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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
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.
Opioid agonist therapy guards against self-harm, suicide
FROM THE LANCET PSYCHIATRY
Cessation of opioid agonist therapy (OAT) significantly increases the risk of self-harm and death by suicide in the first month after stopping the treatment in new findings that highlight the need for “advanced safety planning” during this critical time.
Investigators found that 4 weeks after stopping OAT, the risk of death by suicide was almost five times higher and the risk of hospital admission for self-harm was almost three times higher during this period, compared with the 4 weeks after initiation of OAT to treatment end.
These results highlight the importance of a “transition” period when stopping OAT and highlight the need for better supports for patients coming off this treatment, study investigator Prianka Padmanathan, MD, PhD candidate, Population Health Sciences, University of Bristol (England), told this news organization.
She noted the study supports previous findings that OAT “has an important role” in suicide prevention.
“Suicide and self-harm risk is greatly increased during treatment cessation, and advanced safety planning and additional psychosocial support during this time may be required,” Dr. Padmanathan said.
The findings were published online Dec. 15 in The Lancet Psychiatry.
Suicide, self-harm risk
Previous research shows an increased risk for overdose deaths and death in general during the first few weeks of starting and stopping treatment for opioid dependence.
“We wanted to see if the risk of dying by suicide was also elevated during these times,” said Dr. Padmanathan. As suicides are relatively rare, the researchers also looked at self-harm, “which is an important risk factor for suicide.”
, particularly buprenorphine or methadone.
“We tried to exclude people prescribed these drugs for pain and focused specifically on their prescription for opioid dependence,” Dr. Padmanathan said.
They estimated rates and adjusted risk ratios of hospital admissions for nonfatal self-harm and completed suicide during treatment initiation, maintenance, and cessation.
The study included 8,070 patients (69.3% men; mean baseline age, 33.3 years) who received OAT at least once from January 1998 through November 2018. The median treatment time was 84 days. Most of the participants lived in the most deprived neighborhoods and were White.
There were 807 hospital admissions for self-harm (1.99 per 100 person-years) and 46 suicides (0.11 per 100 person-years).
The investigators examined age, sex, socioeconomic status, number of previous OAT treatment episodes, previous self-harm, previous mental illness, and major chronic illness scores as potential confounders.
Need for psychosocial care
Results showed the risk for self-harm was significantly increased while off OAT (aRR, 1.5; 95% confidence interval, 1.21-1.88).
The overall age- and sex-standardized mortality ratio for suicide was 7.5 times higher (95% CI, 5.5-10) in the study cohort, compared with the general population in England between 1998 and 2017.
There was insufficient evidence to show the risk for suicide was higher off, versus on, treatment, but this may be because suicides are relatively rare, Dr. Padmanathan noted.
“The sample may have been too small to enable a difference to be detected. In contrast, self-harm is more common, so there was power to detect a difference there,” she said.
Risk for self-harm was more than double in the first 4 weeks after stopping OAT versus stable periods on treatment (aRR, 2.60; 95% CI, 1.83-3.7). Risk for suicide more than quadrupled during this period (aRR, 4.68; 95% CI, 1.63-13.42).
These new results suggest additional interventions may be in order, Dr. Padmanathan noted.
“We already knew that extra care – for example, providing naloxone when coming off OAT – was important to prevent overdoses. But this study suggests providing psychosocial care and other extra care may also be important to prevent suicides,” she said.
There was no statistical evidence of difference between buprenorphine and methadone in terms of self-harm and suicide risks. However, this may be because the sample was not large enough to detect a difference, said Dr. Padmanathan.
Although there are currently no guidelines to indicate an ideal OAT period, previous study results have suggested extending treatment to 2 years may be beneficial, perhaps reducing self-harm and, therefore, suicides, she noted.
“We think most of these adverse outcomes likely occur during short treatment episodes with an unplanned ending. Extending OAT sufficiently to enable a planned ending might help to reduce these risks,” she added.
‘A window of vulnerability’
Authors of an accompanying editorial note the study “adds weight” to the evidence that OAT is a “lifesaving” treatment.
“It’s critical to recognize that transitions in and out of care are vulnerable periods” when it comes to suicide, the coauthor of the editorial, Paul S. Nestadt, MD, department of psychiatry and behavioral sciences, Johns Hopkins University, Baltimore, told this news organization.
Official suicide statistics may not reflect the entire story, as many deaths that occur because of overdose after treatment cessation are not counted as suicides, he said. “It can be difficult for medical examiners to determine if an overdose was intentional or not,” Dr. Nestadt added.
After treatment has been established, physicians “would be wise to delay treatment cessation” until the patient is in a stable condition and can be closely followed by mental health professionals, the editorialists note.
“We must consider the month following OAT cessation to be a window of vulnerability, not just for relapse but also for suicide,” they write.
The finding that patients prescribed OAT have such a high rate of suicide, compared with the general population, is “troubling” and “highlights the importance of interventions which address both opioid use and suicide risk,” they add.
The editorialists point out the median treatment period of 84 days is less than what is generally recommended, raising the question of whether longer treatment might lower suicide risk after treatment discontinuation.
They also emphasized the need for further study to test potential suicide prevention interventions in the period after treatment cessation.
Dr. Nestadt added the new findings are “quite generalizable outside of the U.K.” and referred to similar studies carried out in Australia and elsewhere.
The study was funded by the Medical Research Council. Dr. Padmanathan was a coapplicant on an a grant awarded to University of Bristol by Bristol and Weston Hospital Charity focusing on suicide prevention for patients presenting to the emergency department with self-harm and harmful substance use. Dr. Nestadt has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE LANCET PSYCHIATRY
Cessation of opioid agonist therapy (OAT) significantly increases the risk of self-harm and death by suicide in the first month after stopping the treatment in new findings that highlight the need for “advanced safety planning” during this critical time.
Investigators found that 4 weeks after stopping OAT, the risk of death by suicide was almost five times higher and the risk of hospital admission for self-harm was almost three times higher during this period, compared with the 4 weeks after initiation of OAT to treatment end.
These results highlight the importance of a “transition” period when stopping OAT and highlight the need for better supports for patients coming off this treatment, study investigator Prianka Padmanathan, MD, PhD candidate, Population Health Sciences, University of Bristol (England), told this news organization.
She noted the study supports previous findings that OAT “has an important role” in suicide prevention.
“Suicide and self-harm risk is greatly increased during treatment cessation, and advanced safety planning and additional psychosocial support during this time may be required,” Dr. Padmanathan said.
The findings were published online Dec. 15 in The Lancet Psychiatry.
Suicide, self-harm risk
Previous research shows an increased risk for overdose deaths and death in general during the first few weeks of starting and stopping treatment for opioid dependence.
“We wanted to see if the risk of dying by suicide was also elevated during these times,” said Dr. Padmanathan. As suicides are relatively rare, the researchers also looked at self-harm, “which is an important risk factor for suicide.”
, particularly buprenorphine or methadone.
“We tried to exclude people prescribed these drugs for pain and focused specifically on their prescription for opioid dependence,” Dr. Padmanathan said.
They estimated rates and adjusted risk ratios of hospital admissions for nonfatal self-harm and completed suicide during treatment initiation, maintenance, and cessation.
The study included 8,070 patients (69.3% men; mean baseline age, 33.3 years) who received OAT at least once from January 1998 through November 2018. The median treatment time was 84 days. Most of the participants lived in the most deprived neighborhoods and were White.
There were 807 hospital admissions for self-harm (1.99 per 100 person-years) and 46 suicides (0.11 per 100 person-years).
The investigators examined age, sex, socioeconomic status, number of previous OAT treatment episodes, previous self-harm, previous mental illness, and major chronic illness scores as potential confounders.
Need for psychosocial care
Results showed the risk for self-harm was significantly increased while off OAT (aRR, 1.5; 95% confidence interval, 1.21-1.88).
The overall age- and sex-standardized mortality ratio for suicide was 7.5 times higher (95% CI, 5.5-10) in the study cohort, compared with the general population in England between 1998 and 2017.
There was insufficient evidence to show the risk for suicide was higher off, versus on, treatment, but this may be because suicides are relatively rare, Dr. Padmanathan noted.
“The sample may have been too small to enable a difference to be detected. In contrast, self-harm is more common, so there was power to detect a difference there,” she said.
Risk for self-harm was more than double in the first 4 weeks after stopping OAT versus stable periods on treatment (aRR, 2.60; 95% CI, 1.83-3.7). Risk for suicide more than quadrupled during this period (aRR, 4.68; 95% CI, 1.63-13.42).
These new results suggest additional interventions may be in order, Dr. Padmanathan noted.
“We already knew that extra care – for example, providing naloxone when coming off OAT – was important to prevent overdoses. But this study suggests providing psychosocial care and other extra care may also be important to prevent suicides,” she said.
There was no statistical evidence of difference between buprenorphine and methadone in terms of self-harm and suicide risks. However, this may be because the sample was not large enough to detect a difference, said Dr. Padmanathan.
Although there are currently no guidelines to indicate an ideal OAT period, previous study results have suggested extending treatment to 2 years may be beneficial, perhaps reducing self-harm and, therefore, suicides, she noted.
“We think most of these adverse outcomes likely occur during short treatment episodes with an unplanned ending. Extending OAT sufficiently to enable a planned ending might help to reduce these risks,” she added.
‘A window of vulnerability’
Authors of an accompanying editorial note the study “adds weight” to the evidence that OAT is a “lifesaving” treatment.
“It’s critical to recognize that transitions in and out of care are vulnerable periods” when it comes to suicide, the coauthor of the editorial, Paul S. Nestadt, MD, department of psychiatry and behavioral sciences, Johns Hopkins University, Baltimore, told this news organization.
Official suicide statistics may not reflect the entire story, as many deaths that occur because of overdose after treatment cessation are not counted as suicides, he said. “It can be difficult for medical examiners to determine if an overdose was intentional or not,” Dr. Nestadt added.
After treatment has been established, physicians “would be wise to delay treatment cessation” until the patient is in a stable condition and can be closely followed by mental health professionals, the editorialists note.
“We must consider the month following OAT cessation to be a window of vulnerability, not just for relapse but also for suicide,” they write.
The finding that patients prescribed OAT have such a high rate of suicide, compared with the general population, is “troubling” and “highlights the importance of interventions which address both opioid use and suicide risk,” they add.
The editorialists point out the median treatment period of 84 days is less than what is generally recommended, raising the question of whether longer treatment might lower suicide risk after treatment discontinuation.
They also emphasized the need for further study to test potential suicide prevention interventions in the period after treatment cessation.
Dr. Nestadt added the new findings are “quite generalizable outside of the U.K.” and referred to similar studies carried out in Australia and elsewhere.
The study was funded by the Medical Research Council. Dr. Padmanathan was a coapplicant on an a grant awarded to University of Bristol by Bristol and Weston Hospital Charity focusing on suicide prevention for patients presenting to the emergency department with self-harm and harmful substance use. Dr. Nestadt has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE LANCET PSYCHIATRY
Cessation of opioid agonist therapy (OAT) significantly increases the risk of self-harm and death by suicide in the first month after stopping the treatment in new findings that highlight the need for “advanced safety planning” during this critical time.
Investigators found that 4 weeks after stopping OAT, the risk of death by suicide was almost five times higher and the risk of hospital admission for self-harm was almost three times higher during this period, compared with the 4 weeks after initiation of OAT to treatment end.
These results highlight the importance of a “transition” period when stopping OAT and highlight the need for better supports for patients coming off this treatment, study investigator Prianka Padmanathan, MD, PhD candidate, Population Health Sciences, University of Bristol (England), told this news organization.
She noted the study supports previous findings that OAT “has an important role” in suicide prevention.
“Suicide and self-harm risk is greatly increased during treatment cessation, and advanced safety planning and additional psychosocial support during this time may be required,” Dr. Padmanathan said.
The findings were published online Dec. 15 in The Lancet Psychiatry.
Suicide, self-harm risk
Previous research shows an increased risk for overdose deaths and death in general during the first few weeks of starting and stopping treatment for opioid dependence.
“We wanted to see if the risk of dying by suicide was also elevated during these times,” said Dr. Padmanathan. As suicides are relatively rare, the researchers also looked at self-harm, “which is an important risk factor for suicide.”
, particularly buprenorphine or methadone.
“We tried to exclude people prescribed these drugs for pain and focused specifically on their prescription for opioid dependence,” Dr. Padmanathan said.
They estimated rates and adjusted risk ratios of hospital admissions for nonfatal self-harm and completed suicide during treatment initiation, maintenance, and cessation.
