Pain

A headache severity score compiled by assessing various migraine symptoms can help predict the likelihood of doctor visits and missed work or school, according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.

“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.

To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.

After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
 

Tracking multiple variables

“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.

“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”

He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.

“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”

The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”

The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.

A headache severity score compiled by assessing various migraine symptoms can help predict the likelihood of doctor visits and missed work or school, according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.

“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.

To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.

After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
 

Tracking multiple variables

“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.

“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”

He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.

“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”

The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”

The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.

A headache severity score compiled by assessing various migraine symptoms can help predict the likelihood of doctor visits and missed work or school, according to an analysis of data from thousands of headache sufferers who recorded variables like pain and duration in a daily digital diary.

“Our hope is that this work serves as foundational basis for better understanding the complexity of headache as a symptom-based condition,” James S. McGinley, PhD, of Vector Psychometric Group in Chapel Hill, N.C., and coauthors wrote. The study was published in Cephalalgia.

To evaluate whether keeping track of daily headache features can produce a useful, predictive score, the researchers reviewed data from migraine patients that were collected via N1‑Headache, a commercial digital health platform. Ultimately, information from 4,380 adults with a self-reported migraine diagnosis was analyzed; the sample was 90% female and their mean age was 37 years. Study participants reported an average of 33 headaches per month over the last 3 months. Nine patient-reported variables were initially considered in calculating the Headache Day Severity (HDS) score: pain intensity, headache duration, aura, pulsating/throbbing pain, unilateral pain, pain aggravation by activity, nausea/vomiting, photophobia, and phonophobia.

After determining that unilateral pain was not a meaningful variable, the researchers’ model found that, for every 1 standard deviation increase in HDS, the patient’s odds of physician visit increased by 71% (odds ratio, 1.71; 95% confidence interval, 1.32-2.21) and the odds of an ED visit increased by 342% (OR, 4.42; 95% CI, 2.23-7.60). They also found that the likelihood of missed work or school increased by 190% (OR, 2.90; 95% CI, 2.56-3.29), the chances of missing household work increased by 237% (OR, 3.37; 95% CI, 3.06-3.72) and the odds of missing other leisure or social activity increased by 228% (OR, 3.28; 95% CI, 2.97-3.64).
 

Tracking multiple variables

“We encourage all of our patients to monitor their headaches; there are just too many variables to try to keep it in your head,” Robert Cowan, MD, professor of neurology and chief of the division of headache medicine at Stanford (Calif.) University, said in an interview. He referenced a previous study from the University of Washington where patients were asked to track their headaches; that data was then compared against their self-reported headaches at a quarterly physician visit.

“What they found was there was absolutely no correlation with reported frequency of headache at the visit and what was seen in the tracker,” he said. “If patients had a headache in the previous 3 days before their visit, they felt that their headaches were poorly controlled. If they hadn’t, they thought their headaches were under good control. So the value of tracking is pretty clear.”

He added that, while not every headache sufferer needs to track their daily routines and symptoms, once those symptoms interfere with your life on a day-to-day basis, it’s probably time to consider keeping tabs on yourself with a tool of some sort. And while this study’s calculated HDS score supports the idea of migraine’s complexity, it also leaves unanswered the question of how to treat patients with severe symptoms.

“Frequently,” he said, “we’ll see patients who say: ‘I can deal with the pain, but the nausea makes it impossible to work, or the light sensitivity makes it impossible to go outside.’ The big question within the headache community is, can you treat migraine and have it address the whole spectrum, from dizziness to light sensitivity to sound sensitivity to vertigo, or should you be going after individual symptoms? That’s a controversy that rages on; I think most of us go for a combination. We’re in a polypharmacy phase: ‘If nausea is a big problem, take this, but we also try to prevent the whole migraine complex, so take this as well.’ ”

The authors acknowledged their study’s limitations, including the inability to determine how many participants’ migraines were formally diagnosed by a trained medical professional and the lack of generalizability of data from a convenience sample, though they added that patients who independently track their own headaches “may be representative of those who would participate in a clinical trial.” In addition, as seven of the nine features were collected in N1‑Headache on a yes/no scale, they recognized that “increasing the number of response options for each item may improve our ability to measure HDS.”

The study was funded by Amgen through the Competitive Grant Program in Migraine Research. The authors declared several potential conflicts of interest, including receiving funding, research support, salary, and honoraria from various pharmaceutical companies.

Muscle symptoms, such as cramps, pain, and other discomfort many patients blame on their recently prescribed statin usually aren’t caused by the drug at all, but by the expectation of such adverse effects, conclude researchers behind the randomized SAMSON trial, now fully published .

It’s common for patients to stop taking their statin because of muscle pain and their belief that the drug itself is to blame. That can sometimes be true, but the SAMSON trial, owing to its unusual design, makes a strong case that such symptoms are usually a nocebo effect.

That is, most statin-related muscle symptoms are likely “driven by the act of taking tablets rather than whether the tablets contain a statin,” concludes the report, which appears in the September 21 issue of the Journal of the American College of Cardiology, with lead authors James P. Howard, PhD, and Frances A. Wood, MPhil, Imperial College London.

SAMSON had been presented at the American Heart Association Scientific Sessions 2020 virtual meeting, covered at the time by this news organization, and simultaneously published in abbreviated form as correspondence in the New England Journal of Medicine.

“SAMSON suggests that the bulk of statin-related intolerable side effects arise from the taking of a tablet, not from statin therapy per se,” agrees an editorial accompanying the new publication.

“The study also demonstrates that the informal experimentation of stopping and restarting a statin to evaluate symptom resolution and reinduction without use of a placebo leads to nocebo symptoms misattributed to the statin,” writes Peter P. Toth, MD, PhD, Johns Hopkins University, Baltimore.

Statin intolerance, he continues, “warrants considerable further investigation, because it undermines standard of care for a very large number of patients worldwide,” leaving them vulnerable to atherosclerotic cardiovascular disease events. “Aches and pains are a fact of life; just because a patient has them does not mean they should be attributed to their statin.”

SAMSON assigned 35 men and 25 women to take atorvastatin 20 mg/day, its matching placebo, or neither pill each for 1 month in randomly alternating order for 12 months, with double-blinding, such that each of the three regimens was maintained for a total of 4 months.

The patients, 77% of whom were prescribed statins for primary prevention and all of whom had a history of stopping the drugs because of adverse effects, documented the severity of any perceived adverse effects on a smartphone app, with a “symptom score” ranging from 0 to 100.

The symptom score averaged 8.0 in months when no tablet was taken, but it was much higher in other months: 15.4 in placebo-pill months and 16.3 in months when atorvastatin was taken. The no-tablet score was significantly lower (P < .001) than either of the two other scores, which themselves were not significantly different from each other.

Eleven patients were unable to complete all 12 one-month segments of the trial, including five because of severe symptoms, but discontinuation was no more likely to occur in the atorvastatin group than in the placebo group.

The authors calculated an overall 0.90 “nocebo ratio” for the study, defined as the difference between symptom intensity on placebo and on no pill, divided by the difference between symptom intensity on atorvastatin and on no pill.

That means, the authors propose, that 90% of the symptom burden felt by patients receiving atorvastatin was also felt on the placebo pill and could be attributed to the nocebo effect.

“Prompt onset and offset of symptoms after starting and stopping tablets is often interpreted by patients and clinicians as evidence of causation. Our data indicate that this is true,” the authors write, but “the causation is from taking a tablet, rather than from the tablet being a statin.”

SAMSON was funded by the British Heart Foundation and supported by the National Institute for Health Research Imperial Biomedical Research Centre and the Imperial Clinical Trials Unit. Dr. Howard is supported by the Wellcome Trust. Dr. Wood declared no conflicts. Disclosures for the other authors are in the report. Dr. Toth discloses serving as a consultant to Amarin, Amgen, AstraZeneca, nio89, Kowa, Merck, Resverlogix, and Theravance; and serving on a speaker’s bureau for Amarin, Amgen, Esperion, and NovoNordisk.

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

Muscle symptoms, such as cramps, pain, and other discomfort many patients blame on their recently prescribed statin usually aren’t caused by the drug at all, but by the expectation of such adverse effects, conclude researchers behind the randomized SAMSON trial, now fully published .

It’s common for patients to stop taking their statin because of muscle pain and their belief that the drug itself is to blame. That can sometimes be true, but the SAMSON trial, owing to its unusual design, makes a strong case that such symptoms are usually a nocebo effect.

That is, most statin-related muscle symptoms are likely “driven by the act of taking tablets rather than whether the tablets contain a statin,” concludes the report, which appears in the September 21 issue of the Journal of the American College of Cardiology, with lead authors James P. Howard, PhD, and Frances A. Wood, MPhil, Imperial College London.

SAMSON had been presented at the American Heart Association Scientific Sessions 2020 virtual meeting, covered at the time by this news organization, and simultaneously published in abbreviated form as correspondence in the New England Journal of Medicine.

“SAMSON suggests that the bulk of statin-related intolerable side effects arise from the taking of a tablet, not from statin therapy per se,” agrees an editorial accompanying the new publication.

“The study also demonstrates that the informal experimentation of stopping and restarting a statin to evaluate symptom resolution and reinduction without use of a placebo leads to nocebo symptoms misattributed to the statin,” writes Peter P. Toth, MD, PhD, Johns Hopkins University, Baltimore.

Statin intolerance, he continues, “warrants considerable further investigation, because it undermines standard of care for a very large number of patients worldwide,” leaving them vulnerable to atherosclerotic cardiovascular disease events. “Aches and pains are a fact of life; just because a patient has them does not mean they should be attributed to their statin.”

SAMSON assigned 35 men and 25 women to take atorvastatin 20 mg/day, its matching placebo, or neither pill each for 1 month in randomly alternating order for 12 months, with double-blinding, such that each of the three regimens was maintained for a total of 4 months.

The patients, 77% of whom were prescribed statins for primary prevention and all of whom had a history of stopping the drugs because of adverse effects, documented the severity of any perceived adverse effects on a smartphone app, with a “symptom score” ranging from 0 to 100.

The symptom score averaged 8.0 in months when no tablet was taken, but it was much higher in other months: 15.4 in placebo-pill months and 16.3 in months when atorvastatin was taken. The no-tablet score was significantly lower (P < .001) than either of the two other scores, which themselves were not significantly different from each other.

Eleven patients were unable to complete all 12 one-month segments of the trial, including five because of severe symptoms, but discontinuation was no more likely to occur in the atorvastatin group than in the placebo group.

The authors calculated an overall 0.90 “nocebo ratio” for the study, defined as the difference between symptom intensity on placebo and on no pill, divided by the difference between symptom intensity on atorvastatin and on no pill.

That means, the authors propose, that 90% of the symptom burden felt by patients receiving atorvastatin was also felt on the placebo pill and could be attributed to the nocebo effect.

“Prompt onset and offset of symptoms after starting and stopping tablets is often interpreted by patients and clinicians as evidence of causation. Our data indicate that this is true,” the authors write, but “the causation is from taking a tablet, rather than from the tablet being a statin.”

SAMSON was funded by the British Heart Foundation and supported by the National Institute for Health Research Imperial Biomedical Research Centre and the Imperial Clinical Trials Unit. Dr. Howard is supported by the Wellcome Trust. Dr. Wood declared no conflicts. Disclosures for the other authors are in the report. Dr. Toth discloses serving as a consultant to Amarin, Amgen, AstraZeneca, nio89, Kowa, Merck, Resverlogix, and Theravance; and serving on a speaker’s bureau for Amarin, Amgen, Esperion, and NovoNordisk.

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

Muscle symptoms, such as cramps, pain, and other discomfort many patients blame on their recently prescribed statin usually aren’t caused by the drug at all, but by the expectation of such adverse effects, conclude researchers behind the randomized SAMSON trial, now fully published .

It’s common for patients to stop taking their statin because of muscle pain and their belief that the drug itself is to blame. That can sometimes be true, but the SAMSON trial, owing to its unusual design, makes a strong case that such symptoms are usually a nocebo effect.

That is, most statin-related muscle symptoms are likely “driven by the act of taking tablets rather than whether the tablets contain a statin,” concludes the report, which appears in the September 21 issue of the Journal of the American College of Cardiology, with lead authors James P. Howard, PhD, and Frances A. Wood, MPhil, Imperial College London.

SAMSON had been presented at the American Heart Association Scientific Sessions 2020 virtual meeting, covered at the time by this news organization, and simultaneously published in abbreviated form as correspondence in the New England Journal of Medicine.

“SAMSON suggests that the bulk of statin-related intolerable side effects arise from the taking of a tablet, not from statin therapy per se,” agrees an editorial accompanying the new publication.

“The study also demonstrates that the informal experimentation of stopping and restarting a statin to evaluate symptom resolution and reinduction without use of a placebo leads to nocebo symptoms misattributed to the statin,” writes Peter P. Toth, MD, PhD, Johns Hopkins University, Baltimore.

Statin intolerance, he continues, “warrants considerable further investigation, because it undermines standard of care for a very large number of patients worldwide,” leaving them vulnerable to atherosclerotic cardiovascular disease events. “Aches and pains are a fact of life; just because a patient has them does not mean they should be attributed to their statin.”

SAMSON assigned 35 men and 25 women to take atorvastatin 20 mg/day, its matching placebo, or neither pill each for 1 month in randomly alternating order for 12 months, with double-blinding, such that each of the three regimens was maintained for a total of 4 months.

The patients, 77% of whom were prescribed statins for primary prevention and all of whom had a history of stopping the drugs because of adverse effects, documented the severity of any perceived adverse effects on a smartphone app, with a “symptom score” ranging from 0 to 100.

The symptom score averaged 8.0 in months when no tablet was taken, but it was much higher in other months: 15.4 in placebo-pill months and 16.3 in months when atorvastatin was taken. The no-tablet score was significantly lower (P < .001) than either of the two other scores, which themselves were not significantly different from each other.

Eleven patients were unable to complete all 12 one-month segments of the trial, including five because of severe symptoms, but discontinuation was no more likely to occur in the atorvastatin group than in the placebo group.

The authors calculated an overall 0.90 “nocebo ratio” for the study, defined as the difference between symptom intensity on placebo and on no pill, divided by the difference between symptom intensity on atorvastatin and on no pill.

That means, the authors propose, that 90% of the symptom burden felt by patients receiving atorvastatin was also felt on the placebo pill and could be attributed to the nocebo effect.

“Prompt onset and offset of symptoms after starting and stopping tablets is often interpreted by patients and clinicians as evidence of causation. Our data indicate that this is true,” the authors write, but “the causation is from taking a tablet, rather than from the tablet being a statin.”

SAMSON was funded by the British Heart Foundation and supported by the National Institute for Health Research Imperial Biomedical Research Centre and the Imperial Clinical Trials Unit. Dr. Howard is supported by the Wellcome Trust. Dr. Wood declared no conflicts. Disclosures for the other authors are in the report. Dr. Toth discloses serving as a consultant to Amarin, Amgen, AstraZeneca, nio89, Kowa, Merck, Resverlogix, and Theravance; and serving on a speaker’s bureau for Amarin, Amgen, Esperion, and NovoNordisk.

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

The United States is facing an opioid crisis in which approximately 10 million people have misused opioids in the past year, and an estimated 2 million people have an opioid use disorder (OUD).¹ Compared with the general population, veterans treated in the Veterans Health Administration (VHA) facilities are at nearly twice the risk for accidental opioid overdose.² The implementation of opioid safety measures in VHA facilities across all care settings is a priority in addressing this public health crisis. Hence, VHA leadership is working to minimize veteran risk of fatal opioid overdoses and to increase veteran access to medication-assisted treatments (MAT) for OUD.³

Since the administration of our survey, the VHA has shifted to using the term medication for opioid use disorder (MOUD) instead of MAT for OUD. However, for consistency with the survey we distributed, we use MAT in this analysis.

Acute care settings represent an opportunity to offer appropriate opioid care and treatment options to patients at risk for OUD or opioid-related overdose. VHA facilities offer 2 outpatient acute care settings for emergent ambulatory care: emergency departments (EDs) and urgent care centers (UCCs). Annually, these settings see an estimated 2.5 million patients each year, making EDs and UCCs critical access points of OUD care for veterans. Partnering with key national VHA stakeholders from Pharmacy Benefits Management (PBM), the Office of Emergency Medicine, and Academic Detailing Services (ADS), we developed the Emergency Department Opioid Safety Initiative (ED OSI) aimed at implementing and evaluating opioid safety measures in VHA outpatient acute care settings.

