Pain

BOSTON – When it comes to relieving migraine, triptans, ergots, and antiemetics are the most effective classes of medications, a new real-world analysis of data on more than 3 million migraine attacks shows.

The findings “align with results of clinical trials and recommendations from clinical treatment guidelines” and provide insights to complement clinical practice, said study investigator Chia-Chun Chiang, MD, a neurologist with Mayo Clinic, Rochester, Minn.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

The power of big data

Despite a wide variety of acute migraine medications that are available, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking, Dr. Chiang explained.

“To the best of our knowledge, this is the first study that simultaneously compared multiple acute migraine medications using a Big Data analysis approach based on real-world patient-provided data,” she said.

The researchers extracted more than 10 million self-reported migraine attack records from a migraine smartphone app called Migraine Buddy, where users can document whether a treatment was helpful, somewhat helpful, unsure, or unhelpful.

They analyzed 25 acute medications among seven classes: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, combination analgesics (acetaminophen/aspirin/caffeine), ergots, antiemetics, and opioids. The newer gepants and ditan medication classes of medications were not included because of the relatively lower numbers of usage when data was extracted (2014-2020).

The researchers employed a two-level nested logistic regression model to analyze the odds of treatment effectiveness of each medication by adjusting concurrent medications and the covariance within the same user.

The final analysis included more than 3.1 million migraine attacks among 278,000 users globally.

Using ibuprofen as the reference, triptans, ergots, and antiemetics had the highest efficacy with mean odds ratios of 4.8, 3.02, and 2.67, respectively, followed by opioids (OR, 2.49), NSAIDs (OR, 1.94), combination analgesics (OR, 1.69), others (OR, 1.49), and acetaminophen (OR, 0.83).

Individual medications with the highest patient-reported effectiveness were eletriptan (Relpax; OR, 6.1), zolmitriptan (Zomig; OR, 5.7) and sumatriptan (Zecuity; OR, 5.2).

This migraine medication comparative effectiveness analysis, based on patient-reported outcomes, “supports and complements the treatment recommendations from national headache societies based on randomized controlled trials and meta-analyses and strongly supports the use of triptans,” Dr. Chiang said.
 

End of trial-and-error?

Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said “This is a great study of Big Data in that it shows the power of the smartphone to collect real-world data and smart researchers like at Mayo Clinic to analyze them.”

“The study sheds light on how different therapeutics compare with each other. The next iteration of this line of research, I would hope, would be to determine if particular medications are effective for a particular migraine population, and even down to individuals with migraine,” said Dr. Lakhan, who wasn’t involved in the study.

“Once those models are appropriately built, long gone will be the era of trial-and-error medicine,” Dr. Lakhan added.

The study had no specific funding. Dr. Chiang has served as a consultant for Satsuma. Dr. Lakhan reports no relevant financial relationships.

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

BOSTON – When it comes to relieving migraine, triptans, ergots, and antiemetics are the most effective classes of medications, a new real-world analysis of data on more than 3 million migraine attacks shows.

The findings “align with results of clinical trials and recommendations from clinical treatment guidelines” and provide insights to complement clinical practice, said study investigator Chia-Chun Chiang, MD, a neurologist with Mayo Clinic, Rochester, Minn.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

The power of big data

Despite a wide variety of acute migraine medications that are available, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking, Dr. Chiang explained.

“To the best of our knowledge, this is the first study that simultaneously compared multiple acute migraine medications using a Big Data analysis approach based on real-world patient-provided data,” she said.

The researchers extracted more than 10 million self-reported migraine attack records from a migraine smartphone app called Migraine Buddy, where users can document whether a treatment was helpful, somewhat helpful, unsure, or unhelpful.

They analyzed 25 acute medications among seven classes: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, combination analgesics (acetaminophen/aspirin/caffeine), ergots, antiemetics, and opioids. The newer gepants and ditan medication classes of medications were not included because of the relatively lower numbers of usage when data was extracted (2014-2020).

The researchers employed a two-level nested logistic regression model to analyze the odds of treatment effectiveness of each medication by adjusting concurrent medications and the covariance within the same user.

The final analysis included more than 3.1 million migraine attacks among 278,000 users globally.

Using ibuprofen as the reference, triptans, ergots, and antiemetics had the highest efficacy with mean odds ratios of 4.8, 3.02, and 2.67, respectively, followed by opioids (OR, 2.49), NSAIDs (OR, 1.94), combination analgesics (OR, 1.69), others (OR, 1.49), and acetaminophen (OR, 0.83).

Individual medications with the highest patient-reported effectiveness were eletriptan (Relpax; OR, 6.1), zolmitriptan (Zomig; OR, 5.7) and sumatriptan (Zecuity; OR, 5.2).

This migraine medication comparative effectiveness analysis, based on patient-reported outcomes, “supports and complements the treatment recommendations from national headache societies based on randomized controlled trials and meta-analyses and strongly supports the use of triptans,” Dr. Chiang said.
 

End of trial-and-error?

Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said “This is a great study of Big Data in that it shows the power of the smartphone to collect real-world data and smart researchers like at Mayo Clinic to analyze them.”

“The study sheds light on how different therapeutics compare with each other. The next iteration of this line of research, I would hope, would be to determine if particular medications are effective for a particular migraine population, and even down to individuals with migraine,” said Dr. Lakhan, who wasn’t involved in the study.

“Once those models are appropriately built, long gone will be the era of trial-and-error medicine,” Dr. Lakhan added.

The study had no specific funding. Dr. Chiang has served as a consultant for Satsuma. Dr. Lakhan reports no relevant financial relationships.

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

BOSTON – When it comes to relieving migraine, triptans, ergots, and antiemetics are the most effective classes of medications, a new real-world analysis of data on more than 3 million migraine attacks shows.

The findings “align with results of clinical trials and recommendations from clinical treatment guidelines” and provide insights to complement clinical practice, said study investigator Chia-Chun Chiang, MD, a neurologist with Mayo Clinic, Rochester, Minn.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

The power of big data

Despite a wide variety of acute migraine medications that are available, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking, Dr. Chiang explained.

“To the best of our knowledge, this is the first study that simultaneously compared multiple acute migraine medications using a Big Data analysis approach based on real-world patient-provided data,” she said.

The researchers extracted more than 10 million self-reported migraine attack records from a migraine smartphone app called Migraine Buddy, where users can document whether a treatment was helpful, somewhat helpful, unsure, or unhelpful.

They analyzed 25 acute medications among seven classes: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, combination analgesics (acetaminophen/aspirin/caffeine), ergots, antiemetics, and opioids. The newer gepants and ditan medication classes of medications were not included because of the relatively lower numbers of usage when data was extracted (2014-2020).

The researchers employed a two-level nested logistic regression model to analyze the odds of treatment effectiveness of each medication by adjusting concurrent medications and the covariance within the same user.

The final analysis included more than 3.1 million migraine attacks among 278,000 users globally.

Using ibuprofen as the reference, triptans, ergots, and antiemetics had the highest efficacy with mean odds ratios of 4.8, 3.02, and 2.67, respectively, followed by opioids (OR, 2.49), NSAIDs (OR, 1.94), combination analgesics (OR, 1.69), others (OR, 1.49), and acetaminophen (OR, 0.83).

Individual medications with the highest patient-reported effectiveness were eletriptan (Relpax; OR, 6.1), zolmitriptan (Zomig; OR, 5.7) and sumatriptan (Zecuity; OR, 5.2).

This migraine medication comparative effectiveness analysis, based on patient-reported outcomes, “supports and complements the treatment recommendations from national headache societies based on randomized controlled trials and meta-analyses and strongly supports the use of triptans,” Dr. Chiang said.
 

End of trial-and-error?

Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said “This is a great study of Big Data in that it shows the power of the smartphone to collect real-world data and smart researchers like at Mayo Clinic to analyze them.”

“The study sheds light on how different therapeutics compare with each other. The next iteration of this line of research, I would hope, would be to determine if particular medications are effective for a particular migraine population, and even down to individuals with migraine,” said Dr. Lakhan, who wasn’t involved in the study.

“Once those models are appropriately built, long gone will be the era of trial-and-error medicine,” Dr. Lakhan added.

The study had no specific funding. Dr. Chiang has served as a consultant for Satsuma. Dr. Lakhan reports no relevant financial relationships.

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

The Food and Drug Administration has approved an expanded indication for atogepant (Qulipta, Abbvie) to include prevention of chronic migraine in adults. The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.

The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.

Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.

The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.

The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.

Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.

The efficacy results are consistent with those in the ADVANCE episodic migraine trial.

The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.

“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.

The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.

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

The Food and Drug Administration has approved an expanded indication for atogepant (Qulipta, Abbvie) to include prevention of chronic migraine in adults. The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.

The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.

Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.

The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.

The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.

Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.

The efficacy results are consistent with those in the ADVANCE episodic migraine trial.

The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.

“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.

The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.

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

The Food and Drug Administration has approved an expanded indication for atogepant (Qulipta, Abbvie) to include prevention of chronic migraine in adults. The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.

The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.

Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.

The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.

The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.

Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.

The efficacy results are consistent with those in the ADVANCE episodic migraine trial.

The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.

“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.

The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.

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

PARIS – For orchestra musicians, performance is everything. So, it’s no wonder that musculoskeletal disorders – a reality for so many of these professionals – are not openly discussed. Physical pain is often pushed aside, unexpressed, until one day the suffering gets to be too much, the ability to play is impacted, and all the effort to keep things under wraps and under control culminates in burnout.

Anne Maugue was one of the speakers at the French College of General Medicine’s 16th Congress of General Medicine. Ms. Maugue is a postdoctoral researcher at Côte d’Azur University, Nice, France. She also plays flute in the Monte-Carlo Philharmonic Orchestra. Through her presentation to the physicians, she sought to raise awareness about MSDs in professional musicians, as well as the associated psychosocial risk factors. “If caught early enough, this pain can often be successfully treated.”
 

High prevalence

“You’re a violinist in a major symphony orchestra. It’s Sunday night, 8 o’clock, and you’ve just come off the stage. A few minutes ago, you felt a sharp pain in your right arm – a pain that is now, already, overwhelming. The conductor accused you of not being focused, of not concentrating. You know that you have another rehearsal in just a few hours, Monday morning. So, what do you do – other than hope that the pain goes away by then? Where can you turn to get help?”

With this opening scenario, Ms. Maugue was able to immediately orient the attendees to the realities that professional musicians face.

Pain is far from anecdotal. In professional orchestras, its prevalence over 12 months is between 41% and 93%. “An elite athlete has a full training staff they can turn to. An elite musician, on the other hand, usually only has their general practitioner – and that’s assuming the musician even reaches out to get treatment to begin with.

“The fact is that most of the time musicians only care about the pain when it becomes chronic, when it causes discomfort that affects their playing,” said Ms. Maugue.

How, then, does one evaluate this problem? In a Danish study, musicians rated the musculoskeletal problems they had experienced in the preceding 7 days. When the researchers compared those reports with findings from a clinical examination, they found that the examiners were not able to identify which musicians had reported problems. Why? Because a diagnosis does not reflect the severity or the impact, both of which are subjective.

“When faced with pain, the musician’s initial reaction is denial,” said Ms. Maugue. “The pain is often attributed to something other than the physicality of playing their instrument. They then turn to self-care, to colleagues. It’s only much later that they consult a medical professional.”

As a result, the physician is seldom aware of the musician’s psychological distress and has no sense of how long it’s been since the pain first started.
 

Work environment

Carrying around an instrument all the time and maintaining nonergonomic postures for extended periods are just two of the factors that put professional musicians at risk of physical pain. Not to be forgotten, Ms. Maugue added, are the work-related pressures. Musicians are not immune to issues with their work environment. They can feel like they aren’t getting the resources they need, proper recognition from their leaders, or support from their colleagues. In the end, such feelings can engender a sense of unfairness – and that acts as a stressor that can give rise to MSDs.

Evidence of this phenomenon can be found in the results of a study that Ms. Maugue conducted. Out of 440 French orchestra musicians (44% women), 64% said they had experienced MSD-related pain in the preceding 12 months and 61% in the preceding 7 days.

Using industrial and organizational psychology scales of measurement, Ms. Maugue was able to show, through hierarchical regression, that “emotional exhaustion and MSD-related pain occur when the environment in which people work causes them to feel a sense of unfairness.”
 

Early detection

Finally, Ms. Maugue encouraged general practitioners to ask every patient whether he or she plays a musical instrument. If the answer is yes, get an idea about any pain that he or she may have been feeling in the back, neck, and upper extremities so that prompt treatment can be given.

“There are other studies underway that are looking to better characterize instrumental activity and to enable more effective management by sports medicine departments,” said Ms. Maugue. “But back to patients with MSDs. It’s important to understand everything about their playing. Where do they practice? How often do they practice? What’s their posture like when they play? What’s the tempo of the music they’re working on? Because what we see in professional musicians is likely to be seen in amateur musicians as well – particularly in young people who study at a conservatory,” where not much is being done to prevent MSDs.

“If professional musicians are given treatment early on, half of them can be permanently cured,” she concluded. “And then, just like elite athletes, they’ll be able to get right back to playing.”

This article was translated from Medscape’s French edition and a version appeared on Medscape.com.

PARIS – For orchestra musicians, performance is everything. So, it’s no wonder that musculoskeletal disorders – a reality for so many of these professionals – are not openly discussed. Physical pain is often pushed aside, unexpressed, until one day the suffering gets to be too much, the ability to play is impacted, and all the effort to keep things under wraps and under control culminates in burnout.

Anne Maugue was one of the speakers at the French College of General Medicine’s 16th Congress of General Medicine. Ms. Maugue is a postdoctoral researcher at Côte d’Azur University, Nice, France. She also plays flute in the Monte-Carlo Philharmonic Orchestra. Through her presentation to the physicians, she sought to raise awareness about MSDs in professional musicians, as well as the associated psychosocial risk factors. “If caught early enough, this pain can often be successfully treated.”
 

High prevalence

“You’re a violinist in a major symphony orchestra. It’s Sunday night, 8 o’clock, and you’ve just come off the stage. A few minutes ago, you felt a sharp pain in your right arm – a pain that is now, already, overwhelming. The conductor accused you of not being focused, of not concentrating. You know that you have another rehearsal in just a few hours, Monday morning. So, what do you do – other than hope that the pain goes away by then? Where can you turn to get help?”