The study included 8,070 patients (69.3% men; mean baseline age, 33.3 years) who received OAT at least once from January 1998 through November 2018. The median treatment time was 84 days. Most of the participants lived in the most deprived neighborhoods and were White.
There were 807 hospital admissions for self-harm (1.99 per 100 person-years) and 46 suicides (0.11 per 100 person-years).
The investigators examined age, sex, socioeconomic status, number of previous OAT treatment episodes, previous self-harm, previous mental illness, and major chronic illness scores as potential confounders.
Need for psychosocial care
Results showed the risk for self-harm was significantly increased while off OAT (aRR, 1.5; 95% confidence interval, 1.21-1.88).
The overall age- and sex-standardized mortality ratio for suicide was 7.5 times higher (95% CI, 5.5-10) in the study cohort, compared with the general population in England between 1998 and 2017.
There was insufficient evidence to show the risk for suicide was higher off, versus on, treatment, but this may be because suicides are relatively rare, Dr. Padmanathan noted.
“The sample may have been too small to enable a difference to be detected. In contrast, self-harm is more common, so there was power to detect a difference there,” she said.
Risk for self-harm was more than double in the first 4 weeks after stopping OAT versus stable periods on treatment (aRR, 2.60; 95% CI, 1.83-3.7). Risk for suicide more than quadrupled during this period (aRR, 4.68; 95% CI, 1.63-13.42).
These new results suggest additional interventions may be in order, Dr. Padmanathan noted.
“We already knew that extra care – for example, providing naloxone when coming off OAT – was important to prevent overdoses. But this study suggests providing psychosocial care and other extra care may also be important to prevent suicides,” she said.
There was no statistical evidence of difference between buprenorphine and methadone in terms of self-harm and suicide risks. However, this may be because the sample was not large enough to detect a difference, said Dr. Padmanathan.
Although there are currently no guidelines to indicate an ideal OAT period, previous study results have suggested extending treatment to 2 years may be beneficial, perhaps reducing self-harm and, therefore, suicides, she noted.
“We think most of these adverse outcomes likely occur during short treatment episodes with an unplanned ending. Extending OAT sufficiently to enable a planned ending might help to reduce these risks,” she added.
‘A window of vulnerability’
Authors of an accompanying editorial note the study “adds weight” to the evidence that OAT is a “lifesaving” treatment.
“It’s critical to recognize that transitions in and out of care are vulnerable periods” when it comes to suicide, the coauthor of the editorial, Paul S. Nestadt, MD, department of psychiatry and behavioral sciences, Johns Hopkins University, Baltimore, told this news organization.
Official suicide statistics may not reflect the entire story, as many deaths that occur because of overdose after treatment cessation are not counted as suicides, he said. “It can be difficult for medical examiners to determine if an overdose was intentional or not,” Dr. Nestadt added.
After treatment has been established, physicians “would be wise to delay treatment cessation” until the patient is in a stable condition and can be closely followed by mental health professionals, the editorialists note.
“We must consider the month following OAT cessation to be a window of vulnerability, not just for relapse but also for suicide,” they write.
The finding that patients prescribed OAT have such a high rate of suicide, compared with the general population, is “troubling” and “highlights the importance of interventions which address both opioid use and suicide risk,” they add.
The editorialists point out the median treatment period of 84 days is less than what is generally recommended, raising the question of whether longer treatment might lower suicide risk after treatment discontinuation.
They also emphasized the need for further study to test potential suicide prevention interventions in the period after treatment cessation.
Dr. Nestadt added the new findings are “quite generalizable outside of the U.K.” and referred to similar studies carried out in Australia and elsewhere.
The study was funded by the Medical Research Council. Dr. Padmanathan was a coapplicant on an a grant awarded to University of Bristol by Bristol and Weston Hospital Charity focusing on suicide prevention for patients presenting to the emergency department with self-harm and harmful substance use. Dr. Nestadt has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Short-acting opioids needed for withdrawal in U.S. hospitals, say experts
The commentary by Robert A. Kleinman, MD, with the Centre for Addiction and Mental Health, and department of psychiatry, University of Toronto, and Sarah E. Wakeman, MD, with the division of general internal medicine at Massachusetts General Hospital, and Harvard Medical School, Boston, was published in Annals of Internal Medicine.
Currently, short-acting opioids are not recommended in the United States for opioid withdrawal symptoms (OWS) management in the hospital, the authors wrote. Instead, withdrawal symptoms are typically treated, followed by methadone or buprenorphine or nonopioid medications, but many patients don’t get enough relief. Undertreated withdrawal can result in patients leaving the hospital against medical advice, which is linked with higher risk of death.
Addiction specialist Elisabeth Poorman, MD, of the University of Illinois Chicago, said in an interview that she agrees it’s time to start shifting the thinking on using short-acting opioids for OWS in hospitals. Use varies greatly by hospital and by clinician, she said.
“It’s time to let evidence guide us and to be flexible,” Dr. Poorman said.
The commentary authors noted that with methadone, patients must wait several hours for maximal symptom reduction, and the full benefits of methadone treatment are not realized until days after initiation.
Rapid initiation of methadone may be feasible in hospitals and has been proposed as an option, but further study is necessary before widespread use, the authors wrote.
Short-acting opioids may address limitations of other opioids
Lofexidine, an alpha-2-adrenergic agonist, is the only drug approved by the Food and Drug Administration specifically for OWS.
“However,” the authors said, “more than half of patients with OWS treated with lofexidine in phase 3 efficacy trials dropped out by day five. Clonidine, another alpha-2-agonist used off label to treat OWS, has similar effects to those of lofexidine. “
Therefore, short-acting opioids may complement methadone and buprenorphine in treating OWS in the hospital by addressing their limitations, the authors wrote.
Dr. Kleinman and Dr. Wakeman also say short-acting opioids may help with starting buprenorphine for patients exposed to fentanyl, because short-acting opioids can relieve withdrawal symptoms while fentanyl is metabolized and excreted.
Supplementation with short-acting opioids within the hospital can relieve withdrawal symptoms and help keep patients comfortable while methadone is titrated to more effective doses for long-term treatment, they wrote.
With short-acting opioids, patients may become more engaged in their care with, for example, a tamper-proof, patient-controlled analgesia pump, which would allow them to have more autonomy in administration of opioids to relieve pain and withdrawal symptoms, the authors wrote.
Dr. Kleinman and Dr. Wakeman noted that many patients who inject drugs already consume short-acting illicit drugs in the hospital, typically in washrooms and smoking areas, so supervised use of short-acting opioids helps eliminate the risk for unwitnessed overdoses.
Barriers to short-acting opioid use
Despite use of short-acting opioids internationally, barriers in the United States include limited prospective, randomized, controlled research on their benefits. There is limited institutional support for such approaches, and concerns and stigma around providing opioids to patients with OUD.
“[M]any institutions have insufficient numbers of providers who are both confident and competent with standard buprenorphine and methadone initiation approaches, a prerequisite before adopting more complex regimens,” the authors wrote.
Short-acting, full-agonist opioids, as a complement to methadone or buprenorphine, is already recommended for inpatients with OUD who are experiencing acute pain.
But the authors argue it should be an option when pain is not present, but methadone or buprenorphine have not provided enough OWS relief.
When short-acting opioids are helpful, according to outside expert
Dr. Poorman agrees and says she has found short-acting opioids simple to use in the hospital and very helpful in two situations.
One is when patients are very clear that they don’t want any medication for opioid use disorder, but they do want to be treated for their acute medical issue.
“I thought that was a fantastic tool to have to demonstrate we’re listening to them and weren’t trying to impose something on them and left the door open to come back when they did want treatment, which many of them did,” Dr. Poorman said.
The second situation is when the patient is uncertain about options but very afraid of precipitated withdrawal from buprenorphine.
She said she then found it easy to switch from those medications to buprenorphine and methadone.
Dr. Poorman described a situation she encountered previously where the patient was injecting heroin several times a day for 30-40 years. He was very clear he wasn’t going to stop injecting heroin, but he needed medical attention. He was willing to get medical attention, but he told his doctor he didn’t want to be uncomfortable while in the hospital.
It was very hard for his doctor to accept relieving his symptoms of withdrawal as part of her job, because she felt as though she was condoning his drug use, Dr. Poorman explained.
But Dr. Poorman said it’s not realistic to think that someone who clearly does not want to stop using is going to stop using because a doctor made that person go through painful withdrawal “that they’ve structured their whole life around avoiding.”
Take-home message
“We need to understand that addiction is very complex. A lot of times people come to us distressed, and it’s a great time to engage them in care but engaging them in care doesn’t mean imposing discomfort or pain on them,” Dr. Poorman noted. Instead, it means “listening to them, helping them be comfortable in a really stressful situation and then letting them know we are always there for them wherever they are on their disease process or recovery journey so that they can come back to us.”
Dr. Wakeman previously served on clinical advisory board for Celero Systems and receives textbook royalties from Springer and author payment from UpToDate. Dr. Kleinman and Dr. Poorman declared no relevant financial relationships.
The commentary by Robert A. Kleinman, MD, with the Centre for Addiction and Mental Health, and department of psychiatry, University of Toronto, and Sarah E. Wakeman, MD, with the division of general internal medicine at Massachusetts General Hospital, and Harvard Medical School, Boston, was published in Annals of Internal Medicine.
Currently, short-acting opioids are not recommended in the United States for opioid withdrawal symptoms (OWS) management in the hospital, the authors wrote. Instead, withdrawal symptoms are typically treated, followed by methadone or buprenorphine or nonopioid medications, but many patients don’t get enough relief. Undertreated withdrawal can result in patients leaving the hospital against medical advice, which is linked with higher risk of death.
Addiction specialist Elisabeth Poorman, MD, of the University of Illinois Chicago, said in an interview that she agrees it’s time to start shifting the thinking on using short-acting opioids for OWS in hospitals. Use varies greatly by hospital and by clinician, she said.
“It’s time to let evidence guide us and to be flexible,” Dr. Poorman said.
The commentary authors noted that with methadone, patients must wait several hours for maximal symptom reduction, and the full benefits of methadone treatment are not realized until days after initiation.
Rapid initiation of methadone may be feasible in hospitals and has been proposed as an option, but further study is necessary before widespread use, the authors wrote.
Short-acting opioids may address limitations of other opioids
Lofexidine, an alpha-2-adrenergic agonist, is the only drug approved by the Food and Drug Administration specifically for OWS.
“However,” the authors said, “more than half of patients with OWS treated with lofexidine in phase 3 efficacy trials dropped out by day five. Clonidine, another alpha-2-agonist used off label to treat OWS, has similar effects to those of lofexidine. “
Therefore, short-acting opioids may complement methadone and buprenorphine in treating OWS in the hospital by addressing their limitations, the authors wrote.
Dr. Kleinman and Dr. Wakeman also say short-acting opioids may help with starting buprenorphine for patients exposed to fentanyl, because short-acting opioids can relieve withdrawal symptoms while fentanyl is metabolized and excreted.
Supplementation with short-acting opioids within the hospital can relieve withdrawal symptoms and help keep patients comfortable while methadone is titrated to more effective doses for long-term treatment, they wrote.
With short-acting opioids, patients may become more engaged in their care with, for example, a tamper-proof, patient-controlled analgesia pump, which would allow them to have more autonomy in administration of opioids to relieve pain and withdrawal symptoms, the authors wrote.
Dr. Kleinman and Dr. Wakeman noted that many patients who inject drugs already consume short-acting illicit drugs in the hospital, typically in washrooms and smoking areas, so supervised use of short-acting opioids helps eliminate the risk for unwitnessed overdoses.
Barriers to short-acting opioid use
Despite use of short-acting opioids internationally, barriers in the United States include limited prospective, randomized, controlled research on their benefits. There is limited institutional support for such approaches, and concerns and stigma around providing opioids to patients with OUD.
“[M]any institutions have insufficient numbers of providers who are both confident and competent with standard buprenorphine and methadone initiation approaches, a prerequisite before adopting more complex regimens,” the authors wrote.
Short-acting, full-agonist opioids, as a complement to methadone or buprenorphine, is already recommended for inpatients with OUD who are experiencing acute pain.
But the authors argue it should be an option when pain is not present, but methadone or buprenorphine have not provided enough OWS relief.
When short-acting opioids are helpful, according to outside expert
Dr. Poorman agrees and says she has found short-acting opioids simple to use in the hospital and very helpful in two situations.
One is when patients are very clear that they don’t want any medication for opioid use disorder, but they do want to be treated for their acute medical issue.
