We urge clinicians, public health professionals, and policy makers to carefully consider the consequences of in utero cannabis exposure identified by Marchand et al. and partner to ensure prioritization of infant and child health during this time of precipitous cannabis legalization and commercialization,” the authors emphasized. “Without necessary safeguards to protect neonatal health, prenatal cannabis use poses a substantial threat to current and future generations of children,” they wrote.
The study received no outside funding. The researchers had no financial conflicts to disclose. The editorialists had no financial conflicts to disclose.
Women who used marijuana during pregnancy were at increased risk for adverse neonatal outcomes, based on data from a meta-analysis of nearly 60,000 individuals.
Marijuana misuse remains a top substance use disorder and studies of prenatal use show a prevalence as high as 22% worldwide, wrote Greg J. Marchand, MD, of the Marchand Institute for Minimally Invasive Surgery, Mesa, Ariz., and colleagues.
“The prevalence of marijuana use during pregnancy may continue to increase, given that there is a suggested association between legalized recreational marijuana and increased use in prenatal and postpartum periods,” they wrote. “Remarkably, 34%-60% of individuals who use marijuana keep using it during pregnancy,” and many women cite a belief that marijuana is safe to use while pregnant, they noted.
Cannabinoid receptors are present in the developing fetus by the start of the second trimester, and exposure to exogenous cannabinoids may be associated with changes in the prefrontal cortex, including development and function, the researchers said. However, previous studies of an association between maternal marijuana use and poor neonatal outcomes have been inconsistent, they added.
In a study published in JAMA Network Open, the researchers identified 16 interventional and observational studies including 59,138 patients; each study included pregnant women who were exposed to marijuana, compared with those not exposed to marijuana, along with neonatal outcomes. The data selection included studies published until Aug. 16, 2021, and 10 studies were published in 2015 or later.
Overall, the risk for seven adverse neonatal outcomes was significantly increased among women who were exposed to marijuana during pregnancy, compared with those not exposed. The researchers identified increased risk for birth weight less than 2,500 g (relative risk, 2.06; P = .005), small for gestational age (RR, 1.61; P < .001), preterm delivery (RR, 1.28; P < .001), and NICU admission (RR, 1.38; P < .001). In addition, they found significant differences in mean birth weight (mean difference, −112.30 g; P < .001), Apgar score at 1 minute (mean difference, −0.26; P = .002), and infant head circumference (mean difference, −0.34cm; P = .02) between women who used marijuana during pregnancy and those who did not.
The study findings were limited by several factors, including the assessment of only cohort studies, which might suffer from bias given their retrospective designs, the researchers noted. Other limitations included the reliance on self-reports, the inability to adjust for tobacco/marijuana coexposure, and the lack of differentiation between levels of use and between different types of marijuana ingestion, they added.
However, the results support an association between marijuana use and adverse neonatal outcomes, and the researchers recommended additional studies of both maternal and neonatal outcomes associated with marijuana exposure. “Given increasing marijuana legalization and use worldwide, raising awareness and educating patients about these adverse outcomes may help to improve neonatal health,” they concluded.
New research prompted new review
The motivation to conduct this analysis at this time was prompted by the publication of several new, high-quality studies on the use of marijuana in pregnancy, according to Dr. Marchand. “It’s been a few years since a full analysis of all of the available data had been done, so we decided it was time to see if the old conclusions still held,” he said in an interview.
Dr. Marchand said he was surprised to see such a clear connection to preterm deliveries and lower birth weights. “When we perform a meta-analysis, we use all of the available data, and some important studies performed as recently as the past few years provided the depth of evidence behind these connections,” he said. “We didn’t have that level of evidence the last time this topic was studied only a few years ago,” he added.
The study is the largest meta-analysis on this topic to date, so the message to clinicians is highly significant, Dr. Marchand said. That message is “that we now have a very high level of evidence to say that smoking marijuana during pregnancy is harmful, and we (physicians especially) can no longer state that we just don’t know,” he said. “This is going to mean that deciding to smoke marijuana during your pregnancy is also deciding to do something that can harm your baby,” he emphasized. “This paper also will force some difficult decisions for mothers who use marijuana to treat medical problems, and there may not be good substitute treatments for some of these conditions, especially chronic pain and anxiety,” Dr. Marchand noted. “This will set up a difficult risk-versus-benefits situation, where these mothers, ideally with the help of their physicians, will have to decide if the risks of stopping marijuana outweigh the possible harm to the unborn baby,” he said.
As for additional research, long-term studies to assess behavioral changes as exposed children grow up would be beneficial, Dr. Marchand said. Such studies “could really help us balance the risk of marijuana exposure in pregnancy, especially if it is being used to treat serious medical conditions,” he noted.
Findings are a call to action
The view among many women that prenatal cannabis use is safe and without consequence “is a false narrative perpetuated by a combination of outdated evidence and recent changes to state-level cannabis policies,” wrote Kara R. Skelton, PhD, of Towson (Md.) University, and Sara E. Benjamin-Neelon, PhD, of Johns Hopkins University, Baltimore, in an accompanying editorial.
The findings from the current study add to the growing evidence that prenatal cannabis use is associated with adverse birth outcomes, they wrote. “Clinician-directed communication about cannabis has been criticized by pregnant women, with recent findings supporting a need for increased cannabis communication by clinicians,” and not only clinicians, but all health professionals who encounter women who are pregnant or attempting pregnancy should not miss the opportunity to communicate the risks of prenatal cannabis use, they emphasized.
The authors highlighted some of the current study’s limitations, including the inability to determine a dose-response association, the reliance on self-reports, and the lack of adjustment for tobacco/marijuana coexposure. However, they noted that the inclusion of recent studies (10 published in 2015 or later) strengthens the results because of the significant increase in the potency of Δ-9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, in recent decades.
“We urge clinicians, public health professionals, and policy makers to carefully consider the consequences of in utero cannabis exposure identified by Marchand et al. and partner to ensure prioritization of infant and child health during this time of precipitous cannabis legalization and commercialization,” the authors emphasized. “Without necessary safeguards to protect neonatal health, prenatal cannabis use poses a substantial threat to current and future generations of children,” they wrote.
The study received no outside funding. The researchers had no financial conflicts to disclose. The editorialists had no financial conflicts to disclose.
FROM JAMA NETWORK OPEN
Doctor’s illegal opioid prescriptions lead to five deaths
According to court documents, between January 2014 and October 2019, family physician David Chisholm, MD, 64, of Wasilla, Alaska, wrote more than 20,000 prescriptions to approximately 350 patients for oxycodone, methadone, and hydrocodone, often prescribing the pills using variations of patients’ names in an attempt to avoid being red-flagged by payers.
When Walmart refused to continue filling the prescriptions, Dr. Chisholm told his staff to advise the patients to use other pharmacies. In addition, he often prescribed combinations of medications, such as concurrent opioids, benzodiazepines, sedatives, and carisoprodol, thus increasing the chances that his patients would become addicted to or overdose on the drugs. Chisholm, who pleaded guilty in June, acknowledged to federal officials that his prescriptions were a significant contributing factor to the overdose deaths of five of his patients during this time, according to a statement by the U.S. Attorney’s Office for the District of Alaska.
According to the Anchorage Daily News, Dr. Chisholm, who was not board certified in pain medicine, said his reason for prescribing the drugs was not to make money but to help patients suffering from chronic pain and because he enjoyed the challenge.
Dr. Chisholm’s attorney, Nick Oberheiden, told CNN his client “sacrificed his reputation as a patient advocate and his years of service to the Alaskan community” in overprescribing opioids. “He expressed his sincere remorse in open court and he accepts the consequences of his misconduct. He hopes that his case serves as a warning to other physicians facing the same dilemma when treating chronic pain.”
He surrendered his medical license in November 2020 before being formally charged in April 2021.
Texas hospital CEO, seven doctors settle kickback
A hospital executive and seven physicians have agreed to pay a total of $1.1 million to settle allegations that they violated the Anti-Kickback Statute and Stark Law. The eight have also agreed to cooperate in investigations and litigation involving other parties.
The Texas physicians involved in the settlement are internist Jaspaul Bhangoo, MD, of Denton; family physician Robert Megna, DO, of Ferris; cardiologist Baxter Montgomery, MD, of Houston; internist Murtaza Mussaji, DO, of Houston; family physician David Sneed, DO, of Austin; family physician Kevin Lewis, DO, of Houston; and family physician Angela Mosley-Nunnery, MD, of Kingwood.
Also settling was Richard DeFoore, former CEO of Jones County Regional Healthcare (dba Stamford Memorial Hospital).
The physicians were accused of accepting payments from organizations in exchange for ordering lab tests from True Health Diagnostics, Little River Healthcare, and Boston Heart. The payments to the physicians were disguised as investment returns but, according to the allegations, were in fact offered in exchange for the doctors’ referrals. Mr. DeFoore, the hospital executive involved in the settlement, allegedly oversaw a similar scheme that benefited the now-defunct Stamford Memorial.
“Paying kickbacks to physicians distorts the medical decision-making process, corrupts our health care system, and increases the cost of healthcare funded by the taxpayer,” Brit Featherston, U.S. attorney for the Eastern District of Texas, said in a statement announcing the agreement. “Laboratories, marketers, and physicians cannot immunize their conduct by attempting to disguise the kickbacks as some sort of investment arrangement.”
Practice administrative assistant sentenced for fraudulent prescriptions
An administrative assistant at an Illinois orthopedics office was sentenced to a year and a day in federal prison for writing fraudulent prescriptions for opioids.
Amanda Biesiada, 39, of Alsip, Ill., who worked as an administrative assistant at Hinsdale Orthopaedics in Westmont, Ill., was not a licensed physician and could not legally write the prescriptions unless instructed to do so and supervised by licensed doctors.
According to a statement by the U.S. Attorney’s Office for the Northern District of Illinois, the prescriptions for hydrocodone, oxycodone, and other controlled substances – 85 prescriptions in all from 2017 to 2019 – were made out to an acquaintance of Biesiada’s and written without the knowledge or approval of the providers in whose names she wrote them.
Federal officials said Ms. Biesiada attempted to conceal the fraudulent prescriptions by marking them “filed in error” in the practice’s prescription system.
Lab owner pleads guilty to $6.9 million testing fraud scheme
A Florida lab owner has pleaded guilty to conspiracy to defraud Medicare through false and fraudulent claims totaling more than $6.9 million.
According to court documents, Christopher Licata, 45, of Delray Beach, Fla., admitted to bribing patient brokers to refer orders for medically unnecessary genetic testing to his lab. The tests were then billed to Medicare.
Mr. Licata and the patient brokers entered sham agreements meant to disguise the true purpose of the payments, according to a statement from the Department of Justice. The 45-year-old owner of Boca Toxicology (dba Lab Dynamics) pleaded guilty to one count of conspiring to commit health care fraud.
The scheme began in 2018; however, once the pandemic began, Mr. Licata shifted strategies, playing on patients’ fears of COVID-19 to bundle inexpensive COVID tests with more expensive medically unnecessary tests. These tests included respiratory pathogen panels and genetic testing for cardiovascular disease, cancer, diabetes, Alzheimer’s disease, and other illnesses. In all, Mr. Licata’s laboratory submitted over $6.9 million in false and fraudulent claims to Medicare for these unnecessary tests, according to the DOJ statement.
The case is a part of the U.S. Attorney General’s COVID-19 Fraud Enforcement Task Force that was established to enhance the efforts of agencies and governments across the country to combat and prevent pandemic-related fraud.
Mr. Licata faces a maximum penalty of 10 years in prison. His sentencing is scheduled for March 24.
A version of this article first appeared on Medscape.com.
According to court documents, between January 2014 and October 2019, family physician David Chisholm, MD, 64, of Wasilla, Alaska, wrote more than 20,000 prescriptions to approximately 350 patients for oxycodone, methadone, and hydrocodone, often prescribing the pills using variations of patients’ names in an attempt to avoid being red-flagged by payers.
When Walmart refused to continue filling the prescriptions, Dr. Chisholm told his staff to advise the patients to use other pharmacies. In addition, he often prescribed combinations of medications, such as concurrent opioids, benzodiazepines, sedatives, and carisoprodol, thus increasing the chances that his patients would become addicted to or overdose on the drugs. Chisholm, who pleaded guilty in June, acknowledged to federal officials that his prescriptions were a significant contributing factor to the overdose deaths of five of his patients during this time, according to a statement by the U.S. Attorney’s Office for the District of Alaska.
According to the Anchorage Daily News, Dr. Chisholm, who was not board certified in pain medicine, said his reason for prescribing the drugs was not to make money but to help patients suffering from chronic pain and because he enjoyed the challenge.
Dr. Chisholm’s attorney, Nick Oberheiden, told CNN his client “sacrificed his reputation as a patient advocate and his years of service to the Alaskan community” in overprescribing opioids. “He expressed his sincere remorse in open court and he accepts the consequences of his misconduct. He hopes that his case serves as a warning to other physicians facing the same dilemma when treating chronic pain.”
He surrendered his medical license in November 2020 before being formally charged in April 2021.
Texas hospital CEO, seven doctors settle kickback
A hospital executive and seven physicians have agreed to pay a total of $1.1 million to settle allegations that they violated the Anti-Kickback Statute and Stark Law. The eight have also agreed to cooperate in investigations and litigation involving other parties.
The Texas physicians involved in the settlement are internist Jaspaul Bhangoo, MD, of Denton; family physician Robert Megna, DO, of Ferris; cardiologist Baxter Montgomery, MD, of Houston; internist Murtaza Mussaji, DO, of Houston; family physician David Sneed, DO, of Austin; family physician Kevin Lewis, DO, of Houston; and family physician Angela Mosley-Nunnery, MD, of Kingwood.
Also settling was Richard DeFoore, former CEO of Jones County Regional Healthcare (dba Stamford Memorial Hospital).
The physicians were accused of accepting payments from organizations in exchange for ordering lab tests from True Health Diagnostics, Little River Healthcare, and Boston Heart. The payments to the physicians were disguised as investment returns but, according to the allegations, were in fact offered in exchange for the doctors’ referrals. Mr. DeFoore, the hospital executive involved in the settlement, allegedly oversaw a similar scheme that benefited the now-defunct Stamford Memorial.
“Paying kickbacks to physicians distorts the medical decision-making process, corrupts our health care system, and increases the cost of healthcare funded by the taxpayer,” Brit Featherston, U.S. attorney for the Eastern District of Texas, said in a statement announcing the agreement. “Laboratories, marketers, and physicians cannot immunize their conduct by attempting to disguise the kickbacks as some sort of investment arrangement.”
Practice administrative assistant sentenced for fraudulent prescriptions
An administrative assistant at an Illinois orthopedics office was sentenced to a year and a day in federal prison for writing fraudulent prescriptions for opioids.
Amanda Biesiada, 39, of Alsip, Ill., who worked as an administrative assistant at Hinsdale Orthopaedics in Westmont, Ill., was not a licensed physician and could not legally write the prescriptions unless instructed to do so and supervised by licensed doctors.
According to a statement by the U.S. Attorney’s Office for the Northern District of Illinois, the prescriptions for hydrocodone, oxycodone, and other controlled substances – 85 prescriptions in all from 2017 to 2019 – were made out to an acquaintance of Biesiada’s and written without the knowledge or approval of the providers in whose names she wrote them.
Federal officials said Ms. Biesiada attempted to conceal the fraudulent prescriptions by marking them “filed in error” in the practice’s prescription system.
Lab owner pleads guilty to $6.9 million testing fraud scheme
A Florida lab owner has pleaded guilty to conspiracy to defraud Medicare through false and fraudulent claims totaling more than $6.9 million.
According to court documents, Christopher Licata, 45, of Delray Beach, Fla., admitted to bribing patient brokers to refer orders for medically unnecessary genetic testing to his lab. The tests were then billed to Medicare.
Mr. Licata and the patient brokers entered sham agreements meant to disguise the true purpose of the payments, according to a statement from the Department of Justice. The 45-year-old owner of Boca Toxicology (dba Lab Dynamics) pleaded guilty to one count of conspiring to commit health care fraud.
The scheme began in 2018; however, once the pandemic began, Mr. Licata shifted strategies, playing on patients’ fears of COVID-19 to bundle inexpensive COVID tests with more expensive medically unnecessary tests. These tests included respiratory pathogen panels and genetic testing for cardiovascular disease, cancer, diabetes, Alzheimer’s disease, and other illnesses. In all, Mr. Licata’s laboratory submitted over $6.9 million in false and fraudulent claims to Medicare for these unnecessary tests, according to the DOJ statement.
The case is a part of the U.S. Attorney General’s COVID-19 Fraud Enforcement Task Force that was established to enhance the efforts of agencies and governments across the country to combat and prevent pandemic-related fraud.
Mr. Licata faces a maximum penalty of 10 years in prison. His sentencing is scheduled for March 24.
A version of this article first appeared on Medscape.com.
According to court documents, between January 2014 and October 2019, family physician David Chisholm, MD, 64, of Wasilla, Alaska, wrote more than 20,000 prescriptions to approximately 350 patients for oxycodone, methadone, and hydrocodone, often prescribing the pills using variations of patients’ names in an attempt to avoid being red-flagged by payers.
When Walmart refused to continue filling the prescriptions, Dr. Chisholm told his staff to advise the patients to use other pharmacies. In addition, he often prescribed combinations of medications, such as concurrent opioids, benzodiazepines, sedatives, and carisoprodol, thus increasing the chances that his patients would become addicted to or overdose on the drugs. Chisholm, who pleaded guilty in June, acknowledged to federal officials that his prescriptions were a significant contributing factor to the overdose deaths of five of his patients during this time, according to a statement by the U.S. Attorney’s Office for the District of Alaska.