With this opening scenario, Ms. Maugue was able to immediately orient the attendees to the realities that professional musicians face.

Pain is far from anecdotal. In professional orchestras, its prevalence over 12 months is between 41% and 93%. “An elite athlete has a full training staff they can turn to. An elite musician, on the other hand, usually only has their general practitioner – and that’s assuming the musician even reaches out to get treatment to begin with.

“The fact is that most of the time musicians only care about the pain when it becomes chronic, when it causes discomfort that affects their playing,” said Ms. Maugue.

How, then, does one evaluate this problem? In a Danish study, musicians rated the musculoskeletal problems they had experienced in the preceding 7 days. When the researchers compared those reports with findings from a clinical examination, they found that the examiners were not able to identify which musicians had reported problems. Why? Because a diagnosis does not reflect the severity or the impact, both of which are subjective.

“When faced with pain, the musician’s initial reaction is denial,” said Ms. Maugue. “The pain is often attributed to something other than the physicality of playing their instrument. They then turn to self-care, to colleagues. It’s only much later that they consult a medical professional.”

As a result, the physician is seldom aware of the musician’s psychological distress and has no sense of how long it’s been since the pain first started.
 

Work environment

Carrying around an instrument all the time and maintaining nonergonomic postures for extended periods are just two of the factors that put professional musicians at risk of physical pain. Not to be forgotten, Ms. Maugue added, are the work-related pressures. Musicians are not immune to issues with their work environment. They can feel like they aren’t getting the resources they need, proper recognition from their leaders, or support from their colleagues. In the end, such feelings can engender a sense of unfairness – and that acts as a stressor that can give rise to MSDs.

Evidence of this phenomenon can be found in the results of a study that Ms. Maugue conducted. Out of 440 French orchestra musicians (44% women), 64% said they had experienced MSD-related pain in the preceding 12 months and 61% in the preceding 7 days.

Using industrial and organizational psychology scales of measurement, Ms. Maugue was able to show, through hierarchical regression, that “emotional exhaustion and MSD-related pain occur when the environment in which people work causes them to feel a sense of unfairness.”
 

Early detection

Finally, Ms. Maugue encouraged general practitioners to ask every patient whether he or she plays a musical instrument. If the answer is yes, get an idea about any pain that he or she may have been feeling in the back, neck, and upper extremities so that prompt treatment can be given.

“There are other studies underway that are looking to better characterize instrumental activity and to enable more effective management by sports medicine departments,” said Ms. Maugue. “But back to patients with MSDs. It’s important to understand everything about their playing. Where do they practice? How often do they practice? What’s their posture like when they play? What’s the tempo of the music they’re working on? Because what we see in professional musicians is likely to be seen in amateur musicians as well – particularly in young people who study at a conservatory,” where not much is being done to prevent MSDs.

“If professional musicians are given treatment early on, half of them can be permanently cured,” she concluded. “And then, just like elite athletes, they’ll be able to get right back to playing.”

This article was translated from Medscape’s French edition and a version appeared on Medscape.com.

PARIS – For orchestra musicians, performance is everything. So, it’s no wonder that musculoskeletal disorders – a reality for so many of these professionals – are not openly discussed. Physical pain is often pushed aside, unexpressed, until one day the suffering gets to be too much, the ability to play is impacted, and all the effort to keep things under wraps and under control culminates in burnout.

Anne Maugue was one of the speakers at the French College of General Medicine’s 16th Congress of General Medicine. Ms. Maugue is a postdoctoral researcher at Côte d’Azur University, Nice, France. She also plays flute in the Monte-Carlo Philharmonic Orchestra. Through her presentation to the physicians, she sought to raise awareness about MSDs in professional musicians, as well as the associated psychosocial risk factors. “If caught early enough, this pain can often be successfully treated.”
 

High prevalence

“You’re a violinist in a major symphony orchestra. It’s Sunday night, 8 o’clock, and you’ve just come off the stage. A few minutes ago, you felt a sharp pain in your right arm – a pain that is now, already, overwhelming. The conductor accused you of not being focused, of not concentrating. You know that you have another rehearsal in just a few hours, Monday morning. So, what do you do – other than hope that the pain goes away by then? Where can you turn to get help?”

With this opening scenario, Ms. Maugue was able to immediately orient the attendees to the realities that professional musicians face.

Pain is far from anecdotal. In professional orchestras, its prevalence over 12 months is between 41% and 93%. “An elite athlete has a full training staff they can turn to. An elite musician, on the other hand, usually only has their general practitioner – and that’s assuming the musician even reaches out to get treatment to begin with.

“The fact is that most of the time musicians only care about the pain when it becomes chronic, when it causes discomfort that affects their playing,” said Ms. Maugue.

How, then, does one evaluate this problem? In a Danish study, musicians rated the musculoskeletal problems they had experienced in the preceding 7 days. When the researchers compared those reports with findings from a clinical examination, they found that the examiners were not able to identify which musicians had reported problems. Why? Because a diagnosis does not reflect the severity or the impact, both of which are subjective.

“When faced with pain, the musician’s initial reaction is denial,” said Ms. Maugue. “The pain is often attributed to something other than the physicality of playing their instrument. They then turn to self-care, to colleagues. It’s only much later that they consult a medical professional.”

As a result, the physician is seldom aware of the musician’s psychological distress and has no sense of how long it’s been since the pain first started.
 

Work environment

Carrying around an instrument all the time and maintaining nonergonomic postures for extended periods are just two of the factors that put professional musicians at risk of physical pain. Not to be forgotten, Ms. Maugue added, are the work-related pressures. Musicians are not immune to issues with their work environment. They can feel like they aren’t getting the resources they need, proper recognition from their leaders, or support from their colleagues. In the end, such feelings can engender a sense of unfairness – and that acts as a stressor that can give rise to MSDs.

Evidence of this phenomenon can be found in the results of a study that Ms. Maugue conducted. Out of 440 French orchestra musicians (44% women), 64% said they had experienced MSD-related pain in the preceding 12 months and 61% in the preceding 7 days.

Using industrial and organizational psychology scales of measurement, Ms. Maugue was able to show, through hierarchical regression, that “emotional exhaustion and MSD-related pain occur when the environment in which people work causes them to feel a sense of unfairness.”
 

Early detection

Finally, Ms. Maugue encouraged general practitioners to ask every patient whether he or she plays a musical instrument. If the answer is yes, get an idea about any pain that he or she may have been feeling in the back, neck, and upper extremities so that prompt treatment can be given.

“There are other studies underway that are looking to better characterize instrumental activity and to enable more effective management by sports medicine departments,” said Ms. Maugue. “But back to patients with MSDs. It’s important to understand everything about their playing. Where do they practice? How often do they practice? What’s their posture like when they play? What’s the tempo of the music they’re working on? Because what we see in professional musicians is likely to be seen in amateur musicians as well – particularly in young people who study at a conservatory,” where not much is being done to prevent MSDs.

“If professional musicians are given treatment early on, half of them can be permanently cured,” she concluded. “And then, just like elite athletes, they’ll be able to get right back to playing.”

This article was translated from Medscape’s French edition and a version appeared on Medscape.com.

Both pain relief and neurological improvements persisted in patients with diabetic neuropathy 2 years after they began receiving treatment with 10 kHz of spinal cord stimulation, according to research that released early, prior to its presentation at the annual meeting of the American Academy of Neurology.

The data represents the longest follow-up available for spinal cord stimulation at a frequency higher than the 60 Hz initially approved for diabetic neuropathy by the Food and Drug Administration, according to lead author Erika A. Petersen, MD, a professor of neurosurgery and the residency program director at the University of Arkansas for Medical Sciences, Little Rock.

University of Arkansas

“You would expect that somebody who continues to have diabetes for 24 months and has neuropathy would have worse neuropathy after 2 years, and what we’re seeing is that people were stable or better in terms of their nerve function at 2 years,” Dr. Petersen said in an interview. “So that’s really revolutionary.”
 

Encouraging preliminary findings

The findings are “promising and preliminary,” John D. Markman, MD, a professor in neurology and neurosurgery, vice chair for clinical research, and director of the Translational Pain Research Program at the University of Rochester (N.Y.) Medical Center, said in an interview. Dr. Markman, who was not involved in this study, said that, though the results are encouraging, it’s “less clear how much of [the pain improvement] is due to what we would consider to be on-target, pain-relieving benefit from stimulation versus other factors like expectation.” The crossover rate and amount of reduction in pain intensity are promising, but “I think that excitement is weighed against the fact that this is an open-label study.”

An underused treatment

Although spinal cord stimulation has been around since the late 1960s, its use only picked up steam in the 2000s, when it became more frequently used to treat chronic nerve damage related to neuropathic pain syndromes, Dr. Petersen explained. The FDA approved the treatment’s new indication for diabetic neuropathy in 2015, and data from Abbott and Medtronic have shown benefits from spinal cord stimulation at 60 Hz, but some patients are uncomfortable with the vibration or tingling feelings the devices can cause at that frequency.

“They describe creepy crawlies or ants crawling over the feet, or pins and needles, and painful sensitivity,” Dr. Petersen said. “You create a vibration feeling in the same zone where they already have those feelings of buzzing and pain and vibration, and it’s sometimes actually even more uncomfortable and less satisfying to them in terms of relief” with the spinal cord stimulation at 60 Hz, she said, “so there’s a lot of attrition in terms of who will actually use it.”

At 10 kHz, however, “people don’t feel any vibration or tingling associated with it; it just jams the signal of the pain,” she said. The difference between the frequencies is like that between “a lifeguard whistle and a dog whistle.”
 

Testing high-frequency stimulation

The new findings included the 24-month follow-up data from a randomized controlled trial that assessed the effectiveness of high-frequency spinal cord stimulation for painful diabetic neuropathy. The original 216 participants enrolled in the trial had diabetic neuropathy symptoms for at least 12 months and either could no not tolerate or did not respond to medications. Enrollment criteria also included lower-limb pain intensity of at least 5 on a 0-10 visual analogy scale and hemoglobin A1c of no more than 10%.

For the first 6 months of the trial – before crossover was offered – participants were randomly assigned to receive either 10 kHz of spinal cord stimulation along with conventional medical management or to receive conventional medical management alone. The 6-month data from 187 patients, as reported in April 2021 in JAMA Neurology, revealed that 79% of those receiving spinal cord stimulation experienced at least 50% improved pain relief without worsening of their baseline neurologic deficits, compared with only 5% of those receiving only conventional treatments.

Average pain levels increased 2% in the control participants compared with a decrease of 76% in those with the spinal cord stimulation devices. In addition, 62% of the patients receiving spinal cord stimulation demonstration neurologic improvement in reflexes, strength, movement and sensation, compared with 3% of those in the control group. The study’s findings led the FDA to approve the device using 10 kHz.

At 6 months, 93% of control patients crossed over to receiving spinal cord stimulation while none with the devices opted to stop their spinal cord stimulation. The 12-month data revealed that 85% of those receiving spinal cord stimulation experienced at least 50% pain relief, with the average pain relief at 74%. Patients also reported statistically significant improved quality of life as well as less interference with sleep, mood, and daily activities from pain.

Two years after baseline, patients’ pain relief was maintained with average 80% improvement, and 66% of patients showed neurologic improvement since baseline. Though no patients had devices removed because of ineffectiveness, five patients’ devices were removed because of infection while infections in three other patients resolved.

“Being able to offer something that is not a pharmaceutical, without the side effects, that shows an even longer durability to that response is a really important finding at this point,” Dr. Petersen said.
 

Surgical considerations

Among the estimated 37 million Americans with type 1 or 2 diabetes, approximately one quarter of them experience some level of painful diabetic neuropathy, but medication and other medical management strategies are not always adequate in treating their pain. After a 1-week trial of spinal cord stimulation, the devices are implanted under the skin and rechargeable through the skin for up to 10 years, after which they can be replaced.

An appropriate candidate for spinal cord stimulation would be someone for whom existing non-invasive pain relief options, including medications, are ineffective or intolerable, Dr. Petersen and Dr. Markman both said. An adequate trial of medication is not “one size fits all” and will vary by each patient, added Dr. Markman, who is also interested in whether this study’s participants were able to have a reduction in use of pain relief medications.

“I think there’s a significant number of patients out there who can benefit from this, so I think that’s why it’s promising and exciting,” Dr. Markman said. “I do think it’s important to see if this actually allows them to be on less medication or whether stimulation turns out to be another treatment in addition to their baseline treatments.” The challenge is identifying “which patients are most likely to be benefiting from this and which are most likely to be harmed.”

Aside from infection from implantation, other possible risks include pain at the battery site and, in rare cases, a need for reoperation because of migration of the leads, he said.
 

Improvement in symptom severity and quality of life

After the wound from the implant has completely healed, Dr. Petersen said patients using the devices do not have any activity restrictions outside of magnetic interference, such as MRIs. “I’ve had people go back-country kayaking, scuba diving, fishing with their grandkids, all sorts of all sorts of things. If patients need to go through a scanner of any kind, they should ask whether it’s safe for pacemakers since these devices are like a “pacemaker for pain.

“I had a patient bring solar chargers with him so that he could recharge his battery in the backwoods while kayaking because that’s the level of improvement in pain that he got – from barely being able to walk down the hall to feeling comfortable being off the grid and active again,” Dr. Petersen said. “Those kinds of improvements in quality of life are massive.”

The study findings may also suggest that spinal cord stimulation can benefit a broader population of patients experiencing neuropathic pain, Dr. Markman said.

“There’s an extraordinary unmet need for treatments for neuropathy, and one important question here is the extent to which diabetic peripheral neuropathy and the response that we’re seeing here is a proxy for a broader effect across many neuropathies that are caused by other conditions other than diabetes,” Dr. Markman said. “There’s a lot of reason to think that this will be helpful not just for diabetes-related neuropathic pain, but for other types of neuropathic pain that have similar clinical presentations or clinical symptom patterns to diabetic peripheral neuropathy.”

The study was funded by Nevro, who manufactures the devices. Dr. Petersen and Dr. Markman both reported consulting with, receiving support from, holding stock options with, and serving on the data safety monitoring boards and advisory boards of numerous pharmaceutical companies.

Both pain relief and neurological improvements persisted in patients with diabetic neuropathy 2 years after they began receiving treatment with 10 kHz of spinal cord stimulation, according to research that released early, prior to its presentation at the annual meeting of the American Academy of Neurology.