“I thought that was a fantastic tool to have to demonstrate we’re listening to them and weren’t trying to impose something on them and left the door open to come back when they did want treatment, which many of them did,” Dr. Poorman said.
The second situation is when the patient is uncertain about options but very afraid of precipitated withdrawal from buprenorphine.
She said she then found it easy to switch from those medications to buprenorphine and methadone.
Dr. Poorman described a situation she encountered previously where the patient was injecting heroin several times a day for 30-40 years. He was very clear he wasn’t going to stop injecting heroin, but he needed medical attention. He was willing to get medical attention, but he told his doctor he didn’t want to be uncomfortable while in the hospital.
It was very hard for his doctor to accept relieving his symptoms of withdrawal as part of her job, because she felt as though she was condoning his drug use, Dr. Poorman explained.
But Dr. Poorman said it’s not realistic to think that someone who clearly does not want to stop using is going to stop using because a doctor made that person go through painful withdrawal “that they’ve structured their whole life around avoiding.”
Take-home message
“We need to understand that addiction is very complex. A lot of times people come to us distressed, and it’s a great time to engage them in care but engaging them in care doesn’t mean imposing discomfort or pain on them,” Dr. Poorman noted. Instead, it means “listening to them, helping them be comfortable in a really stressful situation and then letting them know we are always there for them wherever they are on their disease process or recovery journey so that they can come back to us.”
Dr. Wakeman previously served on clinical advisory board for Celero Systems and receives textbook royalties from Springer and author payment from UpToDate. Dr. Kleinman and Dr. Poorman declared no relevant financial relationships.
The commentary by Robert A. Kleinman, MD, with the Centre for Addiction and Mental Health, and department of psychiatry, University of Toronto, and Sarah E. Wakeman, MD, with the division of general internal medicine at Massachusetts General Hospital, and Harvard Medical School, Boston, was published in Annals of Internal Medicine.
Currently, short-acting opioids are not recommended in the United States for opioid withdrawal symptoms (OWS) management in the hospital, the authors wrote. Instead, withdrawal symptoms are typically treated, followed by methadone or buprenorphine or nonopioid medications, but many patients don’t get enough relief. Undertreated withdrawal can result in patients leaving the hospital against medical advice, which is linked with higher risk of death.
Addiction specialist Elisabeth Poorman, MD, of the University of Illinois Chicago, said in an interview that she agrees it’s time to start shifting the thinking on using short-acting opioids for OWS in hospitals. Use varies greatly by hospital and by clinician, she said.
“It’s time to let evidence guide us and to be flexible,” Dr. Poorman said.
The commentary authors noted that with methadone, patients must wait several hours for maximal symptom reduction, and the full benefits of methadone treatment are not realized until days after initiation.
Rapid initiation of methadone may be feasible in hospitals and has been proposed as an option, but further study is necessary before widespread use, the authors wrote.
Short-acting opioids may address limitations of other opioids
Lofexidine, an alpha-2-adrenergic agonist, is the only drug approved by the Food and Drug Administration specifically for OWS.
“However,” the authors said, “more than half of patients with OWS treated with lofexidine in phase 3 efficacy trials dropped out by day five. Clonidine, another alpha-2-agonist used off label to treat OWS, has similar effects to those of lofexidine. “
Therefore, short-acting opioids may complement methadone and buprenorphine in treating OWS in the hospital by addressing their limitations, the authors wrote.
Dr. Kleinman and Dr. Wakeman also say short-acting opioids may help with starting buprenorphine for patients exposed to fentanyl, because short-acting opioids can relieve withdrawal symptoms while fentanyl is metabolized and excreted.
Supplementation with short-acting opioids within the hospital can relieve withdrawal symptoms and help keep patients comfortable while methadone is titrated to more effective doses for long-term treatment, they wrote.
With short-acting opioids, patients may become more engaged in their care with, for example, a tamper-proof, patient-controlled analgesia pump, which would allow them to have more autonomy in administration of opioids to relieve pain and withdrawal symptoms, the authors wrote.
Dr. Kleinman and Dr. Wakeman noted that many patients who inject drugs already consume short-acting illicit drugs in the hospital, typically in washrooms and smoking areas, so supervised use of short-acting opioids helps eliminate the risk for unwitnessed overdoses.
Barriers to short-acting opioid use
Despite use of short-acting opioids internationally, barriers in the United States include limited prospective, randomized, controlled research on their benefits. There is limited institutional support for such approaches, and concerns and stigma around providing opioids to patients with OUD.
“[M]any institutions have insufficient numbers of providers who are both confident and competent with standard buprenorphine and methadone initiation approaches, a prerequisite before adopting more complex regimens,” the authors wrote.
Short-acting, full-agonist opioids, as a complement to methadone or buprenorphine, is already recommended for inpatients with OUD who are experiencing acute pain.
But the authors argue it should be an option when pain is not present, but methadone or buprenorphine have not provided enough OWS relief.
When short-acting opioids are helpful, according to outside expert
Dr. Poorman agrees and says she has found short-acting opioids simple to use in the hospital and very helpful in two situations.
One is when patients are very clear that they don’t want any medication for opioid use disorder, but they do want to be treated for their acute medical issue.
“I thought that was a fantastic tool to have to demonstrate we’re listening to them and weren’t trying to impose something on them and left the door open to come back when they did want treatment, which many of them did,” Dr. Poorman said.
The second situation is when the patient is uncertain about options but very afraid of precipitated withdrawal from buprenorphine.
She said she then found it easy to switch from those medications to buprenorphine and methadone.
Dr. Poorman described a situation she encountered previously where the patient was injecting heroin several times a day for 30-40 years. He was very clear he wasn’t going to stop injecting heroin, but he needed medical attention. He was willing to get medical attention, but he told his doctor he didn’t want to be uncomfortable while in the hospital.
It was very hard for his doctor to accept relieving his symptoms of withdrawal as part of her job, because she felt as though she was condoning his drug use, Dr. Poorman explained.
But Dr. Poorman said it’s not realistic to think that someone who clearly does not want to stop using is going to stop using because a doctor made that person go through painful withdrawal “that they’ve structured their whole life around avoiding.”
Take-home message
“We need to understand that addiction is very complex. A lot of times people come to us distressed, and it’s a great time to engage them in care but engaging them in care doesn’t mean imposing discomfort or pain on them,” Dr. Poorman noted. Instead, it means “listening to them, helping them be comfortable in a really stressful situation and then letting them know we are always there for them wherever they are on their disease process or recovery journey so that they can come back to us.”
Dr. Wakeman previously served on clinical advisory board for Celero Systems and receives textbook royalties from Springer and author payment from UpToDate. Dr. Kleinman and Dr. Poorman declared no relevant financial relationships.
FROM ANNALS OF INTERNAL MEDICINE
U.S. overdose deaths hit an all-time high
a 28.5% increase from the previous year.
Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.
The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.
The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.
“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.
“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.
Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”
Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”
Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support.
Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.
In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.
“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
Fake pills, fentanyl a huge issue
Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.
“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.
Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.
The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.
“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.
National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.
Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”
Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.
A version of this article first appeared on Medscape.com.
a 28.5% increase from the previous year.
Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.
The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.
The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.
“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.
“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.
Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”
Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”
Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support.
Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.
In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.
“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
Fake pills, fentanyl a huge issue
Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.
“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.
Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.
The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.
“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.
National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.
Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”
Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.
A version of this article first appeared on Medscape.com.
a 28.5% increase from the previous year.
Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.
The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.
The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.
“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.
“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.
Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”
Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”
Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support.
Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.
In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.
“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
Fake pills, fentanyl a huge issue
Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.
“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.
Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.
The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.
“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.
National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.
Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”
Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.
A version of this article first appeared on Medscape.com.
Warn patients about illicit drugs doctored with fentanyl
Fentanyl is now threatening overdoses in patients exposed to essentially any of the full array of recreational drugs – not just opioids – that are being sold illicitly, according to an overview of the problem presented at the virtual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“Fentanyl can now be found in cocaine and methamphetamine. At this point, there is really no way to predict what is in a [street] drug,” Edwin A. Salsitz, MD, said at the meeting, sponsored by Medscape Live. He is associate clinical professor of medicine who works in the division of chemical dependency at Mount Sinai Beth Israel Medical Center in New York.
As proof of the frequency with which fentanyl is now being used as an additive, most patients with a drug use disorder, regardless of their drug of choice, are testing positive for fentanyl at Dr. Salsitz’s center. Many of those with positive fentanyl tests are unaware that their drugs had been doctored with this agent.
Relative to drugs sold as an opioid, such as heroin or oxycodone, the fentanyl dose in nonopioid drugs is typically more modest, but Dr. Salsitz pointed out that those expecting cocaine or methamphetamine often “have no heroin tolerance, so they are more vulnerable” to the adverse effects of fentanyl, including an overdose.
Although opioid tolerance might improve the chances for surviving a fentanyl overdose, the toxicology of fentanyl is not the same as other opioids. Death from heroin is typically a result of respiratory depression, but the onset is relatively slow, providing a greater opportunity to administer a reversal agent, such as naloxone.
Fentanyl not only produces respiratory depression but skeletal muscle rigidity. The rapid onset of “wooden chest syndrome” can occur within minutes, making the opportunity for intervention much smaller, Dr. Salsitz said.
To illustrate the phenomenon, Dr. Salsitz recounted a case.
After an argument with his mother, a 26-year-old male with a long history of intravenous drug use went to his bedroom. His mother, responding to the sound of a loud thud, rushed to the bedroom to find her son on the floor with a needle still in his arm. Resuscitation efforts by the mother and by the emergency responders, who arrived quickly, failed.
“The speed of his death made it clear that it was fentanyl related, and the postmortem toxicology confirmed that the exposure involved both heroin and fentanyl,” Dr. Salsitz said.
After the first wave of deaths in the opioid epidemic, which was attributed to inappropriate use of prescription opioids, the second wave was driven by heroin. In that wave, patients who became addicted to prescription opioids but were having more difficulty gaining access to them, turned to far cheaper and readily available street heroin. The third wave, driven by fentanyl, began several years ago when sellers of heroin began adding this synthetic opioid, which is relatively cheap, to intensify the high.
It is not expected to end quickly. The fentanyl added to heroin was never a prescription version. Rather, Dr. Salsitz said, it is synthesized in laboratories in China, Mexico, and the United States. It is relatively easy to produce and compact, which makes it easy to transport.
Exacerbating the risks that fentanyl poses when added to street drugs, even more potent versions, such as carfentanil, are also being added to cocaine, methamphetamines, and other nonopioid illicit drugs. When compared on a per-milligram basis, fentanyl is about 100 times more potent than heroin, but carfentanil is about 100 times more potent than fentanyl, according to Dr. Salsitz.
When the third wave of deaths in the opioid epidemic began around 2013, prescriptions of fentanyl, like many other opioid-type therapies were declining. The “perfect storm” that initiated the opioid epidemic was a product of intense focus on pain control and a misperception that prescription opioids posed a low risk of abuse potential, Dr. Salsitz said. By the time fentanyl was driving opioid deaths, the risks of opioids were widely appreciated and their use for prescription analgesia was declining.
Citing several cases, Dr. Salsitz noted that only 20 years after clinicians were being successfully sued for not offering enough analgesia, they were now going to jail for prescribing these drugs too liberally.
According to Dr. Salsitz, While psychiatrists might not have a role in this issue, Dr. Salsitz did see a role for these specialists in protecting patients from the adverse consequences of using illicit drugs doctored with fentanyl.
Noting that individuals with psychiatric disorders are more likely than the general population to self-medicate with drugs purchased illegally, Dr. Salsitz encouraged psychiatrists “to get involved” in asking about drug use and counseling patients on the risks of fentanyl substitution or additives.
“The message is that no one knows what are in these drugs, anymore,” he said.
In addition to making patients aware that many street drugs are now contaminated with fentanyl, Dr. Salsitz provided some safety tips. He suggested instructing patients to take a low dose of any newly acquired drug to gauge its effect, to avoid taking drugs alone, and to avoid mixing drugs. He also recommended using rapid fentanyl test strips in order to detect fentanyl contamination.
Even for the many psychiatrists who do not feel comfortable managing addiction, Dr. Salsitz recommended a proactive approach to address the current threat.
Test strips as an intervention
The seriousness of fentanyl contamination of illicit drugs, including cocaine and methamphetamine, was corroborated by two investigators at the School of Public Health and the Albert Einstein Medical School of Brown University, Providence, R.I. Brandon D.L. Marshall, PhD, associate professor of epidemiology in the School of Public Health, called fentanyl-contaminated cannabis “extremely rare,” but he said that it is being found in counterfeit prescription pills as well as in crystal methamphetamine and in both crack and powder cocaine.