The US Department of Veterans Affairs (VA)/Department of Defense (DoD) Clinical Practice Guidelines for Opioid Therapy for Chronic Pain (CPG) makes recommendations for the initiation and continuation of opioids, risk mitigation, taper of opioids, and opioid therapy for acute pain in VHA facilities.⁴ Using these recommendations, we developed the broad aims of the ED OSI quality improvement (QI) program. The CPG is clear about the prioritization of safe opioid prescribing practices. New opioid prescriptions written in the ED have been associated with continued and chronic opioid use.⁵ At the time of prescription, patients not currently and chronically on opioids who receive more than a 3-day supply are at increased risk of becoming long-term opioid users.⁶ Given the annual volume of patients seen, VHA ED/UCCs are a crucial area for implementing better opioid prescribing practices.

The CPG also includes recommendations for the prescribing or coprescribing of naloxone rescue kits. The administration of naloxone following opioid overdose has been found to be an effective measure against fatal overdose. Increasing provider awareness of common risk factors for opioid-related overdose (eg, frequent ED visits or hospitalizations) helps facilitate a discussion on naloxone prescribing at discharge. Prior studies provide evidence that naloxone distribution and accompanying education also are effective in reducing opioid overdose mortalityand ED visits related to adverse opioid-related events.^7,8

Similarly, the guidelines provide recommendations for the use of MAT for veterans with OUD. MAT for OUD is considered a first-line treatment option for patients with moderate-to-severe OUD. When used to treat patients with unsafe opioid use, this treatment helps alleviate symptoms of withdrawal, which can increase opioid taper adherence and has a protective effect against opioid overdose mortality.⁹ MAT initiated in the ED can increase patient engagement to addiction services.¹⁰

These 3 CPG recommendations serve as the basis for the broad goals of the ED OSI program. We aim to develop, implement, and evaluate programs and initiatives to (aim 1) reduce inappropriate opioid prescribing from VHA EDs; (aim 2) increase naloxone distribution from VHA EDs; and (aim 3) increase access to MAT initiation from VHA EDs through the implementation of ED-based MAT-initiation programs with EDs across the VHA. Aim 1 was a focused and strategic QI effort to implement an ED-based program to reduce inappropriate opioid prescribing. The ED OSI prescribing program offered a 4-step bundled approach: (1) sharing of opioid prescribing dashboard data with ED medical director and academic detailer; (2) education of ED providers and implementation of toolkit resources; (3) academic detailers conduct audit and feedback session(s) with highest prescribers; and (4) quarterly reports of opioid prescribing data to ED providers.

Results from the pilot suggested that our program was associated with accelerating the rate at which ED prescribing rates decreased.¹¹ In addition, the pilot found that ED-based QI initiatives in VHA facilities are a feasible practice. As we work to develop and implement the next 2 phases of the QI program, a major consideration is to identify facilitators and address any existing barriers to the implementation of naloxone distribution (aim 2) and MAT-initiation (aim 3) programs for treatment-naïve patients from VHA EDs. To date, there have been no recent published studies examining the barriers and facilitators to use or implementation of MAT initiation or naloxone distribution in VHA facilities or, more specifically, from VHA EDs.¹² As part of our QI program, we set out to better understand VHA ED provider perceptions of barriers and facilitators to implementation of programs aimed at increasing naloxone distribution and initiation of MAT for treatment-naïve patients in the ED.

Methods 

This project received a QI designation from the Office of PBM Academic Detailing Service Institutional Review Board at the Edward Hines, Jr. Veterans Affairs Hospital VA Medical Center (VAMC). This designation was reviewed and approved by the Rocky Mountain Regional VAMC Research and Development service. In addition, we received national union approval to disseminate this survey nationally across all VA Integrated Service Networks (VISNs).

Survey

We worked with VHA subject matter experts, key stakeholders, and the VA Collaborative Evaluation Center (VACE) to develop the survey. Subject matter experts and stakeholders included VHA emergency medicine leadership, ADS leadership, and mental health and substance treatment providers. VACE is an interdisciplinary group of mixed-method researchers. The survey questions aimed to capture perceptions and experiences regarding naloxone distribution and new MAT initiation of VHA ED/UCC providers.

We used a variety of survey question formats. Close-ended questions with a predefined list of answer options were used to capture discrete domains, such as demographic information, comfort level, and experience level. To capture health care provider (HCP) perceptions on barriers and facilitators, we used multiple-answer multiple-choice questions. Built into this question format was a free-response option, which allowed respondents to offer additional barriers or facilitators. Respondents also had the option of not answering individual questions.

We identified physicians, nurse practitioners (NPs), and physician assistants (PAs) who saw at least 100 patients in the ED or UCC in at least one 3-month period in the prior year and obtained an email address for each. In total, 2228 ED or UCC providers across 132 facilities were emailed a survey; 1883 (84.5%) were ED providers and 345 (15.5%) were UCC providers.

We used Research Electronic Data Capture (REDCap) software to build and disseminate the survey via email. Surveys were initially disseminated in late January 2019. During the 3-month survey period, recipients received 3 automated email reminders from REDCap to complete the survey. Survey data were exported from REDCap. Results were analyzed using descriptive statistics analyses with Microsoft Excel.

Results 

One respondent received the survey in error and was excluded from the analysis. The survey response rate was 16.7%: 372 responses from 103 unique facilities. Each VISN had a mean 20 respondents. The majority of respondents (n = 286, 76.9%) worked in highly complex level 1 facilities characterized by high patient volume and more high-risk patients and were teaching and research facilities. Respondents were asked to describe their most recent ED or UCC role. While 281 respondents (75.5%) were medical doctors, 61 respondents (16.4%) were NPs, 30 (8.1%) were PAs, and 26 (7.0%) were ED/UCC chiefs or medical directors (Table 1). Most respondents (80.4%) reported at least 10 years of health care experience.

The majority of respondents (72.9%) believed that HCPs at their VHA facility should be prescribing naloxone. When asked to specify which HCPs should be prescribing naloxone, most HCP respondents selected pharmacists (76.4%) and substance abuse providers (71.6%). Less than half of respondents (45.0%) felt that VA ED/UCC providers also should be prescribing naloxone. However, 58.1% of most HCP respondents reported being comfortable or very comfortable with prescribing naloxone to a patient in the ED or UCC who already had an existing prescription of opioids. Similarly, 52.7% of respondents reported being comfortable or very comfortable with coprescribing naloxone when discharging a patient with an opioid prescription from the ED/UCC. Notably, while 36.7% of PAs reported being comfortable/very comfortable coprescribing naloxone, 46.7% reported being comfortable/very comfortable prescribing naloxone to a patient with an existing opioid prescription. Physicians and NPs expressed similar levels of comfort with coprescribing and prescribing naloxone.

Respondents across provider types indicated a number of barriers to prescribing naloxone to medically appropriate patients (Table 2). Many respondents indicated prescribing naloxone was beyond the ED/UCC provider scope of practice (35.2%), followed by the perceived stigma associated with naloxone (33.3%), time required to prescribe naloxone (23.9%), and concern with patient’s ability to use naloxone (22.8%).

Discussion

To the best of our knowledge, there have not been any studies examining HCP perceptions of the barriers and facilitators to naloxone distribution or the initiation of MAT in VHA ED and UCCs. Veterans are at an increased risk of overdose when compared with the general population, and increasing access to opioid safety measures (eg, safer prescribing practices, naloxone distribution) and treatment with MAT for OUD across all clinical settings has been a VHA priority.³

National guidance from VHA leadership, the Centers for Disease Control and Prevention (CDC), the US Surgeon General, and the US Department of Health and Human Services (HHS) call for an all-hands-on-deck approach to combatting opioid overdose with naloxone distribution or MAT (such as buprenorphine) initiation.¹³ VHA ED and UCC settings provide acute outpatient care to patients with medical or psychiatric illnesses or injuries that the patient believes requires emergent or immediate medical attention or for which there is a critical need for treatment to prevent deterioration of the condition or the possible impairment of recovery.¹⁴ However, ED and UCC environments are often regarded as settings meant to stabilize a patient until they can be seen by a primary care or long-term care provider.

A major barrier identified by HCPs was that MAT for OUD was outside their ED/UCC scope of practice, which suggests a need for a top-down or peer-to-peer reexamination of the role of HCPs in ED/UCC settings. Any naloxone distribution and/or MAT-initiation program in VHA ED/UCCs should consider education about the role of ED/UCC HCPs in opioid safety and treatment. According to a VHA Support Service Center (VSSC) employee report database, in fiscal year 2018, per diem/fee-basis and contract HCPs comprised nearly 40% of clinical emergency medicine physician full-time equivalent employees, which presents a unique barrier to HCP education. Fee-basis and per diem HCPs may be less aware of, engaged in, or committed to VHA goals. Additionally, short-term HCPs may have fewer opportunities for training and education regarding naloxone or MAT use.

Only 25.3% of HCPs reported that their facility leadership was supportive or very supportive of MAT prescribing. This suggests that facility leadership should be engaged in any efforts to implement a MAT-initiation program in the facility’s ED. Engaging leadership in efforts to implement ED-based MAT programs will allow for a better understanding of leadership goals as related to opioid safety and an opportunity to address concerns regarding prescribing MAT in the ED. We recommend engaging facility leadership early in MAT implementation efforts. Respectively, 12.4% and 28.2% of HCP respondents reported discomfort prescribing naloxone or using MAT, suggesting a need for more education. Similarly, only 6.8% of HCPs reported comfort with using MAT.

A consideration for implementing ED/UCC-based MAT should be the inclusion of a training component. An evidence-based clinical treatment pathway that is appropriate to the ED/UCC setting and facility on the administration of MAT also could be beneficial. A clinical treatment pathway that includes ED/UCC-initiated discharge recommendations would address HCP concerns of unclear follow-up plans and system for referral of care. To this end, a key implementation task is coordinating with other outpatient services (eg, pain management clinic, substance use disorder treatment clinic) equipped for long-term patient follow-up to develop a system for referral of care. For example, as part of the clinical treatment pathway, an ED can develop a system of referral for patients initiated on MAT in the ED in which patients are referred for follow-up at the facility’s substance use disorder treatment clinic to be seen within 72 hours to continue the administration of MAT (such as buprenorphine).

In addition to HCP education, results suggest that patient/veteran education regarding naloxone and/or MAT should be considered. HCPs indicated that having help from a pharmacist to educate the patient about the medications would be a facilitator to naloxone distribution and MAT initiation. Similarly, patient knowledge of the medications also was endorsed as a facilitator. As such, a consideration for any future ED/UCC-based naloxone distribution or MAT-initiation programs in the VHA should be patient education whether by a clinically trained professional or an educational campaign for veterans.

Expanded naloxone distribution and initiation of MAT for OUD for EDs/UCCs across the VHA could impact the lives of veterans on long-term opioid therapy, with OUD, or who are otherwise at risk for opioid overdose. Steps taken to address the barriers and leverage the facilitators identified by HCP respondents can greatly reduce current obstacles to widespread implementation of ED/UCC-based naloxone distribution and MAT initiation nationally within the VHA.

Limitations

This survey had a low response rate (16.7%). One potential explanation for the low response rate is that when the survey was deployed, many of the VHA ED/UCC physicians were per-diem employees. Per-diem physicians may be less engaged and aware of site facilitators or barriers to naloxone and MAT prescribing. This, too, may have potentially skewed the collected data. However, the survey did not ask HCPs to disclose their employment status; thus, exact rates of per diem respondents are unknown.

We aimed to capture only self-perceived barriers to prescribing naloxone and MAT in the ED, but we did not capture or measure HCP respondent’s actual prescribing rates of MAT or naloxone. Understanding HCP perceptions of naloxone distribution and MAT initiation in the ED may have been further informed by comparing HCP responses to their actual clinical practice as related to their prescribing of these medications. In future research, we will link HCPs with the actual numbers of naloxone and MAT medications prescribed. Additionally, we do not know how many of these barriers or proposed facilitators will impact clinical practice.

Conclusions

A key aim for VHA leadership is to increase veteran access to naloxone distribution and MAT for OUD across clinical areas. The present study aimed to identify HCP perceptions of barriers and facilitators to the naloxone distribution and MAT-initiation programs in VHA ED/UCCs to inform the development of a targeted QI program to implement these opioid safety measures. Although the survey yielded a low response rate, results allowed us to identify important action items for our QI program, such as the development of clear protocols, follow-up plans, and systems for referral of care and HCP educational materials related to MAT and naloxone. We hope this work will serve as the basis for ED/UCC-tailored programs that can provide customized educational programs for HCPs designed to overcome known barriers to naloxone and MAT initiation.

Acknowledgments
This work was supported by the VA Office of Specialty Care Services 10P11 and through funding provided by the Comprehensive Addiction and Recovery Act (CARA).

The United States is facing an opioid crisis in which approximately 10 million people have misused opioids in the past year, and an estimated 2 million people have an opioid use disorder (OUD).¹ Compared with the general population, veterans treated in the Veterans Health Administration (VHA) facilities are at nearly twice the risk for accidental opioid overdose.² The implementation of opioid safety measures in VHA facilities across all care settings is a priority in addressing this public health crisis. Hence, VHA leadership is working to minimize veteran risk of fatal opioid overdoses and to increase veteran access to medication-assisted treatments (MAT) for OUD.³

Since the administration of our survey, the VHA has shifted to using the term medication for opioid use disorder (MOUD) instead of MAT for OUD. However, for consistency with the survey we distributed, we use MAT in this analysis.

Acute care settings represent an opportunity to offer appropriate opioid care and treatment options to patients at risk for OUD or opioid-related overdose. VHA facilities offer 2 outpatient acute care settings for emergent ambulatory care: emergency departments (EDs) and urgent care centers (UCCs). Annually, these settings see an estimated 2.5 million patients each year, making EDs and UCCs critical access points of OUD care for veterans. Partnering with key national VHA stakeholders from Pharmacy Benefits Management (PBM), the Office of Emergency Medicine, and Academic Detailing Services (ADS), we developed the Emergency Department Opioid Safety Initiative (ED OSI) aimed at implementing and evaluating opioid safety measures in VHA outpatient acute care settings.

The US Department of Veterans Affairs (VA)/Department of Defense (DoD) Clinical Practice Guidelines for Opioid Therapy for Chronic Pain (CPG) makes recommendations for the initiation and continuation of opioids, risk mitigation, taper of opioids, and opioid therapy for acute pain in VHA facilities.⁴ Using these recommendations, we developed the broad aims of the ED OSI quality improvement (QI) program. The CPG is clear about the prioritization of safe opioid prescribing practices. New opioid prescriptions written in the ED have been associated with continued and chronic opioid use.⁵ At the time of prescription, patients not currently and chronically on opioids who receive more than a 3-day supply are at increased risk of becoming long-term opioid users.⁶ Given the annual volume of patients seen, VHA ED/UCCs are a crucial area for implementing better opioid prescribing practices.

The CPG also includes recommendations for the prescribing or coprescribing of naloxone rescue kits. The administration of naloxone following opioid overdose has been found to be an effective measure against fatal overdose. Increasing provider awareness of common risk factors for opioid-related overdose (eg, frequent ED visits or hospitalizations) helps facilitate a discussion on naloxone prescribing at discharge. Prior studies provide evidence that naloxone distribution and accompanying education also are effective in reducing opioid overdose mortalityand ED visits related to adverse opioid-related events.^7,8

Similarly, the guidelines provide recommendations for the use of MAT for veterans with OUD. MAT for OUD is considered a first-line treatment option for patients with moderate-to-severe OUD. When used to treat patients with unsafe opioid use, this treatment helps alleviate symptoms of withdrawal, which can increase opioid taper adherence and has a protective effect against opioid overdose mortality.⁹ MAT initiated in the ED can increase patient engagement to addiction services.¹⁰

These 3 CPG recommendations serve as the basis for the broad goals of the ED OSI program. We aim to develop, implement, and evaluate programs and initiatives to (aim 1) reduce inappropriate opioid prescribing from VHA EDs; (aim 2) increase naloxone distribution from VHA EDs; and (aim 3) increase access to MAT initiation from VHA EDs through the implementation of ED-based MAT-initiation programs with EDs across the VHA. Aim 1 was a focused and strategic QI effort to implement an ED-based program to reduce inappropriate opioid prescribing. The ED OSI prescribing program offered a 4-step bundled approach: (1) sharing of opioid prescribing dashboard data with ED medical director and academic detailer; (2) education of ED providers and implementation of toolkit resources; (3) academic detailers conduct audit and feedback session(s) with highest prescribers; and (4) quarterly reports of opioid prescribing data to ED providers.