The data represents the longest follow-up available for spinal cord stimulation at a frequency higher than the 60 Hz initially approved for diabetic neuropathy by the Food and Drug Administration, according to lead author Erika A. Petersen, MD, a professor of neurosurgery and the residency program director at the University of Arkansas for Medical Sciences, Little Rock.

University of Arkansas

“You would expect that somebody who continues to have diabetes for 24 months and has neuropathy would have worse neuropathy after 2 years, and what we’re seeing is that people were stable or better in terms of their nerve function at 2 years,” Dr. Petersen said in an interview. “So that’s really revolutionary.”
 

Encouraging preliminary findings

The findings are “promising and preliminary,” John D. Markman, MD, a professor in neurology and neurosurgery, vice chair for clinical research, and director of the Translational Pain Research Program at the University of Rochester (N.Y.) Medical Center, said in an interview. Dr. Markman, who was not involved in this study, said that, though the results are encouraging, it’s “less clear how much of [the pain improvement] is due to what we would consider to be on-target, pain-relieving benefit from stimulation versus other factors like expectation.” The crossover rate and amount of reduction in pain intensity are promising, but “I think that excitement is weighed against the fact that this is an open-label study.”

An underused treatment

Although spinal cord stimulation has been around since the late 1960s, its use only picked up steam in the 2000s, when it became more frequently used to treat chronic nerve damage related to neuropathic pain syndromes, Dr. Petersen explained. The FDA approved the treatment’s new indication for diabetic neuropathy in 2015, and data from Abbott and Medtronic have shown benefits from spinal cord stimulation at 60 Hz, but some patients are uncomfortable with the vibration or tingling feelings the devices can cause at that frequency.

“They describe creepy crawlies or ants crawling over the feet, or pins and needles, and painful sensitivity,” Dr. Petersen said. “You create a vibration feeling in the same zone where they already have those feelings of buzzing and pain and vibration, and it’s sometimes actually even more uncomfortable and less satisfying to them in terms of relief” with the spinal cord stimulation at 60 Hz, she said, “so there’s a lot of attrition in terms of who will actually use it.”

At 10 kHz, however, “people don’t feel any vibration or tingling associated with it; it just jams the signal of the pain,” she said. The difference between the frequencies is like that between “a lifeguard whistle and a dog whistle.”
 

Testing high-frequency stimulation

The new findings included the 24-month follow-up data from a randomized controlled trial that assessed the effectiveness of high-frequency spinal cord stimulation for painful diabetic neuropathy. The original 216 participants enrolled in the trial had diabetic neuropathy symptoms for at least 12 months and either could no not tolerate or did not respond to medications. Enrollment criteria also included lower-limb pain intensity of at least 5 on a 0-10 visual analogy scale and hemoglobin A1c of no more than 10%.

For the first 6 months of the trial – before crossover was offered – participants were randomly assigned to receive either 10 kHz of spinal cord stimulation along with conventional medical management or to receive conventional medical management alone. The 6-month data from 187 patients, as reported in April 2021 in JAMA Neurology, revealed that 79% of those receiving spinal cord stimulation experienced at least 50% improved pain relief without worsening of their baseline neurologic deficits, compared with only 5% of those receiving only conventional treatments.

Average pain levels increased 2% in the control participants compared with a decrease of 76% in those with the spinal cord stimulation devices. In addition, 62% of the patients receiving spinal cord stimulation demonstration neurologic improvement in reflexes, strength, movement and sensation, compared with 3% of those in the control group. The study’s findings led the FDA to approve the device using 10 kHz.

At 6 months, 93% of control patients crossed over to receiving spinal cord stimulation while none with the devices opted to stop their spinal cord stimulation. The 12-month data revealed that 85% of those receiving spinal cord stimulation experienced at least 50% pain relief, with the average pain relief at 74%. Patients also reported statistically significant improved quality of life as well as less interference with sleep, mood, and daily activities from pain.

Two years after baseline, patients’ pain relief was maintained with average 80% improvement, and 66% of patients showed neurologic improvement since baseline. Though no patients had devices removed because of ineffectiveness, five patients’ devices were removed because of infection while infections in three other patients resolved.

“Being able to offer something that is not a pharmaceutical, without the side effects, that shows an even longer durability to that response is a really important finding at this point,” Dr. Petersen said.
 

Surgical considerations

Among the estimated 37 million Americans with type 1 or 2 diabetes, approximately one quarter of them experience some level of painful diabetic neuropathy, but medication and other medical management strategies are not always adequate in treating their pain. After a 1-week trial of spinal cord stimulation, the devices are implanted under the skin and rechargeable through the skin for up to 10 years, after which they can be replaced.

An appropriate candidate for spinal cord stimulation would be someone for whom existing non-invasive pain relief options, including medications, are ineffective or intolerable, Dr. Petersen and Dr. Markman both said. An adequate trial of medication is not “one size fits all” and will vary by each patient, added Dr. Markman, who is also interested in whether this study’s participants were able to have a reduction in use of pain relief medications.

“I think there’s a significant number of patients out there who can benefit from this, so I think that’s why it’s promising and exciting,” Dr. Markman said. “I do think it’s important to see if this actually allows them to be on less medication or whether stimulation turns out to be another treatment in addition to their baseline treatments.” The challenge is identifying “which patients are most likely to be benefiting from this and which are most likely to be harmed.”

Aside from infection from implantation, other possible risks include pain at the battery site and, in rare cases, a need for reoperation because of migration of the leads, he said.
 

Improvement in symptom severity and quality of life

After the wound from the implant has completely healed, Dr. Petersen said patients using the devices do not have any activity restrictions outside of magnetic interference, such as MRIs. “I’ve had people go back-country kayaking, scuba diving, fishing with their grandkids, all sorts of all sorts of things. If patients need to go through a scanner of any kind, they should ask whether it’s safe for pacemakers since these devices are like a “pacemaker for pain.

“I had a patient bring solar chargers with him so that he could recharge his battery in the backwoods while kayaking because that’s the level of improvement in pain that he got – from barely being able to walk down the hall to feeling comfortable being off the grid and active again,” Dr. Petersen said. “Those kinds of improvements in quality of life are massive.”

The study findings may also suggest that spinal cord stimulation can benefit a broader population of patients experiencing neuropathic pain, Dr. Markman said.

“There’s an extraordinary unmet need for treatments for neuropathy, and one important question here is the extent to which diabetic peripheral neuropathy and the response that we’re seeing here is a proxy for a broader effect across many neuropathies that are caused by other conditions other than diabetes,” Dr. Markman said. “There’s a lot of reason to think that this will be helpful not just for diabetes-related neuropathic pain, but for other types of neuropathic pain that have similar clinical presentations or clinical symptom patterns to diabetic peripheral neuropathy.”

The study was funded by Nevro, who manufactures the devices. Dr. Petersen and Dr. Markman both reported consulting with, receiving support from, holding stock options with, and serving on the data safety monitoring boards and advisory boards of numerous pharmaceutical companies.

Both pain relief and neurological improvements persisted in patients with diabetic neuropathy 2 years after they began receiving treatment with 10 kHz of spinal cord stimulation, according to research that released early, prior to its presentation at the annual meeting of the American Academy of Neurology.

The data represents the longest follow-up available for spinal cord stimulation at a frequency higher than the 60 Hz initially approved for diabetic neuropathy by the Food and Drug Administration, according to lead author Erika A. Petersen, MD, a professor of neurosurgery and the residency program director at the University of Arkansas for Medical Sciences, Little Rock.

University of Arkansas

“You would expect that somebody who continues to have diabetes for 24 months and has neuropathy would have worse neuropathy after 2 years, and what we’re seeing is that people were stable or better in terms of their nerve function at 2 years,” Dr. Petersen said in an interview. “So that’s really revolutionary.”
 

Encouraging preliminary findings

The findings are “promising and preliminary,” John D. Markman, MD, a professor in neurology and neurosurgery, vice chair for clinical research, and director of the Translational Pain Research Program at the University of Rochester (N.Y.) Medical Center, said in an interview. Dr. Markman, who was not involved in this study, said that, though the results are encouraging, it’s “less clear how much of [the pain improvement] is due to what we would consider to be on-target, pain-relieving benefit from stimulation versus other factors like expectation.” The crossover rate and amount of reduction in pain intensity are promising, but “I think that excitement is weighed against the fact that this is an open-label study.”

An underused treatment

Although spinal cord stimulation has been around since the late 1960s, its use only picked up steam in the 2000s, when it became more frequently used to treat chronic nerve damage related to neuropathic pain syndromes, Dr. Petersen explained. The FDA approved the treatment’s new indication for diabetic neuropathy in 2015, and data from Abbott and Medtronic have shown benefits from spinal cord stimulation at 60 Hz, but some patients are uncomfortable with the vibration or tingling feelings the devices can cause at that frequency.

“They describe creepy crawlies or ants crawling over the feet, or pins and needles, and painful sensitivity,” Dr. Petersen said. “You create a vibration feeling in the same zone where they already have those feelings of buzzing and pain and vibration, and it’s sometimes actually even more uncomfortable and less satisfying to them in terms of relief” with the spinal cord stimulation at 60 Hz, she said, “so there’s a lot of attrition in terms of who will actually use it.”

At 10 kHz, however, “people don’t feel any vibration or tingling associated with it; it just jams the signal of the pain,” she said. The difference between the frequencies is like that between “a lifeguard whistle and a dog whistle.”
 

Testing high-frequency stimulation

The new findings included the 24-month follow-up data from a randomized controlled trial that assessed the effectiveness of high-frequency spinal cord stimulation for painful diabetic neuropathy. The original 216 participants enrolled in the trial had diabetic neuropathy symptoms for at least 12 months and either could no not tolerate or did not respond to medications. Enrollment criteria also included lower-limb pain intensity of at least 5 on a 0-10 visual analogy scale and hemoglobin A1c of no more than 10%.

For the first 6 months of the trial – before crossover was offered – participants were randomly assigned to receive either 10 kHz of spinal cord stimulation along with conventional medical management or to receive conventional medical management alone. The 6-month data from 187 patients, as reported in April 2021 in JAMA Neurology, revealed that 79% of those receiving spinal cord stimulation experienced at least 50% improved pain relief without worsening of their baseline neurologic deficits, compared with only 5% of those receiving only conventional treatments.

Average pain levels increased 2% in the control participants compared with a decrease of 76% in those with the spinal cord stimulation devices. In addition, 62% of the patients receiving spinal cord stimulation demonstration neurologic improvement in reflexes, strength, movement and sensation, compared with 3% of those in the control group. The study’s findings led the FDA to approve the device using 10 kHz.

At 6 months, 93% of control patients crossed over to receiving spinal cord stimulation while none with the devices opted to stop their spinal cord stimulation. The 12-month data revealed that 85% of those receiving spinal cord stimulation experienced at least 50% pain relief, with the average pain relief at 74%. Patients also reported statistically significant improved quality of life as well as less interference with sleep, mood, and daily activities from pain.

Two years after baseline, patients’ pain relief was maintained with average 80% improvement, and 66% of patients showed neurologic improvement since baseline. Though no patients had devices removed because of ineffectiveness, five patients’ devices were removed because of infection while infections in three other patients resolved.

“Being able to offer something that is not a pharmaceutical, without the side effects, that shows an even longer durability to that response is a really important finding at this point,” Dr. Petersen said.
 

Surgical considerations

Among the estimated 37 million Americans with type 1 or 2 diabetes, approximately one quarter of them experience some level of painful diabetic neuropathy, but medication and other medical management strategies are not always adequate in treating their pain. After a 1-week trial of spinal cord stimulation, the devices are implanted under the skin and rechargeable through the skin for up to 10 years, after which they can be replaced.

An appropriate candidate for spinal cord stimulation would be someone for whom existing non-invasive pain relief options, including medications, are ineffective or intolerable, Dr. Petersen and Dr. Markman both said. An adequate trial of medication is not “one size fits all” and will vary by each patient, added Dr. Markman, who is also interested in whether this study’s participants were able to have a reduction in use of pain relief medications.

“I think there’s a significant number of patients out there who can benefit from this, so I think that’s why it’s promising and exciting,” Dr. Markman said. “I do think it’s important to see if this actually allows them to be on less medication or whether stimulation turns out to be another treatment in addition to their baseline treatments.” The challenge is identifying “which patients are most likely to be benefiting from this and which are most likely to be harmed.”

Aside from infection from implantation, other possible risks include pain at the battery site and, in rare cases, a need for reoperation because of migration of the leads, he said.
 

Improvement in symptom severity and quality of life

After the wound from the implant has completely healed, Dr. Petersen said patients using the devices do not have any activity restrictions outside of magnetic interference, such as MRIs. “I’ve had people go back-country kayaking, scuba diving, fishing with their grandkids, all sorts of all sorts of things. If patients need to go through a scanner of any kind, they should ask whether it’s safe for pacemakers since these devices are like a “pacemaker for pain.

“I had a patient bring solar chargers with him so that he could recharge his battery in the backwoods while kayaking because that’s the level of improvement in pain that he got – from barely being able to walk down the hall to feeling comfortable being off the grid and active again,” Dr. Petersen said. “Those kinds of improvements in quality of life are massive.”

The study findings may also suggest that spinal cord stimulation can benefit a broader population of patients experiencing neuropathic pain, Dr. Markman said.

“There’s an extraordinary unmet need for treatments for neuropathy, and one important question here is the extent to which diabetic peripheral neuropathy and the response that we’re seeing here is a proxy for a broader effect across many neuropathies that are caused by other conditions other than diabetes,” Dr. Markman said. “There’s a lot of reason to think that this will be helpful not just for diabetes-related neuropathic pain, but for other types of neuropathic pain that have similar clinical presentations or clinical symptom patterns to diabetic peripheral neuropathy.”

The study was funded by Nevro, who manufactures the devices. Dr. Petersen and Dr. Markman both reported consulting with, receiving support from, holding stock options with, and serving on the data safety monitoring boards and advisory boards of numerous pharmaceutical companies.