He also advocated the use of fentanyl test strips.
“Test strips are an efficient, inexpensive, and effective way to determine whether fentanyl or related analogs are present in illicit drugs,” he said, noting that he is involved in a trial designed to determine whether fentanyl test strips can reduce the risk of fatal and nonfatal overdoses.
In a pilot study conducted in Baltimore, 69% of the 103 participants engaged in harm reduction behavior after using a fentanyl test strip and receiving a positive result (Addict Behav. 2020;110:106529). It is notable that 86% of the participants had a least one positive result when using the strips. More than half were surprised by the result.
One of the findings from this study was “that the lasting benefit of fentanyl test strip distribution is the opportunity to engage in discussions around safety and relationship building with historically underserved communities,” said the lead author, Ju Nyeong Park, PhD, assistant professor of medicine and epidemiology at Brown University. She moved to Brown after performing this work at Johns Hopkins University, Baltimore.
Dr. Park noted that “many patients in the community already know that they are using drugs containing fentanyl,” but for those who are concerned and wish to avoid contaminated drugs, fentanyl test strips “are a quick screening tool.” However, while the strips are helpful, she cautioned that they cannot be considered a definitive tool for detecting harm in illicit drugs.
“There may also be other chemicals present in tested drugs that confer risk,” she said.
Medscape Live and this news organization are owned by the same parent company. Dr. Salsitz, Dr. Marshall, and Dr. Park reported no potential conflicts of interest.
Fentanyl is now threatening overdoses in patients exposed to essentially any of the full array of recreational drugs – not just opioids – that are being sold illicitly, according to an overview of the problem presented at the virtual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“Fentanyl can now be found in cocaine and methamphetamine. At this point, there is really no way to predict what is in a [street] drug,” Edwin A. Salsitz, MD, said at the meeting, sponsored by Medscape Live. He is associate clinical professor of medicine who works in the division of chemical dependency at Mount Sinai Beth Israel Medical Center in New York.
As proof of the frequency with which fentanyl is now being used as an additive, most patients with a drug use disorder, regardless of their drug of choice, are testing positive for fentanyl at Dr. Salsitz’s center. Many of those with positive fentanyl tests are unaware that their drugs had been doctored with this agent.
Relative to drugs sold as an opioid, such as heroin or oxycodone, the fentanyl dose in nonopioid drugs is typically more modest, but Dr. Salsitz pointed out that those expecting cocaine or methamphetamine often “have no heroin tolerance, so they are more vulnerable” to the adverse effects of fentanyl, including an overdose.
Although opioid tolerance might improve the chances for surviving a fentanyl overdose, the toxicology of fentanyl is not the same as other opioids. Death from heroin is typically a result of respiratory depression, but the onset is relatively slow, providing a greater opportunity to administer a reversal agent, such as naloxone.
Fentanyl not only produces respiratory depression but skeletal muscle rigidity. The rapid onset of “wooden chest syndrome” can occur within minutes, making the opportunity for intervention much smaller, Dr. Salsitz said.
To illustrate the phenomenon, Dr. Salsitz recounted a case.
After an argument with his mother, a 26-year-old male with a long history of intravenous drug use went to his bedroom. His mother, responding to the sound of a loud thud, rushed to the bedroom to find her son on the floor with a needle still in his arm. Resuscitation efforts by the mother and by the emergency responders, who arrived quickly, failed.
“The speed of his death made it clear that it was fentanyl related, and the postmortem toxicology confirmed that the exposure involved both heroin and fentanyl,” Dr. Salsitz said.
After the first wave of deaths in the opioid epidemic, which was attributed to inappropriate use of prescription opioids, the second wave was driven by heroin. In that wave, patients who became addicted to prescription opioids but were having more difficulty gaining access to them, turned to far cheaper and readily available street heroin. The third wave, driven by fentanyl, began several years ago when sellers of heroin began adding this synthetic opioid, which is relatively cheap, to intensify the high.
It is not expected to end quickly. The fentanyl added to heroin was never a prescription version. Rather, Dr. Salsitz said, it is synthesized in laboratories in China, Mexico, and the United States. It is relatively easy to produce and compact, which makes it easy to transport.
Exacerbating the risks that fentanyl poses when added to street drugs, even more potent versions, such as carfentanil, are also being added to cocaine, methamphetamines, and other nonopioid illicit drugs. When compared on a per-milligram basis, fentanyl is about 100 times more potent than heroin, but carfentanil is about 100 times more potent than fentanyl, according to Dr. Salsitz.
When the third wave of deaths in the opioid epidemic began around 2013, prescriptions of fentanyl, like many other opioid-type therapies were declining. The “perfect storm” that initiated the opioid epidemic was a product of intense focus on pain control and a misperception that prescription opioids posed a low risk of abuse potential, Dr. Salsitz said. By the time fentanyl was driving opioid deaths, the risks of opioids were widely appreciated and their use for prescription analgesia was declining.
Citing several cases, Dr. Salsitz noted that only 20 years after clinicians were being successfully sued for not offering enough analgesia, they were now going to jail for prescribing these drugs too liberally.
According to Dr. Salsitz, While psychiatrists might not have a role in this issue, Dr. Salsitz did see a role for these specialists in protecting patients from the adverse consequences of using illicit drugs doctored with fentanyl.
Noting that individuals with psychiatric disorders are more likely than the general population to self-medicate with drugs purchased illegally, Dr. Salsitz encouraged psychiatrists “to get involved” in asking about drug use and counseling patients on the risks of fentanyl substitution or additives.
“The message is that no one knows what are in these drugs, anymore,” he said.
In addition to making patients aware that many street drugs are now contaminated with fentanyl, Dr. Salsitz provided some safety tips. He suggested instructing patients to take a low dose of any newly acquired drug to gauge its effect, to avoid taking drugs alone, and to avoid mixing drugs. He also recommended using rapid fentanyl test strips in order to detect fentanyl contamination.
Even for the many psychiatrists who do not feel comfortable managing addiction, Dr. Salsitz recommended a proactive approach to address the current threat.
Test strips as an intervention
The seriousness of fentanyl contamination of illicit drugs, including cocaine and methamphetamine, was corroborated by two investigators at the School of Public Health and the Albert Einstein Medical School of Brown University, Providence, R.I. Brandon D.L. Marshall, PhD, associate professor of epidemiology in the School of Public Health, called fentanyl-contaminated cannabis “extremely rare,” but he said that it is being found in counterfeit prescription pills as well as in crystal methamphetamine and in both crack and powder cocaine.
He also advocated the use of fentanyl test strips.
“Test strips are an efficient, inexpensive, and effective way to determine whether fentanyl or related analogs are present in illicit drugs,” he said, noting that he is involved in a trial designed to determine whether fentanyl test strips can reduce the risk of fatal and nonfatal overdoses.
In a pilot study conducted in Baltimore, 69% of the 103 participants engaged in harm reduction behavior after using a fentanyl test strip and receiving a positive result (Addict Behav. 2020;110:106529). It is notable that 86% of the participants had a least one positive result when using the strips. More than half were surprised by the result.
One of the findings from this study was “that the lasting benefit of fentanyl test strip distribution is the opportunity to engage in discussions around safety and relationship building with historically underserved communities,” said the lead author, Ju Nyeong Park, PhD, assistant professor of medicine and epidemiology at Brown University. She moved to Brown after performing this work at Johns Hopkins University, Baltimore.
Dr. Park noted that “many patients in the community already know that they are using drugs containing fentanyl,” but for those who are concerned and wish to avoid contaminated drugs, fentanyl test strips “are a quick screening tool.” However, while the strips are helpful, she cautioned that they cannot be considered a definitive tool for detecting harm in illicit drugs.
“There may also be other chemicals present in tested drugs that confer risk,” she said.
Medscape Live and this news organization are owned by the same parent company. Dr. Salsitz, Dr. Marshall, and Dr. Park reported no potential conflicts of interest.
Fentanyl is now threatening overdoses in patients exposed to essentially any of the full array of recreational drugs – not just opioids – that are being sold illicitly, according to an overview of the problem presented at the virtual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“Fentanyl can now be found in cocaine and methamphetamine. At this point, there is really no way to predict what is in a [street] drug,” Edwin A. Salsitz, MD, said at the meeting, sponsored by Medscape Live. He is associate clinical professor of medicine who works in the division of chemical dependency at Mount Sinai Beth Israel Medical Center in New York.
As proof of the frequency with which fentanyl is now being used as an additive, most patients with a drug use disorder, regardless of their drug of choice, are testing positive for fentanyl at Dr. Salsitz’s center. Many of those with positive fentanyl tests are unaware that their drugs had been doctored with this agent.
Relative to drugs sold as an opioid, such as heroin or oxycodone, the fentanyl dose in nonopioid drugs is typically more modest, but Dr. Salsitz pointed out that those expecting cocaine or methamphetamine often “have no heroin tolerance, so they are more vulnerable” to the adverse effects of fentanyl, including an overdose.
Although opioid tolerance might improve the chances for surviving a fentanyl overdose, the toxicology of fentanyl is not the same as other opioids. Death from heroin is typically a result of respiratory depression, but the onset is relatively slow, providing a greater opportunity to administer a reversal agent, such as naloxone.
Fentanyl not only produces respiratory depression but skeletal muscle rigidity. The rapid onset of “wooden chest syndrome” can occur within minutes, making the opportunity for intervention much smaller, Dr. Salsitz said.
To illustrate the phenomenon, Dr. Salsitz recounted a case.
After an argument with his mother, a 26-year-old male with a long history of intravenous drug use went to his bedroom. His mother, responding to the sound of a loud thud, rushed to the bedroom to find her son on the floor with a needle still in his arm. Resuscitation efforts by the mother and by the emergency responders, who arrived quickly, failed.
“The speed of his death made it clear that it was fentanyl related, and the postmortem toxicology confirmed that the exposure involved both heroin and fentanyl,” Dr. Salsitz said.
After the first wave of deaths in the opioid epidemic, which was attributed to inappropriate use of prescription opioids, the second wave was driven by heroin. In that wave, patients who became addicted to prescription opioids but were having more difficulty gaining access to them, turned to far cheaper and readily available street heroin. The third wave, driven by fentanyl, began several years ago when sellers of heroin began adding this synthetic opioid, which is relatively cheap, to intensify the high.
It is not expected to end quickly. The fentanyl added to heroin was never a prescription version. Rather, Dr. Salsitz said, it is synthesized in laboratories in China, Mexico, and the United States. It is relatively easy to produce and compact, which makes it easy to transport.
Exacerbating the risks that fentanyl poses when added to street drugs, even more potent versions, such as carfentanil, are also being added to cocaine, methamphetamines, and other nonopioid illicit drugs. When compared on a per-milligram basis, fentanyl is about 100 times more potent than heroin, but carfentanil is about 100 times more potent than fentanyl, according to Dr. Salsitz.
When the third wave of deaths in the opioid epidemic began around 2013, prescriptions of fentanyl, like many other opioid-type therapies were declining. The “perfect storm” that initiated the opioid epidemic was a product of intense focus on pain control and a misperception that prescription opioids posed a low risk of abuse potential, Dr. Salsitz said. By the time fentanyl was driving opioid deaths, the risks of opioids were widely appreciated and their use for prescription analgesia was declining.
Citing several cases, Dr. Salsitz noted that only 20 years after clinicians were being successfully sued for not offering enough analgesia, they were now going to jail for prescribing these drugs too liberally.
According to Dr. Salsitz, While psychiatrists might not have a role in this issue, Dr. Salsitz did see a role for these specialists in protecting patients from the adverse consequences of using illicit drugs doctored with fentanyl.
Noting that individuals with psychiatric disorders are more likely than the general population to self-medicate with drugs purchased illegally, Dr. Salsitz encouraged psychiatrists “to get involved” in asking about drug use and counseling patients on the risks of fentanyl substitution or additives.
“The message is that no one knows what are in these drugs, anymore,” he said.
In addition to making patients aware that many street drugs are now contaminated with fentanyl, Dr. Salsitz provided some safety tips. He suggested instructing patients to take a low dose of any newly acquired drug to gauge its effect, to avoid taking drugs alone, and to avoid mixing drugs. He also recommended using rapid fentanyl test strips in order to detect fentanyl contamination.
Even for the many psychiatrists who do not feel comfortable managing addiction, Dr. Salsitz recommended a proactive approach to address the current threat.