Results from the pilot suggested that our program was associated with accelerating the rate at which ED prescribing rates decreased.¹¹ In addition, the pilot found that ED-based QI initiatives in VHA facilities are a feasible practice. As we work to develop and implement the next 2 phases of the QI program, a major consideration is to identify facilitators and address any existing barriers to the implementation of naloxone distribution (aim 2) and MAT-initiation (aim 3) programs for treatment-naïve patients from VHA EDs. To date, there have been no recent published studies examining the barriers and facilitators to use or implementation of MAT initiation or naloxone distribution in VHA facilities or, more specifically, from VHA EDs.¹² As part of our QI program, we set out to better understand VHA ED provider perceptions of barriers and facilitators to implementation of programs aimed at increasing naloxone distribution and initiation of MAT for treatment-naïve patients in the ED.

Methods 

This project received a QI designation from the Office of PBM Academic Detailing Service Institutional Review Board at the Edward Hines, Jr. Veterans Affairs Hospital VA Medical Center (VAMC). This designation was reviewed and approved by the Rocky Mountain Regional VAMC Research and Development service. In addition, we received national union approval to disseminate this survey nationally across all VA Integrated Service Networks (VISNs).

Survey

We worked with VHA subject matter experts, key stakeholders, and the VA Collaborative Evaluation Center (VACE) to develop the survey. Subject matter experts and stakeholders included VHA emergency medicine leadership, ADS leadership, and mental health and substance treatment providers. VACE is an interdisciplinary group of mixed-method researchers. The survey questions aimed to capture perceptions and experiences regarding naloxone distribution and new MAT initiation of VHA ED/UCC providers.

We used a variety of survey question formats. Close-ended questions with a predefined list of answer options were used to capture discrete domains, such as demographic information, comfort level, and experience level. To capture health care provider (HCP) perceptions on barriers and facilitators, we used multiple-answer multiple-choice questions. Built into this question format was a free-response option, which allowed respondents to offer additional barriers or facilitators. Respondents also had the option of not answering individual questions.

We identified physicians, nurse practitioners (NPs), and physician assistants (PAs) who saw at least 100 patients in the ED or UCC in at least one 3-month period in the prior year and obtained an email address for each. In total, 2228 ED or UCC providers across 132 facilities were emailed a survey; 1883 (84.5%) were ED providers and 345 (15.5%) were UCC providers.

We used Research Electronic Data Capture (REDCap) software to build and disseminate the survey via email. Surveys were initially disseminated in late January 2019. During the 3-month survey period, recipients received 3 automated email reminders from REDCap to complete the survey. Survey data were exported from REDCap. Results were analyzed using descriptive statistics analyses with Microsoft Excel.

Results 

One respondent received the survey in error and was excluded from the analysis. The survey response rate was 16.7%: 372 responses from 103 unique facilities. Each VISN had a mean 20 respondents. The majority of respondents (n = 286, 76.9%) worked in highly complex level 1 facilities characterized by high patient volume and more high-risk patients and were teaching and research facilities. Respondents were asked to describe their most recent ED or UCC role. While 281 respondents (75.5%) were medical doctors, 61 respondents (16.4%) were NPs, 30 (8.1%) were PAs, and 26 (7.0%) were ED/UCC chiefs or medical directors (Table 1). Most respondents (80.4%) reported at least 10 years of health care experience.

The majority of respondents (72.9%) believed that HCPs at their VHA facility should be prescribing naloxone. When asked to specify which HCPs should be prescribing naloxone, most HCP respondents selected pharmacists (76.4%) and substance abuse providers (71.6%). Less than half of respondents (45.0%) felt that VA ED/UCC providers also should be prescribing naloxone. However, 58.1% of most HCP respondents reported being comfortable or very comfortable with prescribing naloxone to a patient in the ED or UCC who already had an existing prescription of opioids. Similarly, 52.7% of respondents reported being comfortable or very comfortable with coprescribing naloxone when discharging a patient with an opioid prescription from the ED/UCC. Notably, while 36.7% of PAs reported being comfortable/very comfortable coprescribing naloxone, 46.7% reported being comfortable/very comfortable prescribing naloxone to a patient with an existing opioid prescription. Physicians and NPs expressed similar levels of comfort with coprescribing and prescribing naloxone.

Respondents across provider types indicated a number of barriers to prescribing naloxone to medically appropriate patients (Table 2). Many respondents indicated prescribing naloxone was beyond the ED/UCC provider scope of practice (35.2%), followed by the perceived stigma associated with naloxone (33.3%), time required to prescribe naloxone (23.9%), and concern with patient’s ability to use naloxone (22.8%).

Discussion

To the best of our knowledge, there have not been any studies examining HCP perceptions of the barriers and facilitators to naloxone distribution or the initiation of MAT in VHA ED and UCCs. Veterans are at an increased risk of overdose when compared with the general population, and increasing access to opioid safety measures (eg, safer prescribing practices, naloxone distribution) and treatment with MAT for OUD across all clinical settings has been a VHA priority.³

National guidance from VHA leadership, the Centers for Disease Control and Prevention (CDC), the US Surgeon General, and the US Department of Health and Human Services (HHS) call for an all-hands-on-deck approach to combatting opioid overdose with naloxone distribution or MAT (such as buprenorphine) initiation.¹³ VHA ED and UCC settings provide acute outpatient care to patients with medical or psychiatric illnesses or injuries that the patient believes requires emergent or immediate medical attention or for which there is a critical need for treatment to prevent deterioration of the condition or the possible impairment of recovery.¹⁴ However, ED and UCC environments are often regarded as settings meant to stabilize a patient until they can be seen by a primary care or long-term care provider.

A major barrier identified by HCPs was that MAT for OUD was outside their ED/UCC scope of practice, which suggests a need for a top-down or peer-to-peer reexamination of the role of HCPs in ED/UCC settings. Any naloxone distribution and/or MAT-initiation program in VHA ED/UCCs should consider education about the role of ED/UCC HCPs in opioid safety and treatment. According to a VHA Support Service Center (VSSC) employee report database, in fiscal year 2018, per diem/fee-basis and contract HCPs comprised nearly 40% of clinical emergency medicine physician full-time equivalent employees, which presents a unique barrier to HCP education. Fee-basis and per diem HCPs may be less aware of, engaged in, or committed to VHA goals. Additionally, short-term HCPs may have fewer opportunities for training and education regarding naloxone or MAT use.

Only 25.3% of HCPs reported that their facility leadership was supportive or very supportive of MAT prescribing. This suggests that facility leadership should be engaged in any efforts to implement a MAT-initiation program in the facility’s ED. Engaging leadership in efforts to implement ED-based MAT programs will allow for a better understanding of leadership goals as related to opioid safety and an opportunity to address concerns regarding prescribing MAT in the ED. We recommend engaging facility leadership early in MAT implementation efforts. Respectively, 12.4% and 28.2% of HCP respondents reported discomfort prescribing naloxone or using MAT, suggesting a need for more education. Similarly, only 6.8% of HCPs reported comfort with using MAT.

A consideration for implementing ED/UCC-based MAT should be the inclusion of a training component. An evidence-based clinical treatment pathway that is appropriate to the ED/UCC setting and facility on the administration of MAT also could be beneficial. A clinical treatment pathway that includes ED/UCC-initiated discharge recommendations would address HCP concerns of unclear follow-up plans and system for referral of care. To this end, a key implementation task is coordinating with other outpatient services (eg, pain management clinic, substance use disorder treatment clinic) equipped for long-term patient follow-up to develop a system for referral of care. For example, as part of the clinical treatment pathway, an ED can develop a system of referral for patients initiated on MAT in the ED in which patients are referred for follow-up at the facility’s substance use disorder treatment clinic to be seen within 72 hours to continue the administration of MAT (such as buprenorphine).

In addition to HCP education, results suggest that patient/veteran education regarding naloxone and/or MAT should be considered. HCPs indicated that having help from a pharmacist to educate the patient about the medications would be a facilitator to naloxone distribution and MAT initiation. Similarly, patient knowledge of the medications also was endorsed as a facilitator. As such, a consideration for any future ED/UCC-based naloxone distribution or MAT-initiation programs in the VHA should be patient education whether by a clinically trained professional or an educational campaign for veterans.

Expanded naloxone distribution and initiation of MAT for OUD for EDs/UCCs across the VHA could impact the lives of veterans on long-term opioid therapy, with OUD, or who are otherwise at risk for opioid overdose. Steps taken to address the barriers and leverage the facilitators identified by HCP respondents can greatly reduce current obstacles to widespread implementation of ED/UCC-based naloxone distribution and MAT initiation nationally within the VHA.

Limitations

This survey had a low response rate (16.7%). One potential explanation for the low response rate is that when the survey was deployed, many of the VHA ED/UCC physicians were per-diem employees. Per-diem physicians may be less engaged and aware of site facilitators or barriers to naloxone and MAT prescribing. This, too, may have potentially skewed the collected data. However, the survey did not ask HCPs to disclose their employment status; thus, exact rates of per diem respondents are unknown.

We aimed to capture only self-perceived barriers to prescribing naloxone and MAT in the ED, but we did not capture or measure HCP respondent’s actual prescribing rates of MAT or naloxone. Understanding HCP perceptions of naloxone distribution and MAT initiation in the ED may have been further informed by comparing HCP responses to their actual clinical practice as related to their prescribing of these medications. In future research, we will link HCPs with the actual numbers of naloxone and MAT medications prescribed. Additionally, we do not know how many of these barriers or proposed facilitators will impact clinical practice.

Conclusions

A key aim for VHA leadership is to increase veteran access to naloxone distribution and MAT for OUD across clinical areas. The present study aimed to identify HCP perceptions of barriers and facilitators to the naloxone distribution and MAT-initiation programs in VHA ED/UCCs to inform the development of a targeted QI program to implement these opioid safety measures. Although the survey yielded a low response rate, results allowed us to identify important action items for our QI program, such as the development of clear protocols, follow-up plans, and systems for referral of care and HCP educational materials related to MAT and naloxone. We hope this work will serve as the basis for ED/UCC-tailored programs that can provide customized educational programs for HCPs designed to overcome known barriers to naloxone and MAT initiation.

Acknowledgments
This work was supported by the VA Office of Specialty Care Services 10P11 and through funding provided by the Comprehensive Addiction and Recovery Act (CARA).

The United States is facing an opioid crisis in which approximately 10 million people have misused opioids in the past year, and an estimated 2 million people have an opioid use disorder (OUD).¹ Compared with the general population, veterans treated in the Veterans Health Administration (VHA) facilities are at nearly twice the risk for accidental opioid overdose.² The implementation of opioid safety measures in VHA facilities across all care settings is a priority in addressing this public health crisis. Hence, VHA leadership is working to minimize veteran risk of fatal opioid overdoses and to increase veteran access to medication-assisted treatments (MAT) for OUD.³

Since the administration of our survey, the VHA has shifted to using the term medication for opioid use disorder (MOUD) instead of MAT for OUD. However, for consistency with the survey we distributed, we use MAT in this analysis.

Acute care settings represent an opportunity to offer appropriate opioid care and treatment options to patients at risk for OUD or opioid-related overdose. VHA facilities offer 2 outpatient acute care settings for emergent ambulatory care: emergency departments (EDs) and urgent care centers (UCCs). Annually, these settings see an estimated 2.5 million patients each year, making EDs and UCCs critical access points of OUD care for veterans. Partnering with key national VHA stakeholders from Pharmacy Benefits Management (PBM), the Office of Emergency Medicine, and Academic Detailing Services (ADS), we developed the Emergency Department Opioid Safety Initiative (ED OSI) aimed at implementing and evaluating opioid safety measures in VHA outpatient acute care settings.

The US Department of Veterans Affairs (VA)/Department of Defense (DoD) Clinical Practice Guidelines for Opioid Therapy for Chronic Pain (CPG) makes recommendations for the initiation and continuation of opioids, risk mitigation, taper of opioids, and opioid therapy for acute pain in VHA facilities.⁴ Using these recommendations, we developed the broad aims of the ED OSI quality improvement (QI) program. The CPG is clear about the prioritization of safe opioid prescribing practices. New opioid prescriptions written in the ED have been associated with continued and chronic opioid use.⁵ At the time of prescription, patients not currently and chronically on opioids who receive more than a 3-day supply are at increased risk of becoming long-term opioid users.⁶ Given the annual volume of patients seen, VHA ED/UCCs are a crucial area for implementing better opioid prescribing practices.

The CPG also includes recommendations for the prescribing or coprescribing of naloxone rescue kits. The administration of naloxone following opioid overdose has been found to be an effective measure against fatal overdose. Increasing provider awareness of common risk factors for opioid-related overdose (eg, frequent ED visits or hospitalizations) helps facilitate a discussion on naloxone prescribing at discharge. Prior studies provide evidence that naloxone distribution and accompanying education also are effective in reducing opioid overdose mortalityand ED visits related to adverse opioid-related events.^7,8

Similarly, the guidelines provide recommendations for the use of MAT for veterans with OUD. MAT for OUD is considered a first-line treatment option for patients with moderate-to-severe OUD. When used to treat patients with unsafe opioid use, this treatment helps alleviate symptoms of withdrawal, which can increase opioid taper adherence and has a protective effect against opioid overdose mortality.⁹ MAT initiated in the ED can increase patient engagement to addiction services.¹⁰

These 3 CPG recommendations serve as the basis for the broad goals of the ED OSI program. We aim to develop, implement, and evaluate programs and initiatives to (aim 1) reduce inappropriate opioid prescribing from VHA EDs; (aim 2) increase naloxone distribution from VHA EDs; and (aim 3) increase access to MAT initiation from VHA EDs through the implementation of ED-based MAT-initiation programs with EDs across the VHA. Aim 1 was a focused and strategic QI effort to implement an ED-based program to reduce inappropriate opioid prescribing. The ED OSI prescribing program offered a 4-step bundled approach: (1) sharing of opioid prescribing dashboard data with ED medical director and academic detailer; (2) education of ED providers and implementation of toolkit resources; (3) academic detailers conduct audit and feedback session(s) with highest prescribers; and (4) quarterly reports of opioid prescribing data to ED providers.

Results from the pilot suggested that our program was associated with accelerating the rate at which ED prescribing rates decreased.¹¹ In addition, the pilot found that ED-based QI initiatives in VHA facilities are a feasible practice. As we work to develop and implement the next 2 phases of the QI program, a major consideration is to identify facilitators and address any existing barriers to the implementation of naloxone distribution (aim 2) and MAT-initiation (aim 3) programs for treatment-naïve patients from VHA EDs. To date, there have been no recent published studies examining the barriers and facilitators to use or implementation of MAT initiation or naloxone distribution in VHA facilities or, more specifically, from VHA EDs.¹² As part of our QI program, we set out to better understand VHA ED provider perceptions of barriers and facilitators to implementation of programs aimed at increasing naloxone distribution and initiation of MAT for treatment-naïve patients in the ED.

Methods 

This project received a QI designation from the Office of PBM Academic Detailing Service Institutional Review Board at the Edward Hines, Jr. Veterans Affairs Hospital VA Medical Center (VAMC). This designation was reviewed and approved by the Rocky Mountain Regional VAMC Research and Development service. In addition, we received national union approval to disseminate this survey nationally across all VA Integrated Service Networks (VISNs).

Survey

We worked with VHA subject matter experts, key stakeholders, and the VA Collaborative Evaluation Center (VACE) to develop the survey. Subject matter experts and stakeholders included VHA emergency medicine leadership, ADS leadership, and mental health and substance treatment providers. VACE is an interdisciplinary group of mixed-method researchers. The survey questions aimed to capture perceptions and experiences regarding naloxone distribution and new MAT initiation of VHA ED/UCC providers.

We used a variety of survey question formats. Close-ended questions with a predefined list of answer options were used to capture discrete domains, such as demographic information, comfort level, and experience level. To capture health care provider (HCP) perceptions on barriers and facilitators, we used multiple-answer multiple-choice questions. Built into this question format was a free-response option, which allowed respondents to offer additional barriers or facilitators. Respondents also had the option of not answering individual questions.

We identified physicians, nurse practitioners (NPs), and physician assistants (PAs) who saw at least 100 patients in the ED or UCC in at least one 3-month period in the prior year and obtained an email address for each. In total, 2228 ED or UCC providers across 132 facilities were emailed a survey; 1883 (84.5%) were ED providers and 345 (15.5%) were UCC providers.

We used Research Electronic Data Capture (REDCap) software to build and disseminate the survey via email. Surveys were initially disseminated in late January 2019. During the 3-month survey period, recipients received 3 automated email reminders from REDCap to complete the survey. Survey data were exported from REDCap. Results were analyzed using descriptive statistics analyses with Microsoft Excel.

Results 

One respondent received the survey in error and was excluded from the analysis. The survey response rate was 16.7%: 372 responses from 103 unique facilities. Each VISN had a mean 20 respondents. The majority of respondents (n = 286, 76.9%) worked in highly complex level 1 facilities characterized by high patient volume and more high-risk patients and were teaching and research facilities. Respondents were asked to describe their most recent ED or UCC role. While 281 respondents (75.5%) were medical doctors, 61 respondents (16.4%) were NPs, 30 (8.1%) were PAs, and 26 (7.0%) were ED/UCC chiefs or medical directors (Table 1). Most respondents (80.4%) reported at least 10 years of health care experience.