According to the Anchorage Daily News, Dr. Chisholm, who was not board certified in pain medicine, said his reason for prescribing the drugs was not to make money but to help patients suffering from chronic pain and because he enjoyed the challenge.
Dr. Chisholm’s attorney, Nick Oberheiden, told CNN his client “sacrificed his reputation as a patient advocate and his years of service to the Alaskan community” in overprescribing opioids. “He expressed his sincere remorse in open court and he accepts the consequences of his misconduct. He hopes that his case serves as a warning to other physicians facing the same dilemma when treating chronic pain.”
He surrendered his medical license in November 2020 before being formally charged in April 2021.
Texas hospital CEO, seven doctors settle kickback
A hospital executive and seven physicians have agreed to pay a total of $1.1 million to settle allegations that they violated the Anti-Kickback Statute and Stark Law. The eight have also agreed to cooperate in investigations and litigation involving other parties.
The Texas physicians involved in the settlement are internist Jaspaul Bhangoo, MD, of Denton; family physician Robert Megna, DO, of Ferris; cardiologist Baxter Montgomery, MD, of Houston; internist Murtaza Mussaji, DO, of Houston; family physician David Sneed, DO, of Austin; family physician Kevin Lewis, DO, of Houston; and family physician Angela Mosley-Nunnery, MD, of Kingwood.
Also settling was Richard DeFoore, former CEO of Jones County Regional Healthcare (dba Stamford Memorial Hospital).
The physicians were accused of accepting payments from organizations in exchange for ordering lab tests from True Health Diagnostics, Little River Healthcare, and Boston Heart. The payments to the physicians were disguised as investment returns but, according to the allegations, were in fact offered in exchange for the doctors’ referrals. Mr. DeFoore, the hospital executive involved in the settlement, allegedly oversaw a similar scheme that benefited the now-defunct Stamford Memorial.
“Paying kickbacks to physicians distorts the medical decision-making process, corrupts our health care system, and increases the cost of healthcare funded by the taxpayer,” Brit Featherston, U.S. attorney for the Eastern District of Texas, said in a statement announcing the agreement. “Laboratories, marketers, and physicians cannot immunize their conduct by attempting to disguise the kickbacks as some sort of investment arrangement.”
Practice administrative assistant sentenced for fraudulent prescriptions
An administrative assistant at an Illinois orthopedics office was sentenced to a year and a day in federal prison for writing fraudulent prescriptions for opioids.
Amanda Biesiada, 39, of Alsip, Ill., who worked as an administrative assistant at Hinsdale Orthopaedics in Westmont, Ill., was not a licensed physician and could not legally write the prescriptions unless instructed to do so and supervised by licensed doctors.
According to a statement by the U.S. Attorney’s Office for the Northern District of Illinois, the prescriptions for hydrocodone, oxycodone, and other controlled substances – 85 prescriptions in all from 2017 to 2019 – were made out to an acquaintance of Biesiada’s and written without the knowledge or approval of the providers in whose names she wrote them.
Federal officials said Ms. Biesiada attempted to conceal the fraudulent prescriptions by marking them “filed in error” in the practice’s prescription system.
Lab owner pleads guilty to $6.9 million testing fraud scheme
A Florida lab owner has pleaded guilty to conspiracy to defraud Medicare through false and fraudulent claims totaling more than $6.9 million.
According to court documents, Christopher Licata, 45, of Delray Beach, Fla., admitted to bribing patient brokers to refer orders for medically unnecessary genetic testing to his lab. The tests were then billed to Medicare.
Mr. Licata and the patient brokers entered sham agreements meant to disguise the true purpose of the payments, according to a statement from the Department of Justice. The 45-year-old owner of Boca Toxicology (dba Lab Dynamics) pleaded guilty to one count of conspiring to commit health care fraud.
The scheme began in 2018; however, once the pandemic began, Mr. Licata shifted strategies, playing on patients’ fears of COVID-19 to bundle inexpensive COVID tests with more expensive medically unnecessary tests. These tests included respiratory pathogen panels and genetic testing for cardiovascular disease, cancer, diabetes, Alzheimer’s disease, and other illnesses. In all, Mr. Licata’s laboratory submitted over $6.9 million in false and fraudulent claims to Medicare for these unnecessary tests, according to the DOJ statement.
The case is a part of the U.S. Attorney General’s COVID-19 Fraud Enforcement Task Force that was established to enhance the efforts of agencies and governments across the country to combat and prevent pandemic-related fraud.
Mr. Licata faces a maximum penalty of 10 years in prison. His sentencing is scheduled for March 24.
A version of this article first appeared on Medscape.com.
Ketamine an ‘intriguing new therapy’ for alcoholism
Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.
Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.
The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.
The study was published online Jan. 11 in the American Journal of Psychiatry.
Target depression
Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.
“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.
Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.
To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.
All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.
Participants were randomly allocated to one of four groups:
1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy
2. three saline infusions plus psychological therapy
3. three ketamine infusions plus alcohol education
4. three saline infusions plus alcohol education
The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.
(mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.
The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).
There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
Growing evidence
These findings support some other studies that have also suggested a benefit of ketamine in AUD.
As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.
“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.
“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.
Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
An ‘Intriguing new therapy’
Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”
“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.
“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.
The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.
Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.
The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.
The study was published online Jan. 11 in the American Journal of Psychiatry.
Target depression
Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.
“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.
Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.
To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.
All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.
Participants were randomly allocated to one of four groups:
1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy
2. three saline infusions plus psychological therapy
3. three ketamine infusions plus alcohol education
4. three saline infusions plus alcohol education
The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.
(mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.
The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).
There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
Growing evidence
These findings support some other studies that have also suggested a benefit of ketamine in AUD.
As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.
“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.
“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.
Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
An ‘Intriguing new therapy’
Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”
“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.
“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.
The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.
Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.
The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.
The study was published online Jan. 11 in the American Journal of Psychiatry.
Target depression
Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.
“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.
Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.
To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.
All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.
Participants were randomly allocated to one of four groups:
1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy
2. three saline infusions plus psychological therapy
3. three ketamine infusions plus alcohol education
4. three saline infusions plus alcohol education
The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.
(mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.
The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).
There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
Growing evidence
These findings support some other studies that have also suggested a benefit of ketamine in AUD.
As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.
“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.
“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.
Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
An ‘Intriguing new therapy’
Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”
“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.
“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.
The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
How to screen for and treat teen alcohol use
THE CASE
Paul F* is a 16-year-old White boy who lives with his mother and spends some weekends with his father who has shared custody. He recently presented to the clinic for treatment due to an arrest for disorderly conduct at school. He and a friend were found drinking liquor outside the school building when they were scheduled to be in class. Paul reported that he and his friends often drink at school and at extracurricular functions. He has been using alcohol for the past 2 years, with escalating consumption (5 or more drinks per episode) in the past year. Paul has been drinking most days of the week and has even driven under the influence at times. He said, “I just feel happier when I am drinking.” An accomplished soccer player recruited by colleges, Paul recently was suspended from the team due to his poor grades. His response was, “It’s stupid anyway. What’s the point of playing?”
●
* The patient’s name and some personal details have been changed to protect his identity.
Alcohol is the number 1 substance of abuse for adolescents, used more than tobacco or drugs.1-3 In 2007 and again in 2016, the Surgeon General of the United States issued reports to highlight this important topic,1,2 noting that early and repeated exposure to alcohol during this crucial time of brain development increases the risk for future problems, including addiction.2
Adolescent alcohol use is often underestimated by parents and physicians, including misjudging how much, how often, and how young children are when they begin to drink.1 Boys and girls tend to start drinking at similar ages (13.9 and 14.4 years, respectively),3 but as girls age, they tend to drink more and binge more.4 In 2019, 1 in 4 adolescents reported drinking and more than 4 million reported at least 1 episode of binge drinking in the prior month.4 These numbers have further ramifications: early drinking is associated with alcohol dependence, relapse, use of other substances, risky sexual behaviors, injurious behaviors, suicide, motor vehicle accidents, and dating violence.4-6
Diagnosing alcohol use disorder
The range of alcohol use includes consumption, bingeing, abuse, and dependence.7,8 Consumption is defined as the drinking of alcoholic beverages. Bingeing is the consumption of more than 5 drinks for men or 4 drinks for women in 2 hours, according to the National Institute on Alcohol Abuse and Alcoholism.7 However, the criterion is slightly different for the Substance Abuse and Mental Health Services Administration, which broadens the timeframe to “on the same occasion.”9 While previously known as separate disorders, alcohol abuse (or misuse) and alcohol dependence are now diagnostically classified together as alcohol use disorders (AUDs), per the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5).8 AUD is further stratified as mild, moderate, or severe, depending on the number of criteria that are met by the patient (TABLE).8,10
Alcohol screening
Currently, the US Preventive Services Task Force (USPSTF) does not recommend screening adolescents ages 12 to 17 for AUD, and has instead issued an “I” statement (insufficient evidence).11 While the USPSTF recognizes the potential burdens of adolescent alcohol use, the potential harms of screening include “stigma, anxiety, labeling, discrimination, privacy concerns, and interference with the patient–clinician relationship.”11 The USPSTF also notes that it “did not find any evidence that specifically examined the harms of screening for alcohol use in adolescents.”11
This is at odds with recommendations from the American Academy of Pediatrics (AAP), which in 2011 released a policy statement advocating screening, brief intervention, and referral to treatment for adolescent substance use.12 In the United States, even though 83% of adolescents see a physician at least once each year,12,13 alcohol misuse screening still varies, occurring in the range of 50% to 86% of office visits.12 When screening does occur, it is often based on clinical impression only.12 Studies have shown that when a screening tool is not used, up to two-thirds of substance use disorders may be missed.12-15
Continue to: A full and complete biopsychosocial interview
A full and complete biopsychosocial interview with adolescents is a necessity, and should include queries about alcohol, drugs, and other substances. Acknowledgment of use should trigger further investigation into the substance use areas. Interviews may start with open-ended questions about alcohol use at home or at school before moving to more personalized and detailed questioning and use of screening tools.16
While various screening instruments exist, for the sake of brevity we provide as an example the Screening to Brief Intervention (S2BI) tool. It is an efficient, single-page tool that can help clinicians in their routine care of adolescents to quickly stratify the patient risk of substance use disorder as none/low, moderate, or severe.12 It can be found here: www.mcpap.com/pdf/S2Bi%20Toolkit.pdf (see page 10).
For all patients, but particularly for adolescents, confidentiality is important, and many specialty societies have created language to address this issue.12 Discuss confidentiality with both the adolescent patient and the patient’s caregiver simultaneously, with dialogue that includes: (a) the need to speak with adolescents alone during the office visit, (b) the benefits of confidentiality in the physician–patient relationship, and (c) the need to disclose selected information to keep patients safe.12 Describing the process for required disclosures is essential. Benefits of disclosure include further support for the adolescent patient as well as appropriate parental participation and support for possible referrals.12
Treating AUD
Treatment for AUD should be multifaceted. Screen for comorbid mood disorders, such as generalized anxiety,17,18 social anxiety,18 and depression,19 as well as for insomnia.18 Studies have demonstrated a strong link between insomnia and anxiety, and again between anxiety and AUD.17-19 Finally, screen for adverse childhood events such as trauma, victimization, and abuse.20 Addressing issues discovered in screening allows for more targeted and personalized treatment of AUD.
The National Institute on Drug Abuse categorizes evidence-based treatment into 3 areas: behavioral therapies, family therapies, and medications.21
Continue to: Behavioral therapies
Behavioral therapies can include group therapy, cognitive behavioral therapy (CBT), motivational enhancement therapy, 12-Step facilitation, and contingency management, in which small rewards or incentives are given for participation in treatment to reinforce positive behaviors.21
Family-based therapies, such as brief strategic family therapy, functional family therapy, and multisystem therapy recognize that adolescents exist in systems of families in communities, and that the patient’s success in treatment may be supported by these relationships.21
Some medications may achieve modest benefit for treatment of adolescents with AUD. Naltrexone, acamprosate, and disulfiram have all been used successfully to treat AUD in adults21; some physicians may choose to use these medications “off label” in adolescents. Bupropion has been used successfully in the treatment of nicotine use disorder,21 and a small study in 2005 showed some success with bupropion in treating adolescents with attention-deficit/hyperactivity disorder, comorbid depression, and substance use disorder.22 Naltrexone has also been studied in adolescents with opioid use disorder, although these were not large studies.23
Adolescents with serious, sustained issues with AUD may require more in-depth treatments such as an intensive outpatient program, a partial hospitalization program, or a residential treatment program.15 The least-restrictive environment is preferable.15 Families are generally included as part of the treatment and recovery process in those settings.21 Some patients may require detoxification prior to referral to residential treatment settings; the American Society of Addiction Medicine has published a comprehensive guideline on alcohol withdrawal.24
Paul’s family physician diagnosed his condition as AUD and referred him for CBT with a psychologist, who treated him for both the AUD and an underlying depressive disorder that was later identified. CBT focused on cognitive restructuring of depressive thoughts as well as support for continued abstinence from alcohol. The patient, with family support, declined antidepressant medication.
After 6 months of treatment, Paul and his parents were pleased with his progress. His grades improved to the point that he was permitted to play soccer again, and he was seriously looking at his future college options.
CORRESPONDENCE
Scott A. Fields, PhD, 3200 MacCorkle Avenue Southeast, 5th Floor, Robert C. Byrd Clinical Teaching Center, Department of Family Medicine, Charleston, WV 25304; [email protected]
1. US Department of Health and Human Services. The Surgeon General’s Call to Action to Prevent and Reduce Underage Drinking. Washington, DC; US Department of Health and Human Services, Office of the Surgeon General. 2007.
2. US Department of Health and Human Services. Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC; US Department of Health and Human Services, Office of the Surgeon General. 2016.
3. Hingson R, White A. New research findings since the 2007 Surgeon General’s Call to Action to Prevent and Reduce Underage Drinking: A review. J Stud Alcohol Drugs Suppl. 2014; 75:158-169.
4. National Institute on Alcohol Abuse and Alcoholism. Underage drinking. National Institute of Health. Accessed December 22, 2021. www.niaaa.nih.gov/publications/brochures-and-fact-sheets/underage-drinking.
5. Hingson R, Zha W, Iannotti R, et al. Physician advice to adolescents about drinking and other health behaviors. Pediatrics. 2013;131:249-257.
6. Schaus JF, Sole ML, McCoy TP, et al. Screening for high-risk drinking in a college student health center: characterizing students based on quantity, frequency, and harms. J Stud Alcohol Drugs Suppl. 2009;16:34-44.
7. National Institute on Alcohol Abuse and Alcoholism. Drinking levels defined. Accessed December 27, 2021. www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking
8. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Arlington, VA; American Psychiatric Association. 2013.
9. Substance Abuse and Mental Health Services Administration. Bringing down binge drinking. Accessed December 27, 2021. www.samhsa.gov/sites/default/files/programs_campaigns/nation_prevention_week/data-binge-drinking.pdf
10. Grant BF, Goldstein RB, Saha TD, et al. Epidemiology of DSM-5 Alcohol Use Disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiatry. 2015;72:757-766.
11. USPSTF. Screening and behavioral counseling interventions to reduce unhealthy alcohol use in adolescents and adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;320:1899-1909.
12. Levy SJ, Williams JF, Committee on Substance Use and Prevention. Substance use screening, brief intervention, and referral to treatment. Pediatrics. 2016;138:e20161211.
13. MacKay AP, Duran CP. Adolescent Health in the United States. National Center for Health Statistics, Centers for Disease Control and Prevention. 2007.
14. Haller DM, Meynard A, Lefebvre D, et al. Effectiveness of training family physicians to deliver a brief intervention to address excessive substance use among young patients: a cluster randomized controlled trial. CMAJ. 2014;186:E263-E272.
15. Borus J, Parhami I, Levy S. Screening, brief intervention, and referral to treatment. Child Adolesc Psychiatric Clin N Am. 2016;25:579-601.
16. Knight J, Roberts T, Gabrielli J, et al. Adolescent alcohol and substance use and abuse. Performing preventive services: A bright futures handbook. Accessed December 22, 2021. American Academy of Pediatrics. https://ocfcpacourts.us/wp-content/uploads/2020/06/Adolescent_Alcohol_and_Substance_Abuse_001005.pdf
17. Dyer ML, Heron J, Hickman M, et al. Alcohol use in late adolescence and early adulthood: the role of generalized anxiety disorder and drinking to cope motives. Drug Alcohol Depend. 2019;204:107480.
18. Blumenthal H, Taylor DJ, Cloutier RM, et al. The links between social anxiety disorder, insomnia symptoms, and alcohol use disorders: findings from a large sample of adolescents in the United States. Behav Ther. 2019;50:50-59.
19. Pedrelli P, Shapero B, Archibald A, et al. Alcohol use and depression during adolescence and young adulthood: a summary and interpretation of mixed findings. Curr Addict Rep. 2016;3:91-97.
20. Davis JP, Dworkin ER, Helton J, et al. Extending poly-victimization theory: differential effects of adolescents’ experiences of victimization on substance use disorder diagnoses upon treatment entry. Child Abuse Negl. 2019; 89:165-177.
21. NIDA. Principles of adolescent substance use disorder treatment: a research-based guide. Accessed December 22, 2021. www.drugabuse.gov/publications/principles-adolescent-substance-use-disorder-treatment-research-based-guide
22. Solhkhah R, Wilens TE, Daly J, et al. Bupropion SR for the treatment of substance-abusing outpatient adolescents with attention-deficit/hyperactivity disorder and mood disorders. J Child Adolesc Psychopharmacol. 2005:15:777-786.