Acute pain is a primary symptom for many patients who present to the emergency department (ED). The ED team is challenged with relieving pain while limiting harm from medications.¹ A 2017 National Health Interview Survey showed that compared with nonveterans, more veterans reported pain in the previous 3 months, and the rate of severe pain was 40% higher in the veteran group especially among those who served during the era of wars in Afghanistan and Iraq.²

The American College of Emergency Physicians guidelines pain management guidelines recommend patient-centered shared decision making that includes patient education about treatment goals and expectations, and short- and long-term risks, as well as a preference toward pharmacologic treatment with nonopioid analgesics except for patients with severe pain or pain refractory to other drug and treatment modalities.³ There is a lack of evidence regarding superior efficacy of either opioid or nonopioid analgesics; therefore, the use of nonopioid analgesics, such as oral or topical nonsteroidal anti-inflammatory drugs (NSAIDs) or central analgesics, such as acetaminophen, is preferred for treating acute pain to mitigate adverse effects (AEs) and risks associated with opioid use.^1,3,4 The US Department of Veterans Affairs (VA) and Department of Defense (DoD) guideline on managing opioid therapy for chronic pain, updated in 2017 and 2022, similarly recommends alternatives to opioids for mild-to-moderate acute pain and encourages multimodal pain care.⁵ However, use of other pharmacologic treatments, such as NSAIDs, is limited by AE profiles, patient contraindications, and severity of acute pain etiologies. There is a need for the expanded use of nonpharmacologic treatments for addressing pain in the veteran population.

The American College of Emergency Physicians guidelines recommend nonpharmacologic modalities, such as applying heat or cold, physical therapy, cognitive behavioral therapy, and acupuncture.³ A 2014 study reported that 37% to 46% of active duty and reserve military personnel use complementary and alternative medicine (CAM) for a variety of ailments, and there is increasing interest in the use of CAM as adjuncts to traditional therapies.⁶ According to one study, some CAM therapies are used significantly more by military personnel than used by civilians.⁷ However, the percentage of the veteran population using acupuncture in this study was small, and more information is needed to assess its use.

Auricular acupuncture originated in traditional Chinese medicine.⁸ Contemporary auricular acupuncture experts view this modality as a self-contained microsystem mapping portions of the ear to specific parts of the body and internal organs. The analgesic effects may be mediated through the central nervous system by local release of endorphins through nerve fiber activation and neurotransmitters—including serotonin, dopamine, and norepinephrine—leading to pre- and postsynaptic suppression of pain transmission.

Battlefield acupuncture (BFA) uses 5 set points anatomically located on each ear.⁹ Practitioners use small semipermanent, dartlike acupuncture needles. Patients could experience pain relief in a few minutes, which can last minutes, hours, days, weeks, or months depending on the pathology of the pain. This procedure developed in 2001 has been studied for different pain types and has shown benefit when used for postsurgical pain, chronic spinal cord injury−related neuropathic pain, and general chronic pain, as well as for other indications, such as insomnia, depression, and weight loss.^8,10-13 In 2018, a randomized controlled trial compared postintervention numeric rating scale (NRS) pain scores in patients presenting to the ED with acute or acute-on-chronic lower back pain who received BFA as an adjunct to standard care vs standard care alone.¹⁴ Patients receiving BFA as an adjunct to standard care were found to have mean postintervention pain scores 1.7 points lower than those receiving standard care alone. This study demonstrated that BFA was feasible and well tolerated for lower back pain in the ED as an adjunct to standard care. The study was limited by the adjunct use of BFA rather than as monotherapy and by the practitioners’ discretion regarding standard care, which was not defined by the study’s authors.

The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in Chicago, Illinois, offers several CAM modalities, such as exercise/movement therapy, chiropractic, art/music therapy, and relaxation workshops, which are widely used by veterans. Recent evidence suggests BFA could reduce pain scores as an adjunct or an alternative to pharmacologic therapy. We are interested in how CAM therapies, such as BFA, can help avoid AEs associated with opioid or NSAID therapy.

At the JBVAMC ED, ketorolac 15 mg is the preferred first-line treatment of acute, noncancer pain, based on the results of previous studies. In 2018 BFA was offered first to veterans presenting with acute or acute-on-chronic pain to the ED; however, its effectiveness for pain reduction vs ketorolac has not been evaluated in this patient population. Limited literature is available on BFA and its use in the ED. To our knowledge, this was the first observational study assessing the difference between a single session of BFA vs a single dose of ketorolac in treating noncancer acute or acute-on-chronic pain in the ED.

Methods

This study was a retrospective chart review of patients who presented to the JBVAMC ED with acute pain or acute-on-chronic pain, who received ketorolac or BFA. The study population was generated from a list of all IV and intramuscular (IM) ketorolac unit dose orders verified from June 1, 2018, through August 30, 2019, and a list of all BFA procedure notes signed from June 1, 2018, through August 30, 2019. Patients were included in the study if they had documented administration of IV or IM ketorolac or BFA between June 1, 2018, and August 30, 2019. Patients who received ketorolac doses other than 15 mg, the intervention was administered outside of the ED, received adjunct treatment in addition to the treatment intervention in the ED, had no baseline NRS pain score documented before the intervention, had an NRS pain score of < 4, had no postintervention NRS pain score documented within 6 hours, had a treatment indication other than pain, or had active cancer were excluded. As in previous JBVAMC studies, we used NRS pain score cutoffs (mild, moderate, severe, and very severe) based on Woo and colleagues’ meta-analysis and excluded scores < 4.¹⁵

Endpoints

The primary endpoint was the mean difference in NRS pain score before and after the intervention, determined by comparing the NRS pain score documented at triage to the ED with the first documented NRS pain score at least 30 minutes to 6 hours after treatment administration. The secondary endpoints included the number of patients prescribed pain medication at discharge, the number of patients who were discharged with no medications, and the number of patients admitted to the hospital. The safety endpoint included any AEs of the intervention. Subgroup analyses were performed comparing the mean difference in NRS pain score among subgroups classified by severity of baseline NRS pain score and pain location.

Statistical Analysis

Baseline characteristics and endpoints were analyzed using descriptive statistics. Categorical data were analyzed using Fisher exact test and z test for proportions, and continuous data were compared using t test and paired t test. An 80% power calculation determined that 84 patients per group were needed to detect a statistically significant difference in pain score reduction of 1.3 at a type-1 error rate of 0.05. The sample size was based on a calculation performed in a previously published study that compared IV ketorolac at 3 single-dose regimens for treating acute pain in the ED.¹⁶ The 1.3 pain score reduction is considered the minimum clinically significant difference in pain that could be detected with the NRS.¹⁷

Results

Sixty-one patients received BFA during the study period: 31 were excluded (26 received adjunct treatment in the ED, 2 had active cancer documented, 2 had an indication other than pain, and 1 received BFA outside of the ED), leaving 30 patients in the BFA cohort. During the study period, 1299 patients received ketorolac. These patients were selected using a random number generator and then screened to determine inclusion or exclusion in the study. We continued to randomly select patients for the ketorolac group until we had a similar number in each treatment group. Of these 148 patients who were randomly selected to be reviewed, 116 were excluded: 48 received adjunct treatment in the ED, 24 had no postintervention NRS pain score documented within 6 hours, 18 received ketorolac doses other than 15 mg, 12 received ketorolac outside the ED, 9 had no baseline NRS pain score documented, 3 presented with a NRS pain score of ≤ 3, and 2 had active cancer documented. The ketorolac cohort comprised 31 patients.

Baseline characteristics were similar between the 2 groups except for the average baseline NRS pain score, which was statistically significantly higher in the BFA vs ketorolac group (8.7 vs 7.7, respectively; P = .02). The mean age was 51 years in the BFA group and 48 years in the ketorolac group. Most patients in each cohort were male: 80% in the BFA group and 71% in the ketorolac group. The most common types of pain documented as the chief ED presentation included back, lower extremity, and head.

Endpoints

The mean difference in NRS pain score was 3.9 for the BFA group and 5.1 for the ketorolac group. Both were clinically and statistically significant reductions (P = .03 and P < .01), but the difference between the intervention groups in NRS score reduction was not statistically significant (P = .07).

For the secondary endpoint of outpatient prescriptions written at discharge, there was no significant difference between the groups except for oral NSAIDs, which were more likely to be prescribed to patients who received ketorolac (P = .01).

Subgroup Analysis

An analysis was performed for subgroups classified by baseline NRS pain score (mild: 4; moderate, 5 - 6; severe, 7 - 9; and very severe, 10). Data for mild pain was limited because a small number of patients received interventions. For moderate pain, the mean difference in NRS pain score for BFA and ketorolac was 3.5 and 3.8, respectively; for severe pain, 3.4 and 5.3; and for very severe pain, 4.6 and 6.4. There was a larger difference in the preintervention and postintervention NRS pain scores within severe pain and very severe pain groups.

Discussion

Both interventions resulted in a significant reduction in the mean NRS pain score of about 4 to 5 points within their group, and BFA resulted in a similar NRS pain score reduction compared with ketorolac 15 mg. Because the baseline NRS pain scores were significantly different between the BFA and ketorolac groups, a subgroup analysis revealed that BFA reduced mean NRS pain score in patients with severe and very severe pain but appears to be less beneficial for moderate pain, unlike the ketorolac results that showed a large reduction in all pain groups except for the small sample of patients with mild pain.

In this study, more patients in the BFA group presented to the ED with lower extremity pain, such as gout or neuropathy, compared with the ketorolac group; however, BFA did not result in a significantly different pain score reduction in this subgroup compared with ketorolac. Patients receiving BFA were more likely to receive topical analgesics or muscle relaxants at discharge; whereas those receiving ketorolac were significantly more likely to receive oral NSAIDs. Patients in this study also were more likely to be admitted to the hospital if they received ketorolac; however, for these patients, pain was secondary to their chief presentation, and the admitting physician’s familiarity with ketorolac might have been the reason for choosing this intervention. Reasons for the admissions were surgical observation, psychiatric stabilization, kidney/gallstones, rule out of acute coronary syndrome, pneumonia, and proctitis in the ketorolac group, and suicidal ideations in the BFA group.

Limitations

As a limited number of patients received BFA at JBVAMC, the study was not sufficiently powered to detect a difference in the primary outcome. Because BFA required a consultation to be entered in the electronic health record, in addition to time needed to perform the procedure, practitioners might have preferred IV/IM ketorolac during busy times in the ED, potentially leading to underrepresentation in the BFA group. Prescribing preferences might have differed among the rotating physicians, timing of the documentation of the NRS pain score could have differed based on the treatment intervention, and the investigators were unable to control or accurately assess whether patients had taken an analgesic medication before presenting to the ED. Because pain and the treating physician are subjective, patients who reported a higher baseline pain severity might have been more likely to be discharged with topical analgesics or muscle relaxants. One way to correct for this subjectivity would be to conduct a larger prospective trial with a single treating physician. Finally, ED encounters in this study were short, and there was no follow-up permitting identification of AEs.

Conclusions

NRS pain score reduction with BFA did not differ compared with ketorolac 15 mg for treating acute and acute-on-chronic pain in the ED. Although this study was underpowered, these results add to the limited existing literature, suggesting that both interventions could result in clinically significant pain score reductions for patients presenting to the ED with severe and very severe pain, making BFA a viable nonpharmacologic option. Future studies could include investigating the benefit of BFA in the veteran population by studying larger samples in the ED, surveying patients after their interventions to identify rates AEs, and exploring the use of BFA for chronic pain in the outpatient setting.

Acute pain is a primary symptom for many patients who present to the emergency department (ED). The ED team is challenged with relieving pain while limiting harm from medications.¹ A 2017 National Health Interview Survey showed that compared with nonveterans, more veterans reported pain in the previous 3 months, and the rate of severe pain was 40% higher in the veteran group especially among those who served during the era of wars in Afghanistan and Iraq.²

The American College of Emergency Physicians guidelines pain management guidelines recommend patient-centered shared decision making that includes patient education about treatment goals and expectations, and short- and long-term risks, as well as a preference toward pharmacologic treatment with nonopioid analgesics except for patients with severe pain or pain refractory to other drug and treatment modalities.³ There is a lack of evidence regarding superior efficacy of either opioid or nonopioid analgesics; therefore, the use of nonopioid analgesics, such as oral or topical nonsteroidal anti-inflammatory drugs (NSAIDs) or central analgesics, such as acetaminophen, is preferred for treating acute pain to mitigate adverse effects (AEs) and risks associated with opioid use.^1,3,4 The US Department of Veterans Affairs (VA) and Department of Defense (DoD) guideline on managing opioid therapy for chronic pain, updated in 2017 and 2022, similarly recommends alternatives to opioids for mild-to-moderate acute pain and encourages multimodal pain care.⁵ However, use of other pharmacologic treatments, such as NSAIDs, is limited by AE profiles, patient contraindications, and severity of acute pain etiologies. There is a need for the expanded use of nonpharmacologic treatments for addressing pain in the veteran population.

The American College of Emergency Physicians guidelines recommend nonpharmacologic modalities, such as applying heat or cold, physical therapy, cognitive behavioral therapy, and acupuncture.³ A 2014 study reported that 37% to 46% of active duty and reserve military personnel use complementary and alternative medicine (CAM) for a variety of ailments, and there is increasing interest in the use of CAM as adjuncts to traditional therapies.⁶ According to one study, some CAM therapies are used significantly more by military personnel than used by civilians.⁷ However, the percentage of the veteran population using acupuncture in this study was small, and more information is needed to assess its use.

Auricular acupuncture originated in traditional Chinese medicine.⁸ Contemporary auricular acupuncture experts view this modality as a self-contained microsystem mapping portions of the ear to specific parts of the body and internal organs. The analgesic effects may be mediated through the central nervous system by local release of endorphins through nerve fiber activation and neurotransmitters—including serotonin, dopamine, and norepinephrine—leading to pre- and postsynaptic suppression of pain transmission.

Battlefield acupuncture (BFA) uses 5 set points anatomically located on each ear.⁹ Practitioners use small semipermanent, dartlike acupuncture needles. Patients could experience pain relief in a few minutes, which can last minutes, hours, days, weeks, or months depending on the pathology of the pain. This procedure developed in 2001 has been studied for different pain types and has shown benefit when used for postsurgical pain, chronic spinal cord injury−related neuropathic pain, and general chronic pain, as well as for other indications, such as insomnia, depression, and weight loss.^8,10-13 In 2018, a randomized controlled trial compared postintervention numeric rating scale (NRS) pain scores in patients presenting to the ED with acute or acute-on-chronic lower back pain who received BFA as an adjunct to standard care vs standard care alone.¹⁴ Patients receiving BFA as an adjunct to standard care were found to have mean postintervention pain scores 1.7 points lower than those receiving standard care alone. This study demonstrated that BFA was feasible and well tolerated for lower back pain in the ED as an adjunct to standard care. The study was limited by the adjunct use of BFA rather than as monotherapy and by the practitioners’ discretion regarding standard care, which was not defined by the study’s authors.