The majority of respondents (72.9%) believed that HCPs at their VHA facility should be prescribing naloxone. When asked to specify which HCPs should be prescribing naloxone, most HCP respondents selected pharmacists (76.4%) and substance abuse providers (71.6%). Less than half of respondents (45.0%) felt that VA ED/UCC providers also should be prescribing naloxone. However, 58.1% of most HCP respondents reported being comfortable or very comfortable with prescribing naloxone to a patient in the ED or UCC who already had an existing prescription of opioids. Similarly, 52.7% of respondents reported being comfortable or very comfortable with coprescribing naloxone when discharging a patient with an opioid prescription from the ED/UCC. Notably, while 36.7% of PAs reported being comfortable/very comfortable coprescribing naloxone, 46.7% reported being comfortable/very comfortable prescribing naloxone to a patient with an existing opioid prescription. Physicians and NPs expressed similar levels of comfort with coprescribing and prescribing naloxone.

Respondents across provider types indicated a number of barriers to prescribing naloxone to medically appropriate patients (Table 2). Many respondents indicated prescribing naloxone was beyond the ED/UCC provider scope of practice (35.2%), followed by the perceived stigma associated with naloxone (33.3%), time required to prescribe naloxone (23.9%), and concern with patient’s ability to use naloxone (22.8%).

Discussion

To the best of our knowledge, there have not been any studies examining HCP perceptions of the barriers and facilitators to naloxone distribution or the initiation of MAT in VHA ED and UCCs. Veterans are at an increased risk of overdose when compared with the general population, and increasing access to opioid safety measures (eg, safer prescribing practices, naloxone distribution) and treatment with MAT for OUD across all clinical settings has been a VHA priority.³

National guidance from VHA leadership, the Centers for Disease Control and Prevention (CDC), the US Surgeon General, and the US Department of Health and Human Services (HHS) call for an all-hands-on-deck approach to combatting opioid overdose with naloxone distribution or MAT (such as buprenorphine) initiation.¹³ VHA ED and UCC settings provide acute outpatient care to patients with medical or psychiatric illnesses or injuries that the patient believes requires emergent or immediate medical attention or for which there is a critical need for treatment to prevent deterioration of the condition or the possible impairment of recovery.¹⁴ However, ED and UCC environments are often regarded as settings meant to stabilize a patient until they can be seen by a primary care or long-term care provider.

A major barrier identified by HCPs was that MAT for OUD was outside their ED/UCC scope of practice, which suggests a need for a top-down or peer-to-peer reexamination of the role of HCPs in ED/UCC settings. Any naloxone distribution and/or MAT-initiation program in VHA ED/UCCs should consider education about the role of ED/UCC HCPs in opioid safety and treatment. According to a VHA Support Service Center (VSSC) employee report database, in fiscal year 2018, per diem/fee-basis and contract HCPs comprised nearly 40% of clinical emergency medicine physician full-time equivalent employees, which presents a unique barrier to HCP education. Fee-basis and per diem HCPs may be less aware of, engaged in, or committed to VHA goals. Additionally, short-term HCPs may have fewer opportunities for training and education regarding naloxone or MAT use.

Only 25.3% of HCPs reported that their facility leadership was supportive or very supportive of MAT prescribing. This suggests that facility leadership should be engaged in any efforts to implement a MAT-initiation program in the facility’s ED. Engaging leadership in efforts to implement ED-based MAT programs will allow for a better understanding of leadership goals as related to opioid safety and an opportunity to address concerns regarding prescribing MAT in the ED. We recommend engaging facility leadership early in MAT implementation efforts. Respectively, 12.4% and 28.2% of HCP respondents reported discomfort prescribing naloxone or using MAT, suggesting a need for more education. Similarly, only 6.8% of HCPs reported comfort with using MAT.

A consideration for implementing ED/UCC-based MAT should be the inclusion of a training component. An evidence-based clinical treatment pathway that is appropriate to the ED/UCC setting and facility on the administration of MAT also could be beneficial. A clinical treatment pathway that includes ED/UCC-initiated discharge recommendations would address HCP concerns of unclear follow-up plans and system for referral of care. To this end, a key implementation task is coordinating with other outpatient services (eg, pain management clinic, substance use disorder treatment clinic) equipped for long-term patient follow-up to develop a system for referral of care. For example, as part of the clinical treatment pathway, an ED can develop a system of referral for patients initiated on MAT in the ED in which patients are referred for follow-up at the facility’s substance use disorder treatment clinic to be seen within 72 hours to continue the administration of MAT (such as buprenorphine).

In addition to HCP education, results suggest that patient/veteran education regarding naloxone and/or MAT should be considered. HCPs indicated that having help from a pharmacist to educate the patient about the medications would be a facilitator to naloxone distribution and MAT initiation. Similarly, patient knowledge of the medications also was endorsed as a facilitator. As such, a consideration for any future ED/UCC-based naloxone distribution or MAT-initiation programs in the VHA should be patient education whether by a clinically trained professional or an educational campaign for veterans.

Expanded naloxone distribution and initiation of MAT for OUD for EDs/UCCs across the VHA could impact the lives of veterans on long-term opioid therapy, with OUD, or who are otherwise at risk for opioid overdose. Steps taken to address the barriers and leverage the facilitators identified by HCP respondents can greatly reduce current obstacles to widespread implementation of ED/UCC-based naloxone distribution and MAT initiation nationally within the VHA.

Limitations

This survey had a low response rate (16.7%). One potential explanation for the low response rate is that when the survey was deployed, many of the VHA ED/UCC physicians were per-diem employees. Per-diem physicians may be less engaged and aware of site facilitators or barriers to naloxone and MAT prescribing. This, too, may have potentially skewed the collected data. However, the survey did not ask HCPs to disclose their employment status; thus, exact rates of per diem respondents are unknown.

We aimed to capture only self-perceived barriers to prescribing naloxone and MAT in the ED, but we did not capture or measure HCP respondent’s actual prescribing rates of MAT or naloxone. Understanding HCP perceptions of naloxone distribution and MAT initiation in the ED may have been further informed by comparing HCP responses to their actual clinical practice as related to their prescribing of these medications. In future research, we will link HCPs with the actual numbers of naloxone and MAT medications prescribed. Additionally, we do not know how many of these barriers or proposed facilitators will impact clinical practice.

Conclusions

A key aim for VHA leadership is to increase veteran access to naloxone distribution and MAT for OUD across clinical areas. The present study aimed to identify HCP perceptions of barriers and facilitators to the naloxone distribution and MAT-initiation programs in VHA ED/UCCs to inform the development of a targeted QI program to implement these opioid safety measures. Although the survey yielded a low response rate, results allowed us to identify important action items for our QI program, such as the development of clear protocols, follow-up plans, and systems for referral of care and HCP educational materials related to MAT and naloxone. We hope this work will serve as the basis for ED/UCC-tailored programs that can provide customized educational programs for HCPs designed to overcome known barriers to naloxone and MAT initiation.

Acknowledgments
This work was supported by the VA Office of Specialty Care Services 10P11 and through funding provided by the Comprehensive Addiction and Recovery Act (CARA).

A 66-year-old woman is discharged from the hospital after an MI. Her discharge medications include atorvastatin 40 mg, lisinopril 20 mg, acetylsalicylic acid 81 mg, and clopidogrel 75 mg. At this patient’s follow-up appointment, she mentions that she has muscle pain and stiffness in both legs and her back. Her labs include thyroid-stimulating hormone of 2.0 and vitamin D of 40. She stops the atorvastatin for 2 weeks with resolution of her symptoms.

Which treatment recommendation would you make for this patient?

A. Restart atorvastatin

B. Start rosuvastatin twice a week

C. Start ezetimibe

D. Start a PCSK9 inhibitor

We often see high-risk cardiovascular disease patients who are concerned about muscle side effects brought on by statins. I think we all can agree that this patient needs aggressive medical therapy for prevention of secondary cardiovascular events. I would restart her atorvastatin.

Neilsen and Nordestgaard found that early statin discontinuation rates increased from 6% in 1995 to 18% in 2010.¹

Early statin discontinuation correlated with negative statin-related news stories, their paper states. This suggests either an increased awareness of side effects or a possible nocebo effect.
 

Statin rechallenge results

Joy and colleagues reported the results on eight patients who had developed myalgias within 3 weeks of starting a statin. These patients, who received placebo or statin, completed an N-of-1 trial with three double-blind, crossover comparisons separated by 3-week washout periods.

Patients were evaluated pain on a visual analog scale (VAS). For each N-of-1 trial there was no statistically significant difference in pain or myalgia score between those who took statin and placebo. Five of the eight patients chose to continue on statins at the end of the trial.

Herrett and colleagues performed a more extensive series of N-of-1 trials involving 200 patients who had stopped or were considering stopping statins because of muscle symptoms.³ Participants either received 2 months of atorvastatin 20 mg or placebo for 2-month blocks six times. They rated their muscle symptoms on a VAS at the end of each block. There was no difference in muscle symptom scores between the statin and placebo periods.

Wood and colleagues took it a step further, when they studied an N-of-1 trial that included statin, placebo, and no treatment.⁴ Each participant received four bottles of atorvastatin 20 mg, four bottles of placebo, and four empty bottles. Each month they used treatment from the bottles based on random sequence and reported daily symptom scores. The mean symptom intensity was 8.0 during no-tablet months, 15.4 during placebo months (P < .001, compared with no-tablet months), and 16.3 during statin months (P < .001, compared with no-tablet months; P = .39, compared with placebo).

Taylor and colleagues studied 120 patients who had prior statin-associated muscle complaints.⁵ Each patient received either simvastatin 20 mg or placebo for 4 weeks, and then were switched for an additional 4 weeks. A total of 43 patients (36%) had pain on simvastatin but not placebo, 21 (17%) had no pain with either treatment, 21 (17%) reported pain with both treatments, and 35 (29%) had pain with placebo but not simvastatin. These studies support the concept of nocebo effect in patients who have muscle symptoms on statins.

So what should be done? Brennan and Roy did a retrospective study of 118 patients referred to a lipid clinic as being statin intolerant to two or more statins.⁶ Most of the patients were able to tolerate a statin: 71% tolerated same statin rechallenge, 53% tolerated statin switch, and 57% tolerated a nonstatin therapy.

In the Prosisa study, only 27% of patients who reported statin-associated muscle symptoms had reappearance of muscle symptoms after rechallenge with a statin.7
 

Research implications

Rechallenge with the same statin seems to be a reasonable first step, followed by switching to a different statin. I also share the concept of nocebo effect with my patients, and tell them I believe they have an excellent chance of tolerating the statin.

Pearl: The majority of patients with muscle symptoms while taking a statin likely have a nocebo effect, and are likely to tolerate rechallenge with the same statin.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Nielsen SF and Nordestgaard BG. Eur Heart J. 2016;37:908-16.

2. Joy TR et al. Ann Intern Med. 2014;160:301-10.

3. Herrett E et al. BMJ. 2021 Feb 24;372:n135.

4. Wood FA et al. N Engl J Med 2020;383:2182-4.

5. Taylor BA et al. Atherosclerosis. 2017;256:100-4.

6. Brennen ET and Roy TR. Can J Card. 2017;33(5):666-73.

7. Bonaiti Fet al. Atherosclerosis. 2020;315:E13-4.

A 66-year-old woman is discharged from the hospital after an MI. Her discharge medications include atorvastatin 40 mg, lisinopril 20 mg, acetylsalicylic acid 81 mg, and clopidogrel 75 mg. At this patient’s follow-up appointment, she mentions that she has muscle pain and stiffness in both legs and her back. Her labs include thyroid-stimulating hormone of 2.0 and vitamin D of 40. She stops the atorvastatin for 2 weeks with resolution of her symptoms.

Which treatment recommendation would you make for this patient?

A. Restart atorvastatin

B. Start rosuvastatin twice a week

C. Start ezetimibe

D. Start a PCSK9 inhibitor

We often see high-risk cardiovascular disease patients who are concerned about muscle side effects brought on by statins. I think we all can agree that this patient needs aggressive medical therapy for prevention of secondary cardiovascular events. I would restart her atorvastatin.

Neilsen and Nordestgaard found that early statin discontinuation rates increased from 6% in 1995 to 18% in 2010.¹

Early statin discontinuation correlated with negative statin-related news stories, their paper states. This suggests either an increased awareness of side effects or a possible nocebo effect.
 

Statin rechallenge results

Joy and colleagues reported the results on eight patients who had developed myalgias within 3 weeks of starting a statin. These patients, who received placebo or statin, completed an N-of-1 trial with three double-blind, crossover comparisons separated by 3-week washout periods.

Patients were evaluated pain on a visual analog scale (VAS). For each N-of-1 trial there was no statistically significant difference in pain or myalgia score between those who took statin and placebo. Five of the eight patients chose to continue on statins at the end of the trial.

Herrett and colleagues performed a more extensive series of N-of-1 trials involving 200 patients who had stopped or were considering stopping statins because of muscle symptoms.³ Participants either received 2 months of atorvastatin 20 mg or placebo for 2-month blocks six times. They rated their muscle symptoms on a VAS at the end of each block. There was no difference in muscle symptom scores between the statin and placebo periods.

Wood and colleagues took it a step further, when they studied an N-of-1 trial that included statin, placebo, and no treatment.⁴ Each participant received four bottles of atorvastatin 20 mg, four bottles of placebo, and four empty bottles. Each month they used treatment from the bottles based on random sequence and reported daily symptom scores. The mean symptom intensity was 8.0 during no-tablet months, 15.4 during placebo months (P < .001, compared with no-tablet months), and 16.3 during statin months (P < .001, compared with no-tablet months; P = .39, compared with placebo).

Taylor and colleagues studied 120 patients who had prior statin-associated muscle complaints.⁵ Each patient received either simvastatin 20 mg or placebo for 4 weeks, and then were switched for an additional 4 weeks. A total of 43 patients (36%) had pain on simvastatin but not placebo, 21 (17%) had no pain with either treatment, 21 (17%) reported pain with both treatments, and 35 (29%) had pain with placebo but not simvastatin. These studies support the concept of nocebo effect in patients who have muscle symptoms on statins.

So what should be done? Brennan and Roy did a retrospective study of 118 patients referred to a lipid clinic as being statin intolerant to two or more statins.⁶ Most of the patients were able to tolerate a statin: 71% tolerated same statin rechallenge, 53% tolerated statin switch, and 57% tolerated a nonstatin therapy.

In the Prosisa study, only 27% of patients who reported statin-associated muscle symptoms had reappearance of muscle symptoms after rechallenge with a statin.7
 

Research implications

Rechallenge with the same statin seems to be a reasonable first step, followed by switching to a different statin. I also share the concept of nocebo effect with my patients, and tell them I believe they have an excellent chance of tolerating the statin.

Pearl: The majority of patients with muscle symptoms while taking a statin likely have a nocebo effect, and are likely to tolerate rechallenge with the same statin.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Nielsen SF and Nordestgaard BG. Eur Heart J. 2016;37:908-16.

2. Joy TR et al. Ann Intern Med. 2014;160:301-10.

3. Herrett E et al. BMJ. 2021 Feb 24;372:n135.

4. Wood FA et al. N Engl J Med 2020;383:2182-4.

5. Taylor BA et al. Atherosclerosis. 2017;256:100-4.

6. Brennen ET and Roy TR. Can J Card. 2017;33(5):666-73.

7. Bonaiti Fet al. Atherosclerosis. 2020;315:E13-4.

A 66-year-old woman is discharged from the hospital after an MI. Her discharge medications include atorvastatin 40 mg, lisinopril 20 mg, acetylsalicylic acid 81 mg, and clopidogrel 75 mg. At this patient’s follow-up appointment, she mentions that she has muscle pain and stiffness in both legs and her back. Her labs include thyroid-stimulating hormone of 2.0 and vitamin D of 40. She stops the atorvastatin for 2 weeks with resolution of her symptoms.

Which treatment recommendation would you make for this patient?

A. Restart atorvastatin

B. Start rosuvastatin twice a week

C. Start ezetimibe

D. Start a PCSK9 inhibitor

We often see high-risk cardiovascular disease patients who are concerned about muscle side effects brought on by statins. I think we all can agree that this patient needs aggressive medical therapy for prevention of secondary cardiovascular events. I would restart her atorvastatin.

Neilsen and Nordestgaard found that early statin discontinuation rates increased from 6% in 1995 to 18% in 2010.¹

Early statin discontinuation correlated with negative statin-related news stories, their paper states. This suggests either an increased awareness of side effects or a possible nocebo effect.
 