23. Camenga DR, Colon-Rivera HA, Muvvala SB. Medications for maintenance treatment of opioid use disorder in adolescents. J Stud Alcohol Drugs. 2019;80:393-402.
24. American Society of Addiction Medicine. The ASAM clinical practice guideline on alcohol withdrawal management. Accessed December 22, 2021. www.asam.org/quality-care/clinical-guidelines/alcohol-withdrawal-management-guideline
THE CASE
Paul F* is a 16-year-old White boy who lives with his mother and spends some weekends with his father who has shared custody. He recently presented to the clinic for treatment due to an arrest for disorderly conduct at school. He and a friend were found drinking liquor outside the school building when they were scheduled to be in class. Paul reported that he and his friends often drink at school and at extracurricular functions. He has been using alcohol for the past 2 years, with escalating consumption (5 or more drinks per episode) in the past year. Paul has been drinking most days of the week and has even driven under the influence at times. He said, “I just feel happier when I am drinking.” An accomplished soccer player recruited by colleges, Paul recently was suspended from the team due to his poor grades. His response was, “It’s stupid anyway. What’s the point of playing?”
●
* The patient’s name and some personal details have been changed to protect his identity.
Alcohol is the number 1 substance of abuse for adolescents, used more than tobacco or drugs.1-3 In 2007 and again in 2016, the Surgeon General of the United States issued reports to highlight this important topic,1,2 noting that early and repeated exposure to alcohol during this crucial time of brain development increases the risk for future problems, including addiction.2
Adolescent alcohol use is often underestimated by parents and physicians, including misjudging how much, how often, and how young children are when they begin to drink.1 Boys and girls tend to start drinking at similar ages (13.9 and 14.4 years, respectively),3 but as girls age, they tend to drink more and binge more.4 In 2019, 1 in 4 adolescents reported drinking and more than 4 million reported at least 1 episode of binge drinking in the prior month.4 These numbers have further ramifications: early drinking is associated with alcohol dependence, relapse, use of other substances, risky sexual behaviors, injurious behaviors, suicide, motor vehicle accidents, and dating violence.4-6
Diagnosing alcohol use disorder
The range of alcohol use includes consumption, bingeing, abuse, and dependence.7,8 Consumption is defined as the drinking of alcoholic beverages. Bingeing is the consumption of more than 5 drinks for men or 4 drinks for women in 2 hours, according to the National Institute on Alcohol Abuse and Alcoholism.7 However, the criterion is slightly different for the Substance Abuse and Mental Health Services Administration, which broadens the timeframe to “on the same occasion.”9 While previously known as separate disorders, alcohol abuse (or misuse) and alcohol dependence are now diagnostically classified together as alcohol use disorders (AUDs), per the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5).8 AUD is further stratified as mild, moderate, or severe, depending on the number of criteria that are met by the patient (TABLE).8,10
Alcohol screening
Currently, the US Preventive Services Task Force (USPSTF) does not recommend screening adolescents ages 12 to 17 for AUD, and has instead issued an “I” statement (insufficient evidence).11 While the USPSTF recognizes the potential burdens of adolescent alcohol use, the potential harms of screening include “stigma, anxiety, labeling, discrimination, privacy concerns, and interference with the patient–clinician relationship.”11 The USPSTF also notes that it “did not find any evidence that specifically examined the harms of screening for alcohol use in adolescents.”11
This is at odds with recommendations from the American Academy of Pediatrics (AAP), which in 2011 released a policy statement advocating screening, brief intervention, and referral to treatment for adolescent substance use.12 In the United States, even though 83% of adolescents see a physician at least once each year,12,13 alcohol misuse screening still varies, occurring in the range of 50% to 86% of office visits.12 When screening does occur, it is often based on clinical impression only.12 Studies have shown that when a screening tool is not used, up to two-thirds of substance use disorders may be missed.12-15
Continue to: A full and complete biopsychosocial interview
A full and complete biopsychosocial interview with adolescents is a necessity, and should include queries about alcohol, drugs, and other substances. Acknowledgment of use should trigger further investigation into the substance use areas. Interviews may start with open-ended questions about alcohol use at home or at school before moving to more personalized and detailed questioning and use of screening tools.16
While various screening instruments exist, for the sake of brevity we provide as an example the Screening to Brief Intervention (S2BI) tool. It is an efficient, single-page tool that can help clinicians in their routine care of adolescents to quickly stratify the patient risk of substance use disorder as none/low, moderate, or severe.12 It can be found here: www.mcpap.com/pdf/S2Bi%20Toolkit.pdf (see page 10).
For all patients, but particularly for adolescents, confidentiality is important, and many specialty societies have created language to address this issue.12 Discuss confidentiality with both the adolescent patient and the patient’s caregiver simultaneously, with dialogue that includes: (a) the need to speak with adolescents alone during the office visit, (b) the benefits of confidentiality in the physician–patient relationship, and (c) the need to disclose selected information to keep patients safe.12 Describing the process for required disclosures is essential. Benefits of disclosure include further support for the adolescent patient as well as appropriate parental participation and support for possible referrals.12
Treating AUD
Treatment for AUD should be multifaceted. Screen for comorbid mood disorders, such as generalized anxiety,17,18 social anxiety,18 and depression,19 as well as for insomnia.18 Studies have demonstrated a strong link between insomnia and anxiety, and again between anxiety and AUD.17-19 Finally, screen for adverse childhood events such as trauma, victimization, and abuse.20 Addressing issues discovered in screening allows for more targeted and personalized treatment of AUD.
The National Institute on Drug Abuse categorizes evidence-based treatment into 3 areas: behavioral therapies, family therapies, and medications.21
Continue to: Behavioral therapies
Behavioral therapies can include group therapy, cognitive behavioral therapy (CBT), motivational enhancement therapy, 12-Step facilitation, and contingency management, in which small rewards or incentives are given for participation in treatment to reinforce positive behaviors.21
Family-based therapies, such as brief strategic family therapy, functional family therapy, and multisystem therapy recognize that adolescents exist in systems of families in communities, and that the patient’s success in treatment may be supported by these relationships.21
Some medications may achieve modest benefit for treatment of adolescents with AUD. Naltrexone, acamprosate, and disulfiram have all been used successfully to treat AUD in adults21; some physicians may choose to use these medications “off label” in adolescents. Bupropion has been used successfully in the treatment of nicotine use disorder,21 and a small study in 2005 showed some success with bupropion in treating adolescents with attention-deficit/hyperactivity disorder, comorbid depression, and substance use disorder.22 Naltrexone has also been studied in adolescents with opioid use disorder, although these were not large studies.23
Adolescents with serious, sustained issues with AUD may require more in-depth treatments such as an intensive outpatient program, a partial hospitalization program, or a residential treatment program.15 The least-restrictive environment is preferable.15 Families are generally included as part of the treatment and recovery process in those settings.21 Some patients may require detoxification prior to referral to residential treatment settings; the American Society of Addiction Medicine has published a comprehensive guideline on alcohol withdrawal.24
Paul’s family physician diagnosed his condition as AUD and referred him for CBT with a psychologist, who treated him for both the AUD and an underlying depressive disorder that was later identified. CBT focused on cognitive restructuring of depressive thoughts as well as support for continued abstinence from alcohol. The patient, with family support, declined antidepressant medication.
After 6 months of treatment, Paul and his parents were pleased with his progress. His grades improved to the point that he was permitted to play soccer again, and he was seriously looking at his future college options.
CORRESPONDENCE
Scott A. Fields, PhD, 3200 MacCorkle Avenue Southeast, 5th Floor, Robert C. Byrd Clinical Teaching Center, Department of Family Medicine, Charleston, WV 25304; [email protected]
THE CASE
Paul F* is a 16-year-old White boy who lives with his mother and spends some weekends with his father who has shared custody. He recently presented to the clinic for treatment due to an arrest for disorderly conduct at school. He and a friend were found drinking liquor outside the school building when they were scheduled to be in class. Paul reported that he and his friends often drink at school and at extracurricular functions. He has been using alcohol for the past 2 years, with escalating consumption (5 or more drinks per episode) in the past year. Paul has been drinking most days of the week and has even driven under the influence at times. He said, “I just feel happier when I am drinking.” An accomplished soccer player recruited by colleges, Paul recently was suspended from the team due to his poor grades. His response was, “It’s stupid anyway. What’s the point of playing?”
●
* The patient’s name and some personal details have been changed to protect his identity.
Alcohol is the number 1 substance of abuse for adolescents, used more than tobacco or drugs.1-3 In 2007 and again in 2016, the Surgeon General of the United States issued reports to highlight this important topic,1,2 noting that early and repeated exposure to alcohol during this crucial time of brain development increases the risk for future problems, including addiction.2
Adolescent alcohol use is often underestimated by parents and physicians, including misjudging how much, how often, and how young children are when they begin to drink.1 Boys and girls tend to start drinking at similar ages (13.9 and 14.4 years, respectively),3 but as girls age, they tend to drink more and binge more.4 In 2019, 1 in 4 adolescents reported drinking and more than 4 million reported at least 1 episode of binge drinking in the prior month.4 These numbers have further ramifications: early drinking is associated with alcohol dependence, relapse, use of other substances, risky sexual behaviors, injurious behaviors, suicide, motor vehicle accidents, and dating violence.4-6
Diagnosing alcohol use disorder
The range of alcohol use includes consumption, bingeing, abuse, and dependence.7,8 Consumption is defined as the drinking of alcoholic beverages. Bingeing is the consumption of more than 5 drinks for men or 4 drinks for women in 2 hours, according to the National Institute on Alcohol Abuse and Alcoholism.7 However, the criterion is slightly different for the Substance Abuse and Mental Health Services Administration, which broadens the timeframe to “on the same occasion.”9 While previously known as separate disorders, alcohol abuse (or misuse) and alcohol dependence are now diagnostically classified together as alcohol use disorders (AUDs), per the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5).8 AUD is further stratified as mild, moderate, or severe, depending on the number of criteria that are met by the patient (TABLE).8,10
Alcohol screening
Currently, the US Preventive Services Task Force (USPSTF) does not recommend screening adolescents ages 12 to 17 for AUD, and has instead issued an “I” statement (insufficient evidence).11 While the USPSTF recognizes the potential burdens of adolescent alcohol use, the potential harms of screening include “stigma, anxiety, labeling, discrimination, privacy concerns, and interference with the patient–clinician relationship.”11 The USPSTF also notes that it “did not find any evidence that specifically examined the harms of screening for alcohol use in adolescents.”11
This is at odds with recommendations from the American Academy of Pediatrics (AAP), which in 2011 released a policy statement advocating screening, brief intervention, and referral to treatment for adolescent substance use.12 In the United States, even though 83% of adolescents see a physician at least once each year,12,13 alcohol misuse screening still varies, occurring in the range of 50% to 86% of office visits.12 When screening does occur, it is often based on clinical impression only.12 Studies have shown that when a screening tool is not used, up to two-thirds of substance use disorders may be missed.12-15
Continue to: A full and complete biopsychosocial interview
A full and complete biopsychosocial interview with adolescents is a necessity, and should include queries about alcohol, drugs, and other substances. Acknowledgment of use should trigger further investigation into the substance use areas. Interviews may start with open-ended questions about alcohol use at home or at school before moving to more personalized and detailed questioning and use of screening tools.16
While various screening instruments exist, for the sake of brevity we provide as an example the Screening to Brief Intervention (S2BI) tool. It is an efficient, single-page tool that can help clinicians in their routine care of adolescents to quickly stratify the patient risk of substance use disorder as none/low, moderate, or severe.12 It can be found here: www.mcpap.com/pdf/S2Bi%20Toolkit.pdf (see page 10).
For all patients, but particularly for adolescents, confidentiality is important, and many specialty societies have created language to address this issue.12 Discuss confidentiality with both the adolescent patient and the patient’s caregiver simultaneously, with dialogue that includes: (a) the need to speak with adolescents alone during the office visit, (b) the benefits of confidentiality in the physician–patient relationship, and (c) the need to disclose selected information to keep patients safe.12 Describing the process for required disclosures is essential. Benefits of disclosure include further support for the adolescent patient as well as appropriate parental participation and support for possible referrals.12
Treating AUD
Treatment for AUD should be multifaceted. Screen for comorbid mood disorders, such as generalized anxiety,17,18 social anxiety,18 and depression,19 as well as for insomnia.18 Studies have demonstrated a strong link between insomnia and anxiety, and again between anxiety and AUD.17-19 Finally, screen for adverse childhood events such as trauma, victimization, and abuse.20 Addressing issues discovered in screening allows for more targeted and personalized treatment of AUD.
The National Institute on Drug Abuse categorizes evidence-based treatment into 3 areas: behavioral therapies, family therapies, and medications.21
Continue to: Behavioral therapies
Behavioral therapies can include group therapy, cognitive behavioral therapy (CBT), motivational enhancement therapy, 12-Step facilitation, and contingency management, in which small rewards or incentives are given for participation in treatment to reinforce positive behaviors.21
Family-based therapies, such as brief strategic family therapy, functional family therapy, and multisystem therapy recognize that adolescents exist in systems of families in communities, and that the patient’s success in treatment may be supported by these relationships.21
Some medications may achieve modest benefit for treatment of adolescents with AUD. Naltrexone, acamprosate, and disulfiram have all been used successfully to treat AUD in adults21; some physicians may choose to use these medications “off label” in adolescents. Bupropion has been used successfully in the treatment of nicotine use disorder,21 and a small study in 2005 showed some success with bupropion in treating adolescents with attention-deficit/hyperactivity disorder, comorbid depression, and substance use disorder.22 Naltrexone has also been studied in adolescents with opioid use disorder, although these were not large studies.23
Adolescents with serious, sustained issues with AUD may require more in-depth treatments such as an intensive outpatient program, a partial hospitalization program, or a residential treatment program.15 The least-restrictive environment is preferable.15 Families are generally included as part of the treatment and recovery process in those settings.21 Some patients may require detoxification prior to referral to residential treatment settings; the American Society of Addiction Medicine has published a comprehensive guideline on alcohol withdrawal.24
Paul’s family physician diagnosed his condition as AUD and referred him for CBT with a psychologist, who treated him for both the AUD and an underlying depressive disorder that was later identified. CBT focused on cognitive restructuring of depressive thoughts as well as support for continued abstinence from alcohol. The patient, with family support, declined antidepressant medication.
After 6 months of treatment, Paul and his parents were pleased with his progress. His grades improved to the point that he was permitted to play soccer again, and he was seriously looking at his future college options.
CORRESPONDENCE
Scott A. Fields, PhD, 3200 MacCorkle Avenue Southeast, 5th Floor, Robert C. Byrd Clinical Teaching Center, Department of Family Medicine, Charleston, WV 25304; [email protected]
1. US Department of Health and Human Services. The Surgeon General’s Call to Action to Prevent and Reduce Underage Drinking. Washington, DC; US Department of Health and Human Services, Office of the Surgeon General. 2007.
2. US Department of Health and Human Services. Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC; US Department of Health and Human Services, Office of the Surgeon General. 2016.
3. Hingson R, White A. New research findings since the 2007 Surgeon General’s Call to Action to Prevent and Reduce Underage Drinking: A review. J Stud Alcohol Drugs Suppl. 2014; 75:158-169.
4. National Institute on Alcohol Abuse and Alcoholism. Underage drinking. National Institute of Health. Accessed December 22, 2021. www.niaaa.nih.gov/publications/brochures-and-fact-sheets/underage-drinking.
5. Hingson R, Zha W, Iannotti R, et al. Physician advice to adolescents about drinking and other health behaviors. Pediatrics. 2013;131:249-257.
6. Schaus JF, Sole ML, McCoy TP, et al. Screening for high-risk drinking in a college student health center: characterizing students based on quantity, frequency, and harms. J Stud Alcohol Drugs Suppl. 2009;16:34-44.
7. National Institute on Alcohol Abuse and Alcoholism. Drinking levels defined. Accessed December 27, 2021. www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking
8. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Arlington, VA; American Psychiatric Association. 2013.
9. Substance Abuse and Mental Health Services Administration. Bringing down binge drinking. Accessed December 27, 2021. www.samhsa.gov/sites/default/files/programs_campaigns/nation_prevention_week/data-binge-drinking.pdf
10. Grant BF, Goldstein RB, Saha TD, et al. Epidemiology of DSM-5 Alcohol Use Disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiatry. 2015;72:757-766.
11. USPSTF. Screening and behavioral counseling interventions to reduce unhealthy alcohol use in adolescents and adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;320:1899-1909.
12. Levy SJ, Williams JF, Committee on Substance Use and Prevention. Substance use screening, brief intervention, and referral to treatment. Pediatrics. 2016;138:e20161211.
13. MacKay AP, Duran CP. Adolescent Health in the United States. National Center for Health Statistics, Centers for Disease Control and Prevention. 2007.
14. Haller DM, Meynard A, Lefebvre D, et al. Effectiveness of training family physicians to deliver a brief intervention to address excessive substance use among young patients: a cluster randomized controlled trial. CMAJ. 2014;186:E263-E272.
15. Borus J, Parhami I, Levy S. Screening, brief intervention, and referral to treatment. Child Adolesc Psychiatric Clin N Am. 2016;25:579-601.
16. Knight J, Roberts T, Gabrielli J, et al. Adolescent alcohol and substance use and abuse. Performing preventive services: A bright futures handbook. Accessed December 22, 2021. American Academy of Pediatrics. https://ocfcpacourts.us/wp-content/uploads/2020/06/Adolescent_Alcohol_and_Substance_Abuse_001005.pdf
17. Dyer ML, Heron J, Hickman M, et al. Alcohol use in late adolescence and early adulthood: the role of generalized anxiety disorder and drinking to cope motives. Drug Alcohol Depend. 2019;204:107480.