Test strips as an intervention
The seriousness of fentanyl contamination of illicit drugs, including cocaine and methamphetamine, was corroborated by two investigators at the School of Public Health and the Albert Einstein Medical School of Brown University, Providence, R.I. Brandon D.L. Marshall, PhD, associate professor of epidemiology in the School of Public Health, called fentanyl-contaminated cannabis “extremely rare,” but he said that it is being found in counterfeit prescription pills as well as in crystal methamphetamine and in both crack and powder cocaine.
He also advocated the use of fentanyl test strips.
“Test strips are an efficient, inexpensive, and effective way to determine whether fentanyl or related analogs are present in illicit drugs,” he said, noting that he is involved in a trial designed to determine whether fentanyl test strips can reduce the risk of fatal and nonfatal overdoses.
In a pilot study conducted in Baltimore, 69% of the 103 participants engaged in harm reduction behavior after using a fentanyl test strip and receiving a positive result (Addict Behav. 2020;110:106529). It is notable that 86% of the participants had a least one positive result when using the strips. More than half were surprised by the result.
One of the findings from this study was “that the lasting benefit of fentanyl test strip distribution is the opportunity to engage in discussions around safety and relationship building with historically underserved communities,” said the lead author, Ju Nyeong Park, PhD, assistant professor of medicine and epidemiology at Brown University. She moved to Brown after performing this work at Johns Hopkins University, Baltimore.
Dr. Park noted that “many patients in the community already know that they are using drugs containing fentanyl,” but for those who are concerned and wish to avoid contaminated drugs, fentanyl test strips “are a quick screening tool.” However, while the strips are helpful, she cautioned that they cannot be considered a definitive tool for detecting harm in illicit drugs.
“There may also be other chemicals present in tested drugs that confer risk,” she said.
Medscape Live and this news organization are owned by the same parent company. Dr. Salsitz, Dr. Marshall, and Dr. Park reported no potential conflicts of interest.
FROM PSYCHOPHARMACOLOGY UPDATE
Good news, bad news for buprenorphine in opioid use disorder
Misuse of buprenorphine in the United States by patients with opioid use disorder (OUD) dropped sharply between 2015 and 2019, new research shows.
Analyses of data from the National Survey on Drug Use and Health also showed that about 50% of the patients with OUD were not receiving substance use treatment – and that some may be misusing buprenorphine in an effort to self-treat their addiction.
Interestingly, there was no association between buprenorphine misuse and income among those with OUD or with race, ethnicity, or insurance status regardless of OUD status, which bucks commonly held perceptions of those with the disorder.
Overall, the findings “underscore the need to pursue actions that expand access to buprenorphine-based OUD treatment, to develop strategies to monitor and reduce buprenorphine misuse, and to address associated conditions,” the investigators, led by Beth Han, MD, PhD, National Institute on Drug Abuse (NIDA), write.
The study was published online October 15 in JAMA Network Open.
Opioid deaths
Centers for Disease Control and Prevention data Of those deaths, 69,710 involved opioids.
Buprenorphine, a medication approved by the U.S. Food and Drug Administration to treat OUD, has been shown to reduce opioid cravings and withdrawal symptoms and lower overdose risk.
The new survey included responses from 214,505 adults. Of these, 51.7% were women, 45.5% were age 50 years or older, and 63.9% were non-Hispanic White.
Responses were collected between 2015-2019 as part of an annual survey administered annually by the Substance Abuse and Mental Health Services Administration.
Misuse was defined as any use outside the prescribed amount, frequency, duration, or indication.
In 2019, hydrocodone, oxycodone, codeine, and tramadol were the most misused prescription opioid products. An estimated 2.4 million adults used buprenorphine, with 1.7 million reporting no misuse in the past 12 months.
While buprenorphine misuse was stable between 2015 and 2019 among individuals without OUD, misuse declined significantly among those with OUD – from 20.5% in 2015 to 15.9% in 2019 (P = .04).
A different picture of misuse
The demographic data reveals a picture of buprenorphine misuse that researchers note is quite different from common perceptions about people with substance use.
Those with OUD who misused buprenorphine were more likely to be non-Hispanic White (82.9% vs. 73.6%, respectively) and less likely to live in large metropolitan areas (47.7% vs. 58.1%).
Among participants with OUD, buprenorphine misuse was significantly associated with age, especially in those between 24 and 34 years (adjusted odds ratio [aOR], 2.9; 95% confidence interval, 1.4-5.8) and between 35 and 49 years (aOR, 2.3; 95% CI, 1.2-4.5).
It was also significantly associated with living in nonmetropolitan areas (aOR, 1.8; 95% CI, 1.0-3.0) and having past-year polysubstance use and use disorders (aOR, 3.9; 95% CI, 1.3-11.2); but negatively associated with past-year treatment for illicit drug use–only treatment (aOR, 0.4; 95% CI, 0.3-0.7).
There was no significant association between buprenorphine misuse and income in participants with OUD or with race, ethnicity, or insurance status, regardless of OUD status.
“Perceptions that persons of racial and ethnic minority groups and people living in poverty are more likely to misuse their medication are incorrect,” the researchers write.
“Nevertheless, these factors have been found to be important factors associated with opioid harms and receipt of buprenorphine treatment,” they add.
Between 2015 and 2017, the largest increase in opioid-related drug overdose deaths was among Black people aged 25 to 34, and the largest increase involving synthetic opioids was among Hispanic individuals aged 45 to 54. At the same time, White people were more likely to receive buprenorphine treatment for OUD.
‘Don’t exaggerate concerns’
Among survey participants with OUD, 57% of those who had misused buprenorphine in the past year had received no substance use treatment. Among those with OUD who had not misused the drug in the past year, 49% had received no treatment for their addiction.
The most common reason for buprenorphine misuse cited by those with OUD was “because I am hooked” (27.3%), which researchers said suggests people may be taking buprenorphine without a prescription to self-treat their OUD.
The investigators note that although buprenorphine is inexpensive and effective, clinicians currently must receive a federal waiver to prescribe it to more than 30 patients at a time.
Concern over potential misuse may be one reason some clinicians have been reluctant to complete the training process. However, the study results showed misuse rates of other opioids, including oxycodone and hydrocodone, were higher than those reported for buprenorphine.
“Many other prescription opioids are misused at much higher rates,” co-investigator Wilson Compton, MD, MPE, deputy director of NIDA, told this news organization.
“While there are concerns about all of them, we want to make sure that people don’t exaggerate the concerns – and understanding that oxycodone and hydrocodone are so much more frequently misused is important,” added Dr. Compton.
Symptom of inadequate access?
Commenting on the research, Bobby Mukkamala, MD, chair of the American Medical Association Board of Trustees, said individuals who misuse buprenorphine “commonly do so to alleviate uncontrolled pain or symptoms of withdrawal.”
“So-called misuse of buprenorphine is a symptom of inadequate access to physicians to treat opioid use disorder,” said Dr. Mukkamala, who also chairs the AMA Substance Use and Pain Care Task Force.
A 2020 study from the U.S. Department of Health & Human Services showed 40% of U.S. counties have no clinicians with a federal waiver permitting them to prescribe buprenorphine in an office setting.
In April, the HHS released new practice guidelines that allow certain practitioners licensed under state law who have a valid Drug Enforcement Administration registration to treat up to 30 patients with buprenorphine without having to complete requirements related to training, counseling, and other ancillary services known as an “X-waiver.”
The move was welcomed by many in the field, but Dr. Mukkamala said the agency did not go far enough.
“The AMA supports removing the federal X-waiver requirement to help destigmatize the provision of buprenorphine as well as remove the many administrative barriers that come with the federal requirement,” he said.
The study was funded by the National Institute on Drug Abuse. The study authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Misuse of buprenorphine in the United States by patients with opioid use disorder (OUD) dropped sharply between 2015 and 2019, new research shows.
Analyses of data from the National Survey on Drug Use and Health also showed that about 50% of the patients with OUD were not receiving substance use treatment – and that some may be misusing buprenorphine in an effort to self-treat their addiction.
Interestingly, there was no association between buprenorphine misuse and income among those with OUD or with race, ethnicity, or insurance status regardless of OUD status, which bucks commonly held perceptions of those with the disorder.
Overall, the findings “underscore the need to pursue actions that expand access to buprenorphine-based OUD treatment, to develop strategies to monitor and reduce buprenorphine misuse, and to address associated conditions,” the investigators, led by Beth Han, MD, PhD, National Institute on Drug Abuse (NIDA), write.
The study was published online October 15 in JAMA Network Open.
Opioid deaths
Centers for Disease Control and Prevention data Of those deaths, 69,710 involved opioids.
Buprenorphine, a medication approved by the U.S. Food and Drug Administration to treat OUD, has been shown to reduce opioid cravings and withdrawal symptoms and lower overdose risk.
The new survey included responses from 214,505 adults. Of these, 51.7% were women, 45.5% were age 50 years or older, and 63.9% were non-Hispanic White.
Responses were collected between 2015-2019 as part of an annual survey administered annually by the Substance Abuse and Mental Health Services Administration.
Misuse was defined as any use outside the prescribed amount, frequency, duration, or indication.
In 2019, hydrocodone, oxycodone, codeine, and tramadol were the most misused prescription opioid products. An estimated 2.4 million adults used buprenorphine, with 1.7 million reporting no misuse in the past 12 months.
While buprenorphine misuse was stable between 2015 and 2019 among individuals without OUD, misuse declined significantly among those with OUD – from 20.5% in 2015 to 15.9% in 2019 (P = .04).
A different picture of misuse
The demographic data reveals a picture of buprenorphine misuse that researchers note is quite different from common perceptions about people with substance use.
Those with OUD who misused buprenorphine were more likely to be non-Hispanic White (82.9% vs. 73.6%, respectively) and less likely to live in large metropolitan areas (47.7% vs. 58.1%).
Among participants with OUD, buprenorphine misuse was significantly associated with age, especially in those between 24 and 34 years (adjusted odds ratio [aOR], 2.9; 95% confidence interval, 1.4-5.8) and between 35 and 49 years (aOR, 2.3; 95% CI, 1.2-4.5).
It was also significantly associated with living in nonmetropolitan areas (aOR, 1.8; 95% CI, 1.0-3.0) and having past-year polysubstance use and use disorders (aOR, 3.9; 95% CI, 1.3-11.2); but negatively associated with past-year treatment for illicit drug use–only treatment (aOR, 0.4; 95% CI, 0.3-0.7).
There was no significant association between buprenorphine misuse and income in participants with OUD or with race, ethnicity, or insurance status, regardless of OUD status.
“Perceptions that persons of racial and ethnic minority groups and people living in poverty are more likely to misuse their medication are incorrect,” the researchers write.
“Nevertheless, these factors have been found to be important factors associated with opioid harms and receipt of buprenorphine treatment,” they add.
Between 2015 and 2017, the largest increase in opioid-related drug overdose deaths was among Black people aged 25 to 34, and the largest increase involving synthetic opioids was among Hispanic individuals aged 45 to 54. At the same time, White people were more likely to receive buprenorphine treatment for OUD.
‘Don’t exaggerate concerns’
Among survey participants with OUD, 57% of those who had misused buprenorphine in the past year had received no substance use treatment. Among those with OUD who had not misused the drug in the past year, 49% had received no treatment for their addiction.
The most common reason for buprenorphine misuse cited by those with OUD was “because I am hooked” (27.3%), which researchers said suggests people may be taking buprenorphine without a prescription to self-treat their OUD.
The investigators note that although buprenorphine is inexpensive and effective, clinicians currently must receive a federal waiver to prescribe it to more than 30 patients at a time.
Concern over potential misuse may be one reason some clinicians have been reluctant to complete the training process. However, the study results showed misuse rates of other opioids, including oxycodone and hydrocodone, were higher than those reported for buprenorphine.
“Many other prescription opioids are misused at much higher rates,” co-investigator Wilson Compton, MD, MPE, deputy director of NIDA, told this news organization.
“While there are concerns about all of them, we want to make sure that people don’t exaggerate the concerns – and understanding that oxycodone and hydrocodone are so much more frequently misused is important,” added Dr. Compton.
Symptom of inadequate access?
Commenting on the research, Bobby Mukkamala, MD, chair of the American Medical Association Board of Trustees, said individuals who misuse buprenorphine “commonly do so to alleviate uncontrolled pain or symptoms of withdrawal.”
“So-called misuse of buprenorphine is a symptom of inadequate access to physicians to treat opioid use disorder,” said Dr. Mukkamala, who also chairs the AMA Substance Use and Pain Care Task Force.
A 2020 study from the U.S. Department of Health & Human Services showed 40% of U.S. counties have no clinicians with a federal waiver permitting them to prescribe buprenorphine in an office setting.