The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in Chicago, Illinois, offers several CAM modalities, such as exercise/movement therapy, chiropractic, art/music therapy, and relaxation workshops, which are widely used by veterans. Recent evidence suggests BFA could reduce pain scores as an adjunct or an alternative to pharmacologic therapy. We are interested in how CAM therapies, such as BFA, can help avoid AEs associated with opioid or NSAID therapy.

At the JBVAMC ED, ketorolac 15 mg is the preferred first-line treatment of acute, noncancer pain, based on the results of previous studies. In 2018 BFA was offered first to veterans presenting with acute or acute-on-chronic pain to the ED; however, its effectiveness for pain reduction vs ketorolac has not been evaluated in this patient population. Limited literature is available on BFA and its use in the ED. To our knowledge, this was the first observational study assessing the difference between a single session of BFA vs a single dose of ketorolac in treating noncancer acute or acute-on-chronic pain in the ED.

Methods

This study was a retrospective chart review of patients who presented to the JBVAMC ED with acute pain or acute-on-chronic pain, who received ketorolac or BFA. The study population was generated from a list of all IV and intramuscular (IM) ketorolac unit dose orders verified from June 1, 2018, through August 30, 2019, and a list of all BFA procedure notes signed from June 1, 2018, through August 30, 2019. Patients were included in the study if they had documented administration of IV or IM ketorolac or BFA between June 1, 2018, and August 30, 2019. Patients who received ketorolac doses other than 15 mg, the intervention was administered outside of the ED, received adjunct treatment in addition to the treatment intervention in the ED, had no baseline NRS pain score documented before the intervention, had an NRS pain score of < 4, had no postintervention NRS pain score documented within 6 hours, had a treatment indication other than pain, or had active cancer were excluded. As in previous JBVAMC studies, we used NRS pain score cutoffs (mild, moderate, severe, and very severe) based on Woo and colleagues’ meta-analysis and excluded scores < 4.¹⁵

Endpoints

The primary endpoint was the mean difference in NRS pain score before and after the intervention, determined by comparing the NRS pain score documented at triage to the ED with the first documented NRS pain score at least 30 minutes to 6 hours after treatment administration. The secondary endpoints included the number of patients prescribed pain medication at discharge, the number of patients who were discharged with no medications, and the number of patients admitted to the hospital. The safety endpoint included any AEs of the intervention. Subgroup analyses were performed comparing the mean difference in NRS pain score among subgroups classified by severity of baseline NRS pain score and pain location.

Statistical Analysis

Baseline characteristics and endpoints were analyzed using descriptive statistics. Categorical data were analyzed using Fisher exact test and z test for proportions, and continuous data were compared using t test and paired t test. An 80% power calculation determined that 84 patients per group were needed to detect a statistically significant difference in pain score reduction of 1.3 at a type-1 error rate of 0.05. The sample size was based on a calculation performed in a previously published study that compared IV ketorolac at 3 single-dose regimens for treating acute pain in the ED.¹⁶ The 1.3 pain score reduction is considered the minimum clinically significant difference in pain that could be detected with the NRS.¹⁷

Results

Sixty-one patients received BFA during the study period: 31 were excluded (26 received adjunct treatment in the ED, 2 had active cancer documented, 2 had an indication other than pain, and 1 received BFA outside of the ED), leaving 30 patients in the BFA cohort. During the study period, 1299 patients received ketorolac. These patients were selected using a random number generator and then screened to determine inclusion or exclusion in the study. We continued to randomly select patients for the ketorolac group until we had a similar number in each treatment group. Of these 148 patients who were randomly selected to be reviewed, 116 were excluded: 48 received adjunct treatment in the ED, 24 had no postintervention NRS pain score documented within 6 hours, 18 received ketorolac doses other than 15 mg, 12 received ketorolac outside the ED, 9 had no baseline NRS pain score documented, 3 presented with a NRS pain score of ≤ 3, and 2 had active cancer documented. The ketorolac cohort comprised 31 patients.

Baseline characteristics were similar between the 2 groups except for the average baseline NRS pain score, which was statistically significantly higher in the BFA vs ketorolac group (8.7 vs 7.7, respectively; P = .02). The mean age was 51 years in the BFA group and 48 years in the ketorolac group. Most patients in each cohort were male: 80% in the BFA group and 71% in the ketorolac group. The most common types of pain documented as the chief ED presentation included back, lower extremity, and head.

Endpoints

The mean difference in NRS pain score was 3.9 for the BFA group and 5.1 for the ketorolac group. Both were clinically and statistically significant reductions (P = .03 and P < .01), but the difference between the intervention groups in NRS score reduction was not statistically significant (P = .07).

For the secondary endpoint of outpatient prescriptions written at discharge, there was no significant difference between the groups except for oral NSAIDs, which were more likely to be prescribed to patients who received ketorolac (P = .01).

Subgroup Analysis

An analysis was performed for subgroups classified by baseline NRS pain score (mild: 4; moderate, 5 - 6; severe, 7 - 9; and very severe, 10). Data for mild pain was limited because a small number of patients received interventions. For moderate pain, the mean difference in NRS pain score for BFA and ketorolac was 3.5 and 3.8, respectively; for severe pain, 3.4 and 5.3; and for very severe pain, 4.6 and 6.4. There was a larger difference in the preintervention and postintervention NRS pain scores within severe pain and very severe pain groups.

Discussion

Both interventions resulted in a significant reduction in the mean NRS pain score of about 4 to 5 points within their group, and BFA resulted in a similar NRS pain score reduction compared with ketorolac 15 mg. Because the baseline NRS pain scores were significantly different between the BFA and ketorolac groups, a subgroup analysis revealed that BFA reduced mean NRS pain score in patients with severe and very severe pain but appears to be less beneficial for moderate pain, unlike the ketorolac results that showed a large reduction in all pain groups except for the small sample of patients with mild pain.

In this study, more patients in the BFA group presented to the ED with lower extremity pain, such as gout or neuropathy, compared with the ketorolac group; however, BFA did not result in a significantly different pain score reduction in this subgroup compared with ketorolac. Patients receiving BFA were more likely to receive topical analgesics or muscle relaxants at discharge; whereas those receiving ketorolac were significantly more likely to receive oral NSAIDs. Patients in this study also were more likely to be admitted to the hospital if they received ketorolac; however, for these patients, pain was secondary to their chief presentation, and the admitting physician’s familiarity with ketorolac might have been the reason for choosing this intervention. Reasons for the admissions were surgical observation, psychiatric stabilization, kidney/gallstones, rule out of acute coronary syndrome, pneumonia, and proctitis in the ketorolac group, and suicidal ideations in the BFA group.

Limitations

As a limited number of patients received BFA at JBVAMC, the study was not sufficiently powered to detect a difference in the primary outcome. Because BFA required a consultation to be entered in the electronic health record, in addition to time needed to perform the procedure, practitioners might have preferred IV/IM ketorolac during busy times in the ED, potentially leading to underrepresentation in the BFA group. Prescribing preferences might have differed among the rotating physicians, timing of the documentation of the NRS pain score could have differed based on the treatment intervention, and the investigators were unable to control or accurately assess whether patients had taken an analgesic medication before presenting to the ED. Because pain and the treating physician are subjective, patients who reported a higher baseline pain severity might have been more likely to be discharged with topical analgesics or muscle relaxants. One way to correct for this subjectivity would be to conduct a larger prospective trial with a single treating physician. Finally, ED encounters in this study were short, and there was no follow-up permitting identification of AEs.

Conclusions

NRS pain score reduction with BFA did not differ compared with ketorolac 15 mg for treating acute and acute-on-chronic pain in the ED. Although this study was underpowered, these results add to the limited existing literature, suggesting that both interventions could result in clinically significant pain score reductions for patients presenting to the ED with severe and very severe pain, making BFA a viable nonpharmacologic option. Future studies could include investigating the benefit of BFA in the veteran population by studying larger samples in the ED, surveying patients after their interventions to identify rates AEs, and exploring the use of BFA for chronic pain in the outpatient setting.

Acute pain is a primary symptom for many patients who present to the emergency department (ED). The ED team is challenged with relieving pain while limiting harm from medications.¹ A 2017 National Health Interview Survey showed that compared with nonveterans, more veterans reported pain in the previous 3 months, and the rate of severe pain was 40% higher in the veteran group especially among those who served during the era of wars in Afghanistan and Iraq.²

The American College of Emergency Physicians guidelines pain management guidelines recommend patient-centered shared decision making that includes patient education about treatment goals and expectations, and short- and long-term risks, as well as a preference toward pharmacologic treatment with nonopioid analgesics except for patients with severe pain or pain refractory to other drug and treatment modalities.³ There is a lack of evidence regarding superior efficacy of either opioid or nonopioid analgesics; therefore, the use of nonopioid analgesics, such as oral or topical nonsteroidal anti-inflammatory drugs (NSAIDs) or central analgesics, such as acetaminophen, is preferred for treating acute pain to mitigate adverse effects (AEs) and risks associated with opioid use.^1,3,4 The US Department of Veterans Affairs (VA) and Department of Defense (DoD) guideline on managing opioid therapy for chronic pain, updated in 2017 and 2022, similarly recommends alternatives to opioids for mild-to-moderate acute pain and encourages multimodal pain care.⁵ However, use of other pharmacologic treatments, such as NSAIDs, is limited by AE profiles, patient contraindications, and severity of acute pain etiologies. There is a need for the expanded use of nonpharmacologic treatments for addressing pain in the veteran population.

The American College of Emergency Physicians guidelines recommend nonpharmacologic modalities, such as applying heat or cold, physical therapy, cognitive behavioral therapy, and acupuncture.³ A 2014 study reported that 37% to 46% of active duty and reserve military personnel use complementary and alternative medicine (CAM) for a variety of ailments, and there is increasing interest in the use of CAM as adjuncts to traditional therapies.⁶ According to one study, some CAM therapies are used significantly more by military personnel than used by civilians.⁷ However, the percentage of the veteran population using acupuncture in this study was small, and more information is needed to assess its use.

Auricular acupuncture originated in traditional Chinese medicine.⁸ Contemporary auricular acupuncture experts view this modality as a self-contained microsystem mapping portions of the ear to specific parts of the body and internal organs. The analgesic effects may be mediated through the central nervous system by local release of endorphins through nerve fiber activation and neurotransmitters—including serotonin, dopamine, and norepinephrine—leading to pre- and postsynaptic suppression of pain transmission.

Battlefield acupuncture (BFA) uses 5 set points anatomically located on each ear.⁹ Practitioners use small semipermanent, dartlike acupuncture needles. Patients could experience pain relief in a few minutes, which can last minutes, hours, days, weeks, or months depending on the pathology of the pain. This procedure developed in 2001 has been studied for different pain types and has shown benefit when used for postsurgical pain, chronic spinal cord injury−related neuropathic pain, and general chronic pain, as well as for other indications, such as insomnia, depression, and weight loss.^8,10-13 In 2018, a randomized controlled trial compared postintervention numeric rating scale (NRS) pain scores in patients presenting to the ED with acute or acute-on-chronic lower back pain who received BFA as an adjunct to standard care vs standard care alone.¹⁴ Patients receiving BFA as an adjunct to standard care were found to have mean postintervention pain scores 1.7 points lower than those receiving standard care alone. This study demonstrated that BFA was feasible and well tolerated for lower back pain in the ED as an adjunct to standard care. The study was limited by the adjunct use of BFA rather than as monotherapy and by the practitioners’ discretion regarding standard care, which was not defined by the study’s authors.

The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in Chicago, Illinois, offers several CAM modalities, such as exercise/movement therapy, chiropractic, art/music therapy, and relaxation workshops, which are widely used by veterans. Recent evidence suggests BFA could reduce pain scores as an adjunct or an alternative to pharmacologic therapy. We are interested in how CAM therapies, such as BFA, can help avoid AEs associated with opioid or NSAID therapy.

At the JBVAMC ED, ketorolac 15 mg is the preferred first-line treatment of acute, noncancer pain, based on the results of previous studies. In 2018 BFA was offered first to veterans presenting with acute or acute-on-chronic pain to the ED; however, its effectiveness for pain reduction vs ketorolac has not been evaluated in this patient population. Limited literature is available on BFA and its use in the ED. To our knowledge, this was the first observational study assessing the difference between a single session of BFA vs a single dose of ketorolac in treating noncancer acute or acute-on-chronic pain in the ED.

Methods

This study was a retrospective chart review of patients who presented to the JBVAMC ED with acute pain or acute-on-chronic pain, who received ketorolac or BFA. The study population was generated from a list of all IV and intramuscular (IM) ketorolac unit dose orders verified from June 1, 2018, through August 30, 2019, and a list of all BFA procedure notes signed from June 1, 2018, through August 30, 2019. Patients were included in the study if they had documented administration of IV or IM ketorolac or BFA between June 1, 2018, and August 30, 2019. Patients who received ketorolac doses other than 15 mg, the intervention was administered outside of the ED, received adjunct treatment in addition to the treatment intervention in the ED, had no baseline NRS pain score documented before the intervention, had an NRS pain score of < 4, had no postintervention NRS pain score documented within 6 hours, had a treatment indication other than pain, or had active cancer were excluded. As in previous JBVAMC studies, we used NRS pain score cutoffs (mild, moderate, severe, and very severe) based on Woo and colleagues’ meta-analysis and excluded scores < 4.¹⁵

Endpoints

The primary endpoint was the mean difference in NRS pain score before and after the intervention, determined by comparing the NRS pain score documented at triage to the ED with the first documented NRS pain score at least 30 minutes to 6 hours after treatment administration. The secondary endpoints included the number of patients prescribed pain medication at discharge, the number of patients who were discharged with no medications, and the number of patients admitted to the hospital. The safety endpoint included any AEs of the intervention. Subgroup analyses were performed comparing the mean difference in NRS pain score among subgroups classified by severity of baseline NRS pain score and pain location.