18. Blumenthal H, Taylor DJ, Cloutier RM, et al. The links between social anxiety disorder, insomnia symptoms, and alcohol use disorders: findings from a large sample of adolescents in the United States. Behav Ther. 2019;50:50-59.
19. Pedrelli P, Shapero B, Archibald A, et al. Alcohol use and depression during adolescence and young adulthood: a summary and interpretation of mixed findings. Curr Addict Rep. 2016;3:91-97.
20. Davis JP, Dworkin ER, Helton J, et al. Extending poly-victimization theory: differential effects of adolescents’ experiences of victimization on substance use disorder diagnoses upon treatment entry. Child Abuse Negl. 2019; 89:165-177.
21. NIDA. Principles of adolescent substance use disorder treatment: a research-based guide. Accessed December 22, 2021. www.drugabuse.gov/publications/principles-adolescent-substance-use-disorder-treatment-research-based-guide
22. Solhkhah R, Wilens TE, Daly J, et al. Bupropion SR for the treatment of substance-abusing outpatient adolescents with attention-deficit/hyperactivity disorder and mood disorders. J Child Adolesc Psychopharmacol. 2005:15:777-786.
23. Camenga DR, Colon-Rivera HA, Muvvala SB. Medications for maintenance treatment of opioid use disorder in adolescents. J Stud Alcohol Drugs. 2019;80:393-402.
24. American Society of Addiction Medicine. The ASAM clinical practice guideline on alcohol withdrawal management. Accessed December 22, 2021. www.asam.org/quality-care/clinical-guidelines/alcohol-withdrawal-management-guideline
1. US Department of Health and Human Services. The Surgeon General’s Call to Action to Prevent and Reduce Underage Drinking. Washington, DC; US Department of Health and Human Services, Office of the Surgeon General. 2007.
2. US Department of Health and Human Services. Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC; US Department of Health and Human Services, Office of the Surgeon General. 2016.
3. Hingson R, White A. New research findings since the 2007 Surgeon General’s Call to Action to Prevent and Reduce Underage Drinking: A review. J Stud Alcohol Drugs Suppl. 2014; 75:158-169.
4. National Institute on Alcohol Abuse and Alcoholism. Underage drinking. National Institute of Health. Accessed December 22, 2021. www.niaaa.nih.gov/publications/brochures-and-fact-sheets/underage-drinking.
5. Hingson R, Zha W, Iannotti R, et al. Physician advice to adolescents about drinking and other health behaviors. Pediatrics. 2013;131:249-257.
6. Schaus JF, Sole ML, McCoy TP, et al. Screening for high-risk drinking in a college student health center: characterizing students based on quantity, frequency, and harms. J Stud Alcohol Drugs Suppl. 2009;16:34-44.
7. National Institute on Alcohol Abuse and Alcoholism. Drinking levels defined. Accessed December 27, 2021. www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking
8. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Arlington, VA; American Psychiatric Association. 2013.
9. Substance Abuse and Mental Health Services Administration. Bringing down binge drinking. Accessed December 27, 2021. www.samhsa.gov/sites/default/files/programs_campaigns/nation_prevention_week/data-binge-drinking.pdf
10. Grant BF, Goldstein RB, Saha TD, et al. Epidemiology of DSM-5 Alcohol Use Disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiatry. 2015;72:757-766.
11. USPSTF. Screening and behavioral counseling interventions to reduce unhealthy alcohol use in adolescents and adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;320:1899-1909.
12. Levy SJ, Williams JF, Committee on Substance Use and Prevention. Substance use screening, brief intervention, and referral to treatment. Pediatrics. 2016;138:e20161211.
13. MacKay AP, Duran CP. Adolescent Health in the United States. National Center for Health Statistics, Centers for Disease Control and Prevention. 2007.
14. Haller DM, Meynard A, Lefebvre D, et al. Effectiveness of training family physicians to deliver a brief intervention to address excessive substance use among young patients: a cluster randomized controlled trial. CMAJ. 2014;186:E263-E272.
15. Borus J, Parhami I, Levy S. Screening, brief intervention, and referral to treatment. Child Adolesc Psychiatric Clin N Am. 2016;25:579-601.
16. Knight J, Roberts T, Gabrielli J, et al. Adolescent alcohol and substance use and abuse. Performing preventive services: A bright futures handbook. Accessed December 22, 2021. American Academy of Pediatrics. https://ocfcpacourts.us/wp-content/uploads/2020/06/Adolescent_Alcohol_and_Substance_Abuse_001005.pdf
17. Dyer ML, Heron J, Hickman M, et al. Alcohol use in late adolescence and early adulthood: the role of generalized anxiety disorder and drinking to cope motives. Drug Alcohol Depend. 2019;204:107480.
18. Blumenthal H, Taylor DJ, Cloutier RM, et al. The links between social anxiety disorder, insomnia symptoms, and alcohol use disorders: findings from a large sample of adolescents in the United States. Behav Ther. 2019;50:50-59.
19. Pedrelli P, Shapero B, Archibald A, et al. Alcohol use and depression during adolescence and young adulthood: a summary and interpretation of mixed findings. Curr Addict Rep. 2016;3:91-97.
20. Davis JP, Dworkin ER, Helton J, et al. Extending poly-victimization theory: differential effects of adolescents’ experiences of victimization on substance use disorder diagnoses upon treatment entry. Child Abuse Negl. 2019; 89:165-177.
21. NIDA. Principles of adolescent substance use disorder treatment: a research-based guide. Accessed December 22, 2021. www.drugabuse.gov/publications/principles-adolescent-substance-use-disorder-treatment-research-based-guide
22. Solhkhah R, Wilens TE, Daly J, et al. Bupropion SR for the treatment of substance-abusing outpatient adolescents with attention-deficit/hyperactivity disorder and mood disorders. J Child Adolesc Psychopharmacol. 2005:15:777-786.
23. Camenga DR, Colon-Rivera HA, Muvvala SB. Medications for maintenance treatment of opioid use disorder in adolescents. J Stud Alcohol Drugs. 2019;80:393-402.
24. American Society of Addiction Medicine. The ASAM clinical practice guideline on alcohol withdrawal management. Accessed December 22, 2021. www.asam.org/quality-care/clinical-guidelines/alcohol-withdrawal-management-guideline
Dramatic increase in driving high after cannabis legislation
Since Canada legalized marijuana in 2018, there has been a dramatic increase in the number of individuals driving while high, new research shows.
Investigators studied over 4,000 drivers treated after a motor vehicle collision in British Columbia trauma centers and found that, before cannabis was legalized, a THC level greater than 0 ng/mL in the blood was present in roughly 10% of drivers. After the drug was legalized this percentage increased to 18%. The percentages of injured drivers with at least 2 ng/mL, the Canadian legal limit, and at least 5 ng/mL more than doubled.
“It’s concerning that we’re seeing such a dramatic increase,” study investigator Jeffrey Brubacher, MD, associate professor, department of emergency medicine, University of British Columbia, Vancouver, said in a press release.
“There are serious risks associated with driving after cannabis use and our findings suggest more [work] is needed to deter this dangerous behavior in light of legalization,” he said.
The study was published online Jan. 12 in the New England Journal of Medicine.
Impact of legalization?
The investigators note that the Canadian government introduced a law aiming to prevent cannabis-impaired driving by establishing penalties and criminal charges for drivers found with a whole-blood THC level of 2 ng/mL, with more severe penalties for those with a THC level of greater than 5 ng/mL or greater than 2.5 ng/mL combined with a blood alcohol level of .05%.
Cannabis use is “associated with cognitive deficits and psychomotor impairment, and there is evidence that it increases the risk of motor vehicle crashes, especially at higher THC levels,” they noted.
“I’m an emergency physician at Vancouver General Hospital’s trauma center. We’ve been measuring drug levels in injured drivers since 2013 here in British Columbia and, in particular, we’ve been measuring THC levels,” Dr. Brubacher said in an interview. “We thought it would be interesting and important to see what would happen after legalization.”
The investigators studied 4,339 drivers – 3,550 whose accident took place before legalization of cannabis, and 789 after legalization – who had been moderately injured in a motor vehicle collision and presented to four British Columbia trauma centers between January 2013 and March 2020.
said Dr. Brubacher. Drivers included in the study had excess blood remaining after the clinical testing had been completed, which was then used for drug analysis.
Insufficient laws
After legalization there was an increased prevalence of drivers with a THC level greater than 0 ng/mL, a TCH level of at least 2 ng/mL, and a THC level of at least 5 ng/mL.
The largest increases in a THC level of at least 2 ng/mL were in drivers 50 years of age or older and among male drivers (adjusted prevalence ratio, 5.18; 95% confidence interval, 2.49-10.78 and aPR, 2.44; 95% CI, 1.60-3.74, respectively).
“There were no significant changes in the prevalence of drivers testing positive for alcohol,” the authors reported.
Dr. Brubacher said the evidence suggests these new laws “are not enough to stop everyone from driving after using cannabis.”
The findings have implications for clinicians and patients and for policymakers, he said. “My moderately conservative recommendations are that, if you are going to smoke cannabis, wait at least 4 hours after smoking before you drive. Edibles last longer, and patients should wait least 8 hours after ingesting [edibles] before driving. And of course, if you continue to feel the effects of the THC, you should avoid driving altogether until the time has elapsed and you no longer feel any effects.”
Dr. Brubacher hopes policy makers will use the study’s findings to “design public information campaigns and enforcement measures that encourage drivers, especially older drivers, to separate cannabis use from driving.”
Additionally, “policy makers shouldn’t lose sight of drinking and driving because that’s an even bigger problem than the risk of driving under the influence of cannabis.”
Focus on older adults
In a comment, Anees Bahji, MD, an International Collaborative Addiction Medicine research fellow at the British Columbia Centre on Substance Use, called the study “interesting and relevant.”
He raised several questions regarding the “correlation between the level of a substance in a person’s system and the degree of impairment.” For example, “does the same level of THC in the blood affect us all the same way? And to what extent do the levels detected at the time of the analysis correlate with the level in the person’s system at the time of driving?”
An additional consideration “is for individuals with cannabis use disorder and for those who have developed tolerance to the psychoactive effects of THC: Does it affect their driving skills in the same way as someone who is cannabis naive?” asked Dr. Bahji, a clinical assistant professor at the University of Calgary (Alta.) who was not involved with the study.
Also commenting, Eric Sevigny, PhD, associate professor of criminal justice and criminology at Georgia State University, Atlanta, described it as a “well-designed study that adds yet another data point for considering appropriate road safety policy responses alongside ongoing cannabis liberalization.”
However, the findings “cannot say much about whether cannabis legalization leads to an increase in cannabis-impaired driving, because current research finds little correlation between biological THC concentrations and driving performance,” said Dr. Sevigny, who was not involved with the study.
The finding of “higher THC prevalence among older adults is also relevant for road safety, as this population has a number of concomitant risk factors, such as cognitive decline and prescription drug use,” Dr. Sevigny added.
The study was supported by the Canadian Institutes of Health Research. Dr. Brubacher and Dr. Sevigny disclosed no relevant financial relationships. Dr. Bahji reported receiving research funding from the Canadian Institutes of Health Research, the Calgary Health Trust, the American Psychiatric Association, NIDA, and the University of Calgary.
A version of this article first appeared on Medscape.com.
Since Canada legalized marijuana in 2018, there has been a dramatic increase in the number of individuals driving while high, new research shows.
Investigators studied over 4,000 drivers treated after a motor vehicle collision in British Columbia trauma centers and found that, before cannabis was legalized, a THC level greater than 0 ng/mL in the blood was present in roughly 10% of drivers. After the drug was legalized this percentage increased to 18%. The percentages of injured drivers with at least 2 ng/mL, the Canadian legal limit, and at least 5 ng/mL more than doubled.
“It’s concerning that we’re seeing such a dramatic increase,” study investigator Jeffrey Brubacher, MD, associate professor, department of emergency medicine, University of British Columbia, Vancouver, said in a press release.
“There are serious risks associated with driving after cannabis use and our findings suggest more [work] is needed to deter this dangerous behavior in light of legalization,” he said.
The study was published online Jan. 12 in the New England Journal of Medicine.
Impact of legalization?
The investigators note that the Canadian government introduced a law aiming to prevent cannabis-impaired driving by establishing penalties and criminal charges for drivers found with a whole-blood THC level of 2 ng/mL, with more severe penalties for those with a THC level of greater than 5 ng/mL or greater than 2.5 ng/mL combined with a blood alcohol level of .05%.
Cannabis use is “associated with cognitive deficits and psychomotor impairment, and there is evidence that it increases the risk of motor vehicle crashes, especially at higher THC levels,” they noted.
“I’m an emergency physician at Vancouver General Hospital’s trauma center. We’ve been measuring drug levels in injured drivers since 2013 here in British Columbia and, in particular, we’ve been measuring THC levels,” Dr. Brubacher said in an interview. “We thought it would be interesting and important to see what would happen after legalization.”
The investigators studied 4,339 drivers – 3,550 whose accident took place before legalization of cannabis, and 789 after legalization – who had been moderately injured in a motor vehicle collision and presented to four British Columbia trauma centers between January 2013 and March 2020.
said Dr. Brubacher. Drivers included in the study had excess blood remaining after the clinical testing had been completed, which was then used for drug analysis.
Insufficient laws
After legalization there was an increased prevalence of drivers with a THC level greater than 0 ng/mL, a TCH level of at least 2 ng/mL, and a THC level of at least 5 ng/mL.
The largest increases in a THC level of at least 2 ng/mL were in drivers 50 years of age or older and among male drivers (adjusted prevalence ratio, 5.18; 95% confidence interval, 2.49-10.78 and aPR, 2.44; 95% CI, 1.60-3.74, respectively).
“There were no significant changes in the prevalence of drivers testing positive for alcohol,” the authors reported.
Dr. Brubacher said the evidence suggests these new laws “are not enough to stop everyone from driving after using cannabis.”
The findings have implications for clinicians and patients and for policymakers, he said. “My moderately conservative recommendations are that, if you are going to smoke cannabis, wait at least 4 hours after smoking before you drive. Edibles last longer, and patients should wait least 8 hours after ingesting [edibles] before driving. And of course, if you continue to feel the effects of the THC, you should avoid driving altogether until the time has elapsed and you no longer feel any effects.”
Dr. Brubacher hopes policy makers will use the study’s findings to “design public information campaigns and enforcement measures that encourage drivers, especially older drivers, to separate cannabis use from driving.”
Additionally, “policy makers shouldn’t lose sight of drinking and driving because that’s an even bigger problem than the risk of driving under the influence of cannabis.”
Focus on older adults
In a comment, Anees Bahji, MD, an International Collaborative Addiction Medicine research fellow at the British Columbia Centre on Substance Use, called the study “interesting and relevant.”
He raised several questions regarding the “correlation between the level of a substance in a person’s system and the degree of impairment.” For example, “does the same level of THC in the blood affect us all the same way? And to what extent do the levels detected at the time of the analysis correlate with the level in the person’s system at the time of driving?”
An additional consideration “is for individuals with cannabis use disorder and for those who have developed tolerance to the psychoactive effects of THC: Does it affect their driving skills in the same way as someone who is cannabis naive?” asked Dr. Bahji, a clinical assistant professor at the University of Calgary (Alta.) who was not involved with the study.
Also commenting, Eric Sevigny, PhD, associate professor of criminal justice and criminology at Georgia State University, Atlanta, described it as a “well-designed study that adds yet another data point for considering appropriate road safety policy responses alongside ongoing cannabis liberalization.”
However, the findings “cannot say much about whether cannabis legalization leads to an increase in cannabis-impaired driving, because current research finds little correlation between biological THC concentrations and driving performance,” said Dr. Sevigny, who was not involved with the study.
The finding of “higher THC prevalence among older adults is also relevant for road safety, as this population has a number of concomitant risk factors, such as cognitive decline and prescription drug use,” Dr. Sevigny added.
The study was supported by the Canadian Institutes of Health Research. Dr. Brubacher and Dr. Sevigny disclosed no relevant financial relationships. Dr. Bahji reported receiving research funding from the Canadian Institutes of Health Research, the Calgary Health Trust, the American Psychiatric Association, NIDA, and the University of Calgary.
A version of this article first appeared on Medscape.com.
Since Canada legalized marijuana in 2018, there has been a dramatic increase in the number of individuals driving while high, new research shows.
Investigators studied over 4,000 drivers treated after a motor vehicle collision in British Columbia trauma centers and found that, before cannabis was legalized, a THC level greater than 0 ng/mL in the blood was present in roughly 10% of drivers. After the drug was legalized this percentage increased to 18%. The percentages of injured drivers with at least 2 ng/mL, the Canadian legal limit, and at least 5 ng/mL more than doubled.
“It’s concerning that we’re seeing such a dramatic increase,” study investigator Jeffrey Brubacher, MD, associate professor, department of emergency medicine, University of British Columbia, Vancouver, said in a press release.
“There are serious risks associated with driving after cannabis use and our findings suggest more [work] is needed to deter this dangerous behavior in light of legalization,” he said.
The study was published online Jan. 12 in the New England Journal of Medicine.
Impact of legalization?
The investigators note that the Canadian government introduced a law aiming to prevent cannabis-impaired driving by establishing penalties and criminal charges for drivers found with a whole-blood THC level of 2 ng/mL, with more severe penalties for those with a THC level of greater than 5 ng/mL or greater than 2.5 ng/mL combined with a blood alcohol level of .05%.
Cannabis use is “associated with cognitive deficits and psychomotor impairment, and there is evidence that it increases the risk of motor vehicle crashes, especially at higher THC levels,” they noted.