Statin rechallenge results

Joy and colleagues reported the results on eight patients who had developed myalgias within 3 weeks of starting a statin. These patients, who received placebo or statin, completed an N-of-1 trial with three double-blind, crossover comparisons separated by 3-week washout periods.

Patients were evaluated pain on a visual analog scale (VAS). For each N-of-1 trial there was no statistically significant difference in pain or myalgia score between those who took statin and placebo. Five of the eight patients chose to continue on statins at the end of the trial.

Herrett and colleagues performed a more extensive series of N-of-1 trials involving 200 patients who had stopped or were considering stopping statins because of muscle symptoms.³ Participants either received 2 months of atorvastatin 20 mg or placebo for 2-month blocks six times. They rated their muscle symptoms on a VAS at the end of each block. There was no difference in muscle symptom scores between the statin and placebo periods.

Wood and colleagues took it a step further, when they studied an N-of-1 trial that included statin, placebo, and no treatment.⁴ Each participant received four bottles of atorvastatin 20 mg, four bottles of placebo, and four empty bottles. Each month they used treatment from the bottles based on random sequence and reported daily symptom scores. The mean symptom intensity was 8.0 during no-tablet months, 15.4 during placebo months (P < .001, compared with no-tablet months), and 16.3 during statin months (P < .001, compared with no-tablet months; P = .39, compared with placebo).

Taylor and colleagues studied 120 patients who had prior statin-associated muscle complaints.⁵ Each patient received either simvastatin 20 mg or placebo for 4 weeks, and then were switched for an additional 4 weeks. A total of 43 patients (36%) had pain on simvastatin but not placebo, 21 (17%) had no pain with either treatment, 21 (17%) reported pain with both treatments, and 35 (29%) had pain with placebo but not simvastatin. These studies support the concept of nocebo effect in patients who have muscle symptoms on statins.

So what should be done? Brennan and Roy did a retrospective study of 118 patients referred to a lipid clinic as being statin intolerant to two or more statins.⁶ Most of the patients were able to tolerate a statin: 71% tolerated same statin rechallenge, 53% tolerated statin switch, and 57% tolerated a nonstatin therapy.

In the Prosisa study, only 27% of patients who reported statin-associated muscle symptoms had reappearance of muscle symptoms after rechallenge with a statin.7
 

Research implications

Rechallenge with the same statin seems to be a reasonable first step, followed by switching to a different statin. I also share the concept of nocebo effect with my patients, and tell them I believe they have an excellent chance of tolerating the statin.

Pearl: The majority of patients with muscle symptoms while taking a statin likely have a nocebo effect, and are likely to tolerate rechallenge with the same statin.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Nielsen SF and Nordestgaard BG. Eur Heart J. 2016;37:908-16.

2. Joy TR et al. Ann Intern Med. 2014;160:301-10.

3. Herrett E et al. BMJ. 2021 Feb 24;372:n135.

4. Wood FA et al. N Engl J Med 2020;383:2182-4.

5. Taylor BA et al. Atherosclerosis. 2017;256:100-4.

6. Brennen ET and Roy TR. Can J Card. 2017;33(5):666-73.

7. Bonaiti Fet al. Atherosclerosis. 2020;315:E13-4.

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.

Orthopedic researchers from New York University have proposed standardizing prescribing patterns for patients after fracture surgery so as to include low-dose opioids.

In a paper presented at the annual meeting of the American Academy of Orthopaedic Surgeons, researchers from NYU reported on the implementation of their multimodal strategy, dubbed the “lopioid protocol.”

According to the 2019 National Survey on Drug Use and Health, orthopedic surgeons are the third-highest opioid prescribers in the United States.

Kennneth A. Egol, MD, vice chair of the department of orthopedic surgery at NYU, who is the first author of the study, was motivated to help create the protocol following misconceptions that orthopedic surgeons were helping to fuel the opioid epidemic.

Dr. Egol pointed to the year 1995, when pain became the fifth vital sign after body temperature, pulse rate, respiratory rate, and blood pressure.

Since then, in light of the opioid epidemic, the focus of physicians has shifted away from prescribing strong pain medication and reducing pain scores to zero to instead reducing pain to a manageable level.

Reducing opioid prescriptions can be challenging when patients are prescribed an anti-inflammatory and they subsequently ask their physician for a “pain pill.” Patients sometimes don’t understand that inflammation is what causes pain.

It can also be difficult to convince patients that medications that they can buy over the counter can adequately control their pain, as confirmed in numerous studies.

Multimodal pain therapy aims to reduce the need for opioids by supplementing their use with other oral medications and, at times, long-lasting regional nerve blocks.

Anti-inflammatories act at the site of injury or surgery where inflammation is occurring. Nerves then carry the pain signal to the brain. These signals can be dampened by medications such as gabapentin that act on the nerves themselves. The pain signal is received in the brain, where opioids act by binding to receptors in the brain.

The so-called lopioid protocol does not eliminate opioids completely but rather uses “safer” opioids, such as tramadol, in lieu of stronger narcotics.

The protocol began at NYU on Jan. 1, 2019. It consists in the prescribing of tramadol, meloxicam, gabapentin, and acetaminophen.

The study presented at the AAOS meeting demonstrated statistically significant reductions in visual analogue pain scores at discharge and subsequent medication refills for the 931 patients in the lopioid group, compared with a group of 848 patients who received narcotic prescriptions containing oxycodone from the year prior to the protocol initiation.

Educating patients on the rationale for the prescription combination can help to allay their fears. Dr. Egol thinks it’s important for physicians to explain the dangers of opioids to patients. He said in an interview that he also believes surgeons need to “give [patients] an understanding of why we are pursuing these protocols. They also need to know we will not ignore their pain and concerns.”

Brannon Orton, MD, is an orthopedic surgeon at Confluence Health, in Moses Lake, Wash. He sees a large number of trauma patients and thinks NYU is doing a good job of addressing a difficult problem in orthopedics – especially in the field of trauma.

He said in an interview: “Managing narcotics postoperatively can be challenging due to the fact that many people come into these fractures with a history of narcotic use.” Not only are they used to turning to opioids for pain relief, but they also may have built up a tolerance to them.

Although he hasn’t been using the lopioid protocol specifically, he has been following a multimodal approach regarding the postoperative use of narcotics. Of the study by Dr. Egol and colleagues, he said, “I think their paper presents an effective way of decreasing use of oral narcotics and still adequately managing patients’ pain postoperatively.” Dr. Orton’s own practice utilizes tramadol, acetaminophen, and ibuprofen after fracture surgery.

From Dr. Orton’s perspective, a significant challenge in implementing the lopioid protocol in practice is simply sticking to the plan. “It can become difficult when patients are pressuring staff or physicians for more narcotics. However, I feel that if everybody is on the same page with the plan, then it can be very doable.”

Dr. Egol and NYU try to limit narcotic prescriptions beginning with the patient’s initial visit to the ED. The ED physicians at his institution only “prescribe small amounts of narcotics. Our ED people really limit the amount of opioids prescribed.”

Dr. Egol recommends that all practitioners begin with nonnarcotic medication, even if treating a fracture nonoperatively. “Start low and go higher. I always try to start with NSAIDs and Tylenol,” he said.

Dr. Egol and Dr. Orton reported no relevant financial disclosures.

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

Orthopedic researchers from New York University have proposed standardizing prescribing patterns for patients after fracture surgery so as to include low-dose opioids.

In a paper presented at the annual meeting of the American Academy of Orthopaedic Surgeons, researchers from NYU reported on the implementation of their multimodal strategy, dubbed the “lopioid protocol.”

According to the 2019 National Survey on Drug Use and Health, orthopedic surgeons are the third-highest opioid prescribers in the United States.

Kennneth A. Egol, MD, vice chair of the department of orthopedic surgery at NYU, who is the first author of the study, was motivated to help create the protocol following misconceptions that orthopedic surgeons were helping to fuel the opioid epidemic.

Dr. Egol pointed to the year 1995, when pain became the fifth vital sign after body temperature, pulse rate, respiratory rate, and blood pressure.

Since then, in light of the opioid epidemic, the focus of physicians has shifted away from prescribing strong pain medication and reducing pain scores to zero to instead reducing pain to a manageable level.

Reducing opioid prescriptions can be challenging when patients are prescribed an anti-inflammatory and they subsequently ask their physician for a “pain pill.” Patients sometimes don’t understand that inflammation is what causes pain.

It can also be difficult to convince patients that medications that they can buy over the counter can adequately control their pain, as confirmed in numerous studies.

Multimodal pain therapy aims to reduce the need for opioids by supplementing their use with other oral medications and, at times, long-lasting regional nerve blocks.

Anti-inflammatories act at the site of injury or surgery where inflammation is occurring. Nerves then carry the pain signal to the brain. These signals can be dampened by medications such as gabapentin that act on the nerves themselves. The pain signal is received in the brain, where opioids act by binding to receptors in the brain.

The so-called lopioid protocol does not eliminate opioids completely but rather uses “safer” opioids, such as tramadol, in lieu of stronger narcotics.

The protocol began at NYU on Jan. 1, 2019. It consists in the prescribing of tramadol, meloxicam, gabapentin, and acetaminophen.

The study presented at the AAOS meeting demonstrated statistically significant reductions in visual analogue pain scores at discharge and subsequent medication refills for the 931 patients in the lopioid group, compared with a group of 848 patients who received narcotic prescriptions containing oxycodone from the year prior to the protocol initiation.

Educating patients on the rationale for the prescription combination can help to allay their fears. Dr. Egol thinks it’s important for physicians to explain the dangers of opioids to patients. He said in an interview that he also believes surgeons need to “give [patients] an understanding of why we are pursuing these protocols. They also need to know we will not ignore their pain and concerns.”

Brannon Orton, MD, is an orthopedic surgeon at Confluence Health, in Moses Lake, Wash. He sees a large number of trauma patients and thinks NYU is doing a good job of addressing a difficult problem in orthopedics – especially in the field of trauma.

He said in an interview: “Managing narcotics postoperatively can be challenging due to the fact that many people come into these fractures with a history of narcotic use.” Not only are they used to turning to opioids for pain relief, but they also may have built up a tolerance to them.

Although he hasn’t been using the lopioid protocol specifically, he has been following a multimodal approach regarding the postoperative use of narcotics. Of the study by Dr. Egol and colleagues, he said, “I think their paper presents an effective way of decreasing use of oral narcotics and still adequately managing patients’ pain postoperatively.” Dr. Orton’s own practice utilizes tramadol, acetaminophen, and ibuprofen after fracture surgery.

From Dr. Orton’s perspective, a significant challenge in implementing the lopioid protocol in practice is simply sticking to the plan. “It can become difficult when patients are pressuring staff or physicians for more narcotics. However, I feel that if everybody is on the same page with the plan, then it can be very doable.”

Dr. Egol and NYU try to limit narcotic prescriptions beginning with the patient’s initial visit to the ED. The ED physicians at his institution only “prescribe small amounts of narcotics. Our ED people really limit the amount of opioids prescribed.”

Dr. Egol recommends that all practitioners begin with nonnarcotic medication, even if treating a fracture nonoperatively. “Start low and go higher. I always try to start with NSAIDs and Tylenol,” he said.

Dr. Egol and Dr. Orton reported no relevant financial disclosures.

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

Orthopedic researchers from New York University have proposed standardizing prescribing patterns for patients after fracture surgery so as to include low-dose opioids.

In a paper presented at the annual meeting of the American Academy of Orthopaedic Surgeons, researchers from NYU reported on the implementation of their multimodal strategy, dubbed the “lopioid protocol.”

According to the 2019 National Survey on Drug Use and Health, orthopedic surgeons are the third-highest opioid prescribers in the United States.

Kennneth A. Egol, MD, vice chair of the department of orthopedic surgery at NYU, who is the first author of the study, was motivated to help create the protocol following misconceptions that orthopedic surgeons were helping to fuel the opioid epidemic.

Dr. Egol pointed to the year 1995, when pain became the fifth vital sign after body temperature, pulse rate, respiratory rate, and blood pressure.

Since then, in light of the opioid epidemic, the focus of physicians has shifted away from prescribing strong pain medication and reducing pain scores to zero to instead reducing pain to a manageable level.

Reducing opioid prescriptions can be challenging when patients are prescribed an anti-inflammatory and they subsequently ask their physician for a “pain pill.” Patients sometimes don’t understand that inflammation is what causes pain.

It can also be difficult to convince patients that medications that they can buy over the counter can adequately control their pain, as confirmed in numerous studies.

Multimodal pain therapy aims to reduce the need for opioids by supplementing their use with other oral medications and, at times, long-lasting regional nerve blocks.

Anti-inflammatories act at the site of injury or surgery where inflammation is occurring. Nerves then carry the pain signal to the brain. These signals can be dampened by medications such as gabapentin that act on the nerves themselves. The pain signal is received in the brain, where opioids act by binding to receptors in the brain.

The so-called lopioid protocol does not eliminate opioids completely but rather uses “safer” opioids, such as tramadol, in lieu of stronger narcotics.

The protocol began at NYU on Jan. 1, 2019. It consists in the prescribing of tramadol, meloxicam, gabapentin, and acetaminophen.

The study presented at the AAOS meeting demonstrated statistically significant reductions in visual analogue pain scores at discharge and subsequent medication refills for the 931 patients in the lopioid group, compared with a group of 848 patients who received narcotic prescriptions containing oxycodone from the year prior to the protocol initiation.

Educating patients on the rationale for the prescription combination can help to allay their fears. Dr. Egol thinks it’s important for physicians to explain the dangers of opioids to patients. He said in an interview that he also believes surgeons need to “give [patients] an understanding of why we are pursuing these protocols. They also need to know we will not ignore their pain and concerns.”

Brannon Orton, MD, is an orthopedic surgeon at Confluence Health, in Moses Lake, Wash. He sees a large number of trauma patients and thinks NYU is doing a good job of addressing a difficult problem in orthopedics – especially in the field of trauma.

He said in an interview: “Managing narcotics postoperatively can be challenging due to the fact that many people come into these fractures with a history of narcotic use.” Not only are they used to turning to opioids for pain relief, but they also may have built up a tolerance to them.

Although he hasn’t been using the lopioid protocol specifically, he has been following a multimodal approach regarding the postoperative use of narcotics. Of the study by Dr. Egol and colleagues, he said, “I think their paper presents an effective way of decreasing use of oral narcotics and still adequately managing patients’ pain postoperatively.” Dr. Orton’s own practice utilizes tramadol, acetaminophen, and ibuprofen after fracture surgery.

From Dr. Orton’s perspective, a significant challenge in implementing the lopioid protocol in practice is simply sticking to the plan. “It can become difficult when patients are pressuring staff or physicians for more narcotics. However, I feel that if everybody is on the same page with the plan, then it can be very doable.”

Dr. Egol and NYU try to limit narcotic prescriptions beginning with the patient’s initial visit to the ED. The ED physicians at his institution only “prescribe small amounts of narcotics. Our ED people really limit the amount of opioids prescribed.”

Dr. Egol recommends that all practitioners begin with nonnarcotic medication, even if treating a fracture nonoperatively. “Start low and go higher. I always try to start with NSAIDs and Tylenol,” he said.

Dr. Egol and Dr. Orton reported no relevant financial disclosures.

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

Opioid overdose deaths were significantly higher during 2020, but occurrences were not homogeneous across nine states. Male deaths were higher than in the 2 previous years in two states, according to a new, granular examination of data collected by researchers at the Massachusetts General Hospital (Mass General), Boston.

The analysis also showed that synthetic opioids such as fentanyl played an outsized role in most of the states that were reviewed. Additional drugs of abuse found in decedents, such as cocaine and psychostimulants, were more prevalent in some states than in others.

The Centers for Disease Control and Prevention used provisional death data in its recent report. It found that opioid-related deaths substantially rose in 2020 and that synthetic opioids were a primary driver.

The current Mass General analysis provides a more timely and detailed dive, senior author Mohammad Jalali, PhD, who is a senior scientist at Mass General’s Institute for Technology Assessment, told this news organization.

The findings, which have not yet been peer reviewed, were published in MedRxiv.
 

Shifting sands of opioid use disorder

Dr. Jalali and colleagues used a decision analysis approach to study opioid data in the hopes of providing better tools for policymakers to analyze and project trends and also to be better prepared to address the shifting sands of opioid use disorder in the United States.

They attempted to collect data on confirmed opioid overdose deaths from all 50 states and Washington, D.C. to assess what might have changed during the COVID-19 pandemic. Only nine states provided enough data for the analysis, which has been submitted to a peer reviewed publication.