Statistical Analysis

Baseline characteristics and endpoints were analyzed using descriptive statistics. Categorical data were analyzed using Fisher exact test and z test for proportions, and continuous data were compared using t test and paired t test. An 80% power calculation determined that 84 patients per group were needed to detect a statistically significant difference in pain score reduction of 1.3 at a type-1 error rate of 0.05. The sample size was based on a calculation performed in a previously published study that compared IV ketorolac at 3 single-dose regimens for treating acute pain in the ED.¹⁶ The 1.3 pain score reduction is considered the minimum clinically significant difference in pain that could be detected with the NRS.¹⁷

Results

Sixty-one patients received BFA during the study period: 31 were excluded (26 received adjunct treatment in the ED, 2 had active cancer documented, 2 had an indication other than pain, and 1 received BFA outside of the ED), leaving 30 patients in the BFA cohort. During the study period, 1299 patients received ketorolac. These patients were selected using a random number generator and then screened to determine inclusion or exclusion in the study. We continued to randomly select patients for the ketorolac group until we had a similar number in each treatment group. Of these 148 patients who were randomly selected to be reviewed, 116 were excluded: 48 received adjunct treatment in the ED, 24 had no postintervention NRS pain score documented within 6 hours, 18 received ketorolac doses other than 15 mg, 12 received ketorolac outside the ED, 9 had no baseline NRS pain score documented, 3 presented with a NRS pain score of ≤ 3, and 2 had active cancer documented. The ketorolac cohort comprised 31 patients.

Baseline characteristics were similar between the 2 groups except for the average baseline NRS pain score, which was statistically significantly higher in the BFA vs ketorolac group (8.7 vs 7.7, respectively; P = .02). The mean age was 51 years in the BFA group and 48 years in the ketorolac group. Most patients in each cohort were male: 80% in the BFA group and 71% in the ketorolac group. The most common types of pain documented as the chief ED presentation included back, lower extremity, and head.

Endpoints

The mean difference in NRS pain score was 3.9 for the BFA group and 5.1 for the ketorolac group. Both were clinically and statistically significant reductions (P = .03 and P < .01), but the difference between the intervention groups in NRS score reduction was not statistically significant (P = .07).

For the secondary endpoint of outpatient prescriptions written at discharge, there was no significant difference between the groups except for oral NSAIDs, which were more likely to be prescribed to patients who received ketorolac (P = .01).

Subgroup Analysis

An analysis was performed for subgroups classified by baseline NRS pain score (mild: 4; moderate, 5 - 6; severe, 7 - 9; and very severe, 10). Data for mild pain was limited because a small number of patients received interventions. For moderate pain, the mean difference in NRS pain score for BFA and ketorolac was 3.5 and 3.8, respectively; for severe pain, 3.4 and 5.3; and for very severe pain, 4.6 and 6.4. There was a larger difference in the preintervention and postintervention NRS pain scores within severe pain and very severe pain groups.

Discussion

Both interventions resulted in a significant reduction in the mean NRS pain score of about 4 to 5 points within their group, and BFA resulted in a similar NRS pain score reduction compared with ketorolac 15 mg. Because the baseline NRS pain scores were significantly different between the BFA and ketorolac groups, a subgroup analysis revealed that BFA reduced mean NRS pain score in patients with severe and very severe pain but appears to be less beneficial for moderate pain, unlike the ketorolac results that showed a large reduction in all pain groups except for the small sample of patients with mild pain.

In this study, more patients in the BFA group presented to the ED with lower extremity pain, such as gout or neuropathy, compared with the ketorolac group; however, BFA did not result in a significantly different pain score reduction in this subgroup compared with ketorolac. Patients receiving BFA were more likely to receive topical analgesics or muscle relaxants at discharge; whereas those receiving ketorolac were significantly more likely to receive oral NSAIDs. Patients in this study also were more likely to be admitted to the hospital if they received ketorolac; however, for these patients, pain was secondary to their chief presentation, and the admitting physician’s familiarity with ketorolac might have been the reason for choosing this intervention. Reasons for the admissions were surgical observation, psychiatric stabilization, kidney/gallstones, rule out of acute coronary syndrome, pneumonia, and proctitis in the ketorolac group, and suicidal ideations in the BFA group.

Limitations

As a limited number of patients received BFA at JBVAMC, the study was not sufficiently powered to detect a difference in the primary outcome. Because BFA required a consultation to be entered in the electronic health record, in addition to time needed to perform the procedure, practitioners might have preferred IV/IM ketorolac during busy times in the ED, potentially leading to underrepresentation in the BFA group. Prescribing preferences might have differed among the rotating physicians, timing of the documentation of the NRS pain score could have differed based on the treatment intervention, and the investigators were unable to control or accurately assess whether patients had taken an analgesic medication before presenting to the ED. Because pain and the treating physician are subjective, patients who reported a higher baseline pain severity might have been more likely to be discharged with topical analgesics or muscle relaxants. One way to correct for this subjectivity would be to conduct a larger prospective trial with a single treating physician. Finally, ED encounters in this study were short, and there was no follow-up permitting identification of AEs.

Conclusions

NRS pain score reduction with BFA did not differ compared with ketorolac 15 mg for treating acute and acute-on-chronic pain in the ED. Although this study was underpowered, these results add to the limited existing literature, suggesting that both interventions could result in clinically significant pain score reductions for patients presenting to the ED with severe and very severe pain, making BFA a viable nonpharmacologic option. Future studies could include investigating the benefit of BFA in the veteran population by studying larger samples in the ED, surveying patients after their interventions to identify rates AEs, and exploring the use of BFA for chronic pain in the outpatient setting.

For women with excessive menstrual blood loss, the contraceptive levonorgestrel 52 mg delivered via an intrauterine device (IUD) reduced monthly blood loss by more than 90% over six monthly cycles, a multicenter open-label study reports.

Median blood loss decreased by more than 90% in the first three cycles. Overall, treatment was successful in 81.8% of 99 patients (95% confidence interval, 74.2%-89.4%), according to findings published in Obstetrics & Gynecology.

Racially diverse cohort

Conducted at 29 U.S. sites prior to seeking FDA registration for this new use, the phase 3 open-label trial of the 52 mg progestin-releasing IUD enrolled 105 participants with a mean age of 35.4 years. Unlike previous trials, this one included obese or severely obese women (44.8%), with 42 participants having a body mass index (BMI) of more than 35 kg/m², and also 28 nulliparous women (27.6%).

Those with abnormalities such as fibroids or coagulopathies were excluded. Although most of the cohort was White (n = 68), the study included Black (n = 25), Asian (n = 4), and Hispanic (n = 10) women, plus 7 from other minorities, suggesting the results would be widely applicable.

Mean baseline blood loss in the cohort ranged from 73 mL to 520 mL (median, 143 mL). Of 89 treated women with follow-up, participants had a median absolute blood-loss decreases of 93.3% (86.1%-97.8%) at cycle three and 97.6% (90.4%-100%) at cycle six. Median bleeding reductions at cycle six were similar between women with and without obesity at 97.6% and 97.5%, respectively, and between nulliparous and parous women at 97.0% and 98.1%, respectively (P = .43). The study, however, was not sufficiently powered to fully analyze these subgroups, the authors acknowledged.

Although results were overall comparable with those of a previous study on a different IUD, the expulsion rate was somewhat higher, at 9%, than the 6% reported in the earlier study.

Brigham and Women’s Hospital

“Although this strategy for reducing blood loss is not new, this study is notable because it looked at high-BMI women and nulliparous women,” said Kathryn J. Gray, MD, PhD, an attending physician in the department of obstetrics and gynecology at Brigham and Women’s Hospital in Boston, who was not involved in the research.“No prior trials have included patients with BMIs exceeding 35 kg/m² or nulliparous patients, while this study enrolled a full array of patients, which allowed exploratory analyses of these subpopulations,” Dr. Creinin confirmed.

According to Dr. Gray, the IUD approach has advantages over systemic treatment with oral medication. “First, treatment is not user-dependent so the user doesn’t have to remember to take it. In addition, because the medication is locally targeted in the uterus, it is more effective and there is less fluctuation and variability in drug levels than when taken orally.”

As to treatment durability, Dr. Creinin said, “Long-term studies in a population being treated for heavy menstrual bleeding would be helpful to have an idea of how long this effect lasts. Still, there is no reason to expect that the effect will not last for many years.”

And with this treatment, he added, both patient and clinician can readily detect its effect. “If bleeding begins to increase, they will know!”

Would there be a lingering residual effect even after removal of the IUD? “That is an excellent question that remains to be answered,” Dr. Creinin said. “There are no data on when the heavy bleeding returns, but it would be expected to do so.”

This study was funded, designed, and supervised by Medicines360, which also provided the study treatment. Dr. Creinin disclosed financial relationships with various private-sector companies, including Medicines360, Organon, Fuji Pharma, GlaxoSmithKline, and Merck & Co. Multiple study coauthors disclosed similar financial ties to industry partners, including Medicines360. Dr. Gray had no potential conflicts of interest with regard to her comments.

For women with excessive menstrual blood loss, the contraceptive levonorgestrel 52 mg delivered via an intrauterine device (IUD) reduced monthly blood loss by more than 90% over six monthly cycles, a multicenter open-label study reports.

Median blood loss decreased by more than 90% in the first three cycles. Overall, treatment was successful in 81.8% of 99 patients (95% confidence interval, 74.2%-89.4%), according to findings published in Obstetrics & Gynecology.

Racially diverse cohort

Conducted at 29 U.S. sites prior to seeking FDA registration for this new use, the phase 3 open-label trial of the 52 mg progestin-releasing IUD enrolled 105 participants with a mean age of 35.4 years. Unlike previous trials, this one included obese or severely obese women (44.8%), with 42 participants having a body mass index (BMI) of more than 35 kg/m², and also 28 nulliparous women (27.6%).

Those with abnormalities such as fibroids or coagulopathies were excluded. Although most of the cohort was White (n = 68), the study included Black (n = 25), Asian (n = 4), and Hispanic (n = 10) women, plus 7 from other minorities, suggesting the results would be widely applicable.

Mean baseline blood loss in the cohort ranged from 73 mL to 520 mL (median, 143 mL). Of 89 treated women with follow-up, participants had a median absolute blood-loss decreases of 93.3% (86.1%-97.8%) at cycle three and 97.6% (90.4%-100%) at cycle six. Median bleeding reductions at cycle six were similar between women with and without obesity at 97.6% and 97.5%, respectively, and between nulliparous and parous women at 97.0% and 98.1%, respectively (P = .43). The study, however, was not sufficiently powered to fully analyze these subgroups, the authors acknowledged.

Although results were overall comparable with those of a previous study on a different IUD, the expulsion rate was somewhat higher, at 9%, than the 6% reported in the earlier study.

Brigham and Women’s Hospital

“Although this strategy for reducing blood loss is not new, this study is notable because it looked at high-BMI women and nulliparous women,” said Kathryn J. Gray, MD, PhD, an attending physician in the department of obstetrics and gynecology at Brigham and Women’s Hospital in Boston, who was not involved in the research.“No prior trials have included patients with BMIs exceeding 35 kg/m² or nulliparous patients, while this study enrolled a full array of patients, which allowed exploratory analyses of these subpopulations,” Dr. Creinin confirmed.

According to Dr. Gray, the IUD approach has advantages over systemic treatment with oral medication. “First, treatment is not user-dependent so the user doesn’t have to remember to take it. In addition, because the medication is locally targeted in the uterus, it is more effective and there is less fluctuation and variability in drug levels than when taken orally.”

As to treatment durability, Dr. Creinin said, “Long-term studies in a population being treated for heavy menstrual bleeding would be helpful to have an idea of how long this effect lasts. Still, there is no reason to expect that the effect will not last for many years.”

And with this treatment, he added, both patient and clinician can readily detect its effect. “If bleeding begins to increase, they will know!”

Would there be a lingering residual effect even after removal of the IUD? “That is an excellent question that remains to be answered,” Dr. Creinin said. “There are no data on when the heavy bleeding returns, but it would be expected to do so.”

This study was funded, designed, and supervised by Medicines360, which also provided the study treatment. Dr. Creinin disclosed financial relationships with various private-sector companies, including Medicines360, Organon, Fuji Pharma, GlaxoSmithKline, and Merck & Co. Multiple study coauthors disclosed similar financial ties to industry partners, including Medicines360. Dr. Gray had no potential conflicts of interest with regard to her comments.

For women with excessive menstrual blood loss, the contraceptive levonorgestrel 52 mg delivered via an intrauterine device (IUD) reduced monthly blood loss by more than 90% over six monthly cycles, a multicenter open-label study reports.

Median blood loss decreased by more than 90% in the first three cycles. Overall, treatment was successful in 81.8% of 99 patients (95% confidence interval, 74.2%-89.4%), according to findings published in Obstetrics & Gynecology.

Racially diverse cohort

Conducted at 29 U.S. sites prior to seeking FDA registration for this new use, the phase 3 open-label trial of the 52 mg progestin-releasing IUD enrolled 105 participants with a mean age of 35.4 years. Unlike previous trials, this one included obese or severely obese women (44.8%), with 42 participants having a body mass index (BMI) of more than 35 kg/m², and also 28 nulliparous women (27.6%).

Those with abnormalities such as fibroids or coagulopathies were excluded. Although most of the cohort was White (n = 68), the study included Black (n = 25), Asian (n = 4), and Hispanic (n = 10) women, plus 7 from other minorities, suggesting the results would be widely applicable.

Mean baseline blood loss in the cohort ranged from 73 mL to 520 mL (median, 143 mL). Of 89 treated women with follow-up, participants had a median absolute blood-loss decreases of 93.3% (86.1%-97.8%) at cycle three and 97.6% (90.4%-100%) at cycle six. Median bleeding reductions at cycle six were similar between women with and without obesity at 97.6% and 97.5%, respectively, and between nulliparous and parous women at 97.0% and 98.1%, respectively (P = .43). The study, however, was not sufficiently powered to fully analyze these subgroups, the authors acknowledged.

Although results were overall comparable with those of a previous study on a different IUD, the expulsion rate was somewhat higher, at 9%, than the 6% reported in the earlier study.