“I’m an emergency physician at Vancouver General Hospital’s trauma center. We’ve been measuring drug levels in injured drivers since 2013 here in British Columbia and, in particular, we’ve been measuring THC levels,” Dr. Brubacher said in an interview. “We thought it would be interesting and important to see what would happen after legalization.”
The investigators studied 4,339 drivers – 3,550 whose accident took place before legalization of cannabis, and 789 after legalization – who had been moderately injured in a motor vehicle collision and presented to four British Columbia trauma centers between January 2013 and March 2020.
said Dr. Brubacher. Drivers included in the study had excess blood remaining after the clinical testing had been completed, which was then used for drug analysis.
Insufficient laws
After legalization there was an increased prevalence of drivers with a THC level greater than 0 ng/mL, a TCH level of at least 2 ng/mL, and a THC level of at least 5 ng/mL.
The largest increases in a THC level of at least 2 ng/mL were in drivers 50 years of age or older and among male drivers (adjusted prevalence ratio, 5.18; 95% confidence interval, 2.49-10.78 and aPR, 2.44; 95% CI, 1.60-3.74, respectively).
“There were no significant changes in the prevalence of drivers testing positive for alcohol,” the authors reported.
Dr. Brubacher said the evidence suggests these new laws “are not enough to stop everyone from driving after using cannabis.”
The findings have implications for clinicians and patients and for policymakers, he said. “My moderately conservative recommendations are that, if you are going to smoke cannabis, wait at least 4 hours after smoking before you drive. Edibles last longer, and patients should wait least 8 hours after ingesting [edibles] before driving. And of course, if you continue to feel the effects of the THC, you should avoid driving altogether until the time has elapsed and you no longer feel any effects.”
Dr. Brubacher hopes policy makers will use the study’s findings to “design public information campaigns and enforcement measures that encourage drivers, especially older drivers, to separate cannabis use from driving.”
Additionally, “policy makers shouldn’t lose sight of drinking and driving because that’s an even bigger problem than the risk of driving under the influence of cannabis.”
Focus on older adults
In a comment, Anees Bahji, MD, an International Collaborative Addiction Medicine research fellow at the British Columbia Centre on Substance Use, called the study “interesting and relevant.”
He raised several questions regarding the “correlation between the level of a substance in a person’s system and the degree of impairment.” For example, “does the same level of THC in the blood affect us all the same way? And to what extent do the levels detected at the time of the analysis correlate with the level in the person’s system at the time of driving?”
An additional consideration “is for individuals with cannabis use disorder and for those who have developed tolerance to the psychoactive effects of THC: Does it affect their driving skills in the same way as someone who is cannabis naive?” asked Dr. Bahji, a clinical assistant professor at the University of Calgary (Alta.) who was not involved with the study.
Also commenting, Eric Sevigny, PhD, associate professor of criminal justice and criminology at Georgia State University, Atlanta, described it as a “well-designed study that adds yet another data point for considering appropriate road safety policy responses alongside ongoing cannabis liberalization.”
However, the findings “cannot say much about whether cannabis legalization leads to an increase in cannabis-impaired driving, because current research finds little correlation between biological THC concentrations and driving performance,” said Dr. Sevigny, who was not involved with the study.
The finding of “higher THC prevalence among older adults is also relevant for road safety, as this population has a number of concomitant risk factors, such as cognitive decline and prescription drug use,” Dr. Sevigny added.
The study was supported by the Canadian Institutes of Health Research. Dr. Brubacher and Dr. Sevigny disclosed no relevant financial relationships. Dr. Bahji reported receiving research funding from the Canadian Institutes of Health Research, the Calgary Health Trust, the American Psychiatric Association, NIDA, and the University of Calgary.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Orally dissolving buprenorphine tied to severe tooth decay, FDA warns
Orally dissolving medications containing buprenorphine are linked to severe dental problems, including total tooth loss, the U.S. Food and Drug Administration warns in a safety communication.
The oral side effects of these medications, which are used to treat opioid use disorder (OUD) and pain, include cavities/tooth decay, including rampant caries; dental abscesses/infection; tooth erosion; fillings falling out; and, in some cases, total tooth loss.
Multiple cases have been reported even in patients with no history of dental problems.
The FDA is adding a warning about the risk of dental problems to the prescribing information and the patient medication guide for all buprenorphine-containing medicines dissolved in the mouth.
The FDA emphasizes, however, that buprenorphine remains “an important treatment option for OUD and pain, and the benefits of these medicines clearly outweigh the risks.”
More than 300 reported cases
Buprenorphine was approved in 2002 as a sublingual tablet, and in 2015 as a film to be placed inside the cheek to treat pain. Both delivery methods have been associated with dental problems.
Since buprenorphine was approved, the FDA has identified 305 cases of dental problems associated with orally dissolving buprenorphine, including 131 classified as serious.
There may be other cases, the FDA says, as this represents only cases reported to the FDA or published in the medical literature.
, but those as young as 18 years old were also affected.
Most cases occurred in patients using the medicines for OUD; however, 28 cases of dental problems occurred in patients using it to treat pain.
In 26 cases, patients had no prior history of dental problems. Some dental problems developed as soon as 2 weeks after treatment began; the median time to diagnosis was about 2 years after starting treatment.
Among all 305 cases reported, 113 involved two or more teeth.
The most common treatment for the dental problems was tooth extraction/removal, which was reported in 71 cases. Other cases required root canals, dental surgery, and other procedures such as crowns and implants.
Recommendations
The FDA says health care providers should counsel patients that severe and extensive tooth decay, tooth loss, and tooth fracture have been reported with the use of transmucosal buprenorphine-containing medicines and emphasize the importance of visiting their dentist to closely monitor their teeth.
Patients should be counseled to continue taking buprenorphine medications as prescribed and not stop suddenly without first talking to their health care provider, as this could lead to serious consequences, including relapse, misuse or abuse of other opioids, overdose, and death.
Patients are also being advised to take extra steps to help lessen the risk of serious dental problems.
Patients should also be educated on strategies to maintain or improve oral health while taking transmucosal buprenorphine medicines.
Counsel them that after the medicine is completely dissolved, the patient should take a large sip of water, swish it gently around the teeth and gums, swallow, and wait at least 1 hour before brushing their teeth, as the FDA advises. This will allow time for the mouth to gradually return to oral homeostasis and avoid any mechanical damage that may occur due to brushing.
The FDA also advises that patients tell their provider about any history of tooth problems, including cavities, and schedule a dentist visit soon after starting the medicine.
Dental problems related to transmucosal buprenorphine-containing medicines should be reported to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Orally dissolving medications containing buprenorphine are linked to severe dental problems, including total tooth loss, the U.S. Food and Drug Administration warns in a safety communication.
The oral side effects of these medications, which are used to treat opioid use disorder (OUD) and pain, include cavities/tooth decay, including rampant caries; dental abscesses/infection; tooth erosion; fillings falling out; and, in some cases, total tooth loss.
Multiple cases have been reported even in patients with no history of dental problems.
The FDA is adding a warning about the risk of dental problems to the prescribing information and the patient medication guide for all buprenorphine-containing medicines dissolved in the mouth.
The FDA emphasizes, however, that buprenorphine remains “an important treatment option for OUD and pain, and the benefits of these medicines clearly outweigh the risks.”
More than 300 reported cases
Buprenorphine was approved in 2002 as a sublingual tablet, and in 2015 as a film to be placed inside the cheek to treat pain. Both delivery methods have been associated with dental problems.
Since buprenorphine was approved, the FDA has identified 305 cases of dental problems associated with orally dissolving buprenorphine, including 131 classified as serious.
There may be other cases, the FDA says, as this represents only cases reported to the FDA or published in the medical literature.
, but those as young as 18 years old were also affected.
Most cases occurred in patients using the medicines for OUD; however, 28 cases of dental problems occurred in patients using it to treat pain.
In 26 cases, patients had no prior history of dental problems. Some dental problems developed as soon as 2 weeks after treatment began; the median time to diagnosis was about 2 years after starting treatment.
Among all 305 cases reported, 113 involved two or more teeth.
The most common treatment for the dental problems was tooth extraction/removal, which was reported in 71 cases. Other cases required root canals, dental surgery, and other procedures such as crowns and implants.
Recommendations
The FDA says health care providers should counsel patients that severe and extensive tooth decay, tooth loss, and tooth fracture have been reported with the use of transmucosal buprenorphine-containing medicines and emphasize the importance of visiting their dentist to closely monitor their teeth.
Patients should be counseled to continue taking buprenorphine medications as prescribed and not stop suddenly without first talking to their health care provider, as this could lead to serious consequences, including relapse, misuse or abuse of other opioids, overdose, and death.
Patients are also being advised to take extra steps to help lessen the risk of serious dental problems.
Patients should also be educated on strategies to maintain or improve oral health while taking transmucosal buprenorphine medicines.
Counsel them that after the medicine is completely dissolved, the patient should take a large sip of water, swish it gently around the teeth and gums, swallow, and wait at least 1 hour before brushing their teeth, as the FDA advises. This will allow time for the mouth to gradually return to oral homeostasis and avoid any mechanical damage that may occur due to brushing.
The FDA also advises that patients tell their provider about any history of tooth problems, including cavities, and schedule a dentist visit soon after starting the medicine.
Dental problems related to transmucosal buprenorphine-containing medicines should be reported to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Orally dissolving medications containing buprenorphine are linked to severe dental problems, including total tooth loss, the U.S. Food and Drug Administration warns in a safety communication.
The oral side effects of these medications, which are used to treat opioid use disorder (OUD) and pain, include cavities/tooth decay, including rampant caries; dental abscesses/infection; tooth erosion; fillings falling out; and, in some cases, total tooth loss.
Multiple cases have been reported even in patients with no history of dental problems.
The FDA is adding a warning about the risk of dental problems to the prescribing information and the patient medication guide for all buprenorphine-containing medicines dissolved in the mouth.
The FDA emphasizes, however, that buprenorphine remains “an important treatment option for OUD and pain, and the benefits of these medicines clearly outweigh the risks.”
More than 300 reported cases
Buprenorphine was approved in 2002 as a sublingual tablet, and in 2015 as a film to be placed inside the cheek to treat pain. Both delivery methods have been associated with dental problems.
Since buprenorphine was approved, the FDA has identified 305 cases of dental problems associated with orally dissolving buprenorphine, including 131 classified as serious.
There may be other cases, the FDA says, as this represents only cases reported to the FDA or published in the medical literature.
, but those as young as 18 years old were also affected.
Most cases occurred in patients using the medicines for OUD; however, 28 cases of dental problems occurred in patients using it to treat pain.
In 26 cases, patients had no prior history of dental problems. Some dental problems developed as soon as 2 weeks after treatment began; the median time to diagnosis was about 2 years after starting treatment.
Among all 305 cases reported, 113 involved two or more teeth.
The most common treatment for the dental problems was tooth extraction/removal, which was reported in 71 cases. Other cases required root canals, dental surgery, and other procedures such as crowns and implants.
Recommendations
The FDA says health care providers should counsel patients that severe and extensive tooth decay, tooth loss, and tooth fracture have been reported with the use of transmucosal buprenorphine-containing medicines and emphasize the importance of visiting their dentist to closely monitor their teeth.
Patients should be counseled to continue taking buprenorphine medications as prescribed and not stop suddenly without first talking to their health care provider, as this could lead to serious consequences, including relapse, misuse or abuse of other opioids, overdose, and death.
Patients are also being advised to take extra steps to help lessen the risk of serious dental problems.
Patients should also be educated on strategies to maintain or improve oral health while taking transmucosal buprenorphine medicines.
Counsel them that after the medicine is completely dissolved, the patient should take a large sip of water, swish it gently around the teeth and gums, swallow, and wait at least 1 hour before brushing their teeth, as the FDA advises. This will allow time for the mouth to gradually return to oral homeostasis and avoid any mechanical damage that may occur due to brushing.
The FDA also advises that patients tell their provider about any history of tooth problems, including cavities, and schedule a dentist visit soon after starting the medicine.
Dental problems related to transmucosal buprenorphine-containing medicines should be reported to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Should psychiatry categorize ‘substance-induced paraphilia?’
‘substance-induced paraphilia?’
The dopamine receptors of the brain get their fair share amid the didactics we receive in residency. From discussions of antipsychotics and schizophrenia to stimulants and ADHD, dopamine plays a key role. Depending on the program and interest of faculty, methamphetamine may get its own lecture or be mixed in with other stimulants of abuse. During that discussion, a comment might be made in passing on the impact of methamphetamine on sexual desire and activity.
Experiences in the emergency department caring for patients who are intoxicated from methamphetamine then effectively make up for any gaps in trainees’ knowledge base. From patients engaging in self-pleasing pursuits in the emergency room to unfiltered reports of sexual exploits and desires, the impact of methamphetamine on sexual behavior quickly becomes apparent. Those experiences are later reinforced when residents are exposed to more long-term rehabilitation programs and have more in-depth conversations with patients about the sex-culture surrounding methamphetamine.
It is common to hear that, under the influence of methamphetamine, any available body will become an acceptable sexual partner – at times resulting in significant regrets, dangerous sexual activity, and complicated questions surrounding consent. Some early studies have found up to 72% increase in risky sexual behavior in methamphetamine users.1 This is particularly problematic as society has recently taken on the difficult and important work to re-examine the role and nature of consent in sexual activities. This falls within the larger #MeToo movement and has led to advocating for harsher sentencing of sexual offenders.
Yet simultaneously, society has also reconsidered its approach to apportioning blame on drug users.2 This shift to a more compassionate stance has resulted in a desire to treat and care for a disorder, rather than punish and condemn a poor choice. As forensic psychiatrists, we have noted this significant change. Where substance use disorders were once considered a risk factor for recidivism, they are now considered a disability that not only warrants treatment but can also diminish the share of blame one may be responsible for.
The convergence of those two societal movements often plays out in the courtroom, and in our experience when faced with those two opposing viewpoints, triers of fact (judges and juries) often favor punishing sexual offense over empathizing with an addictive disorder. While certainly not implying methamphetamine use condones sexual offense, we do posit the particular relationship between methamphetamine use and sexual activity should be explained to those entrusted with deciding guilt.
Examples of such problems are extremely common. A routine case involves IK,3 a 48-year-old male without significant history of legal problems, arrested for indecent exposure. His history of mental illness is closely intertwined with a history of substance use, leading to many psychiatric hospitalizations for methamphetamine-induced psychosis. After many hospitalizations he was placed in an assertive community treatment (ACT) team.
One day, IK is approached by an industrious drug dealer who frequents multiple board-and-cares in search for customers interested in relapsing. IK uses methamphetamine and within hours finds himself having walked miles away, naked, in the middle of an RV park. He subsequently describes the experience of unrelenting sexual desire, accompanied by ideas of reference involving billboards encouraging him to demonstrate his sexual prowess, as well as auditory hallucinations of women cheering him on. This leads to him pleasing himself publicly and his subsequent arrest.
Interviewing IK, 3 months later, he is embarrassed and apologetic. He is cognizant of the inappropriate nature of the incident and the foolishness of his actions. However, when asked whether he considers himself a sexual offender, he protests that he would never act in such a manner if not under the influence of methamphetamine. He points to his lack of significant sexual urges when sober, his lack of prior sexual offense, his lack of sexually violent offense, and his lack of unusual sexual interests.
It is unclear to us how society will or should adjudicate on such a case. It is not under the purview of forensic psychiatry to become a trier of fact. However, psychiatry should have a better working framework of how to discuss and conceptualize such situations, especially considering the dire consequences for those involved.
While any criminal conviction already has the potential to destroy a person’s life, sexual crimes bring particularly serious consequences. Entry into the national sex offender registry, in addition to carrying an unshakable stigma, comes with additional degrees of lost freedom. These individuals are prohibited from living or working in areas that have children in proximity, subjecting them to the outskirts of society and greatly restricting any chance of economic escape from poverty. Parks, libraries, and shopping malls can become off limits. Privacy for these individuals is nonexistent; from websites they visit to where they travel physically can be monitored. Even where they live and a detailed physical description are often easily accessible by members of their community.
When should it be permissible to consider sex offender status for someone on the grounds of a mental illness? A patient with obsessive-compulsive disorder might have sadistic obsessions and compulsions to commit violent sexual acts, which, along with being repugnant to society, are entirely ego-dystonic to the suffering patient. Psychosis is often characterized as involving a loss of insight and impaired reality testing. If society accepts insanity as grounds to mitigate sentencing, then why not permit it for grounds to wave the designation of sex offender to those with certain disorders, including substance use disorder? Wherever we come down on this issue,
Should IK have to register as a sex offender? Regardless of the circumstances, he did publicly masturbate. Society has determined that public sexual displays are a crime worth carrying the pariah status of sex offender – why should an exception be made for methamphetamine use? On the other hand, it is difficult to claim that IK’s behavior was entirely of his own free will. Most triers of fact will have never experienced that amount of dopamine reward. They can’t attest to the remaining free will after experiencing more pleasurable salience and positive reinforcement than ever naturally possible.
How we deal with the behavioral consequences, and other sequelae, of methamphetamine use is a growing problem. Access to and use of methamphetamine is no longer reserved for soldiers patrolling the jungles of Vietnam. Once thought to be a scourge of the West Coast, methamphetamine is now widely available throughout the United States.4 The use of methamphetamine is likely to continue to expand as society keeps pursuing the decriminalizing of drug use. Psychiatrists practicing in areas heavily affected by methamphetamine see firsthand the burden it places on community resources in the form of increased psychosis, emergency room utilization, medical resource strain, and encounters with police.5
The presence of mental illness is tied to a small but statistically significant risk of violence. However, substance use is a well-established risk factor for violence.6 What is often missed is that many sexual offenders have not committed a violent offense. However, like IK, they have been charged with indecent exposure or other nonviolent sexual offenses, such as prostitution and solicitation. Those nonviolent offenses are driven by poor judgment and impulsivity, the trademarks of substance use. The answer cannot be to incarcerate, and eventually add to the sex offender registry, the growing number of these individuals.