These states were Alaska, Connecticut, Indiana, Massachusetts, North Carolina, Rhode Island, Colorado, Utah, and Wyoming.

“Drug overdose data are collected and reported more slowly than COVID-19 data,” Dr. Jalali said in a press release. The data reflected a lag time of about 4 to 8 months in Massachusetts and North Carolina to more than a year in Maryland and Ohio, he noted.

The reporting lag “has clouded the understanding of the effects of the COVID-19 pandemic on opioid-related overdose deaths,” said Dr. Jalali.

Commenting on the findings, Brandon Marshall, PhD, associate professor of epidemiology at Brown University, Providence, R.I, said that “the overall pattern of what’s being reported here is not surprising,” given the national trends seen in the CDC data.

“This paper adds a deeper dive into some of the sociodemographic trends that we’re starting to observe in specific states,” Dr. Marshall said.

Also commenting for this news organization, Brian Fuehrlein, MD, PhD, director of the psychiatric emergency department at the VA Connecticut Healthcare System in West Haven, Connecticut, noted that the current study “highlights things that we are currently seeing at VA Connecticut.”
 

Decrease in heroin, rise in fentanyl

The investigators found a significant reduction in overdose deaths that involved heroin in Alaska, Connecticut, Indiana, Massachusetts, North Carolina, and Rhode Island. That was a new trend for Alaska, Indiana, and Rhode Island, although with only 3 years of data, it’s hard to say whether it will continue, Dr. Jalali noted.

The decrease in heroin involvement seemed to continue a trend previously observed in Colorado, Connecticut, Massachusetts, and North Carolina.

In Connecticut, heroin was involved in 36% of deaths in 2018, 30% in 2019, and 16% in 2020, according to the study.

“We have begun seeing more and more heroin-negative, fentanyl-positive drug screens,” said Dr. Fuehrlein, who is also associate professor of psychiatry at Yale University, New Haven, Conn.

“There is a shift from fentanyl being an adulterant to fentanyl being what is sold and used exclusively,” he added.

In 2020, 92% (n = 887) of deaths in Connecticut involved synthetic opioids, continuing a trend. In Alaska, however, synthetic opioids were involved in 60% (44) of deaths, which is a big jump from 23% (9) in 2018.

Synthetic opioids were involved in the largest percentage of overdoses in all of the states studied. The fewest deaths, 17 (49%), occurred in Wyoming.

Cocaine is also increasingly found in addition to other substances in decedents. In Alaska, about 14% of individuals who overdosed in 2020 also had cocaine in their system, which was a jump from 2% in the prior year.

In Colorado, 19% (94) of those who died also had taken cocaine, up from 13% in 2019. Cocaine was also frequently found in those who died in the northeast: 39% (467) of those who died in Massachusetts, 29% (280) in Connecticut, and 47% (109) in Rhode Island.

There was also an increase in psychostimulants found in those who had died in Massachusetts in 2020.
 

More male overdoses in 2020

Results also showed that, compared to 2019, significantly more men died from overdoses in 2020 in Colorado (61% vs. 70%, P = .017) and Indiana (62% vs. 70%, P = .026).

This finding was unexpected, said Dr. Marshall, who has observed the same phenomenon in Rhode Island. He is the scientific director of PreventOverdoseRI, Rhode Island’s drug overdose surveillance and information dashboard.

Dr. Marshall and his colleagues conducted a study that also found disproportionate increases in overdoses among men. The findings of that study will be published in September.

“We’re still trying to wrap our head around why that is,” he said. He added that a deeper dive into the Rhode Island data showed that the deaths were increased especially among middle-aged men who had been diagnosed with depression and anxiety.

The same patterns were not seen among women in either Dr. Jalali’s study or his own analysis of the Rhode Island data, said Dr. Marshall.

“That suggests the COVID-19 pandemic impacted men who are at risk for overdose in some particularly severe way,” he noted.

Dr. Fuehrlein said he believes a variety of factors have led to an increase in overdose deaths during the pandemic, including the fact that many patients who would normally seek help avoided care or dropped out of treatment because of COVID fears. In addition, other support systems, such as group therapy and Narcotics Anonymous, were unavailable.

The pandemic increased stress, which can lead to worsening substance use, said Dr. Fuehrlein. He also noted that regular opioid suppliers were often not available, which led some to buy from different dealers, “which can lead to overdose if the fentanyl content is different.”
 

Identifying at-risk individuals

Dr. Jalali and colleagues note that clinicians and policymakers could use the new study to help identify and treat at-risk individuals.

“Practitioners and policy makers can use our findings to help them anticipate which groups of people might be most affected by opioid overdose and which types of policy interventions might be most effective given each state’s unique situation,” said lead study author Gian-Gabriel P. Garcia, PhD, in a press release. At the time of the study, Dr. Garcia was a postdoctoral fellow at Mass General and Harvard Medical School. He is currently an assistant professor at Georgia Tech, Atlanta.

Dr. Marshall pointed out that Dr. Jalali’s study is also relevant for emergency departments.

ED clinicians “are and will be seeing patients coming in who have no idea they were exposed to an opioid, nevermind fentanyl,” he said. ED clinicians can discuss with patients various harm reduction techniques, including the use of naloxone as well as test strips that can detect fentanyl in the drug supply, he added.

“Given the increasing use of fentanyl, which is very dangerous in overdose, clinicians need to be well versed in a harm reduction/overdose prevention approach to patient care,” Dr. Fuehrlein agreed.

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

Opioid overdose deaths were significantly higher during 2020, but occurrences were not homogeneous across nine states. Male deaths were higher than in the 2 previous years in two states, according to a new, granular examination of data collected by researchers at the Massachusetts General Hospital (Mass General), Boston.

The analysis also showed that synthetic opioids such as fentanyl played an outsized role in most of the states that were reviewed. Additional drugs of abuse found in decedents, such as cocaine and psychostimulants, were more prevalent in some states than in others.

The Centers for Disease Control and Prevention used provisional death data in its recent report. It found that opioid-related deaths substantially rose in 2020 and that synthetic opioids were a primary driver.

The current Mass General analysis provides a more timely and detailed dive, senior author Mohammad Jalali, PhD, who is a senior scientist at Mass General’s Institute for Technology Assessment, told this news organization.

The findings, which have not yet been peer reviewed, were published in MedRxiv.
 

Shifting sands of opioid use disorder

Dr. Jalali and colleagues used a decision analysis approach to study opioid data in the hopes of providing better tools for policymakers to analyze and project trends and also to be better prepared to address the shifting sands of opioid use disorder in the United States.

They attempted to collect data on confirmed opioid overdose deaths from all 50 states and Washington, D.C. to assess what might have changed during the COVID-19 pandemic. Only nine states provided enough data for the analysis, which has been submitted to a peer reviewed publication.

These states were Alaska, Connecticut, Indiana, Massachusetts, North Carolina, Rhode Island, Colorado, Utah, and Wyoming.

“Drug overdose data are collected and reported more slowly than COVID-19 data,” Dr. Jalali said in a press release. The data reflected a lag time of about 4 to 8 months in Massachusetts and North Carolina to more than a year in Maryland and Ohio, he noted.

The reporting lag “has clouded the understanding of the effects of the COVID-19 pandemic on opioid-related overdose deaths,” said Dr. Jalali.

Commenting on the findings, Brandon Marshall, PhD, associate professor of epidemiology at Brown University, Providence, R.I, said that “the overall pattern of what’s being reported here is not surprising,” given the national trends seen in the CDC data.

“This paper adds a deeper dive into some of the sociodemographic trends that we’re starting to observe in specific states,” Dr. Marshall said.

Also commenting for this news organization, Brian Fuehrlein, MD, PhD, director of the psychiatric emergency department at the VA Connecticut Healthcare System in West Haven, Connecticut, noted that the current study “highlights things that we are currently seeing at VA Connecticut.”
 

Decrease in heroin, rise in fentanyl

The investigators found a significant reduction in overdose deaths that involved heroin in Alaska, Connecticut, Indiana, Massachusetts, North Carolina, and Rhode Island. That was a new trend for Alaska, Indiana, and Rhode Island, although with only 3 years of data, it’s hard to say whether it will continue, Dr. Jalali noted.

The decrease in heroin involvement seemed to continue a trend previously observed in Colorado, Connecticut, Massachusetts, and North Carolina.

In Connecticut, heroin was involved in 36% of deaths in 2018, 30% in 2019, and 16% in 2020, according to the study.

“We have begun seeing more and more heroin-negative, fentanyl-positive drug screens,” said Dr. Fuehrlein, who is also associate professor of psychiatry at Yale University, New Haven, Conn.

“There is a shift from fentanyl being an adulterant to fentanyl being what is sold and used exclusively,” he added.

In 2020, 92% (n = 887) of deaths in Connecticut involved synthetic opioids, continuing a trend. In Alaska, however, synthetic opioids were involved in 60% (44) of deaths, which is a big jump from 23% (9) in 2018.

Synthetic opioids were involved in the largest percentage of overdoses in all of the states studied. The fewest deaths, 17 (49%), occurred in Wyoming.

Cocaine is also increasingly found in addition to other substances in decedents. In Alaska, about 14% of individuals who overdosed in 2020 also had cocaine in their system, which was a jump from 2% in the prior year.

In Colorado, 19% (94) of those who died also had taken cocaine, up from 13% in 2019. Cocaine was also frequently found in those who died in the northeast: 39% (467) of those who died in Massachusetts, 29% (280) in Connecticut, and 47% (109) in Rhode Island.

There was also an increase in psychostimulants found in those who had died in Massachusetts in 2020.
 

More male overdoses in 2020

Results also showed that, compared to 2019, significantly more men died from overdoses in 2020 in Colorado (61% vs. 70%, P = .017) and Indiana (62% vs. 70%, P = .026).

This finding was unexpected, said Dr. Marshall, who has observed the same phenomenon in Rhode Island. He is the scientific director of PreventOverdoseRI, Rhode Island’s drug overdose surveillance and information dashboard.

Dr. Marshall and his colleagues conducted a study that also found disproportionate increases in overdoses among men. The findings of that study will be published in September.

“We’re still trying to wrap our head around why that is,” he said. He added that a deeper dive into the Rhode Island data showed that the deaths were increased especially among middle-aged men who had been diagnosed with depression and anxiety.

The same patterns were not seen among women in either Dr. Jalali’s study or his own analysis of the Rhode Island data, said Dr. Marshall.

“That suggests the COVID-19 pandemic impacted men who are at risk for overdose in some particularly severe way,” he noted.

Dr. Fuehrlein said he believes a variety of factors have led to an increase in overdose deaths during the pandemic, including the fact that many patients who would normally seek help avoided care or dropped out of treatment because of COVID fears. In addition, other support systems, such as group therapy and Narcotics Anonymous, were unavailable.

The pandemic increased stress, which can lead to worsening substance use, said Dr. Fuehrlein. He also noted that regular opioid suppliers were often not available, which led some to buy from different dealers, “which can lead to overdose if the fentanyl content is different.”
 

Identifying at-risk individuals

Dr. Jalali and colleagues note that clinicians and policymakers could use the new study to help identify and treat at-risk individuals.

“Practitioners and policy makers can use our findings to help them anticipate which groups of people might be most affected by opioid overdose and which types of policy interventions might be most effective given each state’s unique situation,” said lead study author Gian-Gabriel P. Garcia, PhD, in a press release. At the time of the study, Dr. Garcia was a postdoctoral fellow at Mass General and Harvard Medical School. He is currently an assistant professor at Georgia Tech, Atlanta.

Dr. Marshall pointed out that Dr. Jalali’s study is also relevant for emergency departments.

ED clinicians “are and will be seeing patients coming in who have no idea they were exposed to an opioid, nevermind fentanyl,” he said. ED clinicians can discuss with patients various harm reduction techniques, including the use of naloxone as well as test strips that can detect fentanyl in the drug supply, he added.

“Given the increasing use of fentanyl, which is very dangerous in overdose, clinicians need to be well versed in a harm reduction/overdose prevention approach to patient care,” Dr. Fuehrlein agreed.

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

Opioid overdose deaths were significantly higher during 2020, but occurrences were not homogeneous across nine states. Male deaths were higher than in the 2 previous years in two states, according to a new, granular examination of data collected by researchers at the Massachusetts General Hospital (Mass General), Boston.

The analysis also showed that synthetic opioids such as fentanyl played an outsized role in most of the states that were reviewed. Additional drugs of abuse found in decedents, such as cocaine and psychostimulants, were more prevalent in some states than in others.

The Centers for Disease Control and Prevention used provisional death data in its recent report. It found that opioid-related deaths substantially rose in 2020 and that synthetic opioids were a primary driver.

The current Mass General analysis provides a more timely and detailed dive, senior author Mohammad Jalali, PhD, who is a senior scientist at Mass General’s Institute for Technology Assessment, told this news organization.

The findings, which have not yet been peer reviewed, were published in MedRxiv.
 

Shifting sands of opioid use disorder

Dr. Jalali and colleagues used a decision analysis approach to study opioid data in the hopes of providing better tools for policymakers to analyze and project trends and also to be better prepared to address the shifting sands of opioid use disorder in the United States.

They attempted to collect data on confirmed opioid overdose deaths from all 50 states and Washington, D.C. to assess what might have changed during the COVID-19 pandemic. Only nine states provided enough data for the analysis, which has been submitted to a peer reviewed publication.

These states were Alaska, Connecticut, Indiana, Massachusetts, North Carolina, Rhode Island, Colorado, Utah, and Wyoming.

“Drug overdose data are collected and reported more slowly than COVID-19 data,” Dr. Jalali said in a press release. The data reflected a lag time of about 4 to 8 months in Massachusetts and North Carolina to more than a year in Maryland and Ohio, he noted.

The reporting lag “has clouded the understanding of the effects of the COVID-19 pandemic on opioid-related overdose deaths,” said Dr. Jalali.

Commenting on the findings, Brandon Marshall, PhD, associate professor of epidemiology at Brown University, Providence, R.I, said that “the overall pattern of what’s being reported here is not surprising,” given the national trends seen in the CDC data.

“This paper adds a deeper dive into some of the sociodemographic trends that we’re starting to observe in specific states,” Dr. Marshall said.

Also commenting for this news organization, Brian Fuehrlein, MD, PhD, director of the psychiatric emergency department at the VA Connecticut Healthcare System in West Haven, Connecticut, noted that the current study “highlights things that we are currently seeing at VA Connecticut.”
 

Decrease in heroin, rise in fentanyl

The investigators found a significant reduction in overdose deaths that involved heroin in Alaska, Connecticut, Indiana, Massachusetts, North Carolina, and Rhode Island. That was a new trend for Alaska, Indiana, and Rhode Island, although with only 3 years of data, it’s hard to say whether it will continue, Dr. Jalali noted.

The decrease in heroin involvement seemed to continue a trend previously observed in Colorado, Connecticut, Massachusetts, and North Carolina.

In Connecticut, heroin was involved in 36% of deaths in 2018, 30% in 2019, and 16% in 2020, according to the study.

“We have begun seeing more and more heroin-negative, fentanyl-positive drug screens,” said Dr. Fuehrlein, who is also associate professor of psychiatry at Yale University, New Haven, Conn.

“There is a shift from fentanyl being an adulterant to fentanyl being what is sold and used exclusively,” he added.

In 2020, 92% (n = 887) of deaths in Connecticut involved synthetic opioids, continuing a trend. In Alaska, however, synthetic opioids were involved in 60% (44) of deaths, which is a big jump from 23% (9) in 2018.

Synthetic opioids were involved in the largest percentage of overdoses in all of the states studied. The fewest deaths, 17 (49%), occurred in Wyoming.

Cocaine is also increasingly found in addition to other substances in decedents. In Alaska, about 14% of individuals who overdosed in 2020 also had cocaine in their system, which was a jump from 2% in the prior year.

In Colorado, 19% (94) of those who died also had taken cocaine, up from 13% in 2019. Cocaine was also frequently found in those who died in the northeast: 39% (467) of those who died in Massachusetts, 29% (280) in Connecticut, and 47% (109) in Rhode Island.

There was also an increase in psychostimulants found in those who had died in Massachusetts in 2020.
 

More male overdoses in 2020

Results also showed that, compared to 2019, significantly more men died from overdoses in 2020 in Colorado (61% vs. 70%, P = .017) and Indiana (62% vs. 70%, P = .026).

This finding was unexpected, said Dr. Marshall, who has observed the same phenomenon in Rhode Island. He is the scientific director of PreventOverdoseRI, Rhode Island’s drug overdose surveillance and information dashboard.

Dr. Marshall and his colleagues conducted a study that also found disproportionate increases in overdoses among men. The findings of that study will be published in September.