Brigham and Women’s Hospital

“Although this strategy for reducing blood loss is not new, this study is notable because it looked at high-BMI women and nulliparous women,” said Kathryn J. Gray, MD, PhD, an attending physician in the department of obstetrics and gynecology at Brigham and Women’s Hospital in Boston, who was not involved in the research.“No prior trials have included patients with BMIs exceeding 35 kg/m² or nulliparous patients, while this study enrolled a full array of patients, which allowed exploratory analyses of these subpopulations,” Dr. Creinin confirmed.

According to Dr. Gray, the IUD approach has advantages over systemic treatment with oral medication. “First, treatment is not user-dependent so the user doesn’t have to remember to take it. In addition, because the medication is locally targeted in the uterus, it is more effective and there is less fluctuation and variability in drug levels than when taken orally.”

As to treatment durability, Dr. Creinin said, “Long-term studies in a population being treated for heavy menstrual bleeding would be helpful to have an idea of how long this effect lasts. Still, there is no reason to expect that the effect will not last for many years.”

And with this treatment, he added, both patient and clinician can readily detect its effect. “If bleeding begins to increase, they will know!”

Would there be a lingering residual effect even after removal of the IUD? “That is an excellent question that remains to be answered,” Dr. Creinin said. “There are no data on when the heavy bleeding returns, but it would be expected to do so.”

This study was funded, designed, and supervised by Medicines360, which also provided the study treatment. Dr. Creinin disclosed financial relationships with various private-sector companies, including Medicines360, Organon, Fuji Pharma, GlaxoSmithKline, and Merck & Co. Multiple study coauthors disclosed similar financial ties to industry partners, including Medicines360. Dr. Gray had no potential conflicts of interest with regard to her comments.

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women&#039;s Hospital

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

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women&#039;s Hospital

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

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women&#039;s Hospital

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

Cluster headache and migraine have strong ties to the circadian system at multiple levels, say new findings that could have significant treatment implications.

A meta-analysis of 16 studies showed a circadian pattern in 71% of cluster headache attacks (3,490 of 4,953), with a clear circadian peak between 9:00 p.m. and 3:00 a.m.

Migraine was also associated with a circadian pattern in 50% of cases (2,698 of 5,385) across eight studies, with a clear circadian trough between 11:00 p.m. and 7:00 a.m.

Seasonal peaks were also evident for cluster headache (spring and autumn) and migraine (April to October).

“In the short term, these findings help us explain the timing to patients – for example, it is possible that a headache at 8 a.m. is due to their internal body clock instead of their pillow, or breakfast food, or morning medications,” lead investigator Mark Burish, MD, PhD, associate professor, department of neurosurgery, at University of Texas Health Houston, told this news organization.

“In the long term, these findings do suggest that medications that target the circadian system could be effective in migraine and headache patients,” Dr. Burish added.

The study was published online in Neurology.


 

Treatment implications?

Across studies, chronotype was “highly variable” for both cluster headache and migraine, the investigators report.

Cluster headache was associated with lower melatonin and higher cortisol levels, compared with non–cluster headache controls.

On a genetic level, cluster headache was associated with two core circadian genes (CLOCK and REV-ERB–alpha), and five of the nine genes that increase the likelihood of having cluster headache are genes with a circadian pattern of expression.

Migraine headache was associated with lower urinary melatonin levels and with the core circadian genes, CK1-delta and ROR-alpha, and 110 of the 168 genes associated with migraine were clock-controlled genes.

“The data suggest that both of these headache disorders are highly circadian at multiple levels, especially cluster headache,” Dr. Burish said in a release.

“This reinforces the importance of the hypothalamus – the area of the brain that houses the primary biological clock – and its role in cluster headache and migraine. It also raises the question of the genetics of triggers such as sleep changes that are known triggers for migraine and are cues for the body’s circadian rhythm,” Dr. Burish said.

“We hope that future research will look into circadian medications as a new treatment option for migraine and cluster headache patients,” Dr. Burish told this news organization.
 

Importance of sleep regulation

The authors of an accompanying editorial note that even though the study doesn’t have immediate clinical implications, it offers a better understanding of the way chronobiologic factors may influence treatment.

“At a minimum, interventions known to regulate and improve sleep (e.g., melatonin, cognitive behavioral therapy), and which are safe and straightforward to introduce, may be useful in some individuals susceptible to circadian misalignment or sleep disorders,” write Heidi Sutherland, PhD, and Lyn Griffiths, PhD, with Queensland University of Technology, Brisbane, Australia.

“Treatment of comorbidities (e.g., insomnia) that result in sleep disturbances may also help headache management. Furthermore, chronobiological aspects of any pharmacological interventions should be considered, as some frequently used headache and migraine drugs can modulate circadian cycles and influence the expression of circadian genes (e.g., verapamil), or have sleep-related side effects,” they add.

A limitation of the study was the lack of information on factors that could influence the circadian cycle, such as medications; other disorders, such as bipolar disorder; or circadian rhythm issues, such as night-shift work.

The study was supported by grants from the Japan Society for the Promotion of Science, the National Institutes of Health, The Welch Foundation, and The Will Erwin Headache Research Foundation. Dr. Burish is an unpaid member of the medical advisory board of Clusterbusters, and a site investigator for a cluster headache clinical trial funded by Lundbeck. Dr. Sutherland has received grant funding from the U.S. Migraine Research Foundation, and received institute support from Queensland University of Technology for genetics research. Dr. Griffiths has received grant funding from the Australian NHMRC, U.S. Department of Defense, and the U.S. Migraine Research Foundation, and consultancy funding from TEVA.

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

Cluster headache and migraine have strong ties to the circadian system at multiple levels, say new findings that could have significant treatment implications.

A meta-analysis of 16 studies showed a circadian pattern in 71% of cluster headache attacks (3,490 of 4,953), with a clear circadian peak between 9:00 p.m. and 3:00 a.m.

Migraine was also associated with a circadian pattern in 50% of cases (2,698 of 5,385) across eight studies, with a clear circadian trough between 11:00 p.m. and 7:00 a.m.

Seasonal peaks were also evident for cluster headache (spring and autumn) and migraine (April to October).

“In the short term, these findings help us explain the timing to patients – for example, it is possible that a headache at 8 a.m. is due to their internal body clock instead of their pillow, or breakfast food, or morning medications,” lead investigator Mark Burish, MD, PhD, associate professor, department of neurosurgery, at University of Texas Health Houston, told this news organization.

“In the long term, these findings do suggest that medications that target the circadian system could be effective in migraine and headache patients,” Dr. Burish added.

The study was published online in Neurology.


 

Treatment implications?

Across studies, chronotype was “highly variable” for both cluster headache and migraine, the investigators report.

Cluster headache was associated with lower melatonin and higher cortisol levels, compared with non–cluster headache controls.

On a genetic level, cluster headache was associated with two core circadian genes (CLOCK and REV-ERB–alpha), and five of the nine genes that increase the likelihood of having cluster headache are genes with a circadian pattern of expression.

Migraine headache was associated with lower urinary melatonin levels and with the core circadian genes, CK1-delta and ROR-alpha, and 110 of the 168 genes associated with migraine were clock-controlled genes.

“The data suggest that both of these headache disorders are highly circadian at multiple levels, especially cluster headache,” Dr. Burish said in a release.

“This reinforces the importance of the hypothalamus – the area of the brain that houses the primary biological clock – and its role in cluster headache and migraine. It also raises the question of the genetics of triggers such as sleep changes that are known triggers for migraine and are cues for the body’s circadian rhythm,” Dr. Burish said.

“We hope that future research will look into circadian medications as a new treatment option for migraine and cluster headache patients,” Dr. Burish told this news organization.
 

Importance of sleep regulation

The authors of an accompanying editorial note that even though the study doesn’t have immediate clinical implications, it offers a better understanding of the way chronobiologic factors may influence treatment.

“At a minimum, interventions known to regulate and improve sleep (e.g., melatonin, cognitive behavioral therapy), and which are safe and straightforward to introduce, may be useful in some individuals susceptible to circadian misalignment or sleep disorders,” write Heidi Sutherland, PhD, and Lyn Griffiths, PhD, with Queensland University of Technology, Brisbane, Australia.

“Treatment of comorbidities (e.g., insomnia) that result in sleep disturbances may also help headache management. Furthermore, chronobiological aspects of any pharmacological interventions should be considered, as some frequently used headache and migraine drugs can modulate circadian cycles and influence the expression of circadian genes (e.g., verapamil), or have sleep-related side effects,” they add.

A limitation of the study was the lack of information on factors that could influence the circadian cycle, such as medications; other disorders, such as bipolar disorder; or circadian rhythm issues, such as night-shift work.

The study was supported by grants from the Japan Society for the Promotion of Science, the National Institutes of Health, The Welch Foundation, and The Will Erwin Headache Research Foundation. Dr. Burish is an unpaid member of the medical advisory board of Clusterbusters, and a site investigator for a cluster headache clinical trial funded by Lundbeck. Dr. Sutherland has received grant funding from the U.S. Migraine Research Foundation, and received institute support from Queensland University of Technology for genetics research. Dr. Griffiths has received grant funding from the Australian NHMRC, U.S. Department of Defense, and the U.S. Migraine Research Foundation, and consultancy funding from TEVA.

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

Cluster headache and migraine have strong ties to the circadian system at multiple levels, say new findings that could have significant treatment implications.

A meta-analysis of 16 studies showed a circadian pattern in 71% of cluster headache attacks (3,490 of 4,953), with a clear circadian peak between 9:00 p.m. and 3:00 a.m.

Migraine was also associated with a circadian pattern in 50% of cases (2,698 of 5,385) across eight studies, with a clear circadian trough between 11:00 p.m. and 7:00 a.m.

Seasonal peaks were also evident for cluster headache (spring and autumn) and migraine (April to October).

“In the short term, these findings help us explain the timing to patients – for example, it is possible that a headache at 8 a.m. is due to their internal body clock instead of their pillow, or breakfast food, or morning medications,” lead investigator Mark Burish, MD, PhD, associate professor, department of neurosurgery, at University of Texas Health Houston, told this news organization.

“In the long term, these findings do suggest that medications that target the circadian system could be effective in migraine and headache patients,” Dr. Burish added.

The study was published online in Neurology.


 

Treatment implications?

Across studies, chronotype was “highly variable” for both cluster headache and migraine, the investigators report.

Cluster headache was associated with lower melatonin and higher cortisol levels, compared with non–cluster headache controls.

On a genetic level, cluster headache was associated with two core circadian genes (CLOCK and REV-ERB–alpha), and five of the nine genes that increase the likelihood of having cluster headache are genes with a circadian pattern of expression.

Migraine headache was associated with lower urinary melatonin levels and with the core circadian genes, CK1-delta and ROR-alpha, and 110 of the 168 genes associated with migraine were clock-controlled genes.

“The data suggest that both of these headache disorders are highly circadian at multiple levels, especially cluster headache,” Dr. Burish said in a release.

“This reinforces the importance of the hypothalamus – the area of the brain that houses the primary biological clock – and its role in cluster headache and migraine. It also raises the question of the genetics of triggers such as sleep changes that are known triggers for migraine and are cues for the body’s circadian rhythm,” Dr. Burish said.

“We hope that future research will look into circadian medications as a new treatment option for migraine and cluster headache patients,” Dr. Burish told this news organization.
 

Importance of sleep regulation

The authors of an accompanying editorial note that even though the study doesn’t have immediate clinical implications, it offers a better understanding of the way chronobiologic factors may influence treatment.

“At a minimum, interventions known to regulate and improve sleep (e.g., melatonin, cognitive behavioral therapy), and which are safe and straightforward to introduce, may be useful in some individuals susceptible to circadian misalignment or sleep disorders,” write Heidi Sutherland, PhD, and Lyn Griffiths, PhD, with Queensland University of Technology, Brisbane, Australia.

“Treatment of comorbidities (e.g., insomnia) that result in sleep disturbances may also help headache management. Furthermore, chronobiological aspects of any pharmacological interventions should be considered, as some frequently used headache and migraine drugs can modulate circadian cycles and influence the expression of circadian genes (e.g., verapamil), or have sleep-related side effects,” they add.

A limitation of the study was the lack of information on factors that could influence the circadian cycle, such as medications; other disorders, such as bipolar disorder; or circadian rhythm issues, such as night-shift work.

The study was supported by grants from the Japan Society for the Promotion of Science, the National Institutes of Health, The Welch Foundation, and The Will Erwin Headache Research Foundation. Dr. Burish is an unpaid member of the medical advisory board of Clusterbusters, and a site investigator for a cluster headache clinical trial funded by Lundbeck. Dr. Sutherland has received grant funding from the U.S. Migraine Research Foundation, and received institute support from Queensland University of Technology for genetics research. Dr. Griffiths has received grant funding from the Australian NHMRC, U.S. Department of Defense, and the U.S. Migraine Research Foundation, and consultancy funding from TEVA.

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

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

DENVER – Using antidepressants to treat osteoarthritis pain can benefit some individuals but appears to have a clinically unimportant reduction in pain when looking at all patients who have tried them, according to a study presented at the OARSI 2023 World Congress. The review was also published in the Cochrane Database of Systematic Reviews in October 2022.

In terms of implications for clinical practice, the findings “seem to suggest there is a subgroup that is more likely to respond to antidepressants,” Anita Wluka, PhD, MBBS, a professor in the School of Public Health and Preventive Medicine at Monash University in Melbourne, told attendees. The findings also raise an important research question: “How can we identify the patient phenotype likely to benefit so we can [minimize the] risk of those adverse events and effects?”

Osteoarthritis pain is heterogeneous, and an estimated 30% of the pain is neuropathic-like, likely including central and peripheral sensitization, Dr. Wluka said. Given that antidepressants affect multiple sites along these pathways, multiple organizations have issued a conditional recommendation for duloxetine in their osteoarthritis guidelines, including OARSI, the European Alliance of Associations for Rheumatology, and the American College of Rheumatology.

The Cochrane Collaboration therefore conducted a systematic review and meta-analysis of research on the benefits and harms of using antidepressants to treat symptomatic knee and hip osteoarthritis. The review included studies through January 2021 whose participants had knee and/or hip osteoarthritis and which compared antidepressant therapy with placebo or another intervention for at least 6 weeks. The authors looked at seven outcomes: overall pain on a 0-10 scale, clinical response (at least a 50% reduction in 24‐hour mean pain), physical function using the Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality of life using the EQ-5D, the proportion of participants withdrawing because of adverse events, the proportion who experienced any adverse events, and the proportion who experienced serious adverse events.