Yet, as psychiatrists, we seem at a loss for how to treat these patients. The prescription of allowing them to spend a night in the ED with a complementary sandwich garnished with olanzapine often feels like enabling. Substance use treatment programs are too limited, and the wait list is rarely shorter than the time it takes our patient to purchase their next hit.
There are no effective pharmacologic treatments for methamphetamine use disorder.7 The recommendations of cognitive-behavioral therapy, family and group therapy, contingency management, and a 12-step program may be sufficient for the most motivated and well-supported patients but are inadequate for the vast majority.8 As much as we want to laud the merits of community psychiatry and the ACT [assertive community treatment] model of care, it is hard to carry that banner while confronted with the reality these patients face on a day-to-day basis during any shift in the emergency room. Eventually the countless encounters with homeless, helplessly meth-addicted patients ending in discharge back to the streets begins to tarnish the bright rhetoric surrounding community care, which starts to sound more and more like abandonment of patients to suffer in futility.9
It is not up to forensic psychiatrists, or even psychiatry as a whole, to fix the myriad of inadequacies surrounding how society handles those suffering from methamphetamine addiction. However, it is essential for psychiatry to study and educate society on the interaction of methamphetamine use and sexual behavior. There has been some exploration into other risk factors for paraphilic behavior while under the influence of substances, but there is a dearth of information on this topic. Establishing a nomenclature called “substance-induced paraphilia” might be a way to bring clarity to such instances in both a forensic and general psychiatric setting.
Dr. Compton is a psychiatry resident at University of California, San Diego. His background includes medical education, mental health advocacy, work with underserved populations, and brain cancer research. Dr. Compton has no conflicts of interest. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.
References
1. Psychol Addict Behav. 2016;30(2)147-57.
2. Monitor Psychol. 2019;50(6).
3. IK’s case has been modified in certain ways to maintain confidentiality.
4. J Psychoactive Drugs. 2000;(2):137-41.
5. Acad Emerg Med. 2020 Nov;27(11):1116-25.
6. Swanson JW. Mental disorder, substance abuse, and community violence: An epidemiological approach, in: Monahan J and Steadman HJ, eds. “Violence and Mental Disorder: Developments in Risk Assessment” (Chicago: University of Chicago Press, 1994, pp. 101-36).
7. Addiction. 2004 Jun;99(6)708-17.
8. Am Fam Physician. 2007 Oct 15;76(8):1169-74.
9. Perspect Biol Med. 2021;64(1)70-81.
The dopamine receptors of the brain get their fair share amid the didactics we receive in residency. From discussions of antipsychotics and schizophrenia to stimulants and ADHD, dopamine plays a key role. Depending on the program and interest of faculty, methamphetamine may get its own lecture or be mixed in with other stimulants of abuse. During that discussion, a comment might be made in passing on the impact of methamphetamine on sexual desire and activity.
Experiences in the emergency department caring for patients who are intoxicated from methamphetamine then effectively make up for any gaps in trainees’ knowledge base. From patients engaging in self-pleasing pursuits in the emergency room to unfiltered reports of sexual exploits and desires, the impact of methamphetamine on sexual behavior quickly becomes apparent. Those experiences are later reinforced when residents are exposed to more long-term rehabilitation programs and have more in-depth conversations with patients about the sex-culture surrounding methamphetamine.
It is common to hear that, under the influence of methamphetamine, any available body will become an acceptable sexual partner – at times resulting in significant regrets, dangerous sexual activity, and complicated questions surrounding consent. Some early studies have found up to 72% increase in risky sexual behavior in methamphetamine users.1 This is particularly problematic as society has recently taken on the difficult and important work to re-examine the role and nature of consent in sexual activities. This falls within the larger #MeToo movement and has led to advocating for harsher sentencing of sexual offenders.
Yet simultaneously, society has also reconsidered its approach to apportioning blame on drug users.2 This shift to a more compassionate stance has resulted in a desire to treat and care for a disorder, rather than punish and condemn a poor choice. As forensic psychiatrists, we have noted this significant change. Where substance use disorders were once considered a risk factor for recidivism, they are now considered a disability that not only warrants treatment but can also diminish the share of blame one may be responsible for.
The convergence of those two societal movements often plays out in the courtroom, and in our experience when faced with those two opposing viewpoints, triers of fact (judges and juries) often favor punishing sexual offense over empathizing with an addictive disorder. While certainly not implying methamphetamine use condones sexual offense, we do posit the particular relationship between methamphetamine use and sexual activity should be explained to those entrusted with deciding guilt.
Examples of such problems are extremely common. A routine case involves IK,3 a 48-year-old male without significant history of legal problems, arrested for indecent exposure. His history of mental illness is closely intertwined with a history of substance use, leading to many psychiatric hospitalizations for methamphetamine-induced psychosis. After many hospitalizations he was placed in an assertive community treatment (ACT) team.
One day, IK is approached by an industrious drug dealer who frequents multiple board-and-cares in search for customers interested in relapsing. IK uses methamphetamine and within hours finds himself having walked miles away, naked, in the middle of an RV park. He subsequently describes the experience of unrelenting sexual desire, accompanied by ideas of reference involving billboards encouraging him to demonstrate his sexual prowess, as well as auditory hallucinations of women cheering him on. This leads to him pleasing himself publicly and his subsequent arrest.
Interviewing IK, 3 months later, he is embarrassed and apologetic. He is cognizant of the inappropriate nature of the incident and the foolishness of his actions. However, when asked whether he considers himself a sexual offender, he protests that he would never act in such a manner if not under the influence of methamphetamine. He points to his lack of significant sexual urges when sober, his lack of prior sexual offense, his lack of sexually violent offense, and his lack of unusual sexual interests.
It is unclear to us how society will or should adjudicate on such a case. It is not under the purview of forensic psychiatry to become a trier of fact. However, psychiatry should have a better working framework of how to discuss and conceptualize such situations, especially considering the dire consequences for those involved.
While any criminal conviction already has the potential to destroy a person’s life, sexual crimes bring particularly serious consequences. Entry into the national sex offender registry, in addition to carrying an unshakable stigma, comes with additional degrees of lost freedom. These individuals are prohibited from living or working in areas that have children in proximity, subjecting them to the outskirts of society and greatly restricting any chance of economic escape from poverty. Parks, libraries, and shopping malls can become off limits. Privacy for these individuals is nonexistent; from websites they visit to where they travel physically can be monitored. Even where they live and a detailed physical description are often easily accessible by members of their community.
When should it be permissible to consider sex offender status for someone on the grounds of a mental illness? A patient with obsessive-compulsive disorder might have sadistic obsessions and compulsions to commit violent sexual acts, which, along with being repugnant to society, are entirely ego-dystonic to the suffering patient. Psychosis is often characterized as involving a loss of insight and impaired reality testing. If society accepts insanity as grounds to mitigate sentencing, then why not permit it for grounds to wave the designation of sex offender to those with certain disorders, including substance use disorder? Wherever we come down on this issue,
Should IK have to register as a sex offender? Regardless of the circumstances, he did publicly masturbate. Society has determined that public sexual displays are a crime worth carrying the pariah status of sex offender – why should an exception be made for methamphetamine use? On the other hand, it is difficult to claim that IK’s behavior was entirely of his own free will. Most triers of fact will have never experienced that amount of dopamine reward. They can’t attest to the remaining free will after experiencing more pleasurable salience and positive reinforcement than ever naturally possible.
How we deal with the behavioral consequences, and other sequelae, of methamphetamine use is a growing problem. Access to and use of methamphetamine is no longer reserved for soldiers patrolling the jungles of Vietnam. Once thought to be a scourge of the West Coast, methamphetamine is now widely available throughout the United States.4 The use of methamphetamine is likely to continue to expand as society keeps pursuing the decriminalizing of drug use. Psychiatrists practicing in areas heavily affected by methamphetamine see firsthand the burden it places on community resources in the form of increased psychosis, emergency room utilization, medical resource strain, and encounters with police.5
The presence of mental illness is tied to a small but statistically significant risk of violence. However, substance use is a well-established risk factor for violence.6 What is often missed is that many sexual offenders have not committed a violent offense. However, like IK, they have been charged with indecent exposure or other nonviolent sexual offenses, such as prostitution and solicitation. Those nonviolent offenses are driven by poor judgment and impulsivity, the trademarks of substance use. The answer cannot be to incarcerate, and eventually add to the sex offender registry, the growing number of these individuals.
Yet, as psychiatrists, we seem at a loss for how to treat these patients. The prescription of allowing them to spend a night in the ED with a complementary sandwich garnished with olanzapine often feels like enabling. Substance use treatment programs are too limited, and the wait list is rarely shorter than the time it takes our patient to purchase their next hit.
There are no effective pharmacologic treatments for methamphetamine use disorder.7 The recommendations of cognitive-behavioral therapy, family and group therapy, contingency management, and a 12-step program may be sufficient for the most motivated and well-supported patients but are inadequate for the vast majority.8 As much as we want to laud the merits of community psychiatry and the ACT [assertive community treatment] model of care, it is hard to carry that banner while confronted with the reality these patients face on a day-to-day basis during any shift in the emergency room. Eventually the countless encounters with homeless, helplessly meth-addicted patients ending in discharge back to the streets begins to tarnish the bright rhetoric surrounding community care, which starts to sound more and more like abandonment of patients to suffer in futility.9
It is not up to forensic psychiatrists, or even psychiatry as a whole, to fix the myriad of inadequacies surrounding how society handles those suffering from methamphetamine addiction. However, it is essential for psychiatry to study and educate society on the interaction of methamphetamine use and sexual behavior. There has been some exploration into other risk factors for paraphilic behavior while under the influence of substances, but there is a dearth of information on this topic. Establishing a nomenclature called “substance-induced paraphilia” might be a way to bring clarity to such instances in both a forensic and general psychiatric setting.
Dr. Compton is a psychiatry resident at University of California, San Diego. His background includes medical education, mental health advocacy, work with underserved populations, and brain cancer research. Dr. Compton has no conflicts of interest. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.
References
1. Psychol Addict Behav. 2016;30(2)147-57.
2. Monitor Psychol. 2019;50(6).
3. IK’s case has been modified in certain ways to maintain confidentiality.
4. J Psychoactive Drugs. 2000;(2):137-41.
5. Acad Emerg Med. 2020 Nov;27(11):1116-25.
6. Swanson JW. Mental disorder, substance abuse, and community violence: An epidemiological approach, in: Monahan J and Steadman HJ, eds. “Violence and Mental Disorder: Developments in Risk Assessment” (Chicago: University of Chicago Press, 1994, pp. 101-36).
7. Addiction. 2004 Jun;99(6)708-17.
8. Am Fam Physician. 2007 Oct 15;76(8):1169-74.
9. Perspect Biol Med. 2021;64(1)70-81.
The dopamine receptors of the brain get their fair share amid the didactics we receive in residency. From discussions of antipsychotics and schizophrenia to stimulants and ADHD, dopamine plays a key role. Depending on the program and interest of faculty, methamphetamine may get its own lecture or be mixed in with other stimulants of abuse. During that discussion, a comment might be made in passing on the impact of methamphetamine on sexual desire and activity.
Experiences in the emergency department caring for patients who are intoxicated from methamphetamine then effectively make up for any gaps in trainees’ knowledge base. From patients engaging in self-pleasing pursuits in the emergency room to unfiltered reports of sexual exploits and desires, the impact of methamphetamine on sexual behavior quickly becomes apparent. Those experiences are later reinforced when residents are exposed to more long-term rehabilitation programs and have more in-depth conversations with patients about the sex-culture surrounding methamphetamine.
It is common to hear that, under the influence of methamphetamine, any available body will become an acceptable sexual partner – at times resulting in significant regrets, dangerous sexual activity, and complicated questions surrounding consent. Some early studies have found up to 72% increase in risky sexual behavior in methamphetamine users.1 This is particularly problematic as society has recently taken on the difficult and important work to re-examine the role and nature of consent in sexual activities. This falls within the larger #MeToo movement and has led to advocating for harsher sentencing of sexual offenders.
Yet simultaneously, society has also reconsidered its approach to apportioning blame on drug users.2 This shift to a more compassionate stance has resulted in a desire to treat and care for a disorder, rather than punish and condemn a poor choice. As forensic psychiatrists, we have noted this significant change. Where substance use disorders were once considered a risk factor for recidivism, they are now considered a disability that not only warrants treatment but can also diminish the share of blame one may be responsible for.
The convergence of those two societal movements often plays out in the courtroom, and in our experience when faced with those two opposing viewpoints, triers of fact (judges and juries) often favor punishing sexual offense over empathizing with an addictive disorder. While certainly not implying methamphetamine use condones sexual offense, we do posit the particular relationship between methamphetamine use and sexual activity should be explained to those entrusted with deciding guilt.
Examples of such problems are extremely common. A routine case involves IK,3 a 48-year-old male without significant history of legal problems, arrested for indecent exposure. His history of mental illness is closely intertwined with a history of substance use, leading to many psychiatric hospitalizations for methamphetamine-induced psychosis. After many hospitalizations he was placed in an assertive community treatment (ACT) team.
One day, IK is approached by an industrious drug dealer who frequents multiple board-and-cares in search for customers interested in relapsing. IK uses methamphetamine and within hours finds himself having walked miles away, naked, in the middle of an RV park. He subsequently describes the experience of unrelenting sexual desire, accompanied by ideas of reference involving billboards encouraging him to demonstrate his sexual prowess, as well as auditory hallucinations of women cheering him on. This leads to him pleasing himself publicly and his subsequent arrest.
Interviewing IK, 3 months later, he is embarrassed and apologetic. He is cognizant of the inappropriate nature of the incident and the foolishness of his actions. However, when asked whether he considers himself a sexual offender, he protests that he would never act in such a manner if not under the influence of methamphetamine. He points to his lack of significant sexual urges when sober, his lack of prior sexual offense, his lack of sexually violent offense, and his lack of unusual sexual interests.
It is unclear to us how society will or should adjudicate on such a case. It is not under the purview of forensic psychiatry to become a trier of fact. However, psychiatry should have a better working framework of how to discuss and conceptualize such situations, especially considering the dire consequences for those involved.
While any criminal conviction already has the potential to destroy a person’s life, sexual crimes bring particularly serious consequences. Entry into the national sex offender registry, in addition to carrying an unshakable stigma, comes with additional degrees of lost freedom. These individuals are prohibited from living or working in areas that have children in proximity, subjecting them to the outskirts of society and greatly restricting any chance of economic escape from poverty. Parks, libraries, and shopping malls can become off limits. Privacy for these individuals is nonexistent; from websites they visit to where they travel physically can be monitored. Even where they live and a detailed physical description are often easily accessible by members of their community.
When should it be permissible to consider sex offender status for someone on the grounds of a mental illness? A patient with obsessive-compulsive disorder might have sadistic obsessions and compulsions to commit violent sexual acts, which, along with being repugnant to society, are entirely ego-dystonic to the suffering patient. Psychosis is often characterized as involving a loss of insight and impaired reality testing. If society accepts insanity as grounds to mitigate sentencing, then why not permit it for grounds to wave the designation of sex offender to those with certain disorders, including substance use disorder? Wherever we come down on this issue,
Should IK have to register as a sex offender? Regardless of the circumstances, he did publicly masturbate. Society has determined that public sexual displays are a crime worth carrying the pariah status of sex offender – why should an exception be made for methamphetamine use? On the other hand, it is difficult to claim that IK’s behavior was entirely of his own free will. Most triers of fact will have never experienced that amount of dopamine reward. They can’t attest to the remaining free will after experiencing more pleasurable salience and positive reinforcement than ever naturally possible.
How we deal with the behavioral consequences, and other sequelae, of methamphetamine use is a growing problem. Access to and use of methamphetamine is no longer reserved for soldiers patrolling the jungles of Vietnam. Once thought to be a scourge of the West Coast, methamphetamine is now widely available throughout the United States.4 The use of methamphetamine is likely to continue to expand as society keeps pursuing the decriminalizing of drug use. Psychiatrists practicing in areas heavily affected by methamphetamine see firsthand the burden it places on community resources in the form of increased psychosis, emergency room utilization, medical resource strain, and encounters with police.5
The presence of mental illness is tied to a small but statistically significant risk of violence. However, substance use is a well-established risk factor for violence.6 What is often missed is that many sexual offenders have not committed a violent offense. However, like IK, they have been charged with indecent exposure or other nonviolent sexual offenses, such as prostitution and solicitation. Those nonviolent offenses are driven by poor judgment and impulsivity, the trademarks of substance use. The answer cannot be to incarcerate, and eventually add to the sex offender registry, the growing number of these individuals.
Yet, as psychiatrists, we seem at a loss for how to treat these patients. The prescription of allowing them to spend a night in the ED with a complementary sandwich garnished with olanzapine often feels like enabling. Substance use treatment programs are too limited, and the wait list is rarely shorter than the time it takes our patient to purchase their next hit.