“We’re still trying to wrap our head around why that is,” he said. He added that a deeper dive into the Rhode Island data showed that the deaths were increased especially among middle-aged men who had been diagnosed with depression and anxiety.

The same patterns were not seen among women in either Dr. Jalali’s study or his own analysis of the Rhode Island data, said Dr. Marshall.

“That suggests the COVID-19 pandemic impacted men who are at risk for overdose in some particularly severe way,” he noted.

Dr. Fuehrlein said he believes a variety of factors have led to an increase in overdose deaths during the pandemic, including the fact that many patients who would normally seek help avoided care or dropped out of treatment because of COVID fears. In addition, other support systems, such as group therapy and Narcotics Anonymous, were unavailable.

The pandemic increased stress, which can lead to worsening substance use, said Dr. Fuehrlein. He also noted that regular opioid suppliers were often not available, which led some to buy from different dealers, “which can lead to overdose if the fentanyl content is different.”
 

Identifying at-risk individuals

Dr. Jalali and colleagues note that clinicians and policymakers could use the new study to help identify and treat at-risk individuals.

“Practitioners and policy makers can use our findings to help them anticipate which groups of people might be most affected by opioid overdose and which types of policy interventions might be most effective given each state’s unique situation,” said lead study author Gian-Gabriel P. Garcia, PhD, in a press release. At the time of the study, Dr. Garcia was a postdoctoral fellow at Mass General and Harvard Medical School. He is currently an assistant professor at Georgia Tech, Atlanta.

Dr. Marshall pointed out that Dr. Jalali’s study is also relevant for emergency departments.

ED clinicians “are and will be seeing patients coming in who have no idea they were exposed to an opioid, nevermind fentanyl,” he said. ED clinicians can discuss with patients various harm reduction techniques, including the use of naloxone as well as test strips that can detect fentanyl in the drug supply, he added.

“Given the increasing use of fentanyl, which is very dangerous in overdose, clinicians need to be well versed in a harm reduction/overdose prevention approach to patient care,” Dr. Fuehrlein agreed.

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

In a year when emergency department visits dropped by almost 18%, visits for benzodiazepine overdoses did the opposite, according to a report from the Centers for Disease Control and Prevention.

The actual increase in the number of overdose visits for benzodiazepine overdoses was quite small – from 15,547 in 2019 to 15,830 in 2020 (1.8%) – but the 11 million fewer ED visits magnified its effect, Stephen Liu, PhD, and associates said in the Morbidity and Mortality Weekly Report.

The rate of benzodiazepine overdose visits to all visits increased by 23.7% from 2019 (24.22 per 100,000 ED visits) to 2020 (29.97 per 100,000), with the larger share going to those involving opioids, which were up by 34.4%, compared with overdose visits not involving opioids (21.0%), the investigators said, based on data reported by 32 states and the District of Columbia to the CDC’s Drug Overdose Surveillance and Epidemiology system. All of the rate changes are statistically significant.

The number of overdose visits without opioid coinvolvement actually dropped, from 2019 (12,276) to 2020 (12,218), but not by enough to offset the decline in total visits, noted Dr. Liu, of the CDC’s National Center for Injury Prevention and Control and associates.

The number of deaths from benzodiazepine overdose, on the other hand, did not drop in 2020. Those data, coming from 23 states participating in the CDC’s State Unintentional Drug Overdose Reporting System, were available only for the first half of the year.

In those 6 months, benzodiazepines were involved in more than 2,700 overdose deaths, with second-quarter deaths increasing by 43% from 2019 (1,004) to 2020 (1,435). The first quarter of 2020 also showed an increase, but exact numbers were not provided in the report. Overdose deaths rose by 22% for prescription forms of benzodiazepine and 520% for illicit forms in Q2 of 2020, compared with 2019, the researchers said.

Almost all of the benzodiazepine deaths (93%) in the first half of 2020 also involved opioids, mostly in the form of illicitly manufactured fentanyls (67% of all deaths). Between Q2 of 2019 and Q2 of 2020, involvement of illicit fentanyls in benzodiazepine overdose deaths increased from almost 57% to 71%, Dr. Liu and associates reported.

“Despite progress in reducing coprescribing [of opioids and benzodiazepines] before 2019, this study suggests a reversal in the decline in benzodiazepine deaths from 2017 to 2019, driven in part by increasing involvement of [illicitly manufactured fentanyls] in benzodiazepine deaths and influxes of illicit benzodiazepines,” they wrote.

[email protected]

In a year when emergency department visits dropped by almost 18%, visits for benzodiazepine overdoses did the opposite, according to a report from the Centers for Disease Control and Prevention.

The actual increase in the number of overdose visits for benzodiazepine overdoses was quite small – from 15,547 in 2019 to 15,830 in 2020 (1.8%) – but the 11 million fewer ED visits magnified its effect, Stephen Liu, PhD, and associates said in the Morbidity and Mortality Weekly Report.

The rate of benzodiazepine overdose visits to all visits increased by 23.7% from 2019 (24.22 per 100,000 ED visits) to 2020 (29.97 per 100,000), with the larger share going to those involving opioids, which were up by 34.4%, compared with overdose visits not involving opioids (21.0%), the investigators said, based on data reported by 32 states and the District of Columbia to the CDC’s Drug Overdose Surveillance and Epidemiology system. All of the rate changes are statistically significant.

The number of overdose visits without opioid coinvolvement actually dropped, from 2019 (12,276) to 2020 (12,218), but not by enough to offset the decline in total visits, noted Dr. Liu, of the CDC’s National Center for Injury Prevention and Control and associates.

The number of deaths from benzodiazepine overdose, on the other hand, did not drop in 2020. Those data, coming from 23 states participating in the CDC’s State Unintentional Drug Overdose Reporting System, were available only for the first half of the year.

In those 6 months, benzodiazepines were involved in more than 2,700 overdose deaths, with second-quarter deaths increasing by 43% from 2019 (1,004) to 2020 (1,435). The first quarter of 2020 also showed an increase, but exact numbers were not provided in the report. Overdose deaths rose by 22% for prescription forms of benzodiazepine and 520% for illicit forms in Q2 of 2020, compared with 2019, the researchers said.

Almost all of the benzodiazepine deaths (93%) in the first half of 2020 also involved opioids, mostly in the form of illicitly manufactured fentanyls (67% of all deaths). Between Q2 of 2019 and Q2 of 2020, involvement of illicit fentanyls in benzodiazepine overdose deaths increased from almost 57% to 71%, Dr. Liu and associates reported.

“Despite progress in reducing coprescribing [of opioids and benzodiazepines] before 2019, this study suggests a reversal in the decline in benzodiazepine deaths from 2017 to 2019, driven in part by increasing involvement of [illicitly manufactured fentanyls] in benzodiazepine deaths and influxes of illicit benzodiazepines,” they wrote.

[email protected]

In a year when emergency department visits dropped by almost 18%, visits for benzodiazepine overdoses did the opposite, according to a report from the Centers for Disease Control and Prevention.

The actual increase in the number of overdose visits for benzodiazepine overdoses was quite small – from 15,547 in 2019 to 15,830 in 2020 (1.8%) – but the 11 million fewer ED visits magnified its effect, Stephen Liu, PhD, and associates said in the Morbidity and Mortality Weekly Report.

The rate of benzodiazepine overdose visits to all visits increased by 23.7% from 2019 (24.22 per 100,000 ED visits) to 2020 (29.97 per 100,000), with the larger share going to those involving opioids, which were up by 34.4%, compared with overdose visits not involving opioids (21.0%), the investigators said, based on data reported by 32 states and the District of Columbia to the CDC’s Drug Overdose Surveillance and Epidemiology system. All of the rate changes are statistically significant.

The number of overdose visits without opioid coinvolvement actually dropped, from 2019 (12,276) to 2020 (12,218), but not by enough to offset the decline in total visits, noted Dr. Liu, of the CDC’s National Center for Injury Prevention and Control and associates.

The number of deaths from benzodiazepine overdose, on the other hand, did not drop in 2020. Those data, coming from 23 states participating in the CDC’s State Unintentional Drug Overdose Reporting System, were available only for the first half of the year.

In those 6 months, benzodiazepines were involved in more than 2,700 overdose deaths, with second-quarter deaths increasing by 43% from 2019 (1,004) to 2020 (1,435). The first quarter of 2020 also showed an increase, but exact numbers were not provided in the report. Overdose deaths rose by 22% for prescription forms of benzodiazepine and 520% for illicit forms in Q2 of 2020, compared with 2019, the researchers said.

Almost all of the benzodiazepine deaths (93%) in the first half of 2020 also involved opioids, mostly in the form of illicitly manufactured fentanyls (67% of all deaths). Between Q2 of 2019 and Q2 of 2020, involvement of illicit fentanyls in benzodiazepine overdose deaths increased from almost 57% to 71%, Dr. Liu and associates reported.

“Despite progress in reducing coprescribing [of opioids and benzodiazepines] before 2019, this study suggests a reversal in the decline in benzodiazepine deaths from 2017 to 2019, driven in part by increasing involvement of [illicitly manufactured fentanyls] in benzodiazepine deaths and influxes of illicit benzodiazepines,” they wrote.

[email protected]

A Maryland-based physician assistant was sentenced to 37 months in federal prison for conspiracy to distribute and dispense oxycodone, fentanyl, methadone, and alprazolam at a pain management clinic.

Niyazz/ThinkStock

A U.S. District Judge sentenced William Soyke, 68, of Hanover, Penn., for acting outside the scope of professional practice and not for a legitimate medical purpose, according to the U.S. Attorney’s Office in Maryland. The 37-month prison term will be followed by 3 years of supervised release.

According to the plea agreement, Mr. Soyke worked as a physician assistant with Rosen-Hoffberg Rehabilitation and Pain Management from 2011 to 2018, where he treated patients during follow-up doctor appointments. As a physician assistant, Mr. Soyke had privileges to prescribe controlled substance medications, but was required to operate under a delegation agreement with the Rosen-Hoffberg owners.  

In his plea, Mr. Soyke said that he believed the owners, Norman Rosen, MD, and Howard Hoffberg, MD, prescribed excessive levels of opioids. Despite Mr. Soyke’s attempts to lower patient’s prescription doses, both doctors overruled the PA’s opinion, according to the plea agreement. Also, if another health care provider within the practice declined to treat a patient because of the patient’s aberrant behavior – such as failing a drug screening test for illicit drugs or selling their prescriptions – Dr. Rosen and Dr. Hoffberg would assume that patient’s care, the report continued.

As stated in the plea agreement, Mr. Sokye was aware that many of the patients presenting to Rosen-Hoffberg Rehabilitation and Pain Management did not have a legitimate medical need for the oxycodone, fentanyl, alprazolam, and methadone they were being prescribed. Nevertheless, Mr. Soyke issued prescriptions for these drugs to patients without a legitimate medical need and outside the bounds of acceptable medical practice, according to the release.

Mr. Soyke also admitted that in several instances he engaged in sexual, physical contact with female patients who were attempting to get prescriptions, the plea agreement stated. Specifically, Mr. Soyke asked some female customers to engage in a range of motion test, and while they were bending over, he would position himself behind them such that his genitalia would rub against the customers’ buttocks through their clothes. These patients often submitted to this sexual abuse for fear of not getting the medications to which they were addicted, according to the press release.

Although the female patients complained to Dr. Rosen and Dr. Hoffberg about Mr. Soyke’s behavior, the doctors did not fire Mr. Soyke because the PA saw the largest number of patients at the practice and generated significant revenue, according to federal officials.

Dr. Hoffberg, the associate medical director and part-owner of the practice, pleaded guilty in June to accepting kickbacks from pharmaceutical company Insys Therapeutics in exchange for prescribing an opioid drug called Subsys (a fentanyl sublingual spray) marketed by Insys for breakthrough pain in cancer patients for off-label purposes. He will be sentenced in September and faces a maximum of 5 years in federal prison.

Mr. Soyke pled guilty to a federal drug charge in July 2019. In announcing the guilty plea then, U.S. Attorney Robert Hur said, “Opioid overdoses are killing thousands of Marylanders each year, and opioid addiction is fueled by health care providers who prescribe drugs for people without a legitimate medical need. Doctors and other medical professionals who irresponsibly write opioid prescriptions are acting like street-corner drug pushers.”

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

A Maryland-based physician assistant was sentenced to 37 months in federal prison for conspiracy to distribute and dispense oxycodone, fentanyl, methadone, and alprazolam at a pain management clinic.

Niyazz/ThinkStock

A U.S. District Judge sentenced William Soyke, 68, of Hanover, Penn., for acting outside the scope of professional practice and not for a legitimate medical purpose, according to the U.S. Attorney’s Office in Maryland. The 37-month prison term will be followed by 3 years of supervised release.

According to the plea agreement, Mr. Soyke worked as a physician assistant with Rosen-Hoffberg Rehabilitation and Pain Management from 2011 to 2018, where he treated patients during follow-up doctor appointments. As a physician assistant, Mr. Soyke had privileges to prescribe controlled substance medications, but was required to operate under a delegation agreement with the Rosen-Hoffberg owners.  

In his plea, Mr. Soyke said that he believed the owners, Norman Rosen, MD, and Howard Hoffberg, MD, prescribed excessive levels of opioids. Despite Mr. Soyke’s attempts to lower patient’s prescription doses, both doctors overruled the PA’s opinion, according to the plea agreement. Also, if another health care provider within the practice declined to treat a patient because of the patient’s aberrant behavior – such as failing a drug screening test for illicit drugs or selling their prescriptions – Dr. Rosen and Dr. Hoffberg would assume that patient’s care, the report continued.

As stated in the plea agreement, Mr. Sokye was aware that many of the patients presenting to Rosen-Hoffberg Rehabilitation and Pain Management did not have a legitimate medical need for the oxycodone, fentanyl, alprazolam, and methadone they were being prescribed. Nevertheless, Mr. Soyke issued prescriptions for these drugs to patients without a legitimate medical need and outside the bounds of acceptable medical practice, according to the release.

Mr. Soyke also admitted that in several instances he engaged in sexual, physical contact with female patients who were attempting to get prescriptions, the plea agreement stated. Specifically, Mr. Soyke asked some female customers to engage in a range of motion test, and while they were bending over, he would position himself behind them such that his genitalia would rub against the customers’ buttocks through their clothes. These patients often submitted to this sexual abuse for fear of not getting the medications to which they were addicted, according to the press release.

Although the female patients complained to Dr. Rosen and Dr. Hoffberg about Mr. Soyke’s behavior, the doctors did not fire Mr. Soyke because the PA saw the largest number of patients at the practice and generated significant revenue, according to federal officials.

Dr. Hoffberg, the associate medical director and part-owner of the practice, pleaded guilty in June to accepting kickbacks from pharmaceutical company Insys Therapeutics in exchange for prescribing an opioid drug called Subsys (a fentanyl sublingual spray) marketed by Insys for breakthrough pain in cancer patients for off-label purposes. He will be sentenced in September and faces a maximum of 5 years in federal prison.

Mr. Soyke pled guilty to a federal drug charge in July 2019. In announcing the guilty plea then, U.S. Attorney Robert Hur said, “Opioid overdoses are killing thousands of Marylanders each year, and opioid addiction is fueled by health care providers who prescribe drugs for people without a legitimate medical need. Doctors and other medical professionals who irresponsibly write opioid prescriptions are acting like street-corner drug pushers.”

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

A Maryland-based physician assistant was sentenced to 37 months in federal prison for conspiracy to distribute and dispense oxycodone, fentanyl, methadone, and alprazolam at a pain management clinic.

Niyazz/ThinkStock

A U.S. District Judge sentenced William Soyke, 68, of Hanover, Penn., for acting outside the scope of professional practice and not for a legitimate medical purpose, according to the U.S. Attorney’s Office in Maryland. The 37-month prison term will be followed by 3 years of supervised release.

According to the plea agreement, Mr. Soyke worked as a physician assistant with Rosen-Hoffberg Rehabilitation and Pain Management from 2011 to 2018, where he treated patients during follow-up doctor appointments. As a physician assistant, Mr. Soyke had privileges to prescribe controlled substance medications, but was required to operate under a delegation agreement with the Rosen-Hoffberg owners.  

In his plea, Mr. Soyke said that he believed the owners, Norman Rosen, MD, and Howard Hoffberg, MD, prescribed excessive levels of opioids. Despite Mr. Soyke’s attempts to lower patient’s prescription doses, both doctors overruled the PA’s opinion, according to the plea agreement. Also, if another health care provider within the practice declined to treat a patient because of the patient’s aberrant behavior – such as failing a drug screening test for illicit drugs or selling their prescriptions – Dr. Rosen and Dr. Hoffberg would assume that patient’s care, the report continued.