The researchers considered a change on the pain scale of 0.5-1 points to be “slight to small,” a difference above 1 up to 2 to be “moderate,” and a difference greater than 2 points to be “large.” In assessing quality of life function on a scale of 0-100, a slight to small difference was 5-10, a moderate difference was 11-20, and a large difference was above 20.

Of the 18 articles the researchers identified for qualitative synthesis, 9 met the criteria for qualitative synthesis in the meta-analysis, including 7 studies only on the knee and 2 that included the knees and hips. All nine studies compared antidepressants with placebo, with or without NSAIDs. Most focused on serotonin and norepinephrine reuptake inhibitors (SNRIs) – six studies on duloxetine and one on milnacipran – while one included fluvoxamine and one included nortriptyline.

The trials included a combined 2,122 participants who were predominantly female with an average age range of 54-66. Trials ranged from 8 to 16 weeks. Five of the trials carried risk of attrition and reporting bias, and only one trial had low risk of bias across all domains.

In five trials with SNRIs and one trial with tricyclics (nortriptyline) totaling 1,904 participants, 45% of those receiving antidepressants had a clinical response, compared with 29% of patients who received placebo (risk ratio, 1.55; 95% CI, 1.31-1.92). This absolute improvement in pain occurred in 16% more participants taking antidepressants, giving a number needed to treat (NNT) of 6. Average improvement in WOMAC physical function was 10.5 points with placebo and 16.2 points with antidepressants, indicating a “small, clinically unimportant response,” the researchers concluded.

Withdrawals because of adverse events included 11% of the antidepressant group and 5% of the placebo group (RR, 2.15; 95% CI, 1.56-2.87), putting the NNT for a harmful outcome at 17.

For all nine trials together, however, the mean reduction in pain from antidepressants was 2.3 points, compared with 1.7 points with placebo, a statistically significant but ”clinically unimportant improvement,” the researchers concluded. Adverse events occurred in 64% of the antidepressant group, compared with 49% of the placebo group (RR, 1.27; 95% CI, 1.15-1.41), which put the NNT for a harmful outcome at 7. No significant difference in serious adverse events occurred between the groups.

The analysis was limited by the low number of trials, most of which were sponsored by industry and most of which used duloxetine. Further, few of the studies enrolled patients with osteoarthritis of the hip, none assessed medium- or long-term effects, and none stratified the participants for different types of pain (neuropathic-like or central or peripheral pain sensitization).

“My general impression is that there was a statistically significant difference found in favor of duloxetine and the antidepressants,” David J. Hunter, MBBS, PhD, MSc, of the University of Sydney, said after the presentation. “There is a real risk of harm, which I think is important to take into consideration, but at least for me as a clinician and in advising other clinicians, it’s one tool in our armamentarium. I think it’s really important to allow patients to make an informed decision about the potential benefit, the real risk of harm, and the fact that it is quite useful in some patients, and I use it in my clinical practice.”

Jeffrey N. Katz, MD, MS, of Brigham and Women’s Hospital in Boston, said he uses antidepressants in the same way in his practice and that other types of medications, such as TNF inhibitors, also carry risk of harm that may exceed that of antidepressants.

“I’ve had lots of people start duloxetine, and if they stop it, it’s usually because they just don’t tolerate it very well,” Dr. Katz said.

“We don’t want to throw too many things away,” Dr. Hunter added. “Our patients don’t necessarily have a lot of choices here from a pharmacologic perspective, so I think it’s one of those options that I want to keep in my tool kit, and that’s not necessarily going to change.”

The research did not involve outside funding, and Dr. Wluka reported having no industry disclosures. Disclosure information was unavailable for Dr. Katz and Dr. Hunter. The Congress was sponsored by the Osteoarthritis Research Society International.

DENVER – Using antidepressants to treat osteoarthritis pain can benefit some individuals but appears to have a clinically unimportant reduction in pain when looking at all patients who have tried them, according to a study presented at the OARSI 2023 World Congress. The review was also published in the Cochrane Database of Systematic Reviews in October 2022.

In terms of implications for clinical practice, the findings “seem to suggest there is a subgroup that is more likely to respond to antidepressants,” Anita Wluka, PhD, MBBS, a professor in the School of Public Health and Preventive Medicine at Monash University in Melbourne, told attendees. The findings also raise an important research question: “How can we identify the patient phenotype likely to benefit so we can [minimize the] risk of those adverse events and effects?”

Osteoarthritis pain is heterogeneous, and an estimated 30% of the pain is neuropathic-like, likely including central and peripheral sensitization, Dr. Wluka said. Given that antidepressants affect multiple sites along these pathways, multiple organizations have issued a conditional recommendation for duloxetine in their osteoarthritis guidelines, including OARSI, the European Alliance of Associations for Rheumatology, and the American College of Rheumatology.

The Cochrane Collaboration therefore conducted a systematic review and meta-analysis of research on the benefits and harms of using antidepressants to treat symptomatic knee and hip osteoarthritis. The review included studies through January 2021 whose participants had knee and/or hip osteoarthritis and which compared antidepressant therapy with placebo or another intervention for at least 6 weeks. The authors looked at seven outcomes: overall pain on a 0-10 scale, clinical response (at least a 50% reduction in 24‐hour mean pain), physical function using the Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality of life using the EQ-5D, the proportion of participants withdrawing because of adverse events, the proportion who experienced any adverse events, and the proportion who experienced serious adverse events.

The researchers considered a change on the pain scale of 0.5-1 points to be “slight to small,” a difference above 1 up to 2 to be “moderate,” and a difference greater than 2 points to be “large.” In assessing quality of life function on a scale of 0-100, a slight to small difference was 5-10, a moderate difference was 11-20, and a large difference was above 20.

Of the 18 articles the researchers identified for qualitative synthesis, 9 met the criteria for qualitative synthesis in the meta-analysis, including 7 studies only on the knee and 2 that included the knees and hips. All nine studies compared antidepressants with placebo, with or without NSAIDs. Most focused on serotonin and norepinephrine reuptake inhibitors (SNRIs) – six studies on duloxetine and one on milnacipran – while one included fluvoxamine and one included nortriptyline.

The trials included a combined 2,122 participants who were predominantly female with an average age range of 54-66. Trials ranged from 8 to 16 weeks. Five of the trials carried risk of attrition and reporting bias, and only one trial had low risk of bias across all domains.

In five trials with SNRIs and one trial with tricyclics (nortriptyline) totaling 1,904 participants, 45% of those receiving antidepressants had a clinical response, compared with 29% of patients who received placebo (risk ratio, 1.55; 95% CI, 1.31-1.92). This absolute improvement in pain occurred in 16% more participants taking antidepressants, giving a number needed to treat (NNT) of 6. Average improvement in WOMAC physical function was 10.5 points with placebo and 16.2 points with antidepressants, indicating a “small, clinically unimportant response,” the researchers concluded.

Withdrawals because of adverse events included 11% of the antidepressant group and 5% of the placebo group (RR, 2.15; 95% CI, 1.56-2.87), putting the NNT for a harmful outcome at 17.

For all nine trials together, however, the mean reduction in pain from antidepressants was 2.3 points, compared with 1.7 points with placebo, a statistically significant but ”clinically unimportant improvement,” the researchers concluded. Adverse events occurred in 64% of the antidepressant group, compared with 49% of the placebo group (RR, 1.27; 95% CI, 1.15-1.41), which put the NNT for a harmful outcome at 7. No significant difference in serious adverse events occurred between the groups.

The analysis was limited by the low number of trials, most of which were sponsored by industry and most of which used duloxetine. Further, few of the studies enrolled patients with osteoarthritis of the hip, none assessed medium- or long-term effects, and none stratified the participants for different types of pain (neuropathic-like or central or peripheral pain sensitization).

“My general impression is that there was a statistically significant difference found in favor of duloxetine and the antidepressants,” David J. Hunter, MBBS, PhD, MSc, of the University of Sydney, said after the presentation. “There is a real risk of harm, which I think is important to take into consideration, but at least for me as a clinician and in advising other clinicians, it’s one tool in our armamentarium. I think it’s really important to allow patients to make an informed decision about the potential benefit, the real risk of harm, and the fact that it is quite useful in some patients, and I use it in my clinical practice.”

Jeffrey N. Katz, MD, MS, of Brigham and Women’s Hospital in Boston, said he uses antidepressants in the same way in his practice and that other types of medications, such as TNF inhibitors, also carry risk of harm that may exceed that of antidepressants.

“I’ve had lots of people start duloxetine, and if they stop it, it’s usually because they just don’t tolerate it very well,” Dr. Katz said.

“We don’t want to throw too many things away,” Dr. Hunter added. “Our patients don’t necessarily have a lot of choices here from a pharmacologic perspective, so I think it’s one of those options that I want to keep in my tool kit, and that’s not necessarily going to change.”

The research did not involve outside funding, and Dr. Wluka reported having no industry disclosures. Disclosure information was unavailable for Dr. Katz and Dr. Hunter. The Congress was sponsored by the Osteoarthritis Research Society International.

DENVER – Using antidepressants to treat osteoarthritis pain can benefit some individuals but appears to have a clinically unimportant reduction in pain when looking at all patients who have tried them, according to a study presented at the OARSI 2023 World Congress. The review was also published in the Cochrane Database of Systematic Reviews in October 2022.

In terms of implications for clinical practice, the findings “seem to suggest there is a subgroup that is more likely to respond to antidepressants,” Anita Wluka, PhD, MBBS, a professor in the School of Public Health and Preventive Medicine at Monash University in Melbourne, told attendees. The findings also raise an important research question: “How can we identify the patient phenotype likely to benefit so we can [minimize the] risk of those adverse events and effects?”

Osteoarthritis pain is heterogeneous, and an estimated 30% of the pain is neuropathic-like, likely including central and peripheral sensitization, Dr. Wluka said. Given that antidepressants affect multiple sites along these pathways, multiple organizations have issued a conditional recommendation for duloxetine in their osteoarthritis guidelines, including OARSI, the European Alliance of Associations for Rheumatology, and the American College of Rheumatology.

The Cochrane Collaboration therefore conducted a systematic review and meta-analysis of research on the benefits and harms of using antidepressants to treat symptomatic knee and hip osteoarthritis. The review included studies through January 2021 whose participants had knee and/or hip osteoarthritis and which compared antidepressant therapy with placebo or another intervention for at least 6 weeks. The authors looked at seven outcomes: overall pain on a 0-10 scale, clinical response (at least a 50% reduction in 24‐hour mean pain), physical function using the Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality of life using the EQ-5D, the proportion of participants withdrawing because of adverse events, the proportion who experienced any adverse events, and the proportion who experienced serious adverse events.

The researchers considered a change on the pain scale of 0.5-1 points to be “slight to small,” a difference above 1 up to 2 to be “moderate,” and a difference greater than 2 points to be “large.” In assessing quality of life function on a scale of 0-100, a slight to small difference was 5-10, a moderate difference was 11-20, and a large difference was above 20.

Of the 18 articles the researchers identified for qualitative synthesis, 9 met the criteria for qualitative synthesis in the meta-analysis, including 7 studies only on the knee and 2 that included the knees and hips. All nine studies compared antidepressants with placebo, with or without NSAIDs. Most focused on serotonin and norepinephrine reuptake inhibitors (SNRIs) – six studies on duloxetine and one on milnacipran – while one included fluvoxamine and one included nortriptyline.

The trials included a combined 2,122 participants who were predominantly female with an average age range of 54-66. Trials ranged from 8 to 16 weeks. Five of the trials carried risk of attrition and reporting bias, and only one trial had low risk of bias across all domains.

In five trials with SNRIs and one trial with tricyclics (nortriptyline) totaling 1,904 participants, 45% of those receiving antidepressants had a clinical response, compared with 29% of patients who received placebo (risk ratio, 1.55; 95% CI, 1.31-1.92). This absolute improvement in pain occurred in 16% more participants taking antidepressants, giving a number needed to treat (NNT) of 6. Average improvement in WOMAC physical function was 10.5 points with placebo and 16.2 points with antidepressants, indicating a “small, clinically unimportant response,” the researchers concluded.

Withdrawals because of adverse events included 11% of the antidepressant group and 5% of the placebo group (RR, 2.15; 95% CI, 1.56-2.87), putting the NNT for a harmful outcome at 17.

For all nine trials together, however, the mean reduction in pain from antidepressants was 2.3 points, compared with 1.7 points with placebo, a statistically significant but ”clinically unimportant improvement,” the researchers concluded. Adverse events occurred in 64% of the antidepressant group, compared with 49% of the placebo group (RR, 1.27; 95% CI, 1.15-1.41), which put the NNT for a harmful outcome at 7. No significant difference in serious adverse events occurred between the groups.

The analysis was limited by the low number of trials, most of which were sponsored by industry and most of which used duloxetine. Further, few of the studies enrolled patients with osteoarthritis of the hip, none assessed medium- or long-term effects, and none stratified the participants for different types of pain (neuropathic-like or central or peripheral pain sensitization).

“My general impression is that there was a statistically significant difference found in favor of duloxetine and the antidepressants,” David J. Hunter, MBBS, PhD, MSc, of the University of Sydney, said after the presentation. “There is a real risk of harm, which I think is important to take into consideration, but at least for me as a clinician and in advising other clinicians, it’s one tool in our armamentarium. I think it’s really important to allow patients to make an informed decision about the potential benefit, the real risk of harm, and the fact that it is quite useful in some patients, and I use it in my clinical practice.”

Jeffrey N. Katz, MD, MS, of Brigham and Women’s Hospital in Boston, said he uses antidepressants in the same way in his practice and that other types of medications, such as TNF inhibitors, also carry risk of harm that may exceed that of antidepressants.

“I’ve had lots of people start duloxetine, and if they stop it, it’s usually because they just don’t tolerate it very well,” Dr. Katz said.

“We don’t want to throw too many things away,” Dr. Hunter added. “Our patients don’t necessarily have a lot of choices here from a pharmacologic perspective, so I think it’s one of those options that I want to keep in my tool kit, and that’s not necessarily going to change.”

The research did not involve outside funding, and Dr. Wluka reported having no industry disclosures. Disclosure information was unavailable for Dr. Katz and Dr. Hunter. The Congress was sponsored by the Osteoarthritis Research Society International.