There are no effective pharmacologic treatments for methamphetamine use disorder.7 The recommendations of cognitive-behavioral therapy, family and group therapy, contingency management, and a 12-step program may be sufficient for the most motivated and well-supported patients but are inadequate for the vast majority.8 As much as we want to laud the merits of community psychiatry and the ACT [assertive community treatment] model of care, it is hard to carry that banner while confronted with the reality these patients face on a day-to-day basis during any shift in the emergency room. Eventually the countless encounters with homeless, helplessly meth-addicted patients ending in discharge back to the streets begins to tarnish the bright rhetoric surrounding community care, which starts to sound more and more like abandonment of patients to suffer in futility.9
It is not up to forensic psychiatrists, or even psychiatry as a whole, to fix the myriad of inadequacies surrounding how society handles those suffering from methamphetamine addiction. However, it is essential for psychiatry to study and educate society on the interaction of methamphetamine use and sexual behavior. There has been some exploration into other risk factors for paraphilic behavior while under the influence of substances, but there is a dearth of information on this topic. Establishing a nomenclature called “substance-induced paraphilia” might be a way to bring clarity to such instances in both a forensic and general psychiatric setting.
Dr. Compton is a psychiatry resident at University of California, San Diego. His background includes medical education, mental health advocacy, work with underserved populations, and brain cancer research. Dr. Compton has no conflicts of interest. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.
References
1. Psychol Addict Behav. 2016;30(2)147-57.
2. Monitor Psychol. 2019;50(6).
3. IK’s case has been modified in certain ways to maintain confidentiality.
4. J Psychoactive Drugs. 2000;(2):137-41.
5. Acad Emerg Med. 2020 Nov;27(11):1116-25.
6. Swanson JW. Mental disorder, substance abuse, and community violence: An epidemiological approach, in: Monahan J and Steadman HJ, eds. “Violence and Mental Disorder: Developments in Risk Assessment” (Chicago: University of Chicago Press, 1994, pp. 101-36).
7. Addiction. 2004 Jun;99(6)708-17.
8. Am Fam Physician. 2007 Oct 15;76(8):1169-74.
9. Perspect Biol Med. 2021;64(1)70-81.
‘substance-induced paraphilia?’
‘substance-induced paraphilia?’
Scheduled Acetaminophen to Minimize Neuropsychiatric Symptoms in Wernicke-Korsakoff Syndrome
To manage the physical, cognitive, and emotional symptoms of a veteran hospitalized for Wernicke-Korsakoff syndrome secondary to chronic alcohol overuse, acetaminophen was administered in place of psychoactive medications.
Alcohol is the most common substance misused by veterans. 1 Veterans may m isuse alcohol as a result of mental illness or posttraumatic stress disorder (PTSD), having difficulties adjusting to civilian life, or because of heavy drinking habits acquired before leaving active duty. 2 One potential long-term effect of chronic alcohol misuse is Wernicke-Korsakoff syndrome (WKS), a neuropsychiatric condition secondary to a deficiency of thiamine. 3 The disease is characterized by altered mental status, oculomotor findings, and ataxia. 3 Patients with WKS may exhibit challenging behaviors, including aggression, disinhibition, and lack of awareness of their illness. 4 Due to long-standing cognitive and physical deficits, many patients require lifelong care with a focus on a palliative approach. 3
The mainstay of pharmacologic management for the neuropsychiatric symptoms of WKS continues to be psychoactive medications, such as antipsychotics, benzodiazepines, antidepressants, and anticonvulsant medications.4-6 Though atypical antipsychotic medications remain the most widely used, they have a high adverse effect (AE) profile.5,6 Among the potential AEs are metabolic syndrome, anticholinergic effects, QTc prolongation, orthostatic hypotension, extrapyramidal effects, sedation, and falls. There also is a US Food and Drug Administration boxed warning for increased risk of mortality.7 With the goal of improving and maintaining patient safety, pharmacologic interventions with lower AEs may be beneficial in the management of the neuropsychiatric symptoms of WKS.
This case describes a veteran who was initially hospitalized due to confusion, ataxia, and nystagmus secondary to chronic alcohol overuse. The aim of the case was to consider the use of acetaminophen in place of psychoactive medications as a way to manage neuropsychiatric symptoms of WKS even when pain was not present.
Case Presentation
A veteran presented to the local US Department of Veterans Affairs (VA) emergency department (ED) due to their spouse’s concern of acute onset confusion and ambulatory difficulties. The veteran’s medical history included extensive alcohol misuse, mild asthma, and diet-controlled hyperlipidemia. On initial evaluation, the veteran displayed symptoms of ataxia and confusion. When asked why the veteran was at the ED, the response was, “I just came to the hospital to find my sister.” Based on their medical history, clinical evaluation, and altered mental status, the veteran was admitted to the acute care medical service with a presumptive diagnosis of WKS.
On admission, the laboratory evaluation revealed normal alanine transaminase (ALT) and aspartate transaminase (AST) levels but markedly elevated γ-glutamyl transferase (GGT) consistent with alcohol toxicity. COVID-19 testing was negative. Magnetic resonance imaging (MRI) of the brain revealed evidence of alterations in the mammillary bodies and moderately severe cortical and cerebellar volume loss suggestive of long-standing alcohol use.
The veteran was hospitalized for 12 days and treated with high-dose IV thiamine, which resulted in improvement of their ophthalmic disorder (nystagmus) and ataxia. However, they continued to exhibit poor recall, confusion, and occasional agitation characterized by verbal outbursts and aggression toward the staff.
The veteran’s spouse worked full time and did not feel capable of providing the necessary follow-up care at home. The safest discharge plan found was to transfer the veteran to the local VA community living center (CLC) for physical therapy and further support of their marked cognitive decline and agitation.
Following admission to the CLC, the veteran was placed in a secured memory unit with staff trained specifically on management of veterans with cognitive impairment and behavioral concerns. As the veteran did not have decisional capacity on admission, the staff arranged a meeting with the spouse. Based on that conversation, the goals of care were to focus on a palliative approach and the hope that the veteran would one day be able to return home to their spouse.
At the CLC, the veteran was initially treated with thiamine 200 mg orally once daily and albuterol inhaler as needed. A clinical psychologist performed a comprehensive psychological evaluation on admission, which confirmed evidence of WKS with symptoms, including confusion, disorientation, and confabulation. There was no evidence of cultural diversity factors regarding the veteran’s delusional beliefs.
After the first full day in the CLC, the nursing staff observed anger and agitation that seemed to start midafternoon and continued until around dinnertime. The veteran displayed verbal outbursts, refusal to cooperate with the staff, and multiple attempts to leave the CLC. With the guidance of a geriatric psychiatrist, risperidone 1 mg once daily as needed was initiated, and staff continued with verbal redirection, both with limited efficacy. After 3 days, due to safety concerns for the veteran, other CLC patients, and CLC staff, risperidone dosing was increased to 1 mg twice daily, which had limited efficacy. Lorazepam 1 mg once daily also was added. A careful medication review was performed to minimize any potential AEs or interactions that might have contributed to the veteran’s behavior, but no pharmacologic interventions were found to fully abate their behavioral issues.
After 5 weeks of ongoing intermittent behavioral issues, the medical team again met to discuss new treatment options.A case reported by Husebo and colleagues used scheduled acetaminophen to help relieve neuropsychiatric symptoms of dementia in a patient who exhibited similar behavioral issues and did not respond well to antipsychotics or benzodiazepines.8 Although our veteran did not express or exhibit obvious pain, the medical team chose to trial this intervention, and the veteran was started on acetaminophen 650 mg orally 3 times daily. A comprehensive metabolic panel, including GGT and thyroid-stimulating hormone, was performed before starting acetaminophen; no abnormalities were noted. The clinical examination did not reveal physical abnormalities other than ataxia.
After 5 days of therapy with the scheduled acetaminophen, the veteran’s clinical behavior dramatically improved. The veteran exhibited infrequent agitated behavior and became cooperative with staff. Three days later, the scheduled lorazepam was discontinued, and eventually they were tapered off risperidone. One month after starting scheduled acetaminophen, the veteran had improved to a point where the staff determined a safe discharge plan could be initiated. The veteran’s nystagmus resolved and behavioral issues improved, although cognitive impairment persisted.
Due to COVID-19, a teleconference was scheduled with the veteran’s spouse to discuss a discharge plan. The spouse was pleased that the veteran had progressed adequately both functionally and behaviorally to make a safe discharge home possible. The spouse arranged to take family leave from their job to help support the veteran after discharge. The veteran was able to return home with a safe discharge plan 1 week later. The acetaminophen was continued with twice-daily dosing and was continued because there were no new behavioral issues. This was done to enhance postfacility adherence and minimize the risk of drug-drug interactions. Attempts to follow up with the veteran postdischarge were unfortunately unsuccessful as the family lived out of the local area.
Discussion
Alcohol misuse is a common finding in many US veterans, as well as in the general population.1,3 As a result, it is not uncommon to see patients with physical and psychological symptoms related to this abuse. Many of these patients will become verbally and physically abusive, thus having appropriate pharmacologic and nonpharmacologic interventions is important.
In this case study, the veteran was diagnosed with WKS and exhibited physical, cognitive, and emotional symptoms consistent with this disease. Although the physical symptoms improved with thiamine and abstinence from alcohol, their cognitive impairment, verbal outbursts, and aggressive demeanor persisted.
After using antipsychotic and anxiolytic medications with minimal clinical improvement, a trial of acetaminophen 650 mg 3 times daily was instituted. The patient’s behavior improved; demeanor became calmer, and they were easily redirected by the nursing staff. Psychological support was again employed, which enhanced and supported the veteran’s calmer demeanor. Although there is limited medical literature on the use of acetaminophen in clinical situations not related to pain, there has been research documenting its effect on social interaction.9,10
Acetaminophen is an analgesic medication that acts through central neural mechanisms. It has been hypothesized that social and physical pain rely on shared neurochemical underpinnings, and some of the regions of the brain involved in affective experience of physical pain also have been found to be involved in the experience of social pain.11 Acetaminophen may impact an individual’s social well-being as social pain processes.11 It has been shown to blunt reactivity to both physical pain as well as negative stimuli.11
Conclusions
A 2019 survey on alcohol and drug use found 5.6% of adults aged ≥ 18 have an alcohol use disorder.12 In severe cases, this can result in WKS. Although replacement of thiamine is critical for physical improvement, psychological deficits may persist. Small studies have advanced the concept of using scheduled acetaminophen even when the patient is not verbalizing or displaying pain.13 Although more research needs to be done on this topic, this palliative approach may be worth considering, especially if the risks of antipsychotics and anxiolytics outweigh the benefits.
1. National Institute on Drug Abuse. Substance use and military life drug facts. Published October 2019. Accessed November 10, 2021. https://www.drugabuse.gov/publications/drugfacts/substance-use-military-life
2. National Veterans Foundation. What statistics show about veteran substance abuse and why proper treatment is important. Published March 30, 2016. Accessed November 10, 2021. https://nvf.org/veteran-substance-abuse-statistics
3. National Center for Biotechnology Information. Korsakoff syndrome. Updated July 10, 2020. Accessed November 10, 2021. https://www.ncbi.nlm.nih.gov/books/NBK539854
4. Gerridzen IJ, Goossensen MA. Patients with Korsakoff syndrome in nursing homes: characteristics, comorbidity, and use of psychotropic drugs. Int Psychogeriatr. 2014;26(1):115-121. doi:10.1017/S1041610213001543
5. Press D, Alexander M. Management of neuropsychiatric symptoms of dementia. Updated October 2021. Accessed November 10, 2021. https://www.uptodate.com/contents/management-of-neuropsychiatric-symptoms-of-dementia
6. Steinberg M, Lyketsos CG. Atypical antipsychotic use in patients with dementia: Managing safety concerns. Am J Psychiatry. 2012;169(9):900-906. doi:10.1176/appi.ajp.2012.12030342
7. Jibson MD. Second-generation antipsychotic medications: pharmacology, administration, and side effects. https://www.uptodate.com/contents/second-generation-antipsychotic-medications-pharmacology-administration-and-side-effects
8. Husebo BS, Ballard C, Sandvik R, Nilsen OB, Aarsland D. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ. 2011;343:d4065. doi:10.1136/bmj.d4065
9. Fung K, Alden LE. Once hurt, twice shy: social pain contributes to social anxiety. Emotion. 2017;(2):231-239. doi:10.1037/emo0000223
10. Roberts ID, Krajbich I, Cheavens JS, Campo JV, Way BM. Acetaminophen Reduces Distrust in Individuals with Borderline Personality Disorder Features. Clin Psychol Sci. 2018;6(1):145-154. doi:10.1177/2167702617731374
11. Dewall CN, Macdonald G, Webster GD, et al. Acetaminophen reduces social pain: behavioral and neural evidence. Psychol Sci. 2010;21(7):931-937. doi:10.1177/0956797610374741
12. National Institute on Alcohol Abuse and Alcoholism. Alcohol facts and statistics. Updated June 2021. Accessed November 2, 202November 10, 2021. https://www.niaaa.nih.gov/publications/brochures-and-fact-sheets/alcohol-facts-and-statistics
13. Chibnall JT, Tait RC, Harman B, Luebbert RA. Effect of acetaminophen on behavior, well-being, and psychotropic medication use in nursing home residents with moderate-to-severe dementia. J Am Geriatrics Soc. 2005;53(11):1921-9. doi:10.1111/j.1532-5415.2005.53572.x
To manage the physical, cognitive, and emotional symptoms of a veteran hospitalized for Wernicke-Korsakoff syndrome secondary to chronic alcohol overuse, acetaminophen was administered in place of psychoactive medications.
To manage the physical, cognitive, and emotional symptoms of a veteran hospitalized for Wernicke-Korsakoff syndrome secondary to chronic alcohol overuse, acetaminophen was administered in place of psychoactive medications.
Alcohol is the most common substance misused by veterans. 1 Veterans may m isuse alcohol as a result of mental illness or posttraumatic stress disorder (PTSD), having difficulties adjusting to civilian life, or because of heavy drinking habits acquired before leaving active duty. 2 One potential long-term effect of chronic alcohol misuse is Wernicke-Korsakoff syndrome (WKS), a neuropsychiatric condition secondary to a deficiency of thiamine. 3 The disease is characterized by altered mental status, oculomotor findings, and ataxia. 3 Patients with WKS may exhibit challenging behaviors, including aggression, disinhibition, and lack of awareness of their illness. 4 Due to long-standing cognitive and physical deficits, many patients require lifelong care with a focus on a palliative approach. 3
The mainstay of pharmacologic management for the neuropsychiatric symptoms of WKS continues to be psychoactive medications, such as antipsychotics, benzodiazepines, antidepressants, and anticonvulsant medications.4-6 Though atypical antipsychotic medications remain the most widely used, they have a high adverse effect (AE) profile.5,6 Among the potential AEs are metabolic syndrome, anticholinergic effects, QTc prolongation, orthostatic hypotension, extrapyramidal effects, sedation, and falls. There also is a US Food and Drug Administration boxed warning for increased risk of mortality.7 With the goal of improving and maintaining patient safety, pharmacologic interventions with lower AEs may be beneficial in the management of the neuropsychiatric symptoms of WKS.
This case describes a veteran who was initially hospitalized due to confusion, ataxia, and nystagmus secondary to chronic alcohol overuse. The aim of the case was to consider the use of acetaminophen in place of psychoactive medications as a way to manage neuropsychiatric symptoms of WKS even when pain was not present.
Case Presentation
A veteran presented to the local US Department of Veterans Affairs (VA) emergency department (ED) due to their spouse’s concern of acute onset confusion and ambulatory difficulties. The veteran’s medical history included extensive alcohol misuse, mild asthma, and diet-controlled hyperlipidemia. On initial evaluation, the veteran displayed symptoms of ataxia and confusion. When asked why the veteran was at the ED, the response was, “I just came to the hospital to find my sister.” Based on their medical history, clinical evaluation, and altered mental status, the veteran was admitted to the acute care medical service with a presumptive diagnosis of WKS.
On admission, the laboratory evaluation revealed normal alanine transaminase (ALT) and aspartate transaminase (AST) levels but markedly elevated γ-glutamyl transferase (GGT) consistent with alcohol toxicity. COVID-19 testing was negative. Magnetic resonance imaging (MRI) of the brain revealed evidence of alterations in the mammillary bodies and moderately severe cortical and cerebellar volume loss suggestive of long-standing alcohol use.
The veteran was hospitalized for 12 days and treated with high-dose IV thiamine, which resulted in improvement of their ophthalmic disorder (nystagmus) and ataxia. However, they continued to exhibit poor recall, confusion, and occasional agitation characterized by verbal outbursts and aggression toward the staff.
The veteran’s spouse worked full time and did not feel capable of providing the necessary follow-up care at home. The safest discharge plan found was to transfer the veteran to the local VA community living center (CLC) for physical therapy and further support of their marked cognitive decline and agitation.
Following admission to the CLC, the veteran was placed in a secured memory unit with staff trained specifically on management of veterans with cognitive impairment and behavioral concerns. As the veteran did not have decisional capacity on admission, the staff arranged a meeting with the spouse. Based on that conversation, the goals of care were to focus on a palliative approach and the hope that the veteran would one day be able to return home to their spouse.
At the CLC, the veteran was initially treated with thiamine 200 mg orally once daily and albuterol inhaler as needed. A clinical psychologist performed a comprehensive psychological evaluation on admission, which confirmed evidence of WKS with symptoms, including confusion, disorientation, and confabulation. There was no evidence of cultural diversity factors regarding the veteran’s delusional beliefs.