In April, the HHS released new practice guidelines that allow certain practitioners licensed under state law who have a valid Drug Enforcement Administration registration to treat up to 30 patients with buprenorphine without having to complete requirements related to training, counseling, and other ancillary services known as an “X-waiver.”
The move was welcomed by many in the field, but Dr. Mukkamala said the agency did not go far enough.
“The AMA supports removing the federal X-waiver requirement to help destigmatize the provision of buprenorphine as well as remove the many administrative barriers that come with the federal requirement,” he said.
The study was funded by the National Institute on Drug Abuse. The study authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Misuse of buprenorphine in the United States by patients with opioid use disorder (OUD) dropped sharply between 2015 and 2019, new research shows.
Analyses of data from the National Survey on Drug Use and Health also showed that about 50% of the patients with OUD were not receiving substance use treatment – and that some may be misusing buprenorphine in an effort to self-treat their addiction.
Interestingly, there was no association between buprenorphine misuse and income among those with OUD or with race, ethnicity, or insurance status regardless of OUD status, which bucks commonly held perceptions of those with the disorder.
Overall, the findings “underscore the need to pursue actions that expand access to buprenorphine-based OUD treatment, to develop strategies to monitor and reduce buprenorphine misuse, and to address associated conditions,” the investigators, led by Beth Han, MD, PhD, National Institute on Drug Abuse (NIDA), write.
The study was published online October 15 in JAMA Network Open.
Opioid deaths
Centers for Disease Control and Prevention data Of those deaths, 69,710 involved opioids.
Buprenorphine, a medication approved by the U.S. Food and Drug Administration to treat OUD, has been shown to reduce opioid cravings and withdrawal symptoms and lower overdose risk.
The new survey included responses from 214,505 adults. Of these, 51.7% were women, 45.5% were age 50 years or older, and 63.9% were non-Hispanic White.
Responses were collected between 2015-2019 as part of an annual survey administered annually by the Substance Abuse and Mental Health Services Administration.
Misuse was defined as any use outside the prescribed amount, frequency, duration, or indication.
In 2019, hydrocodone, oxycodone, codeine, and tramadol were the most misused prescription opioid products. An estimated 2.4 million adults used buprenorphine, with 1.7 million reporting no misuse in the past 12 months.
While buprenorphine misuse was stable between 2015 and 2019 among individuals without OUD, misuse declined significantly among those with OUD – from 20.5% in 2015 to 15.9% in 2019 (P = .04).
A different picture of misuse
The demographic data reveals a picture of buprenorphine misuse that researchers note is quite different from common perceptions about people with substance use.
Those with OUD who misused buprenorphine were more likely to be non-Hispanic White (82.9% vs. 73.6%, respectively) and less likely to live in large metropolitan areas (47.7% vs. 58.1%).
Among participants with OUD, buprenorphine misuse was significantly associated with age, especially in those between 24 and 34 years (adjusted odds ratio [aOR], 2.9; 95% confidence interval, 1.4-5.8) and between 35 and 49 years (aOR, 2.3; 95% CI, 1.2-4.5).
It was also significantly associated with living in nonmetropolitan areas (aOR, 1.8; 95% CI, 1.0-3.0) and having past-year polysubstance use and use disorders (aOR, 3.9; 95% CI, 1.3-11.2); but negatively associated with past-year treatment for illicit drug use–only treatment (aOR, 0.4; 95% CI, 0.3-0.7).
There was no significant association between buprenorphine misuse and income in participants with OUD or with race, ethnicity, or insurance status, regardless of OUD status.
“Perceptions that persons of racial and ethnic minority groups and people living in poverty are more likely to misuse their medication are incorrect,” the researchers write.
“Nevertheless, these factors have been found to be important factors associated with opioid harms and receipt of buprenorphine treatment,” they add.
Between 2015 and 2017, the largest increase in opioid-related drug overdose deaths was among Black people aged 25 to 34, and the largest increase involving synthetic opioids was among Hispanic individuals aged 45 to 54. At the same time, White people were more likely to receive buprenorphine treatment for OUD.
‘Don’t exaggerate concerns’
Among survey participants with OUD, 57% of those who had misused buprenorphine in the past year had received no substance use treatment. Among those with OUD who had not misused the drug in the past year, 49% had received no treatment for their addiction.
The most common reason for buprenorphine misuse cited by those with OUD was “because I am hooked” (27.3%), which researchers said suggests people may be taking buprenorphine without a prescription to self-treat their OUD.
The investigators note that although buprenorphine is inexpensive and effective, clinicians currently must receive a federal waiver to prescribe it to more than 30 patients at a time.
Concern over potential misuse may be one reason some clinicians have been reluctant to complete the training process. However, the study results showed misuse rates of other opioids, including oxycodone and hydrocodone, were higher than those reported for buprenorphine.
“Many other prescription opioids are misused at much higher rates,” co-investigator Wilson Compton, MD, MPE, deputy director of NIDA, told this news organization.
“While there are concerns about all of them, we want to make sure that people don’t exaggerate the concerns – and understanding that oxycodone and hydrocodone are so much more frequently misused is important,” added Dr. Compton.
Symptom of inadequate access?
Commenting on the research, Bobby Mukkamala, MD, chair of the American Medical Association Board of Trustees, said individuals who misuse buprenorphine “commonly do so to alleviate uncontrolled pain or symptoms of withdrawal.”
“So-called misuse of buprenorphine is a symptom of inadequate access to physicians to treat opioid use disorder,” said Dr. Mukkamala, who also chairs the AMA Substance Use and Pain Care Task Force.
A 2020 study from the U.S. Department of Health & Human Services showed 40% of U.S. counties have no clinicians with a federal waiver permitting them to prescribe buprenorphine in an office setting.
In April, the HHS released new practice guidelines that allow certain practitioners licensed under state law who have a valid Drug Enforcement Administration registration to treat up to 30 patients with buprenorphine without having to complete requirements related to training, counseling, and other ancillary services known as an “X-waiver.”
The move was welcomed by many in the field, but Dr. Mukkamala said the agency did not go far enough.
“The AMA supports removing the federal X-waiver requirement to help destigmatize the provision of buprenorphine as well as remove the many administrative barriers that come with the federal requirement,” he said.
The study was funded by the National Institute on Drug Abuse. The study authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Opioid prescribing mapped: Alabama highest, New York lowest
Medicare beneficiaries in Alabama were more likely to get a prescription for an opioid than in any other state in 2019, based on newly released data.
That year, opioids represented 6.48% of all drug claims for part D enrollees in the state, just ahead of Utah at 6.41%. Idaho, at 6.07%, was the only other state with an opioid prescribing rate over 6%, while Oklahoma came in at an even 6.0%, according to the latest update of the Centers for Medicare & Medicaid Services’ dataset.
The lowest rate in 2019 belonged to New York, where 2.51% of drug claims, including original prescriptions and refills, involved an opioid. Rhode Island was next at 2.87%, followed by New Jersey (3.23%), Massachusetts (3.26%), and North Dakota (3.39%),
Altogether, Medicare part D processed 1.5 billion drug claims in 2019, of which 66.1 million, or 4.41%, involved opioids. Both of the opioid numbers were down from 2018, when opioids represented 4.68% (70.2 million) of the 1.5 billion total claims, and from 2014, when opioids were involved in 5.73% (81,026,831) of the 1.41 billion drug claims, the CMS data show. That works out to 5.77% fewer opioids in 2019, compared with 2014, despite the increase in total volume.
from 2014 to 2019, with Hawaii showing the smallest decline as it slipped 0.41 percentage points from 3.9% to 3.49%, according to the CMS.
In 2019, part D beneficiaries in Vermont were the most likely to receive a long-acting opioid, which accounted for 20.14% of all opioid prescriptions in the state, while Kentucky had the lowest share of prescriptions written for long-acting forms at 6.41%. The national average was 11.02%, dropping from 11.79% in 2018 and 12.75% in 2014, the CMS reported.
Medicare beneficiaries in Alabama were more likely to get a prescription for an opioid than in any other state in 2019, based on newly released data.
That year, opioids represented 6.48% of all drug claims for part D enrollees in the state, just ahead of Utah at 6.41%. Idaho, at 6.07%, was the only other state with an opioid prescribing rate over 6%, while Oklahoma came in at an even 6.0%, according to the latest update of the Centers for Medicare & Medicaid Services’ dataset.
The lowest rate in 2019 belonged to New York, where 2.51% of drug claims, including original prescriptions and refills, involved an opioid. Rhode Island was next at 2.87%, followed by New Jersey (3.23%), Massachusetts (3.26%), and North Dakota (3.39%),
Altogether, Medicare part D processed 1.5 billion drug claims in 2019, of which 66.1 million, or 4.41%, involved opioids. Both of the opioid numbers were down from 2018, when opioids represented 4.68% (70.2 million) of the 1.5 billion total claims, and from 2014, when opioids were involved in 5.73% (81,026,831) of the 1.41 billion drug claims, the CMS data show. That works out to 5.77% fewer opioids in 2019, compared with 2014, despite the increase in total volume.
from 2014 to 2019, with Hawaii showing the smallest decline as it slipped 0.41 percentage points from 3.9% to 3.49%, according to the CMS.
In 2019, part D beneficiaries in Vermont were the most likely to receive a long-acting opioid, which accounted for 20.14% of all opioid prescriptions in the state, while Kentucky had the lowest share of prescriptions written for long-acting forms at 6.41%. The national average was 11.02%, dropping from 11.79% in 2018 and 12.75% in 2014, the CMS reported.
Medicare beneficiaries in Alabama were more likely to get a prescription for an opioid than in any other state in 2019, based on newly released data.
That year, opioids represented 6.48% of all drug claims for part D enrollees in the state, just ahead of Utah at 6.41%. Idaho, at 6.07%, was the only other state with an opioid prescribing rate over 6%, while Oklahoma came in at an even 6.0%, according to the latest update of the Centers for Medicare & Medicaid Services’ dataset.
The lowest rate in 2019 belonged to New York, where 2.51% of drug claims, including original prescriptions and refills, involved an opioid. Rhode Island was next at 2.87%, followed by New Jersey (3.23%), Massachusetts (3.26%), and North Dakota (3.39%),
Altogether, Medicare part D processed 1.5 billion drug claims in 2019, of which 66.1 million, or 4.41%, involved opioids. Both of the opioid numbers were down from 2018, when opioids represented 4.68% (70.2 million) of the 1.5 billion total claims, and from 2014, when opioids were involved in 5.73% (81,026,831) of the 1.41 billion drug claims, the CMS data show. That works out to 5.77% fewer opioids in 2019, compared with 2014, despite the increase in total volume.
from 2014 to 2019, with Hawaii showing the smallest decline as it slipped 0.41 percentage points from 3.9% to 3.49%, according to the CMS.
In 2019, part D beneficiaries in Vermont were the most likely to receive a long-acting opioid, which accounted for 20.14% of all opioid prescriptions in the state, while Kentucky had the lowest share of prescriptions written for long-acting forms at 6.41%. The national average was 11.02%, dropping from 11.79% in 2018 and 12.75% in 2014, the CMS reported.
Opioid overdoses tied to lasting cognitive impairment
Opioid overdoses usually aren’t fatal, but a new review of numerous studies, mostly case reports and case series, suggests that they can have long-lasting effects on cognition, possibly because of hypoxia resulting from respiratory depression.
Erin L. Winstanley, PhD, MA, and associates noted in the review that opioids cause about 80% of worldwide deaths from illicit drug use, and the Centers for Disease Control and Prevention’s provisional August 2021 number of more than 88,000 opioid-caused deaths in the United States is the highest ever recorded – a 27% increase over what was reported last December. That number suggests that the opioid epidemic continues to rage, but the study results also show that the neurological consequences of nonfatal overdoses are an important public health problem.
And that’s something that may be overlooked, according to Mark S. Gold, MD, who was not involved with the study and was asked to comment on the review, which was published in the Journal of Addiction Science.
“Assuming that an overdose has no effect on the brain, mood, and behavior is not supported by experience or the literature. He is a University of Florida, Gainesville, Emeritus Eminent Scholar, adjunct professor of psychiatry at Washington University in St. Louis, and a member of the clinical council of Washington University’s Public Health Institute.
A common pattern among patients with opioid use disorder (OUD) is that they undergo treatment with medication-assisted therapy (MAT), only to drop out of treatment and then repeat the treatment at a later date. That suggests that physicians should take a harder look at the limitations of MAT and other treatments, Dr. Gold said.