As stated in the plea agreement, Mr. Sokye was aware that many of the patients presenting to Rosen-Hoffberg Rehabilitation and Pain Management did not have a legitimate medical need for the oxycodone, fentanyl, alprazolam, and methadone they were being prescribed. Nevertheless, Mr. Soyke issued prescriptions for these drugs to patients without a legitimate medical need and outside the bounds of acceptable medical practice, according to the release.

Mr. Soyke also admitted that in several instances he engaged in sexual, physical contact with female patients who were attempting to get prescriptions, the plea agreement stated. Specifically, Mr. Soyke asked some female customers to engage in a range of motion test, and while they were bending over, he would position himself behind them such that his genitalia would rub against the customers’ buttocks through their clothes. These patients often submitted to this sexual abuse for fear of not getting the medications to which they were addicted, according to the press release.

Although the female patients complained to Dr. Rosen and Dr. Hoffberg about Mr. Soyke’s behavior, the doctors did not fire Mr. Soyke because the PA saw the largest number of patients at the practice and generated significant revenue, according to federal officials.

Dr. Hoffberg, the associate medical director and part-owner of the practice, pleaded guilty in June to accepting kickbacks from pharmaceutical company Insys Therapeutics in exchange for prescribing an opioid drug called Subsys (a fentanyl sublingual spray) marketed by Insys for breakthrough pain in cancer patients for off-label purposes. He will be sentenced in September and faces a maximum of 5 years in federal prison.

Mr. Soyke pled guilty to a federal drug charge in July 2019. In announcing the guilty plea then, U.S. Attorney Robert Hur said, “Opioid overdoses are killing thousands of Marylanders each year, and opioid addiction is fueled by health care providers who prescribe drugs for people without a legitimate medical need. Doctors and other medical professionals who irresponsibly write opioid prescriptions are acting like street-corner drug pushers.”

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

The novel calcitonin gene-related peptide (CGRP) antagonist atogepant is safe and effective for the preventive treatment of migraine, full results from a phase 3 trial suggest.

AbbVie, the company developing the oral therapy, announced topline results of the ADVANCE trial of atogepant last year. Safety results were presented in April at the 2021 annual meeting of the American Academy of Neurology.

The full results were published online Aug. 19 in the New England Journal of Medicine ahead of the upcoming target action date of the U.S. Food and Drug Administration.

The multicenter study included nearly 900 patients who were randomly assigned to receive either placebo or one of three doses of atogepant for 12 weeks. The mean number of monthly migraine days decreased by about 4 for all three doses of the active treatment, compared with a reduction of 2.5 days with placebo.

All doses effective

The study included 873 patients with episodic migraine with or without aura. Patients who were not assigned to the placebo control group received either 10 mg, 30 mg, or 60 mg of atogepant once daily.

After a 4-week screening period, all patients received treatment for 12 weeks and then entered a 4-week safety follow-up period. In total, the participants completed eight scheduled clinical visits.

The mean reduction from baseline in the mean number of migraine days per month was 3.7 with the 10-mg dose of atogepant, 3.9 with the 30-mg dose, 4.2 with the 60-mg dose, and 2.5 with placebo. The differences between each active dose and placebo was statistically significant (P < .001).

Treatment with the CGRP inhibitor was also associated with a reduction in the mean number of headache days per month. The mean reduction from baseline was 3.9 days for the 10-mg dose, 4.0 days for the 30-mg dose, 4.2 days for the 60-mg dose, and 2.5 days for placebo (P < .001 for all comparisons with placebo).

In addition, for 55.6% of the 10-mg group, 58.7% of the 30-mg group, 60.8% of the 60-mg group, and 29.0% of the control group, there was a reduction of at least 50% in the 3-month average number of migraine days per month (P < .001 for each vs. placebo).

The most commonly reported adverse events (AEs) among patients who received atogepant were constipation (6.9%-7.7% across doses), nausea (4.4%-6.1%), and upper respiratory tract infection (1.4%-3.9%). Frequency of AEs did not differ between the active-treatment groups and the control group, and no relationships between AEs and atogepant dose were observed.
 

Multidose flexibility

“Side effects were pretty even across the board,” said Dr. Ailani. She noted that the reported AEs were expected because of atogepant’s mechanism of action. In addition, the rate of discontinuation in the study was low.

The proportion of participants who experienced a reduction in monthly migraine days of at least 50% grew as time passed. “By the end of this study, your chance of having a greater than 50% response is about 75%,” Dr. Ailani said.

“Imagine telling your patient, ‘You stick on this drug for 3 months, and I can almost guarantee you that you’re going to get better,’” she added.

Although the treatment has no drug-drug contraindications, drug-drug interactions may occur. “The availability of various doses would allow clinicians to adjust treatment to avoid potential drug-drug interactions,” said Dr. Ailani. “That multidose flexibility is very important.”

An FDA decision on atogepant could be made in the coming months. “I’m hopeful, as a clinician, that it is positive news, because we really have waited a long time for something like this,” Dr. Ailani said.

“You can easily identify patients who would do well on this medication,” she added.

In a different study of atogepant among patients with chronic migraine, there were recruitment delays because of the pandemic. That study is now almost complete, Dr. Ailani reported.
 

“Well-conducted study”

Commenting on the findings, Kathleen B. Digre, MD, chief of the division of headache and neuro-ophthalmology at the University of Utah Health, Salt Lake City, expressed enthusiasm for the experimental drug. “I’m excited to see another treatment modality for migraine,” said Dr. Digre, who was not involved with the research. “It was a very well-conducted study,” she added.

The treatment arms were almost identical in regard to disease severity, and all the doses showed an effect. Although the difference in reduction of monthly migraine days in comparison with placebo was numerically small, “for people who have frequent migraine, it’s important,” Dr. Digre said.

The results for atogepant should be viewed in a larger context, however. “Even though it’s a treatment that works better than placebo for well-matched controls, it may not be a medication that everybody’s going to respond to,” she noted. “And we can’t generalize it for some of the most disabled people, which is for chronic migraine,” she said.

It is significant that the study was published in the New England Journal of Medicine, Dr. Digre noted. “Sometimes migraine is dismissed as not important and not affecting people’s lives,” she said. “That makes me very happy to see migraine being taken seriously by our major journals.”

In addition, she noted that the prospects for FDA approval of atogepant seem favorable. “I’m hopeful that they will approve it, because it’s got a low side-effect profile, plus it’s effective.”

Migraine-specific preventive therapy has emerged only in the past few years. “I’m so excited to see this surge of preventive medicine for migraine,” Dr. Digre said. “It’s so important, because we see so many people who are disabled by migraine,” she added.

The study was funded by Allergan before atogepant was acquired by AbbVie. Dr. Ailani has received honoraria from AbbVie for consulting, has received compensation from Allergan and AbbVie for participating in a speakers’ bureau, and has received clinical trial grants from Allergan. Dr. Digre has reported no relevant financial relationships.

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

The novel calcitonin gene-related peptide (CGRP) antagonist atogepant is safe and effective for the preventive treatment of migraine, full results from a phase 3 trial suggest.

AbbVie, the company developing the oral therapy, announced topline results of the ADVANCE trial of atogepant last year. Safety results were presented in April at the 2021 annual meeting of the American Academy of Neurology.

The full results were published online Aug. 19 in the New England Journal of Medicine ahead of the upcoming target action date of the U.S. Food and Drug Administration.

The multicenter study included nearly 900 patients who were randomly assigned to receive either placebo or one of three doses of atogepant for 12 weeks. The mean number of monthly migraine days decreased by about 4 for all three doses of the active treatment, compared with a reduction of 2.5 days with placebo.

All doses effective

The study included 873 patients with episodic migraine with or without aura. Patients who were not assigned to the placebo control group received either 10 mg, 30 mg, or 60 mg of atogepant once daily.

After a 4-week screening period, all patients received treatment for 12 weeks and then entered a 4-week safety follow-up period. In total, the participants completed eight scheduled clinical visits.

The mean reduction from baseline in the mean number of migraine days per month was 3.7 with the 10-mg dose of atogepant, 3.9 with the 30-mg dose, 4.2 with the 60-mg dose, and 2.5 with placebo. The differences between each active dose and placebo was statistically significant (P < .001).

Treatment with the CGRP inhibitor was also associated with a reduction in the mean number of headache days per month. The mean reduction from baseline was 3.9 days for the 10-mg dose, 4.0 days for the 30-mg dose, 4.2 days for the 60-mg dose, and 2.5 days for placebo (P < .001 for all comparisons with placebo).

In addition, for 55.6% of the 10-mg group, 58.7% of the 30-mg group, 60.8% of the 60-mg group, and 29.0% of the control group, there was a reduction of at least 50% in the 3-month average number of migraine days per month (P < .001 for each vs. placebo).

The most commonly reported adverse events (AEs) among patients who received atogepant were constipation (6.9%-7.7% across doses), nausea (4.4%-6.1%), and upper respiratory tract infection (1.4%-3.9%). Frequency of AEs did not differ between the active-treatment groups and the control group, and no relationships between AEs and atogepant dose were observed.
 

Multidose flexibility

“Side effects were pretty even across the board,” said Dr. Ailani. She noted that the reported AEs were expected because of atogepant’s mechanism of action. In addition, the rate of discontinuation in the study was low.

The proportion of participants who experienced a reduction in monthly migraine days of at least 50% grew as time passed. “By the end of this study, your chance of having a greater than 50% response is about 75%,” Dr. Ailani said.

“Imagine telling your patient, ‘You stick on this drug for 3 months, and I can almost guarantee you that you’re going to get better,’” she added.

Although the treatment has no drug-drug contraindications, drug-drug interactions may occur. “The availability of various doses would allow clinicians to adjust treatment to avoid potential drug-drug interactions,” said Dr. Ailani. “That multidose flexibility is very important.”

An FDA decision on atogepant could be made in the coming months. “I’m hopeful, as a clinician, that it is positive news, because we really have waited a long time for something like this,” Dr. Ailani said.

“You can easily identify patients who would do well on this medication,” she added.

In a different study of atogepant among patients with chronic migraine, there were recruitment delays because of the pandemic. That study is now almost complete, Dr. Ailani reported.
 

“Well-conducted study”

Commenting on the findings, Kathleen B. Digre, MD, chief of the division of headache and neuro-ophthalmology at the University of Utah Health, Salt Lake City, expressed enthusiasm for the experimental drug. “I’m excited to see another treatment modality for migraine,” said Dr. Digre, who was not involved with the research. “It was a very well-conducted study,” she added.

The treatment arms were almost identical in regard to disease severity, and all the doses showed an effect. Although the difference in reduction of monthly migraine days in comparison with placebo was numerically small, “for people who have frequent migraine, it’s important,” Dr. Digre said.

The results for atogepant should be viewed in a larger context, however. “Even though it’s a treatment that works better than placebo for well-matched controls, it may not be a medication that everybody’s going to respond to,” she noted. “And we can’t generalize it for some of the most disabled people, which is for chronic migraine,” she said.

It is significant that the study was published in the New England Journal of Medicine, Dr. Digre noted. “Sometimes migraine is dismissed as not important and not affecting people’s lives,” she said. “That makes me very happy to see migraine being taken seriously by our major journals.”

In addition, she noted that the prospects for FDA approval of atogepant seem favorable. “I’m hopeful that they will approve it, because it’s got a low side-effect profile, plus it’s effective.”

Migraine-specific preventive therapy has emerged only in the past few years. “I’m so excited to see this surge of preventive medicine for migraine,” Dr. Digre said. “It’s so important, because we see so many people who are disabled by migraine,” she added.

The study was funded by Allergan before atogepant was acquired by AbbVie. Dr. Ailani has received honoraria from AbbVie for consulting, has received compensation from Allergan and AbbVie for participating in a speakers’ bureau, and has received clinical trial grants from Allergan. Dr. Digre has reported no relevant financial relationships.

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

The novel calcitonin gene-related peptide (CGRP) antagonist atogepant is safe and effective for the preventive treatment of migraine, full results from a phase 3 trial suggest.

AbbVie, the company developing the oral therapy, announced topline results of the ADVANCE trial of atogepant last year. Safety results were presented in April at the 2021 annual meeting of the American Academy of Neurology.

The full results were published online Aug. 19 in the New England Journal of Medicine ahead of the upcoming target action date of the U.S. Food and Drug Administration.

The multicenter study included nearly 900 patients who were randomly assigned to receive either placebo or one of three doses of atogepant for 12 weeks. The mean number of monthly migraine days decreased by about 4 for all three doses of the active treatment, compared with a reduction of 2.5 days with placebo.

All doses effective

The study included 873 patients with episodic migraine with or without aura. Patients who were not assigned to the placebo control group received either 10 mg, 30 mg, or 60 mg of atogepant once daily.

After a 4-week screening period, all patients received treatment for 12 weeks and then entered a 4-week safety follow-up period. In total, the participants completed eight scheduled clinical visits.

The mean reduction from baseline in the mean number of migraine days per month was 3.7 with the 10-mg dose of atogepant, 3.9 with the 30-mg dose, 4.2 with the 60-mg dose, and 2.5 with placebo. The differences between each active dose and placebo was statistically significant (P < .001).

Treatment with the CGRP inhibitor was also associated with a reduction in the mean number of headache days per month. The mean reduction from baseline was 3.9 days for the 10-mg dose, 4.0 days for the 30-mg dose, 4.2 days for the 60-mg dose, and 2.5 days for placebo (P < .001 for all comparisons with placebo).

In addition, for 55.6% of the 10-mg group, 58.7% of the 30-mg group, 60.8% of the 60-mg group, and 29.0% of the control group, there was a reduction of at least 50% in the 3-month average number of migraine days per month (P < .001 for each vs. placebo).

The most commonly reported adverse events (AEs) among patients who received atogepant were constipation (6.9%-7.7% across doses), nausea (4.4%-6.1%), and upper respiratory tract infection (1.4%-3.9%). Frequency of AEs did not differ between the active-treatment groups and the control group, and no relationships between AEs and atogepant dose were observed.
 

Multidose flexibility

“Side effects were pretty even across the board,” said Dr. Ailani. She noted that the reported AEs were expected because of atogepant’s mechanism of action. In addition, the rate of discontinuation in the study was low.

The proportion of participants who experienced a reduction in monthly migraine days of at least 50% grew as time passed. “By the end of this study, your chance of having a greater than 50% response is about 75%,” Dr. Ailani said.

“Imagine telling your patient, ‘You stick on this drug for 3 months, and I can almost guarantee you that you’re going to get better,’” she added.

Although the treatment has no drug-drug contraindications, drug-drug interactions may occur. “The availability of various doses would allow clinicians to adjust treatment to avoid potential drug-drug interactions,” said Dr. Ailani. “That multidose flexibility is very important.”

An FDA decision on atogepant could be made in the coming months. “I’m hopeful, as a clinician, that it is positive news, because we really have waited a long time for something like this,” Dr. Ailani said.

“You can easily identify patients who would do well on this medication,” she added.

In a different study of atogepant among patients with chronic migraine, there were recruitment delays because of the pandemic. That study is now almost complete, Dr. Ailani reported.
 

“Well-conducted study”

Commenting on the findings, Kathleen B. Digre, MD, chief of the division of headache and neuro-ophthalmology at the University of Utah Health, Salt Lake City, expressed enthusiasm for the experimental drug. “I’m excited to see another treatment modality for migraine,” said Dr. Digre, who was not involved with the research. “It was a very well-conducted study,” she added.

The treatment arms were almost identical in regard to disease severity, and all the doses showed an effect. Although the difference in reduction of monthly migraine days in comparison with placebo was numerically small, “for people who have frequent migraine, it’s important,” Dr. Digre said.

The results for atogepant should be viewed in a larger context, however. “Even though it’s a treatment that works better than placebo for well-matched controls, it may not be a medication that everybody’s going to respond to,” she noted. “And we can’t generalize it for some of the most disabled people, which is for chronic migraine,” she said.

It is significant that the study was published in the New England Journal of Medicine, Dr. Digre noted. “Sometimes migraine is dismissed as not important and not affecting people’s lives,” she said. “That makes me very happy to see migraine being taken seriously by our major journals.”

In addition, she noted that the prospects for FDA approval of atogepant seem favorable. “I’m hopeful that they will approve it, because it’s got a low side-effect profile, plus it’s effective.”

Migraine-specific preventive therapy has emerged only in the past few years. “I’m so excited to see this surge of preventive medicine for migraine,” Dr. Digre said. “It’s so important, because we see so many people who are disabled by migraine,” she added.

The study was funded by Allergan before atogepant was acquired by AbbVie. Dr. Ailani has received honoraria from AbbVie for consulting, has received compensation from Allergan and AbbVie for participating in a speakers’ bureau, and has received clinical trial grants from Allergan. Dr. Digre has reported no relevant financial relationships.

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