After the first full day in the CLC, the nursing staff observed anger and agitation that seemed to start midafternoon and continued until around dinnertime. The veteran displayed verbal outbursts, refusal to cooperate with the staff, and multiple attempts to leave the CLC. With the guidance of a geriatric psychiatrist, risperidone 1 mg once daily as needed was initiated, and staff continued with verbal redirection, both with limited efficacy. After 3 days, due to safety concerns for the veteran, other CLC patients, and CLC staff, risperidone dosing was increased to 1 mg twice daily, which had limited efficacy. Lorazepam 1 mg once daily also was added. A careful medication review was performed to minimize any potential AEs or interactions that might have contributed to the veteran’s behavior, but no pharmacologic interventions were found to fully abate their behavioral issues.
After 5 weeks of ongoing intermittent behavioral issues, the medical team again met to discuss new treatment options.A case reported by Husebo and colleagues used scheduled acetaminophen to help relieve neuropsychiatric symptoms of dementia in a patient who exhibited similar behavioral issues and did not respond well to antipsychotics or benzodiazepines.8 Although our veteran did not express or exhibit obvious pain, the medical team chose to trial this intervention, and the veteran was started on acetaminophen 650 mg orally 3 times daily. A comprehensive metabolic panel, including GGT and thyroid-stimulating hormone, was performed before starting acetaminophen; no abnormalities were noted. The clinical examination did not reveal physical abnormalities other than ataxia.
After 5 days of therapy with the scheduled acetaminophen, the veteran’s clinical behavior dramatically improved. The veteran exhibited infrequent agitated behavior and became cooperative with staff. Three days later, the scheduled lorazepam was discontinued, and eventually they were tapered off risperidone. One month after starting scheduled acetaminophen, the veteran had improved to a point where the staff determined a safe discharge plan could be initiated. The veteran’s nystagmus resolved and behavioral issues improved, although cognitive impairment persisted.
Due to COVID-19, a teleconference was scheduled with the veteran’s spouse to discuss a discharge plan. The spouse was pleased that the veteran had progressed adequately both functionally and behaviorally to make a safe discharge home possible. The spouse arranged to take family leave from their job to help support the veteran after discharge. The veteran was able to return home with a safe discharge plan 1 week later. The acetaminophen was continued with twice-daily dosing and was continued because there were no new behavioral issues. This was done to enhance postfacility adherence and minimize the risk of drug-drug interactions. Attempts to follow up with the veteran postdischarge were unfortunately unsuccessful as the family lived out of the local area.
Discussion
Alcohol misuse is a common finding in many US veterans, as well as in the general population.1,3 As a result, it is not uncommon to see patients with physical and psychological symptoms related to this abuse. Many of these patients will become verbally and physically abusive, thus having appropriate pharmacologic and nonpharmacologic interventions is important.
In this case study, the veteran was diagnosed with WKS and exhibited physical, cognitive, and emotional symptoms consistent with this disease. Although the physical symptoms improved with thiamine and abstinence from alcohol, their cognitive impairment, verbal outbursts, and aggressive demeanor persisted.
After using antipsychotic and anxiolytic medications with minimal clinical improvement, a trial of acetaminophen 650 mg 3 times daily was instituted. The patient’s behavior improved; demeanor became calmer, and they were easily redirected by the nursing staff. Psychological support was again employed, which enhanced and supported the veteran’s calmer demeanor. Although there is limited medical literature on the use of acetaminophen in clinical situations not related to pain, there has been research documenting its effect on social interaction.9,10
Acetaminophen is an analgesic medication that acts through central neural mechanisms. It has been hypothesized that social and physical pain rely on shared neurochemical underpinnings, and some of the regions of the brain involved in affective experience of physical pain also have been found to be involved in the experience of social pain.11 Acetaminophen may impact an individual’s social well-being as social pain processes.11 It has been shown to blunt reactivity to both physical pain as well as negative stimuli.11
Conclusions
A 2019 survey on alcohol and drug use found 5.6% of adults aged ≥ 18 have an alcohol use disorder.12 In severe cases, this can result in WKS. Although replacement of thiamine is critical for physical improvement, psychological deficits may persist. Small studies have advanced the concept of using scheduled acetaminophen even when the patient is not verbalizing or displaying pain.13 Although more research needs to be done on this topic, this palliative approach may be worth considering, especially if the risks of antipsychotics and anxiolytics outweigh the benefits.
Alcohol is the most common substance misused by veterans. 1 Veterans may m isuse alcohol as a result of mental illness or posttraumatic stress disorder (PTSD), having difficulties adjusting to civilian life, or because of heavy drinking habits acquired before leaving active duty. 2 One potential long-term effect of chronic alcohol misuse is Wernicke-Korsakoff syndrome (WKS), a neuropsychiatric condition secondary to a deficiency of thiamine. 3 The disease is characterized by altered mental status, oculomotor findings, and ataxia. 3 Patients with WKS may exhibit challenging behaviors, including aggression, disinhibition, and lack of awareness of their illness. 4 Due to long-standing cognitive and physical deficits, many patients require lifelong care with a focus on a palliative approach. 3
The mainstay of pharmacologic management for the neuropsychiatric symptoms of WKS continues to be psychoactive medications, such as antipsychotics, benzodiazepines, antidepressants, and anticonvulsant medications.4-6 Though atypical antipsychotic medications remain the most widely used, they have a high adverse effect (AE) profile.5,6 Among the potential AEs are metabolic syndrome, anticholinergic effects, QTc prolongation, orthostatic hypotension, extrapyramidal effects, sedation, and falls. There also is a US Food and Drug Administration boxed warning for increased risk of mortality.7 With the goal of improving and maintaining patient safety, pharmacologic interventions with lower AEs may be beneficial in the management of the neuropsychiatric symptoms of WKS.
This case describes a veteran who was initially hospitalized due to confusion, ataxia, and nystagmus secondary to chronic alcohol overuse. The aim of the case was to consider the use of acetaminophen in place of psychoactive medications as a way to manage neuropsychiatric symptoms of WKS even when pain was not present.
Case Presentation
A veteran presented to the local US Department of Veterans Affairs (VA) emergency department (ED) due to their spouse’s concern of acute onset confusion and ambulatory difficulties. The veteran’s medical history included extensive alcohol misuse, mild asthma, and diet-controlled hyperlipidemia. On initial evaluation, the veteran displayed symptoms of ataxia and confusion. When asked why the veteran was at the ED, the response was, “I just came to the hospital to find my sister.” Based on their medical history, clinical evaluation, and altered mental status, the veteran was admitted to the acute care medical service with a presumptive diagnosis of WKS.
On admission, the laboratory evaluation revealed normal alanine transaminase (ALT) and aspartate transaminase (AST) levels but markedly elevated γ-glutamyl transferase (GGT) consistent with alcohol toxicity. COVID-19 testing was negative. Magnetic resonance imaging (MRI) of the brain revealed evidence of alterations in the mammillary bodies and moderately severe cortical and cerebellar volume loss suggestive of long-standing alcohol use.
The veteran was hospitalized for 12 days and treated with high-dose IV thiamine, which resulted in improvement of their ophthalmic disorder (nystagmus) and ataxia. However, they continued to exhibit poor recall, confusion, and occasional agitation characterized by verbal outbursts and aggression toward the staff.
The veteran’s spouse worked full time and did not feel capable of providing the necessary follow-up care at home. The safest discharge plan found was to transfer the veteran to the local VA community living center (CLC) for physical therapy and further support of their marked cognitive decline and agitation.
Following admission to the CLC, the veteran was placed in a secured memory unit with staff trained specifically on management of veterans with cognitive impairment and behavioral concerns. As the veteran did not have decisional capacity on admission, the staff arranged a meeting with the spouse. Based on that conversation, the goals of care were to focus on a palliative approach and the hope that the veteran would one day be able to return home to their spouse.
At the CLC, the veteran was initially treated with thiamine 200 mg orally once daily and albuterol inhaler as needed. A clinical psychologist performed a comprehensive psychological evaluation on admission, which confirmed evidence of WKS with symptoms, including confusion, disorientation, and confabulation. There was no evidence of cultural diversity factors regarding the veteran’s delusional beliefs.
After the first full day in the CLC, the nursing staff observed anger and agitation that seemed to start midafternoon and continued until around dinnertime. The veteran displayed verbal outbursts, refusal to cooperate with the staff, and multiple attempts to leave the CLC. With the guidance of a geriatric psychiatrist, risperidone 1 mg once daily as needed was initiated, and staff continued with verbal redirection, both with limited efficacy. After 3 days, due to safety concerns for the veteran, other CLC patients, and CLC staff, risperidone dosing was increased to 1 mg twice daily, which had limited efficacy. Lorazepam 1 mg once daily also was added. A careful medication review was performed to minimize any potential AEs or interactions that might have contributed to the veteran’s behavior, but no pharmacologic interventions were found to fully abate their behavioral issues.
After 5 weeks of ongoing intermittent behavioral issues, the medical team again met to discuss new treatment options.A case reported by Husebo and colleagues used scheduled acetaminophen to help relieve neuropsychiatric symptoms of dementia in a patient who exhibited similar behavioral issues and did not respond well to antipsychotics or benzodiazepines.8 Although our veteran did not express or exhibit obvious pain, the medical team chose to trial this intervention, and the veteran was started on acetaminophen 650 mg orally 3 times daily. A comprehensive metabolic panel, including GGT and thyroid-stimulating hormone, was performed before starting acetaminophen; no abnormalities were noted. The clinical examination did not reveal physical abnormalities other than ataxia.
After 5 days of therapy with the scheduled acetaminophen, the veteran’s clinical behavior dramatically improved. The veteran exhibited infrequent agitated behavior and became cooperative with staff. Three days later, the scheduled lorazepam was discontinued, and eventually they were tapered off risperidone. One month after starting scheduled acetaminophen, the veteran had improved to a point where the staff determined a safe discharge plan could be initiated. The veteran’s nystagmus resolved and behavioral issues improved, although cognitive impairment persisted.
Due to COVID-19, a teleconference was scheduled with the veteran’s spouse to discuss a discharge plan. The spouse was pleased that the veteran had progressed adequately both functionally and behaviorally to make a safe discharge home possible. The spouse arranged to take family leave from their job to help support the veteran after discharge. The veteran was able to return home with a safe discharge plan 1 week later. The acetaminophen was continued with twice-daily dosing and was continued because there were no new behavioral issues. This was done to enhance postfacility adherence and minimize the risk of drug-drug interactions. Attempts to follow up with the veteran postdischarge were unfortunately unsuccessful as the family lived out of the local area.
Discussion
Alcohol misuse is a common finding in many US veterans, as well as in the general population.1,3 As a result, it is not uncommon to see patients with physical and psychological symptoms related to this abuse. Many of these patients will become verbally and physically abusive, thus having appropriate pharmacologic and nonpharmacologic interventions is important.
In this case study, the veteran was diagnosed with WKS and exhibited physical, cognitive, and emotional symptoms consistent with this disease. Although the physical symptoms improved with thiamine and abstinence from alcohol, their cognitive impairment, verbal outbursts, and aggressive demeanor persisted.
After using antipsychotic and anxiolytic medications with minimal clinical improvement, a trial of acetaminophen 650 mg 3 times daily was instituted. The patient’s behavior improved; demeanor became calmer, and they were easily redirected by the nursing staff. Psychological support was again employed, which enhanced and supported the veteran’s calmer demeanor. Although there is limited medical literature on the use of acetaminophen in clinical situations not related to pain, there has been research documenting its effect on social interaction.9,10
Acetaminophen is an analgesic medication that acts through central neural mechanisms. It has been hypothesized that social and physical pain rely on shared neurochemical underpinnings, and some of the regions of the brain involved in affective experience of physical pain also have been found to be involved in the experience of social pain.11 Acetaminophen may impact an individual’s social well-being as social pain processes.11 It has been shown to blunt reactivity to both physical pain as well as negative stimuli.11
Conclusions
A 2019 survey on alcohol and drug use found 5.6% of adults aged ≥ 18 have an alcohol use disorder.12 In severe cases, this can result in WKS. Although replacement of thiamine is critical for physical improvement, psychological deficits may persist. Small studies have advanced the concept of using scheduled acetaminophen even when the patient is not verbalizing or displaying pain.13 Although more research needs to be done on this topic, this palliative approach may be worth considering, especially if the risks of antipsychotics and anxiolytics outweigh the benefits.
1. National Institute on Drug Abuse. Substance use and military life drug facts. Published October 2019. Accessed November 10, 2021. https://www.drugabuse.gov/publications/drugfacts/substance-use-military-life
2. National Veterans Foundation. What statistics show about veteran substance abuse and why proper treatment is important. Published March 30, 2016. Accessed November 10, 2021. https://nvf.org/veteran-substance-abuse-statistics
3. National Center for Biotechnology Information. Korsakoff syndrome. Updated July 10, 2020. Accessed November 10, 2021. https://www.ncbi.nlm.nih.gov/books/NBK539854
4. Gerridzen IJ, Goossensen MA. Patients with Korsakoff syndrome in nursing homes: characteristics, comorbidity, and use of psychotropic drugs. Int Psychogeriatr. 2014;26(1):115-121. doi:10.1017/S1041610213001543
5. Press D, Alexander M. Management of neuropsychiatric symptoms of dementia. Updated October 2021. Accessed November 10, 2021. https://www.uptodate.com/contents/management-of-neuropsychiatric-symptoms-of-dementia
6. Steinberg M, Lyketsos CG. Atypical antipsychotic use in patients with dementia: Managing safety concerns. Am J Psychiatry. 2012;169(9):900-906. doi:10.1176/appi.ajp.2012.12030342
7. Jibson MD. Second-generation antipsychotic medications: pharmacology, administration, and side effects. https://www.uptodate.com/contents/second-generation-antipsychotic-medications-pharmacology-administration-and-side-effects
8. Husebo BS, Ballard C, Sandvik R, Nilsen OB, Aarsland D. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ. 2011;343:d4065. doi:10.1136/bmj.d4065
9. Fung K, Alden LE. Once hurt, twice shy: social pain contributes to social anxiety. Emotion. 2017;(2):231-239. doi:10.1037/emo0000223
10. Roberts ID, Krajbich I, Cheavens JS, Campo JV, Way BM. Acetaminophen Reduces Distrust in Individuals with Borderline Personality Disorder Features. Clin Psychol Sci. 2018;6(1):145-154. doi:10.1177/2167702617731374
11. Dewall CN, Macdonald G, Webster GD, et al. Acetaminophen reduces social pain: behavioral and neural evidence. Psychol Sci. 2010;21(7):931-937. doi:10.1177/0956797610374741
12. National Institute on Alcohol Abuse and Alcoholism. Alcohol facts and statistics. Updated June 2021. Accessed November 2, 202November 10, 2021. https://www.niaaa.nih.gov/publications/brochures-and-fact-sheets/alcohol-facts-and-statistics
13. Chibnall JT, Tait RC, Harman B, Luebbert RA. Effect of acetaminophen on behavior, well-being, and psychotropic medication use in nursing home residents with moderate-to-severe dementia. J Am Geriatrics Soc. 2005;53(11):1921-9. doi:10.1111/j.1532-5415.2005.53572.x
1. National Institute on Drug Abuse. Substance use and military life drug facts. Published October 2019. Accessed November 10, 2021. https://www.drugabuse.gov/publications/drugfacts/substance-use-military-life
2. National Veterans Foundation. What statistics show about veteran substance abuse and why proper treatment is important. Published March 30, 2016. Accessed November 10, 2021. https://nvf.org/veteran-substance-abuse-statistics
3. National Center for Biotechnology Information. Korsakoff syndrome. Updated July 10, 2020. Accessed November 10, 2021. https://www.ncbi.nlm.nih.gov/books/NBK539854
4. Gerridzen IJ, Goossensen MA. Patients with Korsakoff syndrome in nursing homes: characteristics, comorbidity, and use of psychotropic drugs. Int Psychogeriatr. 2014;26(1):115-121. doi:10.1017/S1041610213001543
5. Press D, Alexander M. Management of neuropsychiatric symptoms of dementia. Updated October 2021. Accessed November 10, 2021. https://www.uptodate.com/contents/management-of-neuropsychiatric-symptoms-of-dementia
6. Steinberg M, Lyketsos CG. Atypical antipsychotic use in patients with dementia: Managing safety concerns. Am J Psychiatry. 2012;169(9):900-906. doi:10.1176/appi.ajp.2012.12030342
7. Jibson MD. Second-generation antipsychotic medications: pharmacology, administration, and side effects. https://www.uptodate.com/contents/second-generation-antipsychotic-medications-pharmacology-administration-and-side-effects
8. Husebo BS, Ballard C, Sandvik R, Nilsen OB, Aarsland D. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ. 2011;343:d4065. doi:10.1136/bmj.d4065
9. Fung K, Alden LE. Once hurt, twice shy: social pain contributes to social anxiety. Emotion. 2017;(2):231-239. doi:10.1037/emo0000223
10. Roberts ID, Krajbich I, Cheavens JS, Campo JV, Way BM. Acetaminophen Reduces Distrust in Individuals with Borderline Personality Disorder Features. Clin Psychol Sci. 2018;6(1):145-154. doi:10.1177/2167702617731374
11. Dewall CN, Macdonald G, Webster GD, et al. Acetaminophen reduces social pain: behavioral and neural evidence. Psychol Sci. 2010;21(7):931-937. doi:10.1177/0956797610374741
12. National Institute on Alcohol Abuse and Alcoholism. Alcohol facts and statistics. Updated June 2021. Accessed November 2, 202November 10, 2021. https://www.niaaa.nih.gov/publications/brochures-and-fact-sheets/alcohol-facts-and-statistics
13. Chibnall JT, Tait RC, Harman B, Luebbert RA. Effect of acetaminophen on behavior, well-being, and psychotropic medication use in nursing home residents with moderate-to-severe dementia. J Am Geriatrics Soc. 2005;53(11):1921-9. doi:10.1111/j.1532-5415.2005.53572.x