Although the review found some associations between neurocognitive deficits and opioid overdose, the authors point out that it is difficult to make direct comparisons because of biases and differences in methodology among the included studies. They were not able to reach conclusions about the prevalence of brain injuries following nonfatal opioid overdoses. Few included studies controlled for confounding factors that might contribute to or explain neurocognitive impairments, reported Dr. Winstanley, associate professor in the department of behavioral medicine and psychiatry at the University of West Virginia, Morgantown, and associates.
Still, distinct patterns emerged from the analysis of almost 3,500 subjects in 79 studies in 21 countries. Twenty-nine studies reported diagnoses of leukoencephalopathy, which affects white matter. Spongiform leukoencephalopathy is known to occur secondarily after exposure to a variety of toxic agents, including carbon monoxide poisoning and drugs of abuse. The damage can lead to erosion of higher cerebral function. The condition can occur from 2 to 180 days after a hypoxic brain injury, potentially complicating efforts to attribute it specifically to an opioid overdose. Amnestic syndrome was also reported in some studies. One study found that about 39% of people seeking buprenorphine treatment suffered from neurocognitive impairment.
Dr. Gold called the study’s findings novel and of public health importance. “Each overdose takes a toll on the body, and especially the brain,” he said.
Better documentation needed
The variability in symptoms, as well as their timing, present challenges to initial treatment, which often occur before a patient reaches the hospital. This is a vital window because the length of time of inadequate respiration because of opioid overdose is likely to predict the extent of brain injury. The duration of inadequate respiration may not be captured in electronic medical records, and emergency departments don’t typically collect toxicology information, which may lead health care providers to attribute neurocognitive impairments to ongoing drug use rather than an acute anoxic or hypoxic episode. Further neurocognitive damage may have a delayed onset, and better documentation of these events could help physicians determine whether those symptoms stem from the acute event.
Dr. Winstanley and associates called for more research, including prospective case-control studies to identify brain changes following opioid-related overdose.
The authors also suggested that physicians might want to consider screening patients who experience prolonged anoxia or hypoxia for neurocognitive impairments and brain injuries. Dr. Gold agreed.
“Clinicians working with OUD patients should take these data to heart and take a comprehensive history of previous overdoses, loss of consciousness, head trauma, and following up on the history with neuropsychological and other tests of brain function,” Dr. Gold said. “After an assessment, rehabilitation and treatment might then be more personalized and effective.”
Dr. Gold had no relevant financial disclosures.
Opioid overdoses usually aren’t fatal, but a new review of numerous studies, mostly case reports and case series, suggests that they can have long-lasting effects on cognition, possibly because of hypoxia resulting from respiratory depression.
Erin L. Winstanley, PhD, MA, and associates noted in the review that opioids cause about 80% of worldwide deaths from illicit drug use, and the Centers for Disease Control and Prevention’s provisional August 2021 number of more than 88,000 opioid-caused deaths in the United States is the highest ever recorded – a 27% increase over what was reported last December. That number suggests that the opioid epidemic continues to rage, but the study results also show that the neurological consequences of nonfatal overdoses are an important public health problem.
And that’s something that may be overlooked, according to Mark S. Gold, MD, who was not involved with the study and was asked to comment on the review, which was published in the Journal of Addiction Science.
“Assuming that an overdose has no effect on the brain, mood, and behavior is not supported by experience or the literature. He is a University of Florida, Gainesville, Emeritus Eminent Scholar, adjunct professor of psychiatry at Washington University in St. Louis, and a member of the clinical council of Washington University’s Public Health Institute.
A common pattern among patients with opioid use disorder (OUD) is that they undergo treatment with medication-assisted therapy (MAT), only to drop out of treatment and then repeat the treatment at a later date. That suggests that physicians should take a harder look at the limitations of MAT and other treatments, Dr. Gold said.
Although the review found some associations between neurocognitive deficits and opioid overdose, the authors point out that it is difficult to make direct comparisons because of biases and differences in methodology among the included studies. They were not able to reach conclusions about the prevalence of brain injuries following nonfatal opioid overdoses. Few included studies controlled for confounding factors that might contribute to or explain neurocognitive impairments, reported Dr. Winstanley, associate professor in the department of behavioral medicine and psychiatry at the University of West Virginia, Morgantown, and associates.
Still, distinct patterns emerged from the analysis of almost 3,500 subjects in 79 studies in 21 countries. Twenty-nine studies reported diagnoses of leukoencephalopathy, which affects white matter. Spongiform leukoencephalopathy is known to occur secondarily after exposure to a variety of toxic agents, including carbon monoxide poisoning and drugs of abuse. The damage can lead to erosion of higher cerebral function. The condition can occur from 2 to 180 days after a hypoxic brain injury, potentially complicating efforts to attribute it specifically to an opioid overdose. Amnestic syndrome was also reported in some studies. One study found that about 39% of people seeking buprenorphine treatment suffered from neurocognitive impairment.
Dr. Gold called the study’s findings novel and of public health importance. “Each overdose takes a toll on the body, and especially the brain,” he said.
Better documentation needed
The variability in symptoms, as well as their timing, present challenges to initial treatment, which often occur before a patient reaches the hospital. This is a vital window because the length of time of inadequate respiration because of opioid overdose is likely to predict the extent of brain injury. The duration of inadequate respiration may not be captured in electronic medical records, and emergency departments don’t typically collect toxicology information, which may lead health care providers to attribute neurocognitive impairments to ongoing drug use rather than an acute anoxic or hypoxic episode. Further neurocognitive damage may have a delayed onset, and better documentation of these events could help physicians determine whether those symptoms stem from the acute event.
Dr. Winstanley and associates called for more research, including prospective case-control studies to identify brain changes following opioid-related overdose.
The authors also suggested that physicians might want to consider screening patients who experience prolonged anoxia or hypoxia for neurocognitive impairments and brain injuries. Dr. Gold agreed.
“Clinicians working with OUD patients should take these data to heart and take a comprehensive history of previous overdoses, loss of consciousness, head trauma, and following up on the history with neuropsychological and other tests of brain function,” Dr. Gold said. “After an assessment, rehabilitation and treatment might then be more personalized and effective.”
Dr. Gold had no relevant financial disclosures.
Opioid overdoses usually aren’t fatal, but a new review of numerous studies, mostly case reports and case series, suggests that they can have long-lasting effects on cognition, possibly because of hypoxia resulting from respiratory depression.
Erin L. Winstanley, PhD, MA, and associates noted in the review that opioids cause about 80% of worldwide deaths from illicit drug use, and the Centers for Disease Control and Prevention’s provisional August 2021 number of more than 88,000 opioid-caused deaths in the United States is the highest ever recorded – a 27% increase over what was reported last December. That number suggests that the opioid epidemic continues to rage, but the study results also show that the neurological consequences of nonfatal overdoses are an important public health problem.
And that’s something that may be overlooked, according to Mark S. Gold, MD, who was not involved with the study and was asked to comment on the review, which was published in the Journal of Addiction Science.
“Assuming that an overdose has no effect on the brain, mood, and behavior is not supported by experience or the literature. He is a University of Florida, Gainesville, Emeritus Eminent Scholar, adjunct professor of psychiatry at Washington University in St. Louis, and a member of the clinical council of Washington University’s Public Health Institute.
A common pattern among patients with opioid use disorder (OUD) is that they undergo treatment with medication-assisted therapy (MAT), only to drop out of treatment and then repeat the treatment at a later date. That suggests that physicians should take a harder look at the limitations of MAT and other treatments, Dr. Gold said.
Although the review found some associations between neurocognitive deficits and opioid overdose, the authors point out that it is difficult to make direct comparisons because of biases and differences in methodology among the included studies. They were not able to reach conclusions about the prevalence of brain injuries following nonfatal opioid overdoses. Few included studies controlled for confounding factors that might contribute to or explain neurocognitive impairments, reported Dr. Winstanley, associate professor in the department of behavioral medicine and psychiatry at the University of West Virginia, Morgantown, and associates.
Still, distinct patterns emerged from the analysis of almost 3,500 subjects in 79 studies in 21 countries. Twenty-nine studies reported diagnoses of leukoencephalopathy, which affects white matter. Spongiform leukoencephalopathy is known to occur secondarily after exposure to a variety of toxic agents, including carbon monoxide poisoning and drugs of abuse. The damage can lead to erosion of higher cerebral function. The condition can occur from 2 to 180 days after a hypoxic brain injury, potentially complicating efforts to attribute it specifically to an opioid overdose. Amnestic syndrome was also reported in some studies. One study found that about 39% of people seeking buprenorphine treatment suffered from neurocognitive impairment.
Dr. Gold called the study’s findings novel and of public health importance. “Each overdose takes a toll on the body, and especially the brain,” he said.
Better documentation needed
The variability in symptoms, as well as their timing, present challenges to initial treatment, which often occur before a patient reaches the hospital. This is a vital window because the length of time of inadequate respiration because of opioid overdose is likely to predict the extent of brain injury. The duration of inadequate respiration may not be captured in electronic medical records, and emergency departments don’t typically collect toxicology information, which may lead health care providers to attribute neurocognitive impairments to ongoing drug use rather than an acute anoxic or hypoxic episode. Further neurocognitive damage may have a delayed onset, and better documentation of these events could help physicians determine whether those symptoms stem from the acute event.
Dr. Winstanley and associates called for more research, including prospective case-control studies to identify brain changes following opioid-related overdose.
The authors also suggested that physicians might want to consider screening patients who experience prolonged anoxia or hypoxia for neurocognitive impairments and brain injuries. Dr. Gold agreed.
“Clinicians working with OUD patients should take these data to heart and take a comprehensive history of previous overdoses, loss of consciousness, head trauma, and following up on the history with neuropsychological and other tests of brain function,” Dr. Gold said. “After an assessment, rehabilitation and treatment might then be more personalized and effective.”
Dr. Gold had no relevant financial disclosures.
FROM THE JOURNAL OF ADDICTION SCIENCE
Growing proportion of cardiac arrests in U.S. considered opioid related
Observational data indicate that the number of hospitalizations for cardiac arrests linked to opioid use roughly doubled from 2012 to 2018.
“This was an observational study, so we cannot conclude that all of the arrests were caused by opioids, but the findings do suggest the opioid epidemic is a contributor to increasing rates,” Senada S. Malik, of the University of New England, Portland, Maine, reported at the virtual annual congress of the European Society of Cardiology.
The data were drawn from the Nationwide Inpatient Sample (NIS) from 2012 to 2018, the most recent period available. Cardiac arrests were considered opioid related if there was a secondary diagnosis of opioid disease. The rates of opioid-associated hospitalizations for these types of cardiac arrests climbed from about 800 per year in 2012 to 1,500 per year in 2018, a trend that was statistically significant (P < .05).
The profile of patients with an opioid-associated cardiac arrest was different from those without secondary diagnosis of opioid disease. This included a younger age and lower rates of comorbidities: heart failure (21.2% vs. 40.6%; P < .05), renal failure (14.3% vs. 30.2%; P < .05), diabetes (19.5% vs. 35.4%; P < .05), and hypertension (43.4% vs. 64.9%; P < .05).
Mortality from opioid-associated cardiac arrest is lower
These features might explain the lower rate of in-hospital mortality for opioid-associated cardiac arrests (56.7% vs. 61.2%), according to Ms. Malik, who performed this research in collaboration with Wilbert S. Aronow, MD, director of cardiology research, Westchester Medical Center, Valhalla, N.Y.
When compared to those without a history of opioid use on admission, those with opioid-associated cardiac arrest were more likely to be depressed (18.8% vs. 9.0%), to smoke (37.0% vs. 21.8%) and to abuse alcohol (16.9% vs. 7.1%), according to the NIS data.
While these findings are based on cardiac arrests brought to a hospital, some opioid-induced cardiac arrests never result in hospital admission, according to data included in a recently issued scientific statement from the American Heart Association.
Rate of opioid-associated cardiac arrests underestimated
In that statement, which was focused on opioid-associated out-of-hospital cardiac arrests (OA-OHCA), numerous studies were cited to support the conclusion that these events are common and underestimated. One problem is that opioid-induced cardiac arrests are not always accurately differentiated from cardiac arrests induced by use of other substances, such as barbiturates, cocaine, or alcohol.
For this and other reasons, the data are inconsistent. One study based on emergency medical service (EMS) response data concluded that 9% of all out-of-hospital cardiac arrests are opioid associated.
In another study using potentially more accurate autopsy data, 60% of the non–cardiac-associated cardiac arrests were found to occur in individuals with potentially lethal serum concentrations of opioids. As 40% of out-of-hospital cardiac arrests were considered non–cardiac related, this suggested that 15% of all out-of-hospital cardiac arrests are opioid related.
In the NIS data, the incident curves of opioid-related cardiac arrests appeared to be flattening in 2018, the last year of data collection, but there was no indication they were declining.
Patterns of opioid-induced cardiac arrests evolving
The patterns of opioid-induced cardiac arrest have changed and are likely to continue to change in response to the evolving opioid epidemic, according to the AHA scientific statement. The authors described three waves of opioid abuse. The first, which was related to the promotion of prescription opioids to treat chronic pain that ultimately led to high rates of opioid addiction, peaked in 2012 when rates of these prescriptions began to fall. At that time a second wave, attributed to patients switching to less expensive nonprescription heroin, was already underway. A third wave, attributed to growth in the use of synthetic opioids, such as fentanyl, began in 2013 and is ongoing, according to data cited in the AHA statement.
Recognizing the role of opioids in rising rates of cardiac arrest is important for promoting strategies of effective treatment and prevention, according to Cameron Dezfulian, MD, medical director of the adult congenital heart disease program at Texas Children’s Hospital, Houston. Dr. Dezfulian was vice chair and leader of the writing committee for the AHA scientific statement on OA-OHCA. He said there are plenty of data to support the need for greater attention to the role of opioids in cardiac arrest.
“The recent data affirms the trends many of us have observed without our emergency rooms and ICUs: a steady increase in the proportion of OA-OHCA, primarily in young and otherwise healthy individuals,” he said.
He calls not only for more awareness at the front lines of health are but also for a more comprehensive approach.
“Public health policies and community- and hospital-based interventions are needed to reduce the mortality due to OA-OHCA, which is distinct from the traditional cardiac etiology,” Dr. Dezfulian said.
In opioid-induced cardiac arrest, as in other types of cardiac arrest, prompt initiation of cardiopulmonary resuscitation is essential, but early administration of the opioid antagonist naloxone can also be lifesaving, according to treatment strategies outlined in the AHA scientific statement. The fact that OA-OHCA typically occur in patients with structurally and electrophysiologically normal hearts is emphasized in the AHA statement. So is the enormous public health toll of OA-OHCA.
Death due to opioid overdose, which includes cardiac arrests, is now the leading cause of mortality in the U.S. among individuals between the ages of 25 and 64 years, according to the statement.
Ms. Malik reports no potential conflicts of interest. Dr. Dezfulian reports a financial relationship with Mallinckrodt.
Observational data indicate that the number of hospitalizations for cardiac arrests linked to opioid use roughly doubled from 2012 to 2018.
“This was an observational study, so we cannot conclude that all of the arrests were caused by opioids, but the findings do suggest the opioid epidemic is a contributor to increasing rates,” Senada S. Malik, of the University of New England, Portland, Maine, reported at the virtual annual congress of the European Society of Cardiology.
The data were drawn from the Nationwide Inpatient Sample (NIS) from 2012 to 2018, the most recent period available. Cardiac arrests were considered opioid related if there was a secondary diagnosis of opioid disease. The rates of opioid-associated hospitalizations for these types of cardiac arrests climbed from about 800 per year in 2012 to 1,500 per year in 2018, a trend that was statistically significant (P < .05).
The profile of patients with an opioid-associated cardiac arrest was different from those without secondary diagnosis of opioid disease. This included a younger age and lower rates of comorbidities: heart failure (21.2% vs. 40.6%; P < .05), renal failure (14.3% vs. 30.2%; P < .05), diabetes (19.5% vs. 35.4%; P < .05), and hypertension (43.4% vs. 64.9%; P < .05).
Mortality from opioid-associated cardiac arrest is lower
These features might explain the lower rate of in-hospital mortality for opioid-associated cardiac arrests (56.7% vs. 61.2%), according to Ms. Malik, who performed this research in collaboration with Wilbert S. Aronow, MD, director of cardiology research, Westchester Medical Center, Valhalla, N.Y.
When compared to those without a history of opioid use on admission, those with opioid-associated cardiac arrest were more likely to be depressed (18.8% vs. 9.0%), to smoke (37.0% vs. 21.8%) and to abuse alcohol (16.9% vs. 7.1%), according to the NIS data.
While these findings are based on cardiac arrests brought to a hospital, some opioid-induced cardiac arrests never result in hospital admission, according to data included in a recently issued scientific statement from the American Heart Association.
Rate of opioid-associated cardiac arrests underestimated
In that statement, which was focused on opioid-associated out-of-hospital cardiac arrests (OA-OHCA), numerous studies were cited to support the conclusion that these events are common and underestimated. One problem is that opioid-induced cardiac arrests are not always accurately differentiated from cardiac arrests induced by use of other substances, such as barbiturates, cocaine, or alcohol.
For this and other reasons, the data are inconsistent. One study based on emergency medical service (EMS) response data concluded that 9% of all out-of-hospital cardiac arrests are opioid associated.
In another study using potentially more accurate autopsy data, 60% of the non–cardiac-associated cardiac arrests were found to occur in individuals with potentially lethal serum concentrations of opioids. As 40% of out-of-hospital cardiac arrests were considered non–cardiac related, this suggested that 15% of all out-of-hospital cardiac arrests are opioid related.
In the NIS data, the incident curves of opioid-related cardiac arrests appeared to be flattening in 2018, the last year of data collection, but there was no indication they were declining.
Patterns of opioid-induced cardiac arrests evolving
The patterns of opioid-induced cardiac arrest have changed and are likely to continue to change in response to the evolving opioid epidemic, according to the AHA scientific statement. The authors described three waves of opioid abuse. The first, which was related to the promotion of prescription opioids to treat chronic pain that ultimately led to high rates of opioid addiction, peaked in 2012 when rates of these prescriptions began to fall. At that time a second wave, attributed to patients switching to less expensive nonprescription heroin, was already underway. A third wave, attributed to growth in the use of synthetic opioids, such as fentanyl, began in 2013 and is ongoing, according to data cited in the AHA statement.
Recognizing the role of opioids in rising rates of cardiac arrest is important for promoting strategies of effective treatment and prevention, according to Cameron Dezfulian, MD, medical director of the adult congenital heart disease program at Texas Children’s Hospital, Houston. Dr. Dezfulian was vice chair and leader of the writing committee for the AHA scientific statement on OA-OHCA. He said there are plenty of data to support the need for greater attention to the role of opioids in cardiac arrest.
“The recent data affirms the trends many of us have observed without our emergency rooms and ICUs: a steady increase in the proportion of OA-OHCA, primarily in young and otherwise healthy individuals,” he said.
He calls not only for more awareness at the front lines of health are but also for a more comprehensive approach.
“Public health policies and community- and hospital-based interventions are needed to reduce the mortality due to OA-OHCA, which is distinct from the traditional cardiac etiology,” Dr. Dezfulian said.
In opioid-induced cardiac arrest, as in other types of cardiac arrest, prompt initiation of cardiopulmonary resuscitation is essential, but early administration of the opioid antagonist naloxone can also be lifesaving, according to treatment strategies outlined in the AHA scientific statement. The fact that OA-OHCA typically occur in patients with structurally and electrophysiologically normal hearts is emphasized in the AHA statement. So is the enormous public health toll of OA-OHCA.
Death due to opioid overdose, which includes cardiac arrests, is now the leading cause of mortality in the U.S. among individuals between the ages of 25 and 64 years, according to the statement.
Ms. Malik reports no potential conflicts of interest. Dr. Dezfulian reports a financial relationship with Mallinckrodt.
Observational data indicate that the number of hospitalizations for cardiac arrests linked to opioid use roughly doubled from 2012 to 2018.
“This was an observational study, so we cannot conclude that all of the arrests were caused by opioids, but the findings do suggest the opioid epidemic is a contributor to increasing rates,” Senada S. Malik, of the University of New England, Portland, Maine, reported at the virtual annual congress of the European Society of Cardiology.
The data were drawn from the Nationwide Inpatient Sample (NIS) from 2012 to 2018, the most recent period available. Cardiac arrests were considered opioid related if there was a secondary diagnosis of opioid disease. The rates of opioid-associated hospitalizations for these types of cardiac arrests climbed from about 800 per year in 2012 to 1,500 per year in 2018, a trend that was statistically significant (P < .05).
The profile of patients with an opioid-associated cardiac arrest was different from those without secondary diagnosis of opioid disease. This included a younger age and lower rates of comorbidities: heart failure (21.2% vs. 40.6%; P < .05), renal failure (14.3% vs. 30.2%; P < .05), diabetes (19.5% vs. 35.4%; P < .05), and hypertension (43.4% vs. 64.9%; P < .05).
Mortality from opioid-associated cardiac arrest is lower
These features might explain the lower rate of in-hospital mortality for opioid-associated cardiac arrests (56.7% vs. 61.2%), according to Ms. Malik, who performed this research in collaboration with Wilbert S. Aronow, MD, director of cardiology research, Westchester Medical Center, Valhalla, N.Y.
When compared to those without a history of opioid use on admission, those with opioid-associated cardiac arrest were more likely to be depressed (18.8% vs. 9.0%), to smoke (37.0% vs. 21.8%) and to abuse alcohol (16.9% vs. 7.1%), according to the NIS data.
While these findings are based on cardiac arrests brought to a hospital, some opioid-induced cardiac arrests never result in hospital admission, according to data included in a recently issued scientific statement from the American Heart Association.
Rate of opioid-associated cardiac arrests underestimated
In that statement, which was focused on opioid-associated out-of-hospital cardiac arrests (OA-OHCA), numerous studies were cited to support the conclusion that these events are common and underestimated. One problem is that opioid-induced cardiac arrests are not always accurately differentiated from cardiac arrests induced by use of other substances, such as barbiturates, cocaine, or alcohol.
For this and other reasons, the data are inconsistent. One study based on emergency medical service (EMS) response data concluded that 9% of all out-of-hospital cardiac arrests are opioid associated.
In another study using potentially more accurate autopsy data, 60% of the non–cardiac-associated cardiac arrests were found to occur in individuals with potentially lethal serum concentrations of opioids. As 40% of out-of-hospital cardiac arrests were considered non–cardiac related, this suggested that 15% of all out-of-hospital cardiac arrests are opioid related.
In the NIS data, the incident curves of opioid-related cardiac arrests appeared to be flattening in 2018, the last year of data collection, but there was no indication they were declining.
Patterns of opioid-induced cardiac arrests evolving
The patterns of opioid-induced cardiac arrest have changed and are likely to continue to change in response to the evolving opioid epidemic, according to the AHA scientific statement. The authors described three waves of opioid abuse. The first, which was related to the promotion of prescription opioids to treat chronic pain that ultimately led to high rates of opioid addiction, peaked in 2012 when rates of these prescriptions began to fall. At that time a second wave, attributed to patients switching to less expensive nonprescription heroin, was already underway. A third wave, attributed to growth in the use of synthetic opioids, such as fentanyl, began in 2013 and is ongoing, according to data cited in the AHA statement.
Recognizing the role of opioids in rising rates of cardiac arrest is important for promoting strategies of effective treatment and prevention, according to Cameron Dezfulian, MD, medical director of the adult congenital heart disease program at Texas Children’s Hospital, Houston. Dr. Dezfulian was vice chair and leader of the writing committee for the AHA scientific statement on OA-OHCA. He said there are plenty of data to support the need for greater attention to the role of opioids in cardiac arrest.
“The recent data affirms the trends many of us have observed without our emergency rooms and ICUs: a steady increase in the proportion of OA-OHCA, primarily in young and otherwise healthy individuals,” he said.
He calls not only for more awareness at the front lines of health are but also for a more comprehensive approach.
“Public health policies and community- and hospital-based interventions are needed to reduce the mortality due to OA-OHCA, which is distinct from the traditional cardiac etiology,” Dr. Dezfulian said.
In opioid-induced cardiac arrest, as in other types of cardiac arrest, prompt initiation of cardiopulmonary resuscitation is essential, but early administration of the opioid antagonist naloxone can also be lifesaving, according to treatment strategies outlined in the AHA scientific statement. The fact that OA-OHCA typically occur in patients with structurally and electrophysiologically normal hearts is emphasized in the AHA statement. So is the enormous public health toll of OA-OHCA.
Death due to opioid overdose, which includes cardiac arrests, is now the leading cause of mortality in the U.S. among individuals between the ages of 25 and 64 years, according to the statement.
Ms. Malik reports no potential conflicts of interest. Dr. Dezfulian reports a financial relationship with Mallinckrodt.
FROM ESC 2021